SUNDAY - June 10, 2007---------------------------- Previous Week News Alerts / Return to Today's News Alerts

3X Dose Vitamin D and Calcium Cuts Women's Cancer Risk.
Boosting your vitamin D intake can dramatically reduce your risk of breast and other cancers, a new study found. The research adds to growing evidence that vitamin D can help protect against many forms of cancer as well as other diseases, Creighton University researchers said. Joan Lappe, a Creighton University professor of medicine and nursing and lead author of the study, said, "What we can say from our study is that 1,100 international units (IUs) a day of vitamin D definitely decreased the incidence of cancer." Lappe's team followed 1,179 study participants who were all postmenopausal and lived in rural Nebraska. Dividing the study group into 3, one group took 1,400 to 1,500 milligrams of supplementary calcium a day, another group took that same amount of calcium plus 1,100 IUs of vitamin D daily, while the third group took placebo pills every day. After four years, those in the combination vitamin D and calcium group had a 60 percent lower risk of developing cancer, compared to the placebo group. The calcium-only group had a 47 percent reduced risk. When the researchers looked at results from just the last three years of the trial, they found the combination calcium-and-vitamin D group had a 77 percent reduced risk of cancers, compared to the placebo group. The risk for the calcium-only group was essentially unchanged. In May, Harvard Medical School researchers reported in the Archives of Internal Medicine that high intakes of vitamin D and calcium cut the risk of breast cancer by nearly one-third in premenopausal women, but not women past menopause. Dr. Michael Holick, professor of medicine, physiology and biophysics at the Boston University School of Medicine and a long-time vitamin D researcher, said the Lappe study adds to growing evidence of the health and disease-fighting effects of vitamin D. To date, both Lappe and Holick said, high intake of vitamin D has been found to reduce the risk of many forms of cancer as well as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and high blood pressure. Dr. Lappe recommends vitamin D3 supplements, over D2, because D3 is more active, she said.

UK Fertility rate 'at 26-year high'
The United Kingdom's fertility rate has hit its highest level since 1980 as more women in their late 30s and 40s have babies, official figures show. The Office for National Statistics data revealed women are having 1.87 children on average - up from 1.8 in 2005. But experts predicted it was unlikely to keep rising, as the rate is due largely to pregnancies in older women. The highest percentage increase for any age group was for women from 35 to 39 which rose by 7% in a year. Fertility rates have also doubled for women aged 40 and over in the last 20 years. Professor Danny Dorling, an expert in human geography at Sheffield University, said the changes in recent years were being driven by the change in university admissions during the 1980s.

Umbilical Cord Beats Marrow for Leukemia Transplants.
Transplanted blood cells from umbilical cords appear to give better results than the bone marrow transplants that have been standard for leukemia patients, a new study finds. "From my point of view, it now demonstrates that cord blood can be considered a first-line therapy and not an afterthought," said lead researcher Dr. John E. Wagner, director of the bone marrow transplant program at the University of Minnesota. His team published its findings in the June 9 issue of The Lancet. .

Genetic Analysis Reveals Changes - Hypertrophic Cardiomyopathy.
The one-gene, one-disease concept is elegant, but incomplete. A single gene mutation can cause many other genes to start—or stop—working, and it may be these changes that ultimately cause clinical symptoms. Identifying the complete set of affected genes used to appear impossible. Not anymore. .

Now Playing: CELL MIGRATION LIVE!
Johns Hopkins researchers have found a way to directly observe cell migration - in real time and in living tissue. In a report in the June 5 issue of Developmental Cell, the scientists say their advance could lead to strategies for controlling both normal growth and the spread of cancer, processes that depend on the programmed, organized movement of cells across space. movie: The Genetics of Cell Motility and Invasion

Type 1 Diabetes and Crohn's Disease Genes Identified.
A major collaboration of UK scientists has provided an insight into the genetics underlying a number of diseases including Crohn's disease, a type of inflammatory bowel disease, and type 1 diabetes. The Crohn's and type 1 research, led by Cambridge University scientists, has identified for the first time a gene linking these two autoimmune diseases. .

Scientists Propose the Kind of Chemistry that Led to Life.
Before life emerged on earth, either a primitive kind of metabolism or an RNA-like duplicating machinery must have set the stage – so experts believe. But what preceded these pre-life steps? .

Cancer Drug Enhances Long-Term Memory.
A drug used to treat cancer has been shown to enhance long-term memory and strengthen neural connections in the brain, according to a new study by UC Irvine scientists. .

STRICTLY SCIENCE

Centromeres were derived from telomeres during the evolution of the eukaryotic chromosome.
The centromere is the DNA region of the eukaryotic chromosome that determines kinetochore formation and sister chromatid cohesion. Centromeres interact with spindle microtubules to ensure the segregation of chromatids during mitosis and of homologous chromosomes in meiosis. The origin of centromeres, therefore, is inseparable from the evolution of cytoskeletal components that distribute chromosomes to offspring cells. Although the origin of the nucleus has been debated, no explanation for the evolutionary appearance of centromeres is available. We propose an evolutionary scenario: The centromeres originated from telomeres. The breakage of the ancestral circular genophore activated the transposition of retroelements at DNA ends that allowed the formation of telomeres by a recombination-dependent replication mechanism. Afterward, the modification of the tubulin-based cytoskeleton that allowed specific subtelomeric repeats to be recognized as new cargo gave rise to the first centromere. This switch from actin-based genophore partition to a tubulin-based mechanism generated a transition period during which both types of cytoskeleton contributed to fidelity of chromosome segregation. During the transition, pseudodicentric chromosomes increased the tendency toward chromosomal breakage and instability. This instability generated multiple telocentric chromosomes that eventually evolved into metacentric or holocentric chromosomes.. PNAS Published online before print June 8, Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0703808104



SATURDAY - June 9, 2007---------------------------- Previous Week News Alerts / Return to Today's News Alerts

Umbilical Cord Blood Adds Graft Options in Childhood Leukemia.
For children with leukemia who need a transplant, five-year disease-free survival rates from allogeneic cord blood appear to equal those from allele-matched bone marrow or peripheral blood stem cells.

Flexibility Marks How and When to Take Abortion Drug.
The choice of a vaginal or sublingual route for misoprostol, if used alone for early abortion, and the timing of doses leaves women several safe and effective options.

Postpartum Depression: A Risk for New Dads, Too.
Postpartum depression has gotten a softer face in recent years as celebrity mothers, such as Brooke Shields, who've experienced its devastating symptoms, have begun to share their personal stories.

US House of Representatives/Senate Backs Stem Cell Research.
For the second straight year, the U.S. House and Senate have each passed a measure to allow federally funded embryonic research. But the legislation is almost certain to be vetoed by President George W. Bush when he returns from a trip to Europe.

Second Life, or Not?
An activist group is raising a ruckus about what it says may be the first effort to patent an entirely synthetic free-living organism. It says the patent application, filed by maverick genome sequencer Craig Venter's institute on an idea that has likely not yet been achieved, would tie up a new technology and could aid bioterrorists. But others say there's nothing new or surprising about the patenting effort.

Diet Proves 'Eat More, Weigh Less' Can Work.
Eating more water-rich foods, especially fruits and vegetables, fats helped women drop more pounds than simply moderating fat intake.

Molecular Holograms Are Coming Into Focus.
3D images of individual molecules may soon be possible thanks to a breakthrough in holography by Swiss scientists. The technique would be useful to biologists interested in how the shapes of proteins and other components of life relate to their function.

STRICTLY SCIENCE

RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription.
Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome. Science 8 June 2007: Vol. 316. no. 5830, pp. 1484 - 1488 DOI: 10.1126/science.1138341

Importance of Non-Gene Transcription.
Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome. Science 8 June 2007: Vol. 316. no. 5830, pp. 1477 - 1480 DOI: 10.1126/science.1142618.

Target Identification Tool.
In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these protein-DNA interactions comprehensively across entire mammalian genomes, we developed a large-scale chromatin immunoprecipitation assay (ChIPSeq) based on direct ultrahigh-throughput DNA sequencing. This sequence census method was then used to map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known as REST, for repressor element–1 silencing transcription factor) to 1946 locations in the human genome. The data display sharp resolution of binding position [±50 base pairs (bp)], which facilitated our finding motifs and allowed us to identify noncanonical NRSF-binding motifs. These ChIPSeq data also have high sensitivity and specificity [ROC (receiver operator characteristic) area 0.96] and statistical confidence (P <10–4), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development. Science 8 June 2007: Vol. 316. no. 5830, pp. 1497 - 1502 DOI: 10.1126/science.1141319.



FRIDAY - June 8, 2007---------------------------- Previous Week News Alerts / Return to Today's News Alerts

Why So Much Asthma in US Children?
A chemical - 'perfluorinated compounds,' or PFCs - commonly used to make fabric protectors, stain repellants and non-stick surfaces, increases the allergic response in mice when they are exposed to it, and may be the basis of the 60% increase in Asthma in western cultures over the past several decades. In addition, the very persistant PFOAs can contribute to thyroid problems, immune changes and cancer (testicular, liver and pancreatic) in laboratory animals. People exposed to PFOA at work may be at higher risk for pancreas, testis and prostate cancers. Over the past 5 decades PFOA has become so widespread a contaminant that almost everyone tested has measurable amounts in their bodies. Indeed a recent study by scientists at Johns Hopkins University found that 100% of Baltimore newborns were contaminated by PFOA. The levels used in this experiment, however, were much higher than those commonly detected in people. As stated by the authors, “the persistence of PFOA in the environment in combination with these findings suggest that exposure to PFOA, although not allergenic itself, may enhance an individual’s response to commonly encountered environmental allergens.” Future studies will be needed to determine the mechanism by which PFOA exactly alters the immune response. The concentrations used in this experiment are much higher than what is found in human blood and the experiment duration was quite brief (4 days). Therefore, it is not known what affect long-term exposure to environmentally relevant levels of PFOA may have on the immune system or chronic asthma. However, the findings of this study are important given the likelihood of childhood exposure to PFOA and related chemicals and the strong trend in the US toward higher rates of asthma in children.

Alarm Over Gender-Bending Chemical.
An unusual mix of public health advocates, environmentalists and laundry workers joined yesterday in a petition demanding that federal authorities ban a chemical additive found in some household detergents and other cleaning agents. The petition, which was submitted to the federal Environmental Protection Agency, also called for studies of human risks related to the dirt-lifting agents called nonylphenol ethoxylates, or NPEs. Studies have shown NPEs to be potent gender-benders, believed to be responsible for transforming male fish into females in waterways worldwide. Marine scientists at Stony Brook University say NPEs are the likely culprit in the decline of male winter flounder in Jamaica Bay. The groups calling for a ban of NPEs say the transformed fish may be "the proverbial canaries in the coal mine," and that human safety issues have yet to be uncovered. The EPA had no comment on the petition yesterday. European and Canadian regulators have banned NPEs in domestic laundry detergents and other cleaning agents. Petitioners, including the Sierra Club, want the EPA to require appropriate labeling of products with NPEs and to eventually ban their use in consumer products. "Nonylphenol ethoxylates are in the larger class of chemicals we refer to as endocrine disrupters. That's the concern," said Dr. Michael McCally, executive director of the Washington, D.C.-based Physicians for Social Responsibility, a public health advocacy organization, and one of the petition's signers. "NPEs ... affect gene expression by turning on or off certain genes," McCally said. As a class, endocrine disrupters are known for mimicking the female hormone estrogen, the reason some marine species have become females. McCally, a clinical professor of preventive medicine at The Mount Sinai Hospital in Manhattan, theorizes that medical conditions that are far more insidious, requiring decades to manifest, could be caused by endocrine disrupters.

Small RNAs, Not Just Proteins, Hold Big Power In Halting Cancer.
Cold Spring Harbor Laboratory (CSHL) researchers led by Lin He, Xingyue He, and Professor and Howard Hughes Medical Investigator (HHMI) Greg Hannon have identified a family of micro RNAs (miRNAs) that enable a critical tumor suppressor network, called the p53 pathway, to fight cancer growth. "At CSHL, we are moving simultaneously on several fronts to understand the p53 pathway because damage to this pathway is something that almost all cancers have in common," said CSHL Cancer Center Deputy Director and HHMI Scott Lowe. "Collaboration among different CSHL research laboratories has not only found that p53 can arrest the growth and even eradicate cancers, but we've revealed something very surprising about what makes this pathway so powerful," said Hannon. CSHL research published by Nature earlier this year, concluded that even in the latest stages of cancer, reactivation of a previously damaged p53 pathway caused cancer tumors to stop growing and even eliminate themselves by activating an immune response in surrounding healthy cells. Most suspected that proteins would be revealed as key to the power of p53, but this latest research published June 6 by Nature now identifies miRNAs as a critical force behind the anti-proliferation potential of p53. The fact that p53 uses miRNAs to stop tumor cell growth reveals a completely new dimension of this critical cancer fighting pathway and its ability to trigger the genetic death of cancer cells. The fact that p53 uses miRNAs to stop tumor cell growth reveals a completely new dimension of this critical cancer fighting pathway and its ability to trigger the genetic death of cancer cells.

Hormone Ignites the Body's Fat-Burning Furnace.
Researchers have identified a master hormone that allows the body to fuel itself with stored fat during times of fasting. The hormone mobilizes lipids from fat cells, and then directs the liver to transform those lipids into energy-rich molecules that circulate throughout the body. Their findings reveal a more complete picture of the far-reaching role of the hormone, fibroblast growth factor 21 (FGF21), which is already in development as a treatment for type 2 diabetes. The team found FGF21 induces the hibernation-like state of torpor that conserves energy in fasting animals. The hormone, fibroblast growth factor 21 (FGF21), is expressed in the liver and drives the production of so-called ketone bodies, according to two studies reported in the June issue of Cell Metabolism. The findings may explain the fat-burning benefits sometimes seen in high-fat, low-carbohydrate diets, such as the Atkins diet, said Eleftheria Maratos-Flier, M.D., of Beth Israel Deaconess Medical Center. And the discovery may lead to new approaches to obesity, according to Dr. Maratos-Flier "We think these findings would increase the desirability of a drug that (might work through this mechanism) to increase fat oxidation in the liver. One area we are keen on exploring is the other actions that FGF21 may have on the body,” Mangelsdorf said. An accompanying study, led by Steven Kliewer, Ph.D., of the University of Texas Southwestern Medical Center in Dallas, also found that the hormone breaks down fat - both in animals forced to fast, as well as those with chronically elevated concentrations of FGF21. "It's startling that you can give one hormone and flip the whole metabolic profile," Dr. Kliewer said. What's more the hormone appears to counteract the effects of too much food. "When you step back, the whole thing makes sense," Dr. Kliewer said.

Cannabis Compound Reduces Skin Allergies in Mice.
Cannabis can reduce allergic skin reactions, a new study suggests. The findings may lead to new drugs based on tetrahydrocannabinol (THC), the active ingredient in the plant, to treat allergy and autoimmune disorders. Andreas Zimmer at the University of Bonn in Germany, and colleagues created a group of mice that lack the receptor for endocannabinoids – forms of THC produced naturally in the body. The team noticed that the mice soon developed a severe skin allergy to the nickel in the metal tags the researchers had fastened to their ears. Zimmer exposed the ears of mice with normal endocannabinoid receptors to a chemical irritant causing a severe skin reaction similar to that caused by poison ivy in humans. Within a matter of minutes, the amount of an endocannabinoid called anandamide jumped from undetectable levels to about 300 picomoles per gram of analysed tissue. When Zimmer's team applied 30 micrograms of synthetic THC to the animals' ears it reduced the skin irritation by half. For comparison, a cannabis cigarette contains as much as 150 milligrams of THC. Ramesh Ganju at the Harvard Cancer Center in Boston, Massachusetts, US, believes that a study he published in 2006 could help explain what the European researchers found. He dunked T cells – immune cells that flag foreign particles in the body and trigger allergy – into a solution containing synthetic THC causing them to become up to 70% less attracted to cytokine signals (Molecular Immunology, DOI:10.1016/j.molimm.2006.01.005). Ganju says that Zimmer's findings provide further evidence that endocannabinoids "probably have a role in autoimmune diseases". Published: Science (DOI: 10.1126/science.1142265).




THURSDAY - June 7, 2007---------------------------- Previous Week News Alerts / Return to Today's News Alerts

BREAKTHROUGHS IN STEM CELL RESEARCH

Two Significant Stem Cell Advances Announced.

A pair of stem cell discoveries announced Wednesday may one day surmount both the ethical and technical hurdles confronting such research, setting the stage for medical advances.

In the first study, scientists at the Harvard Stem Cell Institute managed to create stem cells from non-viable mouse embryos, potentially opening a new source of cells for experiments and research. The Harvard University research - published in Nature - managed to convert the "genetic identity" of a mouse embryo by temporarily halting its development at a very early stage, then inserting the genetic components from a different mouse. "The practical payoff is that our experiments in mice suggest that you might be able to use very large numbers of fertilized embryos routinely discarded in IVF clinics to do human somatic cell nuclear transplantation in order to generate embryonic stem cell lines," said Kevin Eggan, senior author and a principal faculty member. The possibility of using unrelated human embryos, in theory more plentiful as many are created but never implanted during the IVF process, and either discarded or frozen, would give purpose to otherwise wasted embryos.

In the second study, investigators at the Whitehead Institute for Biomedical Research in Cambridge, Mass., succeeding in creating cells identical to embryonic stem cells from adult skin cells in mice, bypassing both the need for eggs and the need to destroy early embryos. Scientists used a retrovirus to activate four specific transcription genes found in cells just under a mouse's skin surface - the fibroblast cells. Transcription genes regulate groups of other genes. The four cells had previously been identified by Japanese researchers at Kyoto University, Japan. "The cells we reprogrammed were remarkably similar to embryonic stem cells," said Marius Wernig, lead author of this study and a postdoctoral researcher at the Rudolf Jaenisch Lab at the Whitehead Institute. "We can basically reverse development in a culture dish." Not only were the reprogrammed cells identical to embryonic stem cells, including the ability to be pluruipotent, they were also able to give rise to live mice and their DNA could be transmitted to succeeding generations. In other words, they could do everything a traditional stem cell could do. "This opens up a new field in stem cell research," said Konrad Hochedlinger, co-author of the paper, previously a member of the Jaenisch lab and now with the Harvard Stem Cell Institute and Massachusetts General Hospital. "There should be no fear of epigenetic reprogramming [passing on flaws, such as cancer] in using these cells." The advance was strengthened further by the fact that three different teams of researchers - from the Whitehead Institute in Cambridge, Massachusetts, the Harvard Stem Cell Institute, and Kyoto University in Japan - produced exactly the same result using the same technique.

But there remains one big caveat. "A human is not a mouse," said Wernig. "It's important to continue, if not intensify, our research on human embryonic stem cells. The method we used to reprogram the mouse cells would not be safe to use in human cells. A lot more work needs to be done." Eggan's paper is published online June 6 in the journal Nature. The other papers are published in the inaugural issue of the journal Cell Stem Cell.

Researchers ID Genes for At Least Seven Common Diseases.
"This is a tour-de-force. It's going to revolutionize medicine." says Anne M. Bowcock, a professor of genetics at Washington University School of Medicine and author of an accompanying editorial in Nature. In the largest study to date of the genetics of diseases, researchers say they've substantially increased the number of genes believed to play a role in the development of common illnesses, ranging from bipolar disorder to diabetes. For the new research, the authors concentrated on seven diseases and found genetic links for each one: bipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis, and type 1 and type 2 diabetes. "Six months ago, we probably knew about 10 different genetic risk factors across those diseases. We now know closer to 30..." says Peter Donnelly, of the Department of Statistics at the University of Oxford in England. Knowing the genetic components of a disease will lead to individualized medicine, where treatments are based on one's own risk for an illness.

Aging Stem Cells May Hold Answers To Diseases of Aging.
As stem cells in bone marrow grow older, genetic mutations accumulate which could be the root of blood diseases striking us as we age. "This and our previous work points out why older people are more likely to get blood diseases, such as leukemia or anemia, and are less likely to make new antibodies that would protect them against infections like the flu," said senior author Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and of the Stanford Comprehensive Cancer Center. The work will be published in the June 6 issue of Nature. Previously, Weissman's group has shown that blood-forming stem cells - found in bone marrow - of aging mice became less able to divide and replenish. The question was why. One theory was that cells accumulate genetic mutations over time - but researchers had thought that mutations, which occur during cell division, were unlikely in stem cells as they very rarely divide. The next step is to show whether these results from mice hold true for human blood-forming stem cells. "If this work does extrapolate to humans, then it is absolutely consistent with the idea that blood-forming stem cells are the breeding ground for pre-leukemic mutations," said Weissman, the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research. Funding for this study came from the National Cancer Institute's Center for Cancer Research, the Damon Runyon Cancer Foundation, the California Institute of Regenerative Medicine, a Swedish Medical Research Council scholarship (STINT) and a Cancerfonden grant.



WEDNESDAY - June 6, 2007---------------------------- Previous Week News Alerts / Return to Today's News Alerts

Less Therapy Maintains Survival/Reduces Toxic Effects.
For infants and children with intermediate-risk neuroblastoma, a milder therapy regimen can preserve good long-term survival and minimize toxicity, found an international trial. Three-year overall survival exceeded 90% with the less-intense treatment regimen, which improved on the favorable prognostic track record achieved with standard treatment protocols, reported David Baker, M.B.B.S., of Princess Margaret Hospital in Perth, Australia. The investigational regimen also achieved the goal of minimizing toxicity, particularly renal, cardiac, and ototoxicity, Dr. Baker said at the American Society of Clinical Oncology meeting here. "We were able to achieve an excellent cure rate with a remarkably significant reduction in therapy," said Dr. Baker. Compared with a historical control group, the patients had no decrement in survival with treatment durations that were reduced by as much as 70%.

Can Caffeine Increase the Risk of Miscarriage?
With more than 80 percent of Americans consuming it in some form or another every day, caffeine is easily the nation’s most popular drug, far ahead of nicotine and alcohol. So when studies first suggested decades ago that caffeine could increase the risk of miscarriage, it raised alarm. Why exactly it might pose such a risk remains unclear, but numerous studies in recent years have investigated the link. One of the more unnerving studies was published in The New England Journal of Medicine in 2000. It looked at more than 1,000 pregnant Swedish women and found that those who drank the equivalent of one to three cups of coffee a day had a 30 percent increased risk of miscarriage, while those who had the equivalent of at least five cups had more than double the risk. According to the Department of Health and Human Services, there is now general agreement that low caffeine intake during pregnancy - about 150 milligrams a day, or roughly 1.5 cups of coffee - is safe. THE BOTTOM LINE: Low caffeine intake during pregnancy appears to be safe, while the risk of high intake is unclear.

UK Scientists Plan Stem Cell Cure For AMD Blindness.
In a pioneering project, launched on Tuesday, British scientists aim to repair damaged retinas with cells derived from human embryonic stem cells. Backers say the procedure involves simple surgery that could one day become as routine as cataract operations. The technique is believed capable of restoring vision in the vast majority of patients with age-related macular degeneration (AMD), a leading cause of blindness among the elderly that afflicts around 14 million people in Europe. The new procedure will generate replacement retinal pigment epithelial (RPE) cells from stem cells in the lab, with surgeons then injecting a small patch of new cells, measuring 4 by 6 millimeters, back into the eye. The London Project to Cure AMD brings together scientists from University College London (UCL), Moorfields Eye Hospital in London and the University of Sheffield. By injecting RPE cells derived from stem cells instead, Dr Lyndon Da Cruz of Moorfields hopes the operation can be reduced to a simple 45-minute procedure under local anesthetic. The therapy has been made possible by a 4 million pounds ($8 million) donation from an anonymous U.S. donor, who the project's leaders say had become frustrated by U.S. curbs on stem cell work.

Researchers Pinpoint Colon Cancer Stem Cells for Treatment.
Colon cancer, sometimes called colorectal cancer, arises in the large intestine or rectum and is a leading cause of cancer deaths. Nearly all cases start as benign polyps that over time develop into cancer. "Within a tumor, not all tumor cells are created equal," Dr. Piero Dalerba of Stanford University School of Medicine in California, one of the researchers, said in a telephone interview. "There is a tiny minority population of cells that is very dangerous and has special properties that are different from the majority of tumor cells in the tumor mass," Dalerba added. "The implication of this is that when you try to treat a tumor, you have to target this population of cells." He expressed hope that the finding, published in the Proceedings of the National Academy of Sciences, would lead to treatments to wipe out these cells and eradicate the cancer. The research highlighted the role of a protein called CD44 found in colon cancer stem cells that was found previously in breast, head and neck cancer stem cells. The researchers also found a protein in colon stem cells called CD166 that they said could serve as a target for new treatments.

Novel Technique IDs When the Zygote’s Genome Turns On.
You might say that a mother’s influence begins even before her offspring were just a twinkle in dad’s eye. During egg cell development (oogenesis), the mother deposits gene products - largely messenger RNAs (mRNAs) and some proteins - into the developing egg. These mRNAs take over after fertilization to orchestrate the earliest stages of embryogenesis. As the embryo develops, the fertilized egg (or zygote) cuts the apron strings as it activates its own genome - which contains both maternal and paternal genes - and relies less on the pre-existing maternal mRNAs. To navigate this maternal-to-zygotic transition (MZT) successfully, the zygote must integrate signals that control pre-existing maternal mRNA transcripts with those that activate the zygotic genome. How the embryo manages this phased transition from one class of regulatory mechanisms to another has long remained obscure. In a new study published April 24th, Stefano De Renzis, Eric Wieschaus, and colleagues describe an innovative experimental approach to determine the maternal-versus-zygotic provenance of mRNA transcripts during MZT in the fruit fly Drosophila melanogaster. By matching gene transcripts with their corresponding DNA template across the genome, the researchers identified classes of zygotically and maternally expressed genes and show that the embryo combines (zygotic) transcription with (maternal) message degradation to produce the localized patterns of gene expression required for organizing the early embryo.

Relevance Of Retinoic Acid-Induced Craniofacial Malformations.
In the 19th century, people believed that a pregnant woman could by her imagination, cause fetal defects. Dr. Giovanni Levi's manuscript "Molecular dynamics of retinoic acid-induced craniofacial malformations: implications for the origin of gnathostome jaws" (to appear in the June 6th issue of the online, open-access journal PLoS ONE), revisits some of those concepts from the view of modern molecular genetics. He starts from the observation that high doses of vitamin A or of its derivative, retinoic acid (RA), during early pregnancy is known to dramatically increase the risk of severe craniofacial malformations. How these developmental errors are generated remains, enigmatic as "neural crest cells", which generate most craniofacial structures, do not respond to RA. The authors induced craniofacial defects by treating mouse embryos with RA at precise intervals corresponding to the 3rd to 5th week of human fetal development. The defects induced are profoundly different depending upon the exact moment at which RA is administered. They are associated with the molecular signals instructing neural crest cells to generate various structures of the face by activation of Dlx patterning genes. The most intriguing observation of this study is that the morphological changes in the mouse embryos closely resemble features found in other species. They conclude that modification of a common regulatory mechanism could be at the origin of changes in jaw structures between species.



TUESDAY - June 5, 2007---------------------------- Previous Week News Alerts / Return to Today's News Alerts

Fetuses, Babies at High Risk from Pollutants.
Fetuses and babies are more vulnerable than previously thought to chemical pollutants that can cause disease or disability, even in tiny doses that do not harm adults, some 200 scientists say following a meeting in the North Atlantic Faroe Islands partly sponsored by the U.N.'s World Health Organization. The researchers urged tighter controls on toxic chemicals, some used in making plastics or pesticides, saying that there was a risk of disruptions at key stages of growth that could lead to brain damage, malformation or cancers. "Fetal life and early infancy are periods of remarkable susceptibility to environmental hazards," toxicologists, biologists, pediatricians and other experts from around the world said after the talks. "Toxic exposures to chemical pollutants during these windows of increased susceptibility can cause disease and disability in infants, children, and across the entire span of adult life." In some cases, damage to genes "may also be passed on to subsequent generations," the scientists said. "We are beginning to understand that there are some very sensitive processes that have to happen at a particular time and in a particular sequence," said Philippe Grandjean, scientific chair of the meeting who works at the University of Southern Denmark and the Harvard School of Public Health.

Asthma Doesn't Usually Increase Pregnancy Risks.
Adverse obstetric or pediatric complications are not generally increased in women with asthma, according to a report in the May 15th American Journal of Respiratory and Critical Care Medicine. Previous studies have suggested the possibility of increased risks of pregnancy complications in women with asthma, the authors explain, but these studies have had various statistical shortcomings. To further investigate, Dr. Laila J. Tata from University of Nottingham in the UK and colleagues used data from more than 280,000 pregnancies to compare the risks of obstetric complications and adverse pregnancy outcomes in women with asthma and those without asthma. Asthma did not significantly increase the risk of high blood pressure, diabetes, thyroid disorders, the need for assisted delivery, placental separation from the uterine wall (placental abruption), placenta blocks the opening to the birth canal (placental previa), pre-eclampsia (a condition affecting multiple body systems characterized by high blood pressure and kidney failure), or eclampsia (progression of pre-eclampsia to a life-threatening severity). However, when compared with women without asthma, women with asthma did have a 20-percent increased risk of hemorrhaging during delivery, a 38-percent risk of hemorrhaging after delivery, a 6-percent risk of anemia, and a 57-percent increase risk of depression. They were also 11-percent more likely to deliver by cesarean section. Women with more severe asthma and a history of asthma exacerbations had an increased risk of miscarriage and depression, the researchers note, but increased risk of hemorrhage after delivery was restricted to women with milder asthma and no exacerbations.

Racial Disparities Persist in Preterm Birth Risk.
Black infants are four times as likely to be born before 28 weeks gestation as white infants, an imbalance that hasn't changed in a decade, a new study shows. Because such "extremely pre-term" babies are at much greater risk of death than infants born later, this disparity is a major factor in the continuing infant mortality gap between blacks and whites in the United States, Dr. Ashley H. Schempf of Johns Hopkins Bloomberg School of Public Health in Baltimore and colleagues state. Extremely pre-term infants who do survive are at increased risk of developmental delays and other problems, they point out in the American Journal of Public Health. "There's not a racial disparity that I'm aware of that's as great and as proximally linked to morbidity and mortality as extreme preterm birth," Schempf told Reuters Health. Disparities in preterm birth, defined as delivery before 37 weeks' gestation, have been reduced in recent years. The researchers sought to determine whether a narrowing of the preterm birth gap between 1990 and 2000 might have resulted in a similar shrinkage of the black-white infant mortality gap. But during that decade, the researchers found, the racial disparity in infant mortality did not budge. The findings underscore the importance of continuing research to identify, and address, the factors involved, she added. "Given the sheer magnitude of the disparity and its close link to morbidity and mortality, there are few racial disparities that warrant greater research attention than extremely preterm birth."

Fewer Options for Those Who Seek Natural Births.
The future is uncertain for the popular midwife program at St. Luke's Hospital. The financially strapped hospital is dropping Homestyle Midwifery on Aug. 1 to cut costs. St. Luke's has given the midwife who runs the program the option of staying on in a private practice, but San Francisco Bay Area midwives and obstetricians familiar with the program aren't certain it can survive the change. The potential loss of Homestyle has rippled through the region's natural birthing community, as midwifery programs try to compete in an industry where medical intervention is increasingly common and patients and doctors alike rely on drugs and surgery to get through childbirth. The rates of midwife-attended childbirth climbed every year into the 1990s before hitting a plateau. From the mid-1970s to 2002, midwife-attended births jumped from 1 percent to 8.1 percent. But in 2004, the most recent year for which data is available, about 325,000 births, or 7.9 percent of all births, were attended by a midwife, according to the National Center for Health Statistics. "Support for midwives has always been a problem, and it varies from setting to setting and fiscal year to fiscal year," said Elizabeth Steinfield, a nurse-midwife at St. Luke's who has worked in two other midwifery programs. "Midwives can be very cost-effective if used properly, but if not, people can't figure out why we're around. Our slogan is 'midwifery is the art of doing nothing well'. And it's true - sometimes the best thing to do in childbirth is nothing. But you have to be very well trained to know when that's the right thing to do."

How Chromosomes Got Hitched.
Dividing chromosomes are molecular Siamese twins: two bodies of genetic material joined along a stretch of DNA called the centromere. Centromeres help direct the separation of the chromosomes to ensure that newly formed cells have the right amount of DNA. But no one knows exactly how they evolved. Now there is a controversial new theory - these key innovations started out at the ends of ancient chromosomes. Researchers debate whether centromeres evolved once or many times. The sequence of these stretches of DNA varies quite a bit from organism to organism, suggesting independent origins. Yet centromeres all do the same thing: They keep newly formed chromosomes together at first, then help anchor protein strands that pull chromosomes apart as the cell splits in two. Moreover, the proteins involved in these actions are the same in all organisms. This evidence points to a single origin. Almost 10 years ago, Alfredo Villasante, a molecular biologist at the Autonomous University of Madrid, Spain, discovered a striking fact about the centromeres of fruit flies. Some of the sequence matched repetitive DNA in telomeres, the caps of chromosomes, which often shorten each time a cell divides and play an important role in aging. Knowing that protein strands sometimes attach to telomeres to move chromosomes, he and his colleagues have developed a scenario to explain chromosome and centromere evolution. Villasante assumes that chromosomes were originally circular, just as they are in bacteria today. But sometimes the circles broke open, at which time mobile elements embedded in the genome hopped to the ragged ends, capping them and preventing circles from reforming. Over time, these mobile elements accumulated and became the telomeres, says Villasante. As the sequences expanded and evolved, regions just inside the capped ends became the grandfathers of the centromere, Villasante and his colleagues propose online this week in the Proceedings of the National Academy of Sciences (PLoS).


MONDAY - June 4, 2007---------------------------- Previous Week News Alerts / Return to Today's News Alerts

Cogitating Monkeys Can Calculate Statistics.
Rhesus monkeys turn out to be pretty good statisticians, a study reveals. Tianming Yang and Michael Shadlen at the Howard Hughes Medical Institute and the University of Washington in Seattle, US, tested the reasoning of two rhesus macaques by showing them a series of abstract shapes on a video screen. In each trial, the monkey saw a sequence of 4 of 10 possible shapes then, had to choose which target to look at. The probability that the red target would give the reward was the sum of the probabilities for each of the four shapes; otherwise, the green target yielded the drink. After several weeks of training on thousands of trials per day - clearly, the monkeys are no Einsteins - both macaques learned to match their choices closely to the actual probabilities revealed by the shapes they saw, choosing the correct target more than 75% of the time. The researchers also used electrodes in the brain to record the activity of 64 neurons in the lateral intraparietal area - a region on the side of the brain that is involved in attention and visual processing. "We're seeing neurons that are making computations," says Shadlen. In particular, the neurons appeared to be computing the log likelihood ratio of red versus green rewards - exactly the sort of computation a statistician might do." Reference: Nature (DOI: 10.1038/nature05852).

Folic Acid Could Protect Against Strokes as well as Birth Defects.
Folic acid supplements can reduce the risk of stroke by 30%, according to a review of eight studies involving nearly 17,000 participants. The new findings will add fuel to growing calls for the B vitamin to be routinely added to flour or bread - to protect against birth defects - in countries such as the UK where this is not already practice. Xiaobin Wang at the Children's Memorial Research Center in Chicago, Illinois, US, and colleagues combined existing data from trials looking at the vitamin's effect on cardiovascular disease. The studies, in which people aged around 60 received either placebo pills or daily folic acid supplements, followed participants for between two to six years. The analysis revealed that taking any amount of folic acid lowered the risk of stroke by 18%. Another analysis looking specifically at the effect in countries that do not fortify grain with folic acid, such as Norway, China and Italy, found a 25% drop in stroke among those taking the supplement. When Wang analysed a subgroup of those who took the supplements for at least three years, she found that folic acid reduced the risk of stroke by almost 30%. How folic acid protects against stroke remains unclear. It is known that the vitamin helps the body excrete homocysteine, a by-product of protein breakdown that effects small blood vessels, which has been linked to heart disease and dementia. Journal: Lancet (vol 369, p 1876).

Stanford, India to Train Medical Technology innovators.
The Stanford University Program in Biodesign is partnering with the government of India to establish a new training program, called Stanford-India Biodesign, to help create the next generation of biomedical technology innovators in India. The plan is to bring the Stanford program’s method of “teaching innovation” to Indian engineering, business and medical students through a two-year fellowship pilot project. The fellowship will start with hands-on innovation training at Stanford and progress to immersion in health clinics and hospitals in India where students will identify unmet medical needs specifically targeted for the Indian heath-care environment and create cost-effective solutions to meet those needs. At the end of the program, the fellows will remain in India and lead the further development and testing of these solutions in either a university program, a start-up company or a new unit of an existing company. “With a population over 1 billion strong, along with emerging medical and engineering fields and an exploding need for a stronger medical device industry, India is poised for explosive growth of its nascent medical technology industry,” said Raj Doshi, MD, PhD, a Stanford graduate in both engineering and medicine who has been named the U.S.-based executive director of Stanford-India Biodesign.

What Determines Left-Right Wiring in the Embryonic Worm?
Rockefeller University scientists working to demystify the roundworm Caenorhabditis elegans’ asymmetry have discovered that the arbitrary left-right configurations of two types of olfactory neurons are established during development. In a study released in the journal Cell, they show that embryonic worms have a system of gap junctions that allow growing neurons on the left and right to communicate with each other, a system that dissolves as the worm develops. “A large number of embryonic neurons are heavily interconnected by gap junctions,” says Cori Bargmann, also a Howard Hughes Medical Institute investigator. “They all grow to the midline, communicate with each other and create a conduit of information that links together these two different sides of the brain.” Then, after the gap junctions do their job, they disappear. “This network is transient; we only know about it because we were able to look at this early period (using an electron microscope).” A similar system of extensive gap junctions appears in the developing mammalian brain, but researchers have yet to figure out exactly what it does. In worms, at least, they now know that it’s involved in differentiating the left and right sides.

Microvilli are Molecular Motors Speeding Up Nutrient Processing.
Microvilli are common features on the epithelial cells that line the body's cavities. The core bundle travelling up the center of the microvillus are an array of the structural protein actin, with ladder-like "rungs" connecting the actin bundle to the cell membrane and composed of the motor protein myosin-1a. This myosin, though related to the myosin involved in muscle cell contraction, previously was thought to serve a purely structural role. "The textbook thinking for decades was that microvilli serve as a passive scaffold, a way to amplify the membrane surface area," said Matthew Tyska, assistant professor of Cell and Developmental Biology at Vanderbilt University. In the intestines, an expanded cell surface increases the space for nutrient-processing enzymes and transporters, offering greater capacity for nutrient handling. However, the concentration of myosin motors in a single microvillus is very high, and Tyska questioned the serious force-generating potential of these villi as something more than useful for increased surface area. Tyska's group's findings are reported in the May 21 Journal of Cell Biology with one of their images featured on the issue cover. Through the microscope they have seen the villi in action. "What we're showing is that the microvillus is more than just a scaffold to increase the amount of cell membrane," Tyska said. "It's a little machine that can shed membrane from the tip." But why?