SUNDAY - October 14, 2007----------------------------------------News Archive/Return to Today's News Alerts

Understanding Genomic Changes that Created Modern Humans.

Researchers have answered a genomic question: Which of the thousands of long stretches of DNA in the human genome came first? And which are the duplicates?

The work marks a significant step towards understanding what genomic changes paved the way for modern humans, when these duplications occurred and what the associated costs are - in terms of susceptibility to disease-causing mutations.

Genomes have a remarkable ability to copy a long stretch of DNA from one chromosome and insert it into another region of the genome. The resulting chunks of repeated DNA - called "segmental duplications" - hold many evolutionary secrets and uncovering them is a difficult biological and computational challenge with implications in both medicine and understanding evolution.

The researchers tracked down the ancestral origin of more than two thirds of human long DNA duplications.

Discoveries:

One - that specific regions of the human genome had elevated rates of duplication activity at varying times in recent genomic history, and not a continuously smooth duplication process over evolutionary time;

Two - a large fraction of recent duplications centers around a smaller subset of "core duplicons" or short segments of DNA that form duplications. These cores are focal points of human gene/transcript innovations.

Not all of the duplications in the human genome are created equally. The core duplicons appear to be responsible for recent genetic innovations in the human genome. Including inheritable diseases.

The authors uncovered 14 such core duplicons.

Published October 8, 2007 in Nature Genetics.


Folding - The Mechanics Behind Both Heart & Brain Development.

Folding is extremely important in human brain development. Some of the worst neurological problems - schizophrenia, autism and lissenchephaly (smoothness of the cortex, found with severe retardation) are associated with abnormal brain folding.

Folding is generally what makes higher mammals smart. Albert Einstein had an abnormally folded brain that resulted in his genius. Certain folds in his brain were absent, which might have allowed the area associated with mathematical reasoning to become larger than normal.

Larry A.Taber, Ph.D., is the Dennis and Barbara Kessler Professor of Biomedical Engineering, and Phillip Bayly, Ph.D., Hughes Professor of Mechanical Engineering, at Washington University in St. Louis, are examining mechanical and developmental processes that occur in the folding of the brain's surface, or cortex, giving higher mammalian brains more surface area - hence more intellectual capacity.

The heart and the brain both begin as simple tubes that each loop and fold into totally unique structures.

Looping is a key phenomenon in the early embryo where the tubular heart bends and rotates in precise rotations. Taber has found that the processes of bending and rotation in the embryonic heart are driven by at least two different mechanical forces.

David Van Essen, Ph.D., the Edison Professor of Neurobiology and head of the School of Medicine's Department of Anatomy and Neurobiology, has a theory that tension in axons is the driving force of folding.

"There are only a handful of processes that cells use to create shape and form in the embryo. Developing brain and heart cells have the same basic tool set but somehow they integrate them in different ways. We're concerned primarily with the mechanics of how these organs are constructed." says Taber.

This research will ultimately help us understand the role of physics and mechanics in normal development of the heart and brain. With this information, we will be able to understand the genesis of defects in these most vital organs.


Presented September 27, 2007 at the at the Biomedical Engineering Society Annual Meeting.


In Biology, Polarization is a Good Thing.

Using its own molecular compass, an individual cell in a complex organism knows which way is up or down - apical-basal polarity.

Knowing up from down is essential for a cell in order to perform it's designated tasks. Now it appears that the same compass also defines the direction of cells when they must migrate from back to front. These are the conclusions of a recent study by scientists Michiel Pegtel and John Collard from the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AVL) in the Netherlands.

Many cell types acquire asymmetry for their biological function. Yeast cells, worms, mice and men all use the same cellular compass, made up of a combination of protein complexes essential for spatial orientation. The Par-Tiam1 polarity complex is a crucial component of the compass. Tiam1, early on was identified as a gene that could influence the dissemination of tumour cells.

Now it appears that the Par-Tiam1 complex also controls front-rear orientation of the cell. This way, cells that leave their brethren cells behind after detaching know how to find their way while migrating away. Collard and colleagues showed that mouse skin cells have a functional compass which allows them to migrate in a straight line toward their target. The cells persistently move forward like a caterpillar, continuously expanding and retracting in one direction. But when the Par-Tiam1 complex is disrupted or shut-down, the cells migrate aimlessly in random direction.

Pegtel & Collard: "It is becoming clear that polarity of cells is crucial for embryonic development and function of many biological processes in humans and lower organisms alike. It guides immune cells to sites of infection and directs the organization of the neuronal network. But at the same time, it also prevents detachment of adherent cells; we were very surprised that one protein complex regulates such seemingly opposing tasks". This could explain how Tiam1 is able both to promote and prevent metastasis in different tumours

Published October 9, 2007 in Current Biology.

Ugly Duckling Mole Rats Might Hold Key to Long Life.

The naked mole rat is certainly not one of nature's cuddliest species. These small rodents are hairless, wrinkled, blind and buck-toothed. Stan Braude, Ph.D., lecturer in biology in Arts & Sciences at Washington University in St. Louis, however, is attracted to these animals and has been studying them for over 25 years, with about 20 of those years being in the field in Kenya.

A key component in the aging of any species is oxidative damage, where the cells accrue damage from poisons, environmental toxins and other effects throughout life. In such a long-lived rodent, it was thought that naked mole rats had a very efficient way of repairing oxidative damage. This wasn't the case, however, and current theory points to the strange metabolism of this hairless wonder.

Naked mole rats appear to deal with oxidative stress in pulses, they have the ability to essentially shut down their metabolism when there are hardships, such as lack of food. "Another way to think of it is, their gross life span might be 28 years, but their metabolism is going in these short bursts so maybe the net damage is only 3 or 4 years of net use," said Braude. "They're living their life in pulses."

"If we understand how these different species do it, then the next step is to figure out how we can get those benefits with either drug treatments or changing diet or changing lifestyle," says Braude. "It's nice that we have a mammal that is also [living long], so there' s hope that it's not just a bird and reptile thing."

Monograph To Be Published, online the Washington University in St. Louis News and Information.


SATURDAY - October 13, 2007----------------------------------------News Archive/Return to Today's News Alerts

Stem Cell Nuclei Are Soft 'Hard Drives,' Study Finds.

Biophysicists at the University of Pennsylvania have discovered that the nuclei of human stem cells are particularly soft and flexible, rather than hard, making it easier for stem cells to migrate through the body and to adopt different shapes, but ultimately to put human genes in the correct nuclear "sector" for proper access and expression.

Researchers pulled cell nuclei into microscopic glass tubes under controlled pressures and visualized the shear of the DNA and associated proteins by fluorescence microscopy. The study showed that nuclei in human embryonic stem cells were the most deformable, followed by hematopoietic stem cells, HSCs, that generate a wide range of blood and tissue cells. Both types of stem cells lack lamins A and C, two filamentous proteins that interact to stabilize the inner lining of the nucleus of most tissue cells. Lamins A and C stiffen cell nuclei and are expressed in cells only after gastrulation, when most stem cells generate the specific tissues of complex organisms.

The fluid-like character of the nucleus is shown to be set largely by the DNA and the DNA-attached proteins that form chromatin. The extent of deformation of the nucleus is further modulated by the lamina.

To verify that lamin proteins were responsible for nuclear stiffness, the authors created a line of epithelial cells in which lamin filaments had been almost eliminated. Once as stiff as any other differentiated tissue cell derived from stem cells, the cell became as pliable as HSCs.
"Controlling structural proteins within the nucleus might lead to new means for controlling genomic regulatory factors and for generating stem cells from adult tissue cells," J. David Pajerowski, lead author and a graduate student in Penn's School of Engineering and Applied Science, said.

Researchers also found that over time nuclear deformations in stem cells and hematopoietic cells became resistant to returning to their original shape, which provides evidence of plastic flow similar to that of wet clay in the hands of a sculptor. Continued application of force eventually pulled nuclei into irreversible forms in which genes were re-arranged and massaged into new nuclear locations. Researchers literally visualized the flow of chromatin, the structure that carries DNA, and found irreversible distortions occurring on a timescale of minutes, a long time compared to many other cell processes but short compared to the lifetimes of nuclei in our tissue cells.

Published October 2, 2007 in Proceedings of the National Academy of Sciences PNAS.

Maternal Mortality Ratio Falling Too Slowly to Meet WHO Goal.

The world’s maternal mortality ratio (the number of maternal deaths per 100 000 live births) is declining too slowly to meet Millennium Development Goal (MDG) 5, which aims to reduce the number of women who die in pregnancy and childbirth by three-quarters by 2015.

While an annual decline of 5.5% in maternal mortality ratios between 1990 and 2015 is required to achieve MDG 5, figures released today by WHO, UNICEF, UNFPA and the World Bank show an annual decline of less than 1%. In 2005, 536 000 women died of maternal causes, compared to 576 000 in 1990. 99% of these deaths occurred in developing countries.

The maternal mortality ratio in 2005 was highest in developing regions, with 450 maternal deaths per 100 000 live births, in stark contrast to nine in developed regions and 51 in the countries of the Commonwealth of Independent States (CIS). Moreover, the small drop in the global maternal mortality ratio reflects mainly the declines that have taken place in countries with relatively low levels of maternal mortality. Countries with the highest initial levels of mortality have made virtually no progress over the past 15 years.

The maternal mortality ratio indicates the risk of death a woman faces with each pregnancy. In settings with high fertility, such as sub-Saharan Africa, women face this risk many times in their lifetime.

Announced online October 12, 2007 by the World Health Organization (WHO).



First Asian Genome Sequenced.

Scientists in Beijing announced yesterday that they have sequenced the diploid genome of a Han Chinese individual. The announcement comes on the heels of the completion of Craig Venter’s and James Watson’s personal genomes earlier this year.

Although humans share most of their genome with one another, slight genetic differences may correspond to variation in their susceptibility to diseases and responses to therapeutics.

Han Chinese represent 92% of China’s population and are the largest ethnic group in the world. People in the same ethnic groups can share genetic characteristics that may be useful for targeting future drug treatments.

The Beijing group plans to sequence more individuals in the Asian population so that they can begin to correlate genetic variation with underlying disease. Hudson believes that this is a step in the right direction. “To really understand the spectrum of variation, we’re going to need thousands of sequences, not one or two per population.”

Published September 4, 2007 in PubMed.

Study Finds People Are Programmed to Love Chocolate.

For the first time, scientists have linked the all-too-human preference for a food — chocolate — to a specific, chemical
signature that may be programmed into the metabolic
system and is detectable by laboratory tests. The signature reads ‘chocolate lover’ in some people and indifference to the popular sweet in others, the researchers say.

The study by Swiss and British scientists breaks new ground in a rapidly emerging field that may eventually classify individuals on the basis of their metabolic type, or metabotype, which can ultimately be used to design healthier diets that are customized to an individual’s needs.

Women were not included in the current study in order to avoid any metabolic variations linked to the menstrual cycle, which has been shown in studies by others to influence metabolic differences, Kochhar says. But the researchers plan to include women in future clinical trials on metabolic responses to chocolate to determine if there is a gender-specific response to the treat.

The research was funded by Nestlé.

PTo Be Published November 2, 2007, in the American Chemical Society’s Journal of Proteome Research.


Mothers Who Give Birth With Severe Obstetric Complications Have Higher Risk Of Mental Health Problems And Death.

A mother who gives birth and has severe obstetric complications is at a significantly greater risk of experiencing mental health problems and death, compare to women who give birth without complications. It is important that resources are channeled adequately to make sure that women with severe obstetric complications (SOCs) receive satisfactory care before and after they are discharged from hospital.

Dr Véronique Filippi, London School of Hygiene and Tropical Medicine, UK and team carried out a study of 1,014 women in hospitals in Burkina Faso. 337 of them had SOCs. 199 of them gave birth to a living baby, 64 lost their baby before completion of pregnancy, 74 of them lost their child shortly after birth. Each woman with a SOC was compared to two unmatched control women whose deliveries had no complications - they were all from the same hospital. The researchers followed them all up one year later.

Here are the researchers' findings:

-- Six women in the SOC group died within a year
-- Nobody died in the control group
-- The babies of mothers in the SOC group were 4.5 times more likely to die within twelve months, compared to the babies of the control mothers
-- The chances of experiencing depression within three months was 82% higher among the SOC mothers
-- The SOC mothers were twice as likely to have suicidal thoughts during the twelve months compared to the control mothers
-- 50% more SOC mothers reported that the pregnancy had a negative impact on their lives (within three months of the event) .

The researchers concluded that more effort is needed to reduce maternal mortality and improve maternal health. This could start by targeting women with SOCs for social and financial interventions.


Published October 12, 2007 in the Lancet.

Related material Medscape Today: Sexual Trauma and Pregnancy: A Conceptual Framework.




FRIDAY - October 12, 2007----------------------------------------News Archive/Return to Today's News Alerts

Drug Makers Withdraw Cough, Cold Meds for Infants.

Leading drug makers announced a voluntary withdrawal Thursday of oral cough and cold medicines marketed for use in infants. The move affects only "infant" oral medicines, not those intended and labeled for use in children age 2 and older. And it comes as U.S. regulators review the products' safety, following reports of dozens of deaths since 1969.

Last month, U.S. health experts urged the federal Food and Drug Administration to consider banning the sale of over-the-counter cough and cold medicines for young children. The recommendation, from FDA safety officials, would apply to decongestant use in children under 2, and antihistamines in those younger than 6, according to FDA documents. An FDA advisory panel is scheduled to consider the recommendation during a meeting on Oct. 18 and 19, and will then offer an opinion to the full agency. The FDA typically follows the recommendations of its advisory boards but is not required to do so.

'Dr. Daniel Rauch, director of New York University Medical Center's Pediatric Hospitalist Program, said the manufacturers' decision to withdraw the drugs "confirms multiple years of evidence that these medications don't work and are potentially dangerous. When parents think these medications will work, and they don't, the natural response is to give an infant more medication, leading to potentially dangerous side effects. Kids get sick, and parents need to realize it will pass."

According to the CHPA, the cough and cold medicines that are being withdrawn are:

Dimetapp(R) Decongestant Plus Cough Infant Drops,
Dimetapp(R) Decongestant Infant Drops,
Little Colds(R) Decongestant Plus Cough,
Little Colds(R) Multi-Symptom Cold Formula,
PEDIACARE(R) Infant Drops Decongestant (containing pseudoephedrine),
PEDIACARE(R) Infant Drops Decongestant & Cough (containing pseudoephedrine),
PEDIACARE(R) Infant Dropper Decongestant (containing phenylephrine),
PEDIACARE(R) Infant Dropper Long-Acting Cough,
PEDIACARE(R) Infant Dropper Decongestant & Cough (containing phenylephrine),
Robitussin(R) Infant Cough DM Drops,
Triaminic(R) Infant & Toddler Thin Strips(R) Decongestant,
Triaminic(R) Infant & Toddler Thin Strips(R) Decongestant Plus Cough,
TYLENOL(R) Concentrated Infants' Drops Plus Cold,
TYLENOL(R) Concentrated Infants' Drops Plus Cold & Cough.

Published October 11, 2007 in Consumer Healthcare Products Association.


UCSD Physicians Breathe Life
Into Cutting-Edge Stem Cell Procedure.

Patients living with Myasthenia Gravis (MG) may breathe easier thanks to a rare bone marrow transplant procedure performed at The Bone Marrow Transplant Program at University of California, San Diego Medical Center, the only program in the western United States that has attempted this procedure.

Myasthenia Gravis (MG) is a rare neuromuscular autoimmune disease where the body’s immune system, which normally protects the body, mistakenly attacks itself. The transmission of nerve impulses to muscles is interrupted, which ultimately prevents the muscles from contracting. Without the proper nerve impulses, muscles that control breathing can’t function.

This new procedure reprograms the patient’s stem cells, destroying them with chemotherapy, before re-introducing purified blood-forming stem cells. After the transplant, the modified stem cells build new bone marrow, renewing the immune system with correct signaling, renewing the immune system with cells that don’t attack the body.

After the transplant, patients must take antibiotics to protect them from infection. They cannot go to crowded places and must follow special diet requirements until the immune system is fully recovered, which takes about three months.

Announced online October 9, 2007 by the University of California San Diego.


Mathematicians Help Unlock Secrets of the Immune System.

A group of scientists, led by mathematicians, has taken on the challenge of building a common model of immune responses. Their work will radically improve our understanding of the human immune system by allowing all the scientific disciplines working on it to have a common reference point and language. The mathematicians, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), will investigate how the different cellular components of the immune system work together and devise a theoretical and computational model that can be used by immunologists, mathematicians, computer scientists, physicists and engineers.

The immune system is one of the most fascinating and complex systems in the human body and scientists still do not fully understand how it works. Immunology has traditionally been a qualitative science, describing the cellular and molecular components of the immune system and their functions. However, to advance our understanding of how the body fights disease there is a pressing need to better understand how the components work together as a whole and provide this information in a quantitative format which can be accessed by the entire scientific community.

“Mathematical immunology is maturing into a discipline where modelling helps everyone to interpret data and resolve controversies. Most importantly, it suggests novel experiments allowing for better and more quantitative interpretations.” says Dr Carmen Molína-Paris, network co-ordinator and researcher at the University of Leeds.

Published October 10, 2007 in the quarterly journal of the Biotechnology and Biological Sciences Research Council, (BBSRC).


Evidence Links Stress Caused by September 11 Disaster With Low Birth Weights.

Researchers have found evidence of an increase in low birth weights among babies born in and around New York City in the weeks and months after the terrorist attacks on the World Trade Center. Writing in the journal Human Reproduction [1], they suggest that stress may have contributed to the effect.

Professor Brenda Eskenazi and colleagues studied data from birth certificates of 1,660,401 babies born in New York between January 1996 and December 2002. They divided the babies into those born in New York City (NYC) – whose mothers would, therefore, have been living closest to the disaster zone – and those born in “upstate” New York, which they defined as anyone living outside NYC, including Nassau, Suffolk and Westchester Counties.

Professor Brenda Eskenazi concluded: “We have thoroughly reviewed the literature on preterm birth and low birth weight, and there is, thus far, a paucity of hard data to support the anecdotal information that women are more likely to have a spontaneous preterm birth immediately after a stressful event. Although we can't say for sure that our findings of increased births weighing less than 2,000g immediately after the events of September 11th are directly attributable to preterm delivery, we think that our results support this hypothesis and the paper supports the idea that stressful community events can impact the health of the foetus.”

Published October 26, 2007, by the European Society for Human Reproduction and Embryology.


Long-Life Gene Might Help Lower Cholesterol.

MIT researchers have discovered a link between a gene believed to promote long lifespan and a pathway that flushes cholesterol from the body. The finding could help researchers create drugs that lower the risk of diseases associated with high cholesterol, including atherosclerosis (clogged arteries) and Alzheimer's disease.

The study focused on a gene called SIRT1, which the researchers found prevents cholesterol buildup by activating a cellular pathway that expels cholesterol from the body via HDL (high density lipoprotein or "good cholesterol").

Drugs that enhance the effects of SIRT1 could lower the risk of cholesterol-related diseases, said Leonard Guarente, MIT professor of biology and senior author of a paper on the work. Potential drugs could be based on polyphenols, which are found in red wine and have been shown to enhance SIRT1. However, the quantities naturally found in red wine are not large enough to have a significant impact on cholesterol levels.

"SIRT1 is an important mediator of cholesterol efflux, and as such it's predicted to play a role in the development of age-associated diseases where cholesterol is a contributing factor. If you had a drug that could increase expression of SIRT1, that could replicate the effects of calorie restriction," Guarente said. "This is not going to replace the need for a healthy lifestyle, but it's a supplement that could potentially make you healthier."


Published October 12, 2007 in the journal Molecular Cell.




THURSDAY - October 11, 2007----------------------------------------News Archive/Return to Today's News Alerts

Women With High Or Increasing Blood Pressure Are Up To Three Times More Likely To Develop Diabetes.

One of the largest studies to investigate the relationship between blood pressure and type 2 diabetes has found that women who have high blood pressure levels are three times more likely to develop diabetes than women with low blood pressure levels. This effect was independent of body mass index and other conditions that are known to predispose people to cardiovascular disease and diabetes.

Researchers from the Brigham and Women's Hospital, Harvard Medical School and the Harvard School of Public Health, USA, followed over 38,000 female health professionals for ten years. At the start of the study in 1993, all the women were free of diabetes and cardiovascular disease. Follow-up continued to the end of March 2004, at which point data were nearly 100% complete (97.2% for morbidity and 99.4% for mortality).

'We found that obesity was also a strong and independent risk factor for the development of type 2 diabetes. However, statistical analyses showed that the relationship between blood pressure and the onset of type 2 diabetes was similar among women who were normal weight, overweight or obese. There was a three-fold increase in risk from the lowest to the highest BP category within all three weight categories. This analysis showed that the association between blood pressure and diabetes was not explained by weight alone." said lead author, Dr David Conen, a cardiologist and research fellow.

The authors suggest a possible mechanism for the relation between BP and diabetes may be endothelial dysfunction - a dysfunction of the normal biochemical processes carried out by the layer of cells that line the inner surfaces of blood vessels. 'It may be a precursor of both hypertension and diabetes,' said Dr Conen. 'Thus, the progression of endothelial dysfunction may cause worsening of both BP and blood glucose. This is in line with the fact that both BP and blood glucose occur together as part of the metabolic syndrome.'


Published October 8, 2007 in The European Heart Journal.

UCSD Physicians Breathe Life Into Cutting-Edge Stem Cell Procedure.

Patients living with Myasthenia Gravis (MG) may breathe easier thanks to a rare bone marrow transplant procedure performed at The Bone Marrow Transplant Program at University of California, San Diego Medical Center, the only program in the western United States that has attempted this procedure

Myasthenia Gravis (MG) is a rare neuromuscular autoimmune disease where the body’s immune system, which normally protects the body, mistakenly attacks itself. The transmission of nerve impulses to muscles is interrupted, which ultimately prevents the muscles from contracting. Without the proper nerve impulses, muscles that control breathing can’t function.

This new procedure reprograms the patient’s stem cells, destroying them with chemotherapy, before re-introducing purified blood-forming stem cells. After the transplant, the modified stem cells build new bone marrow, renewing the immune system with correct signaling, renewing the immune system with cells that don’t attack the body.

After the transplant, patients must take antibiotics to protect them from infection. They cannot go to crowded places and must follow special diet requirements until the immune system is fully recovered, which takes about three months.


Announced online October 9, 2007 by the University of California San Diego.


Oct4 Maintains Embryonic Stem Cells' Pluripotency - But Only Before Implantation.

The protein Oct4 plays a major role in embryonic stem cells, acting as a master regulator of the genes that keep the cells in an undifferentiated state. Unsurprisingly, researchers studying adult stem cells have long suspected that Oct4 also is critical in allowing these cells to remain undifferentiated. Indeed, more than 50 studies have reported finding Oct4 activity in adult stem cells.

But those findings are misleading, according to research in the lab of Whitehead Member Rudolf Jaenisch. In a paper, postdoctoral fellow Christopher Lengner has shown that Oct4 is not required to maintain mouse adult stem cells in their undifferentiated state, and that adult tissues function normally in the absence of Oct4. Furthermore, using three independent detection methods in several tissue types in which Oct4-positive adult stem cells had been reported, Lengner found either no trace of Oct4, or so little Oct4 as to be indistinguishable from background readings.

Oct4 is essential in maintaining the pluripotency of embryonic stem cells, but only for a short time before the embryo implants in the uterine wall. After implantation Oct4 is turned off, and the cells differentiate into all of the 200-plus cell types in the body. "We have convincingly shown that Oct4 has no role in adult stem cells," says Lengner.”

Published October 10, 2007 in the journal Cell Stem Cells.

Tumor Metastasis Triggered By An Overabundance Of A Single MicroRNA.

It has been confirmed that microRNAs can cause tumors to metastasize. These tiny molecules fine-tune protein production and play a powerful role in biological processes ranging from development to aging. Now scientists have proved that they can prompt otherwise sedentary cancer cells to move and invade other tissues.

MicroRNAs typically disrupt protein production by binding to the messenger RNAs that copy DNA instructions for proteins and carry them to "translators." at the Whitehead Institute for Biomedical Research (Cambridge, Mass.), Robert Weinberg's postdoctoral fellow Li Ma used a program developed in the lab to search for the target of microRNA-10b. She identified several candidates, including the messenger RNA for a gene called HoxD10.

Generally involved in development, Hox proteins control many genes active in an embryo. Some Hox proteins have also been implicated in cancer. HoxD10, for example, can block the expression of genes required for cancer cells to move -- essentially applying the brakes to a migration process.

To test whether she had removed the brakes during her experiment, awakening the dormant migration process, Ma boosted the level of HoxD10 in the cancer cells with artificially high levels of microRNA-10b. The cells lost their newly acquired abilities to move and invade.

"I was able to fully reverse microRNA-10b induced migration and invasion, suggesting that HoxD10 is indeed a functional target," Ma explains.

"During normal development, this microRNA probably enables cells to move from one part of the embryo to another," adds Weinberg. "Its original function has been co-opted by carcinoma cells.".

Published September 26, 2007, issue of the journal Nature.


Bacteria in Newborn Airways May Raise Asthma Risk.

Newborns who harbor certain types of bacteria in their throats, including Streptococcus pneumoniae, a common cause of pneumonia, and Haemophilus influenzae, which causes upper respiratory infections, are at increased risk for developing recurrent wheeze or asthma early in life, new research shows.

“This finding "opens new perspectives for the understanding and prediction of recurrent wheeze and asthma in young children," lead author Dr. Hans Bisgaard, from Copenhagen University Hospital in Denmark, and colleagues conclude in their report in The New England Journal of Medicine for October 11.

The researchers assessed the development of recurrent wheeze and asthma in 321 newborns who had throat cultures taken at 1 month of age and who were then followed through 5 years of age. Twenty-one percent of infants were colonized with S. pneumoniae, H. influenzae, another type of bacteria called M. catarrhalis, or a combination of these bugs and this finding more than doubled the risk of persistent wheeze, wheeze flare-up, and hospitalization for wheeze.

The prevalence of asthma at age 5 was significantly increased in the children who harbored these organisms as newborns compared with children who did not (33 percent versus 10 percent), the investigators report. In a related editorial, Dr. Erika von Mutius, from University Children's Hospital in Munich, Germany, comments that these findings may be interpreted to suggest that the presence and growth of bacteria in the throat in the first 4 weeks of life "indicates a defective innate immune response very early in life, which promotes the development of asthma."

Published October 11, 2007 in The New England Journal of Medicine.

WEDNESDAY - October 10, 2007----------------------------------------News Archive/Return to Today's News Alerts

Blood Vessels Grown From Patient’s Skin.

From a snippet of a patient’s skin, researchers have grown blood vessels in a laboratory and then implanted them to restore blood flow around the patient’s damaged arteries and veins.

It is the first time blood vessels created entirely from a patient’s own tissues have been used for this purpose. Cytograft Tissue Engineering of Novato, Calif., made the vessels, in a process that takes six to nine months. Because they are derived from patients’ own cells, they eliminate the need for antirejection drugs. And because they are devoid of any synthetic materials or a scaffolding, they avoid complications from inflammatory reactions.

Doctors in Argentina have performed the first human tests of the vessels on six patients, the team reported. Two additional implants have been performed since the report was submitted, said Dr. Todd N. McAllister of Cytograft.

The longest follow-up among these patients has been for 13 months. Cytograft says the vessels hold promise for patients with damaged blood vessels from diabetes, arteriosclerosis, birth defects and other problems. But monitoring for a much longer period will be needed before those uses could become standard, the team said.

Doctors not connected with the company agreed on the importance of the new technique. “A potential benefit may be for infants and children with congenital heart defects,” said Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco. Unlike grafts from cadavers, he added, “the Cytograft vessels should be able to grow as the child does.”

The skin biopsy takes about 15 minutes. Under local anesthesia, a doctor removes a piece of skin, including a strip of vein about an inch long, from the back of the hand or inner wrist. Then technicians use enzymes to extract fibroblast cells from the skin and endothelial cells from the inner lining of the vein. The cells are grown by the millions as sheets in a laboratory. The fibroblasts provide a mechanical backbone for the sheets that are peeled and rolled into a tube.

Although the vessel resembles a vein under the microscope, it has the mechanical strength of an artery, Dr. McAllister said. The technique allows the body over time to remodel the cells from a vein into a vessel with the elasticity of an artery.

Published October 8, 2007 in The New England Journal of Medicine - NEJM.

Which Came First, the Chicken Genome or the Egg Genome?

Which came first, the chicken genome or the egg genome? Or more accurately, which of the thousands of long stretches of repeated
DNA in the human genome came first? And which are the duplicates?

Genomes have a remarkable ability to copy a long stretch of DNA from
one chromosome and insert it into another region of the genome. The
resulting chunks of repeated DNA – called “segmental duplications” – hold many evolutionary secrets. To crack the duplication code and determine which of the DNA segments are originals (ancestral duplications) and which are copies (derivative duplications), the researchers used both algorithmic biology and comparative genomics.

"Identifying the original duplications is a prerequisite to understanding what makes the human genome unstable,” said Pavel Pevzner a UCSD computer science professor.

Over the years, Pevzner has applied the 250-year old algorithmic idea first proposed by 18th century mathematician Leonhard Euler (Euler adopted pi in 1737 making Archimedes' reintroduction of the concept standard) to a variety of problems and demonstrated that it works equally well for a set of seemingly unrelated biological problems including DNA fragment assembly, reconstructing snake venoms, and now dissecting the mosaic structure of segmental duplications.

The researchers plan to continue their exploration of evolution. “We want to figure out how the human genome evolved. In the future, we will combine what we know about the evolution within genomes with comparative genomics in order to extend our view of evolution,” said Pevzner.

Announced online October 7, 2007 at the journal Nature Genetics.


Alzheimer's Disease a Type 3 Form of Diabetes?

Research in the last few years has raised the possibility that Alzheimer's memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling - crucial for memory formation - would stop working in Alzheimer's disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer's removes insulin receptors from nerve cells, rendering those neurons insulin resistant. The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”

“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer's disease.”

Published October, 2007 in the journal FASEB, Federation of American Societies for Experimental Biology.

In the Battle Against Cancer, Husband/Wife Researchers
Find Hope in a Toxic Wasteland.

From death’s soup, the Stierles hope to coax life.

Death sits on the east side of Butte, Montana, in a 40-billion-gallon pit filled with corrosive water the color of a scab. On the opposite side sits the small laboratory of Don and Andrea Stierle, chemistry researchers at Montana Tech of the University of Montana, whose stacks of plastic Petri dishes are smeared with organisms pulled from the pit. Early tests indicate that some of those organisms may help produce the next generation of cancer drugs.

In two papers published recently in peer-reviewed organic chemistry journals, the Stierles reported finding two compounds that showed initial success in killing breast and ovarian cancer cells in lines maintained by the National Institutes of Health. “They’re finding lots of really neat stuff using people who don’t even have their bachelor’s degrees,” said Nicholas Oberlies, who directs the natural products laboratory at RTI International, a large nonprofit research center in North Carolina.

The Stierles won widespread recognition in the scientific community in the mid-1990s for discovering a fungus, native to mountaintops in the Pacific Northwest, that produces taxol, which is commonly used to fight breast and ovarian cancer. The fungus was found next to yew trees, which had long been the primary source of taxol.

The Stierles have turned down job offers from major universities that would have tripled their salaries. “We love Montana, and we love what we do,” said Ms. Stierle.

Published January 26, 2004, issue of the journal Organic Letters.

Enzyme’s Second Messenger Contributes to Cell Overgrowth.

Scientists at the University of California, San Diego (UCSD) School of Medicine have uncovered a novel pathway by which hormones - elevated in inflammation, cancer and cell injury - act on cells to stimulate their growth. Using a mouse model, they discovered that a new subtype of the phospholipase C (PLC) family of enzymes, called PLC-epsilon, has the unique ability to turn on a second and distinct signal that cells require to proliferate.

“In addition, and more surprisingly, we discovered that this enzyme is required for cell growth because it serves a second function when activated by hormones.” said Joan Heller Brown, Ph.D., professor and chair of the department of pharmacology at UCSD.

Many intracellular signaling proteins work as molecular “switches.” When a protein receives a signal, it is activated and passes the signal through to the cell, afterwhich it switches off until another signal is received. G-proteins are a commonly used switch, activated by the binding of guanine nucleotides.

PLC’s normal role is delivering signals from outside the cell to inside the cell by generating “second messengers” that tell cells to contract and secrete. But these signals alone are not enough to cause cells to increase their growth. Simona Citro, Ph.D., found that PLC-є uniquely activates a second and distinctly different signaling cascade. This second signal activates a Ras family of small G proteins associated with cell growth.

“In combination with the first set of signals, this can lead to cell proliferation and could contribute to inflammation or cancer if left unchecked,” said Citro. “PLC plays a critical role in physiological processes including heart function, cell secretion and blood pressure control, so one would not normally want to block its activity,” added Heller Brown. The UCSD researchers’ discovery may enable scientists to target this novel PLC isoform or inhibit only its second function, preventing pathological responses while leaving PLC’s critical positive role intact.

Published September 25, 2007 in Proceedings of the National Academy of Sciences (PNAS).

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Gene Targeting Scientists Win Nobel Prize in Medicine.

Two American scientists and a Briton won the 2007 Nobel Prize in medicine on Monday for groundbreaking discoveries that led to a powerful technique for manipulating mouse genes. The widely used process has helped scientists use mice to study heart disease, diabetes, cancer, cystic fibrosis and other diseases.

The prize is shared by Mario R. Capecchi, 70, of the University of Utah in Salt Lake City; Oliver Smithies, 82, a native of Britain now at University of North Carolina in Chapel Hill, and Sir Martin J. Evans, 66, of Cardiff University in Wales. The Nobel is a particularly striking achievement for Capecchi, (pronounced kuh-PEK'-ee). A native of Italy, he was separated from his mother at age 4 when she was taken to the Dachau concentration camp as a political prisoner during World War II.

For four years, Capecchi lived on the street or in orphanages, "and most of the time hungry," he recalled in a University of Utah publication in 1997. Malnutrition sent him to a hospital where his mother found him on his ninth birthday. Within two weeks they left for the United States, where he went to school for the first time, starting in third grade despite not knowing English.

The three scientists were honored for a technique called gene targeting, which lets scientists deactivate or modify particular genes in mice. That in turn lets them study how those genes affect health and disease. To use this technique, researchers introduce a genetic change into mouse embryonic stem cells. These cells are then injected into mouse embryos. The mice born from these embryos are bred with others, to produce offspring with altered genes. The first mice with genes manipulated in this way were announced in 1989. More than 10,000 different genes in mice have been studied with the technique, the Nobel committee said. That's about half the genes the rodents have.

The three scientists mostly worked separately, although they exchanged information about their research. Evans identified embryonic stem cells in mice, while the gene-targeting technique used on those cells came from work by Capecchi and Smithies.

Capecchi's work has uncovered the roles of genes involved in organ development in mammals, the committee said. Evans has developed strains of gene-altered mice to study cystic fibrosis, and Smithies has created strains to study such conditions as high blood pressure and heart disease.

Published October 8, 2007 by The Nobel Prize Organization.


US National Children's Study Takes Off.

The largest study of child and human health ever conducted in the United States is one step closer to full operation with the award of contracts to 22 new study centers to manage participant recruitment and data collection in 26 communities across the United States. Thursday's announcement of the new study centers for The National Children’s Study builds on the establishment of the first seven centers in 2005.

The National Children's Study will focus on a representative sample of 100,000 children from before birth to age 21. Researchers will gather data on children's genetic makeup and a number of biological, chemical, environmental, physical and psychosocial factors. The study seeks information to prevent and treat some of the nation's most pressing health problems, including autism, birth defects, diabetes, heart disease and obesity.

The study begins either prior to conception or in the first trimester of pregnancy.

"There are a lot of things that happen prior to birth that set the thermostat on how vulnerable you are to risk factors for diseases," says Louise Flick, DrPH, co-principal investigator and professor of nursing from Southern Illinois University Edwardsville School of Nursing. "We are studying children to age 21 because some of the exposures we suspect are important have consequences that take a lot time to develop."

Announced online October 8, 2007 at the The National Children's Study.

Vascular System Mimiced to Nourish Engineered Transplant Tissue.

One day soon, laboratories may grow synthetically engineered tissues such as muscle or cartilage needed for transplants. In a major step forward, Cornell University engineers describe in the journal Nature Materials a microvascular system they have developed that can nourish growing tissues.

The researchers have engineered tiny channels within a water-based gel that mimic a vascular system at the cellular scale and can supply oxygen, essential nutrients and growth factors to feed individual cells. The so-called gel scaffold can hold tens of millions of living cells per milliliter in a 3-D arrangement, such as in the shape of a knee meniscus, to create a template for tissue to form.

In theory, the system could accommodate many kinds of tissue.

Published October, 2007 in the journal Nature Materials.


How Stress Supercharges Learning.

Whether it's a hot stove or a snarling dog, an emotional encounter supercharges learning in a way that
indelibly imprints those experiences in memory. Now researchers have pinpointed a molecular pathway in the brain that underlies stress-induced learning enhancement. Their studies establish how the stress hormone norepinephrine boosts learning by strengthening connections between neurons.

The researchers said their studies also may aid understanding of the learning-enhancing effects of drugs such as methamphetamine, caffeine and nicotine. And the same biochemical mechanism might contribute to the addictive properties of cocaine and caffeine.

"It has long been known that when a person is afraid or scared, norepinephrine is released along with epinephrine, producing the fight-or-flight response throughout the body,” said Richard Huganir who with Roberto Malinow are the lead researchers. Malinow is at Cold Spring Harbor Laboratory, and Huganir is a Howard Hughes Medical Institute investigator at Johns Hopkins University School of Medicine. “And it was known that norepinephrine affects the brain, activating learning to enable those stressful memories to be recalled more readily. Now we have shown how norepinephrine activates that learning—by producing a critical biochemical priming effect on AMPA receptors during states of stress,” he said. “That priming induces migration of more receptors to the synapse, enhancing the strength of those synaptic connections.”

“Many people who study drug addiction believe that exposure to drugs such as cocaine rewires brain circuitry using similar LTP mechanisms. So, we can also use these mutant mice to test whether loss of AMPA receptor phosphorylation affects cocaine-induced behaviors and cocaine addiction,” said Huganir."

Published October 5, 2007, issue of the journal Cell.


Genes Influence People's Choices in Economics Game.
Traditionally, social scientists have been quite hesitant to acknowledge a role for genes in explaining economic behavior. But a study by David Cesarini, a Ph.D. student in MIT's Department of Economics, and by colleagues in Sweden indicates that there is a genetic component to people's perception of what is fair and what is unfair.

Cesarini looked at the ultimatum game, in which a proposer makes an offer to a responder on how to divide a sum of money. This offer is an ultimatum; if the responder rejects it, both parties receive nothing. Because rejections in the game entail a zero payoff for both parties, theories of narrow self-interest predict that any positive amount will be accepted by a responder. The intriguing finding in the laboratory is that responders routinely reject free money, presumably in order to punish proposers for offers perceived as unfair.

To study genetic influence in the game, Cesarini and colleagues took the unusual step of recruiting twins from the Swedish Twin Registry, and had them play the game under controlled circumstances. Because identical twins share the same genes but fraternal twins do not, the researchers were able to detect genetic influences by comparing the similarity with which identical and fraternal twins played the game.

The researchers' findings suggest that genetic influences account for as much as 40 percent of the variation in how people respond to unfair offers. In other words, identical twins were more likely to play with the same strategy than fraternal twins. "Compared to common environmental influences such as upbringing, genetic influences appear to be a much more important source of variation in how people play the game," Cesarini said..

Published October 1, 2007 in Proceedings of the National Academy of Sciences (PNAS).


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Higher Infection Rates for Babies in Pools.
Research in Germany linked higher infection risks, especially for
diarrhea, to babies who swam in pools during their first year of life.

However, the study found no increased risks for atopic diseases -
which is when the immune system is dysregulated, resulting in allergic inflammation.

"In this way, the study shows that allowing babies to swim is possibly not as harmless with regard to infections as has been presumed till now," study co-author, Dr. Joachim Heinrich, said in a statement. He leads the research unit environmental epidemiology at the GSF Institute for Epidemiology.

"The study looked at 2,191 babies who were re-examined at age 6. Besides keeping track of swimming-pool attendances during infancy, the researchers also used parental interviews to determine information about the children’s health and lifestyle.

Those babies that had not taken part in swimming as infants showed a much lower infection rate, especially in the cases of diarrhea and otitis media in the first year of life.

Published October, 2007 in International Journal of Hygiene and Environmental Health.

Cord Blood Service to Debut.
"Women giving birth in Pittsburgh will have the option to make an altruistic decision with life-saving potential starting today. The region's first public-private umbilical cord blood collection service is being offered through Magee-Womens Hospital in Oakland, officials are expected to announce this morning.

""The clinical uses of umbilical stem cells have become increasingly possible for treatments for patients with a variety of disorders, whether they be malignancies from leukemia or sickle-cell anemia," said Dr. Dennis English, vice president of medical affairs at Magee. Cord blood is the blood that remains in the umbilical cord and placenta after birth. It is rich in stem cells, which can be coaxed into growing into different types of tissue or blood cells. It has been used successfully to treat about 70 diseases, and researchers say they believe it has potential to treat more, such as Parkinson's and Alzheimer'.

Obstetricians in Western Pennsylvania already offer pregnant women the option to bank cord blood, but private banks charge about $2,000 to collect the blood and an annual fee of $100 to $200 to store it. Chances that a child would actually need his or her cord blood before age 20 are slim, with estimates ranging from 1 in 2,000 to 1 in 20,000. Families donating cord blood to the public or to research will not be charged a fee, but the blood likely would not be available to them if they needed it later. "It's sort of like if you donate (regular) blood to the blood bank," English said. "Hopefully there would be a specimen available to you, but it wouldn't be yours.".

Announced online By Allison M. Heinrichs, October 8, 2007 in the Pittsburgh Tribune-Review.


Thalidomide Helps Elderly Cancer Patients: Study.
Once shunned for causing limb deformity in unborn children during the 1950s and '60s, thalidomide is now considered a cancer fighter, with scientists testing it on lung, blood and brain cancers. It has also been approved to treat leprosy.

Elderly patients with an aggressive form of blood cancer lived
about 20 months longer when given the drug thalidomide as part
of their treatment, French researchers said. The drug also slowed the spread of myeloma, a disease that accounts for about 1-2 percent of all cancers, usually affects older people, and kills its victims within three years.

Facon and his colleagues analyzed 447 untreated patients aged 65 to 75, giving some the standard drugs and adding thalidomide into the mix for others. They used Pharmion's Thalidomide, currently under review by European regulators for treating multiple myeloma, Facon said. Celgene sells the drug in the United States under the brand name Thalomid.

In a follow-up nearly six years later, the researchers found those who received thalidomide lived on average nearly 52 months, versus 33 months for those on standard therapy. Progression-free survival - the time it takes before the disease worsens - also improved by about 10 months.

"After 50 years of unsuccessful attempts to find new and more effective treatment approaches... we now have extensive evidence to support the introduction of (thalidomide) as the standard of care for elderly patients with multiple myeloma," Antonio Palumbo and Mario Boccadoro of the University of Torino, wrote in a Lancet commentary.

Published October 5, 2007 in the medical journal Lancet.


Netherlands Considers Introducing Preconception Care.

The Health Council of the Netherlands, a scientific advisory body, has recommended that the Dutch government introduce an integrated programme of preconception care, to reduce perinatal mortality, miscarriage, premature birth, and congenital abnormalities.

The Dutch government commissioned the council to draw up its advice because the Netherlands has lost its pre-eminent position on perinatal mortality compared with other European Union countries, partly because of a higher proportion of older mothers and mothers belonging to ethnic minorities.

The council's key message is that current antenatal care, which starts after the eighth week of pregnancy, can miss chances to improve the health of the mother and child. Information on health interventions should be brought forward until at least a month before any planned conception to allow the health benefits a chance to have effect, it says.

Published October 6, 2007 in the British Medical Journal (BMJ).



Find 'Offers Motor Neuron Hope'.
Scientists are hopeful that they have found a way to halt the progression of motor neurone disease (MND). A team at Bath University discovered a causal link between the gene involved in the formation of blood vessels and the development of some forms of MND.

A team at Bath University discovered a causal link between the gene involved in the formation of blood vessels and the development of some forms of MND. Mutant versions of the gene's product - angiogenin - are toxic to motor neurones, so blocking this process may stop the disease, they say.

"The condition affects men more than women and one or two people in every 100,000 will be newly diagnosed with MND each year. In MND, over time, the cells responsible for transmitting the chemical messages that enable muscle movements become injured and subsequently die. Ultimately, the disease fatally interferes with those muscles involved in breathing.

Lead researcher Dr Vasanta Subramanian says: "We have found that mutated versions of this molecule are toxic to motor neurones and affect their ability to put out extensions called the axons. "If we can block the function of the faulty angiogenin in patients in which it is present, this may help to maintain healthy neurones and prevent further progression of the disease."

Published October 4, 2007 in the journal Human Molecular Genetics.

New Cancer Drugs Could Help in Autoimmune Disease.
A new class of drugs used to treat cancer might be effective at suppressing overactive immune systems in patients with autoimmune diseases like Crohn's disease, U.S. researchers say.

"What we would be proposing would be a therapy that would enhance the body's own immune system's ability to regulate itself," said Wayne Hancock of Children's Hospital of Philadelphia. Hancock said drugs known as histone deacetylases inhibitors, or HDACs, which affect compounds involved in the growth and death of cancer cells, bolstered the production of cells that regulate the immune system in mice.

While many companies are working on HDACs, Hancock's study focused on the Merck & Co Inc drug Zolinza, also known by its chemical name suberoylanilide hydroxamic acid, or SAHA. Zolinza is approved in the United States to treat cutaneous T cell lymphoma, a type of skin cancer. Hancock said SAHA appears to bolster the work of regulatory T-cells that suppress the immune system. "Their job is to act as police and dampen down inflammatory responses," he said.

The study offers evidence that a drug could be used to enhance regulatory T-cell production and function. "That hadn't been done before," Hancock said. He and colleagues are working with researchers in Minnesota to try the Merck drug Zolinza in diabetic monkeys with islet cell transplants.

Hancock said the drugs have the potential to treat other autoimmune diseases, like rheumatoid arthritis. So far, they are mostly being studied in cancer, but that could change. "I image a number of companies who have been developing these compounds for oncology will pick up their ears when they hear this," he said.

Published October, 2007 in Nature Medicine.

ignaling molecules secreted by ES cells, rather than the cells themselves, may someday form the basis for new treatment. For example, molecules might be used directly, or the ES cells might be employed to deliver these healing chemicals to where they are needed. Still, "The first challenge is to see how general this is," Benezra cautions. In a commentary accompanying the Science report, Kenneth Chien, Alessandra Moretti and Karl-Ludwig Laugwitz suggest that other stem-cell researchers should make certain to check whether their results arise from the cells themselves, or from chemicals the cells may be secreting. This new finding, Chien remarks, is "one of the most exciting discoveries in the field of cardiac stem cells to date." Published September, 2007 in the Science.