Bone Marrow Microenvironment Can Contribute To Blood Cell Disorder

Disorders of blood cells may begin in the biological environment where the cells develop, not just with the cells themselves, according to a study from researchers at the Massachusetts General Hospital (MGH) and the Peter MacCallum Cancer Center (Peter Mac) in Melbourne, Australia. In Cell, the investigators describe finding that genetic alterations in the bone marrow of mice can cause a type of myeloproliferative syndrome, an overproduction of certain blood cells that also occurs in human patients.



"Previously all myeloproliferative syndromes have been considered to be intrinsic to the blood cells themselves," says Louise Purton, PhD, of the MGH Center for Regenerative Medicine, formerly of Peter Mac, who led the study. "This discovery may help us find better therapies for these disorders, which can be quite difficult to treat, and also for some leukemias."



How the bone marrow microenvironment contributes to the development and maintenance of blood cells has been the subject of intense research interest in recent years. In 2003 MGH researchers found that the bone-forming osteoblasts that line the marrow cavity can regulate the production of hematopoietic (blood system) stem cells. Although it is known that certain blood disorders can affect this microenvironment, the induction of a blood-cell disease by environmental factors alone has not been reported previously.



Purton's team has been studying how a group of vitamin A receptor molecules regulate hematopoietic stem cell (HSC) production and previously showed that the RAR-gamma receptor was critical to HSC renewal. In that work they observed that mice in which RAR-gamma had been knocked out had significantly fewer HSCs and increased numbers of more mature progenitor cells.



In the current study the investigators observed that mice in which RAR-gamma had been knocked out also had abnormal hematopoiesis of mature cells, with an overproduction of several types of white blood cells. In aged knockout mice, the condition was advanced and strongly resembled human myeloproliferative syndromes. When the RAR-gamma-negative knockout mice received transplants of bone marrow from normal mice, the disorder continued despite the presence of donor-derived RAR-gamma-positive hematopoietic cells in the marrow, indicating that the lack of RAR-gamma in the overall microenvironment was behind the disorder.



"There have been reports of patients with myeloproliferative syndromes receiving stem cell transplants and relapsing with an overproliferation of donor-based cells, despite no evidence of any disease in the donors," says Purton. "That indicates that what we observed in these knockout mice may be happening in these patients because their disease also is based in the microenvironment. Understanding how the microenvironment contributes to such diseases may lead us to better therapies. We also hope to examine whether the microenvironment may contribute to the transformation of abnormal noncancerous blood cells into leukemic cells." Purton is an instructor in Medicine at Harvard Medical School and also is associated with the Harvard Stem Cell Institute.

New FDA Approved Treatment For Head Lice Is Safe And Effective In Children As Young As 6 Months Old

A new non-neurotoxic treatment for head lice has been found to have an average of 91.2% treatment success rate after one week, and to be safe in humans from six months of age and up. This is the finding of a study published in Pediatric Dermatology.



Benzyl Alcohol Lotion 5% (known as UlesfiaTM) works by suffocating lice, a method which has been attempted by treating with household items such as mayonnaise, olive oil and petroleum jelly. Studies have shown that overnight treatments with these home remedies may initially appear to kill lice, but later a "resurrection effect" occurs after rinsing, because lice can resist asphyxiation. This is accomplished by the louse's ability to presumably close its spiracles, the external entry points to the breathing apparatus, when submerged. Unlike commonly used asphyxiant remedies, scanning electron microscopy appears to indicate that benzyl alcohol lotion effectively asphyxiates lice by "stunning" the spiracles open, allowing the lotion, comprised of mineral oil and other inactive ingredients, to infiltrate the "honeycomb" respiratory apparatus and kill lice.



The phase III trials were comprised of two multicenter, randomized, double-blind, placebo-controlled trials, conducted among ten geographically diverse sites which assessed the clinical effectiveness and safety of benzyl alcohol lotion. 250 participants took part in the trials and were randomised to treatment or vehicle (lotion but with no active ingredient) groups, treatment was given at day one and day seven, and participants were checked for success at day eight and day 14. On day eight the treatment group had a success rate of 91.2% as an average of both trials, and a 75.6% success rate on day 14; in the vehicle group the success rates were 27.9% and 15.5% respectively.



"Existing over-the-counter head lice treatments contain neurotoxic pesticides as active ingredients, resulting in potential toxicity and other problems, including lengthy applications, odor, ineffective treatment. Resistance has also become a problem now that lice have had such prolonged exposure to these products," said study author Terri L Meinking, PhD, of Global Health Associates of Miami, USA. "This leaves practitioners, parents and patients hoping for a safe, non-neurotoxic cure."



"Since the most popular products have been made readily available, their overuse has caused lice to become resistant just as bacteria have become resistant to many antibiotics," added Meinking. "Because benzyl alcohol lotion kills by suffocation, resistance should not be an issue."



Source:

Jennifer Beal

Wiley-Blackwell

Discovery To Aid Study Of Biological Structures, Molecules

Researchers in the United States and Spain have discovered that a tool widely used in nanoscale imaging works differently in watery environments, a step toward better using the instrument to study biological molecules and structures.



The researchers demonstrated their new understanding of how the instrument - the atomic force microscope - works in water to show detailed properties of a bacterial membrane and a virus called Phi29, said Arvind Raman, a Purdue professor of mechanical engineering.



"People using this kind of instrument to study biological structures need to know how it works in the natural watery environments of molecules and how to interpret images," he said.



An atomic force microscope uses a tiny vibrating probe to yield information about materials and surfaces on the scale of nanometers, or billionths of a meter. Because the instrument enables scientists to "see" objects far smaller than possible using light microscopes, it could be ideal for studying molecules, cell membranes and other biological structures.



The best way to study such structures is in their wet, natural environments. However, the researchers have now discovered that in some respects the vibrating probe's tip behaves the opposite in water as it does in air, said Purdue mechanical engineering doctoral student John Melcher.



Purdue researchers collaborated with scientists at three institutions in Madrid, Spain: Universidad AutГіnoma de Madrid, Instituto de Ciencia de Materiales de Madrid and the Centro Nacional de BiotecnologГ­a.



Findings, which were detailed in a paper appearing online last week in the U.S. publication Proceedings of the National Academy of Sciences, are related to the subtle differences in how the instrument's probe vibrates. The probe is caused to oscillate by a vibrating source at its base. However, the tip of the probe oscillates slightly out of synch with the oscillations at the base. This difference in oscillation is referred to as a "phase contrast," and the tip is said to be out of phase with the base.



Although these differences in phase contrast reveal information about the composition of the material being studied, data can't be properly interpreted unless researchers understand precisely how the phase changes in water as well as in air, Raman said.



If the instrument is operating in air, the tip's phase lags slightly when interacting with a viscous material and advances slightly when scanning over a hard surface. Now researchers have learned the tip operates in the opposite manner when used in water: it lags while passing over a hard object and advances when scanning the gelatinous surface of a biological membrane.



Researchers deposited the membrane and viruses on a sheet of mica. Tests showed the differing properties of the inner and outer sides of the membrane and details about the latticelike protein structure of the membrane. Findings also showed the different properties of the balloonlike head, stiff collar and hollow tail of the Phi29 virus, called a bacteriophage because it infects bacteria.



"The findings suggest that phase contrast in liquids can be used to reveal rapidly the intrinsic variations in local stiffness with molecular resolution, for example, by showing that the head and the collar of an individual virus particle have different stiffness," Raman said.



Notes:

The research was funded by the National Science Foundation and was conducted at the Birck Nanotechnology Center in Purdue's Discovery Park. The biological membrane images were taken at Purdue, and the virus studies were performed at the Universidad AutГіnoma de Madrid. The paper was authored by Melcher; Carolina Carrasco, a postdoctoral researcher at Universidad AutГіnoma de Madrid and the Instituto de Ciencia de Materiales de Madrid; Purdue postdoctoral researcher Xin Xu; JosГ© L. Carrasco, a researcher at Departmento de Estructura de MacomolГ©culas, Centro Nacional de BiotecnologГ­a, Consejo Superior de Investigaciones CientГ­ficas; Julio GГіmez-Herrero and Pedro JosГ© de Pablo, both researchers from Universidad AutГіnoma de Madrid; and Raman.



Source:
Emil Venere


Purdue University

Most valuable prize in German research goes to ten scientists & academics

The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Grants Committee today named the prizewinners of
the DFG's Gottfried Wilhelm Leibniz Programme for 2005. The most valuable research prize in Germany will go to ten scientists
and academics, two women and eight men. The prize of 1.55 million euros funds research work over a five-year period and can
be used flexibly by the prizewinners, depending on their specific requirements.


The programme, established in 1985, aims to improve the working conditions of outstanding researchers, to extend their
research opportunities, to relieve them of administrative work and make it easier for them to employ especially highly
qualified young researchers. Scientists and academics from all research areas can be nominated for the award. The DFG
Nominations Committee considers the nominations it receives for the Gottfried Wilhelm Leibniz Prize and selects researchers
who, above all, can be expected to particularly advance their scientific achievement with this additional boost in funding.
This year's prizewinners again include a number of younger scientists.


Today's decision brings the total number of prizes awarded under the Leibniz Programme to 228. Of these, 49 winners have been
from the humanities, 64 from the life sciences, 81 from the natural sciences and 34 from engineering. Of 130 nominations
received for 2005, the following ten Leibniz Prizewinners were selected:


Prof. Dr. Peter B. Becker (46), Cell Biology/Biochemistry, University of Munich (1.55 million euros)


The biochemist Peter Becker studies chromatin dynamics, in other words, the packaging of DNA. The human genetic code is
contained in long DNA sequences. In order to fit inside a cell, these sequences have to be "packed". The degree of packing is
also determined by the degree to which a DNA sequence is utilised. This complex organisational structure of DNA is called
chromatin. Peter Becker is looking into the question of how the packaging of the DNA relates to the control of gene activity.
Through his research, he has been able to discover a new principle of chromatin dynamics. Amongst other things, he has shown
that the histones - proteins which act as a kind of spool for the DNA - are pushed along the DNA sequence if they get "in the
way" of the activation of certain sections of the DNA. These findings are of great importance for understanding gene activity
relating to the development of cancer and embryo growth.


Peter Becker studied biology in Heidelberg and obtained his doctorate in biochemistry. After spending three years as a
post-doc at the National Institutes of Health (NIH) in the USA he led a group at the European Molecular Biology Laboratory
(EMBL) in Heidelberg from 1991 until 1999. Since 1999 he has held the chair for molecular biology at the Adolf Butenandt
Institute at the Ludwig Maximilians University of Munich.















Prof. Dr. Immanuel F. Bloch (32), Experimental Physics, University of Mainz (1.55 million euros)


Immanuel Bloch achieved his first scientific breakthrough in 1999 with his development of the "Munich Atom Laser" together
with other researchers. This experiment was the first to produce a continuous matter wave beam from Bose-Einstein
condensates. These waves are similar to the beam of light emitted by a laser, but unlike a laser beam, consist of ultracold
atoms. By superposing two such matter waves it is possible to obtain an interference pattern of alternating constructive and
destructive interference of the matter waves in the same way as with conventional lasers. Another area which Immanuel Bloch's
research focuses on is the manipulation of ultracold Bose gases using an optical lattice. Using laser beams he was, for the
first time, able to alter a Bose-Einstein condensate to bring about a phase transition to a state called the Mott isolator.
This state of matter has fundamental new properties, which can be utilised for applications such as the development of
quantum computers.


Immanuel Bloch studied physics at the University of Bonn from 1991 until 1996. Following a one year research visit to
Stanford University in the USA from 1997-98 he obtained his doctorate in Munich in 2000. In 2003, at just 31 years of age, he
was appointed to a professorship at the University of Mainz.


Prof. Dr. Stefanie Dimmeler (37), Molecular Cardiology, University of Frankfurt/Main (1.55 million euros)


Stefanie Dimmeler's field of research is the biology of the blood vessels. She hopes to create the foundation for new methods
of treatment for cardiovascular diseases through improved understanding of the biological and pathological processes in the
vessel wall. The main topic of her research is programmed cell death (apoptosis) in the blood vessel wall, called the
endothelium. Every cell carries in its DNA a kind of self-destruct mechanism, which is set off in response to certain signals
and which is necessary for the regeneration of tissue and for growth. This stop code is usually set off by chemical
messengers, but can also be triggered by damage caused to the cells. Stefanie Dimmeler has studied the fundamental processes
of vascular cell damage and regeneration, thus contributing significantly to the understanding of arteriosclerosis
(thickening and hardening of the arterial walls). Furthermore, her work on the bone marrow-derived precursor cells
(progenitor cells) of blood vessels formed the basis for the first clinical studies of stem cell therapy of heart attack
patients.


Stefanie Dimmeler studied biology in Constance and obtained her doctorate in 1993. She went to the University of Frankfurt in
1995, where she has been the director of molecular cardiology since 1997. She qualified as a professor in 1998 and was
appointed as professor of molecular cardiology at the University of Frankfurt in 2000.


Prof. Dr. Jьrgen GauЯ (44), Physical Chemistry/Theoretical Chemistry, University of Munich (1.55 million euros)



Jьrgen GauЯ is working on theoretical quantum chemistry. This is an area of increasing importance in chemical research.
Experimental studies are increasingly being combined with quantum chemical calculations in order to confirm experimental
data, to simplify the evaluation of the data or indeed enable evaluation, or to gain new insights. Jьrgen GauЯ has made
fundamental contributions to the methodology in this area as well as putting the theory into practice in high-performance
computer programmes that are already being used by a large number of research groups around the world. His work has been
recognised with many national and international prizes, including the famous prize of the Berlin-Brandenburg Academy of
Sciences and the International Academy of Quantum Molecular Science medal.


Jьrgen GauЯ studied chemistry in Cologne and obtained his doctorate there in 1988 with his thesis on theoretical chemistry.
As a postdoctorate researcher he first went to the University of Washington in Seattle, USA, and was subsequently involved in
the Quantum Theory Project at the University of Florida in Gainesville. In 1993 he qualified as a professor at the University
of Karlsruhe and was appointed as a professor at the University of Mainz in 1995. He has held the newly established chair for
theoretical chemistry there since 2001.


Prof. Dr. Gьnther G. Hasinger (50), Astrophysics, Max Planck Institute for Extraterrestrial Physics, Garching (1.55
million euros)


Gьnther Hasinger is one of the world's leading researchers in the field of X-ray astronomy. In 2002 he and his team became
the first to prove the impending merger of two supermassive black holes in a distant galaxy. For the past few years Gьnther
Hasinger has been working on studying the X-ray background. His research has helped to prove that this diffuse faint glow of
X-rays comes essentially from many individual celestial objects. His research on the formation of galaxies has contributed
decisively to massive black holes in the centre of galaxies being regarded as the seeds for their formation, rather than the
product of their development. Gьnther Hasinger is currently involved in studying the cores of active galaxies as well as
being involved in the hunt for dark matter. As part of this work he is actively involved in the development of X-ray
telescope satellites, which it is hoped will provide answers to various questions on the distribution of matter and the early
development of stars and galaxies.


Gьnther Hasinger studied physics at the Ludwig Maximilians University of Munich and completed his doctorate in astronomy
there in 1984. Following his qualification as a professor in 1995 he was first appointed as a professor at the University of
Potsdam, where he was also director of the Astrophysical Institute. Since 2001 he has been the director of the Max Planck
Institute for Extraterrestrial Physics in Garching.


Prof. Dr. Christian Jung (48), Molecular Plant Breeding, University of Kiel (1.55 million euros)


Christian Jung has been researching the breeding of agriculturally cultivated crop plants for many years. For his work he
uses molecular plant genetics, which enables the breeding of plants that are resistant to pathogens through carefully
directed genetic manipulation. He successfully determined a resistance gene to protect sugar beet from threadworms
(nematodes). The gene, which was originally isolated from a wild form of sugar beet, makes cultivated varieties fully
resistant to the nematodes, one of the major pests in sugar beet. Christian Jung has also had great success in isolating
genes which determine the sexual differentiation of plants. This work is of great importance, not only for basic molecular
research, but also for plant breeding as a whole. Through his many years of involvement in the Central Commission for
Biosafety (Zentrale Kommission fьr die Biologische Sicherheit) and public statements on the amendment of the Genetic
Engineering Law Christian Jung has also made an important scientific contribution to the objectification of the debate on
environmentally friendly genetic engineering.


Christian Jung studied agricultural sciences in Gцttingen and worked at the University of Munich after obtaining his
doctorate, where he qualified as a professor in 1992 with his thesis on the molecular genome analysis of crops. In 1993 he
became the director of the Institute of Crop Science and Plant Breeding at the University of Kiel.


Prof. Dr. Axel Ockenfels (35), Experimental Economics, University of Cologne (1.55 million euros)


Axel Ockenfels' research deals with peoples' behaviour when making economic decisions, or, to be more precise, what strategic
and rational factors affect these decisions. Using game theory Axel Ockenfels has developed a behavioural model that can be
used to both explain and predict apparently contradictory economic decision-making patterns. Online auction sites and markets
are a focal point of his research. He uses novel experimental techniques to analyse the strategic bidding behaviour and the
auction rules of Internet platforms and has in this way made highly complex real-life markets accessible to scientifically
sound investigation. His most recent work has dealt with market architecture, promising not only great potential for basic
research but also for the organisation of modern markets. Axel Ockenfels has published several groundbreaking papers in
leading international economic journals and is currently one of the most frequently cited authors of his field of research.



Axel Ockenfels obtained his doctorate in economics from the University of Magdeburg in 1998 and qualified as a professor
three years thereafter. In 2001 he became the leader of an independent junior research group in the DFG's Emmy Noether
Programme. From 2002 until 2003 he led a research group at the Max Planck Institute for Research into Economic Systems in
Jena. He has been a professor of economics and director of the Institute of Energy Economics and the Bonn Laboratory for
Experimental Economics since 2003.


Prof. Dr.-Ing. Wolfgang Peukert (46), Mechanical Process Engineering, University of Erlangen-Nuremberg (1.55 million
euros)


The success of research in engineering is partly measured by its potential for practical application. Researchers attempt to
understand the basic physical and chemical concepts of the interactions between particles and to use these with the aim of
obtaining particular product characteristics. Wolfgang Peukert has shown considerable success at this interface between basic
research and application. One of the focal points of his work is particle properties in the sub-micron size range. The
behaviour of and interaction between particles are decisive for the characteristics of a product. Whereas in the past the
particles of interest were larger than a micron, an increasing number of modern applications demand much smaller particles.
With his research into the properties of particles in the sub-micron and nanometre size range Wolfgang Peukert has shed light
on the scientific relationships and created the basis for the tailor-made design of product properties, and thus for
application.


After studying chemical engineering at the University of Karlsruhe and subsequently obtaining his doctorate in mechanical
process engineering, Wolfgang Peukert joined the R&D department of Hosokawa Micron and worked in Germany and Japan. In 1998
he accepted an appointment to the chair for Particle Technology at the Technical University of Munich and in early 2003 moved
to the Institute of Particle Technology at the University of Erlangen-Nuremberg.


Prof. Dr. Barbara Stollberg-Rilinger (49), Early Modern History, University of Mьnster (1.55 million euros)


Barbara Stollberg-Rilinger's particular interest lies in the political and cultural movements in Europe in the 17th and 18th
centuries. Besides the major philosophical and constitutional developments, such as the renaissance, she is also interested
in the developments in social and communication history, including religious revival movements and new forms of social and
family interaction. Her research is currently concentrated on the question of how the social order of ranks and classes in
the early modern era were constituted through symbolic acts, for instance rituals and ceremonies. Barbara Stollberg-Rilinger
always establishes links to the modern era in her work, and attempts to identify the relationship between developments in the
early modern era and issues pertaining to modernity. Many of her historical interests and methodological approaches also
contribute to the Collaborative Research Centre "Symbolic Communication and Social Value Systems from the Middle Ages to the
French Revolution" in Mьnster, of which she is the spokesperson.


Barbara Stollberg-Rilinger studied early modern and modern European history in Cologne and completed her doctorate in 1985
with her thesis on political metaphor in the absolute sovereign state. She qualified as a professor in 1994 and was appointed
as a university lecturer at the University of Cologne in 1996. She has held the chair for modern history with a particular
emphasis on early modern history at the university of Mьnster since 1997.


Prof. Dr. Andreas Tьnnermann (41), Micro System Technology, University of Jena, Fraunhofer Institute for Applied Optics
and Precision Engineering, Jena (1.55 million euros)


Andreas Tьnnermann has published groundbreaking research on the development of high power fibre lasers, thus laying the
foundation for the production of simple, compact and robust lasers with high beam quality. The low efficiency of conventional
fibre lasers in the past restricted them to use for amplification in communications networks. It was not until the work done
by Andreas Tьnnermann that it became possible to build fibre lasers with both a consistently high power emission signal as
well as ultra short pulses with high beam quality. He also accomplished decisive pioneering work on the improvement of the
optical properties of optical fibres for light emission and thus of their usefulness for lasers. For the first time this
makes high efficiency laser sources that can be used as components in integrated optics available. The work of Andreas
Tьnnermann has opened up new possibilities for the use of modern laser fibres, ranging from basic research and the
development of new materials through to biophotonics.


After completing his doctorate in laser physics at the University of Hannover Andreas Tьnnermann became head of the
department of development at the Laser Zentrum Hannover in 1992. He qualified as a professor of experimental physics in 1997
and was appointed as a professor of applied physics at the University of Jena in 1998, at the age of 34, where he has since
been the director of the Institute of Applied Physics. Simultaneously he is also the director of the Fraunhofer Institute for
Applied Optics and Precision Engineering.


The award ceremony for the Gottfried Wilhelm Leibniz Programme 2005 will take place on 2 March 2005 at the Berlin-Brandenburg
Academy of Science in Berlin. The prizes will be awarded by the President of the DFG, Professor Ernst-Ludwig Winnacker.



Note to editors: Further information on the prizewinners for 2005, including their CVs, details of their key research areas
and photographs will be available at dfg as from 20 January. General information on the Gottfried Wilhelm Leibniz
Programme can also be found at this address.


This release is also available in German


Contact: Cornelia Pretzer

Leibniz prizewinners 2005

cornelia.pretzerdfg

49-228-885-2376

Deutsche Forschungsgemeinschaft

Linking Players In Blood Pressure Control To Metabolic Syndrome

A new study elucidates the connection between an enzyme involved in blood pressure control and symptoms of the metabolic syndrome. The researchers report in the December issue of Cell Metabolism, a publication of Cell Press, that mice lacking the enzyme known as renin are lean and resistant to gaining weight on a high-fat diet, even though they continue to eat just as much and don't exercise more.



The findings suggest that renin-blocking drugs designed for treating high blood pressure might also improve obesity and insulin resistance, according to the researchers. Renin plays an important rate-limiting role in the production of a hormone called angiotensin II (Ang II) that increases blood pressure by constricting blood vessels.



"An overactive renin-angiotensin system has also been associated with obesity and the metabolic syndrome," said Nobuyuki Takahashi of The University of North Carolina at Chapel Hill. "Now we've gained new insight into the mechanism responsible."



The metabolic syndrome is characterized by central obesity, hypertension, abnormally high blood lipid levels, and impaired glucose tolerance, the researchers explained. It also increases the risk of heart disease and type 2 diabetes. While most theories to explain the condition have focused on primary defects of insulin action, the renin-angiotensin system has also been implicated.



Clinical trials have shown that drugs that block other parts of the renin-angiotensin system improve insulin sensitivity and decrease the incidence of type 2 diabetes. Studies have also revealed that mice lacking angiotensinogen, the substrate that renin acts on, are lean and resistant to diet-induced obesity.



In the current study, the researchers generated mice with a predisposition for obesity that were also deficient for renin. They found that the renin-less mice were lean, resistant to diet-induced obesity, and more insulin sensitive than normal mice.



"This metabolically favorable state results partly from an increased metabolic rate and partly from gastrointestinal loss of dietary fat, but not from increased physical activity or decreased food intake," they said. The metabolic effects were explained almost entirely by a lack of Ang II in the absence of renin. Renin's other effects on metabolism were minimal.



"Our findings are particularly relevant since they suggest that renin inhibitors recently approved or under development for the treatment of hypertension are likely to have favorable effects on obesity, insulin sensitivity, and their associated metabolic and cardiovascular consequences," the researchers said.







The researchers include Nobuyuki Takahashi, Feng Li, Kunjie Hua, Jianbei Deng, Chih-Hong Wang, Hyung-Suk Kim, and Joyce B. Harp, of The University of North Carolina at Chapel Hill, in Chapel Hill, NC, USA; Robert R. Bowers, and Timothy J. Bartness, of the Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA.



Source:

Cathleen Genova

Cell Press

Howard J. Federoff, M.D., Ph.D. Of Georgetown University Presented With Bernard Sanberg Memorial Award

The American Society for Neural Therapy and Repair (ASNTR), which held its 16th Annual Meeting April 30 - May 2 in Clearwater Beach, Florida, has awarded The 2009 Bernard Sanberg Memorial Award for Brain Repair to Howard J. Federoff, MD, PhD, Executive Vice President for Health Services and Executive Dean of the School of Medicine at Georgetown University.



The Award is named for Bernard Sanberg, father of Dr. Paul Sanberg, (University of South Florida), a co-founder of the ASNTR. After Bernard Sanberg died of a stroke in 1999, the award bearing his name was established and is given by the ASNTR annually to an individual who has made outstanding research contributions in the field of neural therapy and repair. The award is presented every year at ASNTR's Annual Meeting. The first Bernard Sanberg Memorial Award was given in 2000.



"The annual award is based on the quality of a researcher's contribution and its impact in advancing neural repair," said John Sladek, PhD, professor of pediatrics and neuroscience at the University of Colorado School of Medicine and ASNTR founding president.



Recent past winners include Paul Carvey, PhD, Rush University Medical Center (2008); Barry Hoffer, MD, PhD, NIDA/NIH (2007); and John Sladek, PhD, University of Colorado (2006).



Dr. Federoff is responsible for overseeing biomedical research at Georgetown University as well as advancing the educational and clinical missions of the university. His research interests include gene therapy and neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. He also holds a number of medical patents.



Prior to coming to Georgetown University, Dr. Federoff was Senior Associate Dean for Basic Research, Professor of Oncology and Genetics and Professor of Neurology, Medicine Microbiology and Immunology at the University of Rochester School of Medicine. He was the founding director of the Center for Aging and Development Biology at the Aab Institution of Biomedical Sciences at Rochester.



Source:
Donna Morrison


Cell Transplantation Center of Excellence for Aging and Brain Repair

Nanotubes Used For First Time To Send Signals To Nerve Cells

Texas scientists have added one more trick to the amazing repertoire of carbon nanotubes -- the ability to carry electrical signals to nerve cells.



Nanotubes, tiny hollow carbon filaments about one ten-thousandth the diameter of a human hair, are already famed as one of the most versatile materials ever discovered. A hundred times as strong as steel and one-sixth as dense, able to conduct electricity better than copper or to substitute for silicon in semiconductor chips, carbon nanotubes have been proposed as the basis for everything from elevator cables that could lift payloads into Earth orbit to computers smaller than human cells.



Thin films of carbon nanotubes deposited on transparent plastic can also serve as a surface on which cells can grow. And as researchers at the University of Texas Medical Branch at Galveston (UTMB) and Rice University suggest in a paper published in the May issue of the Journal of Nanoscience and Nanotechnology, these nanotube films could potentially serve as an electrical interface between living tissue and prosthetic devices or biomedical instruments.



"As far as I know, we're the first group to show that you can have some kind of electrical communication between these two things, by stimulating cells through our transparent conductive layer," said Todd Pappas, director of sensory and molecular neuroengineering at UTMB's Center for Biomedical Engineering and one of the study's senior authors. Pappas and UTMB research associate Anton Liopo collaborated on the work with James Tour, director of the Carbon Nanotechnology Laboratory at Rice's Richard E. Smalley Institute for Nanoscale Science and Technology, Rice postdoctoral fellow Michael Stewart and Rice graduate student Jared Hudson.



The group employed two different types of cells in their experiments, neuroblastoma cells commonly used in test-tube experiments and neurons cultured from experimental rats. Both cell types were placed on ten-layer-thick "mats" of single-walled carbon nanotubes (SWNTs) deposited on transparent plastic. This enabled the researchers to use a microscope to position a tiny electrode next to individual cells and record their responses to electrical pulses transmitted through the SWNTs.



In addition to their electrical stimulation experiments, the scientists also studied how different kinds of SWNTs affected the growth and development of neuroblastoma cells. They compared cells placed on mats made of "functionalized" SWNTs, carbon nanotubes with additional molecules attached to their surfaces that may be used to guide cell growth or customize nanotube electrical properties, to cells cultured on unmodified "native" carbon nanotubes and conventional tissue culture plastic.



"Native carbon nanotubes support neuron attachment and growth well -- as we expected, better than the two types of functionalized nanotubes we tested," Pappas said. "Next we want to find a way to functionalize the nanotubes to make neuron attachment and communication better and make these surfaces more biocompatible."



Another avenue Pappas wants to explore is finding out whether nanotubes are sensitive enough to record ongoing electrical activity in cells. "Where we want to get to is a device that can both sense and deliver stimuli to cells for things like prosthetic control," Pappas said. "I think it's definitely doable, and we're pursuing that with Jim Tour and his group. It's great to be able to work with a guy who's on the cutting edge of nanoelectronics technology -- he seems to develop something new every week, and it's really become a great interaction."







The University of Texas Medical Branch at Galveston

Public Affairs Office

301 University Boulevard, Suite 3.102

Galveston, Texas

utmb/



Contact: Jim Kelly

University of Texas Medical Branch at Galveston

Study Suggests Reason For High Incidence Of Cancer In The Prostate

Cancer occurs more frequently in the prostates of men than in any organ other than the skin. While DNA damage caused by exposure to the sun is likely the cause of many skin cancers, the cause of prostate cancer remains largely unknown. Research conducted by the group of Marikki Laiho, M.D., Ph.D., a Professor at the University of Helsinki, Finland, in collaboration with Donna Peehl, Ph.D., an Associate Professor (Research) at Stanford University, US, points to absence of critical mechanisms protecting prostate cells from DNA damage as a key contributor to the development of prostate cancer.


Results of the study will be published in the online Early Edition of the Proceedings of the National Academy of Sciences, USA, during the week of April 9-13.


The investigators used primary cultures of normal epithelial cells derived from patients' surgical specimens to examine responses to DNA damage induced by irradiation or chemicals. These cultured cells are the "progenitor" cells in the prostate in which cancer may originate, and therefore provide a realistic experimental model in which to study carcinogenic processes.


After exposure to DNA damaging agents, cells typically mount several types of defensive mechanisms to allow repair of DNA damage prior to cell division. These mechanisms prevent the passage of damaged genetic material to daughter cells, which would contribute to the conversion of those damaged cells to cancer. One of these protective mechanisms is cell cycle checkpoint arrest, which is mediated by a series of molecular events triggered by DNA damage.


Surprisingly, normal prostate cells were unable to enforce cell cycle checkpoint arrest and continued to proliferate following DNA damage. Early events involving cellular recognition of DNA damage were intact, so lack of checkpoint arrest in these cells was not due to inability to recognize DNA damage. Rather, inability to enforce cell cycle arrest was linked to low levels of the protein Wee1A, a tyrosine kinase that phosphorylates and inhibits cyclin dependent kinase 2 (cdk2). In the absence of Wee1A activity, cdk2 remained active and continued to drive the prostate cells to undergo cell division. In conjunction, slower clearance of DNA damage foci suggested persistent DNA damage. When Wee1A protein was restored in these cells, checkpoint control was rescued, showing that Wee1A was indeed critical to this important pathway.


When using cultured cells, there is always a concern that the in vitro environment may alter cellular behavior. To confirm that the observed results were not an artifact of cell culture, the investigators used a novel model system of "tissue slice cultures", developed by Peehl. Cores of fresh tissue were bored from surgical specimens, then were precision-cut to thicknesses of only a few hundred microns. These slices were incubated and retained their structure and function for several days. The value of tissue slice cultures is that all elements of the whole tissue remain intact, permitting realistic experiments that are not feasible to perform directly in humans. The responses to DNA damage of the normal epithelial cells in these tissues were similar to those of the cell cultures, signifying that defensive mechanisms against DNA damage are indeed lacking in the human prostate.















The lack of Wee1A-mediated DNA damage-induced checkpoint enforcement is not the only defective protective mechanism in prostate cells. In 1995, Peehl in collaboration with another investigator at Stanford, Amato Giaccia, Ph.D., reported in Cancer Research that normal prostatic epithelial cells lacked the p53 response to DNA damage. The p53 protein is a major tumor suppressor and lack of p53 function leads to genomic instability and malignancy. The defects in the two checkpoint enforcement pathways, mediated by p53 in one and by Wee1A in the other, are unrelated, since correcting the Wee1A pathway did not restore p53 function in prostate cells.


The use of human cells and tissues in these studies was key to the medical relevance of the findings. The human prostate is almost unique among mammals in having a high incidence of prostate cancer. Rodents, most commonly used in the laboratory to study mechanisms of cancer, do not develop prostate cancer spontaneously. The absence of at least two key checkpoint elements in the DNA damage response pathways may predispose human prostatic epithelial cells to accrual of DNA lesions and provide a mechanistic basis for the high incidence of cancer in the prostate.


Why prostate cells lack these mechanisms is unknown, but discovery of ways to restore these checkpoints controls might protect against prostate cancer.


The study was funded by the Department of Defense Prostate Cancer Research Program, the Academy of Finland, Biocentrum Helsinki, the Finnish Cancer Organizations and the Finnish Cultural Foundation.


HELSINGIN YLIOPISTO (UNIVERSITY OF HELSINKI)

P.O. Box 33

FIN-00014 Helsinki

helsinki.fi

Adipose Tissue May Be An Alternate Source For Life-Saving Hematopoietic Stem Cell Transplants

Researchers at the University of Pittsburgh School of Medicine have successfully isolated and cultured human hematopoietic stem cells from fat, or adipose, tissue, suggesting that they have found another important source of cells for reconstituting the bone marrow of patients undergoing intensive radiation therapy for blood cancers. They are presenting this ground-breaking research at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) North American Chapter meeting held at the Westin Harbor Castle conference center in Toronto.



Adipose tissue has the ability to rapidly expand or contract in accordance with nutritional constraints. In so doing, it requires rapid adjustment in its blood supply and supporting connective tissue, or stroma. Based on previous reports that the "stromal vascular" fraction of adipose tissue contains stem cells that give rise to pericytes - cells surrounding small blood vessels - the University of Pittsburgh School of Medicine researchers, led by Albert D. Donnenberg, Ph.D., professor and director of the Hematopoietic Stem Cell Laboratory, University of Pittsburgh Cancer Institute, isolated the stromal vascular fraction from human adipose tissue and expanded these cells by growing them in a specialized blood-culturing medium for 21 to 42 days.



Using a cell-sorting method known as flow cytometry, the researchers detected a broad spectrum of blood-forming, or hematopoietic, cells among the cultured cells at varying stages of differentiation. In particular, they observed both early and mature red blood cells. Moreover, they detected CD34+ cells at approximately the same frequency as is present in freshly isolated bone marrow. In bone marrow, CD34+ expression indicates the presence of progenitor cells which give rise to all of the different types of blood cells.



These data indicate that hematopoietic stem cells, or cells that give rise to them, are an integral part of normal adipose tissue, according to Dr. Donnenberg. "We took cells from the stromal vascular fraction of normal adipose tissue and basically gave them bone marrow food to see what would happen. We were able to culture a variety of hematopoietic cells, including blood progenitor cells."



Dr. Donnenberg said that the use of a patient's own bone marrow or blood-derived stem cells for bone marrow reconstitution carries some risk that these cells are contaminated with the patient's own tumor cells. "Since it has been shown in some cases that tumor cells contaminating bone marrow grafts are the source of recurrent malignancies after autologous transplantation, this might be a way of giving patients who need bone marrow reconstitution their own hematopoietic cells derived from a source other than their defective bone marrow," he explained.







In addition to Dr. Donnenberg, J. Peter Rubin, M.D., department of surgery, University of Pittsburgh School of Medicine, was a key co-investigator along with other department of surgery researchers, Vera Donnenberg, Ph.D., Kacey Marra, Ph.D., and Bret Schipper, M.D.



Contact: Jim Swyers


University of Pittsburgh Schools of the Health Sciences

Lipids get new comprehensive classification system

In response to the growing number of lipids expected to be discovered through lipidomics and in anticipation of the
massive amounts of data that will be generated by the lipid community, an international group of scientists has developed a
comprehensive classification, nomenclature, and chemical representation system for lipids. The details of the system appear
in the May issue of the Journal of Lipid Research, an American Society for Biochemistry and Molecular Biology journal.



The new system is part of an effort by the Lipid Metabolites and Pathways Strategy (LIPID MAPS) consortium to produce a
detailed understanding of the structure and function of all the lipids within a cell. The consortium is a large collaborative
effort led by the University of California, San Diego and funded by a $35 million "Glue Grant" from the National Institute of
General Medical Sciences. The five-year grant involves more than 30 researchers at 18 universities, medical research
institutes, and companies across the United States.


The Director of the LIPID MAPS initiative and senior author of the manuscript Dr. Edward A. Dennis, Distinguished Professor
of Chemistry, Biochemistry, and Pharmacology at the University of California, San Diego says: "The goals of the LIPID MAPS
initiative are to characterize known lipids and identify new ones, to quantitate the temporal and spatial changes in lipids
that occur with cellular metabolism, and to develop bioinformatics approaches that establish dynamic lipid networks. In order
to coordinate their efforts with those of other groups, such as the Lipid Bank in Japan, the European Lipidomics Initiative,
and the International Conference on the Biochemistry of Lipids based in Europe and to facilitate international collaboration,
LIPID MAPS initiated the development of a comprehensive classification system for lipids suitable for databasing."


"The classification scheme was designed to be a broad-based scheme covering eukaryotic and prokaryotic sources, to include
new classes of lipids which have been discovered in recent years, to be extensible to accommodate future novel classes and to
be compatible with modern-day informatics requirements," explains the paper's first author Dr. Eoin Fahy, of the San Diego
Supercomputer Center at the University of California, San Diego, who serves as LIPID MAPS' Bioinformatics Project
Coordinator.


In the LIPID MAPS classification scheme, lipids are divided into eight primary categories: fatty acyls, glycerolipids,
glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides. These categories are
based on the functional backbone of the lipid molecule from a chemical standpoint. The categories are further subdivided into
classes and subclasses to handle the existing and emerging arrays of lipid structures.


In conjunction with their proposed lipid classification scheme, the group has also proposed a nomenclature system. "The
nomenclature rules adopted by LIPID MAPS follow existing IUPAC-IUBMB rules closely and should not be viewed as a competing
format," emphasizes Dr. Fahy. "The main differences involve clarification of the use of core structures to simplify
systematic naming of some of the more complex lipids, provision of systematic names for recently discovered lipid classes,
and clarification of abbreviations and shorthand names for lipids."















LIPID MAPS has also devised a common scheme for representing the chemical structures of individual lipids and their
derivatives. The concept underlying the new methodology is that head groups are drawn on the right side and the hydrocarbon
chain extends to the left. In the simplest case of the fatty acid derivatives, the acid group is drawn on the right and the
hydrophobic hydrocarbon chain is on the left.


Another part of the classification system is a 12 digit identifier for each unique lipid molecule, called a LIPID ID. The
identifier is based on the classification scheme and will be used mainly in databases, such as the LIPID MAPS database. "The
format of the LIPID ID provides a systematic means of assigning unique IDs to lipid molecules and allows for the addition of
large numbers of new categories, classes and subclasses in the future," explains Dr. Fahy. "The first two characters (1-2) of
the ID contain the database identifier (e.g. LM for LIPID MAPS). The next two characters (3-4) correspond to the lipid
category, the next two (5-6) to the class within that category and the next two (7-8) to the subclass. The last four
characters of the ID comprise a unique identifier within a particular subclass and are randomly assigned."


The new classification system has already been implemented, and Dr. Dennis, Dr. Fahy and their collaborators from Europe,
Asia, and across the U.S. hope that it will eventually gain widespread acceptance. "Inevitably, there will be some
resistance, possibly from others who have created alternative schemes or who are long-time proponents of other formats,"
acknowledges Dr. Fahy. "However, the Journal of Lipid Research manuscript outlining this classification scheme contains an
international panel of authors (several of whom are not involved with the LIPID MAPS project) and has also been reviewed by
several other experts in the lipid research field, so it represents a well-balanced consensus view of what a modern-day lipid
classification scheme should be."


Examples of the classification scheme and interactive access to it can be viewed on the LIPID MAPS website at lipidmaps.


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



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


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


Contact: Nicole Kresge

nkresgeasbmb

301-634-7415

American Society for Biochemistry and Molecular Biology

asbmb.

Role Of Tiny RNAs In Controlling Stem Cell Fate Identified By Gladstone Scientists

Researchers at the Gladstone Institute of Cardiovascular Disease (GICD) and the University of California, San Francisco have identified for the first time how tiny genetic factors called microRNAs may influence the differentiation of pluripotent embryonic stem (ES) cells into cardiac muscle. As reported in the journal Cell Stem Cell, scientists in the lab of GICD Director, Deepak Srivastava, MD, demonstrated that two microRNAs, miR-1 and miR-133, which have been associated with muscle development, not only encourage heart muscle formation, but also actively suppress genes that could turn the ES cells into undesired cells like neurons or bone.



"Understanding how pluripotent stem cells can be used in therapy requires that we understand the myriad processes and factors that influence cell fate," said Dr. Srivastava. "This work shows that microRNAs can function both in directing how ES cells change into specific cells - as well as preventing these cells from developing into unwanted cell types. "



The differentiation of ES cells into heart cells or any other type of adult cell is a very complicated process involving many factors. MicroRNAS, or miRNAs, seem to act as rheostats or "dimmer switches" to fine-tune levels of important proteins in cells. More than 450 human miRNAs have been described and each is predicted to regulate tens if not hundreds of proteins that may determine cellular differentiation.



While many ES cell-specific miRNAs have been identified, the role of individual miRNAs in ES cell differentiation had not previously been determined. The Gladstone team showed that miRNAs can control how pluripotent stem cells determine their fate, or "cell lineage" - in this case as cardiac muscle cells.



Specifically, they found that miR-1 and miR-133 are active at the early stages of heart cell formation, when an ES cell is first "deciding" to become mesoderm, one of the three basic tissue layers in mammals and other organisms. Activity of either miR-1 or miR-133 in ES cells caused genes that encourage mesoderm formation to be turned on. Equally important, they caused other genes that would have told the cell to become ectoderm or endoderm to turn off. For example, expression of a specific factor called Delta-like 1 was repressed by miR-1. Removal of this factor from cells by other methods also caused the cells to begin transforming into heart cells.



"Our findings provide insight into the fine regulation of cells and genes that is needed for a heart to form," said Kathy Ivey, PhD, a California Institute of Regenerative Medicine (CIRM) postdoctoral fellow and lead author on the study. "By better understanding this complicated system, in the future, we may be able to identify ways to treat or prevent childhood and adult diseases that affect the heart."







The Gladstone team included Alecia Muth, Joshua Arnold, Jason Fish, Edward Hsaio and Bruce Conklin. They were joined by USCF's Frank King, Ru-Fang Yeh and Harold S. Bernstein. The research was supported by the National Institutes of Health, the California Institute of Regenerative Medicine and the Lynda and Stewart Resnick Foundation.



About the Gladstone Institutes



The J. David Gladstone Institutes, affiliated with the University of California, San Francisco (UCSF), is dedicated to the health and welfare of humankind through research into the causes and prevention of some of the world's most devastating diseases. Gladstone is comprised of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease. More information can be found at gladstone.ucsf/.



Source: Valerie Tucker


Gladstone Institutes

Fanconi Anemia: Genetically Corrected Blood Cells Obtained From Patients' Skin Cells

Collaboration research carried out by the teams of Jordi SurrallГ©s, Universitat AutГІnoma de Barcelona (UAB); Juan Carlos IzpisГєa-Belmonte and Angel Raya, Centre for Regenerative Medicine of Barcelona (CMRB); and Juan Antonio Bueren, Centre for Energetic, Environmental and Technological Research (CIEMAT), has resulted in the generation of blood cells from skin cells of patients with a genetic disease known as Fanconi anemia. The process is based on gene therapy and cell reprogramming techniques in which cells similar to embryonic stem cells known as induced pluripotent stem (iPS) cells can be generated. The research article was published in this week's digital version of Nature.



The research demonstrates that, for the first time, in the case of a genetic disease such as Fanconi anemia it is possible to correct the genetic defect in patient-specific skin cells by converting them into cells similar to embryonic stem cells (iPS cells) which later can be differentiated towards blood cells.



These results are the proof of concept that this new therapeutic strategy has the potential of generating tissues using the very skin of those affected with these genetic diseases. This observation is particularly important in diseases such as Fanconi anemia, where one of the main problems lies in the lack of blood cell in the bone marrow of those affected. However, according to researchers, this new therapeutic strategy can be applied to many other genetic diseases by differentiating iPS cells towards healthy tissues these patients lack.



The generation of blood cells in this research was carried out in vitro, in cell culture plates, which places the research in a preclinical environment. It remains unknown whether they would generate blood cells after being transplanted. Moreover, the transplant of embryonic stem cells in animals has revealed that these cells can cause tumours. Therefore, the possibility of treating Fanconi anemia patients by transplanting iPS cells must wait until the efficacy and safety of these new discoveries are demonstrated in experimental models.



Researchers taking part in the study are confident that in the next few years it will be possible to improve the efficacy and safety of this new scientific discovery, and that some time in the future, clinical professionals will be able to cure patients suffering from genetic diseases such as Fanconi anemia.



UAB and CIEMAT, leading research centres in Fanconi anemia



Fanconi anemia is a rare hereditary disease which mainly affects the bone marrow and causes it to produce less blood cells. The lack of white blood cells makes individuals more vulnerable to infections, while the lack of platelets or red blood cells may prevent clotting or lead to fatigue. Treatment includes transplanting healthy blood stem cells from the bone marrow or umbilical cord of a compatible donor or, if possible, a relative. Unfortunately, few patients can find a healthy and compatible donor.



UAB, through the Research Group directed by Dr Jordi SurrallГ©s, professor at the Department of Genetics and Microbiology, and CIEMAT, through the group led by Dr Juan Antonio Bueren, director of the Hematopoiesis and Gene Therapy Division, are two of the world's leading centres in the research on Fanconi anemia. In recent years they have made many important contributions to help understand the genetic mechanisms of the disease. These past few years, the Office of the Vice-Rector for Strategic Projects at UAB has cofinanced translational research on Fanconi anemia as a model disease in biomedical and biotechnological research.



Source:
Maria Jesus Delgado


Universitat Autonoma de Barcelona

Boston University, Fraunhofer Gesellschaft Form Alliance To Accelerate Biomedical Innovation

Seeking to accelerate the delivery of biomedical engineering advances to the medical care of patients, Boston University and its College of Engineering are joining the German research and development organization Fraunhofer Gesellschaft to create the Boston University-Fraunhofer Alliance for Medical Devices, Instrumentation and Diagnostics. BU and Munich-based Fraunhofer will jointly fund the five-year, $5 million initiative.



Combining the innovation and translational technology development experience of Boston University and Fraunhofer, the alliance will allow for the accelerated translation of advanced biomedical research into products that can be manufactured and used in clinical applications. The alliance will leverage the most promising research innovations in labs throughout Boston University, particularly in its College of Engineering, said Andre Sharon, a BU engineering professor and director of the BU-based Fraunhofer Center for Manufacturing Innovation.



Boston University Provost David K. Campbell said, "Boston University has enjoyed a long and productive collaboration with Fraunhofer Gesellschaft, and this alliance will raise that collaboration to the next level."


Hans-Jorg Bullinger, president of Fraunhofer Gesellschaft, Europe's largest applied R&D organization, noted, "Based on Professor Sharon's outstanding track record and the excellent results from our long-standing collaboration with Boston University, we are confident that this initiative will be very successful and will lead to the development of new medical technologies."



Sharon said, "The alliance will leverage other independently funded research activities at Boston University as a continuous source of medically relevant innovations. In conjunction with Fraunhofer, the selected research will be efficiently developed into deployable technologies in a time-efficient and cost-effective manner."



The alliance seeks to take advantage of the two institutions' respective strengths. Advanced biomedical engineering research being conducted throughout BU's College of Engineering, College of Arts and Sciences, and Medical School generally proceeds to the laboratory bench level. Fraunhofer hopes to take these innovations and convert them into working medical devices and instruments that can be licensed to existing companies or created by new, spin-off ventures.



The alliance is expected to use another recently funded initiative as a wellspring. Last year, the Wallace H. Coulter Foundation awarded a $4.9 million grant to Boston University to enhance collaboration between researchers in Biomedical Engineering, and clinicians and researchers at the BU Medical School. The Coulter program shares the goal of accelerating translation of biomedical innovations to patient care.



"This alliance with Fraunhofer will add fuel to our translational research program in biomedical engineering," said BU College of Engineering Dean Kenneth R. Lutchen. "Indeed, throughout the College are world-class and top-ranked faculty working at the interface of engineering and medicine, and this initiative will further accelerate our most promising research in this area so improved medical care can be delivered to patients as soon as possible."
















"The BU-Fraunhofer Alliance for Medical Instrumentation, Devices and Diagnostics embodies, amplifies and lends cohesion to some of the best biomedical research in physics, chemistry and engineering on Boston University's Charles River Campus," said Engineering Professor Charles DeLisi. "Along with clinical colleagues the participating faculty are poised to make important contributions to research and translational medicine."



Fraunhofer Gesellschaft is also very active in biomedical research. Current activities include plant-based vaccine development, medical imaging, array-based diagnostics, surgical micro-tools development, and other novel devices and instrumentation.



The Fraunhofer Center for Manufacturing Innovation was established at Boston University in 1994. Working with BU faculty, students and international interns, the Center scales up basic research into advanced industrial technologies that meet the needs of client companies. Clients represent a range of industries both locally and globally.



Among the promising innovations under consideration for initial support by the alliance are efforts to create disposable diagnostic chips that can detect disease at the molecular level, an optically guided colon cancer detection and treatment system, and an array-based medical diagnostic tool.






Founded in 1839, Boston University is an internationally recognized institution of higher education and research. With more than 30,000 students, it is the fourth largest independent university in the United States. BU contains 17 colleges and schools along with a number of multi-disciplinary centers and institutes which are central to the school's research and teaching mission.



Contact: Mike Seele


Boston University

'Hot' Oxygen Atoms On Titanium Dioxide Motivated By More Than Just Temperature

Like two ballroom dancers waltzing together, the two atoms of an oxygen molecule severed by a metal catalyst usually behave identically. But new research reveals that on a particular catalyst, split oxygen atoms act like a couple dancing the tango: one oxygen atom plants itself while the other shimmies away, probably with energy partially stolen from the stationary one.



Scientists from the Department of Energy's Pacific Northwest National Laboratory found the unanticipated behavior while studying how oxygen interacts with reduced titanium oxide surfaces. The chemists are trying to understand how molecular oxygen -- the stuff we breathe -- interacts with metals and metal oxides, which are used as catalysts in a variety of environmental and energy applications. Researchers worldwide are exploring the use of titanium dioxide, especially in hydrogen production for solar fuel cells.



The team was a bit surprised by the unequal sharing of resources among the oxygen atoms.



"It is unique that one atom stays in place and the other one is mobile and probably gets most of the energy," says lead scientist Igor Lyubinetsky, who performed the work at the DOE's Environmental Molecular Sciences Laboratory, a national scientific user facility located on the PNNL campus, with funding by DOE's Office of Basic Energy Sciences. Their work will be published as the cover article in the Journal of Physical Chemistry C on February 21, 2008, and previously appeared online January 5, 2008.



Researchers have yet to determine if this short-lived extra mobility plays a role in chemical reactions, but understanding the basic chemistry might be important in processes that break down pollutants or split water to generate hydrogen.



Previous research has revealed much about how oxygen molecules interact with metals. For example, when molecular oxygen (O2) hits a platinum surface, the platinum helps split the molecule apart and each oxygen atom zips over the surface in opposite directions, eventually sticking to the metal. Chemists call the pumped up atoms "hot" because the extra energy released by the breaking and reforming bonds gives the atoms their boost.



Titanium dioxide is not only a popular catalyst, but it also serves as a great model oxide to study basic chemistry. PNNL scientists, led by Lyubinetsky, wanted to know if molecular oxygen behaved on titanium dioxide the way it behaves on metals such as platinum. Oxides have different properties than metals: Rust, for example, is iron oxide, which flakes off from iron metal.



To find out, the team started with a slice of titanium oxide crystal, oriented so that titanium and oxygen atoms line up on the surface in alternating strips, forming grooves of titanium troughs between oxygen rows. By heating the sample, the team created imperfections on the surface, or spots where an oxygen atom vacated its row. Using scanning tunneling microscopy, the researchers found that molecular oxygen only broke apart when it encountered a vacancy, indicating that oxygen molecules bounce along flawless titanium oxide surfaces and don't react, as expected from previous results.
















The team also expected one of the atoms to make the vacancy its home, and the second to situate itself right next to its former partner. Instead, the chemists found that the second oxygen behaved like a "hot" atom and was free to move one or two crystal lattice spaces away. Out of 110 molecules the team counted, more than three quarters of the hot atoms hopped one or two spaces away before becoming mired on the surface.



"This is one of the first time chemists have looked at oxygen on metal oxides at the atomic level, and this finding was unexpected," says Lyubinetsky.



But a skittering atom requires some sort of energy to propel it, so the researchers explored how a splitting oxygen molecule divvied up its energetic resources. The team found that a free oxygen atom at room temperature (about 20 C or 68 F) is virtually immobile on a titanium oxide surface. However, previous calculations have suggested that the energy is released from the rearrangement of the bonds -- from within the oxygen molecule and between the oxygen atom and titanium surface -- and the team has concluded this might be the source of the hot atom's burst after its partner anchored itself in the vacancy: the calculated energy was about two to three times that required to get an immobilized oxygen unstuck. Lyubinetsky postulates that the hot oxygen atom uses this energy to move around on the titanium oxide surface.



The scientists are trying to better understand the mechanism because it might be significant in basic catalytic chemistry.



"This finding may be important in surface reactivity. We don't know yet," Lyubinetsky says. The chemical event could, for example, be affected by the extra energy the oxygen atom possesses. The effect might also play into whether surface oxygen atoms interfere with the chemistry between the catalyst and other reagents.



In any event, the result will keep chemists tango-ing with new questions for a long time.







Reference: Y. Du, Z. Dohnalek, and I. Lyubinetsky, Transient Mobility of Oxygen Adatoms upon O2 Dissociation on Reduced TiO2(110), J. Phys. Chem. C, 2008, 10.1021/jp077677u. Published online January 5, 2008; print February 21, 2008



The William R. Wiley Environmental Molecular Sciences Laboratory is a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory.



Pacific Northwest National Laboratory is a DOE Office of Science national laboratory that solves complex problems in energy, national security and the environment, and advances scientific frontiers in the chemical, biological, materials, environmental and computational sciences. PNNL employs 4,000 staff, has a $760 million annual budget, and has been managed by Ohio-based Battelle since the lab's inception in 1965.



Source: Mary Beckman


DOE/Pacific Northwest National Laboratory

Discovery Of Stem Cells In The Pituitary Gland Of Mice Suggests A Means Of Adapting To Stress And Life Changes

A team of researchers led by scientists at Cold Spring Harbor Laboratory have for the first time identified stem cells that allow the pituitary glands of mice to grow even after birth. They found that, in contrast to most adult stem cells, these cells are distinct from those that fuel the initial growth of this important organ. The results suggest a novel way that the hormone-secreting gland may adapt, even in adolescents and adults, to traumatic stress or to normal life changes like pregnancy.



Seeking Adult Stem Cells



Maturity, in some respects, brings diminished possibilities. As a fertilized egg cell repeatedly divides to grow into a mature animal, most of the resulting cells become ever more specialized. But a small number of cells, known as stem cells, remain uncommitted even as they spawn more specialized progeny. The most versatile stem cells, taken from days-old embryos, are able to form any cell type - but studying them in people is controversial. Even in adults, however, other types of stem cell persist that have a more limited repertoire. Some replace specific cells as they wear out; others help to rebuild damaged tissues. Still other stem cells are suspected by some scientists of starting or maintaining cancers.



In spite of their importance, stem cells are hard to spot among the multitude of cells in complex tissue. Several years ago, neuroscientist Grigori Enikolopov, Ph.D., an associate professor at Cold Spring Harbor Laboratory (CSHL), and his colleagues developed a tool to look for stem cells that give rise to new adult brain cells. Researchers had known that a gene called Nestin was active in these neural stem cells. The CSHL team genetically engineered mice so that the same conditions that activate Nestin in a particular cell also make it glow green under ultraviolet light.



Using these mice gives researchers an important pointer to cells that may be adult stem cells. Almost 100 research teams around the world have now used these special mice to help find adult stem cells in hair follicles, liver, muscle, and other tissues.



Looking at the pituitary



One place where stem cells had been suspected - but never found - is the pituitary gland. This organ, which in people is about the size of a pea, sits at the base of the brain, where it secretes hormones that regulate various processes throughout the body. In mice, the gland develops in the embryo, but then has a second growth spurt. "A few weeks after they are born," says Dr. Enikolopov, "the pituitary undergoes massive expansion" that suggests a role for adult stem cells.



Anatoli Gleiberman, Ph.D., a researcher in the lab of pituitary expert M. Geoff Rosenfeld at the University of California, San Diego, initiated a collaboration between the two labs to look for pituitary stem cells. The researchers used the Nestin-tracking mice to identify candidate cells in the anterior pituitary, the section of the organ that secretes hormones. They then used other techniques to show that these are true stem cells. "There are six main lineages in the adult pituitary," says Dr. Enikolopov, "and we can demonstrate that one adult stem cell can generate all six lineages," with each cell type secreting a different hormone.
















A distinct kind of stem cell



These cells differ from most adult stem cells, however. "In most cases that we know," says Dr. Enikolopov, "cells that become stem cells of the adult have been also contributing to embryonic development and continue to serve as stem cells in the adult." The research team demonstrated that adult stem cells in the pituitary did not help construct the embryonic organ.



Their research, the scientists suggest, indicates that the adult mouse pituitary includes two similar - but not identical - types of hormone-producing cells: some that grew in the developing embryo, and some that appeared later. They speculate that having two sets of cells may let the organ respond differently to changing body conditions. Dr. Enikolopov notes that hormones strongly influence human neuropsychiatric phenomena, including stress and depression that are his main research focus. "All are mediated through the pituitary," he said, so changes that happen during the later growth of the gland could have lasting effects.



"Genetic approaches identify adult pituitary stem cells" appears in the April 29, 2008 edition of the Proceedings of the National Academy of Sciences. Along with Dr. Enikolopov, Dr. Michael Geoff Rosenfeld, who is a Howard Hughes Medical Institute Investigator at the University of California at San Diego School of Medicine, is a corresponding author of the paper. The complete citation is as follows: Anatoli S. Gleiberman, Tatyana Michurina, Juan M. Encinas, Jose L. Roig, Peter Krasnov, Francesca Balordi, Gord Fishell, Michael G. Rosenfeld, and Grigori Enikolopov. Click here to access the paper online.



Cold Spring Harbor Laboratory is a private, nonprofit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases and other causes of human suffering.



For more information, visit cshl/.



Source: Jim Bono


Cold Spring Harbor Laboratory

Study Shows Link Between Influenza Virus And Fever

Viruses are microscopically sized parasites. They plant their genes in the cells of their victim in order to 'reprogram' them. The infected cells then no longer produce what they need to live, making lots of new viruses instead.


Luckily, in most cases this hostile takeover does not go unnoticed. This is ensured by the cells' own sensors that recognise alien genetic material. One of them is RIG-I. When RIG-I encounters virus genes, it ensures that the body releases interferon. The interferon then in turn puts killer cells on combat standby, which then destroy the infected cells.


Yet this is only part of the truth. 'According to our results RIG-I appears to play a far more prominent role in the defence against viruses than was previously thought,' Dr. JГјrgen Ruland from the University Hospital Rechts der Isar at the Technical University of Munich explains. As a result, many virus infections are accompanied by a high temperature. That is also what happens with influenza, for example. This symptom cannot be explained by interferon release alone.


In most cases it is cytokines which trigger the fever. 'We have now been able to show, for the first time, that RIG-I also cranks up the production of a central cytokine in the case of a virus infection,' Dr. Hendrik Poeck explains. He and his colleagues Dr. Michael Bscheider and Dr. Olaf GroГџ are the primary authors of the study. This is a reference to interleukin 1, probably the most important cytokine known today.


Do cytokines cause more severe courses of a disease?


When RIG-I comes into contact with a virus gene, it does two things. On the one hand, it ensures that certain immune cells produce pro-interleukin, the precursor of interleukin 1, en masse. At the same time it activates an enzyme via a complicated signalling pathway which transforms pro-interleukin into interleukin 1. 'This interleukin 1 then ensures that the typical symptoms of a virus infection such as fever or shivering occur,' Professor Veit Hornung from the Bonn University Clinic explains.


As yet the researchers do not know how important this newly discovered immune mechanism is for the successful defence against the virus. The release of interleukin may also have negative consequences. 'There is the hypothesis that an overproduction of cytokines may lead to extremely severe courses of virus diseases,' Professor Gunther Hartmann says. Medicines that prevent such a 'cytokine storm' may therefore alleviate the progress of the disease.


Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1beta production. Hendrik Poeck, Michael Bscheider, Olaf Gross, Katrin Finger, Susanne Roth, Manuele Rebsamen, Nicole Hannesschlager, Martin Schlee, Simon Rothenfusser, Winfried Barchet, Hiroki Kato, Shizuo Akira, Satoshi Inoue, Stefan Endres, Christian Peschel, Gunther Hartmann, Veit Hornung & JГјrgen Ruland. Nature Immunology, doi: 10.1038/ni.1824


Source: Bonn, Universitaet

Molecular Probes for Biology Research and Drug Discovery

The Max Planck Society initiates a new "Chemical Genomics Centre" at the crossroads of Biology, Chemistry and Medicine in
Dortmund -


While the field of genetics investigates and influences the life's processes by modifying the genes themselves, the field of
chemical genetics pursues this goal using chemical compounds that modulate the functioning of the gene and its products
(proteins, RNA, etc.). Therefore, chemists, biochemists and biologists from six Max Planck Institutes will work together in
the new "Chemical Genomics Centre" in Dortmund in the search for small molecules that allow the study of fundamental
life-science processes and the involved biological macromolecules. The Max Planck Society invests a total sum of 5 million
euro. The chemical compounds will be designed and made based on natural products analogues, via combinatorial chemistry or
rational design and their biological relevance will be tested subsequently in plants, animals and micro-organisms. In this
way, molecules shall be identified that are capable of targeting disease relevant proteins or that are candidates for crop
protection.


In the past decade it became increasingly clear that all biological processes in principal rely on chemical processes and are
governed by the structure of the participating molecules and their interactions. Biological processes can be treated as
chemical processes and studied in molecular detail. Nevertheless, up to today for only 500 of the over 100.00 proteins
encoded by the human genome a chemical compound is known that interacts with and influences the protein. Therefore research
following the sequencing of the genome is increasingly focussed on the function of its proteins and their interactions with
small molecules (modulators). A new approach for this is Chemical Genomics.


What is chemical genomics?


Chemical genomics uses drug-like molecules as modulating ligands for cell-biology research, to clarify for example the
function of a certain gene product. For a long time such probe-molecules were only found via serendipitous discoveries and
observations. Progress in the automation and parallelisation of chemical synthesis and biological analysis enables the
systematic search of modulators of protein function for the investigation of biological phenomena.



The research approach defined as "chemical genetics" (the study of individual gene products using a combination of chemical
and biological methods), and "chemical genomics" (the analogous study of the products of a gene family has certain advantages
over the genetic methods: The effects of small molecules are generally fast and reversible due to the metabolism and
excretion of the molecules. This enables the transient study of proteins. The effect is tuneable, as a varying concentration
can result in different degrees of phenotype expression. On top of that, the effect can be initiated and studied at different
stages in the development of the organism. Finally, the access to small molecule probes enables anyone to study the effect.
















How to find molecular probes for chemical genetics?


Chemical genetics has as a goal to identify substances or molecules that bind with high affinity and specificity to one or a
few of the around 100.00 different proteins. Methods developed for combinatorial chemistry enable the synthesis of biological
potentially relevant libraries of chemical compounds. An additional source for molecular probes is the isolation or chemical
total synthesis of "natural compounds". These are generally complex molecules synthesized by animals or plants and have been
optimized for a specific purpose over a period of millions of years via an evolutionary process.


The molecular libraries will subsequently be tested in a variety of biological screens. In these automated tests the screens
are monitored via for example optical methods that determine morphological changes of the cells or of complete organisms.
Using fluorescence based methods it is possible to localize and quantify special optical markers. Once a substance with a
specific biological effect has been identified, it will be used as a starting point for the analysis of the effect and the
identification of the involved target protein. Using genome and proteome analysis, the influence of the protein or the active
substance on the complete cell will be investigated. With the generation of this knowledge, the substance can be used as a
tool for extensive biological studies and its therapeutic relevance can be evaluated. In the end, this may lead to the
substance becoming a "lead compound" for the development of new drugs.


Chemical genomics is a powerful new research approach for the fundamental biomedical research. In addition, the approach
promises to have a higher efficiency in the search for lead compounds for drug development, because it integrates chemistry
and biology already in an early stage in the research process. In this way it permits a fast identification of compounds with
high biological relevance.


The Chemical Genomics Centre (CGC) in Dortmund


The Max Planck Society endorses the new interdisciplinary research approach via the founding of an institute-overlapping
Chemical Genomics Centre (CGC). Participating institutes are the Max Planck Institute for Molecular Physiology, Dortmund, for
Molecular Cell Biology and Genetics, Dresden, for Coal Research, Mьlheim, for Plant Breeding Research, Kцln, for Psychiatry,
Mьnchen and the Max Planck Institute for Biochemistry, Martinsried. The design and synthesis of the biologically relevant
compound libraries based for instance will be pursued in Dortmund and Mьlheim. The biological screening and evaluation of the
developed molecular tools will be performed in Kцln for plants and in Dresden, Martinsried, Mьnchen and Dortmund for
mammalian cell lines.


"We are living in the "post genomics" age, which means that we know and have access to the complete genetic information of
not only humans, but also of model organism like the mouse and rat. Also, the genetic information present in important
nutrition plants like beans and rice is known. However, to make the promises of the genetics research reality, it is required
that biology and chemistry form an alliance", says Herbert Waldmann, director at the Max Planck Institute for Molecular
Physiology and coordinator for this multi-institute-spanning initiative of the Max Planck Society. "The CGC is currently the
most important research initiative in its field in Europe. Especially the participation of the pharmaceutical industry is
unique and enables research projects, normally not pursuable by universities or research institutes."


The build-up of the centre is endorsed by the Max Planck Society with a total of 5 million euro for an initial period of 5
years. This should enable the instalment of several junior research groups and support the research activities at the
participating institutes. Furthermore pharmaceutical companies will participate as funding and research partners, financing
additional research groups. All research groups will be hosted in the new labs of the Biomedical Centre Dortmund, in the
immediate vicinity of the Max Planck Institute for Molecular Physiology.


The research groups supported by the companies will perform basic research on new, currently not sufficiently explored, areas
for which, however, great potential for drug development is foreseeable. An example could be the pharmacologically oriented
investigation in the interactions between proteins involved in the signal transduction pathways in the cell, leading to new
approaches to modulate these interactions.


"The CGC creates a dynamic and inspiring research environment for all participants", states Herbert Waldmann. "Research will
start in the summer of 2005 and it is already predictable that this will lead to very interesting and possibly completely
unexpected results."


Related links:


[1] Website of the Chemical Genomics Centre


PDF (102 KB)


Contact:



Prof. Dr. Herbert Waldmann

Max Planck Institute of Molecular Physiology, Dortmund

Tel.: +49 231 133-2400

Fax: +49 231 133-2499

E-mail: herbert.waldmannmpi-dortmund.mpg


Dr. Peter Herter

Max Planck Institute of Molecular Physiology, Dortmund

Tel.: +49 231 133-2500

Fax: +49 231 133-2599

E-mail: peter.hertermpi-dortmund.mpg


Max Planck Society

for the Advancement of Science

Press and Public Relations Department

Hofgartenstrasse 8

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Dr. Andreas Trepte (-1238)


Online-Editor:

Michael Frewin (-1273)


ISSN 0170-4656

Your Body Recycling Itself Captured On Film

Our bodies recycle proteins, the fundamental building blocks that enable cell growth and development. Proteins are made up of a chain of amino acids, and scientists have known since the 1980s that first one in the chain determines the lifetime of a protein. McGill researchers have finally discovered how the cell identifies this first amino acid and caught it on camera.


"There are lots of reasons cells recycle proteins fasting, which causes loss of muscle, growth and remodeling during development, and normal turnover as old proteins are replaced to make new ones," explained lead researcher, Dr. Kalle Gehring, from McGill's Department of Biochemistry. "One way that cells decide which proteins to degrade is the presence of a signal known as an N-degron at the start of the protein. By X-ray crystallography, we discovered that the N-degron is recognized by the UBR box, a component of the cells' recycling system." The powerful technique can pinpoint the exact location of atoms and enabled the team to capture an image of the UBR box, providing insight to this incredibly tiny yet essential part of our bodies' chemical mechanics.


Aside from representing a major advance in our understanding of the life cycle of proteins, the research has important repercussions for Johanson-Blizzard syndrome, a rare disease that causes deformations and mental retardation. This syndrome is caused by a mutation in the UBR box that causes it to lose an essential zinc atom. Better understanding of the structure of the UBR box may help researchers develop treatments for this syndrome.


The research was published in Nature Structural & Molecular Biology and received funding from the Canadian Institutes of Health Research.


Source: McGill University

Gene Therapy Could Save Kids With Rare Metabolic Disorder From A Lifetime Of Eating Cornstarch

A gene therapy treatment that restores a missing liver enzyme in test animals could provide a cure for a rare metabolic disorder in humans, according to Duke University Medical Center researchers.



People born with the disorder, called glycogen storage disease type 1a (GSD-1a), can't make an enzyme that helps the liver store and release glucose, the sugar that all cells use for energy. Without treatment, their blood sugar levels drop dangerously low, causing seizures and organ damage. Eating raw cornstarch, a slowly digested carbohydrate, and avoiding dietary sugar can help people with GSD-1a maintain their glucose levels. However, even a special diet does not prevent the eventual liver damage that results from the absent enzyme, and many adults with the disease develop liver and kidney failure or liver cancer. With treatment, most people with GSD-1a have a relatively normal lifespan



The gene therapy developed at Duke would give liver cells the correct genetic code for manufacturing the enzyme. A modified virus transfers the enzyme genes by infecting liver cells. The virus is not linked to any known human disease, and cannot copy itself and spread to other people, said medical geneticist Dwight Koeberl, M.D., Ph.D., lead study author and an associate professor in the Department of Pediatrics.



The research involved creating a virus so focused on targeting liver cells that only a tiny amount is needed for treatment, minimizing potential side effects. Showing that the virus is safe and effective in small doses is an important step in bringing the treatment to clinical trials in humans.



The gene therapy replaced the missing enzyme in the liver to fully normal levels, and protected both mice and dogs with the disease from low blood glucose for up to a year. "No one has fully corrected the enzyme that produces glucose in the liver before. We think we can correct every cell in the liver," Koeberl said.



The results appear in the March 11 2008 issue of the journal Molecular Therapy. The research was funded by the Children's Fund for GSD Research, the Association for Glycogen Storage Disease and the Duke Children's Miracle Network. Dr. Emory and Mrs. Mary Chapman, and Dr. and Mrs. John Kelly, families of a child with GSD-Ia, also provided support.



The researchers tested the technique on mice bred without the genetic code to make the enzyme, as well as young dogs with a naturally-occurring canine form of glycogen storage disease. The original genetic carrier, a Maltese, was identified by a Georgia breeder, and veterinarians at North Carolina State University College of Veterinary Medicine have worked with Duke to maintain a population of dogs with the disease since the mid-1990s.



The success of the new treatment makes the therapy worth testing in long-term animal studies, Koeberl said. "This is a step along the way toward developing a curative therapy for our patients," he said. The key is finding funding for a years-long trial. "There are not a lot of companies developing treatments for rare diseases," he added.



GSD-Ia occurs in about one of every 100,000 births in the U.S. Duke is treating about 100 patients with the disease.



A long-term study would demonstrate whether gene therapy can prevent complications such as kidney failure and liver cancer, which develop even if people strictly control their diet and blood sugar levels. Other problems associated with the disease include growth restriction, high blood pressure, pancreatitis and persistent hypoglycemia.



"There are definite well-documented limitations to the dietary therapy. People can't just follow a diet and count on living full, healthy lives," Koeberl said.



Lengthy trials are also necessary because the corrected genes don't transfer when liver cells divide and copy themselves. However, the slow rate at which liver cells divide means the treatment may be effective for many years, with only a few boosters needed during an individual's lifetime, Koeberl said.







Study co-authors include Baodong Sun, Songtao Li, Danny Benjamin Jr., Steven Hillman, Andrew Bird, Priya Kishnani and Y.T. Chen, all of Duke; Carlos Pinto, Daniel Kozink, Talmage Brown, Amanda Demaster and Meghan A. Kruse, all of North Carolina State University; Valerie Vaughn at the University of Michigan Medical School; and Mark Jackson at the University of Glasgow, Scotland.



Source: Debbe Geiger


Duke University Medical Center

How Molecules Escape From The Nucleus: Key Advance In Using Microscopy To Reveal Secrets Of Living Cells

By constructing a microscope apparatus that achieves resolution never before possible in living cells, researchers at Albert Einstein College of Medicine of Yeshiva University have illuminated the molecular interactions that occur during one of the most important "trips" in all of biology: the journey of individual messenger Ribonucleic acid (RNA) molecules from the nucleus into the cytoplasm (the area between the nucleus and cell membrane) so that proteins can be made. The results, published in the online edition of Nature, mark a major advance in the use of microscopes for scientific investigation (microscopy). The findings could lead to treatments for disorders such as myotonic dystrophy in which messenger RNA gets stuck inside the nucleus of cells.



Robert Singer, Ph.D., professor and co-chair of anatomy and structural biology, professor of cell biology and neuroscience and co-director of the Gruss-Lipper Biophotonics Center at Einstein, is the study's senior author. His co-author, David GrГјnwald, is at the Kavli Institute of Nanoscience at Delft University of Technology, The Netherlands. Prior to their work, the limit of microscopy resolution was 200 nanometers (billionths of a meter), meaning that molecules closer than that could not be distinguished as separate entities in living cells. In this paper, the researchers improved that resolution limit by 10 fold, successfully differentiating molecules only 20 nanometers apart.



Protein synthesis is arguably the most important of all cellular processes. The instructions for making proteins are encoded in the Deoxyribonucleic acid (DNA) of genes, which reside on chromosomes in the nucleus of a cell. In protein synthesis, DNA instructions of a gene are transcribed, or copied, onto messenger RNA; these molecules of messenger RNA must then travel out of the nucleus and into the cytoplasm, where amino acids are linked together to form the specified proteins.



Molecules shuttling between the nucleus and cytoplasm are known to pass through protein complexes called nuclear pores. After tagging messenger RNA molecules with a yellow fluorescent protein (which appears green in the accompanying image) and tagging the nuclear pore with a red fluorescent protein, the researchers used high-speed cameras to film messenger RNA molecules as they traveled across the pores. The Nature paper reveals the dynamic and surprising mechanism by which nuclear pores "translocate" messenger RNA molecules from the nucleus into the cytoplasm: this is the first time their pore transport has been seen in living cells in real time.



"Up until now, we'd really had no idea how messenger RNA travels through nuclear pores," said Dr. Singer. "Researchers intuitively thought that the squeezing of these molecules through a narrow channel such as the nuclear pore would be the slow part of the translocation process. But to our surprise, we observed that messenger RNA molecules pass rapidly through the nuclear pores, and that the slow events were docking on the nuclear side and then waiting for release into the cytoplasm."
















More specifically, Dr. Singer found that single messenger RNA molecules arrive at the nuclear pore and wait for 80 milliseconds (80 thousandths of a second) to enter; they then pass through the pore breathtakingly fast - in just 5 milliseconds; finally, the molecules wait on the other side of the pore for another 80 milliseconds before being released into the cytoplasm.



The waiting periods observed in this study, and the observation that 10 percent of messenger RNA molecules sit for seconds at nuclear pores without gaining entry, suggest that messenger RNA could be screened for quality at this point.



"Researchers have speculated that messenger RNA molecules that are defective in some way, perhaps because the genes they're derived from are mutated, may be inspected and destroyed before getting into the cytoplasm or a short time later, and the question has been, 'Where might that surveillance be happening?'," said Dr. Singer. "So we're wondering if those messenger RNA molecules that couldn't get through the nuclear pores were subjected to a quality control mechanism that didn't give them a clean bill of health for entry."



In previous research, Dr. Singer studied myotonic dystrophy, a severe inherited disorder marked by wasting of the muscles and caused by a mutation involving repeated DNA sequences of three nucleotides. Dr. Singer found that in the cells of people with myotonic dystrophy, messenger RNA gets stuck in the nucleus and can't enter the cytoplasm. "By understanding how messenger RNA exits the nucleus, we may be able to develop treatments for myotonic dystrophy and other disorders in which messenger RNA transport is blocked," he said.



The paper:
"In Vivo Imaging of Labelled Endogenous ОІ-actin mRNA during Nucleocytoplasmic Transport," was published in the September 15 online edition of Nature.



Source:

Kim Newman

Albert Einstein College of Medicine