Researchers of the Max DelbrГјck Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have gained crucial insight into how mechanosensitivity arises. By measuring electrical impulses in the sensory neurons of mice, the neurobiologists and pain researchers Dr. Stefan G. Lechner and Professor Gary Lewin were able to directly elucidate, for the first time, the emergence of mechanosensitivity. At the same time they were able to show that neurons develop their sensitivity to touch and pain during different developmental phases but always coincidentally with the growth of the neuronal pathways. (EMBO Journal, 2009, doi:10.1038/emboj.2009.73).*
The sensory neurons, which are sensitive to touch and pain, are located in the dorsal root ganglia between the intervertebral discs. The neurons receive the stimulus and convert it into electrical signals that are conveyed to the brain.
Signal transduction has been investigated very thoroughly, which has led to the development of drugs that block the transduction of pain signals to the brain. Very little, however, is known about how stimulus sensitivity actually emerges.
Using the patch-clamp technique in isolated cells of mouse embryos, the MDC researchers succeeded in measuring tiny electrical currents in the cell membranes after a mechanosensory stimulus.
"These measurements are extremely difficult," Dr. Lechner explained, "which is why only very few laboratories in the world are specialized in this area."
The researchers in Berlin-Buch were able to show that the sensory neurons in the mouse embryo have already fully developed their mechanosensitivity competence on embryonic day 13. That corresponds to about the end of the sixth month of pregnancy in humans.
For this development the neurons do not require any nerve growth factor, which is why the researchers suspect that this process is driven by a genetic program. In contrast, the competence to sense pain in the sensory neurons can only develop with the aid of nerve growth factor (NGF). It takes place at a later stage in embryonic development and even after birth.
*Developmental waves of mechanosensitivity acquisition in sensory neuron subtypes during embryonic development
Stefan G Lechner, Henning Frenzel1, Rui Wang1 and Gary R Lewin*
Department of Neuroscience, Max DelbrГјck Center for Molecular Medicine, Berlin-Buch, Germany
*Corresponding author
Source:
Barbara Bachtler
Helmholtz Association of German Research Centres
вторник, 28 июня 2011 г.
суббота, 25 июня 2011 г.
Advances In Therapy Added To Springer Journals Portfolio
As part of its continued commitment to providing high-quality information to professionals in the pharmaceutical industry, Springer has acquired the prestigious journal Advances in Therapy, to be published from 2008. With this move, Springer further enhances its services for clients in the pharmaceutical, healthcare and biotechnology industries.
Advances in Therapy, to be published by Springer Healthcare Communications (SHC), will continue to publish original research from the academic and research community across the globe as well as drug reviews and commissioned articles. Now in its 24th year of publication, the journal is Medline Indexed and has a strong Impact Factor, listed in both the ISI subject categories 'Pharmacology and Pharmacy' and 'Medicine, Research and Experimental'. The first issue of Advances in Therapy published by SHC will be Volume 25, No. 1, 2008.
The key feature of Advances in Therapy is the rapid publication of original research. Continuing this practice, SHC will increase its already rapid publication times to ensure online availability through SpringerLink within six weeks of submission. From 2008, Advances in Therapy will double its publication frequency from bimonthly to monthly.
Stephen Entwistle, Vice President of SHC, said, "Advances in Therapy works closely with pharmaceutical researchers to deliver clinically important results to the academic and industrial community. I am very proud that the journal is now part of the Springer family and I am confident that the journal's inclusion on SpringerLink will speed dissemination of important research worldwide."
Springer (springer/) is the second-largest publisher of journals in the science, technology, and medicine (STM) sector and the largest publisher of STM books. Springer Healthcare Communications offers the full range of communication and publishing strategies to develop high-impact medical education campaigns. The service portfolio includes strategic communications, publication planning, key opinion leader support, congress materials and events, as well as internet-based tools and promotional material.
Springer and SHC are part of Springer Science+Business Media, one of the world's leading suppliers of scientific and specialist literature. The group publishes over 1,700 journals and more than 5,500 new books a year, as well as the largest STM eBook Collection worldwide. Springer has operations in over 20 countries in Europe, the USA, and Asia, and some 5,000 employees.
Advances in Therapy ISSN: 0741-238X
Source: Renate Bayaz
Springer
Advances in Therapy, to be published by Springer Healthcare Communications (SHC), will continue to publish original research from the academic and research community across the globe as well as drug reviews and commissioned articles. Now in its 24th year of publication, the journal is Medline Indexed and has a strong Impact Factor, listed in both the ISI subject categories 'Pharmacology and Pharmacy' and 'Medicine, Research and Experimental'. The first issue of Advances in Therapy published by SHC will be Volume 25, No. 1, 2008.
The key feature of Advances in Therapy is the rapid publication of original research. Continuing this practice, SHC will increase its already rapid publication times to ensure online availability through SpringerLink within six weeks of submission. From 2008, Advances in Therapy will double its publication frequency from bimonthly to monthly.
Stephen Entwistle, Vice President of SHC, said, "Advances in Therapy works closely with pharmaceutical researchers to deliver clinically important results to the academic and industrial community. I am very proud that the journal is now part of the Springer family and I am confident that the journal's inclusion on SpringerLink will speed dissemination of important research worldwide."
Springer (springer/) is the second-largest publisher of journals in the science, technology, and medicine (STM) sector and the largest publisher of STM books. Springer Healthcare Communications offers the full range of communication and publishing strategies to develop high-impact medical education campaigns. The service portfolio includes strategic communications, publication planning, key opinion leader support, congress materials and events, as well as internet-based tools and promotional material.
Springer and SHC are part of Springer Science+Business Media, one of the world's leading suppliers of scientific and specialist literature. The group publishes over 1,700 journals and more than 5,500 new books a year, as well as the largest STM eBook Collection worldwide. Springer has operations in over 20 countries in Europe, the USA, and Asia, and some 5,000 employees.
Advances in Therapy ISSN: 0741-238X
Source: Renate Bayaz
Springer
среда, 22 июня 2011 г.
Encouraging Spinal Cord Regeneration After Injury
Animal research is suggesting new ways to aid recovery after spinal cord injury. New studies demonstrate that diet affects recovery rate and show how to make stem cell therapies safer for spinal injury patients. The findings were presented at Neuroscience 2009, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news on brain science and health.
In other animal studies, researchers identified molecules that encourage spinal cord regeneration and ways to block molecules that discourage it. The findings may help shape therapies for the more than one million people in North America who have spinal cord injuries.
Research released today shows that:
A diet high in fat and low in carbohydrates speeds recovery in rats with spinal cord injuries. The study suggests that dietary content may affect spinal cord injury recovery rates in people (Wolfram Tetzlaff, MD, PhD, abstract 542.10, see attached summary).
In animal studies, stem cell implants pre-screened for "unsafe" immature cells helped repair injured spinal cords without dangerous side effects, like tumor formation. The findings suggest best practices for human stem cell therapies (Masaya Nakamura, MD, PhD, abstract 642.14, see attached summary).
Other findings discussed at the meeting show that:
Researchers are discovering how to encourage the spinal cord to regenerate and form functional connections after injury. Growth factors, enzymes, and molecular tools show promising results in animal models (Eric Frank, PhD, see attached speaker's summary).
"Some injuries harm nerve cells, but the brain often recovers from stress, damage, or disease," said press conference moderator Oswald Steward, PhD, of the University of California, Irvine, an expert on spinal cord injury and synaptic plasticity. "We are learning a great deal about how to encourage the recovery process and harness the plasticity of the nervous system to offer hope to spinal cord injury patients," Steward said.
Full study information is available online here.
This research was supported by national funding agencies, such as the National Institutes of Health, as well as private and philanthropic organizations.
Source:
Kat Snodgrass
Society for Neuroscience
In other animal studies, researchers identified molecules that encourage spinal cord regeneration and ways to block molecules that discourage it. The findings may help shape therapies for the more than one million people in North America who have spinal cord injuries.
Research released today shows that:
A diet high in fat and low in carbohydrates speeds recovery in rats with spinal cord injuries. The study suggests that dietary content may affect spinal cord injury recovery rates in people (Wolfram Tetzlaff, MD, PhD, abstract 542.10, see attached summary).
In animal studies, stem cell implants pre-screened for "unsafe" immature cells helped repair injured spinal cords without dangerous side effects, like tumor formation. The findings suggest best practices for human stem cell therapies (Masaya Nakamura, MD, PhD, abstract 642.14, see attached summary).
Other findings discussed at the meeting show that:
Researchers are discovering how to encourage the spinal cord to regenerate and form functional connections after injury. Growth factors, enzymes, and molecular tools show promising results in animal models (Eric Frank, PhD, see attached speaker's summary).
"Some injuries harm nerve cells, but the brain often recovers from stress, damage, or disease," said press conference moderator Oswald Steward, PhD, of the University of California, Irvine, an expert on spinal cord injury and synaptic plasticity. "We are learning a great deal about how to encourage the recovery process and harness the plasticity of the nervous system to offer hope to spinal cord injury patients," Steward said.
Full study information is available online here.
This research was supported by national funding agencies, such as the National Institutes of Health, as well as private and philanthropic organizations.
Source:
Kat Snodgrass
Society for Neuroscience
воскресенье, 19 июня 2011 г.
Researchers Note Tradeoffs In Auditory Perception
New research published in the open-access journal PLoS Biology
finds error in an often-made assumption in the field of sensory
neuroscience. Merav Ahissar (Hebrew University, Jerusalem, Israel) and
colleagues were studying a key issue regarding the determination of the
greatest amount of task-relevant information that is encoded in our
brain. The researchers showed that contrary to common belief, all of
the information is in fact not available for making perceptual
decisions.
Perception is the process of becoming aware and understanding sensory
information (what we see, hear, taste, etc.) While studying hearing,
Ahissar and colleagues demonstrated that when speech is covered up by
noise, the perception processes of discriminating and understanding the
speech only draw information that is represented at higher cortical
areas rather than from the entire brain. This means that if a listener
is determining whether a speaker said "day" or "night," for example,
the listener is likely to be able to tell the difference. If, however,
a listener must choose between words like "day" and "bay," a finer
discrimination skill is required. Only under certain conditions can the
information pertaining to the fine spectral and temporal details be
used for successful discrimination. One condition, often used in
psychoacoustic experiments, is systematic repetition of the word. A
second condition is when a listener decides to focus solely on word
identification, removing the need for comprehension. The authors note
that these conditions are "non-ecological" and not feasible in most
situations.
The researchers write, "Taken together, the auditory system seems to
favor ecologically more likely conditions and yet retains flexibility
for the less likely ones. Discriminations that are prevalent in natural
situations are fast and still use all low-level information, whereas
discriminations that are less likely to occur are either fast or use
all low-level information. The results presented here, however, show
that the auditory system cannot achieve both."
"Similar defaults and tradeoffs characterize the relations between
processing hierarchies and perception at the various sensory
modalities," they conclude.
Low-level information and high-level perception: The case of
speech in noise
Nahum M, Nelken I, Ahissar M
PLoS Biology (2008). 6(5):e126.
doi:10.1371/journal.pbio.0060126
Click
Here to View Article
About PLoS Biology
PLoS Biology is an open-access, peer-reviewed
general biology journal published by the Public Library of Science
(PLoS), a nonprofit organization of scientists and physicians committed
to making the world's scientific and medical literature a public
resource. New articles are published online weekly; issues are
published monthly. For more information, visit
plosbiology
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization
of scientists and physicians committed to making the world's
scientific and medical literature a freely available public resource.
For more information, visit plos
Written by: Peter M Crosta
finds error in an often-made assumption in the field of sensory
neuroscience. Merav Ahissar (Hebrew University, Jerusalem, Israel) and
colleagues were studying a key issue regarding the determination of the
greatest amount of task-relevant information that is encoded in our
brain. The researchers showed that contrary to common belief, all of
the information is in fact not available for making perceptual
decisions.
Perception is the process of becoming aware and understanding sensory
information (what we see, hear, taste, etc.) While studying hearing,
Ahissar and colleagues demonstrated that when speech is covered up by
noise, the perception processes of discriminating and understanding the
speech only draw information that is represented at higher cortical
areas rather than from the entire brain. This means that if a listener
is determining whether a speaker said "day" or "night," for example,
the listener is likely to be able to tell the difference. If, however,
a listener must choose between words like "day" and "bay," a finer
discrimination skill is required. Only under certain conditions can the
information pertaining to the fine spectral and temporal details be
used for successful discrimination. One condition, often used in
psychoacoustic experiments, is systematic repetition of the word. A
second condition is when a listener decides to focus solely on word
identification, removing the need for comprehension. The authors note
that these conditions are "non-ecological" and not feasible in most
situations.
The researchers write, "Taken together, the auditory system seems to
favor ecologically more likely conditions and yet retains flexibility
for the less likely ones. Discriminations that are prevalent in natural
situations are fast and still use all low-level information, whereas
discriminations that are less likely to occur are either fast or use
all low-level information. The results presented here, however, show
that the auditory system cannot achieve both."
"Similar defaults and tradeoffs characterize the relations between
processing hierarchies and perception at the various sensory
modalities," they conclude.
Low-level information and high-level perception: The case of
speech in noise
Nahum M, Nelken I, Ahissar M
PLoS Biology (2008). 6(5):e126.
doi:10.1371/journal.pbio.0060126
Click
Here to View Article
About PLoS Biology
PLoS Biology is an open-access, peer-reviewed
general biology journal published by the Public Library of Science
(PLoS), a nonprofit organization of scientists and physicians committed
to making the world's scientific and medical literature a public
resource. New articles are published online weekly; issues are
published monthly. For more information, visit
plosbiology
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization
of scientists and physicians committed to making the world's
scientific and medical literature a freely available public resource.
For more information, visit plos
Written by: Peter M Crosta
JГјlich Neutron Scientists Inaugurate Unique Device In The US
A unique large-scale research device from JГјlich has gone into operation in the USA. At the strongest neutron source in the world, the spallation source SNS in Oak Ridge, Tennessee, Forschungszentrum JГјlich inaugurated a so-called neutron spin echo (NSE) spectrometer. The NSE spectrometer enables detailed observations to be made of the motion of proteins and polymers. It will thus help to develop improved plastics or to understand metabolic processes in cells.
"Neutron scattering gives us unique insights into matter and is absolutely indispensable as a scientific method both for basic and also application-oriented research in materials science, medicine and biology," said Prof. Sebastian M. Schmidt, member of the Board of Directors of Forschungszentrum JГјlich. "With our branch office at the SNS we are making the world's strongest pulsed spallation source accessible to German and European scientists." Forschungszentrum JГјlich is the only research institution outside North America that has sole responsibility for operating its own instrument at SNS. "This is a visible sign that JГјlich's long-standing expertise in the construction and operation of neutron instruments is recognized throughout the world," Schmidt added. The experience gained in the construction, operation and utilization of the NSE spectrometer will also be incorporated into the design and implementation of the European Spallation Source (ESS), for which concrete planning work will begin in January.
Neutrons are the electrically neutral building blocks of atomic nuclei. They are generated in research reactors or spallation sources and in special devices, so-called "diffractometers" and "spectrometers", neutrons are guided onto the samples to be investigated. These neutron beams "bounce off" the atoms and molecules of the samples and in doing so they may change their direction and speed. The nature of this "scattering" provides information about the arrangement and motion of the atoms in the sample, which cannot be visualized by complementary methods such as X-rays or electron microscopes. JГјlich scientists use neutrons to investigate, for example, magnetic materials for information technology or so-called soft matter, which includes industrially important plastics as well as proteins of interest to medicine.
"This is the first time that an instrument of this type has been constructed at a neutron source such as SNS. The JГјlich neutron spin echo spectrometer has the highest resolution in the world. We have developed innovative technologies especially for this purpose, such as superconducting coils with extremely homogeneous magnetic fields," said Prof. Dieter Richter from Forschungszentrum JГјlich. Forschungszentrum JГјlich is focusing its expertise in neutron research at the JГјlich Centre for Neutron Science (JCNS) and maintains branch offices at Germany's strongest neutron source, FRM II, at Garching near Munich, as well as at the very high flux reactor in Grenoble, France, and now at the world's strongest neutron source, SNS at Oak Ridge, USA. Richter continued: "With the NSE spectrometer at SNS we will be able to observe the slow movements inside proteins that determine their function. Furthermore, we will be able to investigate the molecular redistributions in polymers which define their mechanical properties and their processibility."
Funding for the device costing roughly € 15 million - designed and constructed by JГјlich scientists - was provided by the German Federal Ministry of Education and Research and the Ministry of Innovation, Science, Research and Technology of the federal state of North Rhine-Westphalia. Yesterday, the device was officially inaugurated at the SNS as part of an international scientific workshop. The guests also included Dr. Beatrix Vierkorn-Rudolph, head of the Subsection for Large Facilities, Energy and Basic Research of the German Federal Ministry of Education and Research, and Dr. Steven Koonin, Under Secretary for Science of the US Department of Energy.
Source: Angela Wenzik
Helmholtz Association of German Research Centres
"Neutron scattering gives us unique insights into matter and is absolutely indispensable as a scientific method both for basic and also application-oriented research in materials science, medicine and biology," said Prof. Sebastian M. Schmidt, member of the Board of Directors of Forschungszentrum JГјlich. "With our branch office at the SNS we are making the world's strongest pulsed spallation source accessible to German and European scientists." Forschungszentrum JГјlich is the only research institution outside North America that has sole responsibility for operating its own instrument at SNS. "This is a visible sign that JГјlich's long-standing expertise in the construction and operation of neutron instruments is recognized throughout the world," Schmidt added. The experience gained in the construction, operation and utilization of the NSE spectrometer will also be incorporated into the design and implementation of the European Spallation Source (ESS), for which concrete planning work will begin in January.
Neutrons are the electrically neutral building blocks of atomic nuclei. They are generated in research reactors or spallation sources and in special devices, so-called "diffractometers" and "spectrometers", neutrons are guided onto the samples to be investigated. These neutron beams "bounce off" the atoms and molecules of the samples and in doing so they may change their direction and speed. The nature of this "scattering" provides information about the arrangement and motion of the atoms in the sample, which cannot be visualized by complementary methods such as X-rays or electron microscopes. JГјlich scientists use neutrons to investigate, for example, magnetic materials for information technology or so-called soft matter, which includes industrially important plastics as well as proteins of interest to medicine.
"This is the first time that an instrument of this type has been constructed at a neutron source such as SNS. The JГјlich neutron spin echo spectrometer has the highest resolution in the world. We have developed innovative technologies especially for this purpose, such as superconducting coils with extremely homogeneous magnetic fields," said Prof. Dieter Richter from Forschungszentrum JГјlich. Forschungszentrum JГјlich is focusing its expertise in neutron research at the JГјlich Centre for Neutron Science (JCNS) and maintains branch offices at Germany's strongest neutron source, FRM II, at Garching near Munich, as well as at the very high flux reactor in Grenoble, France, and now at the world's strongest neutron source, SNS at Oak Ridge, USA. Richter continued: "With the NSE spectrometer at SNS we will be able to observe the slow movements inside proteins that determine their function. Furthermore, we will be able to investigate the molecular redistributions in polymers which define their mechanical properties and their processibility."
Funding for the device costing roughly € 15 million - designed and constructed by JГјlich scientists - was provided by the German Federal Ministry of Education and Research and the Ministry of Innovation, Science, Research and Technology of the federal state of North Rhine-Westphalia. Yesterday, the device was officially inaugurated at the SNS as part of an international scientific workshop. The guests also included Dr. Beatrix Vierkorn-Rudolph, head of the Subsection for Large Facilities, Energy and Basic Research of the German Federal Ministry of Education and Research, and Dr. Steven Koonin, Under Secretary for Science of the US Department of Energy.
Source: Angela Wenzik
Helmholtz Association of German Research Centres
суббота, 18 июня 2011 г.
Study Of Fu-Zheng-Jie-Du-Decoction Action On PTEN Expression In Hepatocellular Carcinoma
Many hepatocellular carcinoma (HCC) patients in China may be treated with Traditional Chinese medicine (TCM). Some say it works, others doubt its effectiveness. These stated that a research group in China had found TCM can down-regulate the expression of PTEN in HCC, which may suppress tumor cell growth and regulate tumor cell invasion and metastasis.
A research article published on January 7, 2008 in the World Journal of Gastroenterology (volume 14, issue 1) addresses this problem. The research group imbedded hepatoma carcinoma tissue in the livers of 48 male athymic mice. The mice were distributed randomly into two groups: The chemotherapy group was treated by intragastric administration with FT207 (Tegafur). The TCM group was treated by intragastric administration with FZJDT (complex prescription of Chinese crude drug) that had been deliquated into 3 kinds of density as the low, middle, and high.
Four weeks later, the researchers found the TCM group had distinct superiority in their survival rate compared with the chemotherapy group. There was less tumor metastasis in the livers of the TCM group than in the chemotherapy group. Particularly the results of immunohistochemistry showed the intensity of PTEN (Phosphatase and Tensin Homolog deleted on Chromosome 10) in the TCM group was higher than in the chemotherapy group.
PTEN was recently identified as a tumor suppressor gene by three American research teams. They found PTEN may suppress tumor cell growth and regulate tumor cell invasion and metastasis through inhibiting many signal pathways of cell proliferation.
FZJDT has been widely used to treat HCC for years in The First Affiliated Hospital of Sun Yat-Sen University. Just what is the mechanism of the Chinese herbs that strengthens the body's resistance and removes toxic substances? Our research showed TCM could markedly increase expression of PTEN in the athymic mice, compared with the chemotherapy group treated with FT207, indicating the anticancer mechanism of the TCM used in this study.
Mechanisms of TCM healing HCC may partially be explained by the enhancing of the expression of PTEN in the liver. The results of this study suggest a promising future for TCM as a combined therapy to treat HCC in China .
6.1 Reference: Yin LR, Chen ZX, Zhang SJ, Sun BG, Liu YD, Huang HZ. Expression of chromosome ten in liver of athymic mice with hepatocellular carcinoma and the effect of Fuzheng Jiedu Decoction. World J Gastroenterol 2008; 14(1): 108-113
wjgnet/1007-9327/14/108.asp
6.2 Correspondence to: Dr. Ze-Xiong Chen, Department of TCM, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
6.3 About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
6.4 About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Jing Zhu
World Journal of Gastroenterology
A research article published on January 7, 2008 in the World Journal of Gastroenterology (volume 14, issue 1) addresses this problem. The research group imbedded hepatoma carcinoma tissue in the livers of 48 male athymic mice. The mice were distributed randomly into two groups: The chemotherapy group was treated by intragastric administration with FT207 (Tegafur). The TCM group was treated by intragastric administration with FZJDT (complex prescription of Chinese crude drug) that had been deliquated into 3 kinds of density as the low, middle, and high.
Four weeks later, the researchers found the TCM group had distinct superiority in their survival rate compared with the chemotherapy group. There was less tumor metastasis in the livers of the TCM group than in the chemotherapy group. Particularly the results of immunohistochemistry showed the intensity of PTEN (Phosphatase and Tensin Homolog deleted on Chromosome 10) in the TCM group was higher than in the chemotherapy group.
PTEN was recently identified as a tumor suppressor gene by three American research teams. They found PTEN may suppress tumor cell growth and regulate tumor cell invasion and metastasis through inhibiting many signal pathways of cell proliferation.
FZJDT has been widely used to treat HCC for years in The First Affiliated Hospital of Sun Yat-Sen University. Just what is the mechanism of the Chinese herbs that strengthens the body's resistance and removes toxic substances? Our research showed TCM could markedly increase expression of PTEN in the athymic mice, compared with the chemotherapy group treated with FT207, indicating the anticancer mechanism of the TCM used in this study.
Mechanisms of TCM healing HCC may partially be explained by the enhancing of the expression of PTEN in the liver. The results of this study suggest a promising future for TCM as a combined therapy to treat HCC in China .
6.1 Reference: Yin LR, Chen ZX, Zhang SJ, Sun BG, Liu YD, Huang HZ. Expression of chromosome ten in liver of athymic mice with hepatocellular carcinoma and the effect of Fuzheng Jiedu Decoction. World J Gastroenterol 2008; 14(1): 108-113
wjgnet/1007-9327/14/108.asp
6.2 Correspondence to: Dr. Ze-Xiong Chen, Department of TCM, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
6.3 About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
6.4 About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Jing Zhu
World Journal of Gastroenterology
пятница, 17 июня 2011 г.
Diffusion Of A Soluble Protein Through A Sensory Cilium
A team of researchers led by Peter Calvert (SUNY Upstate Medical University) has, for the first time, measured the diffusion coefficient of a protein in a primary cilium and in other major compartments of a highly polarized cell. The study appears in the March issue of the Journal of General Physiology .
Transport of proteins to and from cilia is crucial for normal cell function and survival, and interruption of transport has been implicated in degenerative diseases and neoplastic diseases, such as cancer. Researchers believe that cilia impose selective barriers to the movement of proteins, but because of the narrow and complex structure of cilia - with diameters near or below the resolution of light microscopy - this hypothesis has been difficult to examine.
Using confocal and multiphoton microscopy, Calvert and his team - including William Schiesser (Lehigh University) and Edward Pugh (University of California, Davis) - measured the mobility of PAGFP (photoactivatable green fluorescent protein) in the connecting cilium (CC) of retinal rod photoreceptors in frogs, as well as in the subcellular compartments bridged by the CC. In addition, the team measured the overall time for the protein concentration to equilibrate within and between compartments.
The results establish that the CC does not pose a major barrier to protein diffusion within the rod cell, but that the axial diffusion in each of the rod's compartments is substantially delayed relative to that in aqueous solution.
Source:
Rita Sullivan
Rockefeller University Press
Transport of proteins to and from cilia is crucial for normal cell function and survival, and interruption of transport has been implicated in degenerative diseases and neoplastic diseases, such as cancer. Researchers believe that cilia impose selective barriers to the movement of proteins, but because of the narrow and complex structure of cilia - with diameters near or below the resolution of light microscopy - this hypothesis has been difficult to examine.
Using confocal and multiphoton microscopy, Calvert and his team - including William Schiesser (Lehigh University) and Edward Pugh (University of California, Davis) - measured the mobility of PAGFP (photoactivatable green fluorescent protein) in the connecting cilium (CC) of retinal rod photoreceptors in frogs, as well as in the subcellular compartments bridged by the CC. In addition, the team measured the overall time for the protein concentration to equilibrate within and between compartments.
The results establish that the CC does not pose a major barrier to protein diffusion within the rod cell, but that the axial diffusion in each of the rod's compartments is substantially delayed relative to that in aqueous solution.
Source:
Rita Sullivan
Rockefeller University Press
четверг, 16 июня 2011 г.
First Ever High Resolution Observations Of DNA Unfolding
The separation of the two DNA strands occurs in millionths of a second. Consequently, it is extremely difficult to study this phenomenon experimentally and researchers must rely on computational simulations. After four years of fine-tuning an effective physical model and massive use of the supercomputer Mare Nostrum, researchers at IRB Barcelona and the Barcelona Supercomputing Center (BSC) have managed to produce the first realistic simulation of DNA opening at high resolution. The scientists Modesto Orozco, group leader of the Molecular Modelling and Bioinformatics Group at IRB Barcelona, Full Professor of Biochemistry and Molecular Biology at the University of Barcelona and director of the Life Sciences Dept. at the BSC, and Alberto PГ©rez, "Juan de la Cierva" researcher at BSC, currently at the University of California, San Francisco, (U.S.) publish their findings in a leading international chemistry journal, Angewandte Chemie.
Alberto PГ©rez explains that "many of the functions of DNA come about when its two strands separate, when, for example, it has to replicate during cell division or in repair processes. With this study, we propose a mechanism for this process, which in turn, will lead to new experiments for its final corroboration".
The researchers have studied a small DNA fragment, of 12 base pairs (the human genomes has about 3,000 million base pairs), and have obtained 10 million structural snapshots of how DNA unfolds. In this process they have revealed the two main ways by which the natural folded structure move to an unfolded state. "This project", explains Prof. Orozco, "is part of a greater objective of the lab: to attempt to understand the changes that the DNA structure undergoes in biological processes that occur within the cell, such as the expression and repression of genes or DNA replication and transcription."
DNA holds the genetic information of living organisms and its double helical structure was discovered more than 50 years ago by Watson and Crick. DNA and the proteins that modify it are the most important therapeutic targets in several pathologies, and particularly in cancer. The work performed at IRB Barcelona provides a detailed view of the mechanism through which one of the most crucial processes in DNA occurs, and opens up new prospects regarding the connection between physical properties, functionality and pharmacological effect. The final objective is to achieve that new breakthroughs turn DNA into a universal pharmacological target.
Source: Institute for Research in Biomedicine-IRB
Alberto PГ©rez explains that "many of the functions of DNA come about when its two strands separate, when, for example, it has to replicate during cell division or in repair processes. With this study, we propose a mechanism for this process, which in turn, will lead to new experiments for its final corroboration".
The researchers have studied a small DNA fragment, of 12 base pairs (the human genomes has about 3,000 million base pairs), and have obtained 10 million structural snapshots of how DNA unfolds. In this process they have revealed the two main ways by which the natural folded structure move to an unfolded state. "This project", explains Prof. Orozco, "is part of a greater objective of the lab: to attempt to understand the changes that the DNA structure undergoes in biological processes that occur within the cell, such as the expression and repression of genes or DNA replication and transcription."
DNA holds the genetic information of living organisms and its double helical structure was discovered more than 50 years ago by Watson and Crick. DNA and the proteins that modify it are the most important therapeutic targets in several pathologies, and particularly in cancer. The work performed at IRB Barcelona provides a detailed view of the mechanism through which one of the most crucial processes in DNA occurs, and opens up new prospects regarding the connection between physical properties, functionality and pharmacological effect. The final objective is to achieve that new breakthroughs turn DNA into a universal pharmacological target.
Source: Institute for Research in Biomedicine-IRB
Caddisflies' Underwater Silk Adhesive Might Suture Wounds
Like silkworm moths, butterflies and spiders, caddisfly larvae spin silk, but they do so underwater instead on dry land. Now, University of Utah researchers have discovered why the fly's silk is sticky when wet and how that may make it valuable as an adhesive tape during surgery.
"Silk from caddisfly larvae - known to western fly fishermen as 'rock rollers' - may be useful some day as a medical bioadhesive for sticking to wet tissues," says Russell Stewart, an associate professor of bioengineering and principal author of a new study of the fly silk's chemical and structural properties.
"I picture it as sort of a wet Band-Aid, maybe used internally in surgery - like using a piece of tape to close an incision as opposed to sutures," he adds. "Gluing things together underwater is not easy. Have you ever tried to put a Band-Aid on in the shower? This insect has been doing this for 150 million to 200 million years."
The new study, funded by the National Science Foundation, is set for publication this week in Biomacromolecules, a journal of the American Chemical Society.
There are thousands of caddisfly species worldwide in an order of insects named Trichoptera that are related to Lepidoptera, the order that includes moths and butterflies that spin dry silk. Because caddisflies are eaten by trout, fly fishermen use caddisfly lures. Some species spend their larval stages developing underwater, and build an inch-long, tube-shaped case or shelter around themselves using sticky silk and grains of rock or sand. Other species use silk, small sticks and pieces of leaves.
Each larva has a head and four legs that stick out from the tube. The larval case often is conical because it gets wider as the larva grows. A caddisfly larva eventually pupates, sealing off the tube as it develops into an adult fly and then hatches.
Aquatic caddisflies and terrestrial butterflies and moths diverged from a common silk-spinning ancestor some 150 million to 200 million years ago. Caddisflies now live around the world in waters ranging from fast streams to quiet marshes.
"The caddisflies' successful penetration into diverse aquatic habitats is largely due to the inventive use by their larva of underwater silk to build elaborate structures for protection and food gathering," the new study says.
Caddisflies fall into subgroups. Brachycentrus echo, the species Stewart studied, is one of the casemakers, which build their case and then drag it along with them underwater as they forage for food. Some caddisfly larva are retreatmakers, which build a stationary dome-shaped shelter glued to a rock, with a silk net to catch passing food.
From Sea Glue to Sticky Fly Silk
Stewart studies natural adhesives, including glue produced in intertidal ocean waters by the sandcastle worm. It has potential as glue for repairing small broken bones.
He got interested in caddisfly larva adhesive silk tape after he was contacted by a Smithsonian Institution scientist who showed him several of the tube-shaped larval cases.
"We looked inside a case through a microscope and saw these silk struts between the rocks and realized this is really interesting," he says. "So I came home and put on my fly fishing boots and started wandering mountain streams looking for caddisfly larvae."
Stewart and study co-author Ching Shuen Wang - who works in Stewart's lab - studied the caddisfly species B. echo from the lower Provo River about an hour south of Salt Lake City. Bioengineering undergraduate student Nick Ashton gathered the fly larvae and figured out how to keep them alive in the lab.
"There's just a fascinating diversity of these insects. Their adhesive is able to bond to a wide range of surfaces underwater: soft and hard, organic and inorganic. If we could copy this adhesive it would be useful on a wide range of tissue types."
Caddisfly larvae extrude adhesive silk ribbon out of an organ known as the spinneret. The products of two silk glands converge there, so the extruded adhesive looks like a double ribbon with a seam the long way. The larvae weave this sticky mesh back and forth around sand grains, sticks or leaf pieces to create the tubes they occupy.
Stewart and colleagues grew caddisfly larvae in aquariums, but with glass beads instead of the sand and rock grains found in streams. The larvae expanded their rock cases using the beads, which were glued together from the inside by wet silk ribbons.
The researchers broke off some beads to obtain clean samples of silk. They analyzed the silk using several methods, including scanning electron microscopy, which showed how silk fibers stitched together the glass beads from inside of the shelter case.
"It's like using Scotch tape on the inside of a box to hold it together," Stewart says. "It's really like a tape more than anything else - a tape that works underwater."
Stewart hasn't studied the strength of the caddisfly silk, but plans to do so.
"Individual threads aren't very strong, but it lays down dozens of them. If we can copy this material and make tape out of it, the bond strength would go up dramatically."
The Chemistry and Structure of Wet Silk from Caddisflies
Stewart's study included detailed analysis of the chemistry and structure of the caddisfly silk, showing how it is similar to what silkworm moths produce for use in textiles and even to spider web silk, but with adaptations that make it work underwater.
Stewart says his goal was to characterize the adhesive silk fiber "for the purpose of trying to copy it" so a synthetic version can be used as a surgical adhesive.
He found the caddisfly silk is a fiber made of large proteins named fibroin (fye-bro-in) with an amino acid named serine making up a fifth of the amino acids in fibroin.
The key difference between dry silks from moths and butterflies and wet silks from caddisflies is that the serines in the silk from caddisflies are "phosphorylated," meaning phosphates are added to the serines as the fibroin silk protein is synthesized.
"Phosphates are well-known adhesion promoters used in dental fixtures such as crowns or fillings," says Stewart. "They are also in latex paints that are water-based, and the phosphates increase the adhesion of those paints. The paint industry discovered this fairly recently. Caddisflies have been doing this for at least 150 million years."
The phosphates attached to the serines are negatively charged. Other amino acids in the protein are positively charged. Stewart found that is a key factor in making silk underwater. Chains of proteins - each with alternating regions of positive and negative charges - line up in parallel with positive and negative charges attracting each other.
"Imagine those chains aligned side-by-side, but staggered so the pluses and minuses are lined up, which then forms silk fibers with lots and lots of these protein chains in one fiber," Stewart says. "You wouldn't be able to make shirts out of it, but you might be able to make wet Band-Aids."
Stewart made a counterintuitive finding about how wet silks are made. "These fibroin proteins that make up the silks are water-soluble because of the electrical charges. Ironically - and this is our hypothesis for now - the association of those plus or minus charges makes them water-insoluble. This is how you make a silk fiber under water."
Comparison with amino acids from three other caddisfly species found great similarities, suggesting other caddisflies also use phosphorylation to spin silk underwater.
Stewart says caddisfly silk and sandcastle worm glue are similar: their proteins are heavily phosphorylated and have a large number of positively charged amino acids.
He says the ability to make adhesives underwater now has been identified in four phyla - major categories of living organisms - that include caddisflies, sandcastle worms, mussels and sea cucumbers.
"They came to this underwater adhesion solution completely independently," showing that it repeatedly evolved because of its value in helping the creatures live and thrive, Stewart says.
Source:
Lee Siegel
University of Utah
"Silk from caddisfly larvae - known to western fly fishermen as 'rock rollers' - may be useful some day as a medical bioadhesive for sticking to wet tissues," says Russell Stewart, an associate professor of bioengineering and principal author of a new study of the fly silk's chemical and structural properties.
"I picture it as sort of a wet Band-Aid, maybe used internally in surgery - like using a piece of tape to close an incision as opposed to sutures," he adds. "Gluing things together underwater is not easy. Have you ever tried to put a Band-Aid on in the shower? This insect has been doing this for 150 million to 200 million years."
The new study, funded by the National Science Foundation, is set for publication this week in Biomacromolecules, a journal of the American Chemical Society.
There are thousands of caddisfly species worldwide in an order of insects named Trichoptera that are related to Lepidoptera, the order that includes moths and butterflies that spin dry silk. Because caddisflies are eaten by trout, fly fishermen use caddisfly lures. Some species spend their larval stages developing underwater, and build an inch-long, tube-shaped case or shelter around themselves using sticky silk and grains of rock or sand. Other species use silk, small sticks and pieces of leaves.
Each larva has a head and four legs that stick out from the tube. The larval case often is conical because it gets wider as the larva grows. A caddisfly larva eventually pupates, sealing off the tube as it develops into an adult fly and then hatches.
Aquatic caddisflies and terrestrial butterflies and moths diverged from a common silk-spinning ancestor some 150 million to 200 million years ago. Caddisflies now live around the world in waters ranging from fast streams to quiet marshes.
"The caddisflies' successful penetration into diverse aquatic habitats is largely due to the inventive use by their larva of underwater silk to build elaborate structures for protection and food gathering," the new study says.
Caddisflies fall into subgroups. Brachycentrus echo, the species Stewart studied, is one of the casemakers, which build their case and then drag it along with them underwater as they forage for food. Some caddisfly larva are retreatmakers, which build a stationary dome-shaped shelter glued to a rock, with a silk net to catch passing food.
From Sea Glue to Sticky Fly Silk
Stewart studies natural adhesives, including glue produced in intertidal ocean waters by the sandcastle worm. It has potential as glue for repairing small broken bones.
He got interested in caddisfly larva adhesive silk tape after he was contacted by a Smithsonian Institution scientist who showed him several of the tube-shaped larval cases.
"We looked inside a case through a microscope and saw these silk struts between the rocks and realized this is really interesting," he says. "So I came home and put on my fly fishing boots and started wandering mountain streams looking for caddisfly larvae."
Stewart and study co-author Ching Shuen Wang - who works in Stewart's lab - studied the caddisfly species B. echo from the lower Provo River about an hour south of Salt Lake City. Bioengineering undergraduate student Nick Ashton gathered the fly larvae and figured out how to keep them alive in the lab.
"There's just a fascinating diversity of these insects. Their adhesive is able to bond to a wide range of surfaces underwater: soft and hard, organic and inorganic. If we could copy this adhesive it would be useful on a wide range of tissue types."
Caddisfly larvae extrude adhesive silk ribbon out of an organ known as the spinneret. The products of two silk glands converge there, so the extruded adhesive looks like a double ribbon with a seam the long way. The larvae weave this sticky mesh back and forth around sand grains, sticks or leaf pieces to create the tubes they occupy.
Stewart and colleagues grew caddisfly larvae in aquariums, but with glass beads instead of the sand and rock grains found in streams. The larvae expanded their rock cases using the beads, which were glued together from the inside by wet silk ribbons.
The researchers broke off some beads to obtain clean samples of silk. They analyzed the silk using several methods, including scanning electron microscopy, which showed how silk fibers stitched together the glass beads from inside of the shelter case.
"It's like using Scotch tape on the inside of a box to hold it together," Stewart says. "It's really like a tape more than anything else - a tape that works underwater."
Stewart hasn't studied the strength of the caddisfly silk, but plans to do so.
"Individual threads aren't very strong, but it lays down dozens of them. If we can copy this material and make tape out of it, the bond strength would go up dramatically."
The Chemistry and Structure of Wet Silk from Caddisflies
Stewart's study included detailed analysis of the chemistry and structure of the caddisfly silk, showing how it is similar to what silkworm moths produce for use in textiles and even to spider web silk, but with adaptations that make it work underwater.
Stewart says his goal was to characterize the adhesive silk fiber "for the purpose of trying to copy it" so a synthetic version can be used as a surgical adhesive.
He found the caddisfly silk is a fiber made of large proteins named fibroin (fye-bro-in) with an amino acid named serine making up a fifth of the amino acids in fibroin.
The key difference between dry silks from moths and butterflies and wet silks from caddisflies is that the serines in the silk from caddisflies are "phosphorylated," meaning phosphates are added to the serines as the fibroin silk protein is synthesized.
"Phosphates are well-known adhesion promoters used in dental fixtures such as crowns or fillings," says Stewart. "They are also in latex paints that are water-based, and the phosphates increase the adhesion of those paints. The paint industry discovered this fairly recently. Caddisflies have been doing this for at least 150 million years."
The phosphates attached to the serines are negatively charged. Other amino acids in the protein are positively charged. Stewart found that is a key factor in making silk underwater. Chains of proteins - each with alternating regions of positive and negative charges - line up in parallel with positive and negative charges attracting each other.
"Imagine those chains aligned side-by-side, but staggered so the pluses and minuses are lined up, which then forms silk fibers with lots and lots of these protein chains in one fiber," Stewart says. "You wouldn't be able to make shirts out of it, but you might be able to make wet Band-Aids."
Stewart made a counterintuitive finding about how wet silks are made. "These fibroin proteins that make up the silks are water-soluble because of the electrical charges. Ironically - and this is our hypothesis for now - the association of those plus or minus charges makes them water-insoluble. This is how you make a silk fiber under water."
Comparison with amino acids from three other caddisfly species found great similarities, suggesting other caddisflies also use phosphorylation to spin silk underwater.
Stewart says caddisfly silk and sandcastle worm glue are similar: their proteins are heavily phosphorylated and have a large number of positively charged amino acids.
He says the ability to make adhesives underwater now has been identified in four phyla - major categories of living organisms - that include caddisflies, sandcastle worms, mussels and sea cucumbers.
"They came to this underwater adhesion solution completely independently," showing that it repeatedly evolved because of its value in helping the creatures live and thrive, Stewart says.
Source:
Lee Siegel
University of Utah
среда, 15 июня 2011 г.
Link Between Psychological Stress And Overeating Discovered By Yerkes Researchers
Researchers at the Yerkes National Primate Research Center, Emory University, have found socially subordinate female rhesus macaques over consume calorie-rich foods at a significantly higher level than do dominant females.
The study, which is available in the online edition of Physiology and Behavior, is a critical step in understanding the psychological basis for the sharp increase in obesity across all age groups since the mid-1970s. The study also is the first to show how food intake can be reliably and automatically measured, thus identifying the optimal animal model and setting for future obesity studies.
Because the relationship between diet, psychological stress and social and environmental factors is complex, Mark Wilson, PhD, chief of the Division of Psychobiology at Yerkes, and his research team set out to determine whether individuals chronically exposed to psychologically stressful environments over consume calorie-rich foods. To do this, they studied the feeding patterns of socially housed female rhesus macaques, which are organized by a dominance hierarchy that maintains group stability through continual harassment and threat of aggression. Such structure is a constant psychological stress to subordinates.
During the study, female macaques were given access to a sweet but low-fat diet and a high-fat diet for 21 days each. For a 21-day period between each test diet, the group was able to access standard monkey chow only. To track feeding patterns, automated feeders dispensed a pellet of either the low-fat or high-fat chow when activated by a microchip implanted in each female's wrist. Researchers found socially subordinate females consumed significantly more of both the low-fat diet and the high-fat diet throughout a 24-hour period, while socially dominant females ate significantly less than subordinate animals and restricted their feedings to daytime hours.
This difference in feeding behavior resulted in accelerated weight gain and an increase in fat-derived hormones in subordinate females. Dr. Wilson believes this may suggest profound changes in metabolism and the accumulation of body fat.
"Subordinates may be on a trajectory for metabolic problems. As this study shows, they prefer the high-fat diet and, as a result of the stress of being a subordinate, they have higher levels of the hormone cortisol. This may be involved in the redistribution of fat to visceral locations in the body, something that is clinically associated with type II diabetes metabolic syndrome," continued Dr. Wilson.
Using Yerkes' extensive neuroimaging capabilities, Dr. Wilson and his research team next will attempt to determine the neurochemical basis for why subordinate females overeat; specifically, whether appetite signals and brain areas associated with reward and satisfaction differ between subordinate and dominant females.
For more than seven decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of HealthГђfunded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.
Within the fields of microbiology and immunology, neuroscience, psychobiology and sensory-motor systems, the center's research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer's disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Parkinson's and Alzheimer's; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.
Source: Emily Rios
Emory University
The study, which is available in the online edition of Physiology and Behavior, is a critical step in understanding the psychological basis for the sharp increase in obesity across all age groups since the mid-1970s. The study also is the first to show how food intake can be reliably and automatically measured, thus identifying the optimal animal model and setting for future obesity studies.
Because the relationship between diet, psychological stress and social and environmental factors is complex, Mark Wilson, PhD, chief of the Division of Psychobiology at Yerkes, and his research team set out to determine whether individuals chronically exposed to psychologically stressful environments over consume calorie-rich foods. To do this, they studied the feeding patterns of socially housed female rhesus macaques, which are organized by a dominance hierarchy that maintains group stability through continual harassment and threat of aggression. Such structure is a constant psychological stress to subordinates.
During the study, female macaques were given access to a sweet but low-fat diet and a high-fat diet for 21 days each. For a 21-day period between each test diet, the group was able to access standard monkey chow only. To track feeding patterns, automated feeders dispensed a pellet of either the low-fat or high-fat chow when activated by a microchip implanted in each female's wrist. Researchers found socially subordinate females consumed significantly more of both the low-fat diet and the high-fat diet throughout a 24-hour period, while socially dominant females ate significantly less than subordinate animals and restricted their feedings to daytime hours.
This difference in feeding behavior resulted in accelerated weight gain and an increase in fat-derived hormones in subordinate females. Dr. Wilson believes this may suggest profound changes in metabolism and the accumulation of body fat.
"Subordinates may be on a trajectory for metabolic problems. As this study shows, they prefer the high-fat diet and, as a result of the stress of being a subordinate, they have higher levels of the hormone cortisol. This may be involved in the redistribution of fat to visceral locations in the body, something that is clinically associated with type II diabetes metabolic syndrome," continued Dr. Wilson.
Using Yerkes' extensive neuroimaging capabilities, Dr. Wilson and his research team next will attempt to determine the neurochemical basis for why subordinate females overeat; specifically, whether appetite signals and brain areas associated with reward and satisfaction differ between subordinate and dominant females.
For more than seven decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of HealthГђfunded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.
Within the fields of microbiology and immunology, neuroscience, psychobiology and sensory-motor systems, the center's research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer's disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Parkinson's and Alzheimer's; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.
Source: Emily Rios
Emory University
вторник, 14 июня 2011 г.
Boston IVF Egg Freezing Study Results In Pregnancy
Boston IVF today announced a
participant in their fully enrolled egg freezing study has become pregnant.
This is the first pregnancy in Massachusetts to result from egg freezing.
The study was performed by Boston IVF and sponsored by an independent
medical grant from EMD Serono, a biotech company with an area of focus on
infertility.
The process of successfully freezing eggs is very delicate and arduous.
The egg is the largest cell in the human body. It is comprised mostly of
water and thus very difficult to freeze without destroying it. Boston IVF
uses technology that replaces the fluid with molecules that make the egg
less vulnerable to freezing and more viable for fertilization once they are
thawed.
"The pregnancy resulting from this study is a major milestone for
Boston IVF and holds enormous promise for patients who hope to preserve
their fertility by freezing their eggs so that they can become pregnant at
a later time in their lives," said. Dr. Michael Alper, medical director of
Boston IVF and lead investigator in the study. "We now have the option of
suspending a women's biological clock. Egg freezing is also particularly
wonderful for cancer patients who may become sterile from chemotherapy.
Under the leadership of Boston IVF's scientific director, Dr. Douglas
Powers, we plan to continue our research to perfect technologies that will
provide patients with the most effective and safest options for building
families."
Boston IVF is internationally renowned for its technologically advanced
treatments and offers patients the opportunity to participate in research
studies. There are currently ongoing studies both in standard IVF and egg
freezing that offer patients the opportunity to become parents with the
latest technology.
About Boston IVF
Established in 1986, Boston IVF is one of America's most successful
fertility centers. Using a team approach to meet every aspect of patients'
needs, Boston IVF is committed to giving everyone the chance to build a
family. Boston IVF provides patients with unparalleled medical care and the
best experience with the expertise of premier doctors and professional
staff, who are affiliated with Harvard Medical School. It is world renowned
for its highly successful and innovative infertility treatments, highest
quality service, state-of-the-art methods, ongoing scientific research, and
on-site complementary healthcare at its Domar Center. Boston IVF has
convenient locations in Waltham, MA, Brookline, MA, and Quincy, MA, and its
doctors see patients at leading hospitals throughout Massachusetts and
Maine.
Boston IVF
bostonivf/
participant in their fully enrolled egg freezing study has become pregnant.
This is the first pregnancy in Massachusetts to result from egg freezing.
The study was performed by Boston IVF and sponsored by an independent
medical grant from EMD Serono, a biotech company with an area of focus on
infertility.
The process of successfully freezing eggs is very delicate and arduous.
The egg is the largest cell in the human body. It is comprised mostly of
water and thus very difficult to freeze without destroying it. Boston IVF
uses technology that replaces the fluid with molecules that make the egg
less vulnerable to freezing and more viable for fertilization once they are
thawed.
"The pregnancy resulting from this study is a major milestone for
Boston IVF and holds enormous promise for patients who hope to preserve
their fertility by freezing their eggs so that they can become pregnant at
a later time in their lives," said. Dr. Michael Alper, medical director of
Boston IVF and lead investigator in the study. "We now have the option of
suspending a women's biological clock. Egg freezing is also particularly
wonderful for cancer patients who may become sterile from chemotherapy.
Under the leadership of Boston IVF's scientific director, Dr. Douglas
Powers, we plan to continue our research to perfect technologies that will
provide patients with the most effective and safest options for building
families."
Boston IVF is internationally renowned for its technologically advanced
treatments and offers patients the opportunity to participate in research
studies. There are currently ongoing studies both in standard IVF and egg
freezing that offer patients the opportunity to become parents with the
latest technology.
About Boston IVF
Established in 1986, Boston IVF is one of America's most successful
fertility centers. Using a team approach to meet every aspect of patients'
needs, Boston IVF is committed to giving everyone the chance to build a
family. Boston IVF provides patients with unparalleled medical care and the
best experience with the expertise of premier doctors and professional
staff, who are affiliated with Harvard Medical School. It is world renowned
for its highly successful and innovative infertility treatments, highest
quality service, state-of-the-art methods, ongoing scientific research, and
on-site complementary healthcare at its Domar Center. Boston IVF has
convenient locations in Waltham, MA, Brookline, MA, and Quincy, MA, and its
doctors see patients at leading hospitals throughout Massachusetts and
Maine.
Boston IVF
bostonivf/
понедельник, 13 июня 2011 г.
Allergic Response Tied To Lipid Molecules In Cell Membrane
A team of Penn State University researchers is the first to demonstrate that lipid molecules in cell membranes participate in mammals' reactions to allergens in a living cell. The finding will help scientists better understand how allergy symptoms are triggered, and could contribute to the creation of improved drugs to treat them. The work will be reported in the 14 March issue of the Journal of Biological Chemistry.
The team studied clusters of cholesterol-rich lipid molecules that they believe serve as platforms for the receptors that receive antibodies, the proteins that protect the body from allergens. In this case, the team examined IgE antibodies, which upon binding to their receptors initiate a cell's release of histamine--the substance that causes the unpleasant, but beneficial, mucous production, congestion, and itchiness associated with allergies. "This research is basically the molecular foundation for why many people sneeze in the spring," said Ahmed Heikal, an associate professor in the Department of Bioengineering and a leader of the project.
While the idea that lipid clusters--also known as lipid domains--are involved in the allergic response is not new, the Penn State team is the first to document this connection in a living cell under physiological conditions. "No one has observed the domains in action because they are too small and too transient--held together by very weak molecular interactions--to be viewed with a light microscope," said Erin Sheets, a Penn State assistant professor of chemistry who also is a leader of the project. "To overcome this challenge," added Heikal, "we used a combination of imaging and spectroscopy techniques that we are developing in our laboratories.
In their experiment, the researchers first labeled the cell membrane and IgE antibodies with two different fluorescent tags. Next, they introduced an allergen and watched as it bound to receptors on the cell membrane, thus initiating an allergic response.
But to demonstrate that this activity was taking place within the lipid domain, the researchers had to take advantage of a property of fluorescence, called fluorescence lifetime, in which molecules are excited with very short laser pulses. The length of time a molecule remains in its excited state before emitting a photon--the fluorescence lifetime--provides unique information about the fluorescently-labeled molecule's environment and its chemical structure. For example, a particular molecule might relax to its lowest-energy state quickly or slowly depending on whether it is exposed to a solvent.
"We previously showed that our fluorescently-labeled membrane probe has a longer lifetime within a cholesterol-rich lipid domain," said Sheets. "Here we show that changes in this lifetime follow the changes that occur during the first steps in the allergic response process. Our results also show that lipid domains in the cell membrane associate with IgE antibodies and their receptors in the initial stages of an allergic reaction."
In the future, Sheets and Heikal plan to apply the team's discoveries to a project involving aging. During the aging process, T cells, which protect the body from foreign substances like viruses and cancer cells, can lose their ability to signal effectively. Sheets and Heikal plan to use these fluorescence-lifetime imaging tools to examine the structure and integrity of T-cell membranes with a goal of determining why they lose their knack for signalling and how this problem can be corrected.
"We want to compare the effectiveness of signaling in young T cells, which clear out debris quickly, to old T cells, which are not as efficient," said Sheets. "I think it will be a pretty cool application of our technique."
Other Penn State scientists who contributed to this research include Angel Davey and Keith Krise, both Ph.D. students in the Department of Chemistry. The work was funded by Penn State, the National Science Foundation, the Commonwealth of Pennsylvania, the American Chemical Society, and the National Institutes of Health.
Source: Barbara K. Kennedy
Penn State
The team studied clusters of cholesterol-rich lipid molecules that they believe serve as platforms for the receptors that receive antibodies, the proteins that protect the body from allergens. In this case, the team examined IgE antibodies, which upon binding to their receptors initiate a cell's release of histamine--the substance that causes the unpleasant, but beneficial, mucous production, congestion, and itchiness associated with allergies. "This research is basically the molecular foundation for why many people sneeze in the spring," said Ahmed Heikal, an associate professor in the Department of Bioengineering and a leader of the project.
While the idea that lipid clusters--also known as lipid domains--are involved in the allergic response is not new, the Penn State team is the first to document this connection in a living cell under physiological conditions. "No one has observed the domains in action because they are too small and too transient--held together by very weak molecular interactions--to be viewed with a light microscope," said Erin Sheets, a Penn State assistant professor of chemistry who also is a leader of the project. "To overcome this challenge," added Heikal, "we used a combination of imaging and spectroscopy techniques that we are developing in our laboratories.
In their experiment, the researchers first labeled the cell membrane and IgE antibodies with two different fluorescent tags. Next, they introduced an allergen and watched as it bound to receptors on the cell membrane, thus initiating an allergic response.
But to demonstrate that this activity was taking place within the lipid domain, the researchers had to take advantage of a property of fluorescence, called fluorescence lifetime, in which molecules are excited with very short laser pulses. The length of time a molecule remains in its excited state before emitting a photon--the fluorescence lifetime--provides unique information about the fluorescently-labeled molecule's environment and its chemical structure. For example, a particular molecule might relax to its lowest-energy state quickly or slowly depending on whether it is exposed to a solvent.
"We previously showed that our fluorescently-labeled membrane probe has a longer lifetime within a cholesterol-rich lipid domain," said Sheets. "Here we show that changes in this lifetime follow the changes that occur during the first steps in the allergic response process. Our results also show that lipid domains in the cell membrane associate with IgE antibodies and their receptors in the initial stages of an allergic reaction."
In the future, Sheets and Heikal plan to apply the team's discoveries to a project involving aging. During the aging process, T cells, which protect the body from foreign substances like viruses and cancer cells, can lose their ability to signal effectively. Sheets and Heikal plan to use these fluorescence-lifetime imaging tools to examine the structure and integrity of T-cell membranes with a goal of determining why they lose their knack for signalling and how this problem can be corrected.
"We want to compare the effectiveness of signaling in young T cells, which clear out debris quickly, to old T cells, which are not as efficient," said Sheets. "I think it will be a pretty cool application of our technique."
Other Penn State scientists who contributed to this research include Angel Davey and Keith Krise, both Ph.D. students in the Department of Chemistry. The work was funded by Penn State, the National Science Foundation, the Commonwealth of Pennsylvania, the American Chemical Society, and the National Institutes of Health.
Source: Barbara K. Kennedy
Penn State
Detail On How Low Blood Flow Promotes Vascular Disease
Researchers have found the first direct proof that a key protein drives the clogging of arteries in two ways, and that lowering levels of it opens them up, according to study results published in the June edition of the journal Circulation. The work establishes cyclophilin A as an exciting target in the design of drugs against atherosclerosis, the number one cause of heart attacks and strokes, which occur when vessels become completely blocked. While the study was in mice, higher levels of the study protein have also been found in the blood of human patients with diseased blood vessels.
The current results build on three major discoveries in cardiovascular science in the last 20 years. The first is that fast blood flow, as it moves along the straight portions of blood vessel walls, creates frictional force that protects those areas against atherosclerosis. At the points where one vessel branches into two, however, blood flow is slowed, frictional force lessened and atherosclerotic plaques more likely to form. Among the consequences of low flow is the creation of highly reactive molecules called reactive oxygen species, which oxidize molecules they encounter and impair vascular function.
The second discovery was that the reaction of the body's immune system to fatty build-up in arteries is as great a contributor to heart attack risk as the fatty build-up itself. Vessel walls mistake fatty deposits for intruders, akin to bacteria, and call in white blood cells to prevent infection. The same cells, unfortunately, also cause inflammation that contributes to clogs and generate more reactive oxygen species.
In the third discovery, researchers realized that blood vessels to do not just stand by as fatty deposits build up, but instead fight to stay open by aggressively growing (remodeling). Once they reach their growth limit however, the same growth that kept vessels open for so long begins contributing to the clogs by thickening vessel walls. The current study unites the three discoveries by providing strong evidence that cyclophilin A, a protein involved in the immune response, has dual roles in vascular disease. It recruits immune cells that cause inflammation, and it drives pathogenic growth and remodeling, when triggered by reactive oxygen species in diseased blood vessels.
"For years researchers worldwide have sought to determine exactly how low blood flow and the immune reaction to cholesterol deposits, along with the reactive oxygen species created by both, drive the progression of atherosclerosis," said Bradford C. Berk, M.D., Ph.D., professor of Medicine in the Aab Cardiovascular Research Institute within the University of Rochester Medical Center, and senior author of the study. "We are tremendously excited by these results because they provide solid evidence that cyclophilin A is at the center of it all."
Study Details
The study results reflect blood vessel anatomy. Blood flows through the innermost part of a vessel called the lumen. The inside of that inner tube is lined with a layer of endothelial cells, which is surrounded by the fibrous cells of the intima, which is surrounded by a layer of smooth muscle cells in the media. Many blood vessels are muscular because the flexing of such muscle helps to control blood flow (blood pressure).
To examine the reaction of CyPA signaling to the overproduction of reactive oxygen species, Berk's team genetically engineered one group of mice to produce less CyPA, another group to make more, and compared both groups to "normal" mice as all three groups experienced reduced blood flow in the carotid artery. Reduced blood flow increased CyPA expression in the vascular wall, and promoted the migration of smooth muscle cells into the intima, where they began to grow (proliferate) and contribute to the formation of atherosclerotic lesions. Reduced flow, and the related increase in CyPA signaling, also caused the accumulation of inflammatory cells, an important component in the disease-related thickening of vessel walls. The effects were pronounced in the mice with extra capacity for CyPA production, and lessened in those with less CyPA.
Specifically, the current study demonstrated for the first time in a live animal that cyclophilin A (CyPA) is secreted specifically by smooth muscle cells in response to the production of reactive oxygen species with several consequences. First, CyPA signals for the production of pro-inflammatory molecules like E-selectin and vascular cell adhesion molecule 1 (VCAM-1), both of which call in immune cells circulating in the blood to the site of a cholesterol deposit in blood vessel wall and enable them to stick to it. This represents a first step in the inflammatory component of plaque formation.
The team also showed CyPA stimulates important pathways (e.g. the ERK1/2 and JAK/STAT) that drive smooth muscle cells to divide and grow. Furthermore, CyPA may activate matrix metalloproteinases, enzymes that break down the barrier that usually keeps smooth muscle cells out of the intima, the site of their disease-related proliferation.
Along with first author Kimio Satoh, M.D., Ph.D., the paper was co-authored by Tetsuya Matoba, M.D., Ph.D.; Jun Suzuki, M.D., Ph.D.; Michael R. O'Dell, BS; Patrizia Nigro, Ph.D.; Zhaoqiang Cui, Ph.D.; Amy Mohan, BS; Shi Pan, Ph.D.; Lingli Li, M.D., Ph.D.; Zheng-Gen Jin, Ph.D.; Chen Yan, Ph.D.; Jun-ichi Abe, M.D., Ph.D.; and Bradford C. Berk, M.D., Ph.D., all under the auspices of the Aab CVRI and the Department of Medicine within the University of Rochester School of Medicine and Dentistry. The National Institutes of Health and Japan Heart Foundation supported the work.
"Cyclophilin A first gained attention through its association with an existing drug called cyclosporin A, which is widely used to prevent patients from rejecting newly transplanted organs," said Berk, corresponding author for the study and chief executive officer of the Medical Center. "With these results, cyclophilin A becomes an important therapeutic target in its own right because our data proves that lowering CyPA levels, by lessening inflammation and misplaced growth, and should significantly increase blood flow through diseased arteries."
Source: Greg Williams
University of Rochester Medical Center
The current results build on three major discoveries in cardiovascular science in the last 20 years. The first is that fast blood flow, as it moves along the straight portions of blood vessel walls, creates frictional force that protects those areas against atherosclerosis. At the points where one vessel branches into two, however, blood flow is slowed, frictional force lessened and atherosclerotic plaques more likely to form. Among the consequences of low flow is the creation of highly reactive molecules called reactive oxygen species, which oxidize molecules they encounter and impair vascular function.
The second discovery was that the reaction of the body's immune system to fatty build-up in arteries is as great a contributor to heart attack risk as the fatty build-up itself. Vessel walls mistake fatty deposits for intruders, akin to bacteria, and call in white blood cells to prevent infection. The same cells, unfortunately, also cause inflammation that contributes to clogs and generate more reactive oxygen species.
In the third discovery, researchers realized that blood vessels to do not just stand by as fatty deposits build up, but instead fight to stay open by aggressively growing (remodeling). Once they reach their growth limit however, the same growth that kept vessels open for so long begins contributing to the clogs by thickening vessel walls. The current study unites the three discoveries by providing strong evidence that cyclophilin A, a protein involved in the immune response, has dual roles in vascular disease. It recruits immune cells that cause inflammation, and it drives pathogenic growth and remodeling, when triggered by reactive oxygen species in diseased blood vessels.
"For years researchers worldwide have sought to determine exactly how low blood flow and the immune reaction to cholesterol deposits, along with the reactive oxygen species created by both, drive the progression of atherosclerosis," said Bradford C. Berk, M.D., Ph.D., professor of Medicine in the Aab Cardiovascular Research Institute within the University of Rochester Medical Center, and senior author of the study. "We are tremendously excited by these results because they provide solid evidence that cyclophilin A is at the center of it all."
Study Details
The study results reflect blood vessel anatomy. Blood flows through the innermost part of a vessel called the lumen. The inside of that inner tube is lined with a layer of endothelial cells, which is surrounded by the fibrous cells of the intima, which is surrounded by a layer of smooth muscle cells in the media. Many blood vessels are muscular because the flexing of such muscle helps to control blood flow (blood pressure).
To examine the reaction of CyPA signaling to the overproduction of reactive oxygen species, Berk's team genetically engineered one group of mice to produce less CyPA, another group to make more, and compared both groups to "normal" mice as all three groups experienced reduced blood flow in the carotid artery. Reduced blood flow increased CyPA expression in the vascular wall, and promoted the migration of smooth muscle cells into the intima, where they began to grow (proliferate) and contribute to the formation of atherosclerotic lesions. Reduced flow, and the related increase in CyPA signaling, also caused the accumulation of inflammatory cells, an important component in the disease-related thickening of vessel walls. The effects were pronounced in the mice with extra capacity for CyPA production, and lessened in those with less CyPA.
Specifically, the current study demonstrated for the first time in a live animal that cyclophilin A (CyPA) is secreted specifically by smooth muscle cells in response to the production of reactive oxygen species with several consequences. First, CyPA signals for the production of pro-inflammatory molecules like E-selectin and vascular cell adhesion molecule 1 (VCAM-1), both of which call in immune cells circulating in the blood to the site of a cholesterol deposit in blood vessel wall and enable them to stick to it. This represents a first step in the inflammatory component of plaque formation.
The team also showed CyPA stimulates important pathways (e.g. the ERK1/2 and JAK/STAT) that drive smooth muscle cells to divide and grow. Furthermore, CyPA may activate matrix metalloproteinases, enzymes that break down the barrier that usually keeps smooth muscle cells out of the intima, the site of their disease-related proliferation.
Along with first author Kimio Satoh, M.D., Ph.D., the paper was co-authored by Tetsuya Matoba, M.D., Ph.D.; Jun Suzuki, M.D., Ph.D.; Michael R. O'Dell, BS; Patrizia Nigro, Ph.D.; Zhaoqiang Cui, Ph.D.; Amy Mohan, BS; Shi Pan, Ph.D.; Lingli Li, M.D., Ph.D.; Zheng-Gen Jin, Ph.D.; Chen Yan, Ph.D.; Jun-ichi Abe, M.D., Ph.D.; and Bradford C. Berk, M.D., Ph.D., all under the auspices of the Aab CVRI and the Department of Medicine within the University of Rochester School of Medicine and Dentistry. The National Institutes of Health and Japan Heart Foundation supported the work.
"Cyclophilin A first gained attention through its association with an existing drug called cyclosporin A, which is widely used to prevent patients from rejecting newly transplanted organs," said Berk, corresponding author for the study and chief executive officer of the Medical Center. "With these results, cyclophilin A becomes an important therapeutic target in its own right because our data proves that lowering CyPA levels, by lessening inflammation and misplaced growth, and should significantly increase blood flow through diseased arteries."
Source: Greg Williams
University of Rochester Medical Center
воскресенье, 12 июня 2011 г.
Breakthrough In Stem Cell Culturing
For the first time, human embryonic stem cells have been cultured under chemically controlled conditions without the use of animal substances, which is essential for future clinical uses. The method has been developed by researchers at Karolinska Institutet and is presented in the journal Nature Biotechnology.
Embryonic stem cells can be turned into any other type of cell in the body and have potential uses in treatments where sick cells need to be replaced. One problem, however, is that it is difficult to culture and develop human embryonic stem cells without simultaneously contaminating them. They are currently cultured with the help of proteins from animals, which rules out subsequent use in the treatment of humans. Alternatively the stem cells can be cultured on other human cells, known as feeder cells, but these release thousands of uncontrolled proteins and therefore lead to unreliable research results.
A research team at Karolinska Institutet has now managed to produce human stem cells entirely without the use of other cells or substances from animals. Instead they are cultured on a matrix of a single human protein: laminin-511.
"Now, for the first time, we can produce large quantities of human embryonic stem cells in an environment that is completely chemically defined," says professor Karl Tryggvason, who led the study. "This opens up new opportunities for developing different types of cell which can then be tested for the treatment of disease."
Together with researchers at the Harvard Stem Cell Institute, the researchers have also shown that in the same way they can culture what are known as reprogrammed stem cells, which have been converted "back" from tissue cells to stem cells.
Laminin-511 is part of our connective tissue and acts in the body as a matrix to which cells can attach. In the newly formed embryo, the protein is also needed to keep stem cells as stem cells. Once the embryo begins to develop different types of tissue, other types of laminin are needed.
Until now, different types of laminin have not been available to researchers, because they are almost impossible to extract from tissues and difficult to produce. Over the last couple of decades, Karl Tryggvason's research group has cloned the genes for most human laminins, studied their biological role, described two genetic laminin diseases and, in recent years, even managed to produce several types of laminin using gene technology. In this latest experiment, the researchers produced the laminin-511 using recombinant techniques.
Source: Karolinska Institutet
Embryonic stem cells can be turned into any other type of cell in the body and have potential uses in treatments where sick cells need to be replaced. One problem, however, is that it is difficult to culture and develop human embryonic stem cells without simultaneously contaminating them. They are currently cultured with the help of proteins from animals, which rules out subsequent use in the treatment of humans. Alternatively the stem cells can be cultured on other human cells, known as feeder cells, but these release thousands of uncontrolled proteins and therefore lead to unreliable research results.
A research team at Karolinska Institutet has now managed to produce human stem cells entirely without the use of other cells or substances from animals. Instead they are cultured on a matrix of a single human protein: laminin-511.
"Now, for the first time, we can produce large quantities of human embryonic stem cells in an environment that is completely chemically defined," says professor Karl Tryggvason, who led the study. "This opens up new opportunities for developing different types of cell which can then be tested for the treatment of disease."
Together with researchers at the Harvard Stem Cell Institute, the researchers have also shown that in the same way they can culture what are known as reprogrammed stem cells, which have been converted "back" from tissue cells to stem cells.
Laminin-511 is part of our connective tissue and acts in the body as a matrix to which cells can attach. In the newly formed embryo, the protein is also needed to keep stem cells as stem cells. Once the embryo begins to develop different types of tissue, other types of laminin are needed.
Until now, different types of laminin have not been available to researchers, because they are almost impossible to extract from tissues and difficult to produce. Over the last couple of decades, Karl Tryggvason's research group has cloned the genes for most human laminins, studied their biological role, described two genetic laminin diseases and, in recent years, even managed to produce several types of laminin using gene technology. In this latest experiment, the researchers produced the laminin-511 using recombinant techniques.
Source: Karolinska Institutet
суббота, 11 июня 2011 г.
Green Tea Blocks Benefits Of Cancer Drug, USC Study Finds
Contrary to popular assumptions about the health benefits of green tea, researchers at the University of Southern California (USC) have found that the widely used supplement renders a cancer drug used to treat multiple myeloma and mantle cell lymphoma completely ineffective in treating cancer.
The study, which found that a component of green tea extract (GTE) called EGCG destroys any anticancer activity of the drug Velcade in tumor-bearing mice, will be published in a future print edition of the journal, Blood. It is now available online at the journal's pre-publication First Edition website.
"Our finding that GTE or EGCG blocked the therapeutic action of Velcade was completely unexpected," says lead author Axel H. Schönthal, PhD, associate professor in the Department of Microbiology and Immunology at the Keck School of Medicine of USC. "Our hypothesis was that GTE or EGCG would enhance the anti-tumor effects of Velcade, and that a combination of GTE with Velcade (or EGCG with Velcade) would turn out to be a superior cancer treatment as compared to treatment with Velcade alone."
Herbal remedies, including green tea, have become a popular remedy for cancer patients dealing with side effects of chemotherapy. However, these supplements are unregulated and, for most, their beneficial and/or detrimental effects have not been qualified through research.
Using preclinical models and tumor-bearing mice, the researchers found that the unusually effective blockage of Velcade's therapeutic activity was based on the chemical interaction between molecules. The EGCG molecule and the Velcade molecule were able to form chemical bonds, meaning that the Velcade molecule could no longer bind to its intended target inside the tumor cells.
Clincal trials to verify these results in humans would be highly unethical to conduct, because of the predictably unfavorable outcome. Nevertheless, the researchers expect the results of the study to be applicable to cancer patients.
"The most immediate conclusion from our study is the strong advice that patients undergoing cancer therapy with Velcade must avoid green tea, and in particular all of its concentrated products that are freely available from health food stores," says Schönthal. "It is important to spread this message to health care providers who administer Velcade to patients."
Schönthal points out that for patients on Velcade, supplementing with green tea products should reduce the burden of harsh side effects - which might be attractive to the patient, but comes at a high cost.
"Essentially, in addition to not being able to attack tumor cells, Velcade would be unable to cause side effects either," he says. "As a result, the patient would feel a lot better and conclude that the consumption of GTE helped cope with side effects - while in reality, Velcade simply wasn't active in the first place."
The research findings are part of a larger project run by the team called "Yin-Yang Properties of Green Tea Extract in Combination Cancer Chemotherapy: From Encouragingly Beneficial to Dangerously Detrimental."
"Obviously, the combination of GTE or EGCG with Velcade is an example of 'dangerously detrimental,' "Schönthal says. "But we are also studying another well-established chemotherapeutic drug, where the inclusion of EGCG appears to yield an 'encouragingly beneficial' outcome, which is more in line with our original expectation that GTE should be beneficial, not detrimental."
The study was funded by the Multiple Myeloma Research Foundation.
Encouse B. Golden, Philip Y. Lam, Adel Kardosh, Kevin J. Gaffney, Enrique Cadenas, Stan G. Louise, Nicos A. Petasis, Thomas C. Chen, Axel H. Schönthal. "Green Tea Polyphenols Block The Anticancer Effects of Bortezomib And Other Boronic Acid-Based Proteasome Inhibitors." Blood. bloodjournal.hematologylibrary/papbyrecent.dtl
Source: Meghan Lewit
University of Southern California
View drug information on Velcade.
The study, which found that a component of green tea extract (GTE) called EGCG destroys any anticancer activity of the drug Velcade in tumor-bearing mice, will be published in a future print edition of the journal, Blood. It is now available online at the journal's pre-publication First Edition website.
"Our finding that GTE or EGCG blocked the therapeutic action of Velcade was completely unexpected," says lead author Axel H. Schönthal, PhD, associate professor in the Department of Microbiology and Immunology at the Keck School of Medicine of USC. "Our hypothesis was that GTE or EGCG would enhance the anti-tumor effects of Velcade, and that a combination of GTE with Velcade (or EGCG with Velcade) would turn out to be a superior cancer treatment as compared to treatment with Velcade alone."
Herbal remedies, including green tea, have become a popular remedy for cancer patients dealing with side effects of chemotherapy. However, these supplements are unregulated and, for most, their beneficial and/or detrimental effects have not been qualified through research.
Using preclinical models and tumor-bearing mice, the researchers found that the unusually effective blockage of Velcade's therapeutic activity was based on the chemical interaction between molecules. The EGCG molecule and the Velcade molecule were able to form chemical bonds, meaning that the Velcade molecule could no longer bind to its intended target inside the tumor cells.
Clincal trials to verify these results in humans would be highly unethical to conduct, because of the predictably unfavorable outcome. Nevertheless, the researchers expect the results of the study to be applicable to cancer patients.
"The most immediate conclusion from our study is the strong advice that patients undergoing cancer therapy with Velcade must avoid green tea, and in particular all of its concentrated products that are freely available from health food stores," says Schönthal. "It is important to spread this message to health care providers who administer Velcade to patients."
Schönthal points out that for patients on Velcade, supplementing with green tea products should reduce the burden of harsh side effects - which might be attractive to the patient, but comes at a high cost.
"Essentially, in addition to not being able to attack tumor cells, Velcade would be unable to cause side effects either," he says. "As a result, the patient would feel a lot better and conclude that the consumption of GTE helped cope with side effects - while in reality, Velcade simply wasn't active in the first place."
The research findings are part of a larger project run by the team called "Yin-Yang Properties of Green Tea Extract in Combination Cancer Chemotherapy: From Encouragingly Beneficial to Dangerously Detrimental."
"Obviously, the combination of GTE or EGCG with Velcade is an example of 'dangerously detrimental,' "Schönthal says. "But we are also studying another well-established chemotherapeutic drug, where the inclusion of EGCG appears to yield an 'encouragingly beneficial' outcome, which is more in line with our original expectation that GTE should be beneficial, not detrimental."
The study was funded by the Multiple Myeloma Research Foundation.
Encouse B. Golden, Philip Y. Lam, Adel Kardosh, Kevin J. Gaffney, Enrique Cadenas, Stan G. Louise, Nicos A. Petasis, Thomas C. Chen, Axel H. Schönthal. "Green Tea Polyphenols Block The Anticancer Effects of Bortezomib And Other Boronic Acid-Based Proteasome Inhibitors." Blood. bloodjournal.hematologylibrary/papbyrecent.dtl
Source: Meghan Lewit
University of Southern California
View drug information on Velcade.
пятница, 10 июня 2011 г.
Lifespan, Lifetime Reproductive Performance And Paternity Loss Of Within-pair And Extra-pair Offspring In The Coal Tit Periparus Ater
Female birds frequently engage in extra-pair mating behaviour and may thereby increase the genetic quality of offspring in terms of either viability or sexual attractiveness.
In contrast to the first idea, extra-pair offspring did not differ in lifespan from within-pair offspring in the socially monogamous coal tit. Moreover, in contrast to expectations, male within-pair offspring reared more social offspring over their lifetime than male extra-pair offspring.
The crucial task for future studies is to measure extra-pair fertilisation success of male offspring to test whether genetic benefits of extra-pair matings may lie in a higher sexual attractiveness of male extra-pair offspring.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
publishing.royalsociety/proceedingsb
In contrast to the first idea, extra-pair offspring did not differ in lifespan from within-pair offspring in the socially monogamous coal tit. Moreover, in contrast to expectations, male within-pair offspring reared more social offspring over their lifetime than male extra-pair offspring.
The crucial task for future studies is to measure extra-pair fertilisation success of male offspring to test whether genetic benefits of extra-pair matings may lie in a higher sexual attractiveness of male extra-pair offspring.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
publishing.royalsociety/proceedingsb
Wave Generator Discovered In Immune System
Scientists have discovered that torrents of microscopic waves propel white blood cells toward invading microbes. The discovery - recorded on videotape -- holds the potential for better understanding and treatment of cancer and heart disease.
Visible only under a very high-resolution light microscope, the dynamic waves are made of a signaling protein that directs cell movement. This protein and a second key player were already known to trigger cells to move, but their interaction to generate the self-sustaining waves has now been revealed.
"Seeing the wavelike dynamics of this protein, Hem-1, for the first time was easily the most instantly thrilling and illuminating finding in my scientific career," says Orion Weiner, PhD, of the University of California, San Francisco, who led the scientific team. "It immediately suggested how this protein might be organizing cell movement -- an idea that our subsequent experiments validated.
"We never expected to see this sort of complex behavior within cells, but in retrospect it is an absolutely ingenious way to organize cell movement. We're getting our first glimpses that take us beyond knowing that this protein is important for cell motility to learning how it might organize the complex choreography of cell movement."
The videotape of the unsuspected action shows wave upon wave advancing like a series of exploding fireworks. The novel behavior can be viewed at cvri.ucsf/~weiner.
The research findings are reported in the online edition of the journal Public Library of Science (PLoS) Biology. Lead author is Weiner, who is assistant professor of biochemistry at UCSF.
Because the same kind of components scrutinized in the new research also drive cancer cell metastasis, the finding may lead to strategies to block cancer growth. Similarly, faulty regulation of white blood cell movement plays a role in heart attack -- another promising target for applying the new insights of the regulation of cell movement, the authors say.
White blood cells, or neutrophils, are the body's first line of defense against potentially harmful microbes, and are one of the swiftest cells in the body. The wave action that speeds them along is generated by the same kind of three-part circuit that fires electrical signals along a neuron or prods the heart to beat, the researchers observe.
Videotaping allowed the scientists to watch as wave upon wave of the Hem-1 protein push neutrophils toward a chemical signal made by invading microbes. The researchers fluorescently tagged Hem-1 to view its dynamic propulsive power under the microscope.
Self-generating waves of Hem-1 control the pattern of assembly of building blocks of a second protein, actin. This protein physically contacts the cell membrane and prods it forward. But actin is not only an output of Hem-1 action; it also appears to eliminate the Hem-1 that has assembled it, the new research shows. The scientists think that this cycle of Hem-1 propulsion and annihilation is likely to produce the series of waves seen under the microscope.
The cell-propelling circuit contains a third component that makes it self-sustaining. The researchers found evidence that before each Hem-1 protein is eliminated, it recruits an additional Hem-1 right "next door." As each Hem-1 succumbs, a new one appears -- but only on one side. Weiner thinks the structure of actin physically blocks Hem-1 from recruiting its daughter Hem-1 on one side, so Hem-1 is sequentially added only in one direction. This determines the direction of cell movement.
Weiner likens it to a Lego tower on its side. "If you kept adding blocks to one end and removing them from the other, you would have a moving tower that was the same size but kept adding new material. This is very similar to what is going on in a Hem-1 wave," he says.
The Hem-1 recruitment assures the cycle will continue. The cycle, or circuit, of activation, recruitment and inhibition, as it is called, can continue without "orders" from another part of the cell, the scientists report.
"One of the things that I find fascinating about these waves is how relatively simple patterns of protein interaction can generate very complex behaviors," says Weiner. "Evolution has found the same solution to generating waves again and again even with completely different molecules, and at different scales of space and time -- encouraging for those of us who want to uncover general organizing principles in biology."
Weiner is an investigator in both the UCSF Cardiovascular Research Institute and the California Institute for Quantitative Biosciences, or QB3, headquartered at UCSF.
Weiner initiated the research as a postdoctoral fellow in the lab of Marc Kirschner, PhD, professor and chair of systems biology at Harvard Medical School. Kirschner is a co-author on the paper.
The cycle the scientists studied is very similar in concept to the circuit that generates neuronal conduction, the beating of the heart, and many other waves in biology, according to Weiner.
"All of these use a self-activating signal that plants the seeds for its own destruction, even while it is progressing. This results in a wave that moves undiminished because of the self-activation, and in one direction, because of the inhibition it leaves in its wake," he says.
The scientists observed the Hem-1 activation of actin assembly and actin's inhibition of Hem-1 accumulation. The "recruitment" component was not directly observed, but is consistent with their observations and experiments.
In the research, the team used the fluorescently tagged Hem-1 to determine whether the protein participated in the wave action, or was the wave itself.
Using optical tricks to label specific pools of Hem-1, they found that molecules of Hem-1 don't move, but pass information between molecules to generate a wave.
The research is now focusing on how external signals influence this wave generator to guide the cells. They also want to learn if the wave action they have discovered in neutrophils also controls movement and shapes changes in other cells and organisms.
Co-authors on the PLoS paper and collaborators in the research are William Marganski, PhD, a scientist at Ikonisys, in Connecticut; Lani F. Wu, PhD, and Steven Altschuler, PhD, both assistant professors of pharmacology at University of Texas Southwestern.
The research was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, the Endowed Scholars Program, and the Welch Foundation.
UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.
Source: Wallace Ravven
University of California - San Francisco
Visible only under a very high-resolution light microscope, the dynamic waves are made of a signaling protein that directs cell movement. This protein and a second key player were already known to trigger cells to move, but their interaction to generate the self-sustaining waves has now been revealed.
"Seeing the wavelike dynamics of this protein, Hem-1, for the first time was easily the most instantly thrilling and illuminating finding in my scientific career," says Orion Weiner, PhD, of the University of California, San Francisco, who led the scientific team. "It immediately suggested how this protein might be organizing cell movement -- an idea that our subsequent experiments validated.
"We never expected to see this sort of complex behavior within cells, but in retrospect it is an absolutely ingenious way to organize cell movement. We're getting our first glimpses that take us beyond knowing that this protein is important for cell motility to learning how it might organize the complex choreography of cell movement."
The videotape of the unsuspected action shows wave upon wave advancing like a series of exploding fireworks. The novel behavior can be viewed at cvri.ucsf/~weiner.
The research findings are reported in the online edition of the journal Public Library of Science (PLoS) Biology. Lead author is Weiner, who is assistant professor of biochemistry at UCSF.
Because the same kind of components scrutinized in the new research also drive cancer cell metastasis, the finding may lead to strategies to block cancer growth. Similarly, faulty regulation of white blood cell movement plays a role in heart attack -- another promising target for applying the new insights of the regulation of cell movement, the authors say.
White blood cells, or neutrophils, are the body's first line of defense against potentially harmful microbes, and are one of the swiftest cells in the body. The wave action that speeds them along is generated by the same kind of three-part circuit that fires electrical signals along a neuron or prods the heart to beat, the researchers observe.
Videotaping allowed the scientists to watch as wave upon wave of the Hem-1 protein push neutrophils toward a chemical signal made by invading microbes. The researchers fluorescently tagged Hem-1 to view its dynamic propulsive power under the microscope.
Self-generating waves of Hem-1 control the pattern of assembly of building blocks of a second protein, actin. This protein physically contacts the cell membrane and prods it forward. But actin is not only an output of Hem-1 action; it also appears to eliminate the Hem-1 that has assembled it, the new research shows. The scientists think that this cycle of Hem-1 propulsion and annihilation is likely to produce the series of waves seen under the microscope.
The cell-propelling circuit contains a third component that makes it self-sustaining. The researchers found evidence that before each Hem-1 protein is eliminated, it recruits an additional Hem-1 right "next door." As each Hem-1 succumbs, a new one appears -- but only on one side. Weiner thinks the structure of actin physically blocks Hem-1 from recruiting its daughter Hem-1 on one side, so Hem-1 is sequentially added only in one direction. This determines the direction of cell movement.
Weiner likens it to a Lego tower on its side. "If you kept adding blocks to one end and removing them from the other, you would have a moving tower that was the same size but kept adding new material. This is very similar to what is going on in a Hem-1 wave," he says.
The Hem-1 recruitment assures the cycle will continue. The cycle, or circuit, of activation, recruitment and inhibition, as it is called, can continue without "orders" from another part of the cell, the scientists report.
"One of the things that I find fascinating about these waves is how relatively simple patterns of protein interaction can generate very complex behaviors," says Weiner. "Evolution has found the same solution to generating waves again and again even with completely different molecules, and at different scales of space and time -- encouraging for those of us who want to uncover general organizing principles in biology."
Weiner is an investigator in both the UCSF Cardiovascular Research Institute and the California Institute for Quantitative Biosciences, or QB3, headquartered at UCSF.
Weiner initiated the research as a postdoctoral fellow in the lab of Marc Kirschner, PhD, professor and chair of systems biology at Harvard Medical School. Kirschner is a co-author on the paper.
The cycle the scientists studied is very similar in concept to the circuit that generates neuronal conduction, the beating of the heart, and many other waves in biology, according to Weiner.
"All of these use a self-activating signal that plants the seeds for its own destruction, even while it is progressing. This results in a wave that moves undiminished because of the self-activation, and in one direction, because of the inhibition it leaves in its wake," he says.
The scientists observed the Hem-1 activation of actin assembly and actin's inhibition of Hem-1 accumulation. The "recruitment" component was not directly observed, but is consistent with their observations and experiments.
In the research, the team used the fluorescently tagged Hem-1 to determine whether the protein participated in the wave action, or was the wave itself.
Using optical tricks to label specific pools of Hem-1, they found that molecules of Hem-1 don't move, but pass information between molecules to generate a wave.
The research is now focusing on how external signals influence this wave generator to guide the cells. They also want to learn if the wave action they have discovered in neutrophils also controls movement and shapes changes in other cells and organisms.
Co-authors on the PLoS paper and collaborators in the research are William Marganski, PhD, a scientist at Ikonisys, in Connecticut; Lani F. Wu, PhD, and Steven Altschuler, PhD, both assistant professors of pharmacology at University of Texas Southwestern.
The research was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, the Endowed Scholars Program, and the Welch Foundation.
UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.
Source: Wallace Ravven
University of California - San Francisco
четверг, 9 июня 2011 г.
New Role Found For A Cardiac Progenitor Population
In a discovery that could one day lead to an understanding of how to regenerate damaged heart tissue, researchers at the University of California, San Diego have found that parent cells involved in embryonic development of the epicardium - the cell layer surrounding the outside of the heart - give rise to three important types of cells with potential for cardiac repair.
In a study published online in advance of publication in the journal Nature, researchers led by Sylvia Evans, Ph.D., professor of pharmacology at the Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of medicine at UC San Diego, discovered in mice that developing embryonic cells that form the epicardium develop into cardiomyocytes, or muscle cells, as well as into connective tissue and vascular support cells of the heart.
The UCSD team generated mice which enabled lineage studies of epicardial cells, utilizing a marker for these lineages called a T-box transcription factor, Tbx18. "The surprising finding was that during the earliest stages of development, myocytes are also generated from parent cells within the embryonic epicardium," said Evans. The Evans lab went on to demonstrate that, in the adult mouse, epicardial cells have lost their earlier embryonic ability to generate cardiomyocytes.
"Our findings raise the possibility that if we can restore the ability of adult epicardial cells in mammals to generate cardiomyocytes, it may enhance their future potential for cardiac repair following injury, such as a heart attack," said co-first author Jody C. Martin of UCSD's Department of Bioengineering.
While the adult mammalian heart has lost this capacity to generate new heart muscle, according to Evans, other investigators have demonstrated that zebrafish can fully regenerate their hearts following injury. This regeneration is associated with migration of Tbx 18-expressing cells to the site of injury, and the new formation of cardiomycytes. If Tbx18-cell migration is prevented, there is no repair. The UCSD researchers' findings suggest that one reason that zebrafish can regenerate their hearts may be that adult zebrafish epicardium somehow retains the capacity to generate cardiomyocytes.
Additional contributors to the paper include co-first authors Chen-Leng Cai andYunfu Sun, as well as Li Cui, Lei Bu, Lei Yang and Xiaoxue Zhang, UCSD's Skaggs School of Pharmacy; Ju Chen, Kunfu Ouyang and Xingqun Liang, UCSD Department of Medicine; Andrew McCulloch, UCSD Department of Bioengineering; Lianchun Wang, University of Georgia; William B. Stallcup, The Burnham Institute, La Jolla, California; and Christopher P. Denton, Royal Free and University College Medical School, London. The research was funded in part by a grant from the National Institutes of Health and an American Heart Association Scientist Development grant.rchers in determining an individual's cancer risk.
Source: Debra Kain
University of California - San Diego
In a study published online in advance of publication in the journal Nature, researchers led by Sylvia Evans, Ph.D., professor of pharmacology at the Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of medicine at UC San Diego, discovered in mice that developing embryonic cells that form the epicardium develop into cardiomyocytes, or muscle cells, as well as into connective tissue and vascular support cells of the heart.
The UCSD team generated mice which enabled lineage studies of epicardial cells, utilizing a marker for these lineages called a T-box transcription factor, Tbx18. "The surprising finding was that during the earliest stages of development, myocytes are also generated from parent cells within the embryonic epicardium," said Evans. The Evans lab went on to demonstrate that, in the adult mouse, epicardial cells have lost their earlier embryonic ability to generate cardiomyocytes.
"Our findings raise the possibility that if we can restore the ability of adult epicardial cells in mammals to generate cardiomyocytes, it may enhance their future potential for cardiac repair following injury, such as a heart attack," said co-first author Jody C. Martin of UCSD's Department of Bioengineering.
While the adult mammalian heart has lost this capacity to generate new heart muscle, according to Evans, other investigators have demonstrated that zebrafish can fully regenerate their hearts following injury. This regeneration is associated with migration of Tbx 18-expressing cells to the site of injury, and the new formation of cardiomycytes. If Tbx18-cell migration is prevented, there is no repair. The UCSD researchers' findings suggest that one reason that zebrafish can regenerate their hearts may be that adult zebrafish epicardium somehow retains the capacity to generate cardiomyocytes.
Additional contributors to the paper include co-first authors Chen-Leng Cai andYunfu Sun, as well as Li Cui, Lei Bu, Lei Yang and Xiaoxue Zhang, UCSD's Skaggs School of Pharmacy; Ju Chen, Kunfu Ouyang and Xingqun Liang, UCSD Department of Medicine; Andrew McCulloch, UCSD Department of Bioengineering; Lianchun Wang, University of Georgia; William B. Stallcup, The Burnham Institute, La Jolla, California; and Christopher P. Denton, Royal Free and University College Medical School, London. The research was funded in part by a grant from the National Institutes of Health and an American Heart Association Scientist Development grant.rchers in determining an individual's cancer risk.
Source: Debra Kain
University of California - San Diego
среда, 8 июня 2011 г.
Landmark Discovery Of 'Engine' That Drives Cell Movement
How a cell assembles its internal machinery required for cell movement has been revealed for the first time. The discovery, by scientists in Singapore, is published in the October 2008 issue of Cell.
This research by Thomas Leung, Ph.D., and his team in the GSK-IMCB Group at the Institute of Molecular and Cell Biology (IMCB), under Singapore's Agency for Science, Technology and Research (A*STAR), is fundamental to the understanding of how a cell responds to its external environment.
The findings have widespread implications in the fields of cancer growth and spread, wound- healing, learning and memory, and developmental biology.
The researchers discovered a complex of three proteins that directly regulates the myosin network within a cell, thus generating traction force to propel the cell forward. (Myosin is the most common protein found in muscle cells, and is responsible for the elastic and contractile properties of muscle. A different form of myosin is involved in cell movement.)
This action of the tripartite protein complex may be likened to a spring in a toy motorcar - when the protein complex assembles and moves backwards within the cell, it resembles the wound up "engine" of the toy car that has been pulled backwards.
Subsequent disassembling of the protein complex and the resultant forward movement of the cell can be likened to the released spring which unleashes the earlier stored potential energy to propel the car forward.
Michael Sheetz, Ph.D., who is William R Kenan Jr Professor of Cell Biology at the Department of Biological Sciences, Columbia University, and also Distinguished Visiting Professor at the National University of Singapore, said, "This is an exciting paper because Leung's group has discovered an unexpected step in cell migration and contractility - a complex of three proteins including a form of myosin, that is responsible for assembling most of the other myosin components involved in motile processes. The assembly mechanism has been a major mystery and is critical in a variety of diseases from cardiovascular to aging. Now we have a new tool to understand the bases of these critical processes."
Of the three proteins MRCK, LRAP35a and MYO18A, MRCK was discovered by the GSK-IMCB group 10 years ago, while the other two had hitherto unknown functions. Dr. Leung of IMCB said, "The success of the work relies on the commitment and perseverance of the team. A major contributor, Dr. Ivan Tan, is a home-grown scientist who has been working on this project for many years and he has had several clues as to how the system functions for some time, but it was only recently that the jigsaw puzzle was put together. The system has the potential to unravel other as yet undiscovered mechanisms that coordinate the different 'engines' for proper cell migration."
The research by the GSK-IMCB Group is supported by the GlaxoSmithKline (Singapore) Research Fund that was set up in 1989. Louis Lim, Ph.D., head of the GSK-IMCB Group, said, "The 2008 Cell paper represents the culmination of many years of industry and dedication on the part of Dr. Thomas Leung and Dr. Ivan Tan. Dr. Leung has been responsible for defining the role of other signalling enzymes along with other members of the GSK-IMCB Group, and we are very glad to acknowledge the support of the GSK Singapore Research Fund throughout these years."
The GSK-IMCB Group also published a landmark paper entitled, "A brain serine/threonine protein kinase activated by Cdc42 and Rac12," in Nature, in 1994. The paper has been cited more than 900 times by scientists around the world.
For more information, please contact:
Wang Yunshi
Corporate Communications
Agency for Science, Technology and Research (A*STAR)
Notes:
The research findings described in the press release are reported in the paper, "A Tripartite Complex Containing MRCK Modulates Lamellar Actomyosin Retrograde Flow," in the October 3, 2008 print issue of Cell.
Authors: Ivan Tan (a), Jeffery Yonga (b), Jing Ming Donga, Louis Lima (c), and Thomas Leunga (b)
(a)The GSK-IMCB Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore
(b) Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
(c )Department of Molecular Neuroscience, Institute of Neurology, University College London, UK
Institute of Molecular and Cell Biology (IMCB):
IMCB is a member of Singapore's Agency for Science, Technology and Research (A*STAR) and is funded through A*STAR's Biomedical Research Council (BMRC). It is a world-class research institute that focuses its activities on six major fields: Cell Biology, Developmental Biology, Structural Biology, Infectious Diseases, Cancer Biology and Translational Research, with core strengths in cell cycling, cell signalling, cell death, cell motility and protein trafficking. Its recent achievements include leading an international consortium that successfully sequenced the entire pufferfish (Fugu) genome. IMCB was awarded the Nikkei Prize 2000 for Technological Innovation in recognition of its growth into a leading international research centre and its collaboration with industry and research institutes worldwide. Established in 1987, IMCB has 35 independent research groups with more than 400 staff members. For more information, please visit imcb.a-star.sgimcb.a-star.sg.
Agency for Science, Technology and Research (A*STAR):
A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 19 research institutes and consortia and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent. For more information about A*STAR, please visit a-star.sg.
Source: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore
This research by Thomas Leung, Ph.D., and his team in the GSK-IMCB Group at the Institute of Molecular and Cell Biology (IMCB), under Singapore's Agency for Science, Technology and Research (A*STAR), is fundamental to the understanding of how a cell responds to its external environment.
The findings have widespread implications in the fields of cancer growth and spread, wound- healing, learning and memory, and developmental biology.
The researchers discovered a complex of three proteins that directly regulates the myosin network within a cell, thus generating traction force to propel the cell forward. (Myosin is the most common protein found in muscle cells, and is responsible for the elastic and contractile properties of muscle. A different form of myosin is involved in cell movement.)
This action of the tripartite protein complex may be likened to a spring in a toy motorcar - when the protein complex assembles and moves backwards within the cell, it resembles the wound up "engine" of the toy car that has been pulled backwards.
Subsequent disassembling of the protein complex and the resultant forward movement of the cell can be likened to the released spring which unleashes the earlier stored potential energy to propel the car forward.
Michael Sheetz, Ph.D., who is William R Kenan Jr Professor of Cell Biology at the Department of Biological Sciences, Columbia University, and also Distinguished Visiting Professor at the National University of Singapore, said, "This is an exciting paper because Leung's group has discovered an unexpected step in cell migration and contractility - a complex of three proteins including a form of myosin, that is responsible for assembling most of the other myosin components involved in motile processes. The assembly mechanism has been a major mystery and is critical in a variety of diseases from cardiovascular to aging. Now we have a new tool to understand the bases of these critical processes."
Of the three proteins MRCK, LRAP35a and MYO18A, MRCK was discovered by the GSK-IMCB group 10 years ago, while the other two had hitherto unknown functions. Dr. Leung of IMCB said, "The success of the work relies on the commitment and perseverance of the team. A major contributor, Dr. Ivan Tan, is a home-grown scientist who has been working on this project for many years and he has had several clues as to how the system functions for some time, but it was only recently that the jigsaw puzzle was put together. The system has the potential to unravel other as yet undiscovered mechanisms that coordinate the different 'engines' for proper cell migration."
The research by the GSK-IMCB Group is supported by the GlaxoSmithKline (Singapore) Research Fund that was set up in 1989. Louis Lim, Ph.D., head of the GSK-IMCB Group, said, "The 2008 Cell paper represents the culmination of many years of industry and dedication on the part of Dr. Thomas Leung and Dr. Ivan Tan. Dr. Leung has been responsible for defining the role of other signalling enzymes along with other members of the GSK-IMCB Group, and we are very glad to acknowledge the support of the GSK Singapore Research Fund throughout these years."
The GSK-IMCB Group also published a landmark paper entitled, "A brain serine/threonine protein kinase activated by Cdc42 and Rac12," in Nature, in 1994. The paper has been cited more than 900 times by scientists around the world.
For more information, please contact:
Wang Yunshi
Corporate Communications
Agency for Science, Technology and Research (A*STAR)
Notes:
The research findings described in the press release are reported in the paper, "A Tripartite Complex Containing MRCK Modulates Lamellar Actomyosin Retrograde Flow," in the October 3, 2008 print issue of Cell.
Authors: Ivan Tan (a), Jeffery Yonga (b), Jing Ming Donga, Louis Lima (c), and Thomas Leunga (b)
(a)The GSK-IMCB Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore
(b) Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
(c )Department of Molecular Neuroscience, Institute of Neurology, University College London, UK
Institute of Molecular and Cell Biology (IMCB):
IMCB is a member of Singapore's Agency for Science, Technology and Research (A*STAR) and is funded through A*STAR's Biomedical Research Council (BMRC). It is a world-class research institute that focuses its activities on six major fields: Cell Biology, Developmental Biology, Structural Biology, Infectious Diseases, Cancer Biology and Translational Research, with core strengths in cell cycling, cell signalling, cell death, cell motility and protein trafficking. Its recent achievements include leading an international consortium that successfully sequenced the entire pufferfish (Fugu) genome. IMCB was awarded the Nikkei Prize 2000 for Technological Innovation in recognition of its growth into a leading international research centre and its collaboration with industry and research institutes worldwide. Established in 1987, IMCB has 35 independent research groups with more than 400 staff members. For more information, please visit imcb.a-star.sgimcb.a-star.sg.
Agency for Science, Technology and Research (A*STAR):
A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 19 research institutes and consortia and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent. For more information about A*STAR, please visit a-star.sg.
Source: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore
вторник, 7 июня 2011 г.
New Mouse Model Of Bipolar Disorder
Bipolar Disorder (BPD or manic-depressive illness) is one of the most serious of all mental disorders, affecting millions of individuals worldwide. Affected individuals alternate between states of deep depression and mania. While depression is characterized by persistent and long-term sadness or despair, mania is a mental state characterized by great excitement, flight of ideas, a decreased need for sleep, and, sometimes, uncontrollable behavior, hallucinations, or delusions. BPD likely arises from the complex interaction of multiple genes and environmental factors. Unlike some brain diseases, no single gene has been implicated in BPD.
A major limitation to progress in research and treatment has been the lack of an appropriate animal model for BPD. This work was developed to create such a model based on a genetically engineered defect in the GluR6 gene. The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene resides in a genetic linkage region (6q21) associated with BPD. Kainate receptors respond to the neurotransmitter glutamate, and recent research in mood disorders suggests that the glutamatergic system may play a role in causing mood disorders.
Until now, the role of GluR6 in regulating the mood swings of BPD has been unknown. Furthermore, the gene encoding the GluR6 receptor has recently been linked to treatment emergent suicidal ideation with antidepressants in a pharmacogenetic study. Notably, individuals with bipolar disorder are most susceptible to antidepressant-induced dysphoric states. In this study, mice of several strains were used to investigate this issue. Mice who were missing the GluR6 gene were compared with control mice. The mice underwent a series of tests designed to approximate the symptoms of mania. The researchers found that mice that were missing the GluR6 gene exhibited many of these symptoms. They were more active in multiple tests and super-responsive to amphetamine, which is used in animal models to approximate hyperactivity. These mice also exhibited less anxious or more risk-taking type behavior and less despair-type behavior. They also tended to be more aggressive.
Notably, BPD is most often treated with a class of medications known as mood stabilizers; lithium is perhaps the best known of these medications. The researchers found that chronic treatment with lithium reduced hyperactivity, aggressive displays, and some risk-taking type behavior in mice missing the GluR6 gene. When biochemical tests were conducted, they also suggested that GluR6 may play a unique role in regulating some of the symptoms of mania. This new animal of mania permits researchers to better understand bipolar disorder and to screen for new treatments that if successful in the animal model can then be translated to the clinic.
Citation source: Molecular Psychiatry advance online publication 11 MARCH 2008 - 11:00 PM EST.
For further information on this article, please contact the Corresponding Author:
Husseini K. Manji, M.D.
Director, Mood and Anxiety Disorders Program
NIMH-NIH
Bldg. 35, Room 1C-912
35 Convent Drive MSC-3711
Bethesda, MD 20892, USA
Molecular Psychiatry is a peer-reviewed independent journal that publishes groundbreaking research in psychiatry and related fields. The journal's Impact Factor is 11.804, 2nd of 95 in Psychiatry
Website: nature/mp
Editor: Julio Licinio, M.D.
University of Miami Miller School of Medicine
Source: Husseini K. Manji, M.D.
Molecular Psychiatry
A major limitation to progress in research and treatment has been the lack of an appropriate animal model for BPD. This work was developed to create such a model based on a genetically engineered defect in the GluR6 gene. The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene resides in a genetic linkage region (6q21) associated with BPD. Kainate receptors respond to the neurotransmitter glutamate, and recent research in mood disorders suggests that the glutamatergic system may play a role in causing mood disorders.
Until now, the role of GluR6 in regulating the mood swings of BPD has been unknown. Furthermore, the gene encoding the GluR6 receptor has recently been linked to treatment emergent suicidal ideation with antidepressants in a pharmacogenetic study. Notably, individuals with bipolar disorder are most susceptible to antidepressant-induced dysphoric states. In this study, mice of several strains were used to investigate this issue. Mice who were missing the GluR6 gene were compared with control mice. The mice underwent a series of tests designed to approximate the symptoms of mania. The researchers found that mice that were missing the GluR6 gene exhibited many of these symptoms. They were more active in multiple tests and super-responsive to amphetamine, which is used in animal models to approximate hyperactivity. These mice also exhibited less anxious or more risk-taking type behavior and less despair-type behavior. They also tended to be more aggressive.
Notably, BPD is most often treated with a class of medications known as mood stabilizers; lithium is perhaps the best known of these medications. The researchers found that chronic treatment with lithium reduced hyperactivity, aggressive displays, and some risk-taking type behavior in mice missing the GluR6 gene. When biochemical tests were conducted, they also suggested that GluR6 may play a unique role in regulating some of the symptoms of mania. This new animal of mania permits researchers to better understand bipolar disorder and to screen for new treatments that if successful in the animal model can then be translated to the clinic.
Citation source: Molecular Psychiatry advance online publication 11 MARCH 2008 - 11:00 PM EST.
For further information on this article, please contact the Corresponding Author:
Husseini K. Manji, M.D.
Director, Mood and Anxiety Disorders Program
NIMH-NIH
Bldg. 35, Room 1C-912
35 Convent Drive MSC-3711
Bethesda, MD 20892, USA
Molecular Psychiatry is a peer-reviewed independent journal that publishes groundbreaking research in psychiatry and related fields. The journal's Impact Factor is 11.804, 2nd of 95 in Psychiatry
Website: nature/mp
Editor: Julio Licinio, M.D.
University of Miami Miller School of Medicine
Source: Husseini K. Manji, M.D.
Molecular Psychiatry
Diatom Genome Helps Explain Success In Trapping Excess Carbon In Oceans
Diatoms, mighty microscopic algae, have profound influence on climate, producing 20 percent of the oxygen we breathe by capturing atmospheric carbon and in so doing, countering the greenhouse effect. Since their evolutionary origins these photosynthetic wonders have come to acquire advantageous genes from bacterial, animal and plant ancestors enabling them to thrive in today's oceans. These findings, based on the analysis of the latest sequenced diatom genome, Phaeodactylum tricornutum, are published in the 15th October edition of the journal Nature by an international team of researchers led by the U.S. Department of Energy Joint Genome Institute (DOE JGI) and the Ecole Normale SupГ©rieure of Paris.
The researchers compared Phaeodactylum with the diatom Thalassiosira pseudonana, previously sequenced by DOE JGI, revealing a wealth of information about diatom biology, particularly the rapid diversification among the hundreds of thousands of diatom species that exist today. Phaeodactylum was targeted for sequencing due to its value as a diatom model, given the ease with which it can be grown in the lab and the availability of tools to genetically transform it, and the comparisons with the previously sequenced diatom genome of Thalassiosira pseudonana.
"These organisms represent a veritable melting pot of traits - a hybrid of genetic mechanisms contributed by ancestral lineages of plants, animals, and bacteria, and optimized over the relatively short evolutionary timeframe of 180 million years since they first appeared," says first author Chris Bowler of the Ecole Normale SupГ©rieure. "Our findings show that gene transfer between diatoms and other organisms has been extremely common, making diatoms 'transgenic by nature'," he adds.
The wholesale acquisition of genetic material has provided food for thought to researchers bent on characterizing the diatom's staying power and ability to cope with environmental change.
"We believe this is the first time bacterial horizontal gene transfer has been observed in eukaryotes at such scale," says senior author Igor Grigoriev of DOE JGI. "This study gets us closer to explaining the dramatic diversity across the genera of diatoms, morphologically, behaviorally, but we still haven't yet explained all the differences conferred by the genes contributed by the other taxa."
From plants, the diatom inherited photosynthesis, and from animals the production of urea. Bowler speculates that the diatom uses urea to store nitrogen, not to eliminate it like animals do, because nitrogen is a precious nutrient in the ocean. What's more, the tiny alga draws the best of both worlds - it can convert fat into sugar, as well as sugar into fat - extremely useful in times of nutrient shortage.
The team documented more than 300 genes sourced from bacteria and found in both types of diatoms, pointing to their ancient origin and suggesting novel mechanisms of managing nutrients - for example utilization of organic carbon and nitrogen - and detecting cues from their environment.
Diatoms, encapsulated by elaborate lacework-like shells made of glass, are only about one-third of a strand of hair in diameter. "The diatom genomes will help us to understand how they can make these structures at ambient temperatures and pressures, something that humans are not able to do. If we can learn how they do it, we could open up all kinds of new nanotechnologies, like for building miniature silicon chips or for biomedical applications," says Bowler.
Diatoms reside in fresh or salt water and can be divided into two camps, centrics and pennates. The centric Thalassiosira resemble a round "Camembert" cheese box (only much smaller) and pennates like Phaeodactylum look more like a cross between a boomerang and a narrow three-cornered hat - hence the species name, tricornutum. Not only is their shape and habitat diverse, so too is their behavior; for instance, the former get around by floating, the latter by gliding through the water or on surfaces.
The lifestyle of diatoms can be characterized as "bloom or bust." When light and nutrient conditions in the upper reaches of the ocean are favorable, particularly at the onset of spring, diatoms gain an edge and tend to dominate their phytoplankton brethren. When food is scarce, they die and sink, carrying their complement of carbon dioxide to the deeper recesses.
Bowler and his colleagues are also trying to understand the role that iron plays in the Phaeodactylum's development. Iron is even more precious than nitrogen in the ocean and its absence in the southern hemisphere is likely a major cause of oceanic deserts of photosynthesis there. Bowler's team has demonstrated that when iron deficiency occurs processes such as photosynthesis and nitrogen assimilation are suppressed. Other studies, which hail diatoms as champions in capturing carbon dioxide, suggest a bold strategy of using iron as a fertilizer to provoke massive diatom blooms. "Once they have feasted, the weight of their silicon shells, which resemble glass, causes the diatoms to sink to the bottom of the ocean when they die, and the carbon that they assimilated is trapped there for millennia," says Bowler. "By sequestering carbon in this way we could reverse the damage from the burning of fossil fuels."
Notes:
Other DOE JGI authors on the Nature study include Alan Kuo, Robert Otillar, Asaf Salamov, Chris Detter, Erika Lindquist, Susan Lucas, Harris Shapiro, Daniel Rokhsar, and Igor Grigoriev as well as Jane Grimwood and Jeremy Schmutz of JGI at the HudsonAlpha Institute.
The U.S. Department of Energy Joint Genome Institute, supported by the DOE Office of Science, unites the expertise of five DOE national laboratories -- Lawrence Berkeley, Lawrence Livermore, Los Alamos, Oak Ridge, and Pacific Northwest -- along with the HudsonAlpha Institute for Biotechnology to advance genomics in support of the DOE missions related to clean energy generation and environmental characterization and cleanup. DOE JGI's Walnut Creek, Calif., Production Genomics Facility provides integrated high-throughput sequencing and computational analysis that enable systems-based scientific approaches to these challenges. Additional information about DOE JGI can be found at: jgi.doe/.
Source:
David Gilbert
DOE/Joint Genome Institute
The researchers compared Phaeodactylum with the diatom Thalassiosira pseudonana, previously sequenced by DOE JGI, revealing a wealth of information about diatom biology, particularly the rapid diversification among the hundreds of thousands of diatom species that exist today. Phaeodactylum was targeted for sequencing due to its value as a diatom model, given the ease with which it can be grown in the lab and the availability of tools to genetically transform it, and the comparisons with the previously sequenced diatom genome of Thalassiosira pseudonana.
"These organisms represent a veritable melting pot of traits - a hybrid of genetic mechanisms contributed by ancestral lineages of plants, animals, and bacteria, and optimized over the relatively short evolutionary timeframe of 180 million years since they first appeared," says first author Chris Bowler of the Ecole Normale SupГ©rieure. "Our findings show that gene transfer between diatoms and other organisms has been extremely common, making diatoms 'transgenic by nature'," he adds.
The wholesale acquisition of genetic material has provided food for thought to researchers bent on characterizing the diatom's staying power and ability to cope with environmental change.
"We believe this is the first time bacterial horizontal gene transfer has been observed in eukaryotes at such scale," says senior author Igor Grigoriev of DOE JGI. "This study gets us closer to explaining the dramatic diversity across the genera of diatoms, morphologically, behaviorally, but we still haven't yet explained all the differences conferred by the genes contributed by the other taxa."
From plants, the diatom inherited photosynthesis, and from animals the production of urea. Bowler speculates that the diatom uses urea to store nitrogen, not to eliminate it like animals do, because nitrogen is a precious nutrient in the ocean. What's more, the tiny alga draws the best of both worlds - it can convert fat into sugar, as well as sugar into fat - extremely useful in times of nutrient shortage.
The team documented more than 300 genes sourced from bacteria and found in both types of diatoms, pointing to their ancient origin and suggesting novel mechanisms of managing nutrients - for example utilization of organic carbon and nitrogen - and detecting cues from their environment.
Diatoms, encapsulated by elaborate lacework-like shells made of glass, are only about one-third of a strand of hair in diameter. "The diatom genomes will help us to understand how they can make these structures at ambient temperatures and pressures, something that humans are not able to do. If we can learn how they do it, we could open up all kinds of new nanotechnologies, like for building miniature silicon chips or for biomedical applications," says Bowler.
Diatoms reside in fresh or salt water and can be divided into two camps, centrics and pennates. The centric Thalassiosira resemble a round "Camembert" cheese box (only much smaller) and pennates like Phaeodactylum look more like a cross between a boomerang and a narrow three-cornered hat - hence the species name, tricornutum. Not only is their shape and habitat diverse, so too is their behavior; for instance, the former get around by floating, the latter by gliding through the water or on surfaces.
The lifestyle of diatoms can be characterized as "bloom or bust." When light and nutrient conditions in the upper reaches of the ocean are favorable, particularly at the onset of spring, diatoms gain an edge and tend to dominate their phytoplankton brethren. When food is scarce, they die and sink, carrying their complement of carbon dioxide to the deeper recesses.
Bowler and his colleagues are also trying to understand the role that iron plays in the Phaeodactylum's development. Iron is even more precious than nitrogen in the ocean and its absence in the southern hemisphere is likely a major cause of oceanic deserts of photosynthesis there. Bowler's team has demonstrated that when iron deficiency occurs processes such as photosynthesis and nitrogen assimilation are suppressed. Other studies, which hail diatoms as champions in capturing carbon dioxide, suggest a bold strategy of using iron as a fertilizer to provoke massive diatom blooms. "Once they have feasted, the weight of their silicon shells, which resemble glass, causes the diatoms to sink to the bottom of the ocean when they die, and the carbon that they assimilated is trapped there for millennia," says Bowler. "By sequestering carbon in this way we could reverse the damage from the burning of fossil fuels."
Notes:
Other DOE JGI authors on the Nature study include Alan Kuo, Robert Otillar, Asaf Salamov, Chris Detter, Erika Lindquist, Susan Lucas, Harris Shapiro, Daniel Rokhsar, and Igor Grigoriev as well as Jane Grimwood and Jeremy Schmutz of JGI at the HudsonAlpha Institute.
The U.S. Department of Energy Joint Genome Institute, supported by the DOE Office of Science, unites the expertise of five DOE national laboratories -- Lawrence Berkeley, Lawrence Livermore, Los Alamos, Oak Ridge, and Pacific Northwest -- along with the HudsonAlpha Institute for Biotechnology to advance genomics in support of the DOE missions related to clean energy generation and environmental characterization and cleanup. DOE JGI's Walnut Creek, Calif., Production Genomics Facility provides integrated high-throughput sequencing and computational analysis that enable systems-based scientific approaches to these challenges. Additional information about DOE JGI can be found at: jgi.doe/.
Source:
David Gilbert
DOE/Joint Genome Institute
понедельник, 6 июня 2011 г.
Genes Determining Asymmetry Probably Arose In The First Bilaterally Symmetric Organisms
Biologists have tracked down genes that control the handedness of snail shells, and they turn out to be similar to the genes used by humans to set up the left and right sides of the body.
The finding, reported online in advance of publication in Nature by University of California, Berkeley, researchers, indicates that the same genes have been responsible for establishing the left-right asymmetry of animals for 500-650 million years, originating in the last common ancestor of all animals with bilateral body organization, creatures that include everything from worms to humans.
"Previous studies indicated that the methods for breaking left-right symmetry in animals seem to differ widely, so there was nothing suggesting that the common ancestor of humans, snails and other bilateral organisms had a common strategy for left-right asymmetry," said Nipam H. Patel, UC Berkeley professor of integrative biology and of molecular and cell biology, and an investigator of the Howard Hughes Medical Institute.
"Indeed, scientists thought that one of the genes that is critical for setting up left-right asymmetry in vertebrates was only present in vertebrates and related groups and not in any other animals," said UC Berkeley post-doctoral fellow Cristina Grande. "But we found that gene in snails, which has a lot of evolutionary implications. This cellular pathway was present already in the ancestors of most animals."
The finding, the researchers say, could help to track down the ultimate cause of symmetry-breaking in snails and other organisms, and the cascade of gene activation that leads to complex shapes, such as coiled shells.
Despite humans' superficial symmetry - our left and right sides appear to be mirror images - we are anything but symmetric. Most people's hearts are towards the left side of the body, which means the left lung is slightly smaller to make room for the heart, and our intestines are arranged in an asymmetric coil. This asymmetry is unrelated to being left- or right-handed, a preference determined in the brain.
While a small percentage of people have their insides flipped, their overall internal arrangement is a mirror image of the norm. Anyone with a random arrangement of internal organs would be dead, Patel said, because his or her organs wouldn't fit together properly.
Other vertebrates are the same. In fact, scientists have identified a gene called "nodal" that - in all vertebrates checked to date - is expressed on the left side of the body and necessary to set up left-right asymmetry. If nodal doesn't work or is knocked out, internal organs are jumbled and the organism dies.
"In vertebrates, a set of genes tells the body it has to form a heart toward one side, and nodal is one of those genes," said Grande, who recently took a position at the Centro de BiologГa Molecular "Severo Ochoa" in Madrid, Spain.
"There are a lot of asymmetric molecules in the body, that is, molecules that are active on only one side of the body, but nodal is always expressed on the left side in all vertebrates, which is evidence of a conserved pathway," Patel said.
Genes similar to nodal have been found throughout the so-called deuterostomes, one of the three subgroups of bilateral animals that includes not only vertebrates, but also sea urchins and sea squirts.
But the most common lab animals, fruit flies and nematodes, apparently do not have a gene like nodal, despite their asymmetry. As a result, biologists have assumed that fruit flies and all other non-deuterostomes - snails included - use some other mechanism to establish right and left. Fruit flies and nematodes are in the clade Ecdysozoa, while snails and worms are members of the clade Lophotrochozoa.
Grande approached Patel four years ago to collaborate in a test of this assumption in snails, which have an obvious and easy-to-check handedness: Their shell either coils right, like a standard screw, or left. Patel, a biologist who focuses on the genetics and evolution of crustacean and insect development, such as the formation of segments and appendages in shrimps and crabs, invited Grande to join his lab, even though he had never before worked with snails.
Snail handedness becomes obvious very early in the embryo, Patel said. When the four-cell embryo divides to become eight cells, the new cells blossom from their predecessors in a clockwise spiral, in which case the snail ultimately forms a right-handed, or dextral, shell; or a counter-clockwise spiral, creating a left-handed, or sinistral, shell. Biologists had earlier shown that this decision is made by the mother snail, which dumps many proteins and RNA molecules into the egg to jump-start embryonic development and, in the process, imprints her offspring with specific characteristics.
"No one knows what that maternal gene is, and you can't track it down using the standard approach of looking for genetic markers because there are not yet enough markers in snails, so we looked for any molecular entry into the cause of asymmetry," Patel said.
That proved to be the genome of the marine limpet Lottia gigantea, a right-handed snail whose genome was sequenced recently by the Department of Energy's Joint Genome Institute (JGI) in Walnut Creek, Calif. Grande looked for genes in Lottia similar to nodal, and found one, as well as a gene analogous to the gene, Pitx, which is activated by nodal and also involved in setting up left-right asymmetry in vertebrates.
She used this information to look for and find similar genes in the left-handed snail Biomphalaria glabrata, the fresh-water host of the parasite that causes schistosomiasis. Experimental tests showed that nodal and Pitx were active or expressed on the right side of embryos in the right-handed snail Lottia, and on the left side in the left-handed snail Biomphalaria.
A key test of the critical nature of nodal involved treating the snails with a chemical known to inhibit the activity of nodal. While most treated snails died, some lost the asymmetric expression of Pitx and, most strikingly, developed a straight shell, Patel said.
Grande has since found analogs of nodal in the genome of the marine worm Capitella, which was sequenced by JGI, suggesting that nodal is active throughout the Lophotrochozoa.
"Everybody thought using nodal and Pitx for left-right asymmetry was an invention of this one group, the deuterostomes," Grande said. "The fact that we find them setting up asymmetry in snails and worms means that is not true; the ancestor of all bilaterians already used these genes to set up left-right asymmetry."
Because the ancestral snail was right-handed and thus, presumably, expressed nodal and Pitx on the right side of the body - similar to sea urchins, an early offshoot of the deuterostome branch leading to humans - the authors propose that the common ancestor of all bilateral animals had left-right asymmetry controlled by nodal and Pitx expressed on the right side of the body.
The discovery also could help Grande and Patel track down the maternal factors that ultimately determine handedness in snails.
Grande was supported by the Ministerio de Educacion y Ciencia of Spain and UC Berkeley's Center for Integrative Genomics.
Source: Robert Sanders
University of California - Berkeley
The finding, reported online in advance of publication in Nature by University of California, Berkeley, researchers, indicates that the same genes have been responsible for establishing the left-right asymmetry of animals for 500-650 million years, originating in the last common ancestor of all animals with bilateral body organization, creatures that include everything from worms to humans.
"Previous studies indicated that the methods for breaking left-right symmetry in animals seem to differ widely, so there was nothing suggesting that the common ancestor of humans, snails and other bilateral organisms had a common strategy for left-right asymmetry," said Nipam H. Patel, UC Berkeley professor of integrative biology and of molecular and cell biology, and an investigator of the Howard Hughes Medical Institute.
"Indeed, scientists thought that one of the genes that is critical for setting up left-right asymmetry in vertebrates was only present in vertebrates and related groups and not in any other animals," said UC Berkeley post-doctoral fellow Cristina Grande. "But we found that gene in snails, which has a lot of evolutionary implications. This cellular pathway was present already in the ancestors of most animals."
The finding, the researchers say, could help to track down the ultimate cause of symmetry-breaking in snails and other organisms, and the cascade of gene activation that leads to complex shapes, such as coiled shells.
Despite humans' superficial symmetry - our left and right sides appear to be mirror images - we are anything but symmetric. Most people's hearts are towards the left side of the body, which means the left lung is slightly smaller to make room for the heart, and our intestines are arranged in an asymmetric coil. This asymmetry is unrelated to being left- or right-handed, a preference determined in the brain.
While a small percentage of people have their insides flipped, their overall internal arrangement is a mirror image of the norm. Anyone with a random arrangement of internal organs would be dead, Patel said, because his or her organs wouldn't fit together properly.
Other vertebrates are the same. In fact, scientists have identified a gene called "nodal" that - in all vertebrates checked to date - is expressed on the left side of the body and necessary to set up left-right asymmetry. If nodal doesn't work or is knocked out, internal organs are jumbled and the organism dies.
"In vertebrates, a set of genes tells the body it has to form a heart toward one side, and nodal is one of those genes," said Grande, who recently took a position at the Centro de BiologГa Molecular "Severo Ochoa" in Madrid, Spain.
"There are a lot of asymmetric molecules in the body, that is, molecules that are active on only one side of the body, but nodal is always expressed on the left side in all vertebrates, which is evidence of a conserved pathway," Patel said.
Genes similar to nodal have been found throughout the so-called deuterostomes, one of the three subgroups of bilateral animals that includes not only vertebrates, but also sea urchins and sea squirts.
But the most common lab animals, fruit flies and nematodes, apparently do not have a gene like nodal, despite their asymmetry. As a result, biologists have assumed that fruit flies and all other non-deuterostomes - snails included - use some other mechanism to establish right and left. Fruit flies and nematodes are in the clade Ecdysozoa, while snails and worms are members of the clade Lophotrochozoa.
Grande approached Patel four years ago to collaborate in a test of this assumption in snails, which have an obvious and easy-to-check handedness: Their shell either coils right, like a standard screw, or left. Patel, a biologist who focuses on the genetics and evolution of crustacean and insect development, such as the formation of segments and appendages in shrimps and crabs, invited Grande to join his lab, even though he had never before worked with snails.
Snail handedness becomes obvious very early in the embryo, Patel said. When the four-cell embryo divides to become eight cells, the new cells blossom from their predecessors in a clockwise spiral, in which case the snail ultimately forms a right-handed, or dextral, shell; or a counter-clockwise spiral, creating a left-handed, or sinistral, shell. Biologists had earlier shown that this decision is made by the mother snail, which dumps many proteins and RNA molecules into the egg to jump-start embryonic development and, in the process, imprints her offspring with specific characteristics.
"No one knows what that maternal gene is, and you can't track it down using the standard approach of looking for genetic markers because there are not yet enough markers in snails, so we looked for any molecular entry into the cause of asymmetry," Patel said.
That proved to be the genome of the marine limpet Lottia gigantea, a right-handed snail whose genome was sequenced recently by the Department of Energy's Joint Genome Institute (JGI) in Walnut Creek, Calif. Grande looked for genes in Lottia similar to nodal, and found one, as well as a gene analogous to the gene, Pitx, which is activated by nodal and also involved in setting up left-right asymmetry in vertebrates.
She used this information to look for and find similar genes in the left-handed snail Biomphalaria glabrata, the fresh-water host of the parasite that causes schistosomiasis. Experimental tests showed that nodal and Pitx were active or expressed on the right side of embryos in the right-handed snail Lottia, and on the left side in the left-handed snail Biomphalaria.
A key test of the critical nature of nodal involved treating the snails with a chemical known to inhibit the activity of nodal. While most treated snails died, some lost the asymmetric expression of Pitx and, most strikingly, developed a straight shell, Patel said.
Grande has since found analogs of nodal in the genome of the marine worm Capitella, which was sequenced by JGI, suggesting that nodal is active throughout the Lophotrochozoa.
"Everybody thought using nodal and Pitx for left-right asymmetry was an invention of this one group, the deuterostomes," Grande said. "The fact that we find them setting up asymmetry in snails and worms means that is not true; the ancestor of all bilaterians already used these genes to set up left-right asymmetry."
Because the ancestral snail was right-handed and thus, presumably, expressed nodal and Pitx on the right side of the body - similar to sea urchins, an early offshoot of the deuterostome branch leading to humans - the authors propose that the common ancestor of all bilateral animals had left-right asymmetry controlled by nodal and Pitx expressed on the right side of the body.
The discovery also could help Grande and Patel track down the maternal factors that ultimately determine handedness in snails.
Grande was supported by the Ministerio de Educacion y Ciencia of Spain and UC Berkeley's Center for Integrative Genomics.
Source: Robert Sanders
University of California - Berkeley
воскресенье, 5 июня 2011 г.
Dr. Stanley Nathenson Receives Marshall S. Horwitz Faculty Prize For Research Excellence At Einstein
Stanley G. Nathenson, M.D., distinguished professor of microbiology and immunology and of cell biology at the Albert Einstein College of Medicine of Yeshiva University, has received the second annual Marshall S. Horwitz, M.D. Faculty Prize for Research Excellence during a special ceremony at the medical school.
The award was established in memory of a beloved long-time member of the Einstein faculty, Marshall S. Horwitz, M.D., who died in 2005. The award was presented to Dr. Nathenson by Allen M. Spiegel, M.D., The Marilyn and Stanley M. Katz Dean at Einstein.
As part of the program Dr. Nathenson delivered the second annual Marshall S. Horwitz, M.D. Prize Lecture, which focused on his current area of research - transplant immunity and costimulation of T cells.
Since joining the Einstein faculty in 1965, Dr. Nathenson has played a key role in making immunological research an area of excellence at the medical school. An internationally prominent cell biologist and immunologist, Dr. Nathenson gained particular recognition for studies that helped reveal the immunological basis for the rejection of transplanted tissues and organs - research that has led to therapies for overcoming the rejection process. As a result, transplantation has now become a routine medical procedure, extending and enhancing the lives of thousands of people every year.
A member of the National Academy of Sciences, Dr. Nathenson's current research focuses on two costimulatory molecules, B7-1 and B7-2, which have been found to play an important role in activating and regulating T cell immunity - actions that are necessary in preventing tissue or organ rejection during transplantation.
Dr. Nathenson is the author of more than 200 research papers. He currently holds the Samuel H. Golding Chair in Microbiology at Einstein and was named a distinguished professor in 2005.
A resident of Pelham, Dr. Nathenson earned his bachelor's degree from Reed College in 1955 and his medical degree from Washington University School of Medicine in 1959.
Source: Karen Gardner
Albert Einstein College of Medicine
The award was established in memory of a beloved long-time member of the Einstein faculty, Marshall S. Horwitz, M.D., who died in 2005. The award was presented to Dr. Nathenson by Allen M. Spiegel, M.D., The Marilyn and Stanley M. Katz Dean at Einstein.
As part of the program Dr. Nathenson delivered the second annual Marshall S. Horwitz, M.D. Prize Lecture, which focused on his current area of research - transplant immunity and costimulation of T cells.
Since joining the Einstein faculty in 1965, Dr. Nathenson has played a key role in making immunological research an area of excellence at the medical school. An internationally prominent cell biologist and immunologist, Dr. Nathenson gained particular recognition for studies that helped reveal the immunological basis for the rejection of transplanted tissues and organs - research that has led to therapies for overcoming the rejection process. As a result, transplantation has now become a routine medical procedure, extending and enhancing the lives of thousands of people every year.
A member of the National Academy of Sciences, Dr. Nathenson's current research focuses on two costimulatory molecules, B7-1 and B7-2, which have been found to play an important role in activating and regulating T cell immunity - actions that are necessary in preventing tissue or organ rejection during transplantation.
Dr. Nathenson is the author of more than 200 research papers. He currently holds the Samuel H. Golding Chair in Microbiology at Einstein and was named a distinguished professor in 2005.
A resident of Pelham, Dr. Nathenson earned his bachelor's degree from Reed College in 1955 and his medical degree from Washington University School of Medicine in 1959.
Source: Karen Gardner
Albert Einstein College of Medicine
суббота, 4 июня 2011 г.
Environmentally Safe 'Planetary Boundaries' Being Overstepped By The Human Race
Human activities have already pushed the Earth system beyond three of the planet's biophysical thresholds, with consequences that are detrimental or even catastrophic for large parts of the world; six others may well be crossed in the next decades, conclude 29 European, Australian and U.S. scientists in an article in the Sept. 24 issue of the scientific journal Nature. Both Arizona State University and the University of Arizona are represented on the international list of co-authors of this groundbreaking report.
Scientists have been warning for decades that the explosion of human activity since the industrial revolution is pushing the Earth's resources and natural systems to their limits. The data confirm that 6 billion people are capable of generating a global geophysical force the equivalent to some of the great forces of nature - just by going about their daily lives.
This force has given rise to a new era - Anthropocene - in which human actions have become the main driver of global environmental change.
"On a finite planet, at some point, we will tip the vital resources we rely upon into irreversible decline if our consumption is not balanced with regenerative and sustainable activity," says co-author Sander van der Leeuw who directs the School of Human Evolution and Social Change at Arizona State University. Van der Leeuw is an archaeologist and anthropologist specializing in the long term impacts of human activity on the landscape. He also co-directs ASU's Complex Adaptive Systems Initiative that focuses ASU's interdisciplinary strength on large-scale problems where an integrated effort is essential to finding solutions.
Defining planetary boundaries
It started with a fairly simple question: How much pressure can the Earth system take before it begins to crash?
"Until now, the scientific community has not attempted to determine the limits of the Earth system's stability in so many dimensions and make a proposal such as this. We are sending these ideas out through the Nature article to be vetted by the scientific community at large," explains van der Leeuw, whose experience includes leading interdisciplinary initiatives in ASU's College of Liberal Arts and Sciences.
"We expect the debate on global warming to shift as a result, because it is not only greenhouse gas emissions that threaten our planet's equilibrium. There are many other systems and they all interact, so that crossing one boundary may make others even more destabilized," he warns.
Nine boundaries were identified, including climate change, stratospheric ozone, land use change, freshwater use, biological diversity, ocean acidification, nitrogen and phosphorus inputs to the biosphere and oceans, aerosol loading and chemical pollution. The study suggests that three of these boundaries - climate change, biological diversity and nitrogen input to the biosphere - may already have been transgressed.
"We must make these complicated ideas clear in such a way that they can be widely applied. The threats are so enormous that it is too late to be a pessimist," says van der Leeuw.
"A safe operating space for humanity"
Using an interdisciplinary approach, the researchers looked at the data for each of the nine vital processes in the Earth system and identified a critical control variable. Take biodiversity loss, for example, the control variable is the species extinction rate, which is expressed in extinctions per million species per year.
They then explored how the boundaries interact. Here, loss of biodiversity impacts carbon storage (climate change), freshwater, nitrogen and phosphorous cycles, and land systems.
In the Nature report titled "A safe operating space for humanity," the scientists propose bold move: A limit for each boundary that would maintain the conditions for a livable world. For biodiversity, that would be less than 10 extinctions per million species per year. The current status is greater than 100 species per million lost per year, whereas the pre-industrial value was 0.1-1.
The researchers stress that their approach does not offer a complete roadmap for sustainable development, but does provide an important element by identifying critical planetary boundaries.
"Human pressure on the Earth system has reached a scale where abrupt global environmental change can no longer be excluded. To continue to live and operate safely, humanity has to stay away from critical 'hard-wired' thresholds in Earth's environment, and respect the nature of planet's climatic, geophysical, atmospheric and ecological processes," says lead author Professor Johan Rockström, director of the Stockholm Resilience Centre at Stockholm University. "Transgressing planetary boundaries may be devastating for humanity, but if we respect them we have a bright future for centuries ahead," he continues.
Alarm bells for Arizona
"Our attempt to identify planetary boundaries that, if crossed, could have serious environmental and social consequences has a special resonance in the southwest where pressures on biodiversity, land use, and water are likely to intersect with climate change to create tremendous challenges for landscapes and livelihoods," explains co-author Diana Liverman, a professor of geography and development at the University of Arizona.
Liverman, who also is professor of environmental science and a senior fellow of Oxford University's Environmental Change Institute, is currently attending an international climate conference at Oxford, United Kingdom. Participants are discussing the implications for humans and Earth ecosystems of a 4 degree Centigrade global temperature rise.
She adds: "Three of the boundaries we identify - 350 parts per million of atmospheric carbon dioxide, biodiversity extinction rates more than 10 times the background rate, and no more than 35 million tons of nitrogen pollution per year - have already been exceeded with fossil fuel use, land use change, and agricultural pollution, driving us to unsustainable levels that are producing real risks to our survival."
In addition to Liverman, Rockström and van der Leeuw, the group of authors includes Hans Joachim Schellnhuber, Will Steffen, Katherine Richardson, Jonathan Foley and Nobel laureate Paul Crutzen. Other authors are listed on the paper at nature.
Source:
Carol Hughes
Arizona State University
Scientists have been warning for decades that the explosion of human activity since the industrial revolution is pushing the Earth's resources and natural systems to their limits. The data confirm that 6 billion people are capable of generating a global geophysical force the equivalent to some of the great forces of nature - just by going about their daily lives.
This force has given rise to a new era - Anthropocene - in which human actions have become the main driver of global environmental change.
"On a finite planet, at some point, we will tip the vital resources we rely upon into irreversible decline if our consumption is not balanced with regenerative and sustainable activity," says co-author Sander van der Leeuw who directs the School of Human Evolution and Social Change at Arizona State University. Van der Leeuw is an archaeologist and anthropologist specializing in the long term impacts of human activity on the landscape. He also co-directs ASU's Complex Adaptive Systems Initiative that focuses ASU's interdisciplinary strength on large-scale problems where an integrated effort is essential to finding solutions.
Defining planetary boundaries
It started with a fairly simple question: How much pressure can the Earth system take before it begins to crash?
"Until now, the scientific community has not attempted to determine the limits of the Earth system's stability in so many dimensions and make a proposal such as this. We are sending these ideas out through the Nature article to be vetted by the scientific community at large," explains van der Leeuw, whose experience includes leading interdisciplinary initiatives in ASU's College of Liberal Arts and Sciences.
"We expect the debate on global warming to shift as a result, because it is not only greenhouse gas emissions that threaten our planet's equilibrium. There are many other systems and they all interact, so that crossing one boundary may make others even more destabilized," he warns.
Nine boundaries were identified, including climate change, stratospheric ozone, land use change, freshwater use, biological diversity, ocean acidification, nitrogen and phosphorus inputs to the biosphere and oceans, aerosol loading and chemical pollution. The study suggests that three of these boundaries - climate change, biological diversity and nitrogen input to the biosphere - may already have been transgressed.
"We must make these complicated ideas clear in such a way that they can be widely applied. The threats are so enormous that it is too late to be a pessimist," says van der Leeuw.
"A safe operating space for humanity"
Using an interdisciplinary approach, the researchers looked at the data for each of the nine vital processes in the Earth system and identified a critical control variable. Take biodiversity loss, for example, the control variable is the species extinction rate, which is expressed in extinctions per million species per year.
They then explored how the boundaries interact. Here, loss of biodiversity impacts carbon storage (climate change), freshwater, nitrogen and phosphorous cycles, and land systems.
In the Nature report titled "A safe operating space for humanity," the scientists propose bold move: A limit for each boundary that would maintain the conditions for a livable world. For biodiversity, that would be less than 10 extinctions per million species per year. The current status is greater than 100 species per million lost per year, whereas the pre-industrial value was 0.1-1.
The researchers stress that their approach does not offer a complete roadmap for sustainable development, but does provide an important element by identifying critical planetary boundaries.
"Human pressure on the Earth system has reached a scale where abrupt global environmental change can no longer be excluded. To continue to live and operate safely, humanity has to stay away from critical 'hard-wired' thresholds in Earth's environment, and respect the nature of planet's climatic, geophysical, atmospheric and ecological processes," says lead author Professor Johan Rockström, director of the Stockholm Resilience Centre at Stockholm University. "Transgressing planetary boundaries may be devastating for humanity, but if we respect them we have a bright future for centuries ahead," he continues.
Alarm bells for Arizona
"Our attempt to identify planetary boundaries that, if crossed, could have serious environmental and social consequences has a special resonance in the southwest where pressures on biodiversity, land use, and water are likely to intersect with climate change to create tremendous challenges for landscapes and livelihoods," explains co-author Diana Liverman, a professor of geography and development at the University of Arizona.
Liverman, who also is professor of environmental science and a senior fellow of Oxford University's Environmental Change Institute, is currently attending an international climate conference at Oxford, United Kingdom. Participants are discussing the implications for humans and Earth ecosystems of a 4 degree Centigrade global temperature rise.
She adds: "Three of the boundaries we identify - 350 parts per million of atmospheric carbon dioxide, biodiversity extinction rates more than 10 times the background rate, and no more than 35 million tons of nitrogen pollution per year - have already been exceeded with fossil fuel use, land use change, and agricultural pollution, driving us to unsustainable levels that are producing real risks to our survival."
In addition to Liverman, Rockström and van der Leeuw, the group of authors includes Hans Joachim Schellnhuber, Will Steffen, Katherine Richardson, Jonathan Foley and Nobel laureate Paul Crutzen. Other authors are listed on the paper at nature.
Source:
Carol Hughes
Arizona State University
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