Extinction Most Likely For Rare Trees In The Amazon Rainforest

Common tree species in the Amazon will survive even grim scenarios of deforestation and road-building, but rare trees could suffer extinction rates of up to 50 percent, predict Smithsonian scientists and colleagues in the Aug. 12 issue of the journal Proceedings of the National Academy of Science.


How resilient will natural systems prove to be as they weather the next several decades of severe, human-induced global change? The debate is on between proponents of models that maximize and minimize extinction rates.


The Amazon basin contains about 40 percent of the world's remaining rainforest. One of the fundamental characteristics of tropical forests is the presence of very rare tree species. Competing models of relative species abundance, one based on Fisher's alpha statistic and the other based on Preston's lognormal curve, yield different proportions of rare trees in the forest.


Thirty years ago Stephen P. Hubbell, senior scientist at the Center for Tropical Forest Science of the Smithsonian Tropical Research Institute and distinguished professor in the Department of Ecology and Evolution at the University of California, Los Angeles, and his colleague Robin Foster, now at the Field Museum in Chicago, set up a unique experiment to monitor the growth, birth and death of more than 250,000 tropical trees on Panama's Barro Colorado Island. This large "forest dynamics plot" would generate the data needed to build good models that include rare species.


Today the Center for Tropical Forest Science coordinates a Global Earth Observatory-a network of 20 such forest study sites in 17 countries, which maintains "actuarial tables" for more than 3 million trees.


Hubbell works with data from the network to develop and test his neutral theory of biodiversity-an attempt to find a unified explanation of large, complex biological systems that accurately predicts the outcome of major ecological and evolutionary forces of change.


In this offering, the authors use the neutral theory to predict the number of tree species and to test predictions of the Millenium Ecosystems Assessment that forecasts major tree extinctions in the Amazon over the next several decades. First, they estimate that the Brazilian Amazon has (or had) 11,210 large tree species, and, of these, 5,308 species are classified as rare.


Based on optimistic and non-optimistic scenarios for road construction in the Amazon published by the Smithsonian's William Laurance and colleagues in the journal Science in 2004, they predict that the rare species will suffer between 37 and 50 percent extinction, whereas the extinction rate for all trees could be from 20 to 33 percent overall.


Would a simpler Amazon forest lacking many of its rarer trees function? Will the extinction of species other than trees-pollinators, seed predators, carnivores-contribute significantly to the lost of rainforest resilience? This and other biological quandaries remain. The authors exhort: "Although it is an old scientific chestnut, we must once again emphasize how important it is to support continuing basic science on tropical forests."


The Smithsonian Tropical Research Institute, headquartered in Panama City, Panama, is a unit of the Smithsonian Institution. The institute furthers the understanding of tropical nature and its importance to human welfare, trains students to conduct research in the tropics and promotes conservation by increasing public awareness of the beauty and importance of tropical ecosystems. For more information, visit stri.


Ref: Stephen P. Hubbell, Fangliang He, Richard Condit, Luis Borda-de-Agua, and Hans ter Steege. 2008. How many tree species are there in the Amazon and how many of them will go extinct? Proceedings of the National Academy of Science, August 12 early online edition.


Smithsonian Tropical Research Institute

A Step Forward In Virology - Trojan Horse Of Viruses Revealed

Viruses use various tricks and disguises to invade
cells. ETH Zurich researchers have now discovered yet another strategy
used by viruses: the vaccinia virus disguises itself as cell waste, triggers
the formation of evaginations in cells and is suspected to enter the cell
interior before the immune defense even notices. The research results
have been published in Science.


The vaccinia virus has a problem: it is a giant among viruses and needs a
special
strategy in order to infiltrate a cell and reproduce. Professor Ari Helenius
and Postdoc Jason Mercer from ETH Zurich's Institute for Biochemistry have
now discovered what this strategy is. In the process, they stumbled upon new
and surprising findings.


The invasion strategy


In order to infiltrate a cell, the vaccinia virus exploits the cellular
waste disposal
mechanism. When a cell dies, other cells in the vicinity ingest the remains,
without
needing waste disposal experts such as macrophages. The cells recognize
the waste via a special molecule, phosphatidylserine, which sits on the
inner
surface of the double membrane of cells. This special molecule is pushed out
as
soon as the cell dies and is broken into parts. The vaccinia virus itself
also carries
this official waste tag on its surface. "The substance accumulates on the
shell of vaccinia viruses", Jason Mercer explained. The pathogen disguises
itself
as waste material and tricks cells into digesting it, just as they normally
would
with the remains of dead cells. As the immune response is simultaneously
suppressed,
the virus can be ingested as waste without being noticed.


The uptake into the cell itself is via macropinocytosis. The ETH Zurich
researchers
have demonstrated that the vaccinia virus moves along actin-rich
filamentous extensions towards the cell. As soon as they impinge upon the
cell
membrane, an evagination forms, a bleb. The virus itself is the trigger for
the
formation of the evagination. Using a messenger substance to "knock on the
door", the virus triggers a signaling chain reaction inside the cell so that
the bleb
forms, catches the virus and smuggles it into the cell.


Proteins as unsuspecting allies


"The viruses are the Trojan horses that want to enter Troy; the Trojans are
the
many proteins that transmit the signals and open the 'city gates' to the
unwelcome
guest", Ari Helenius said. Aided by Professor Lukas Pelkmans' team, Jason
Mercer examined over 7000 different proteins in order to find out not only
which Trojans let the virus in, but which as well are chiefly involved in
the supply
chain. Using definitive methods, the researchers de-activated each one of
the
suspected proteins to examine their function,and narrowed the vast number of
proteins down to 140 potential culprits. The enzyme kinase PAK1 turned out
to
be an especially "helpful" citizen of Troy. Without PAK1, the pathogen's
trick did
not work and the cell did not form any evaginations.















Until now, very little has been known about the mechanism vaccinia viruses
use
to infiltrate a cell. Professor Helenius, whose research objective is to
find out
what methods and strategies various different viruses employ to invade
somatic
cells, clarified "This strategy is a new one". Other viruses, such as
herpes,
adeno and H1 viruses use macropinocytosis. However the vaccinia virus is the
first one identified that uses apoptotic mimicry as an entry strategy.


Knowledge of the virus strategies and the signal proteins involved in the
ingestion
of a virus by a cell is crucial to finding and developing new agents against
the pathogens. Until now, antiviral medication has targeted the virus
itself. Ari
Helenius, however, is looking for substances that interrupt the signaling
chain
and halt the communication between the virus and the cell. If the cell does
not
ingest a virus, the virus cannot reproduce and is quickly eliminated by the
immune
system. This process also has another big advantage: "Viruses cannot
adapt to the obstruction of the signal chain all that quickly", he said.


Smallpox: a bioterrorist attack?


The vaccinia virus belongs to a family of particularly dangerous viruses,
namely the pox
viruses. The most infamous member, Variola, the casitive agent of smallpox
constituted
a global pandemic disease in the Middle Ages, causing the deaths of millions
of people,
especially among the indigenous population of North America who became
infected by
European settlers. Pox was the first viral disease against which a
vaccination was developed.


In 1771, the first rudimentary vaccine was produced from cowpox viruses,
which protected people from the sequelae of the disease. Since 1978, the
disease has
been classed as eradicated and officially is preserved in only two
laboratories; one in
Atlanta, the other in Novosibirsk. US authorities, however, fear
bioterrorist attacks with
pox viruses. Research on these dangerous pathogens is thus encouraged.


ETH Zurich (Swiss Federal Institute of Technology Zurich) has a student body
of nearly fourteen
thousand students from 80 nations. About 360 professors teach mainly in
engineering
sciences and architecture, system-oriented sciences, mathematics and natural
sciences, as
well as carry out research that is highly valued worldwide. Distinguished by
the successes of
21 Nobel laureates, ETH Zurich is committed to providing its students with
unparalleled education
and outstanding leadership skills.


ETH Zurich

Researchers Discover How Compounds Found In Red Wine Thwart Alzheimer's Disease In Mice

Scientists call it the "French paradox" - a society that, despite consuming food high in cholesterol and saturated fats, has long had low death rates from heart disease. Research has suggested it is the red wine consumed with all that fatty food that may be beneficial - and not only for cardiovascular health but in warding off certain tumors and even Alzheimer's disease.



Now, Alzheimer's researchers at UCLA, in collaboration with Mt. Sinai School of Medicine in New York, have discovered how red wine may reduce the incidence of the disease. Reporting in the Nov. 21 issue of the Journal of Biological Chemistry, David Teplow, a UCLA professor of neurology, and colleagues show how naturally occurring compounds in red wine called polyphenols block the formation of proteins that build the toxic plaques thought to destroy brain cells, and further, how they reduce the toxicity of existing plaques, thus reducing cognitive deterioration.



Polyphenols comprise a chemical class with more than 8,000 members, many of which are found in high concentrations in wine, tea, nuts, berries, cocoa and various plants. Past research has suggested that such polyphenols may inhibit or prevent the buildup of toxic fibers composed primarily of two proteins - AГџ40 and AГџ42 - that deposit in the brain and form the plaques which have long been associated with Alzheimer's. Until now, however, no one understood the mechanics of how polyphenols worked.



Teplow's lab has been studying how amyloid beta (AГџ) is involved in causing Alzheimer's. In this work, researchers monitored how AГџ40 and AГџ42 proteins folded up and stuck to each other to produce aggregates that killed nerve cells in mice. They then treated the proteins with a polyphenol compound extracted from grape seeds. They discovered that polyphenols carried a one-two punch: They blocked the formation of the toxic aggregates of AГџ and also decreased toxicity when they were combined with AГџ before it was added to brain cells.



"What we found is pretty straightforward," Teplow said. "If the AГџ proteins can't assemble, toxic aggregates can't form, and thus there is no toxicity. Our work in the laboratory, and Mt. Sinai's Dr. Giulio Pasinetti's work in mice, suggest that administration of the compound to Alzheimer's patients might block the development of these toxic aggregates, prevent disease development and also ameliorate existing disease."



Human clinical trials are next.



"No disease-modifying treatments of Alzheimer's now exist, and initial clinical trials of a number of different candidate drugs have been disappointing," Teplow said. "So we believe that this is an important next step."







This work was supported by the National Institutes of Health; the Department of Veterans Affairs; the James J. Peters Veterans Affairs Medical Center Geriatric Research Education Clinical Center Program, Polyphenolics (to Giulio Pasinetti); grants from the Japan Human Science Foundation and the Mochida Memorial Foundation for Medical and Pharmaceutical Research; grants from the Alzheimer's Association; and the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at UCLA (to David Teplow). Teplow reports no conflict of interests.



The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks first among its peers nationwide in National Institutes of Health funding. For more information, visit neurology.medsch.ucla.



Source: Mark Wheeler


University of California - Los Angeles

Less Expensive Alternative To Therapeutic Antibodies May Be Synthetic Molecules

Researchers at UT Southwestern Medical Center have developed a simple and inexpensive method to screen small synthetic molecules and pull out a handful that might treat cancer and other diseases less expensively than current methods.



In one screen of more than 300,000 such molecules, called peptoids, the new technique quickly singled out five promising candidates that mimicked an antibody already on the market for treating cancer. One of the compounds blocked the growth of human tumors in a mouse model.



Antibodies are molecules produced by the body to help ward off infection. Natural and manmade antibodies work by latching onto very specific targets such as receptors on the surface of cells.



"Many new drugs being made today are antibodies, but they are extremely expensive to make. Financially, the U.S. health care system is going to have a difficult time accommodating the next 500 drugs being antibodies," said Dr. Thomas Kodadek, chief of translational research at UT Southwestern and senior author of the study, which appears online and in an upcoming issue of the Journal of the American Chemical Society.



"Our results show that a peptoid can attack a harmful receptor in the body with the same precision as an antibody, but would cost much less to develop," said Dr. Kodadek.



Peptoids are designed in the laboratory to resemble chains of natural molecules called peptides. Some peptides are used as medications, such as insulin or antibodies used to treat some cancers, but because the stomach digests them, most can't be taken by mouth and must be injected.



By contrast, peptoids are resistant to the stomach enzymes that degrade natural peptides, so it is possible that they could be swallowed as a pill. Peptoids are much less expensive and easier to manufacture than antibodies, Dr. Kodadek said. They are also much smaller than antibodies, so they might be better at penetrating tumors or other disease sites, he said.



"Our technique is simple and fast, works with existing chemicals and needs no high-tech instrumentation, except for a microscope to detect the fluorescent colors we use to sort the compounds," said Dr. D. Gomika Udugamasooriya, postdoctoral researcher in internal medicine and lead author of the study.



The new technique also has major advantages over traditional screening techniques that are commonly used to discover biologically active compounds from large collections. These screens, which require extensive automation, generally cost $40,000 or more; the new method can be conducted for less than $1,000.



The researchers screened about 300,000 peptoids to see which ones would interact with VEGFR2, a type of molecule on the surface of human cells. VEGFR2 is essential in creating new blood vessels through interaction with the hormone VEGF, which is normally a helpful process but is harmful to the body when the new blood vessels are nourishing a growing tumor.
















A commercially produced antibody is used to treat some cancers by blocking the VEGF-VEGFR2 interaction and thus starving the tumor, but it costs a patient about $20,000 a year, Dr. Kodadek said.



The new screening technology involves hundreds of thousands of peptoids, bound to tiny plastic beads. In the study, the cells with VEGFR2 were labeled to fluoresce red and those lacking VEGFR2 were labeled to fluoresce green. After exposing the beads to the mixture of cells, the beads were examined under a fluorescent microscope. Those bound to red cells - the ones with VEGFR2 - were collected.



This screen, which took a couple of days, isolated five peptoids out of approximately 300,000 screened, showing that the process was an effective way to quickly narrow down a search, Dr. Kodadek said.



The researchers further tested one of the five peptoids that bound most tightly to VEGFR2 and found that it blocked VEGFR2's action in cultured cells. When they gave it in low doses to mice with implanted human bone- and soft-tissue cancer, the peptoid slowed the growth of the tumors and reduced the density of blood vessels leading to them.



"This new technique of rapidly isolating biologically active peptoids offers a way to hasten the drug-discovery process and may ultimately benefit patients by providing them with new therapies at a fraction of the cost of current drugs," Dr. Kodadek said.



Other UT Southwestern researchers who participated in the study were general surgery resident Dr. Sean Dineen and Dr. Rolf Brekken, assistant professor of surgery.



The work was supported by the National Heart, Lung and Blood Institute and The Welch Foundation.







Source: Aline McKenzie


UT Southwestern Medical Center

A Mechanism To Explain Biological "Cross Talk" Between 24 Hour Body Cycle And Metabolism

It's well known that the body's energy levels cycle on a 24 hour, or circadian, schedule, and that this metabolic process is fueled by oxygen. Now, researchers at the University of Pennsylvania School of Medicine have found that a protein called Rev erb coordinates the daily cycles of oxygen carrying heme molecules to maintain the body's correct metabolism.


The research appears online this week in Science Express in advance of print publication in Science.


Many studies, including this one, point to a link between the human internal clock and such metabolic disorders as obesity and diabetes. Proteins such as Rev erb are the gears of the clock and understanding their role is important for fighting these diseases.


"This is the next chapter on Rev erb, a member of a family of cell nucleus proteins that includes receptors for anti diabetic drugs," explains senior author Mitchell A. Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at Penn. About two years ago Lazar's group discovered that Rev erb was a critical component of the circadian clock. In this paper, they found that the activity of Rev erb is controlled by heme.


Heme represents the body's most important way of transporting and using oxygen, which would simply bubble away in the body without being bound to heme. "In a molecular baton hand off, oxygen is transferred from heme in the bloodstream to the heme molecules found inside a cell," says Lazar, of how oxygen reaches cells to run their metabolic needs. One of the most important roles of heme inside cells is to facilitate the use of oxygen to generate energy in the process known as cellular respiration.


The findings further tie together the 24-hour cycle of the body with metabolic function. "Circadian rhythms are our sleep wake cycle and metabolism is how we process food, so it makes sense that there would be biological cross talk between the body's 24 hour rhythm and metabolic function," says Lazar. Indeed, scientists already recognize that getting too much or too little sleep increases the risk of diabetes. The newly discovered circadian/metabolic link could be the focus of a new generation of diabetes treatments.


The Penn group worked with scientists at GlaxoSmithKline, who demonstrated that the Rev erb protein can physically bind to heme in the test tube. The Penn scientists then found that heme, by regulating the activity of Rev erb, reduces the amount of glucose produced by liver cells.


"What's exciting about this is that it puts heme in a central role in the metabolic regulation of the cell," says Lazar. "Not only is it a key component in making energy, but also in the pathway for turning off glucose production." Excessive glucose production by the liver is a major cause of high blood sugar in diabetes.


This work was funded by the National Institute of Diabetes and Digestive and Kidney Disease. Co-authors are first author Lei Yin, Joshua C. Curtin, Mohammed Qatananai, and Nava R. Szwergold, all from Penn and Robert A. Reid, Gregory M. Waitt, Derek J. Parks, Kenneth H. Pearce, and G. Bruce Wisely, from GlaxoSmithKline, Research Triangle Park, NC.


PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.


Penn's School of Medicine is currently ranked #3 in the nation in U.S. News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.


The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary care provider network; two multispecialty satellite facilities; and home care and hospice.


University of Pennsylvania School of Medicine

3600 Market St., Ste 240

Philadelphia, PA 19104

United States

med.upenn

Powerful Integration Of Lipid Metabolic Profiling With Gene Expression Analysis

A recently published research article in the Journal of Proteome Research, authored by researchers from the Nestle Reserarch Center, Genomatix Software GmbH, Rosetta Inpharmatics LLC, CXR Biosciences Ltd, the Cancer Research UK Molecular Pharmacology Unit demonstrates the synergisms and enhanced analytic power of the combination of thorough metabolic profiling with the unique and proprietary microarray analysis methods of Genomatix Software GmbH.



The study elucidated the effects on Mouse lipid metabolism by the disruption of hepatic Cytochrome P450 reductase (POR) in a POR deficient knock-out mouse model. It clearly could demonstrate that though gene expression and lipid metabolism in extrahepatic tissues being sensitive to hepatic POR functionality, the lipidome in general is only minimally affected. Analysis of regulatory pathways and networks, observed expression changes and lipid profiling led to the conclusion that POR can be considered an enzyme critical for the proper functioning of lipid mobilization and metabolism predominantly within the mouse liver with only minor effects on lipid metabolism in the biological system at large.



The concordance between the two analytical platforms (Genomatix transcriptomic vs lipidomic) in the liver was excellent, and serves as a demonstration for the valid approach for generating novel hypГјotheses to unravel protein function that cannot be accomplished with as much confiodence using either platform individually.



"I am very excited about the possibility to overlay metabolic profiles with expression data and pathway information. We see the strategies applied in this study as a prototype for further analyzes bringing together metabolomics and expression analysis in a multiple lines of evidence manner. " says Dr. Martin Seifert, co-author of the study and Vice President Microarray Business and Collaborative Research at Genomatix.







Citation:


Mutch DM, Klocke B, Morrison P, Murray CA, Henderson CJ, Seifert M, Williamson G (2007)

The Disruption of Hepatic Cytochrome P450 Reductase Alters Mouse Lipid Metabolism.

J Proteome Res. 6, 3976-3984
[PUBMED: 17722906]



About Genomatix:



Genomatix is a pioneer and leader in the analysis and understanding of eukaryotic gene regulation. Core competences at Genomatix are annotation driven microarray analysis, ChIP on chip, regulatory network and pathway mining, and promoter analysis on sequence level. Genomatix has published more than 170 peer reviewed scientific papers that have been cited in more than 4,000 papers. Over 35,000 researchers worldwide currently apply Genomatix tools and databases. More information is available from genomatix/.



Source: Klaus May


Genomatix Software GmbH

Fluorescence Microscopy Reveals Why Some Antifreeze Proteins Inhibit Ice Growth Better Than Others

Finding could have medical, commercial applications



Antifreeze or "ice structuring" proteins - found in some fish, insects, plants, fungi and bacteria - attach to the surface of ice crystals to inhibit their growth and keep the host organism from freezing to death. Scientists have been puzzled, however, about why some ice structuring proteins, such as those found in the spruce budworm, are more active than others.



Fluorescence microscopy now has shown how those aggressive proteins protect the cells of the insect, which is native to U.S. and Canadian forests.



The finding could have future applications in medical, agricultural and commercial food industries, according to a team of scientists led by Ido Braslavsky, an assistant professor of physics and astronomy at Ohio University, and Peter Davies, a professor of biochemistry and biology at Queen's University in Canada. They presented the work at the March meeting of the American Physical Society in Denver, Colo.



In the recent study, Davies' lab combined spruce budworm and fish antifreeze proteins with a fluorescent tag. Using a fluorescent microscope, Braslavsky and postdoctoral fellow Natalya Pertaya could observe how the proteins interacted with the surfaces of ice crystals. They found that the hyperactive antifreeze protein from the spruce budworm stops ice crystals from growing in particular directions. The antifreeze proteins from fish are less effective.



Antifreeze proteins, especially the hyperactive type found in the spruce budworm and other organisms, have various potential applications, according to Braslavsky. They could be used to preserve organs and tissues for medical applications such as transplants, and also could prevent frostbite. They also can inhibit crystal growth in ice cream - an application already in use by at least one commercial food manufacturer - as well as protect against agricultural frost damage.






The research was funded by Ohio University's NanoBioTechnology Initiative and the Canadian Institutes of Health Research.



Contacts:


Ido Braslavsky

In collaboration with John Wettlaufer, a professor of physics and geophysics from Yale University, the team also has published a related paper on antifreeze protein research in Biophysical Journal. The paper is available online at biophysj/cgi/rapidpdf/biophysj.106.096297v1.



Note: Images can be downloaded here.



Contact: Andrea Gibson


Ohio University

Access Pharmaceuticals Initiates Program Applying Cobalamin Platform To SiRNA Drug Delivery

ACCESS PHARMACEUTICALS, INC. (OTC Bulletin Board: ACCP) announced that it initiated an internal pre-licensing program to confirm the utility of its proprietary Cobalamin (vitamin B12) platform technology for targeted delivery of siRNA therapies. The program is considered important because, despite the widely publicized potential of RNA therapy, researchers up to now have been stymied in their efforts to design a pharmaceutical product that efficiently transports siRNA therapeutics into the cells they are designed to inhibit or kill.


Access has multiple programs ongoing around use of its Cobalamin technology to facilitate oral absorption of pharmaceuticals, including previously announced collaborations with potential pharma and biotech partners. To date, its successful Cobalamin product development program has focused on the oral delivery of insulin and human growth hormone, two peptides that currently can only be given by injection. Because these two molecules share some of the same physical characteristics as RNA's active components, Access believes its Cobalamin technology could effectively deliver RNA therapy in an oral tablet instead of by injection.


But a more compelling feature of the Cobalamin technology may be its ability to overcome the cellular transport obstacles that have held back fuller development of RNA therapy. The large size and high negative charge of RNA molecules prevents their absorption by target cells. Using the 'Trojan Horse' principle, the Cobalamin nanoparticle technology can encapsulate small fragments of RNA (siRNA) and utilize the Colalamin's vitamin B12 uptake mechanism to transport them into target cells, allowing release of the active drug to initiate the therapeutic effect. Cobalamin's vitamin B12 uptake mechanism offers the potential for targeted delivery of siRNA because most human cells have a requirement for vitamin B12. This is served by cell surface receptors, which facilitate absorption of this vitamin. In many diseases, the demand for vitamin B12 is increased, with a corresponding upregulation of the receptor.


"Access scientists and collaborators have so far demonstrated in preclinical models that Cobalamin formulations are effective in achieving good oral drug delivery of charged peptides such as insulin and human growth hormone," commented David P. Nowotnik, Senior Vice President, Research and Development. "These successes with molecules which share some of the same physical characteristics as siRNA would indicate that we should now be able to generate effective formulations of Cobalamin nanoparticles for delivery of siRNA. We know already from previous work that we can make cancer drugs more effective using the Cobalamin approach, and so we have a sound scientific basis for the future development of Cobalamin RNAi therapeutics."


Cobalamin is Access' proprietary technology based upon the use of vitamin B12 for targeted delivery of drugs to disease sites and for oral drug delivery of drugs that otherwise have poor oral bioavailability. Access has focused its Cobalamin product development program on the oral delivery of insulin and human growth hormone, two peptides that currently can only be given by injection. Since presenting promising results at a major conference in mid-2008, Access has made substantial improvements to the formulation technology. A new Cobalamin-coated insulin-containing nanoparticle formulation delivered orally provided a pharmacological response (lowering of blood glucose levels in an animal model of diabetes) equivalent to greater than 80% of that achieved by insulin delivered subcutaneously. This represents a substantial oral bioavailability, indicating that this formulation has potential for clinical development and ultimate commercialization. Adaptation of this technology has provided a Cobalamin human growth hormone formulation that has demonstrated good efficacy, represented by more than 25% improvement in weight gain, when given orally in an established animal model. Access continues to move both products towards clinical development, and plans to submit an additional patent application to protect the improvements to the technology.















About Access:


Access Pharmaceuticals, Inc. is an emerging biopharmaceutical company that develops and commercializes propriety products for the treatment and supportive care of cancer patients. Access' products include ProLindac™ currently in Phase 2 clinical testing of patients with ovarian cancer, and MuGard™ for the management of patients with mucositis. The company also has other advanced drug delivery technologies including Cobalamin™-mediated targeted delivery and oral drug delivery, its proprietary nanopolymer delivery technology based on the natural vitamin B12 uptake mechanism and Thiarabine, a new generation nucleoside analog which has demonstrated both pre-clinical and clinical activity in certain cancers.


This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, and that involve risks and uncertainties. These statements include those relating to: our cash burn rate, clinical trial plans and timelines and clinical results for ProLindac, MuGard, Thiarabine and Cobalamin and other product candidates, our ability to achieve clinical and commercial success and our ability to successfully develop marketed products. These statements are subject to numerous risks, including but not limited Access' need to obtain additional financing in order to continue the clinical trial and operations and to the risks detailed in Access' Annual Reports on Form 10-K and other reports filed by Access with the Securities and Exchange Commission.


Source: Access Pharmaceuticals, Inc

DNA Ends: Common Tool, Different Job

Every time a cell repairs or replicates its DNA, the resulting single strand is wrapped up by a dedicated protein complex. In eukaryotes or organisms whose cells have a nucleus, this job is handled by a tripartite complex called replication protein A (RPA). Researchers at the Salk Institute for Biological Studies have now unearthed a novel RPA-like complex that specifically homes in on the short single-stranded DNA "tail" end of yeast chromosomes.



Their findings, reported in the online edition of Nature Structural & Molecular Biology, will help scientists to better understand the dynamics that keep chromosomes ends, called telomeres, intact.



"Identification of this new RPA-like complex, which is targeted to a specific region of the genome, suggests that multiple RPA-like complexes have evolved, each making individual contributions to genomic stability," says the study's lead author Vicki Lundblad, Ph.D., a professor in the Molecular Cell Biology Laboratory at the Salk Institute.



With each round of cell division, telomeres - long stretches of repetitive DNA - erode a little bit further. Some have likened this progressive shortening to a genetic biological clock that winds down over time. In fact, when telomeres reach a "critical length," the cell can no longer multiply - a characteristic sign of cellular senescence.



In certain cells, such as our germ cells or baker's yeast cells, which need to divide indefinitely, an enzyme called telomerase elongates telomeres to compensate for the continual attrition at chromosome ends. At the same time, telomerase activity is the main mechanism by which human tumor cells achieve immortal growth.



In addition, the natural ends of chromosomes could potentially look like broken strands of DNA that a cell's repair machinery is designed to fix. This has been a long-standing puzzle, because mending chromosome ends as though they were double-strand breaks would result in either unregulated degradation or end-to-end fusions. Such repair events are lethal for the genome, and in certain settings, can promote the development of cancer.



About 10 years ago, Lundblad discovered that Cdc13, a protein that binds single-stranded telomeric DNA, plays a central role at the telomeres of baker's yeast. But the function of two Cdc13-associated proteins, Stn1 and Ten1, remained unclear.



When members of the Lundblad laboratory searched the Protein Data Bank for relatives of Stn1, they dug up Rpa2, the middle subunit of the RPA complex. In particular, Stn1 and Rpa2 share similarities in a region known as oligonucleotide/oligosaccharide-binding fold or OB-fold, a protein fold that is commonly used to recognize and bind to either DNA or RNA.



Based on these findings, Lundblad and her colleagues developed a model, which predicts that Cdc13, Stn1 and Ten1 come together at the very end of chromosomes to form a telomere-dedicated RPA-like complex they dubbed the t-RPA complex.



Graduate student and first author Hua Gao tested this model, using detailed biochemical experiments which revealed that Stn1 and Ten1 behave just like their counterparts in the conventional RPA complex. However, Stn1 and Ten1 have the same predilection for single-stranded telomeric DNA as Cdc13, thereby helping to ensure that this complex only targets chromosome tips.



According to Lundblad, this finding raises important questions about the potential biological parallels between the conventional RPA complex and the newly discovered t-RPA complex.



"Whereas the conventional RPA complex acts elsewhere in the genome to raise a red flag to attract the attention of the repair machinery," says Lundblad, "curiously, the t-RPA complex performs the exact opposite function at chromosome ends, ensuring that these tips do not become targets for DNA repair."







Lundblad's group is currently working on elucidating what distinguishes the activities of these two RPA complexes from each other. Researchers who also contributed to this work include postdoctoral researcher Rachel B. Cervantes, Ph.D., and graduate students Edward K. Mandell and Joel. H. Otero.



The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.



Contact: Gina Kirchweger


Salk Institute

UK Primary School Children In Groundbreaking Scientific Publication

A group of UK primary school children have achieved a world first by having their school science project accepted for publication in an internationally recognised peer-reviewed Royal Society journal. The paper, which reports novel findings in how bumblebees perceive colour, is published in Biology Letters.



The research was undertaken by 8-10 year old pupils at Blackawton School in Devon, who investigated the way that bumblebees see colours and patterns. The young scientists found evidence that bees are able to learn and remember cues based on colour and pattern in a spatially complex scene. The field of insect colour and pattern vision is generally poorly understood and the findings reported by the school children represent a genuine advance in the field.



"I'm delighted that this work is going to be published in Biology Letters," said Dave Strudwick, Head of Blackawton School. "Our pupils devised, conducted and wrote up an experiment which resulted in genuinely novel findings, so they deserve to be published. But even more importantly, they had the chance to work with an actual scientist and become one themselves - not just watching the scientist at work but actually participating in and creating the whole scientific process. Science shouldn't be seen as something that is detached from the real world - it's just a certain way of looking at things. This project represents a completely different way of working and learning that I hope will be taken up by other schools and in other subjects."



Professor Brian Charlesworth FRS, Editor of Biology Letters said: "This paper represents a world first in high quality scientific publishing and I'm proud that Biology Letters is supporting this highly innovative approach to science education. This is a unique way of encouraging children's engagement with science by getting a group to write about their work in a publishable format. I hope that it will inspire other groups to realise that science is not an exclusive club but something that's available for everybody."



The project was coordinated and funded by Beau Lotto, a neuroscientist based at UCL's Institute of Opthalmology and Head of Lottolab Studio, an innovative research space which creates installations, musical performances and educational programmes, and performs carefully controlled experiments on perception and behaviour. Beau is currently developing a 'living lab' at London's Science Museum, funded by the Wellcome Trust, which enables the public, including school children, to participate, design and run real science experiments on site.



Dr Lotto said "The publication of a scientific paper entirely conceived and written by schoolchildren shows what's possible if we celebrate uncertainty. Real scientific work is full of uncertainty - that's why it's so exciting - but I find that this is what's lacking in education, where subjects are too often presented as a series of dull factual certainties. The publication of this work is an important step in showing what we can achieve if we're prepared to approach science in a way that's creative, daring and, above all, fun."



As with all papers accepted for publication in Biology Letters, the paper successfully went through peer review. The presentation of the paper is unconventional because the paper contains no references due to the inaccessibility of the existing scientific literature to 8-10 year olds. However, it has been published alongside a commentary by Laurence T. Maloney of New York University's Center for Neural Science and Natalie Hempel de Ibarra of Exeter University's Centre for Research in Animal Behaviour.



In their commentary, which is fully referenced and provides background to the research, Hempel and Maloney write: "The experiments are modest in scope but cleverly and correctly designed and carried out with proper controls to avoid possible artefacts. They lack statistical analyses and any discussion of previous experimental work, but they hold their own among experiments carried out by highly-trained specialists. The experimenters have asked a scientific question and answered it well."


Source:

The Royal Society

UCL (University College London)

Science Museum

Wellcome Trust