Iowa State University Researcher Developed Forerunner Of Nobel Research In 1986

This year's Nobel Prize for chemistry was given to researchers for their work on illuminating living cells that enables scientists and researchers to study how genes, proteins, and entire cells operate.



An Iowa State University professor developed another technology producing similar results more than 20 years ago.



Stephen Howell, director of the Plant Sciences Institute at Iowa State, developed the process when working with the firefly luciferase gene that illuminates cells in an organism, just as the Nobel-winning research does. At the time Howell and his staff were conducting research at the University of California, San Diego.



"Fundamentally it's the same sort of thing," said Howell. "Both of the technologies allow you to visualize things that are otherwise very difficult to see. It might be a biochemical process. Maybe it's a gene turning on and off."



At the time of its discovery, Howell's research and the picture of a glowing tobacco plant got the attention of the national press, including an interview on NBC's "Today Show" and other national and international media.



While the two technologies do much the same thing, the major difference between the them is in how they work.



The technology that was awarded the Nobel Prize uses green fluorescent protein (GFP). It involves incorporating the GFP protein into the living cell and then watching what happens with the use of an ultraviolet light. GFP was developed in 1994.



Howell's 1986 technology takes advantage of the chemiluminescence generating properties of luciferase rather than fluorescence. Luciferase technology does not require using an ultraviolet light as does GFP to see the activity in the cell.



Luciferase allows fireflies to glow and is introduced into other organisms by researchers.



Both of the technologies are competitive and complementary, he said.



"In research we've done over the years here, we've used luciferase and GFP," said Howell of the technologies. "Both of them enable us to visualize, and both are important to our field of research."







Source: Steve Howell


Iowa State University

Gene Knockout Makes Female Mice Masculine

The mammalian fucose mutarotase enzyme is known to be involved in incorporating the sugar fucose into protein. Female mice that lack the fucose mutarotase (FucM) gene refuse to let males mount them, and will attempt copulation with other female mice. Researchers writing in BioMed Central's open access journal BMC Genetics created the FucM mouse mutants in order to investigate the role of this enzyme in vivo.



Chankyu Park worked with a team of researchers from the Korea Advanced Institute of Science and Technology and intriguingly gained some insight into the neurological basis of sexual preference. He said, "The FucM knockout mice displayed drastically reduced sexual receptivity, although pregnancy after forced mating attempts by normal sexually experienced males showed that the animals were fertile. The FucM knock-out mice have reduced levels of alpha-fetoprotein, a protein thought to be involved in development of parts of the brain responsible for reproductive behavior".


The mutant female mice were healthy, and behaved normally towards young mice. When approached by male mice, however, they would not adopt the sexually receptive 'lordosis' position. Furthermore, they lost interest in investigating male urine, unlike normal females, and would attempt to mount other females. Speaking about the results, Park said, "We speculate that these behavioural changes are likely to be related to a neurodevelopmental change in pre-optic area of the female mutant brain , becoming similar to that of a normal male".


Source: BioMed Central Limited

Scientists discover that host cell lipids facilitate bacterial movement

When the bacterium Listeria monocytogenes invades the body, it commandeers its host cell's actin cytoskeleton to invade
other cells. In a report published in the Journal of Biological Chemistry, a group of scientists provide insight into the
molecular mechanisms behind this infection technique.


The research appears as the "Paper of the Week" in the March 25 issue of the Journal of Biological Chemistry, an American
Society for Biochemistry and Molecular Biology journal.


Listeria causes a variety of diseases, the most severe being meningoencephalitis, an inflammation of the brain and the
membranes that envelop the brain and spinal cord. Infection begins when the bacterium binds to a receptor on the surface of a
cell, causing the cell to ingest it. The bacterium multiplies inside the cell and then uses a cellular protein called ActA to
stimulate the host cell's actin to form filaments at one end of the bacterium.


"As these filaments lengthen, they drive the bacterium through the cell until it reaches the peripheral or outer cell
membrane," explains Dr. Frederick Southwick of the University of Florida College of Medicine. "Here the growing actin
filaments push the bacterium against the membrane, forming long membrane projections called filopodia. These filopodia push
into adjacent cells and are ingested by them. The bacteria then enter the new cell and begin the cycle anew. Essentially
Listeria takes over or hijacks the host cell's actin cytoskeleton to move within cells, and to spread from cell to cell."



In most cells, two membrane lipids, PIP2 and PIP3, are associated with the formation of new actin filaments. PIP3 is
synthesized from PIP2 by an enzyme called PI3-kinase. The lipids attract and modify the functions of proteins involved in
regulating actin assembly. PIP2 and PIP3 also prevent capping proteins from binding to the ends of actin filaments, allowing
new actin filament assembly.


Because Listeria is capable of stimulating actin assembly and PIP2 and PIP3 are known to localize to regions of new actin
assembly, Dr. Southwick and his colleagues decided to explore the roles these lipids play in Listeria infection.


"We had expected to see PIP2 and PIP3 only at the very back of Listeria where new actin assembly was taking place," recalls
Dr. Southwick. "To our surprise these lipids also localized to the front of the moving bacteria." The researchers also
noticed that Listeria movement slowed down when the bacteria were treated with molecules that inhibited PI3-kinase, proving
that Listeria depend on PI3-kinase to move.


"Our studies show that Listeria is capable of inside-out signaling," explains Dr. Southwick. "Most signals arise from
molecules binding receptors on the outside of the cell. In the case of Listeria, we find that this intracellular pathogen can
harness signals from the inner rather than the outer surface of the cell membrane.















"The most exciting and surprising finding is that an intracellular bacteria is able to attract host cell membrane lipids to
its surface and these membrane lipids facilitate the ability of the bacterium to move within cells. This capability is unique
to Listeria and is not found in another intracellular bacteria, Shigella. Our experiments show that Listeria is a simplified
model system for studying how phosphoinositides regulate the actin cytoskeleton, and this model promises to yield additional
insights into how these phospholipids control the cell's actin cytoskeleton. Our discoveries provide additional fundamental
clues as how cells move."


These findings may also open the door to using PI3-kinase inhibitors or other agents that lower PIP2 and PIP3 levels to slow
the spread of Listeria and control infection in patients who are not responding to antibiotics, although that application is
a long way off, says Dr. Southwick.


The Journal of Biological Chemistry's Papers of the Week is an online feature which highlights the top one percent of papers
received by the journal. Brief summaries of the papers and explanations of why they were selected for this honor can be
accessed directly from the home page of the Journal of Biological Chemistry online at jbc.


The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization
with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and
universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.



Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for
Experimental Biology. The Society's primary purpose is to advance the sciences of biochemistry and molecular biology through
its publications, the Journal of Biological Chemistry, The Journal of Lipid Research, Molecular and Cellular Proteomics, and
Biochemistry and Molecular Biology Education, and the holding of scientific meetings.


For more information about ASBMB, see the Society's website at asbmb.


Contact: Nicole Kresge

nkresgeasbmb

301-634-7415

American Society for Biochemistry and Molecular Biology

asbmb

Top 10 Innovations Of 2010 Announced By The Scientist

The Scientist unveils the best life science innovations of the year



The Scientist, Faculty of 1000's magazine of the life sciences, has announced the winners of the "Top 10 Innovations of 2010." The Scientist invited a panel of expert judges to evaluate life science technologies and determine the ten most exciting tools to hit the life sciences this year.



Molecular chemist Neil Kelleher of Northwestern University, sequencing pioneer Jonathan Rothberg, Princeton University genomicist Amy Caudy, and Pacific Northwest National Laboratory biologist H. Steven Wiley reviewed more than 60 entries in the third annual Top 10 Innovations competition to narrow down the products to the 10 best.



This year's winners include essential tools, such as sequencers, imagers, and cell counters, that have the potential to simplify and streamline work in biology labs; and cutting-edge advances, from tailor-made disease-model cell lines to heart cells derived from induced pluripotent stem cells.



The Gold honor was awarded to Pacific Biosciences, for its breakthrough product PacBio RS, which enables single molecule, real-time, or SMRT, detection of biological processes, for the first time. The Silver went to Sigma-Aldrich and its CompoZr custom zinc-finger nuclease service. This new portfolio of products offers genetically modified mammalian cell lines for a broad spectrum of applications. EMD Millipore's Scepter Handheld Automated Cell Counter claimed bronze as the only handheld, automated cell counter available today.



The Maestro Dynamic, developed by Cambridge Research & Instrumentation is a kinetic all-optical in-vivo fluorescence imaging system that generates real-time images of temporal biodistribution and biological activity. Reinnervate Limited presented Alvetex®, a unique and highly porous polystyrene scaffold that enables the routine, reproducible and cost-effective creation of 3D cell cultures in the laboratory.



The Attune Acoustic Focusing Cytometer from Applied Biosystems also made the Top 10. This product enables scientists to gather statistical data on a large number of heterogeneous cells to study parameters within a cell population, including size, complexity, phenotype and health.



"The 2010 winners represent exceptional combinations of invention, vision and utility and we look forward to seeing how these products will impact the life sciences", said Mary Beth Aberlin, Deputy Editor.



The Top 10 Innovations of 2010:
PacBio RS; Pacific Biosciences
Genetically engineered disease model cell lines; Sigma-Aldrich
Scepter Handheld Automated Cell Counter; EMD Millipore
Diffinity RapidTip™; Diffinity Genomics
iCell Cardiomyocytes; Cellular Dynamics International
Maestro Dynamic; Cambridge Research & Instrumentation
Alvetex®; Reinnervate Limited
Attune Acoustic Focusing Cytometer; Applied Biosystems
Gel Doc EZ Imager; Bio-Rad Laboratories
Preddator microplate dispenser; Redd&Whyte

Read the complete feature in The Scientist's December 2010 issue. The article is available online here.



Source:

Eleanor Howell


Faculty of 1000: Biology and Medicine

Discovery Of New Prion Protein May Offer Insight Into Mad Cow Disease

Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. "Our team has defined a second prion protein called 'Shadoo', that exists in addition to the well-known prion protein called 'PrP' " said Professor David Westaway, director of the Centre for Prions and Protein Folding Diseases at the University of Alberta.



"For decades we believed PrP was a unique nerve protein that folded into an abnormal shape and caused prion disease: end of story. This view is no longer accurate," Westaway adds.



The study was conducted jointly by the University of Toronto, University of Alberta, Case Western Reserve University (Ohio) and the McLaughlin Research Institute (Montana). The research is published in the EMBO Journal and represents a culmination of work initiated at the University of Toronto in 1999, and then continued more recently at the University of Alberta.



This is the first discovery since 1985 of a new brain prion protein. "A second prion protein had been inferred by other research, based on indirect studies and the examination of DNA sequences," said lead author Joel Watts, a graduate student at the University of Toronto's Centre for Research in Neurodegenerative Diseases. "But we not only demonstrate that this theoretical protein really exists and shares several properties with healthy PrP; we have also defined an unexpected alteration in prion infections.



"As the PrP molecule alters shape and accumulates in a prion-affected brain, the Shadoo protein seems to disappear," Watts added. Since proteins in a living cell are the molecules "that do the work, this is likely to be significant," he said.



"Many facets of a prion disease like BSE are puzzling," Westaway said. "The puzzles include the cause of death of brain cells, the function of normal prion proteins, and the rules governing emergence and spread of prions from animal to animal. We believe the Shadoo protein can give us a fresh purchase on these important questions."






This research project was funded by the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council (NSERC).



For more information, please contact:


Professor David Westaway

Centre for Prions and Protein Folding Diseases

Link: prioncentre.ca/

University of Alberta



Joel Watts BSc

Centre for Research in Neurodegenerative Diseases

Link: utoronto.ca/crnd/

University of Toronto



Source: Bev Betkowski


University of Alberta

Protein Regulates Movement Of Mitochondria In Brain Cells

Scientists have identified a protein in the brain that plays a key role in the function of mitochondria - the part of the cell that supplies energy, supports cellular activity, and potentially wards off threats from disease. The discovery, which was reported today in the Journal of Cell Biology, may shed new light on how the brain recovers from stroke.



"Understanding the molecular machinery that helps distribute mitochondria to different parts of the cell has only recently begun to be understood," said University of Rochester Medical Center neurologist David Rempe, M.D., Ph.D., the lead author of the study. "We know that in some disease states that mitochondria function is modified, so understanding how their activity is modulated is important to understanding how the brain responds to a pathological state."



Mitochondria are cellular power plants that generate most of the cell's supply of adenosine triphosphate (ATP), which is used as a source of chemical energy. While mitochondria are present in all of the body's cells, some cells - because of their size and purpose - need to transport mitochondria to distant sites within the cell to maintain proper function. A prominent example is neurons which have a complex cellular structure that consist of a main cell body and dendrites and axons that project out from the cell core and transmit signals to adjoining cells via synapses at their terminus.



"Neurons are at a disadvantage in terms of their anatomy," said Rempe. "They put out enormous arms of axons and dendrites and they have to keep supplying nutrients and everything down these arms. The supply line is very long."



The supply line includes mitochondria which the cell must also push down the axons and dendrites to provide these parts of the cell with energy, help with the transmission of signals, and generally maintain cellular health. Mitochondria are constantly cycling throughout the neuron. Some are stationary while others are moving down the arms of the cell to assume their proper position. Additionally, for reasons not completely understood, at any given time about half of the mobile mitochondria in the neuron are in the process of returning to the cell body - perhaps to be recycled or replenished in some form.



Rempe and his colleagues have discovered a protein that plays a critical role in regulating the movement - or transport - of mitochondria in neuron cells. The protein, which they dubbed hypoxia upregulated mitochondrial movement regulator (HUMMR), is produced in a state of low oxygen called hypoxia. HUMMR is induced by another protein called hypoxic inducible factor 1 alpha (HIF-1) which is responsible for triggering several processes in the cell that help it function in a low oxygen environment.



The primary role of HUMMR is to regulate the proper transport and distribution of mitochondria throughout the cell, essentially ensuring that they are in the correct position. One of the ways that the University of Rochester team was able to determine this is that when HUMMR was expressed at lower than normal levels, they observed that a greater number of the mitochondria began to abandon their posts along the cell's dendrites and axon and return to the cell body proper.
















Understanding the mechanisms that regulate the movement of mitochondria may help scientists identify how the brain's cells ward off and potentially repair damage. An example is the role that mitochondria play as a calcium buffer. One of the mitochondria's functions is to help control the concentration of calcium in the cell, which the organelles can rapidly absorb and store. This capacity is important, particularly in instances when calcium levels in the cell spike during a stroke, a condition which contributes a cascading series of events that ultimately lead to a state called excitotoxicity and cell death.



One of the keys to identifying the function of HUMMR has been the appreciation in that the body operates at a relatively low oxygen level. While the air we breath consists of approximately 20% oxygen, the cells in the brain sit at somewhere between 2-5% oxygen. This creates a "normal" state of hypoxia in the brain.



However, the concentration of oxygen in the brain can drop even further in instances such as a stroke, when blood flow to a portion of the brain is cut off. This decrease in oxygen promotes the expression of HUMMR which, in turn, mobilizes mitochondria. More mitochondria in the correct position may mean the cell has a greater capacity to filter out toxic levels of calcium. Rempe and his colleagues are now investigating the role that HUMMR may play in stroke models, particularly whether or not this activity helps protect vulnerable cells that lie just outside the core areas of the brain that are damaged by stroke.



"Ultimately, these advances in our understanding of the molecular and cell biology of mitochondria have the potential to lead to novel approaches for the prevention and treatment of neurological disorders," said Rempe.



Co-authors include URMC researchers Li Yan, MS, and David Hoffman, D.M.D., Howard Federoff, M.D., Ph.D., and Seung Lim, Ph.D. with Georgetown University, and Pontus Aspenstrom, Ph.D. with the Karolinska Institute in Stockholm, Sweden. The study was funded, in part, by the National Institute of Neurological Disorders and Stroke.



Source:

Mark Michaud

University of Rochester Medical Center

Researchers Discover How To Fight Iron Disorders With A Drug Against Hypertension

We all know that iron deficiencies are dangerous, but also too much iron is bad for our health. Our body stores excess iron in various tissues, where it can lead to organ failure and even death if not treated before irreversible damage has occurred. Researchers from the Innsbruck Medical University, the University of Heidelberg, Germany, and the European Molecular Biology Laboratory (EMBL) now made a surprising discovery that may lead to new therapeutic approaches to treating such disorders. In this week's online issue of the journal Nature Medicine they report that a compound that was frequently used to treat high blood pressure can reverse iron overload in mouse models and has the potential to treat similar conditions in humans.



Our body needs most of its iron to make red blood cells. A lack of the metal can lead to dangerous anemias, but also too much iron can be detrimental as iron promotes the formation of toxic radicals leading to tissue damage. Iron overload is the consequence of one of the most common genetic disorders in Europe, hereditary hemochromatosis, which affects about one in 300 Europeans. Excess iron also accumulates after repeated blood transfusions and can cause organ failure over time. GГјnter Weiss, a clinician from the Innsbruck Medical University, and his collaborators from the University of Heidelberg and EMBL now found out that nifedipine, a substance commonly used to control blood pressure, helps the body deal with too much iron.



"We observed in mice with iron overload that nifedipine helps mobilise iron from stores in the liver and enhances its excretion into the urine," says Weiss, an EMBL alumnus who now heads a lab at the Department for General Internal Medicine at the University of Innsbruck. "These effects make nifedipine a promising candidate for a new drug to treat hereditary hemochromatosis and other iron overload disorders."



Combining electrophysiology, cell biology and molecular investigations, Weiss and his collaborators found out that nifedipine exerts its effect on iron metabolism by acting on a molecule called DMT-1. DMT-1 transports iron across cell membranes. This transport is increased ten to 100-fold by nifedipine, but how exactly the compound brings about its effect is still unknown. Nifedipine is known to block membrane channels that control Ca2+ influx into cells, but if it exerts its effect on iron transport indirectly by changing Ca2+ levels in the cell or by binding directly to DMT-1 in liver and kidney still needs to be determined.



"Understanding the exact molecular mechanism underlying nifedipine's effect on iron transport would be a big step towards developing it into an effective therapy that can be used on patients," says Martina Muckenthaler, an EMBL alumna who is now at the University of Heidelberg. "Taking nifedipine from bench to bedside could be quicker than for other substances, because it has already been used for years to treat patients with high blood pressure. From this we know the drug and its side-effects."



An important step on the way from laboratory to clinic will be targeted pharmacological modifications of the compound to separate nifedipine's effect on iron metabolism from its established action on blood pressure.



"Our discovery is an excellent example of how the combination of basic research and the expertise of clinicians can yield results that are relevant to medicine and could ultimately benefit patients," says Matthias Hentze, Associate Director of EMBL and co-author of the study. "In the Molecular Medicine Partnership Unit (MMPU) between EMBL and the Medical Faculty of Heidelberg University we integrate molecular biology and clinical medicine to gain an understanding of the basis of human diseases. It is very gratifying to see how the collaboration with EMBL alumni and the MMPU yields exciting progress in medicine."






Contact: Anna-Lynn Wegener


European Molecular Biology Laboratory

Computational Biology Group Identifies New Mechanism Of Gene Regulation

MIT scientists have found a new way that DNA can carry out its work that is
about as surprising as discovering that a mold used to cast a metal tool can
also serve as a tool itself, with two complementary shapes each showing
distinct functional roles.



Professor Manolis Kellis and postdoctoral research fellow Alexander Stark
report in the January 1 issue of the journal Genes & Development that in
certain DNA sequences, both strands of a DNA segment can perform useful
functions, each encoding a distinct molecule that helps control cell
functions.



DNA works by complementarity: paired DNA strands serve as a template for
each other during DNA replication, and ordinarily only a single DNA strand
serves as a template to produce RNA strands, which then go on to produce
proteins. The process is similar to the way each bump or dent in a mold is
paired with a corresponding dent or bump in the resulting molded object.



While many RNAs are eventually translated into proteins with specific
functions, some RNA molecules instead act directly, carrying out roles
inside the cell. Certain RNA genes, known as microRNAs, have been shown to
play important regulatory roles in the cell, often coordinating important
events during the development of the embryo. These microRNAs fold into
relatively simple hairpin structures, with two stretches of near-perfect
complementary sequence folding back onto each other. One of the two
'arms' of a hairpin is then processed into a mature microRNA.



The surprising discovery is that for some microRNA genes, both DNA
strands, instead of just one, encode RNA, and both resulting microRNAs
fold into hairpins that are processed into mature microRNAs. In other
words, both the tool and its mold appear to be functional. Kellis and
Stark found two such microRNA pairs in the fruit fly, and eight more such
pairs in the mouse.



The idea that there could be such dual-function strands, where both DNA
strands encode functional RNA products, "had never even been
hypothesized," Kellis says. But followup work confirmed that they did
indeed function in this way. The work suggests that other such unexpected
pairings, with both DNA strands encoding important functions, may also
exist in a variety of species.



This discovery builds on a similar, earlier surprising finding about
microRNA regulation. In December, Stark and Kellis reported that both arms
of a single microRNA hairpin can also produce distinct, functional
microRNAs, with distinct targets. Together, these two findings suggest
that a single gene can encode as many as four different functions - one
hairpin from each of the two DNA strands, and then one microRNA from each
of the two arms of each hairpin.



These recent papers are the latest example of the power of using
computational tools to investigate the genomes of multiple species, known
as comparative genomics. The Kellis group has used this approach to
discover protein-coding genes, RNAs, microRNAs, regulatory motifs, and
targets of individual regulators in diverse organisms ranging from yeast
and fruit flies to mouse and human.



"This represents a new phase in genomics-making biological discoveries
sitting not at the lab bench, but at the computer terminal," Kellis says.



Kellis is the Karl Van Tassel Career Development Assistant Professor in
the Department of Electrical Engineering and Computer Science and an
associate member of the Broad Institute. He grew up in Greece and France
and earned his B.S., M.Eng., and Ph.D. from MIT, and he was appointed to
the faculty here in 2004. At 30, he has already earned numerous awards and
accolades, including a place on the list of the 35 top innovators under 35
by Technology Review magazine in 2006.



Kellis' work is supported in part by grants from the National Institues of
Health and the National Science Foundation. Alex Stark is supported by a
Human Frontier Science Program fellowship.

mit

Lung Cancer-Derived EGFR Mutants Exhibit Intrinsic Differences In Inhibitor Sensitivity

A new study sheds light on how some small-molecule tyrosine kinase inhibitors, including two that are currently being used clinically to treat cancer, interact with wild-type and mutated forms of the epidermal growth factor receptor (EGFR). The research, published in the March issue of the journal Cancer Cell, published by Cell Press, may help to guide rational use of currently available EGFR inhibitors and provides new direction for the design and development of even more potent inhibitors that are tailored to specific EGFR mutants.



Many human malignancies exhibit mutated forms of the EGFR, a tyrosine kinase that plays a critical role in signaling pathways controlling cell proliferation and survival. Although the specific mechanisms are unclear, studies have shown that some EGFR mutations are associated with increased sensitivity to small-molecule tyrosine kinase inhibitors. To better understand how distinct mutant EGFRs interact with inhibitors on a structural level, Dr. Michael J. Eck from Harvard Medical School and the Dana-Farber Cancer Institute and colleagues studied the enzyme activity of two lung cancer-derived EGFR mutants and determined their crystal structures when bound to several different commonly used inhibitors.



The researchers found that the L858R and G719S EGFR mutants disrupt inhibitory interactions within the EGFR, leading to a characteristic overactivation of the enzyme. Structural examination of the inhibitor complexes, which included the drug gefitinib (Iressa), revealed that the mutations can affect the way the inhibitors interact with the enzyme. Interestingly, the inhibitors gefitinib and AEE788 bind much more tightly to the L858R mutant than to the wild-type EGFR. This finding explains the observation that tumors bearing this mutation have been found to be more responsive to treatment with gefitinib.



The researchers conclude that mutations of the EGFR dramatically influence inhibitor binding and suggest that the different EGFR mutations present distinct targets for application and development of inhibitors. "Although structural divergence in the EGFR mutants may complicate pharmacologic intervention by fragmenting the disease, it may also present an advantage in that it introduces the possibility of developing inhibitors even more potently selective for specific mutants over wild-type EGFR. Inhibitors designed specifically to target mutants such as L858R should, in principle, be less toxic due to reduced inhibition of the wild-type kinase," explains Dr. Eck.






The researchers include Cai-Hong Yun, Yiqun Li, Michele S. Woo, and Michael J. Eck of Harvard Medical School and Dana-Farber Cancer Institute in Boston, MA; Titus J. Boggon of Harvard Medical School and Dana-Farber Cancer Institute in Boston, MA and Yale University in New Haven, CT; Heidi Greulich of Dana-Farber Cancer Institute in Boston, MA and The Broad Institute of Harvard and Massachusetts Institute of Technology in Cambridge, MA; Matthew Meyerson of Harvard Medical School and Dana-Farber Cancer Institute in Boston, MA and The Broad Institute of Harvard and Massachusetts Institute of Technology in Cambridge, MA.



This work was supported in part by NIH grants CA080942 (M.J.E.) and CA116020 (M.M.). M.J.E. is the recipient of a Scholar award from the Leukemia and Lymphoma Society.



Yun et al.: "Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of Activation and Insights into Differential Inhibitor Sensitivity." Publishing in Cancer Cell 11, 217-227, March 2007. DOI 10.1016/j.ccr.2006.12.017 cancercell/



Contact: Erin Doonan


Cell Press



View drug information on Iressa.

Jointly Founded Institute Will Develop New Technologies, Speed Diagnostic Advances

The Methodist Hospital, the University of Houston, and Weill Cornell Medical College of Cornell University are combining their expertise in biomedical imaging to advance discoveries in this growing field of biomedical science and its clinical applications.



The three institutions have jointly founded the Institute for Biomedical Imaging Science (IBIS). This Institute will create interdisciplinary programs in the sciences of biomedical imaging and will foster joint training programs to produce the next generation of basic and applied scientists. Biomedical imaging includes magnetic resonance imaging (MRI), CAT scans and other high technologies ranging from molecular imaging to nanotechnology to computer science.



These techniques are used to observe the activities of organs, cells and molecules with the aim of better diagnosis and treatment of many disorders, including those caused by cancer, cardiac malfunction and neurological conditions.



IBIS will bring together a critical mass of scientists from the three partner institutions to work toward developing new technologies and toward improving and extending existing ones. The combined expertise is expected to speed such advances and to increase the likelihood of receiving major grants for research and training.



"The possibilities for collaborative research by this consortium are endless," said Dr. King Li, the director of the IBIS and Chair of Radiology at the Methodist Hospital. "We hope to attract research grants that will lead to discoveries in new technologies and techniques to better unearth diseases at their earliest stages."



"We are establishing a unique research environment, with as many as 50 scientists working together from the three institutions that already are aligned through academic affiliations," said Ioannis Kakadiaris, chair of the IBIS steering committee and director of the Division of Bioimaging and Biocomputation at the University of Houston. "We are thus positioning ourselves to be on the forefront of discoveries in biomedical imaging."







About The Methodist Hospital



The Methodist Hospital is one of the nation's largest private, non-profit hospitals with 935 operating beds. The Methodist Hospital is affiliated with Weill Cornell Medical College and New York Presbyterian Hospital. Dedicated to providing the highest level of patient care, Methodist is the site of numerous medical breakthroughs, such as the world's first multiple-organ transplant in the 1960s, gene therapy for prostate cancer, and the first islet cell transplants in Texas. The hospital is consistently named among the country's top hospitals in numerous specialties in U.S. News and World Report's annual guide to America's Best Hospitals. Methodist was recently named No. 9 on FORTUNE's "100 Best Companies to Work For" list for 2007. Methodist's medical staff includes hundreds of physicians listed in The Best Doctors in America.
















About the University of Houston



The University of Houston, Texas' premier metropolitan research and teaching institution, is home to more than 40 research centers and institutes and sponsors more than 300 partnerships with corporate, civic and governmental entities. UH, the most diverse research university in the country, stands at the forefront of education, research and service with more than 35,000 students.



About Weill Cornell Medical College



Weill Cornell Medical College - located in New York City - is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer and psychiatry - and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. Weill Cornell Medical College is the birthplace of many medical advances - from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., and most recently, the world's first clinical trial for gene therapy for Parkinson's disease. Weill Cornell's Physician Organization includes 650 clinical faculty, who provide the highest quality of care to their patients.



For more information about The Methodist Hospital, visit methodisthealth/.



For more information about UH, visit the university's Newsroom at uh/newsroom.



For more information about Weill Cornell Medical College, visit med.cornell/.



Contact: Lisa Merkl


University of Houston

First International Conference On Multifunctional, Hybrid And Nanomaterials

Elsevier, the world-leading publisher of scientific, technical and medical information products and services, announced Hybrid Materials 2009: The First International Conference on Multifunctional, Hybrid and Nanomaterials which will take place in Tours, France, 15-19 March 2009.



Research in hybrid materials has experienced a 14% annual growth in published papers in recent years with increasing interest from a wide range of industries. This inaugural meeting aims to bring together experts from the various sub-disciplines to share current research and create an interdisciplinary forum for discussion.



ClГ©ment Sanchez, CNRS Research Director at the University of Paris VI and author of some the world's most cited papers on hybrid materials, is one of the four conference chairs. He is enthusiastic about the future of research in this area: "Hybrid materials not only represent a creative approach to design of new materials, but their improved or unusual properties also allow the development of innovative industrial applications. This interdisciplinary research field will open a land of promising applications in many areas including optics, electronics, ionics, mechanics, energy, environment, biology, medicine. The three symposia during Hybrid Materials 2009 will cover all aspects of the chemistry, processing and applications of these advanced materials."



Rumen Duhlev, Publisher at Elsevier and initiator of this project, believes the launch of the conference is extremely timely and fulfils a real need in providing researchers in both academia and industry with a dedicated forum for discussing advances in this interdisciplinary field: "We are really excited to collaborate with some of the world's leading experts on hybrid materials in the creation of this unique international forum, aiming to bring together representatives of disciplines as diverse as inorganic chemistry, polymer science, biomaterials, organic chemistry, catalysis, composites and colleagues from the industry to share knowledge and accelerate progress."



The conference is currently calling for contributions for presentation at the meeting under one of the three following symposia: Biohybrids and biomaterials; Bottom-up approaches to functional nanomaterials and nanocomposites; Functional porous materials. Abstracts should be submitted online at hybridmaterialsconference/ by 15 September 2008.







About Elsevier



Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier's 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (sciencedirect/), MD Consult (mdconsult/), Scopus (info.scopus/), bibliographic databases, and online reference works.



Elsevier (elsevier/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (reedelsevier/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier's ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).



Source: Charlotte Wilkins


Elsevier

Hospital For Special Surgery Finds Statins Could Help Some Women Have A Healthy Pregnancy

Hospital for Special Surgery researchers have found that statins may be able to prevent miscarriages in women who are suffering from pregnancy complications caused by antiphospholipid syndrome (APS), according to a study in mice. In this autoimmune syndrome, the body produces antibodies directed at phospholipids, the main components of cell membranes. This news comes from a study published in the October issue of the Journal of Clinical Investigation that is currently online in advance of print.



In low risk pregnancies, APS is associated with a nine-fold increase in miscarriage. In high-risk pregnancies (women who have had at least three prior losses), APS is associated with a 90 percent risk of miscarriage.



"Statins may work as a treatment for women with APS-induced pregnancy complications," said Guillermina Girardi, Ph.D., associate scientist at Hospital for Special Surgery in New York, who is lead author of the study. "They are drugs that have been shown to be very safe. There are a lot of women who continue to take statins through pregnancy and the drugs have not been shown to produce birth defects." Statins do not increase the risk of bleeding like anticoagulants, the current treatment for patients with APS.



In previous studies, Dr. Girardi and colleagues showed that antiphospholipid (aPL) antibodies in female mice caused inflammation that injured the placentas and induced abortions. These antibodies activate a protein, C5a, that activates another protein, tissue factor, that is expressed on the surface of certain white blood cells called neutrophils. This spurs the neutrophils into action, they attack the placenta, and the fetus dies. While investigators had unveiled this basic chain of events, they didn't know any further details about the mechanism.



To find out, Dr. Girardi and colleagues examined the white blood cells from mice that had APS and discovered that these cells expressed certain receptors called PAR2 (protease-activated receptor 2). Stimulating this receptor led to the activation of white blood cells that attacked the placenta and hurt the fetus. Using an antibody that blocks tissue factor interaction with PAR-2, they inhibited white blood cell activation.



In another experiment, investigators tested a possible treatment. Previous studies had shown that statins, commonly used to regulate cholesterol levels, could downregulate tissue factor (diminish the number of molecules expressed on the surface of the cell). Dr. Girardi and colleagues found that statins not only downregulate tissue factor, but they also downregulate PAR-2 on white blood cells, making the cells less sensitive. So, the researchers injected statins into mice with APS and found that these drugs could prevent white blood cell activation and protect pregnancies.
















Women are advised to discontinue most medications, including statins, during pregnancy, but Dr. Girardi says that no fetal defects have been reported in women who have continued to use statins while pregnant. The researchers say that careful studies should be conducted to confirm the safety of statins in pregnancy in humans. "Women that are antiphospholipid antibody positive and have a history of previous miscarriages are a good group to perform a clinical trial," Dr. Girardi said.



On average, 50 percent to 70 percent of all conceptions fail. There is an association between circulating aPL and pregnancy loss, and between 3 percent and 7 percent of pregnant women have these antibodies.



This study could also have implications for other conditions. "The study reveals a relationship between tissue factor and PAR2 in inflammation that could have implications for understanding chronic inflammatory conditions such as rheumatoid arthritis," said Dr. Girardi. Tissue factor expression on cells that line the circulatory system and certain immune cells is a characteristic feature of acute and chronic inflammation in conditions such as sepsis, atherosclerosis, Crohn's disease, and lupus. Finding a way to manipulate tissue factor and PAR2 could lead to treatments for these diseases.







Other investigators involved in the study are Patricia Redecha and Claus-Werner Franzke from Hospital of Special Surgery, Wolfram Ruf from the Scripps Research Institute, and Nigel Mackman from the University of North Carolina. The research was supported by grants from the Mary Kirkland Center for Lupus Research at Hospital for Special Surgery and the National Institutes of Health.



Dr. Girardi's paper was selected for recognition by the Faculty of 1000 Medicine. This large group of scientists identifies and highlights the most important contributions made in science today.



About Hospital for Special Surgery



Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopedics, rheumatology and rehabilitation. HSS is nationally ranked No. 1 in orthopedics and No. 4 in rheumatology by U.S. News & World Report (2008), and has received Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center. In 2008 and 2007, HSS was a recipient of the HealthGrades Joint Replacement Excellence Award. A member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College, HSS provides orthopedic and rheumatologic patient care at NewYork-Presbyterian Hospital at New York Weill Cornell Medical Center. All Hospital for Special Surgery medical staff are on the faculty of Weill Cornell Medical College. The hospital's research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at hss/.



Source: Phyllis Fisher


Hospital for Special Surgery

Sorrento Therapeutics Announces Completion Of Diverse Library Of Full-Length, Fully Human Antibodies

Sorrento Therapeutics, Inc. (OTC Bulletin Board: SRNE) announced that it has completed the construction of an extensive library of full-length, fully human monoclonal antibodies (mAbs). Initial analysis indicates a potential diversity of more than one trillion unique mAbs. The company believes this makes its library the largest full-length, fully human antibody library available for drug discovery and development partnerships. Importantly, Sorrento Therapeutics' proprietary technologies generate antibodies that are unencumbered by third-party royalty obligations placed on conventional antibody discovery technologies.


"We believe Sorrento Therapeutics has one of the strongest antibody development platforms available. Industry-leading library diversity and the immediate availability of full-length antibodies offer rapid discovery and development timelines. Our proprietary technologies are designed to efficiently identify optimal antibody candidates against potentially any disease target," said Antonius Schuh, Ph.D., chairman and chief executive officer of Sorrento Therapeutics.


Sorrento Therapeutics' proprietary mammalian display system enables the expression and isolation of full-length human antibodies. In contrast, antibody libraries displayed in phage or yeast systems typically generate antibody fragments, which require further configuration into full-length antibodies for therapeutic development. Sorrento Therapeutics uses fluorescence-activated cell sorting (FACS) to rapidly identify high-affinity antibody candidates from its library for immediate downstream development.


The extensive diversity of Sorrento Therapeutics' library of complete antibodies increases the likelihood of identifying candidates with optimal biological activity against validated disease targets. Sorrento Therapeutics' patented technology for the amplification and enrichment of the immunoglobulin variable domain sequences applies ribonucleic acid (RNA) transcription to ensure high representation of the vast diversity of the immunoglobulin gene repertoire. The library was created using an input of antibody-generating source cells from approximately 600 donors and covers all major classes of immunoglobulins (i.e. IgM, IgG1 - 4, IgA, IgD and IgE).


About Sorrento Therapeutics


Sorrento Therapeutics, Inc. is a development-stage biopharmaceutical company focused on applying its proprietary technology platform for the discovery and development of human therapeutic antibodies for the treatment of a variety of disease conditions, including cancer, inflammation, metabolic disease and infectious disease.


Forward-Looking Statements


This press release contains forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements about the potential diversity of more than one trillion unique mAbs and whether the diversity will increase the likelihood of identifying candidates with optimal biological activity against validated disease target. Risks and uncertainties include those risks set forth in Sorrento's filings with the Securities and Exchange Commission. These forward-looking statements represent Sorrento's judgment as of the date of this release. Sorrento disclaims, however, any intent or obligation to update these forward-looking statements.


Source: Sorrento Therapeutics, Inc

Cytomegalovirus: Cell Death May Bring New Life To Treatment Of Retinal Disease

Just days after the first retinal cell gets infected with the common cytomegalovirus, contiguous cells start committing suicide and researchers believe their death may provide clues to better treatment of this potentially blinding infection.



Understanding the cell death may also provide new insight into the larger issue of how the retina responds to assault, whether by infection or a disease process such as diabetes, said Dr. Sally Atherton, virologist and immunologist who chairs the Department of Cellular Biology and Anatomy in the Medical College of Georgia School of Medicine. "We are trying to get to the bottom of the mechanisms of that cell death."



A recent $1.3 million grant from the National Eye Institute is enabling studies of what's likely the body's well-intended effort to stop cytomegalovirus retinitis. "We can try to infect certain cells and see what happens. We can try to inhibit the virus and see what that does. The immediate goal is to look at the apoptosis (cell death) trigger but the bigger picture is really looking at mechanisms of retinal damage during cytomegalovirus infection," Dr. Atherton said. Tools include a mouse model of human disease as well as a retinal cell culture system developed by MCG Assistant Research Scientist Ming Zhang.



Their perusing may identify new treatment targets; a modulator made by infected cells that prompts adjacent cell death could be one such target. And certainly there is plenty to study: "Lots of signaling pathways are activated. There are a whole host of genes that are up-regulated and down-regulated," Dr. Atherton said. Infected cells as well as cells that come in to cart off dead cells may secrete tumor necrosis factor, for example, an immune cell regulator that causes inflammation and also may trigger cell death. "There are various mechanisms by which apoptosis, or cell death, can be induced," Dr. Atherton said.



As activity and damage increase, patients may experience blurred vision and floaters, eye pain and redness. Treatments include antivirals that may need to be injected or implanted directly into the eye or even surgery.



"Normally the retina is neatly stratified. What happens is you get an infection in the most external part of the retina - in humans the virus may actually have been latent in the retina - and it triggers cell death of the next layer and eventually virus spreads deeper into the retina and spreads out more," Dr. Atherton said. "Unchecked it can ruin your vision," especially if it affects the macula, or central part of the retina responsible for highest visual acuity.



Fortunately, despite the fact that most people are infected with this herpesvirus family member that can be found in saliva, blood and semen, it's most typically latent.



Cytomegalovirus retinitis' last big resurrection came with the AIDS epidemic of the 1980s, when nearly half of patients who were dying were going blind as well, Dr. Atherton said. The advent of antiretrovirals to keep HIV in check helped silence cytomegalovirus retinitis as well but today the incidence is again increasing, she said. A suppressed immune system is the primary reason cytomegalovirus becomes active, which means neonates and patients with organ or bone marrow transplants or taking therapy also are increased risk. Scientists aren't certain about the recent, albeit less severe, increase in disease incidence, but HIV patients who have become resistant to their therapy or just tired of taking it, likely are a factor.



Source: Toni Baker


Medical College of Georgia

New Therapeutic Approach Identified For Kidney Disease Associated With Lupus

Investigators have identified a new disease mechanism and therapeutic approach for a type of advanced kidney disease that is a common cause of complications in patients with lupus. The study was led by investigators at Hospital for Special Surgery and appears in the January 25 online Early Edition of the Proceedings of the National Academy of Sciences.


"The standard treatment for lupus kidney disease is to block inflammation," said Lionel Ivashkiv, M.D., associate chief scientific officer at Hospital for Special Surgery in New York City. "This study suggests you might want to target the macrophages, a specific type of white blood cell involved in the disease."


For years, clinicians have known that kidney damage occurs in many patients with lupus, and they have known how the disease triggers the start of kidney disease. Little has been known, however, about one type of lupus kidney disease, proliferative crescentic disease that is associated with adverse outcomes and decreased survival. This type of kidney disease is characterized by abnormal proliferation (growth) of kidney cells that leads to irreversible damage to internal kidney structures that help filter waste and fluids from the blood. This advanced kidney disease leads to kidney failure and it is an important cause of the need for dialysis and transplantation in lupus.


Previous studies have suggested that type I interferons are implicated in promoting the autoimmunity associated with lupus. "We were interested in understanding whether these interferons might work directly on the kidney," Dr. Ivashkiv said. "There is a lot of evidence that the interferons work on the immune system and we wanted to know how interferons affect kidney disease."


To investigate, researchers used a mouse model of lupus. By increasing interferon production, they caused advanced kidney disease to occur in the mice rapidly. "The mice are a strain that will get nephritis over time, but we injected the mice at the very onset of the disease thus causing a very accelerated pattern, so that the mice have complete renal failure in two to four weeks," Dr. Ivashkiv said. They then examined the changes that occurred during the development of the advanced kidney disease by drawing blood samples from the mice, and analyzing their kidneys, and analyzing the macrophages to determine their type, among other experiments.


In the type of kidney disease they were investigating, it has long been known that epithelial cells proliferating out of control form a kind of crescent. These crescent cells compress the glomerulus, the basic filtration unit of the kidney, and prevent it from functioning.


In their experiments, the investigators found that the development of these crescents was associated with infiltrating kidney macrophages that produced growth factors, and the infiltration of these was spurred by interferon type I. They also found that the type of macrophages involved were not the most common type of inflammatory macrophages but so called "alternatively activated macrophages" that are involved in wound healing and induce the proliferation of cells. This is what causes the proliferation and crescentic lesions in the kidney disease.















"This study suggests a new drug target. If you could understand how to target the macrophages and inhibit them or the growth factors that they produce, this might be a different approach to therapy," Dr. Ivashkiv said. "This is an emerging area. Prior to this study, a role of macrophages had just been identified in lupus kidney disease, and this is the first study showing alternatively activated macrophages are involved in proliferative crescentic disease."


The study was conducted by Dr. Lionel Ivashkiv and Dr. Antigoni Triantafyllopoulou, a rheumatology fellow at Hospital for Special Surgery. Dr. Anne Davidson, an expert in lupus models from the Feinstein Institute for Medical Research, Manhasset, N.Y., was a key collaborator. Other authors of the study are Claus-Werner Franzke, Giorgio Perino, and George D. Kalliolias from Hospital for Special Surgery; Surya V. Seshan from Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York; Meera Ramanujam from the Feinstein Institute for Medical Research and Nico van Rooijen from Vrije Universiteit Medical Center in Amsterdam, The Netherlands.


About Hospital for Special Surgery


Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopedics, rheumatology and rehabilitation. HSS is nationally ranked No. 2 in orthopedics, No. 3 in rheumatology and No. 24 in neurology by U.S. News & World Report (2009), and has received Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center, and has one of the lowest infection rates in the country. In 2008 and 2007, HSS was a recipient of the HealthGrades Joint Replacement Excellence Award. A member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College, HSS provides orthopedic and rheumatologic patient care at New York-Presbyterian Hospital at New York Weill Cornell Medical Center. All Hospital for Special Surgery medical staff are on the faculty of Weill Cornell Medical College. The hospital's research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases.


Source: Hospital for Special Surgery

Incidence Of R. felis Infection In Australians May Be Under-Reported

The incidence of human infection with Rickettsia felis (R. felis) in Australia may have been
underestimated in the past because of the similarity between clinical presentations of R. felis
and Rickettsia typhi (R. typhi), according to a case study published in the latest Medical
Journal of Australia.


Human infection with this bacteria has been reported in most parts of the world. Dr Stephen
Graves (PhD), Director of Microbiology at the Hunter Area Pathology Service in Newcastle,
NSW, Dr John Stenos (PhD), Supervising Scientist at the Australian Reckettsial Reference
Laboratory, Geelong Hospital, Victoria, and co-authors describe the first reported cases of
probable human R. felis infection in Australia. The cases involve two adults and three
children in Victoria who contracted a rickettsial disease after exposure to fleas from kittens.


Serological tests showed rising typhus-group rickettsial antibody titres in three of the patients
and high titres in the other two patients. Serological testing on one of the kittens also showed
the presence of typhus-group rickettsial antibodies.


DNA samples from the serum of one of the patients and the cat, and from pooled and crushed
fleas collected from the group of cats that the kittens had been associated with, showed that
the fleas, but not the patient's or cat's serum, were positive for rickettsial DNA. Sequencing
of the DNA showed closest phylogenetic similarity to R. felis, and R. typhi was not detected
in the cat fleas.


Dr Graves said the analyses provided the first molecular evidence of R. felis in cat fleas in
Victoria.


"While genetically a member of the spotted-fever rickettsia group, R. felis behaves clinically
and serologically like a typhus-group rickettsia," he said.


"The human cases reported in this study were only identified serologically, and as the clinical
presentations of R. typhi and R. felis are similar, R. typhi cannot be completely ruled out.
However, given the molecular data from the cat fleas, R. felis is the more likely causative
agent.


"In the past, the incidence of R. felis infection in patients with raised typhus group antibody
levels may have been underestimated, with the causative agent probably reported as R. typhi
when it may have been R. felis - a confusion that has been seen in other studies."


The Medical Journal of Australia is a publication of the Australian Medical Association.


Source:

Medical Journal of Australia

Scientists Are First To Discover Angiogenesis Switch Inside Blood Vessel Cells

Scientists at Schepens Eye Research Institute, an affiliate of Harvard Medical School, are the first to discover a switch inside blood vessel cells that controls angiogenesis (new blood vessel growth). The
switch, they learned, is turned on and off by the balance between two enzymes (known as PI3K and PLCg) that compete for the use of the same lipid membrane to fulfill opposite missions, growth and regression, respectively. This finding could lead to new, more targeted drugs for diseases such as cancer, diabetic retinopathy and macular degeneration. The study, titled "Regulating angiogenesis at the level of PtdIns-4,5P2," is published in the current issue of The EMBO Journal (May 17).


"This is a significant discovery that holds great promise for future treatments," says principal investigator and senior Schepens scientist, Dr. Andrius Kazlauskas, who adds that scientists have long suspected an "intracellular" switching process, but until now have known very little about it. "Current drugs focus on suppressing angiogenesis by inhibiting a mechanism outside the vessel cells, which involves the action of growth factors such as VEGF or vascular endothelial growth factor. While effective in preventing vessel growth, these drugs have little impact on existing, stable vessels," he says. "Our discovery may help design drugs that could dismantle existing vessels by targeting this switch inside the vessel
cells."


Angiogenesis is an important natural process that can be both good and bad for the body. It restores blood flow after injury, prepares a woman's body for pregnancy and increases circulation in a damaged heart. But, it can also nourish cancer tumors and damage delicate retinal tissues when uncontrolled.


The angiogenic process is triggered by what the body perceives as a need for additional blood flow. In the case of disease, it is a mistaken need. In response, the body sends growth factors (such as VEGF) to blood vessels in the "needy area" to bind to receptors on the surface of the endothelial cells. This binding then sets off a series of signaling activities carried out by enzymes within the cells. Two of those enzymes are PI3K and PLCg, which then search for their favorite lipid to use in their respective missions. Until the present study, scientists did not know exactly what those missions were and how they were accomplished.


Kazlauskas and his team were determined to answer those questions. To do so they created laboratory conditions that would allow them to observe the two enzymes separately as they acted on the lipid. In a series of "in vitro" or laboratory experiments that controlled the presence of each enzyme, they began to understand the individual roles of those enzymes.


The research team discovered the following. When the PI3K enzyme acts on the lipid, it converts it (the lipid) into a modified form of itself, which then signals blood vessel cells to proliferate or grow. The team also found that when PLCg acts on the lipid, it cuts the lipid in two, thus preventing PI3K from using that very same lipid to promote vessel growth. Instead, they learned, the resulting two halves of the lipid trigger a series of signaling activities that caused vessels to regress and disappear.


The team concluded that it was the competitive relationship between these two enzymes for the lipid that was at least part of the intracellular switch for which they and other scientists have been searching. They also concluded that blood vessel growth or regression was dependent on the relative activity of the two enzymes and on the amount of the lipid within the endothelial cells.


"Understanding this process opens a whole new avenue for treatment of
angiogenesis-related diseases," says Kazlauskas. "For instance, drugs could be designed to decrease PI3K in cancer patients or those with proliferative diabetic retinopathy or macular degeneration, or designed to increased it in a damaged heart," he says.


Next steps for the research team include identifying the signaling events by which PLCg informs the vessels to undergo regression and the molecules that execute the regression command.


Schepens Eye Research Institute, an affiliate of Harvard Medical School, is
the largest independent eye institute in the world.


hms.harvard/hms/newsroom.asp

Unique New Tool For Analyzing And Comparing Data - Created By Berkeley Lab Scientists

What does uncovering the true authorship of plays attributed to Shakespeare have to do with identifying our genetic ancestors or classifying new life forms? All involve the comparative analysis of long sets of data and all will benefit from a unique new analytical tool developed by researchers at Berkeley Lab.



Sung-Hou Kim, a chemist who holds a joint appointment with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Chemistry Department, led the development of a technique called "feature frequency profiles" (FFP), that makes it possible to compare, classify, index and catalog just about any type of linear information that can be electronically stored. The kinds of information that can be analyzed with the FFP technique include nucleotide base and amino acid sequences, books, documents and possibly images. It could even prove to be the ultimate music organizer.



"I call our technique a tool for demographic phylogeny because it enables us to organize large sets of data into groups and find relationships among these groups," says Kim. "The idea is to organize data sets into groups based on the frequency at which key features occur and then look for relationships. This is the reverse of what is usually done, where you find relationships in the data set then organize the data set into groups based on those relationships."



Using the FFP technique, Kim and his colleagues can create "family trees" that put into easy-to-see perspective the relationships between groups within a data set, whether those groups are books or genomes. The key is to identify the "optimal features" for profiling. For books, the optimal feature consisted of sequences of text about eight letters in length. For mammalian genomes, the optical feature consisted of sequences of nucleotide bases of about 18 base pairs in length. However, to keep their genomic computations manageable, Kim and his colleagues reduced the four-letter DNA alphabet (adenine, guanine, thymine and cytosine) to a two-letter alphabet by using R for the purine nucleic acids and Y for the pyrimidine nucleic acids). In a series of tests run on books and genomes, the FFP technique provided a more comprehensive and in some cases more accurate analysis over the standard analytical tools.



For example, Kim and his colleagues used the FFP technique to create a book tree composed of more than two dozen selected works under the categories of philosophy, mythology, religion, 19th Century fiction, science fiction and children's fiction. Their FFP-based book tree correctly grouped all books by category and author including some, such as the Koran, that were misplaced in a book tree based on a standard word frequency profile analysis. In the case of the Koran, the FFP-based tree placed it in the religion category on the same branch as the King James Bible and the Book of Mormon, whereas the word frequency book tree grouped it in the philosophy category, on the same branch as Plato's The Republic and Socrates' The Apology.
















Kim and his colleagues later applied the FFP technique to a comparative analysis of the works of William Shakespeare, contemporaries such as Christopher Marlowe, plus several works from the Jacobean era that were once attributed to Shakespeare but whose authorships are now in question. The results cast new doubt on Shakespeare having been the author of the play Pericles, Prince of Tyre, and point to his authorship of the comedy Two Noble Kinsmen, for which in the past he has only received partial credit.



"I was stunned when I saw how well the technique worked with books," Kim says.



The next step was the successful application of the technique to the whole genomes of mammals whose phylogenic tree is well established, then on to whole genomes of prokaryote organisms (bacteria and Archaea) and finally on to viruses, for which current comparative genomic analytic tools sometimes cannot be applied.



Collaborating with Kim on this project have been biophysicist Gregory Sims, statistical mathematician Se-Ran Jun and theoretical physicist Guohong Wu. Like Kim, they all hold joint appointments with Berkeley Lab and UC Berkeley.



Exploding Growth of Genome Data



Kim is an internationally recognized authority on protein structures and a pioneer in the field of structural genomics. In 2003, he unveiled a 3-D demographic map of the protein structure universe that for the first time made it possible to organize the structures of this vast assemblage of biological molecules (more than 50 billion known species and growing) into meaningful groups.



"Scientists studying the genomes of different organisms are facing similar problems to those studying protein structures, perhaps even more difficult," Kim says. "Thousands of whole genomes have been or are in the process of being sequenced and we need to have an effective way of comparing and grouping them, and finding relationships among the groups. The FFP method can help us mine the function of gene-coding and non-coding nucleotide base sequences in the genome of a particular species, and can also give us a better understanding of how that species may have evolved, who its closest relatives are and other valuable information."



Currently, comparative genomics studies are based either on measuring the similarities and differences between a set of selected genes in the coding regions of the genomes that are common to the species being compared, or on gene-profiles, in which the presence of certain genes in two or more species yields a similarity score. Species with a higher number of shared genes or similarity scores are presumed to be more closely related than those with a lower number. Both of these methods require an alignable set of common genes in the coding regions, which is not always the case, especially amongst the genomes of rapidly evolving species. Such "gene-centric" comparisons also suffer from an even greater limitation for comparing mammals and other high-order eukaryotes, as Kim explains.



"Coding sequences (exons) total only about one-percent of the entire human genome, with the rest made up of non-coding sequences (introns) whose functions are still largely unknown," he says. "What is needed is an alignment-free method that can be used for comparing entire genomes or genomic regions that may be distantly related, have undergone significant rearrangement, or do not share a common set of genes. We also need a tool that can be used to analyze and compare nongenic regions of genomes as well."



Kim began this quest by turning to the world of books, where comparative analytical tools are well established to ascertain authorship as well as to expose fraud or plagiarism. However, two problems became evident. First, current standard text analysis is based on the frequency at which different words appear, but genomic data consists of long strings of letters not words. Second, analysis based on the frequency of words does not provide local syntax - the relationship between adjoining words, a point that is critical in comparative genomics and turned out to be important in text comparisons as well.



A New Look at Books and Genomes



To overcome the limitations of current text comparison techniques, Kim and his colleagues first undertook an analysis of words in a Webster's English dictionary and found that words with eight to nine letters were optimal for frequency profiling. This finding also proved true for all other books as well.



"Text features longer than eight or nine letters do not occur frequently enough for frequency profile comparisons, and text features shorter in length do not give us enough information to distinguish one book from another," Kim says.



To apply their FFP technique to comparative analysis of books, they "delimiter-stripped" each book - meaning they stripped the text of all punctuation and spaces - then transformed the text into a single long string of letters. A "window" of eight letters in length was then advanced across this string one letter at a time, yielding a frequency profile of the features in which overlapping sequences of text reveal relationships between individual features. Comparing the feature frequency profile for each book analyzed produced astonishingly accurate trees that grouped books by author, genre or historical era.



"This enables us to capture the syntactical idiosyncrasies of specific authors as well as the unique vocabulary associated with a certain genres or subject matter," says Kim. "When we saw the results of our book tree, we knew we were ready for genomes."



Applying the FFP technique to whole genome sequences of mammals produced the exact same family tree as phylogenic trees constructed through traditional approaches based on genetic, morphological, anatomical and fossil data. Kim and his colleagues also used the FFP technique to investigate the existence of a "phylogenic signal" embedded within the non-coding regions of genomes.



"We found a high level of similarity between the phylogeny obtained from the non-coding FFP comparisons and the established gene-based consensus mammalian phylogeny," Kim says. "It shows that evolutionary signals are imprinted in the entire genome and not just in the genes. We think the reason is that the sequence-changing mechanisms don't know if they are changing in a coding or a non-coding region of a genome. In other words, mutations equally affect all parts of the genome, but may be selected or filtered out differently in non-coding versus coding sequences."



In the final phase of their testing, Kim and his colleagues applied the FFP method to a total of 518 genomes, representing eukaryotes and prokaryotes, plus a couple of random genome sequences. For the prokaryotes - bacteria and Archaea, they used amino acid sequences, which are the building blocks of proteins instead of the base sequences used in mammals. This was done because unlike the genomes of mammals, the genomes of prokaryotes consist almost exclusively of sequences that code for proteins, which means that the "proteome" of these microorganisms (their entire complement of proteins) may hold the key to constructing accurate family trees for them.



"There is a lot of controversy surrounding prokaryotes with regards to which demographic group came first on the evolutionary tree," Kim says. "We wanted to test whether our method could provide any new insight on this issue."



Their results showed that the FFP method can be used to group bacteria and Archaea into separate domains, phyla and classes that are in general agreement with currently accepted grouping, but the evolutionary relationships among the groups came out different from those obtained
from traditional genetic and morphology studies. With their FFP technique, Kim and his colleagues were also able to classify microbes that had not been classified before. They also successfully used it to classify the genomes of several hundred viruses.



"No one has been able to figure out the evolutionary relationship between viral groups, but our FFP technique was able to suggest evolutionary relationships between some of these groups. We were very happy to see that," says Kim.



Much work remains to be done with the FFP technique, Kim says, and some of the observations they have made thus far could eventually prove to be wrong. But the groundwork has been laid and with further improvements, the FFP technique could be expanded far beyond books and genomes into the world of music.



"We could really go wild," Kim says, laughing, "and use it to organize all the books and documents, or even all the music ever written into useful demographic groupings."







This work was funded by the National Institutes of Health and by a grant from the Korean Ministry of Education, Science and Technology. A paper describing the research has been published in the Proceedings of the National Academy of Sciences.



Additional Information:



For more about the research of Sung-Hou Kim, visit the Website at chem.berkeley/people/faculty/kim/kimgroup/index.html



Source: Lynn Yarris


DOE/Lawrence Berkeley National Laboratory

Thousands Of Unnecessary Operations Avoided Using Less Invasive Lymph Node Biopsy

Using an ultrasound-guided fine needle to biopsy lymph nodes could spare thousands of melanoma patients every year worldwide from having to undergo unnecessary and sometimes unpleasant surgery to verify whether their cancer has spread, new research indicates.



In a study presented at the European Cancer Conference (ECCO 14) in Barcelona, scientists found that the less invasive technique produced a false positive rate of only one percent, so that 99 percent of patients with healthy lymph nodes were correctly classified.



The study, the largest of its kind to date, tested the accuracy of the new technique in 590 patients with recently diagnosed melanoma who underwent an ultrasound of the lymph node region near their tumours before having the sentinel lymph node cut out for examination. If the ultrasound confirmed cancer or looked suspicious, patients also underwent the fine needle aspiration biopsy before the sentinel node surgery. Survival was tracked for an average of 28 months.



"The fine needle aspiration detected tumour cells in the lymph node of half of the patients who were later shown to have node-positive disease through the surgical sentinel node biopsy procedure. In nearly all the cases that it missed, the tumour deposit in the sentinel node was very small and those patients seem to have an excellent prognosis -- their survival seems similar to that seen in patients with no spread to the lymph nodes," said the study's leader, Dr Christiane Voit, a dermatologist and head of the diagnostic unit at the Skin Cancer Center at Charité -- Universitätsmedizin Berlin, the Medical University of Berlin, Germany. "This study shows that the technique is highly accurate and we are recommending that it should now be performed routinely before automatically performing sentinel lymph node biopsies, as a way to reduce the need for unnecessary sentinel node operations."



Whether cancer has spread to the lymph nodes is the most important factor influencing the prognosis and treatment plan for patients with melanoma. Lymph node surgery for tumour staging has become more refined and less debilitating over the last decade. Traditional operations involve the removal of all lymph tissue from the area that drains the site of the tumour, but in some cancers, including melanoma, doctors now more often cut out only one or two key nodes, called sentinel nodes. If the sentinel node is free of cancer, patients don't need to have more extensive lymph node removal.



However, only 20 percent of patients who have their sentinel lymph nodes excised have cancer that has spread there, so the operation, which can still be accompanied by side effects such as chronic swelling and seroma, is unnecessary for 80 percent of patients.



"Sentinel node biopsy (the excision of only one node instead of all regional lymph nodes) is already an improvement over complete removal of all the lymph nodes in the axilla, groin or neck, but we still need a better way to identify which patients need their sentinel lymph nodes cut out and which don't, so that all those patients who are subjected to unnecessary surgery can avoid it. Ultrasound-guided fine needle aspiration does look better," said Voit, adding that the procedure does not cause the side effects seen in sentinel node biopsy. The sometimes-claimed danger of spreading of tumour cells along the needle tract was not evident in this study, nor in previous studies the group has conducted using the method, Voit added.



The technique, called ultrasound-guided fine needle aspiration cytology, or US-FNAC, has been reported to be useful in replacing the need for a sentinel node biopsy in breast cancer, but has not yet been accepted as a valuable option to avoid surgical sentinel node biopsy in melanoma.







Source: Emma Ross


ECCO-the European CanCer Conference

Weighty Viruses

Viruses are the simplest life forms on our planet, consisting of only DNA or RNA and a shell. After the prokaryotes (bacteria and archebacteria), viruses are the second most common type of organism. In our oceans they are the most common life form. In order to gain a better understanding of the structure and characteristics of these genetically varied little organisms, it would be highly useful to be able to determine their masses and how much these vary within a given population. Researchers in Taiwan have now used very gentle ionization techniques and a miniaturized ion trap of their own devising to accurately analyze the masses of individual, intact viruses.



Previous methods for determining the masses of viruses had a margin of error of approx.15%, which made them too inaccurate to ensure the resolution of small differences in mass. A team led by Huan-Cheng Chang has developed a new concept to attain higher precision. In order to determine their mass, viruses must first be converted to the gas phase, given an electric charge, and accelerated in an electric field. However, this process must leave the viruses intact. The researchers thus chose to use a very gentle method known as LIAD (laser-induced acoustic desorption). The virus particles are released from the sample by laser-induced sound waves. They are then caught in an 'ion trap'. This is an electric field that holds charged particles prisoner by means of its special geometry and alternating voltage. Once trapped, the virus particles are ready for mass determination. Laser light is beamed into the ion trap. If a particle is present, it scatters the light. The scattered light can be detected through the transparent surfaces of the ion trap. A portion of the light is sent to a CCD camera, which records the flight path of the trapped particle. The rest of the light goes to a measuring device that precisely analyzes the scattering signal. The scattered light is different from the initial light beam because the virus particle in the electric field of the ion trap begins to oscillate. This oscillation depends on the mass (and charge) of the virus.



The team was thus able to determine the masses of three different types of viruses with diameters between 80 and 300 nm with an astonishingly low margin of error of 1%. The masses of the viruses can, in combination with other analytical processes, be used to infer how many building blocks are used to make up the shell of the virus or how many copies of the genetic material it contains.



These highly precise measurements were made possible by the special structure of the ion trap; instead of a classic quadrupole ion trap, Chang and co-workers chose to use a cylindrical ion trap (CIT). In this type of trap, the movement of the trapped ions is considerably more complex and not mathematically ascertainable. However, it has the advantage of a much simpler geometry. The team constructed a CIT with smaller dimensions than usual, optimized the geometry, and exchanged the usual terminal electrodes of the cylinder with transparent, electrically conducting plates. This special construction is what made application of the precise light-scattering technique for the mass determination of a single virus possible.





Contact: Huan-Cheng Chang


John Wiley & Sons, Inc.

Gene Implicated In Stress-Induced High Blood Pressure

Do stressful situations make your blood pressure rise? If so, your phosducin gene could be to blame according to a team of researchers, at the University of Freiburg, Germany, and the Medical College of Wisconsin, Milwaukee, that has identified a role for the protein generated by the phosducin gene in modulating blood pressure in response to stress in both mice and humans.



The team, led by Lutz Hein and Ulrich Broeckel, generated mice lacking phosducin and found that they had increased baseline blood pressure when compared with normal mice and that they showed enhanced increases in blood pressure in response to post-operative stress. Analysis in humans indicated that a number of phosducin gene variants were associated with certain stress-dependent blood pressure responses. Further, one gene variant in particular was associated with elevated baseline blood pressure. These data led the authors to suggest that phosducin might be a good target for drugs designed to alleviate stress-induced high blood pressure. In an accompanying commentary, however, Guido Grassi, at Clinica Medica, Italy, notes that further studies are needed before the therapeutic implications of these data can really be determined.



TITLE: Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice



View this article at: jci/articles/view/38433?key=ch6PLgvm06ENhpLnhy41



ACCOMPANYING COMMENTARY
TITLE: Phosducin - a candidate gene for stress-dependent hypertension



View this article at: jci/articles/view/41508?key=JtWzBvLn9C3r9GYN8BN8



Source: Karen Honey


Journal of Clinical Investigation

Molecular ballet unravels, links proteins so cell can direct own movement

A protein called vinculin moves cylinder-like fingers to form a hand to which an arm extended by a protein partner called alpha-actinin can bind, according to St. Jude researchers


As a cell moves forward, physical stress on its skeleton triggers molecular fingers and arms to grasp each other in reinforcing links that stabilize the skeleton, according to images produced by investigators at St. Jude Children's Research Hospital.


The images show how a protein called alpha-actinin partly unravels its structure to free an internal molecular "arm" that reaches out to another protein, called vinculin. This triggers vinculin to partly unravel as well, freeing several molecular "fingers" that assume a shape that allows alpha-actinin to bind to its partner.


The researchers used a technique called X-ray crystallography to create these images, which help explain how alpha-actinin recruits vinculin to help it brace the cell's skeleton during the physically stressful process of cell movement. A report on this work, scheduled for the July 15 issue of Molecular and Cellular Biology, appears in the prepublication online issue.


The discovery is important because without vinculin to reinforce its skeleton, the cell would move rapidly and randomly, making purposeful motion impossible, the researchers said. That means cells could not migrate properly in the developing embryo to take up their final positions, leaving the embryo to wither and die; yet the ability to move purposefully also helps individual cancer cells break away from a tumor and spread to other parts of the body, a process called metastasis. Therefore, discovering how cells direct their movements could help researchers better understand how embryos develop and how some cancers spread.


The cell's skeleton is a network of long rows of a protein called actin linked together by molecules of alpha-actinin. This configuration gives the skeleton a network structure in which many rows of actin are held together in a grid, somewhat like a checkerboard. Along the edge of the skeleton, near the cell membrane, the alpha-actinin molecules do double duty. They not only hold together rows of actin, but they also bind to proteins called integrins.


Integrins are long molecules that pierce the membrane, leaving one end inside the cell and the other end firmly attached to the outside surface along which the cell is moving, according to Tina Izard, Ph.D., an associate member of Hematology-Oncology at St. Jude and the paper's senior author. Integrin's outside end is like a foot that is planted firmly on the ground but does not move, Izard said. Alpha-actinin molecules bound to the skeleton also bind to the end of integrin that is inside the cell. When the cell moves, stress on the "foot" part of the integrin outside the cell is transmitted into the cell to the other end of integrin. From there, the stress shifts to the alpha-actinin molecules that are also bound to the actin rods of the skeleton.















"Each time the moving cell grabs hold of the surface along which it is moving, the skeleton must be reinforced to withstand the stress," Izard said. "This is like dragging yourself along the floor by placing the palms of your hands down and letting the rest of your body flow forward. In the cell, that sort of stress could destroy the link between alpha-actinin and actin molecules and destabilize the cell's skeleton."


Such stress could pull alpha-actinin off the actin, according to Philippe Bois, Ph.D., a Van Vleet Foundation fellow in the St. Jude Department of Biochemistry and the paper's first author. Instead, the stress on alpha-actinin causes it to unravel its structure slightly and extend its arm to vinculin, he said. This triggers vinculin to unravel part of its own structure and extend its fingers. While the flexible fingers on the "head" of vinculin offer a hand for alpha-actinin to bind to, the sturdier back part of vinculin binds to the actin as well. This reinforces alpha-actinin's hold on the skeleton.


"It's this ability of vinculin to reinforce the connections between alpha-actinin molecules and the actin rods of the skeleton that keeps the skeleton stiff enough to withstand the stress of cell movement," Bois said.


This work is a continuation of an earlier project in which Izard and Bois demonstrated the structure of vinculin and showed that it changes its shape by moving individual "cylinders" making up its head, much like the movement of fingers on a hand. The authors named this process "helical bundle conversion" and noted that this conversion was key to cellular movement. A report on that work appeared in the January 8, 2004, issue of Nature.


Other authors include Robert A. Borgon (St. Jude) and Clemens Vonrhein (Global Phasing Limited, Cambridge, UK).


This work was supported in part by the National Institutes of Health, a Cancer Center Support (CORE) grant and ALSAC.


St. Jude Children's Research Hospital


St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization.


For more information, please visit stjude.

Discovery Of Adaptation In Mole Blood That Aids Tunnelling Could Lead To Improved Artificial Human Blood Substitutes

'Super hemoglobin' allows moles to thrive underground. Researchers writing in the open access journal BMC Evolutionary Biology have made the first identification of an adaptation in the blood of Eastern moles which allows more efficient transport of carbon dioxide, facilitating the moles' burrowing behavior.



Kevin Campbell from the University of Manitoba, Canada, worked with a team of researchers to study the blood of three underground species of North American moles. He said, "Unlike terrestrial animals, moles are routinely exposed to conditions of low oxygen and high carbon dioxide. Burrowing is difficult in itself, but is made even more challenging by the requirement to re-breathe their own expired air. We've found that one species, the Eastern mole, appears to be uniquely adapted to underground life through the evolution of a special kind of hemoglobin in their blood that greatly enhances its carbon dioxide carrying capacity".



The researchers determined the genetic code for different hemoglobin components in the three mole species and measured how well these components bind to their usual target molecules. They also tested the oxygen binding properties of whole blood samples. Speaking about the results, Campbell said, "It has been speculated that the main mechanism for the moles adaptation to subterranean life revolves around the molecule 2,3-diphosphoglycerate, or DPG, that modulates hemoglobin's oxygen binding inside the blood cells. However, in the hemoglobin of the eastern mole, the key sites which would normally bind DPG are deleted, thereby allowing for the binding of additional carbon dioxide molecules".



Adds co-author Roy Weber, University of Aarhus, Denmark, "It would be interesting to see if the hemoglobins of other burrowing species exhibit comparable specializations". The team envisions that this line of research could lead to the development of improved artificial human blood substitutes with specially engineered properties.



Notes:


Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole

Kevin L Campbell, Jay F Storz, Anthony V Signore, Hideaki Moriyama, Kenneth C Catania, Alexander P Payson, Joseph Bonaventura, Joerg Stetefeld and Roy E Weber

BMC Evolutionary Biology 2010, 10:214 doi:10.1186/1471-2148-10-214



Source:

Graeme Baldwin


BioMed Central

Learning By Embryos And The Ghost Of Predation Future

Is stress always negative for embryos? We found that embyonic exposure to stressful stimuli can be important to their survival.


When we exposed amphibian (salamander) embryos to predator odours, juveniles showed low levels of activity compared to controls and hid in vegetation; these behaviours often provide protection from predators.


In addition, we used associative learning techniques to train frog embryos so that the tadpoles would later recognize a novel scent as indicating danger.


Therefore, embryos can assimilate information about risk in their environment and modify their behavior as juveniles so that it protects them from some hazards.


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.


Proceedings of the Royal Society B: Biological Sciences