суббота, 28 мая 2011 г.

Avicena Files Composition Of Matter Patent Application For Treatment Of ALS (Lou Gehrig's Disease)

Avicena Group,
Inc. (OTC Bulletin Board: AVGOE), a late stage biotechnology company
focused on commercializing its proprietary cellular energy modulation
technology, announced today that it has filed a composition of matter
patent application with the United States Patent and Trademark Office for
Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's disease), a severe
neurodegenerative disease.



This composition of matter patent broadly covers pharmaceutical
formulations based on creatine derivatives alone or in combination with an
anti-inflammatory compound for the treatment of ALS. The Company believes
that this patent will provide additional IP protection for its current and
future generation drug candidates formulated to treat ALS which extends
beyond the existing use patents previously issued to Avicena with claims in
neurology (US Patents 6,196,115 B1 and 6,706,764 B2). This application will
further extend Avicena's intellectual property portfolio for ALS-02, a drug
candidate that has previously been granted orphan drug designation by the
US FDA.



Belinda Tsao-Nivaggioli, Ph.D., CEO of Avicena, stated, "This patent
application is another key intellectual property milestone that builds
shareholder value and will help us further protect the Company's cellular
energy franchise and the drug candidates we develop for ALS. ALS remains a
leading indication for our technology, and this additional patent
application will support our commercialization work in this important
therapeutic area."



ABOUT ALS



ALS is a neurodegenerative disease that attacks the motor neurons of
the brain and spinal cord that are responsible for voluntary muscle
movement. As these motor neurons degenerate, their ability to send impulses
to the muscle fibers is compromised. The progressive degeneration of motor
neurons eventually leads to neuron death resulting in the brain's inability
to initiate or control muscle movement. Once a patient's muscles no longer
receive the messages that they require to function, muscles begin to
atrophy. With an incidence rate of approximately 1 in 10,000, ALS affects
roughly 30,000 Americans at any given time. Each year, approximately 5,600
new cases of ALS are diagnosed. The two types of ALS are "sporadic ALS,"
which accounts for approximately 85% - 90% of all cases; and "familial
ALS," which accounts for the remaining 10% - 15% of patents.



ABOUT AVICENA



Avicena Group, Inc. (OTC Bulletin Board: AVGOE) is a late stage
biotechnology company focused on developing products based on its
proprietary understanding of the regulation of cellular energy processes.
The company's core technologies, supported by a robust IP portfolio, have
broad applications in both pharmaceuticals and dermaceuticals. Avicena's
pharmaceutical program centers on rare neurological disorders (orphan
diseases). The company is currently analyzing data from its Phase IIb/III
trial in ALS (Amyotrophic Lateral Sclerosis, or Lou Gehrig's disease). Near
term, Avicena intends to initiate a Phase III trial in Huntington's disease
to accompany its on-going Phase III trial in Parkinson's disease. Avicena's
science is well established and its products are safe and well tolerated.
Unlike traditional biotechnology companies, Avicena's clinical programs are
largely funded by government and non-profit organizations. Avicena
presently derives revenue from the sale of proprietary ingredients to skin
care manufacturers.
















SAFE HARBOR



This release may contain forward-looking statements within the meaning
of the federal securities laws. Such forward-looking statements reflect,
among other things, management's current expectations, plans and
strategies, and anticipated financial results, all of which are subject to
known and unknown risks, uncertainties and factors that may cause our
actual results to differ materially from those expressed or implied by
these forward-looking statements. Many of these risks are beyond our
ability to control or predict. See "Risk Factors" under "Item 6.
Management's Discussion and Analysis of Financial Condition and Results of
Operation" from our Annual Report on Form 10-KSB for the year ended
December 31, 2005, and other descriptions in the company's public filings
with the Securities and Exchange Commission for a discussion of such risks,
including the company's need for additional funds, the company's dependence
on a limited number of therapeutic compounds, the stage of the products the
company is developing, uncertainties relating to clinical trials and
regulatory reviews, competition and dependence on collaborative partners,
the company's ability to avoid infringement of the patent rights of others,
and the company's ability to obtain adequate patent protection and to
enforce these rights. Because of these risks, uncertainties and
assumptions, you should not place undue reliance on these forward-looking
statements. Furthermore, forward-looking statements speak only as of the
date they are made. Avicena does not undertake any obligation to update or
review any such forward-looking information, whether as a result of new
information, future events or otherwise.


Avicena Group, Inc.

avicenagroup

Kansas Bridges To Future: Minorities With Potential For Biomedical Sciences

Kansas Bridges to the Future is a research training grant funded by the National Institutes of Health. It partners Kansas State University with Seward County, Dodge City, Garden City and Kansas City Kansas community colleges and Donnelly College in Kansas City, Kan., in a grassroots effort to identify, mentor and guide minority students with potential for biomedical science careers.



Denis Medeiros, head of K-State's department of human nutrition, is the grant's principal investigator. Medeiros wrote the grant after establishing the partnership with the five schools during the last three years. More than 20 minority students have transferred to K-State since the program began in 2003, with more students in the pipeline.



"We proposed a grassroots effort beginning at the community college level to develop biomedical career awareness, enhance the academic preparation skills of selected Bridges' students, seek parental involvement, and devote resources to the community colleges to allow for sufficient academic advisement of these students," Medeiros said. "The overall goal is to increase the number of Kansas minority students pursuing graduate degrees in the biomedical field."



Medeiros said the schools participating in the partnership were selected because their enrollments reflect the diverse population in their parts of Kansas: Seward County, Garden City and Dodge City community colleges have high enrollments of Hispanic students, while Donnelly College and Kansas City Kansas Community College each have a high percentage of African-American students enrolled.



"Many of the community colleges are the first choice of underrepresented minorities in pursuing their higher education goals," Medeiros said. "Many of these students are the first in their families to go to college."



Students identified for the Bridges program receive dual admission to the community college and K-State, with tuition waivers. The students attend a one-week summer institute to make them more aware of scientific investigation and opportunities after their freshman year.



After the second year in the program, the students will have the opportunity to work for eight weeks at K-State in the laboratory of a scientific investigator. Community college instructors also will be given an opportunity to work at a K-State laboratory for an eight-week summer period to help bridge gaps in research training and curriculum development. All students will be prepared in a rigorous foundation of science, chemistry and math, Medeiros said.






The students who come to K-State also take part in the Developing Scholars Program and continue their mentoring with a professor. Other K-State faculty involved with the project include Anita Cortez, co-director of the Developing Scholars Program, and Farrell Webb, associate professor of family studies and human services and associate director of the Developing Scholars Program.



Contact: Denis Medeiros


Kansas State University

How Precursors Of Gene-Regulating Small RNAs Are Sorted By Cellular Machinery

A team of scientists at Cold Spring Harbor Laboratory (CSHL) has determined a hierarchical set of criteria that explain how the molecular precursors of gene-regulating small RNAs are sorted by the cellular machinery.



Led by Benjamin Czech, a group working in the laboratory of CSHL Professor Gregory Hannon posed the question: can distinct patterns be observed in the process that unfolds when double-stranded RNAs enter the RNAi pathway? Shorthand for RNA interference, RNAi is a biological response to double-stranded RNA that can culminate in the regulation of gene expression. It has been observed in a vast range of organisms ranging from plants to worms to flies to man.



An enzyme called Dicer cuts double-stranded RNAs into smaller double-stranded pieces called duplexes. Czech, Hannon and colleagues propose rules governing the next step in the RNAi pathway, in which duplexes are sorted to proteins called Argonautes which are at the core of a molecular complex called RISC (the RNA-Induced Silencing Complex).



"Only one strand of each duplex is chosen," explains Czech, "and which one makes all the difference. In the fruit flies that we used as models for this series of experiments, the selection of one or another strand effectively determines whether the short RNA will seek out and regulate a gene, or whether it will perform another function such as protecting a cell against a viral invader."



The rules determining how a duplex is processed and sorted are discussed in a paper the team published recently in Molecular Cell. These include the overall arrangement of the nucleotides in the duplex; how many bases are paired; where they're paired and unpaired; and how tightly the ends of the duplex are stuck together.



"These rules for sorting are important for two reasons," according to Hannon, who is also an Investigator of the Howard Hughes Medical Institute. "One is that since small RNAs play critical biological roles in nearly every process, understanding which strands of the small RNAs entering RISC act as regulators of gene expression is critical for our fundamental understanding.



"The rules are also important because scientists are hoping to use small RNAs one day as therapeutics. By understanding the rules by which small RNAs are processed and sorted, we move closer to the goal of being able to manipulate the RNAi pathway, bend it to the purpose of addressing disease."



"Hierarchical Rules for Argonaute Loading in Drosophila" appeared in Molecular Cell, Vol. 36, No. 3. The authors are: Benjamin Czech, Rui Zhou, Yaniv Erlich, Julius Brennecke, Richard Binari, Christians Villalta, Assaf gordon, Norbert Perrimon and Gregory J. Hannon.



Source: Peter Tarr


Cold Spring Harbor Laboratory

Researchers Use Light In MRSA Fight

New treatment using a light-activated drug could revolutionise the fight
against hospital "superbug", MRSA (otherwise known as meticillin resistant
staphylococcus aureus) it was revealed at the British Pharmaceutical
Conference (BPC) in Manchester.





MRSA can sometimes live on the skin or in the nose and has no harmful
effects unless it gets under the skin, for example in wounds, where it can
cause infection. If MRSA gets into the bloodstream it can cause serious
infections, for example pneumonia, septicaemia, or osteomyelitis (in the
bones).





Doctors do not apply antibiotics directly to MRSA-infected wounds as they
do not penetrate deep enough into the wound to have an effect, or can
irritate the surrounding skin, slowing down wound healing. Worryingly, MRSA
is now resistant to most types of standard antibiotics.





Investigations underway by Corona Cassidy and co-workers at the School of
Pharmacy, Queen's University of Belfast, move away from the antibiotic
approach. The treatment would involve delivering a drug known as a
'photosensitiser' to infected wounds and activating it using a special type
of light, triggering it to kill the MRSA. The concept is known as
photodynamic antimicrobial chemotherapy or 'PACT'.





In laboratory studies, the team has examined a hydrogel that holds and
then releases the light-reacting drug. The system was effective in killing
the bacteria when the drug was released from the hydrogel.





Miss Cassidy said: "PACT is an exciting potential treatment of
MRSA-infected wounds. More laboratory work must be carried out to optimise
our treatment conditions to ensure that all exposed bacteria are killed."



The British Pharmaceutical Conference 2008 (BPC)





BPC 2008: Pharmacy in the 21st Century: Adding years to life and life to
years. In 2008, as the NHS marks its 60th anniversary year, BPC will examine
how pharmacy and the pharmaceutical services are helping to add years to life
and life to the year of the UK population. The profession of pharmacy plays
an important role in meeting the healthcare challenges associated with the
UK's ageing population.





How can pharmacists contribute to caring for the population as well as
ensuring quality of life? Increasingly, scientists and practitioners have to
consider the cost implications of this conundrum, and the evidence base for
all interventions is becoming of paramount importance: BPC 2008 will debate
these issues and open up discussion on them. Visit: bpc2008





The main sponsors of BPC 2008 are: Boots The Chemists (Lead Sponsor),
AstraZeneca (Associate Sponsor and BPC-PJ Careers Forum Platinum Sponsor),
Pharmacists' Defence Association (PDA) (Associate Sponsor) and GSK (BPC-PJ
Careers Forum Platinum Sponsor).

British Pharmaceutical Conference


View drug information on Photodynamic Therapy.

Common Pain Relievers May Dilute Power Of Flu Shots

With flu vaccination season in full swing, research from the University of Rochester Medical Center cautions that use of many common pain killers -- Advil, Tylenol, aspirin -- at the time of injection may blunt the effect of the shot and have a negative effect on the immune system.


Richard P. Phipps, Ph.D., professor of Environmental Medicine, Microbiology and Immunology, and of Pediatrics, has been studying this issue for years and recently presented his latest findings to an international conference on inflammatory diseases.


"What we've been saying all along, and continue to stress, is that it's probably not a good idea to take common, over-the-counter pain relievers for minor discomfort associated with vaccination," Phipps said. "We have studied this question using virus particles, live virus, and different kinds of pain relievers, in human blood samples and in mice -- and all of our research shows that pain relievers interfere with the effect of the vaccine."


A study by researchers in the Czech Republic reported similar findings in the Oct. 17, 2009, edition of The Lancet. They found that giving acetaminophen, the active ingredient in Tylenol, to infants weakens the immune response to vaccines.


Phipps' research has tested whether production of antibodies using a cell culture system was blunted by over-the-counter pain relievers. He found that a variety of pain relievers -- even though Tylenol and Advil have different ingredients -- seemed to dilute the production of necessary antibodies to protect against illness.


Many of the pain relievers in question are classified as NSAIDs or nonsteroidal anti-inflammatory drugs, which act in part by blocking the cyclooxygenase-2 (cox-2) enzyme. Blocking the cox-2 enzyme is not a good idea in the context of vaccination, however, because the cox-2 enzyme is necessary for the optimal production of B-lymphocytes.


Therefore, when a person takes a medication to reduce pain and fever, he or she might also inadvertently reduce the ability of B cells to make antibodies.


Phipps and colleagues also demonstrated that timing of the administration of pain relievers is important as well, according to the study published earlier this year in the journal Cellular Immunology.


They exposed human cells and mice to ibuprofen, Tylenol, aspirin and naproxen (Aleve) in amounts comparable to doses commonly used by millions of Americans every day to prevent or treat pain and fever, or arthritis, or to prevent heart attack and stroke.


Treatment during the earliest stages of inflammation - or when the first signs of pain, swelling, redness or fever would occur - had the most detrimental effects on the immune system, the study noted.


The connection between NSAIDs and antibody production is still being actively pursued. Phipps said researchers believe ibuprofen, in particular, affects lymphocytes' ability to produce antibodies.


Meanwhile, until a full clinical trial provides a clearer picture, Phipps urges regular users of NSAIDs to be aware of the risks.


"NSAIDs are one of the most commonly used drugs; they are recommended for all age categories, are prescribed for relieving transient pain or in cases of serious inflammatory diseases," Phipps said. "By decreasing antibody synthesis, NSAIDs also have the ability to weaken the immune system which can have serious consequences for children, the elderly and the immune-compromised patients."


The U.S. Public Health Service has funded Phipps' studies. URMC co-investigators on the study in Cellular Immunology include: David Topham, Ph.D., an expert in the immune response to influenza and a principal investigator in the David H. Smith Center for Vaccine Biology and Immunology, and Simona Bancos and Matthew P. Bernard, of the Department of Environmental Medicine, Lung Biology and Disease Program.


One of the nation's top academic medical centers, the University of Rochester Medical Center forms the centerpiece of the University's health research, teaching, patient care, and community outreach missions. The Medical Center receives more than $230 million in external research funding per year and the University of Rochester School of Medicine and Dentistry ranks in the top one-quarter of U.S. medical centers in federal research funding. The University's health care delivery network is anchored by Strong Memorial Hospital - a 739-bed, University-owned teaching hospital. As upstate New York's premier health care delivery network, patients benefit from the Medical Center's robust teaching and biomedical research programs.


Source: University of Rochester Medical Center

Benign Or Malignant? MTOR Makes The Decision

Tuberous sclerosis complex (TSC) is a genetic disorder that results in sufferers developing benign tumors in many parts of their body. It is caused by genetic mutation of either of two genes, TSC1 or TSC2. The proteins encoded by these genes are negative regulators of a signaling pathway that is initiated at the cell surface by a ligand binding to PDGFR and that involves activation of PI3K, AKT, and mTOR. The fact that individuals with TSC develop only benign tumors is somewhat surprising because genetic mutations that cause increased PDGFR, PI3K, and AKT activity are associated with malignant cancer, as are inactivating genetic mutations of other negative regulators of this signaling pathways (including PTEN). In a study appearing online in advance of publication in the March print issue of the Journal of Clinical Investigation, researchers from the Chinese Academy of Medical Sciences and Peking Union Medical College, People's Republic of China, use mouse models of TSC to provide a potential explanation for the fact that individuals with TSC develop only benign tumors.



The lack of malignant tumors in mice expressing decreased levels of TSC1 or TSC2 is associated with decreased PDGFR expression and decreased PI3K and AKT activity, despite increased mTOR activity. Hongbing Zhang and colleagues now show that in mouse cell lines, activation of PI3K or AKT, as well as inhibition of PTEN, results in decreased PDGFR expression and negative feedback to dampen AKT activity, despite increased mTOR activity. Furthermore, inhibiting mTOR restored PDGFR expression levels and AKT activity in mouse cell lines expressing decreased levels of TSC1 or TSC2, and overexpression of active AKT or PDGFR in such cells rendered them able to induce malignant tumors when transplanted into immunocompromised mice. This study therefore demonstrates that increased mTOR activity decreases PDGFR expression and AKT activity in mouse cells expressing decreased levels of TSC1 or TSC2. More importantly, it offers a potential explanation for the observation that humans expressing mutant forms of TSC1 or TSC2 develop only benign tumors.



TITLE: PDGFRs are critical for PI3/Akt activation and negatively regulated by mTOR



AUTHOR CONTACT:

Hongbing Zhang

Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.





JCI table of contents -- February 8, 2006



Contact: Karen Honey


Journal of Clinical Investigation

Scientists Identify Genes That Both Extend Life And Protect Against Cancer

A person is 100 times more likely to get cancer at age 65 than at age 35. But new research reported in the journal Nature Genetics identifies naturally occurring processes that allow many genes to both slow aging and protect against cancer in the much-studied C. elegans roundworm.



Many of the worm genes have counterparts in humans, suggesting that new drugs may some day ensure a long, cancer-free life. The new research and a related study the scientists reported in Science last year indicate that cellular changes leading to longevity antagonize tumor cell growth.



The studies are by scientists at the University of California, San Francisco, who say the research also underscores the deep evolutionary connection between lifespan and cancer.



The worms, known formally as Caenorhabditis elegans, were the stars of a startling 1993 discovery by UCSF biologist Cynthia Kenyon, PhD. She found then that a change in just one gene, called daf-2, doubled the worms' lifespan. This finding led to the understanding that lifespan is regulated by genes and is therefore changeable, rather than the inevitable result of the body's breakdown. The discovery in worms has been confirmed in other animals including mice.



The new research by Kenyon and graduate student Julie Pinkston is reported in the advanced online edition of the journal.



Kenyon is the American Cancer Society Professor and director of the Hillblom Center for the Biology of Aging at UCSF.



"This is very exciting," Kenyon said. "There is a widely held view that any mechanism that slows aging would probably stimulate tumor growth. But we found many genes that increase lifespan, but slow tumor growth. Humans have versions of many of these genes, so this work may lead to treatments that keep us youthful and cancer-free much longer than normal."



Since her early finding that the gene daf-2 and another gene known as daf-16 regulate lifespan, Kenyon's research team has hoped to identify the genes that they in turn affect -- those that more directly affect aging and tumor growth.



"Now we are really getting there," Kenyon said.



The gene daf-2 codes for a receptor for insulin and also for an insulin-like protein that promotes growth. It influences daf-16, which makes a so-called transcription factor -- a protein that determines when and where hundreds of other genes are turned on. The focus of the new study was to identify specific genes regulated by daf-16 which affect cancer and/or lifespan.



The scientists used an established tumor model in the worms. Then, starting with a list of 734 genes known to be targets of daf-16, they identified 29 genes that either promote or suppress tumor cell growth. They did this using several techniques, including RNA interference or RNAi, a powerful tool that allows scientists to control the expression of just one kind of gene at a time.



About half of the genes stimulated tumor growth and half suppressed it, they found. Strikingly, about half of these genes also affect lifespan in animals that do not have tumors, further strengthening the model Kenyon and others have conceived in which the insulin receptor, daf-2, works in concert with the transcription factor daf-16 to link longevity and tumor resistance. The "downstream" genes appear to act in a cumulative way, they found.



The genes that stimulated tumor growth also accelerated aging itself, and the genes that prevented tumor growth slowed down the aging process and extended lifespan. These findings greatly strengthen the view that the controls of lifespan and cancer have deep, common roots, Kenyon and Pinkston conclude.







The research was funded by the National Institutes of Health.



UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.



Source: Wallace Ravven


University of California - San Francisco

Evolution Mystery: Spider Venom And Bacteria Share Same Toxin

It's a case of evolutionary detective work. Biology researchers at Lewis & Clark College and the University of Arizona have found evidence for an ancient transfer of a toxin between ancestors of two very dissimilar organisms--spiders and a bacterium. But the mystery remains as how the toxin passed between the two organisms. Their research is published this month in the journal Bioinformatics, 22(3): 264-268, in an article titled "Lateral gene transfer of a dermonecrotic toxin between spiders and bacteria."



"We are piecing together an historical puzzle with evidence from living descendants of an ancient ancestor," said Greta Binford, assistant professor of biology at Lewis & Clark. Her coresearcher on the project is Matthew Cordes, assistant professor of biochemistry and molecular biophysics at the University of Arizona. The toxin is uniquely found in the venom cocktail of brown or violin spiders, including the brown recluse, and in some Corynebacteria. The toxin from the spider's venom can kill flesh at the bite site; the bacterium causes various illnesses in farm animals.



"Our research was inspired by the fact that we have a group of spiders with a unique toxin, and that toxin also happens to exist outside the animal kingdom in this particular bacterium," she added. "A pattern like this raises the possibility of lateral gene transfer as a explanation." Lateral gene transfer refers to the movement of genes between the genomes of unrelated organisms. This contrasts with vertical transfer of genes from parent to offspring.



Cordes and Binford found a common structural motif at the end of both toxic proteins that is not found in any other proteins. Evidence for common ancestry (homology) of the toxins had previously been noted, but this uniquely shared structural bit is best explained by these toxins being more closely related to each other than they are to any other known protein.



"That one structural detail--which resembles a plug or cork at the end of a barrel-shaped enzyme--is evidence that the spider and bacterium share a relatively recent common ancestor," Cordes said. "Aside from being an example of lateral transfer between very distantly related organisms, this study is an unusual example of using structural motifs in proteins to answer questions about common ancestry when gene sequences are too different to be clear about these relationships."



"We're still left with the question of whether this venom enzyme hopped species from the spider to the bacteria, or the other way around. Either way, the presence of this medically-relevant toxin in one of these groups of organisms is likely the result of transfer from the other lineage," Binford said. "Understanding the importance of this structural motif in the toxic activity may help with developing treatments that minimize the effects of bites of brown recluse and their relatives. If this motif is central to protein function, treatments designed for the spider bites may also work for treating problems caused by the corynebacterial toxin," she added.







OBTAIN A COPY OF THE ARTICLE: Available through Bioinformatics, online at bioinformatics.oxfordjournals/cgi/content/abstract/bti811



Contact: Tania Thompson

taniatlclark

Lewis & Clark College

Mathematical Model Of Fruit Fly Eyes Created By Researchers

Many researchers have tried to create a mathematical model of how cells pack together to form tissue, but most models have many different complicated factors, and no model is universal.



Researchers at Northwestern University have now created a functional equation -- using only two parameters -- to show how cells pack together to create the eyes of Drosophila, better known as the fruit fly. They hope that the pared-down equation can be applied to different kinds of tissues, leading to advances in regenerative medicine.



Sascha Hilgenfeldt, associate professor of engineering sciences and applied mathematics and of mechanical engineering in the McCormick School of Engineering and Applied Science, teamed up with Richard W. Carthew, professor of biochemistry, molecular biology, and cell biology in the Weinberg College of Arts and Sciences, and Sinem Erisken, a McCormick undergraduate studying biomedical engineering, to create the model. Their work was published online Jan. 11 by the Proceedings of the National Academy of Sciences (PNAS).



The interdisciplinary effort among geneticists, engineers and mathematicians began 18 months ago, when Hilgenfeldt, who specializes in foam, soft matter and fluid mechanics, teamed with Carthew, who has studied the biological features of fruit fly eyes.



Hilgenfeldt knew that when it comes to creating a model that shows what determines the shape of functional cells in tissues, the myriad factors -- including the bulk of the cell, what's going on inside of the cell and how the cell forms -- make it very difficult to quantify.



"That's a nightmare for quantitative scientists," he said. "It's extremely complicated."



But the cells in a fruit fly's eye act more like foam in that the structure of the cells depends only on the energy of their interfaces, or the surface where the cells touch. That energy is divided into two parts -- the energy from the stretching of the cells' membranes and the energy of the "glue" (the adhesion molecules) that holds the neighboring cell membranes together. Hilgenfeldt took those two factors and created a quantitative model of cell geometries in the fruit fly retina. So instead of needing to know all the different cell factors to create the model, he just needed the two energy components to create the model.



"It's one of the most quantitative models I've seen for a biological system," Hilgenfeldt said. "For this system, mainly all you need to know is the interfacial energies and everything falls into place."



Such a model helps researchers understand how the presence of the glue energy changes the shape of the eye and will help them study how those adhesion molecules develop and function during embryo development.



Further down the road, having these kinds of models could help scientists learn how to grow regenerative tissues. Hilgenfeldt also hopes to see how far he can take this model -- testing whether it will work in tissues that have much more variation in their cell patterns.



"It is very promising for quantitative science to be able to do something about these complex biological systems," he said.



Though the undergraduate student who worked on the research has graduated, Hilgenfeldt said another undergraduate student will help continue the research through the Research Training Group (RTG) program in applied mathematics. The program emphasizes interdisciplinary research with teams composed of applied mathematicians, scientists and engineers. It is funded by a $2.1 million National Science Foundation grant.



"This is precisely what the grant is supposed to do," Hilgenfeldt said. "Interdisciplinary work across all the stages of academic life -- from undergrad to faculty."







Source: Megan Fellman


Northwestern University

Potential Antidepressant Compounds Discovered By Researcher At The University Of Navarra

Luis Berrade, a researcher with the Drug R&D Unit of the University of Navarra, has discovered new compounds with the potential for anti-depressant activity. All-told, the chemist of the School of Sciences synthesized 51 compounds whose biological characteristics were evaluated by two of the most prestigious groups in this area: the Mediterranean Institute of Neurobiology, located in Italy, and the Department of Pharmacology of the University of Oslo.



The results obtained formed part of his doctoral dissertation, entitled "Design, synthesis and preliminary biological evaluation of new derivatives of benzo[b]-thiophene in the Search for Agents for a New Anti-Depressant Therapy."



As the researcher explained, the new molecules which he designed affect two brain targets which are considered to be keys in the development of processes of depression. One of these is the serotonin transporter, whose reuptake reduction has already been shown to improve mood; the other is the serotoninergic receptor 5-HT7, a therapeutic target for serotonin whose modulation can provoke anti-depressant effects.



Trials in vivo



In order to study these two key targets, Luis Berrade developed chemical structures via the fusion of two similar chemical compounds: the benzo[b]-thiophene ring and arilamine. Following this, he compared the new compounds with a drug currently on the market, Fluoxetine. As a result of this research, he explained, we discovered that nine of these compounds demonstrated greater affinity, in this sense, than the commercial drug. As a consequence of this discovery, in January in vivo trials were begun in order to test their anti-depressant activity in mice.



This study, one of the first in the world in this specialty, was undertaken in collaboration with the Department of Pharmacology of the University of Navarra. Among its objectives was discovering whether these new compounds could reduce the minimum time required for anti-depressant drugs to ameliorate the symptoms of the disease: Currently, the time for an antidepressant to take effect is from three to six weeks, and this is an important factor in patient refusal to continue with these treatments; as a result it is very important to shorten the time required for the positive effects to appear.






This release is also available in Spanish.



Source: Oihane Lakar


Elhuyar Fundazioa

EMBL's 20th Member State Is Luxembourg

The European Molecular Biology Laboratory [EMBL] has announced that Luxembourg is the new member of its international community. Accepted by EMBL's council and ratified by the parliament of Luxembourg, the Grand-Duchy has officially joined the institute as the 20th member state.



"EMBL is a key player in European molecular biology," says FranГ§ois Biltgen, Minister of Culture, Higher Education and Research, Luxembourg, "being part of its international network will provide a boost for Luxembourg's research in the growing field of molecular biology and will integrate its researchers even better into the European scientific community. In return Luxembourg will contribute to EMBL's various activities bringing in complementary strengths and technical expertise."



Through its membership Luxembourg will contribute to EMBL's pursuit of its five missions: to perform basic research in molecular biology; to train scientists, students and visitors at all levels; to offer vital services to scientists in the member states; to develop new instruments and methods in the life sciences and to actively engage in technology transfer activities. As a member state Luxembourg will benefit from the various services and training programmes that EMBL offers for its member states and it will have access to the research facilities at the five EMBL stations in Heidelberg and Hamburg, Germany, Grenoble, France, Hinxton, UK, and Monterotondo, Italy.



The delegate representing Luxembourg in EMBL's council will be Josiane Entringer of the Department for Research and Innovation of the Ministry for Culture, Higher Education and Research.



Luxembourg's activities in the molecular life sciences range from basic research in genetics, molecular biology and biomedicine to more applied areas such as cancer research and the development of health technologies. Since the foundation of its University in 2003, Luxembourg has actively contributed to education and training of Europe's scientific elite.



"We are very pleased to welcome Luxembourg as our new member state," says Iain Mattaj, Director General of EMBL, "Luxembourg has substantially contributed to the progress of research in the life sciences in the past years. Its overlapping research interests and its complementary expertise make it a very valuable addition to EMBL."






Source: Anna-Lynn Wegener


European Molecular Biology Laboratory

Researchers Identify Gene Involved In Breast Cancer

Researchers at the University of Michigan Comprehensive Cancer Center have identified a gene linked to the development of an aggressive form of breast cancer.


The researchers found that the gene, FOXP3, suppresses tumor growth. FOXP3 is located on the X chromosome, which means a single mutation can effectively silence the gene. This is unusual, as only one other gene linked to cancer has been found on the X chromosome.


When one copy of the FOXP3 gene is silenced, the researchers found in studying mice, 90 percent of the mice spontaneously developed cancerous tumors. The researchers also looked at FOXP3 in human breast tissue cells, comparing cancerous and non-cancerous cells. FOXP3 was found to be either deleted or mutated in a substantial portion of the cancer sample: about 80 percent of the cancer tissues studied did not express the gene at all.


In addition, the researchers found FOXP3 to be a repressor of HER-2, a protein that typically marks a more aggressive form of breast cancer. The researchers believe FOXP3 suppresses the HER-2 gene. HER-2 can be activated by many different factors, but the researchers found that when FOXP3 is normal, it keeps HER-2 levels low; when FOXP3 is missing or mutated, HER-2 levels are likely to rise.


The researchers have shown that FOXP3 was reduced or missing in about 80 percent of the more than 600 cases of breast cancer tissue examined. At this point, the researchers do not know if FOXP3 can predict breast cancer risk, like the BRCA1 and BRCA2 genes, both of which are linked to a higher risk of breast cancer.


"FOXP3 defects promote cancer development. We do not know whether this is a genetic defect that puts women at higher risk. For treatment, this gene could be quite important, but for diagnosis, it's too early to tell," says study author Yang Liu, Ph.D., deNancrede Professor of Surgery at the U-M Medical School and co-director of the cancer immunology program at the U-M Comprehensive Cancer Center. Results of the study appear in the journal Cell.


Initially, the researchers were studying FOXP3's role in autoimmune disease, when they noticed that female mice with one copy of the mutated form of the gene were developing breast cancer. Moreover, the tumors expressed high levels of ErbB2, the mouse equivalent of HER-2. Breast cancer is rare in mice, and ErbB2-positive breast cancer is even more rare.


"FOXP3 is the first X chromosome-linked gene that suppresses breast cancer and represses the HER-2/ErbB2 oncogene. Given the significant role HER-2 plays in breast cancer and the widespread defects we found on FOXP3, it is likely that this gene play an important role in suppressing breast cancer," says Pan Zheng, M.D., Ph.D., associate professor of surgery and pathology at the U-M Medical School.


The research is still in early stages. No predictive or diagnostic test is available involving this gene finding. More than 180,000 women will be diagnosed with breast cancer this year, and 40,900 will die from the disease, according to the American Cancer Society.


In addition to Zheng and Liu, U-M study authors were Lizhong Wang, Xing Chang, Huiming Zhang, Weiquan Li, Yan Liu, Yin Wang, Bae Keun Park and Cun-Yu Wang. Additional authors are Tao Zuo, Carl Morrison, Michael W.Y. Chan, Jin-Qing Liu, Chang-gone Liu, Rulong Shen, Xingluo Liu, Tiany Yang, Tim H.-M. Huang, and Richard Love from Ohio State University; and Virginia Godfrey from the University of North Carolina, Chapel Hill.


Funding for the study was from the National Institutes of Health and U.S. Department of Defense.


The University of Michigan has filed a patent application on this research technology, and is currently looking for a corporate partner to help bring the technology to market.


Reference: Cell, Vol. 129, issue 7, pp. 1275-1286


University of Michigan Health System

2901 Hubbard St., Ste. 2400

Ann Arbor, MI 48109-2435

United States

med.umich

New Journal Partnership For 2008 Announced By Elsevier

Elsevier is pleased to announce that in 2008 the leading fatty-acid research journal Prostaglandins, Leukotrienes & Essential Fatty Acids (PLEFA) will become the Official Journal of the International Society for the Study of Fatty Acids and Lipids (ISSFAL).



2008 also marks the journal's 30th Anniversary. PLEFA was founded in 1978 as Prostaglandins and Medicine by the late David F Horrobin, and published by Churchill Livingstone. PLEFA addresses all aspects of the roles of lipids and their metabolites in cellular, organ and whole-organism function, and places a particular emphasis on human studies. The relevance of this research, including into omega-3 fatty acids, to the development of novel treatments for disease is growing.



Current Editor-in-Chief Mehar S Manku comments, "The affiliation of ISSFAL to PLEFA is an important step in both the journal and society's growth and maturity. We warmly welcome ISSFAL members to PLEFA. Many ISSFAL members have previous experience of publication in PLEFA and therefore the association between the parties seems a natural one. We will work together to better understand the role of fatty acids and their several important bioactive metabolites in health and disease. Our common aim is to make PLEFA the leading journal in this field."



In addition, "There is no doubt that in science, communication is crucial. ISSFAL has become the recognised scientific society in the field of lipids in nutrition, and as such needs a recognised medium to facilitate that communication. PLEFA is a key journal in this field, and so a link is logical between the two. ISSFAL is therefore pleased to make PLEFA the Official Journal of the Society. I wish every success for this promising joint venture," states Michel Lagarde, President of ISSFAL.



In 2008, all members of ISSFAL will have full online access to PLEFA, including its 30-year archive, online via a new site: PLEFA







About PLEFA



The role of lipids, including essential fatty acids and their prostaglandin, leukotriene and other derivatives, is now evident in almost all areas of biomedical science. Cell membrane behaviour and cell signalling in all tissues are highly dependent on the lipid constituents of cells. Prostaglandins, Leukotrienes & Essential Fatty Acids aims to cover all aspects of the roles of lipids in cellular, organ and whole organism function, and places a particular emphasis on human studies. Papers concerning all medical specialties are published. Much of the material is particularly relevant to the development of novel treatments for disease. PLEFA is Medline indexed, and has an Impact Factor of 2.261 (Journal Citation Reports ® 2007, Published by Thomson Scientific).
















About ISSFAL



ISSFAL is an International Scientific Society established in 1991, of more than 500 members from more than 40 countries. ISSFAL members are scientists, medical professionals, educators, administrators, communicators and others with an interest in the health effects of dietary fats, oils and lipids; members include researchers carrying out studies on the health effects of omega-3 and omega-6 fatty acids, conjugated linoleic acids, saturated and monounsaturated fatty acids as well as other lipids. ISSFAL is the foremost International Scientific Society dealing exclusively with the health impact of dietary lipids.



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: Andrew Miller


Elsevier

Monkey Studies Important For Brain Science

Studies with non-human primates have made major contributions to our understanding of the brain and will continue to be an important, if small, part of neuroscience research, according to a recent review published in the British medical journal, The Lancet.



Authors John P. Capitanio, professor of psychology at UC Davis and associate director of the California National Primate Research Center, and Professor Marina E. Emborg at the University of Wisconsin-Madison and the Wisconsin National Primate Research Center describe the importance of non-human primates in studies of Alzheimer's disease, Parkinson's disease, neurological complications of AIDS and stress.



"The key contribution of these studies is based on the similarities between the brains of humans and those of non-human primates," said Capitanio, who studies animal behavior. Human and monkey brains show similar organization and structure, and the animals show complex behavior that can be compared to human behavior. However, he said, several complicating factors will always limit the number of animals used, including the financial expense, ethical issues and the relative difficulty of breeding compared to other model animals such as rodents.



All animal models have their strengths and limitations, Capitanio said. But just as a model building helps engineers and architects understand how a structure will work, animal models can help researchers understand body systems.



For example, the drug MPTP -- first synthesized in an illegal drug laboratory -- causes symptoms similar to Parkinson's disease in both humans and monkeys, but not in rats or mice, which lack a crucial enzyme. Researchers are now studying monkeys treated with MPTP to better understand new treatments for Parkinson's disease -- the second most common neurodegenerative disease in people over 65.



"A model is not the real thing, but it can help you understand the real thing," Capitanio said.







The California National Primate Research Center (CNPRC) is part of a network of eight national primate research centers sponsored by the National Center for Research Resources, a division of the National Institutes of Health.



Source: Andy Fell


University of California - Davis

Preventing Toxic Side Effects Of Inflammatory Disease Therapy

Researchers at the University of California, San Diego (UCSD) School of Medicine have developed a mouse model that could help scientists develop better drugs to fight autoimmune and inflammatory disorders such as multiple sclerosis and rheumatoid arthritis.



Inflammation is a process by which the white blood cells and chemicals of the immune system rally to protect the body from infection and foreign substances such as bacteria and viruses. In autoimmune diseases, however, this defense system triggers an inflammatory response when there are no foreign substances to fight off, or the defense system goes into "overdrive" and forgets how to turn off. In these diseases, the body's normally protective immune system attacks and damages its own healthy tissues.



UCSD researcher Mark H. Ginsberg, M.D., professor of Medicine at the University of California, San Diego (UCSD) School of Medicine, and his colleagues have identified a mechanism to selectively disrupt signaling to recruit lymphocytes and monocytes - white blood cells sent to sites of inflammation to fight infection - while maintaining the body's other essential immune system functions. Their findings appear online on February 9 in advance of print publication in the March issue of the Journal of Clinical Investigation.



In the case of certain autoimmune diseases, the alpha 4 integrins cause white blood cells to accumulate at the site of the disease, resulting in inflammation. An integrin is a surface molecule found on the exterior of cells that helps cells adhere and migrate. It is also believed to be responsible for a role in cell signaling, which allows cells to communicate with the extracellular environment. One of the promising treatments for disorders such as multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis - the alpha 4 integrin antagonist - works by blocking cell adhesion. However, this anti-inflammatory therapy could cause adverse side effects, such as impairment of the immune system and the patient's ability to develop new red and white blood cells in the bone marrow, a process called hematopoiesis.



"Our goal was to identify a more specific target of alpha 4 integrin molecules in order to interfere with their roles in disease progression while sparing alpha4 functions required for normal health," said David M. Rose, D.V.M., Ph.D., assistant professor of medicine at UCSD, and co-author of the study.



The research team created mutant mice known as "alpha4(Y991A) mice," in which the alpha4 integrin can no longer bind to a signaling protein inside the cell called paxillin. Previously generated alpha4 integrin deficient mutant mice died at birth because too many aspects of alpha4 function were changed. The new alpha4(Y991A) mice have an impairment only in the interaction between alpha4 and paxillin, and thus have fewer effects on development. The researchers discovered that, in contrast to normal mice, alpha4(Y991A) mice exposed to an inflammatory stimulus recruited fewer circulating white blood cells (B and T cells) to the region of exposure. However, the development of new B and T cells was unaffected.



The authors suggest that these mice are a valuable tool to test models of inflammatory and autoimmune diseases of humans, and that a new class of pharmaceutical agents that target the specific interaction of paxillin and alpha4 integrin could be important future treatments of inflammatory disease.



"We were surprised to find that the mutation actually had very little effect on the animal's development of lymphocytes, the white blood cells that fight infection," said Rose. "This could prove to be an important first step in development of a more effective drug to target alpha4 integrins in autoimmune and inflammatory disease of humans."



Additional co-authors include Kenneth Kaushansky, M.D., Chloй C. Fйral, Jaewon Han, Norman Fox and Gregg J. Silverman, UCSD Department of Medicine.







This research was funded by grants from the National Institutes of Health.



Contact: Debra Kain

ddkainucsd

University of California - San Diego

Agilent Technologies, University Of Michigan Partner On Research To Attack Prostate Cancer Using Systems Biology

Agilent Technologies Inc. (NYSE:A) announced its support of prostate cancer research by the University of Michigan's Center for Translational Pathology (MCTP) through a grant of instruments and funding. The goal is to accelerate research to defeat the disease using a multidisciplinary systems biology approach.


"We see this as an opportunity to partner with a truly advanced lab that is using multiple scientific disciplines to look at very important clinical problems," said Gustavo Salem, Agilent vice president and general manager, Biological Systems Division. "This relationship will give us a better understanding of how to apply our technologies in a clinical research setting and will enable the University of Michigan to accelerate its scientific research."


Agilent is contributing a 1200 Series liquid chromatography (LC) system to be used to separate metabolites from human plasma, and a 1200 Series Rapid Resolution LC coupled to a 6530 Accurate Mass quadrupole time-of-flight mass spectrometer (Q-TOF MS) for the identification of those metabolites.


"We will focus our laboratory research on a systems-biological approach to try to understand the disease at the biochemical and genetic levels simultaneously," explained Christopher Beecher, Ph.D., professor of pathology at the U-M Medical School. "We expect to be able to make a number of discoveries in prostate cancer and to develop new techniques that will be useful universally."


The research team, led by the director of the MCTP, Arul Chinnaiyan, M.D., Ph.D., has already revealed metabolomic profiles of prostate cancer progression by looking at 1,126 metabolites across 262 samples of tissue, blood or urine. The lab is currently trying to unlock the secrets of how prostate tumors gain the ability to spread. The MCTP houses cutting-edge facilities for genomic, proteomic and metabolomic analyses, the three main disciplines used in systems biology.


The collaboration between MCTP and Agilent is a result of Agilent's University Relations Program, which facilitates collaborations with universities around the world. The program sponsors research that advances the science of measurement and provides instructional materials to universities.


About MCTP


The Michigan Center for Translational Pathology is committed to the discovery of the genetic factors involved in the development of a wide variety of diseases, including cancer of the prostate, breast, lung, colon and skin. The center's researchers actively pursue advances in the early detection and treatment of various types of cancer and other diseases, with the eventual goal of creating new targeted therapies. Learn more at med.umich/mctp.


About Agilent Technologies


Agilent Technologies Inc. (NYSE:A) is the world's premier measurement company and a technology leader in communications, electronics, life sciences and chemical analysis. The company's 19,000 employees serve customers in more than 110 countries. Agilent had net revenues of $5.8 billion in fiscal 2008. Information about Agilent is available on the Web at agilent.

Source
Agilent Technologies

News Tips From The Journal Of Neuroscience

1. Mapping the Tectum onto the Hindbrain in Zebrafish

Tomomi Sato, Takanori Hamaoka, Hidenori Aizawa, Toshihiko Hosoya, and Hitoshi Okamoto.



Retinotopic inputs to the optic tectum have been thoroughly mapped, but now Sato et al. map tectal efferents that project to the premotor reticulospinal system of the hindbrain. Stimulation of these efferents trigger eye and tail movements, often as escape behavior. The authors began with a transgenic zebrafish that expressed green fluorescent protein (GFP), driven by the brn3 promoter. GFP labeled the ipsilateral (uncrossed) but not contralateral (crossed) tectobulbar tracts. By combining the cre/loxP and Gal4/UAS systems under the control of brn3a-hsp70, the authors zeroed in on the somatic origin and final projection sites of individual tectal neurons. Within the hindbrain, rhombomeres (r) 2 and 6 received inputs in distinct anterior-posterior patterns, potentially indicative of their role in visuomotor transformations. Reticulospinal neurons in r2 are activated during visually evoked escape behavior. Ectopic expression of ephrinB2a increased the probability that neurons projected to r2.



2. Aggrecan and Perineuronal Nets in Barrel Cortex

Paulette A. McRae, Mary M. Rocco, Gail
Kelly, Joshua C. Brumberg, and Russell
T. Matthews.



The component of the extracellular matrix called the perineuronal net (PN), as its name implies, surrounds the cell body and proximal dendrites of selected cortical neurons. This week, McRae et al. report that the PN in somatosensory barrel cortex is affected by sensory experience. The authors identified the PN by staining with Cat-315, an antibody for the proteoglycan, aggrecan. Neurons ensheathed by lattice-likePNwere enriched in layer IV of mouse barrel cortex. Sensory deprivation, imposed by continuous trimming of right-side whiskers for the first 30 d of postnatal life, reduced the number of neurons expressing Cat-315-positive PN. Sensory deprivation of adult mice had no effect on Cat-315 staining. When whiskers were allowed to regrow after the initial 30 d deprivation, PNs did not recover but instead continued to decline, highlighting the importance of sensory activity during the first postnatal month. Inside the Cat- 315-reactive nets, the main catch was parvalbumin-expressing interneurons.



3. Dendritic Spines Take Shape during LTP

Lulu Y. Chen, Christopher S. Rex,
Malcolm S. Casale, Christine M. Gall,
and Gary Lynch.



Synaptic plasticity often affects the shape of synaptic structures. This week, Chen et al. take this question to the level of single dendritic spines by investigating actin network dynamics following theta burst stimulation (TBS). In rat hippocampal slices, TBS induced phosphorylation of p21-activated kinase (PAK) and its downstream effecter cofilin, signaling proteins that enable actin filament growth. Immunolabeling for phosphorylated (p) cofilin (pCofilin) and pPAK was robust in a small number of synapses, and was transient, beginning about 30-120 s post-TBS. PAK/cofilin-positive synapses were larger, apparently because of a simple rounding up of spines. Occasional enlarged and rounded spines were also seen in control slices. Block ofAMPAreceptors reduced pCofilin immunoreactivity. The authors estimate that the increase in spines with PAK/cofilin activation was in line with the number of synapses in which long-term potentiation (LTP) occurred.



4. Parkinsonian Mice on Treadmills

Giselle M. Petzinger, John P. Walsh,
Garnik Akopian, Elizabeth Hogg, Avery
Abernathy, Pablo Arevalo, Patty
Turnquist, Marta Vuckovic, Beth E.
Fisher, Daniel Togasaki, and Michael
W. Jakowec.



Exercise can result in symptomatic improvement in patients with Parkinson's disease (PD). In this week's Journal, Petzinger et al. report on exercise-induced changes in dopamine transmission in control C57Bl6/J mice and in PD mice that had been treated with 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice will run spontaneously on running wheels, but these mice got the health club treatment: 28 d of 2-30 min sessions on a 6 lane treadmill, 5 d/week (weekends off apparently). By the end of training, both groups were moving at about 1.8 km/h. The treadmill experience improved balance in control and MPTPlesioned mice. Although there was no difference in striatal dopamine (DA) levels between exercised and nonexercised MPTP-lesioned mice, exercise increased striatal DA levels in control mice. In MPTP-lesioned mice, exercise increased evoked vesicular DA release in striatal slices, particularly in dorsal striatum. Exercise also decreased striatal DA transporter and tyrosine hydroxylase immunoreactivity in MPTP-lesioned mice.






Contact: Sara Harris


Society for Neuroscience

High-Speed Injection Of Zebrafish Embryos Will Improve Determination Of Gene Functions, Facilitate Large-Scale Molecule Screening

Funded by an NSERC Idea to Innovations grant and an Ontario Early Researcher Award, Prof. Yu Sun's group, the Advanced Micro and Nanosystems Laboratory (amnl.mie.utoronto.ca/) at the University of Toronto (U of T) recently developed a microrobotic technology for automated microinjection of zebrafish embryos.



Based on computer vision and motion control, the automated microrobotic system is capable of immobilizing a large number of zebrafish embryos into a regular pattern within seconds and injecting 15 embryos (chorion unremoved) per minute with a success rate, survival rate, and phenotypic rate all close to 100%. The system and performance were reported in the journal PLoS ONE in an article entitled, "A Fully Automated Robotic System for Microinjection of Zebrafish Embryos."



Zebrafish is a model organism widely used in life sciences. High-speed injection of zebrafish embryos is important for screening genes in genetics and drug molecules in drug discovery. The automated microrobotic system proves itself as a reliable tool for determining gene functions and more generally, for facilitating large-scale molecule screening.







Disclaimer


The following press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.



The technology was licensed to Marksman Cellject Inc. (marksman-cellject/) for commercialization. Marksman Cellject Inc. is a start-up biotechnology company created by The Innovations Group (TIG) (innovations.utoronto.ca/).



Collaborating with the Toronto Centre for Advanced Reproductive Technology, a fertility clinic (tcartonline/), Marksman Cellject Inc. has received an Ontario Centres of Excellence grant to extend the zebrafish injection technology to mouse/human oocyte/embryo injection for in-vitro fertilization applications.



TIG is part of the Office of Research at U of T with the mandate of commercializing discoveries developed by its researchers and healthcare partners in the areas of Physical Sciences, Information Technology and Life Science for society's benefit. Among TIG's other recent start-ups are Greencore Composites (greencorenfc/), Cast Connex (castconnex/), Opalux (opalux/), and Sketch2 (press release -- here).



Citation: Wang W, Liu X, Gelinas D, Ciruna B, Sun Y (2007) A Fully Automated Robotic System for Microinjection of Zebrafish Embryos. PLoS ONE 2(9): e862. doi:10.1371/journal.pone.0000862



Click here for a link to the published article.



Source: Yu Sun


Public Library of Science

Younger Brains Are Easier To Rewire

A new paper from MIT neuroscientists, in collaboration with Alvaro Pascual-Leone at Beth Israel Deaconess Medical Center, offers evidence that it is easier to rewire the brain early in life. The researchers found that a small part of the brain's visual cortex that processes motion became reorganized only in the brains of subjects who had been born blind, not those who became blind later in life.


The new findings, described in the Oct. 14 issue of the journal Current Biology, shed light on how the brain wires itself during the first few years of life, and could help scientists understand how to optimize the brain's ability to be rewired later in life. That could become increasingly important as medical advances make it possible for congenitally blind people to have their sight restored, said MIT postdoctoral associate Marina Bedny, lead author of the paper.


In the 1950s and '60s, scientists began to think that certain brain functions develop normally only if an individual is exposed to relevant information, such as language or visual information, within a specific time period early in life. After that, they theorized, the brain loses the ability to change in response to new input.


Animal studies supported this theory. For example, cats blindfolded during the first months of life are unable to see normally after the blindfolds are removed. Similar periods of blindfolding in adulthood have no effect on vision.


However, there have been indications in recent years that there is more wiggle room than previously thought, said Bedny, who works in the laboratory of MIT assistant professor Rebecca Saxe, also an author of the Current Biology paper. Many neuroscientists now support the idea of a period early in life after which it is difficult, but not impossible, to rewire the brain.


Bedny, Saxe and their colleagues wanted to determine if a part of the brain known as the middle temporal complex (MT/MST) can be rewired at any time or only early in life. They chose to study MT/MST in part because it is one of the most studied visual areas. In sighted people, the MT region is specialized for motion vision.


In the few rare cases where patients have lost MT function in both hemispheres of the brain, they were unable to sense motion in a visual scene. For example, if someone poured water into a glass, they would see only a standing, frozen stream of water.


Previous studies have shown that in blind people, MT is taken over by sound processing, but those studies didn't distinguish between people who became blind early and late in life.


In the new MIT study, the researchers studied three groups of subjects - sighted, congenitally blind, and those who became blind later in life (age nine or older). Using functional magnetic resonance imaging (fMRI), they tested whether MT in these subjects responded to moving sounds - for example, approaching footsteps.


The results were clear, said Bedny. MT reacted to moving sounds in congenitally blind people, but not in sighted people or people who became blind at a later age.


This suggests that in late-blind individuals, the visual input they received in early years allowed the MT complex to develop its typical visual function, and it couldn't be remade to process sound after the person lost sight. Congenitally blind people never received any visual input, so the region was taken over by auditory input after birth.


"We need to think of early life as a window of opportunity to shape how the brain works," said Bedny. "That's not to say that later experience can't alter things, but it's easier to get organized early on."


Bedny believes that by better understanding how the brain is wired early in life, scientists may be able to learn how to rewire it later in life. There are now very few cases of sight restoration, but if it becomes more common, scientists will need to figure out how to retrain the patient's brain so it can process the new visual input.


"The unresolved question is whether the brain can relearn, and how that learning differs in an adult brain versus a child's brain," said Bedny.


Bedny hopes to study the behavioral consequences of the MT switch in future studies. Those would include whether blind people have an advantage over sighted people in auditory motion processing, and if they have a disadvantage if sight is restored.


Funding: The David and Lucille Packard Foundation and grant from the National Center for Research Resources


Source: "Sensitive period for a multi-modal response in human MT/MST" by, Bedny, M., Konkle, T., Pelphrey, K., Saxe, R., Pascual-Leone, A. Current Biology, 14 October, 2010.


Source:

MIT

Decoding Gene Expression In Cancer Tumors Using Noninvasive Imaging

By correlating images of cancerous liver tissue with gene expression patterns, a research team led by a radiologist at the University of California, San Diego (UCSD) School of Medicine has developed tools that may some day allow physicians to view a CT image of a cancer tumor and discern its genetic activity. The study, designed to help doctors obtain the molecular details of a specific tumor or disease without having to do an invasive biopsy procedure, are published online in Nature Biotechnology.



According to principle investigator Michael Kuo, M.D., assistant professor of interventional radiology at UCSD, the study represents the convergence of two developing fields of medical research: the mapping of the human genome and advances in diagnostic imaging.



The research team, which included investigators from Stanford University School of Medicine, systematically compared features from CT images of liver tumors with gene expression patterns obtained from surgery and tissue biopsies. Once they pinpointed the genomic correlates of the features detected by CT imaging, the researchers found that the two very different aspects of studying cancer - how the tumor looks in a CT scan and how it behaves on a molecular level - had a very strong connection.



"We studied what the various genes were doing and the biological activity they were involved in such as angiogenesis or cell growth. We also looked at how the genes contributed to a particular phenotype in the liver tumor seen on the CT scans, for example, the presence of characteristics vessels, or the tumor's texture and other important diagnostic imaging traits," said Kuo.



The research process sought to reveal the relationship between genetic activity patterns in liver tumors and the tumor's appearance on CT scans, and provide a simple means of translation. The scientists initially began with approximately 135 basic tumor descriptors, and then narrowed down the multitude of traits to the 28 most important diagnostic descriptors, matching those imaging features with a vast stockpile of microarray data generated from human liver cancer samples.



"We found a rich association between the images and the gene expression," Kuo said, adding that out of approximately 7,000 genes in the tumors, the research team was able to consistently associate imaging traits with 75 percent of the genes.



Kuo first conceived of the project in 2001 while he was a radiology resident at Stanford University. "Radiology - while making great technological advances towards capturing more and more detailed information in a non-invasive manner - seemed to be largely unaware to a fundamental shift in medicine towards genomic, personalized medicine," he said. At the time, Stanford Medical School was center to ground-breaking studies of DNA microarrays, lab tools that can screen thousands of genes at a time, developed by Stanford biochemistry professor Patrick Brown, MD, Ph.D. Microarrays were proving to be extremely useful for identifying groups of genes and their patterns in diseases such as cancer, enabling scientists to compare them with normal tissue activity.
















Genomics expert Howard Chang, M.D., assistant professor of dermatology at Stanford, and the paper's lead author, Eran Segal, Ph.D., joined the project in 2004. Chang had been using the gene activity patterns of microarrays to predict cancer outcome. Segal developed algorithms during his doctoral studies at Stanford that played a critical role in the analysis of the massive amounts of data encompassed in the study.



"When we looked at noninvasive images, there were a lot of different patterns that had no known meaning," said Chang. "We thought that maybe we could come up with a way to systematically connect the gene activity seen with microarrays to imaging patterns, enabling us to translate images to gene patterns, and ultimately to the outcome of the disease process."



"Clearly, we are very far from clinical applications of these tools that we developed," said Segal, who is now a computational biologist at the Weizmann Institute of Science in Rehovot, Israel. "But the fact that we saw strong connections between the imaging features and the molecular gene activity data suggests that this could be a promising and fruitful research direction."



Such use of non-invasive imaging to determine unique molecular characteristics of disease could lead to more individualized diagnosis and treatment of patients, according to the researchers.







Additional contributors to this paper include Claude B. Sirlin and Bryan K. Chan, UCSD Department of Radiology; Clara Ooi, Department of Radiology, University of Hong Kong; Adam S. Adler, Epithelial Biology program, Stanford University; Jeremy Gollub, Department of Biochemistry, Stanford University; Xin Chen, Department of Biopharmaceutical Science, University of California, San Francisco; George R. Matcuk, Department of Radiology, University of Southern California; and Christopher T. Barry, UCSD Department of Surgery.



The work was funded by part by a grant from the National Institutes of Health and the Israel Science Foundation.



Contact: Debra Kain


University of California - San Diego

The Launch Of SCI INDIA Marks Expansion Into Asia Of SCI

SCI is securing a foothold in South East Asia with the official launch of SCI India at the Cricket Club of India, Mumbai on 27th November 2007.



Followed by detailed research India was identified as one of the leading chemical markets worldwide, with overwhelming support and enthusiasm towards SCI's Market entry. With its India headquarters based in Mumbai SCI India will offer its membership the opportunity to share information between sectors as diverse as food and agriculture, pharmaceuticals, biotechnology, materials, chemicals, environmental science and safety on a global platform.



Earlier this year SCI formed its India Board of Trustees comprising of high profile scientists and business leaders including Dr. Raghunath Anant Mashelkar, President of the Global Research Alliance and Former Director General of the Council of Scientific and Industrial Research (CSIR), Professor Manmohan M Sharma, Emeritus Professor of Eminence, Mumbai University, Institute of Chemical Technology, Dr. S Sivaram, Director of the National Chemical Laboratory, Dr. A V Ramarao, Director of the Avra Lab. & Former Director of Indian Institute of Chemical Technology, Mr. Rajju Shroff, Chairman & Managing Director of United Phosphorus Limited, Dr. Ian Cliffe, Director-Head, Medicinal Chemistry, New Drug Discovery Research, Ranbaxy Laboratories Limited, Mr. Raj Kapur, Regional Manager -- South Asia, Managing Director -- India, Dow Corning India Pvt. Ltd, Mr . Pradip Dave, Chairman & Managing Director of Aimco Pesticides Limited & President-Pesticides Manufacturers & Formulators Association of India and Mr. D P Misra, Director General of the Indian Chemical Council.



SCI's market entry into India has been timed to meet the Indian Chemical Industry's rapid expansion of production and innovation and SCI-India is well placed to provide the much needed link between scientific discovery, application and business. We have been very encouraged by the engagement we have secured with Indian science and industry alike.



SCI are also proud to present Dr. Rajendra Pachauri a recent Nobel Peace Prize winner for his work on global warming with the SCI Environment Award for significant contribution to improvement in environmental understanding, protection and performance. This Award will be received by Dr. Pachauri's representative during the SCI India launch.







Source: Aparna Deshpande


Society of Chemical Industry

Cleveland Clinic Researchers Unravel A Unique Enzymatic Activity Of An Animal Virus

Cleveland Clinic researchers have discovered a new biochemical pathway that is essential for the reproduction of the animal virus, vesicular stomatitis virus (VSV), a virus belonging to the family that causes rabies, measles, Marburg Disease, and Ebola, and many others.



Amiya K. Banerjee, Ph.D., Section Head of Virology in Cleveland Clinic's Department of Molecular Genetics, and Research Associate Tomoaki Ogino, Ph.D., have found that messenger RNA (mRNA) "capping", a vital reaction that guards against degradation and facilitates efficient translation of cellular messenger mRNA into proteins, is distinctly different for VSV mRNAs. This unconventional capping activity of VSV may serve as a basis for developing therapies to shut down VSV replication specifically without disrupting the capping reaction of cellular mRNAs.



"Finding small molecules that can disrupt VSV mRNA capping activity could lead to discovery of antivirals not only against VSV but other viruses belonging to this class of viruses that are highly pathogenic," Dr. Banerjee said.



Dr. Banerjee's research appeared in the Jan. 12 issue of Molecular Cell
(molecule).



About Cleveland Clinic Lerner Research Institute


The Lerner Research Institute is home to all laboratory-based research at the Cleveland Clinic. Its mission is to understand the causes of human diseases and to develop new treatments and cures. The Lerner Research Institute is ranked among the top 10 in NIH funding among all U.S. research institutes for 2005. More than 1,100 people work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious disease. The Institute also is an integral part of the new Cleveland Clinic Lerner College of Medicine of Case Western Reserve University - training the next generation of physician-scientists.



About Cleveland Clinic


Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,500 full-time salaried physicians at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2005, there were 2.9 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were nearly 54,000 hospital admissions to Cleveland Clinic in 2005.

Cleveland Clinic's Web site address is clevelandclinic.

Frontiers Of Plasmonics: Potential Applications In Physics, Chemistry, Biology And Cancer Therapy

Surface plasmons are quanta of collective oscillations of free electrons at metal-insulator interface, usually excited by photons. Since it was first proposed in 1950s by Ritchie, new interests have been aroused due to recent advances in synthesis and fabrication of various nanostructures. Novel optical properties were frequently reported on these materials, with great potential applications in physics, chemistry, biology and cancer therapy, etc. Some of them have even exhibited enormous economic values. Due to the wide interest and uniqueness of surface plasmons, a new branch of nano-optics has come into being, that is, plasmonics.



Different from the conventional optics restricted by the diffraction limit, plasmonics concerns manipulating light at the nanometer scale. The localized surface plasmons can cause huge enhancement of the electromagnetic field in the nanogaps of nanostructures, which is the physical reason of surface-enhanced Raman scattering (SERS). Apart from light intensity, the polarization of light can also be manipulated through plasmons coupled between nanoparticles, which actually acts as a nanoscale half-wave plate.


Another important property of these plasmonic structures is waveguiding. As well known, the diffraction limitation is the fundamental obstacle to fabricate dielectric photonic components and devices small enough for large- scale integration. However surface plasmons can overcome this limitation. The significant progress in plasmonics has stimulated scientists to develop nano-scale plasmonic analogues of macro- and microscale optical components such as electrooptic devices, transistors and modulators, etc. By combining various nanoscale optical devices, it may be possible to build integrated nanophotonic circuits, offering substantial improvements in bandwidth and speed for next-generation information technologies.



The following articles are related to the recent progress in plasmonics, including fabrications, experimental measurements and theoretical calculations of optical properties of nanostructures. Chen et al. fabricated ordered arrays of metallic nanoparticles and investigated the far-field properties experimentally and theoretically. Bao et al. extended the plasmon hybridization method to include realistic permittivities for metals and calculated the plasmon-induced electromagnetic field enhancements. Yang et al. discussed the physical enhancement properties of SERS and tip-enhanced Raman spectroscopy (TERS) using finite-difference time-domain method. Ameen et al. investigated the electromagnetic interaction of light with polar materials in the infrared region by boundary element method, where they found surface phonons can couple efficiently to infrared light in micron-sized antennas made of polar materials. Gu et al. reviewed the Green's matrix method for solving the surface plasmon resonances and near field in arbitrarily shaped nanostructures and in binary metallic nanostructures. Ma et al. reviewed the recent developments on hyperlens. Guan et al. studied the dual-layer metallic grating structures as SERS substrates, and they demonstrated the advantages of high uniformity, reproducibility and sensitivity of the structures for SERS applications. Guo et al. demonstrated a silver nanowire ring resonator, which offers opportunities for realizing compact plasmonic resonators with tight confinement for hybrid optical and plasmonic signal processing.

Notes:
Chen Z, Zhan P, Dong W, et al. Bottom-up fabrication approaches to novel plasmonic materials. Chinese Sci Bull, 2010, 55: 2600-2607
Bao K, Sobhani H, Nordlander P. Plasmon hybridization for real metals. Chinese Sci Bull, 2010, 55: 2629-2634
Yang Z L, Li Q H, Ruan F X, et al. FDTD for plasmonics: Applications in enhanced Raman spectroscopy. Chinese Sci Bull, 2010, 55: 2635-2642
Ameen M, Garcia-Etxarri A, Schnell M, et al. Infrared phononic nanoantennas: Localized surface phonon polaritons in SiC disks. Chinese Sci Bull, 2010, 55: 2625-2628
Gu Y, Li J, Martin O J F, et al. Solving surface plasmon resonances and near field in metallic nanostructures: Green's matrix method and its applications. Chinese Sci Bull, 2010, 55: 2608-2617
Ma C B, Aguinaldo R, Liu Z W. Advances in the hyperlens. Chinese Sci Bull, 2010, 55: 2618
Guan Z Q, HГҐkanson U, Anttu N, et al. Surface-enhanced Raman scattering on dual-layer metallic grating structures. Chinese Sci Bull, 2010, 55: 2643-2648
Guo X, Zhang X N, Tong L M. Silver nanowire ring resonator. Chinese Sci Bull, 2010, 55: 2649-2651

Source:

Xu HongXing

Science in China Press

Control Of Cell Movement With Light Accomplished In Living Organisms

A precise understanding of cellular growth and movement is the key to developing new treatments for cancer and other disorders caused by dysfunctional cell behavior. Recent breakthroughs in genetic medicine have uncovered how genes control whether cellular proteins are turned 'on' or 'off' at the molecular level, but much remains to be understood about how protein signaling influences cell behavior.



A technique developed in the laboratory of Klaus Hahn, PhD, the Thurman Professor of Pharmacology at the University of North Carolina at Chapel Hill and a member of UNC Lineberger Comprehensive Cancer Center, uses light to manipulate the activity of a protein at precise times and places within a living cell, providing a new tool for scientists who study the fundamentals of protein function.



In a paper published in the journal Nature Cell Biology, a team led by Denise Montell, PhD, of Johns Hopkins School of Medicine, describes how researchers used the technique, which controls protein behavior in cells and animals simply by shining a focused beam of light on the cells where they want the protein to be active, in live fruit flies.



"This finding complements an additional collaboration with Anna Huttenlocher, PhD of the University of Wisconsin-Madison, published earlier this year in the journal Developmental Cell, showing that this technique could be used to control cell movement in live zebrafish as well," said Hahn.



"We have now shown that this technique works in two different living organisms, providing proof of principle that light can be used to activate a key protein. In this case the protein controls cell movement, enabling us to move cells about in animals. This is particularly valuable in studies where cell movement is the focus of the research, including embryonic development, nerve regeneration and cancer metastasis. Now researchers can control where and where particular proteins are activated in animals, providing a heretofore inaccessible level of control," said Hahn.



The new technology is an advance over previous light-directed methods of cellular control that used toxic wavelengths of light, disrupted the cell membrane or could switch proteins 'on' but not 'off'. Unlike some approaches it requires no injection of cofactors or other unnatural materials into the animals being studied.



The researc was the work of a team including Montell, and Xiaobo Wang from Johns Hopkins and Hahn and Yi Wu, PhD, research assistant professor of pharmacology, both from UNC.



This research was supported by the National Institutes of Health and the Cell Migration Consortium.



Source:

Ellen de Graffenreid

University of North Carolina School of Medicine

Python Project: CU-Boulder, Biotech Firm Team Up To Search For Human Cardiac Therapeutics

The University of Colorado at Boulder is teaming up with a Boulder biotechnology company to use pythons, which dramatically increase their heart size for a short time after swallowing prey, as models for new therapeutics to treat cardiac diseases.



Hiberna Corp., a Boulder-based company developing drugs based on natural models of extreme metabolic regulation, has signed an exclusive agreement with the university's Technology Transfer Office on the effort. Hiberna licensed technology developed by CU-Boulder Professor Leslie Leinwand based on the natural ability of pythons to increase their heart size by up to 60 percent and speed their metabolism by 40-fold after feeding episodes.



Leinwand said the ability of pythons and other constricting snakes to enlarge and then decrease their heart muscle mass in just days may help researchers target new drugs for treating cardiac growth in response to disease, which causes human heart muscle to thicken and decreases the size of heart chambers and heart function. Leinwand is a professor in CU-Boulder's molecular, cellular and developmental biology department and director of the University of Colorado Cardiovascular Institute.



Increases in cardiac size are clinically important because heart enlargement in humans resulting from exercise is beneficial, but heart enlargement from high blood pressure is unhealthy, said Leinwand, who studies genetic heart defects. Understanding which genes are involved in regulating the python's rapid heart muscle changes may have implications for treating cardiac hypertrophy, or thickening of the heart muscle, she said.



"This may be a unique path toward potential drug development," Leinwand said of the Burmese python effort. "If we are able to understand the genetic cues involved in rapid python heart muscle increases and decreases, that to me says there is the potential to develop therapeutics for humans."



Leinwand has studied hypertrophic cardiomyopathy, or HCM, a genetic disease marked by a thickening of heart muscle related to a weakness in individual muscle fibers that causes them to work harder to pump blood and consequently enlarge. HCM occurs in one in 500 people in the United States and is the most common cardiac cause of sudden death in young athletes. About 20 genes associated with HCM have been identified and others are being investigated, she said.



In 2006 Leinwand was named a Howard Hughes Medical Institute Professor, one of 20 faculty nationwide to receive a four-year, $1 million undergraduate education award from the Howard Hughes Medical Institute in Chevy Chase, Md. As part of her successful proposal to enhance science education at CU-Boulder, she initiated an undergraduate laboratory research program known as the Python Project.
















In the past two years, CU-Boulder undergraduates working with Leinwand have been studying the genome of the Burmese python, searching out and analyzing particular genes they suspect may be involved in the rapid heart muscle changes.



"Pythons can eat up to 100 percent of their body weight at one sitting, so they have to be able to respond metabolically in a dramatic way," said Leinwand. In addition to the eye-popping changes in heart muscle and metabolism, the python's insulin levels go up 40-fold and their triglycerides rise by more than 100-fold following substantial meals, changes that would "kill a human," she said.



Pythons also exhibit very little muscle loss when at rest, which is of interest to researchers studying diseases like AIDS and cancer and the inevitable process of aging. "We think several of the striking changes we see in python physiology may have significant potential for the pharmaceutical industry," she said.



Hiberna -- which received a $100,000 proof-of-concept investment from CU's Technology Transfer Office to help support the development of the new technology -- has started sequencing the Burmese python genome and also has raised some financial capital for the venture. In addition, Leinwand's colleagues at the University of Colorado Denver and Anschutz Medical Campus are analyzing python gene samples for Hiberna.



Hiberna was founded in 2006 by Tom Marr, who has studied Alaskan mammals that exhibit extraordinary physiological adaptations relevant to human health. One of Marr's star study subjects has been the Arctic ground squirrel, which has the ability to drop it's body temperature to below freezing and reduce its heart rate from 200 beats a minute to just two beats per minute during hibernation.



"There are some striking examples of extreme adaptations by animals in the wild, and I think it's a good idea from a biomedical standpoint to take a closer look at them," Leinwand said. The impetus for her python project came from a 1998 Nature paper by UCLA evolutionary biologist and Pulitzer-prize winning author Jared Diamond on extreme physiological regulation adaptations by pythons.







Leinwand is a co-founding scientist of Hiberna along with Professor Sandy Martin of the UCD School of Medicine's molecular biology department.



Source: Leslie Leinwand


University of Colorado at Boulder

The Birth Of A Fat Cell

Just what causes the birth of a human fat cell is a mystery, but scientists using mathematics to tackle the question have come up with a few predictions about the proteins that influence this process.



The research is intended to increase understanding of how and why preadipocytes, or pre-fat cells, either lie dormant, copy themselves or turn into fat. But the findings eventually could lead to a way to freeze these early cells in their current state before they can ever become the basis of fat tissue, according to Ohio State University researchers.



Every human body needs fat to store and produce energy, but in excess, the tissue made up of fat cells begins to secrete molecules that send out complicated signals. This process can lead to inflammation and, in turn, to insulin resistance or diabetes, and contributes to the development of other diseases.



The scientists focused on three proteins that are known to have an impact on the fate of preadipocytes - one protein that influences inflammation; another that drives the creation of fat cells; and a third that is involved in the proliferation, or copying, of almost all cells in the body.



A series of differential equations determined how the complex interactions among these three proteins would likely affect what happens to pre-fat cells, including conditions most associated with quiescence, or keeping those preadipocytes from turning into fat.



A better appreciation of this process could help researchers more fully understand the causes of disorders associated with excess fat, including obesity and insulin resistance.



"A potential benefit of figuring out this process is to see how we could manipulate certain parameters to arrest cells in this quiescent region, and that could have an effect on obesity," said Huseyin Coskun, a visiting assistant professor in the Department of Mathematics at Ohio State and lead author of the study.



"Obesity is certainly related to the types and amounts of foods people consume. But how the body responds to this can differ from one person to another, and could be related to some abnormalities in these protein interactions. The amount consumed may not be the only reason behind obesity. With this study, we started to understand how protein levels and complex molecular interactions in the body may influence the development of fat cells."



The research is published in a recent issue of the Journal of Theoretical Biology.



Coskun, a mathematician, began this project by reading hundreds of journal articles about the biology behind the transition of preadipocytes into adipocytes, or fat cells. He identified 16 proteins that appeared to be the most active in the process.



He and the research group, a team of math and biology experts, narrowed that number to three high-impact proteins as a starting point. Coskun then designed differential equations based on the biological model that would show how the pre-fat cells behaved under a variety of conditions, depending on the proteins' activity.
















The three proteins are NF-kB, PPAR-gamma and cyclin D. NF-kB initiates inflammation in tissue. PPAR-gamma must be present for adipogenesis, or the creation of fat cells, to occur. And cyclin D is responsible for cell proliferation, or copying and growth, in almost all cells, including pre-fat cells and fat cells.



"The three target proteins of this initial model are the most commonly studied, but their mutual relationships in relation to the creation of fat cells are still not well-known, so we are putting their roles together to see how they contribute to fat cell determination for the first time, as far as we know, in the literature," Coskun said.



The mathematical equations in which these three protein levels were manipulated resulted in a model that helped define the conditions under which pre-fat cells would remain dormant, start copying themselves or turn into fat cells. Two-parameter bifurcation curves are used for interpretation of model outcomes, which itself is a novel approach in terms of mathematical terminology.



The main parameters driving this model were two substances that affect the target proteins: a protein called IkB, which inhibits the inflammatory NF-kB protein, and the concentration of a chemical stimulant, called a mitogen, that stimulates production of cyclin D.



According to the model, if the level of IkB is high and the level of the cyclin D stimulant is low, the pre-fat cells remain dormant. The model then shows what is called a "curve of uncertainty," which predicts the circumstances that are required for preadipocytes to either remain dormant or proliferate in their current state. The region of uncertainty then determines the conditions for coexistence of a pair of these three states: differentiation and quiescence, or proliferation and differentiation.



The researchers also conducted preliminary experiments to test the model's outcomes by exposing mouse cells to TNF-alpha, a mitogen that stimulates cyclin D. They found that the concentrations of the proteins in those cells generally behaved as the model suggested they would. In addition, previous research reports of similar experiments also support the model's outcomes, Coskun said.



He noted that more experiments are needed to further test the model, which also could be expanded to add more proteins to the equations.



Co-authors on the study, all from Ohio State, included Taryn Summerfield of the Department of Obstetrics and Gynecology, Douglas Kniss of the departments of Obstetrics and Gynecology and Biomedical Engineering; and Avner Friedman of the Mathematical Biosciences Institute and the Department of Mathematics.



Source:

Huseyin Coskun

Ohio State University