SUNDAY - January 13, 2008--------------------------------------------------News Archive/Return to Today's News Alerts
Common Molecule Notifies Immune System of Prostate Cancer
In experiments with mice, Howard Hughes Medical Institute investigator James P. Allison and his team have found that the body's immune system can use a surprisingly common molecule, histone H4, to recognize prostate tumors.
The molecule comes from a protein found in all cells of the body; however, immune cells appear to respond to it only when it is present on the surface of cells within a tumor.
Understanding how this protein signals the immune system to respond to malignant cells may help researchers refine immunotherapy strategies that harness the body's own immune system to fight tumors.
Some types of immunotherapy are already being tested in patients, but many questions remain unanswered. “We know very little about how the immune system responds to tumors, especially early tumors,” said Allison, director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center in New York. “Is the tumor at that stage invisible, or can immune cells detect it? And if they can detect it, can they mount a response? Those are the two big questions.”
Allison's research found that immune cells can, in fact, detect prostate cancer, at least in lab mice. However, the immune system mounts only a feeble attack against the tumor.
“The team is now examining the blood of patients with prostate and other cancers to see if people, like mice, carry T cells sensitive to histone. If so, “then we can take those cells out and try to activate them,” said Allison. “Those cells already recognize the tumor. If we can mobilize them, maybe it will have a therapeutic effect.”
Published January 11, 2008 in the journal Science
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A Few Molecules Flip the Angiogenic (tumor blood supply) Switch to 'ON'
The rapid formation of blood vessels, a process known as the angiogenic switch, is required for progression of dormant or micrometastatic tumors to macrometastatic invasive tumors.
New blood vessels may either sprout from preexisting mature ones or form by the recruitment of circulating endothelial progenitor cells (EPCs) from the bone marrow. Although these progenitors can incorporate into human tumors and transplanted tissue, they do so in small numbers. Dingcheng Gao, of the Cancer Genome Research Center, Cold Spring Harbor Laboratory, and his team show that even in low numbers, recruitment of endothelial progenitor cells is pivotal for the progression of micrometastatic tumors into becomming lethal macrometastatic ones.
Using mouse models of lung and breast cancer, the authors demonstrate that about 12% of the endothelial cells within macrometastases are from bone marrow. Remarkably, when the expression of Id1, a transcription factor that promotes angiogenesis, was reduced in this small number of tumor cells, their ability to mobilize from bone marrow decreased by 96%, angiogenesis was blocked, tumor formation decreased, and the animal's survival improved.
The inhibition of Id1 did not affect tumor cell spread or the colonization of organs by malignant cells, but shut off the mobilization and recruitment of particular endothelial progenitor cells that express the cell adhesion molecules Id1, VE-cadherin, and low amounts of CD31. These specific progenitor cells infiltrate micrometastatic lesions and stimulate blood vessel growth turning the micro lesion into a full macrometastic lesion.
Establishing standardized tests to detect and quantify repopulating progenitor cells is next.
Published January 10, 2008 in the journal Science
related autism articles in the American Journal of Human Genetics:
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How Stem Cell Cycle Differs from Normal Cell Cycle
Stem cell self-renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differences in differentiated cell numbers, resulting in significant physiological consequences.
Proliferation is typically regulated in the G1 phase, which is associated with differentiation and cell cycle arrest. However, embryonic stem (ES) cells may lack a G1 checkpoint.
Michael Andäng of the Karolinska Institute and his group report that autocrine/paracrine -aminobutyric acid (GABA) signalling by means of GABAA receptors negatively controls ES cell and peripheral neural crest stem (NCS) cell proliferation, preimplantation embryonic growth and proliferation in the boundary-cap stem cell niche, resulting in an attenuation of neuronal progenies from this stem cell niche.
Activation of GABAA receptors leads to hyperpolarization, increased cell volume and accumulation of stem cells in S phase, thereby causing a rapid decrease in cell proliferation.
GABAA receptors signal through S-phase checkpoint kinases of the phosphatidylinositol-3-OH kinase-related kinase family and the histone variant H2AX. This signalling pathway critically regulates proliferation independently of differentiation, apoptosis and overt damage to DNA.
These results indicate the presence of a fundamentally different mechanism of proliferation control in these stem cells, in comparison with most somatic cells, involving proteins in the DNA damage checkpoint pathway.
Published January 9, 2007 in the journal Nature
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SATURDAY - January 12, 2008-----------------------------------------------News Archive/Return to Today's News Alerts
Children Hardwired to Learn by “Over-Imitation”
Children learn by imitating adults - so much so that they imitate how an adult manipulates an object to make it work even if the adult takes unnecessary steps having nothing to do with that object and how it functions, according to a Yale study.
“Even when you add time pressure, or warn the children not to do the unnecessary actions, they seem unable to avoid reproducing the adult’s irrelevant actions,” said Derek Lyons, doctoral candidate, developmental psychology, and first author of the study. “They have already incorporated the actions into their idea of how the object works.”
Learning by imitation occurs from the simplest preverbal communication to the most complex adult expertise. It is the basis for much of our success as a species. But the instances of “over-imitation,” where children copy behavior that is not needed, are less understandable, Lyons said.
The Yale team found in this study that children follow the adults’ steps faithfully to the point where they actually change their mind about how an object functions.
The study included three-to-five-year-old children who engaged in a series of exercises. In one exercise, the children could see a dinosaur toy through a clear plastic box. The researcher used a sequence of irrelevant, as well as relevant, actions to retrieve the toy, such as tapping the lid of the jar with a feather before unscrewing the lid.
“What of all of this means,” Lyons said, “is that children’s ability to imitate can actually lead to confusion when they see an adult doing something in a disorganized or inefficient way. Watching an adult doing something wrong can make it much harder for kids to do it right.”
For more demonstrations - go to the project website: The Science of Being a Kid.
Published December 4, 2007 in the Proceedings of the National Academy of Sciences - PNAS
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A Common Genetic Variation on Chromosome Seven Linked to Autism
The risk for autism appears to increase in the presence of a common genetic variation on chromosome seven, especially when the condition is inherited from the mother, researchers say.
A variation on a single nucleotide polymorphism (SNP) found in 36% of the alleles of chromosome seven may give rise to autism, according to Aravinda Chakravarti, Ph.D., of Johns Hopkins, and colleagues,.
The contactin associated protein-like 2 (CNTNAP2) gene at position 7q35 on the human chromosome, a member of the neurexin superfamily, causes severe autism with medication-insensitive temporal lobe seizures, language regression, and low IQ. The mutation is most likely a mis-attachment of the axon to the glia via the TAG-1 protein and mislocalization of ion channels at that junction (see Visible Embryo NEWS ALERTS of January 11, 2008).
As neurons navigate along the glial cell scaffold, they move by means of gap junction protein adhesive contacts. Receptors on the cell surface - called integrins - link the extracellular matrix to the intracellular cytoskeleton. Neurons climb the glial "rope ladder", get off the ladder, move a little to the side and start to form the next cortical layer. If these integrins don't release their hold, the next wave of cells climbing the glial ladder pile up producing developmental anomalies leading to abnormal neuron connections.
Autism Spectrum Disorder (ASD) is a catch-all diagnosis for a set of poorly understood neurodevelopmental disorders, with a spectrum of severity. ASD is traditionally diagnosed by the age of 3 years and the severe forms can be accompanied by language regression, seizures, and low IQ.
The publication this week of three autism papers may help lead to early detection of CNTNAP2 mutation carriers - and the early intervention for their ASD children, especially during the critical 12 to 24 months of age of early brain development. Early intervention for ASD children will help some children to emerge relatively undamaged from their disorder, while giving all ASD children opportunities through intensive early instruction that they might never receive without proper diagnosis.
The unraveling of Autism Spectrum Disorder may finally have begun in earnest.
Published January 10, 2008 in the American Journal of Human Genetics
related autism articles in the American Journal of Human Genetics:
A Common Genetic Variant in the Neurexin Superfamily Member CNTNAP2 Increases Familial Risk of Autism
Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Disorders
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USA Updated Pediatric Immunization Schedule Released
The United States of America 2008 immunization schedule for children and adolescents features changes in recommendations for the pneumococcal, influenza, and meningococcal vaccines.
The recommendations were approved by the American Academy of Pediatrics, the CDC's Advisory Committee on Immunization Practices, and the American Academy of Family Physicians.
Three new recommendations are:
A single dose of pneumococcal conjugate vaccine for all healthy children from 24 months of age to 59 months of age who are not completely immunized.
Reduced age limit for use of live-attenuated influenza vaccine from five to two. When a second dose is indicated, the new recommendations state that the time interval between doses can be shortened by two weeks - previously six weeks - now given at four week intervals.
A single dose of quadrivalent meningococcal vaccine for 11-to-18-year-olds who haven't already received the vaccine. The committee also added a reminder about the 2006 Red Book recommendation that quadrivalent meningococcal conjugate vaccines are preferred over quadrivalent polysaccharide vaccines for children ages two to 10 at increased risk of infection.
Lorry Rubin, M.D., of Albert Einstein College of Medicine in New York, a member of the AAP committee, said the yearly tweaking of the vaccine schedule reflects not only improved understanding of immunogenicity, but also concern that children may serve as a reservoir of infection for at-risk groups, such as the elderly or those with compromised immune systems.
Published December 31, 2007 in the journal of the American Academy of Pediatrics
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FRIDAY - January 11, 2008---------------------------------------------------News Archive/Return to Today's News Alerts
Bacterial Infections in Premature Babies More Common Than Realized
Premature babies are subject to a host of threats that can result in fetal/neonatal disease.
Researchers from the University of Alabama–Birmingham Medical School and the Drexel University College of Medicine found that mothers' genital mycoplasmas (bacteria [lacking cell walls]) are a frequent cause of congenital fetal infection.
23% of neonates born between 23 and 32 weeks of gestation are positive in umbilical blood cultures for two genital mycoplasmas : Ureaplasma urealyticum and Mycoplasma hominis.
Although Ureaplasma urealyticum and Mycoplasma are found in 80% of vaginal and cervical fluids, infants are not generally screened for these bacterial infections. The finding that about one-quarter of early preterm infants is already infected at birth is important in reducing adverse outcomes.
Infected newborns had a higher incidence of neonatal systemic inflammatory response syndrome (SIRS), higher incidence of bronchopulmonary dysplasia (BPD), higher serum concentrations of interleukin (IL)-6 and more evidence of placental inflammation than those with negative cultures. The earlier the gestational age at delivery, the higher the rate of a positive umbilical cord blood culture.
“The initial uncertainties of whether genital mycoplasmas can cause fetal/neonatal disease are disappearing in light of the accumulating evidence that these microorganisms have been implicated in neonatal sepsis, pneumonia, meningitis and brain damage. Moreover, colonization of the neonatal respiratory tract with these organisms is a risk factor for chronic lung disease.” write Roberto Romero, MD, Chief of the Perinatology Research Branch and Program Director for Obstetrics and Perinatology at NICHD/NIH; Professor of Molecular Obstetrics and Genetics, Center of Molecular Medicine, Wayne State University, and Thomas J. Garite, MD, Professor Emeritus, Department of Obstetrics and Gynecology, University of California, Irvine,
Published January, 2008 in the American Journal of Obstetrics & Gynecology
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A Need for Glial Cells in Brain Development
The brain forms from the inside out. First the neural tube thickens, on its way to becoming the cortex where higher level activity such as perception and cognition occur. Then the six layers of the brain begin to build one on top of the other - each with a distinct pattern of organization and internal connections.
During fetal development, successive cell migrations follow glial cell trails which radiate out from the early brain. Each group of migrating cells passes through the previous layer, following an inside-out sequence following along the radiating glial cell paths.
As neurons navigate along the glial cell scaffold, they move by means of gap junction protein adhesive contacts. Receptors on the cell surface - called integrins - link the extracellular matrix to the intracellular cytoskeleton. Neurons climb the glial "rope ladder", get off the ladder, move a little to the side and start to form the next cortical layer.
But if these integrins don't release their hold, the next wave of cells climbing the glial ladder may pile up producing developmental anomalies leading to abnormal neuron connections and exhibiting as disturbed human behavior.
Richard Belvindrah, of The Scripps Research Institute, and associates followed two species of mutant mice called, "reeler" and "staggerer" (because of their bizarre motor behavior) to establish if their characteristics resulted from this type of developmental abnormality. Similar problems in the growing human fetus may contribute to the development of certain types of schizophrenia, temporal lobe epilepsy and, perhaps some forms of dyslexia.
Tissue culture analysis showed that normal formation of neuron extensions depended on the expression of ß1 integrin in the glia cell, but not in the neurons.
It seems that what matters for how ß1 integrin affects the layering of the developing cortex is not its expression in neurons but rather its expression in glial cells.
Published December 12, 2008 in The Journal of Neuroscience
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US Ranks Worst In Preventable Deaths Among 19 Industrialized Nations
A new report by a US health foundation has found that Americans get the worst deal in terms of preventable deaths among 19 industrialized nations.
The authors found that while other countries dramatically reduced deaths preventable by effective health care between 1997-8 and 2002-3, the US did so only slightly. If the US had performed as well as the top ranking countries, 101,000 fewer deaths per year could have been prevented, wrote Ellen Nolte and Martin McKee, who are based at the London School of Hygiene and Tropical Medicine.
"The fact that other countries are reducing these preventable deaths more rapidly, yet spending far less, indicates that policy, goals, and efforts to improve health systems make a difference," said Commonwealth Fund Senior Vice President, Cathy Schoen who was startled to see the US falling so far behind.
The measure takes into account a range of conditions that one might reasonably judge to be responsive to effective health care and thereby avoiding early death. These include, for example, appendicitis and high blood pressure, where the type of care required is obvious. It also includes conditions that can be detected with effective screening programmes such as cervical and colon cancer and TB (which is not fatal if treated early).
In more detail, the results showed that:
In 1997-8 the US was in 15th place out of 19 countries on the amenable mortality scale.
By 2002-3 the US had fallen to last place, with 109 deaths amenable to health care for every 100,000 people.
This compared with France at 64, Japan at 71, and Australia at 71 per 100,000, the three top performers in 2002-3. (The other industrialized nations included in the report were: Austria, Canada, Denmark, Finland, Germany, Greece, Ireland, Italy, Netherlands, New Zealand, Norway, Portugal, Spain, Sweden and the United Kingdom.)
Published January/February, 2008 in the journal Health Affairs
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THURSDAY - January 9, 2008------------------------------------------------News Archive/Return to Today's News Alerts
Coffee in Moderation Won't Increase Risk of Miscarriage
Drinking moderate amounts of coffee during pregnancy won't increase a woman's likelihood of miscarrying, new research shows.
"Based on what we've seen, it's not a cause for great concern," Dr. David A. Savitz of Mount Sinai School of Medicine in New York City, the study's first author, told Reuters Health, noting that past research has had similarly "reassuring" results.
But because women in the study consumed a relatively small amount of caffeine - the equivalent of less than two cups of coffee daily in early pregnancy and less later on - the study can't answer the question of whether consuming more might be harmful, he said.
Savitz and his team followed 2,407 pregnant women, 258 of whom miscarried. All of the women reported their caffeine consumption before they became pregnant; 4 weeks after their last menstrual period; and at the time of the interview.
Most women in the study who drank coffee or other caffeinated beverages consumed about 350 milligrams of caffeine daily before they became pregnant and in very early pregnancy, equivalent to 1.7 7-ounce cups of brewed coffee a day. At the time of the interview, their average caffeine intake had fallen to 200 milligrams.
At each of the three time points assessed, there was no statistically significant relationship between the amount of caffeine a woman consumed and her risk of miscarriage. "These data provide evidence to suggest that, within the lower range examined, caffeine intake is not associated with risk of miscarriage," Savitz and his colleagues conclude.
Published January, 2008 in the journal Epidemiology
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Missing Molecules Key to Breast Cancer Spread
By restoring tiny bits of genetic material missing from breast tumors in mice, U.S. researchers were able to block the cancer's ability to spread. Howard Hughes Medical Institute researchers identified that small pieces of ribonucleic acid (RNA) suppress the spread of breast cancer to the lungs and bone.
The finding will help doctors make better treatment decisions and may give rise to a new way of halting the advance of breast cancer, said Dr. Sohail Tavazoie, an oncologist at Memorial Sloan-Kettering Cancer Center in New York. "What's most important to us as cancer doctors is the concern that the cancer is going to come back," said Tavazoie, whose study appears in the journal Nature. The research will give doctors a better way to determine if a particular breast cancer tumor will spread and also add to the list of possible targets that could be used to make drugs that block genes that make cancers spread.
Cancer spreads when bits the primary tumor break off and attack other organs. This process, known as metastasis, is what makes cancer so deadly.
“The tiny RNAs prevent the spread of cancer by interfering with the expression of genes that give cancer cells the ability to proliferate and migrate,” said senior author Joan Massagué, a Howard Hughes Medical Institute researcher at Memorial Sloan-Kettering Cancer Center.
“These findings reveal still more genes that could be targets of drugs to interfere with metastasis,” he said. “Researchers in this field are currently accumulating an inventory of clinically significant genes to explore, and the set we identified has shown such significance.”
Massagué said his group is now designing experiments to ask whether the breast cancer genes regulated by the microRNAs they identified also control metastasis of other types of cancer.
Published January 10, 2008 in the journal Nature
Study: Rare Gene Change Linked to Autism
A rare genetic variation dramatically raises the risk of developing autism, a large study showed, opening new research targets for better understanding the disorder and for treating it.
Research into the causes of autism has focused on genetic causes because so many families have multiple children with the disorder. Thus far, only about 10 percent of autism cases have a known genetic cause. Boston-area researchers estimate the gene glitch they've identified accounts for another 1 percent of cases.
They found a segment of a chromosome which has genes linked to brain development and various developmental disorders was either missing or duplicated far more often in autistic people. The defect was inherited in some cases, but more often the result of a random genetic accident.
The results from the Autism Consortium study, released online Wednesday by the New England Journal of Medicine, confirm those of smaller studies by U.S. and Canadian research groups in the past year. The consortium verified its findings by checking two other DNA databases.
"They really did nail it," said Dr. Andrew Zimmerman, director of the Kennedy Krieger Institute's Center for Autism & Related Disorders in Baltimore, who was not involved in the research.
"Already, the findings are starting to be used to give some parents long-sought answers to burning questions: What caused autism in their child and how likely is it that any future children also would have autism, long known to run in families?
"We've provided very compelling evidence that this particular small stretch of the genome provides an important clue to the biological roots of autism," said lead researcher Mark J. Daly, an assistant genetics professor at Harvard Medical School and an investigator for the consortium, which includes researchers from 14 Boston-area universities and medical centers.
Published January 9, 2008 in the Journal of The American Medical Association
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WEDNESDAY - January 9, 2008----------------------------------------------News Archive/Return to Today's News Alerts
New Meningitis Vaccine Works in Infants
A new type of meningitis vaccine appears to offer protection for babies against several strains of the deadly bacterial form of the disease, British and Canadian researchers report.
The new vaccine, which is not yet licensed in the United States, provides immunity against four strains of meningococcal disease in all age groups, according to a study in the Jan. 9 issue of the Journal of the American Medical Association. There is currently no meningococcal vaccine approved for use in children under 2 in the United States.
"The key message for parents to take from this study is that this vaccine has the potential to reduce the number of cases of meningitis in babies and young children," said study author Dr. Matthew Snape, a pediatrician at the University of Oxford in the United Kingdom.
"There are approximately 1,400 to 2,800 cases of meningococcal infections in the United States per year. Approximately 10 to 14 percent of people experiencing this disease will die, and 20 percent of survivors will have long-term disabilities," said Snape. "The highest rates of disease are seen in children under the age of 2 years."
Meningitis is an infection that occurs in the spinal fluid, and it can be caused by a virus or bacterium, according to the U.S. Centers for Disease Control and Prevention. The bacterial forms of meningitis tend to be more serious, potentially causing brain damage, hearing loss and learning disabilities. Two vaccines - the Haemophilus influenza (Hib) and pneumococcal - can protect youngsters, including babies, against certain strains of bacterial meningitis, but not all. Two other vaccines offer protection against four strains of the Neisseria meningitidis bacteria - one for children aged 2 to 10 and the other for those aged 11 and up - but neither offers protection to babies.
"The study showed that the [Menveo] vaccine was able to stimulate production of protective antibodies against all four meningococcal groups in most of the children receiving the vaccine," said Snape. "For example, for children receiving the vaccine at 2, 3, 4 and 12 months of age, protective antibody levels were seen in 94 percent or above for all the meningococcus types."
Published January 9, 2008 in the Journal of the American Medical Association
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BERT and ERNI Proteins Control Brain Development
Scientists at University College London have discovered how two proteins called BERT and ERNI interact in embryos to control when different organ systems in the body start to form, deepening our understanding of the development of the brain and nervous system and expanding our knowledge of stem cell behavior.
During development, only a few signals instruct cells to form thousands of cell types, so the timing of how cells interpret these signals is critical. An international research team led by Professor Claudio Stern of the UCL Department of Anatomy & Developmental Biology has shown that the first stage of development of the brain and nervous system is, paradoxically, a block on its progression.
A sequence of reactions take place when vertebrate embryos are only a few hours old that together act as a timing mechanism, temporarily preventing the development of neural cells (cells that go on to form the brain and nervous system). This gives a head start to other cells in the embryo which go on to create the body’s internal organs and skin, and prevents the nervous system from developing prematurely.
Dr. Costis Papanayotou of the Stern laboratory discovered a new protein, BERT, which binds with the protein ERNI and other proteins to unblock a gene called Sox2, giving the green light to cells to start forming the brain and nervous system.
“Scientists have been looking for a long time for the switches that determine when cells in the embryo take on specific roles. Our work shows that the proteins BERT and ERNI have an antagonistic relationship: BERT is stronger and overrides ERNI’s suppression of the Sox2 gene, which has a crucial function in setting up the nervous system. As the Sox2 gene is also needed for stem cells to retain their ability to take on a variety of roles in the body and to renew themselves, this research also advances our knowledge of stem cell behavior in adults, which could have implications for this growing area of medical research,” remarks Profesor Stern.
Published January 8, 2008 in the journal PLoS Biology
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Autism Diagnoses Rise After End of Thimerosal in Vaccines
Removing thimerosal, the mercury-based preservative, from childhood vaccines did not stem the rise in autism cases in California, according to investigators here.
Most thimerosal had been removed from common childhood vaccinations by 2001, which should have caused a drop in new cases of autism if the preservative contributed to the occurrence of the condition.
Yet diagnosed cases have increased in recent years, while the levels of thimerosal have dropped to only trace amounts in most childhood vaccines, reported Robert Schechter, M.D., M.Sc., and Judith K. Grether, Ph.D., of the California Department of Public Health.
"The estimated prevalence of autism for children at each year of age from three to 12 years increased throughout the study period," the authors wrote. Per 1,000 children born in 1993, 0.3 had autism at age three, compared with 1.3 per 1,000 births in 2003. The highest estimated occurrence rate - 4.5 cases per 1,000 births - was reached in 2006 for children born in 2000.
"In the last decade, two hypotheses on autism-immunization links were raised that have had a profound impact in the field of autism research and practice and on public health at large," Dr. Fombonne wrote. "One incriminated the measles component of the triple measles-mumps-rubella (MMR) vaccine, the other the amount of thimerosal contained in most other childhood vaccines." Since the 2004 Institute of Medicine report favored the rejection of both hypotheses, "more studies have accumulated that have reinforced this conclusion, one independently reached by scientific and professional committees around the world," he writes.
"Parents of autistic children should be reassured that autism in their child did not occur through immunizations," Dr. Fombonne concluded. "Their autistic children, and their siblings, should be normally vaccinated, and as there is no evidence of mercury poisoning in autism, they should avoid ineffective and dangerous 'treatments' such as chelation therapy for their children."
Published January 9, 2008 in the journal Archives of General Psychiatry
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TUESDAY - January 8, 2008--------------------------------------------------News Archive/Return to Today's News Alerts
Novel Mechanism for Long-Term Learning Identified
Neuroscientists from Carnegie Mellon University and the Max Planck Institute have discovered the mechanism that resolves an apparent paradox: repetitive stimulation might actually reverse early gains in synapse strength which we see as "memory."
Researchers can now explain how brain synapses strengthen in response to new experiences. Previous research at Carnegie Mellon by lead author of the study Alison Barth, has shown a connection between synaptic plasticity, or changes, and learning and memory. However, the mechanisms that constitutes learning over time through continuing training or practice was still unknown.
"We know intuitively that the more we practice something, the better we get, so there had to be something that happened after the N-methyl-D-aspartate (NMDA) receptors switched function which helped synapses to continue to strengthen," said Barth, an assistant professor of biological sciences at the university's Mellon College of Science.
Barth chose to look at the cortex, an area of the brain responsible for a slower form of learning that can improve with additional training, or experience. This area of the brain area may use very different molecular mechanisms than the short-term, episodic memory found in the hippocampus.
Her team found that while the NMDA receptor is required to begin neural strengthening, a second neurotransmitter receptor - the metabotropic glutamate (mGlu) receptor - comes into play. Using an antagonist to block NMDA receptors enhanced synaptic strengthening, while blocking mGlu receptors caused strengthening to stop.
The neural mechanisms of learning and memory have been poorly understood," said Barth. "Establishing the relationship between NMDA and mGlu receptors will allow us to better understand how we learn and perhaps may help us better understand diseases where learning and memory is lost, as in Alzheimer's disease."
Published January 4, 2008 in the journal Science
Related: Science: Rules of Plasticity
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Exposure to Air Pollution Significantly Reduces Fetal Size During Pregnancy
Queensland University of Technology, Australia, senior research fellow Dr Adrian Barnett reports on a study compared the foetus sizes of more than 15,000 ultrasound scans in Brisbane to air pollution levels within a 14km radius of the city.
"The study found that mothers with a higher exposure to air pollution had foetuses that were, on average, smaller in terms of abdominal circumference, head circumference and femur length," Dr Barnett said.
“The 10-year study, which was undertaken by Dr Barnett, Dr Craig Hansen (US Environmental Protection Agency) and Dr Gary Pritchard (PacUser), has been published in the international journal Environmental Health Perspectives. "To our knowledge this is the first study of its kind as it uses ultrasound measurement as a direct estimate of growth, rather than using birth weight as a delayed measure of growth," Dr Barnett said.
The study looked at foetuses between 13 and 26 weeks duration. "When analysing scans from women at different distances to monitoring sites, we found that there was a negative relationship between pollutants such as sulphur dioxide found in diesel emissions, and ultrasound measurement. "If the pollution levels were high the size of the foetus decreased significantly."
“Dr Barnett said with research showing that bigger babies were healthier in childhood and adulthood, foetus size during pregnancy was important. "Birth weight is a major predictor of later health, for example, bigger babies have been shown to have higher IQs in childhood and lower risk of cardiovascular disease in adulthood."
"While we need to get more data from individual mothers before we can be more certain about the effects of air pollution on fetal development, we would recommend that where possible pregnant women reduce their exposure to air pollution."
Published January 1, 2008 in the Journal of Immunology
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New Hope for Patients Recovering From Spinal Injuries
Spinal cord damage blocks the routes the brain uses to send messages to the nerve cells that control walking. For years, doctors believed that the only way injured patients could walk again was to regrow the long nerve highways that link the brain and base of the spinal cord.
Now, for the first time, a UCLA study shows that the central nervous system can reorganize itself and follow new pathways to restore the cellular communication required for movement. The discovery could lead to new therapies for the estimated 250,000 Americans who suffer from traumatic spinal cord injuries. An additional 10,000 cases occur each year, according to the Christopher and Dana Reeve Foundation, which helped fund the UCLA study.
"Imagine the long nerve fibers that run between the cells in the brain and lower spinal cord as major freeways," said Dr. Michael Sofroniew, the study's lead author and a professor of neurobiology at the David Geffen School of Medicine at UCLA. "When there's a traffic accident on the freeway, what do drivers do? They take shorter surface streets. These detours aren't as fast or direct but still allow drivers to reach their destination.
"We saw something similar in our research," he said. "When spinal cord damage blocked direct signals from the brain, under certain conditions the messages were able to make detours around the injury. The message would follow a series of shorter connections to deliver the brain's command to move the legs."
"Our study has identified cells that we can target to try to restore communication between the brain and spinal cord," Sofroniew said. "If we can use existing nerve connections instead of attempting to rebuild the nervous system the way it existed before injury, our job of repairing spinal cord damage will become much easier."
Spinal cord injury involves damage to the nerves enclosed within the spinal canal; most injuries result from trauma to the vertebral column. This affects the brain's ability to send and receive messages below the injury site to the systems that control breathing, movement and digestion. Patients generally experience greater paralysis when injury strikes higher in the spinal column.
Published January 6, 2008 in the journal Nature Medicine
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MONDAY - January 7, 2008---------------------------------------------------News Archive/Return to Today's News Alerts
Obese Mom's Conception Phase Sets the Stage for Infant's Obesity
The number of overweight and obese Americans continues to grow and today, 50 percent of adults are overweight and up to 20 percent are obese. While the number of overweight/obese children is at an all time high, the steady increase of overweight infants - individuals under 11 months old - is extremely alarming.
Researchers have found that pregnant women who are overweight/obese are more likely to give birth to heavier babies, and the risk of overweight children becoming obese adults is nearly nine times greater than for children who are not overweight.
Studies also show that greater body-weight at birth and weight gain early in life increases the risk of becoming overweight or obese as an adult. Inheritance studies show that a child's body mass index (BMI) correlates more closely with the mother's BMI than with it's father's, suggesting that an interaction of both genetic and intrauterine influences, may contribute to later-life obesity risk in the offspring.
A study conducted at the Arkansas Children's Nutrition Center, Little Rock, AR. fed female rats liquid diets to examine the long-term gestational effects of maternal obesity on their offspring. Maternal body weights were monitored three times a week and all rats gave birth naturally. Offspring born to lean or obese rats were raised by surrogate mothers who were fed regular rodent diets to determine if the pups' obesity exposure was limited only during gestation.
What was found:
• at birth, the weight of the pups from both lean and obese moms was similar.
• the amount of calories the pups consumed (relative to their body-weight) suggests that both lean and obese pups consumed the same amount of calories - when both the lean and obese pups were fed a control diet, their body weights remained similar.
• But, when both groups were fed a high-fat diet, the obese pups gained remarkably more weight, suggesting that maternal obesity somehow programs an increased susceptibility to obesity in their offspring, despite a normal birth weight.
• when both groups were fed a control diet, obese pups had a ~ 1.6 times greater fat ratio compared to the lean pups. And, obese pups fed a high-fat diet had a 26 percent greater percent fat ratio and a 60 percent increase in subcutaneous fat mass vs. lean pups.
• high fat feeding significantly increased serum glucose, triglyceride, insulin and leptin levels in both groups. However, the serum insulin and leptin levels increased by 2.2 and 2.3 fold in obese pups compared to lean pups fed the same diet.
These findings add to the evidence that both maternal obesity and genetic background influence offspring's potential for obesity.
Published November 21, 2007 in the journal American Journal of Physiology
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Gene Protects Newborns from Killer Respiratory Disease
Yale School of Medicine researchers have isolated a gene that helps protect newborns from the most common respiratory cause of infant death in the United States - respiratory distress syndrome. This gene, macrophage migration inhibitory factor (MIF), also helps fetal lungs develop, the researchers report this month in the Journal of Immunology.
The overt cause of respiratory distress syndrome is underdeveloped lungs - the more premature the newborns, the more likely they are to have a loss of lung volume caused by air space collapse and poorly developed capillaries. Infants with the syndrome often require mechanical ventilation within the first hours of life.
“The finding is important because prematurity is not only the most common respiratory cause of infant mortality in the U.S., it also tends to be a more serious problem in inner city neighborhoods,” said Richard Bucala, M.D., professor of medicine and pathology, professor of epidemiology at Yale School of Public Health, and senior author of the study.
The research team studied premature mouse pups bred to be deficient in MIF and found that the lungs of these mice were less developed. The mice also had lower levels of vascular endothelial growth factor and corticosterone - two factors that promote lung development. In addition to its role in fetal lung development, the MIF gene also regulates the innate immune response and has been implicated in a number of inflammatory disorders, such as sepsis, acute respiratory distress syndrome in adults, asthma, and autoimmune diseases.
“Because relationships exist between the known human variants of MIF and the severity of other respiratory diseases such as asthma and cystic fibrosis, we are very interested to know whether MIF variants might be associated with a higher risk for developing respiratory distress syndrome or chronic lung disease in premature infants,” said Alia Bazzy-Asaad, chief of the pediatric pulmonary section at Yale School of Medicine and co-author of the study. “We hope to pursue this in future studies.”
Published January 1, 2008 in the Journal of Immunology
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Study Links Ovarian Cancer Survival to Gene Mutation
Ashkenazi Jewish women who have ovarian cancer and a certain mutation in the BRCA1 or BRCA2 gene live longer than those without the gene mutation, according to a study published by the Chaim Sheba Medical Centre in Israel.
Ashkenazi women who had the changes were 28 percent less likely to die from the breast cancer over a period of up to nine years during the study even though such mutations increase the chances of developing breast or ovarian cancer in the first place, researchers said. "It's possible that patients with these mutations respond better to chemotherapy - hopefully, once we learn more about the mechanisms of the response, tailoring individual treatment will further improve survival," said Siegal Sadetzki of the Chaim Sheba Medical Centre, who worked on the study.
Worldwide there are more than 190,000 new cases of ovarian cancer each year, according to the International Agency for Research on Cancer. The disease is more common in women after age 50. The BRCA genes, named for their role in breast cancer, help repair damaged DNA before it can make a cell turn cancerous. In people whose genetic code differs in certain ways - those with the mutations - the repair process goes wrong. Changes in these genes are more common among Ashkenazi Jewish women than for women in the general population and raise the risk of breast and ovarian cancer.
In the study, Israeli researchers also compared five-year survival between 213 Ashkenazi ovarian patients who had the genetic changes and 392 patients who lacked them. After five years, 46 percent of the women with the mutations were still alive, compared with 34.4 percent of others without it, the researchers reported in the Journal of Clinical Oncology.
And the differences were even more pronounced for women with advanced stages of the disease when it is tough to treat. Women with ovarian cancer often have mild or no symptoms until the disease has progressed.
"These findings persisted after controlling for other factors that influence ovarian cancer survival, such as patient age and some biological features of the tumor."
Published January 1, 2008 in the Journal of Clinical Oncology
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SUNDAY - January 6, 2008---------------------------------------------------News Archive/Return to Today's News Alerts
Third Gene Copy Is a Charm
Reports stretching back half a century have suggested that people with Down syndrome may have a reduced risk of breast, colon, and other cancers. The reason has been a mystery, but some researchers suspect it has to do with one or more of the genes on chromosome 21, which people with Down syndrome have three copies of instead of the normal two. A new study backs that idea, linking a gene that is triplicated in Down syndrome to a lower risk of colon cancer in mice.
Geneticists Thomas Sussan of the Johns Hopkins Bloomberg School of Public Health and Roger Reeves of the Johns Hopkins School of Medicine, both in Baltimore, Maryland, and their colleagues mated mice prone to colon cancer with mice commonly used to model Down syndrome. These mice have extra copies of 108 genes--about half as many triplicated genes as in Down syndrome. Offspring that inherited the triplicated genes and the genetic susceptibility to cancer had only half the number of intestinal tumors as their cancer-prone parents, and the tumors that did develop were smaller, the team reports in the 3 January issue of Nature.
Additional experiments with several other mouse strains suggested that a gene called Ets2 - whose human counterpart is triplicated in people with Down syndrome - accounts for much of the protection. Ironically, Reeves says, Ets2 was previously identified as a cancer promoter. He can't explain why having an extra copy of the gene would produce the opposite effect. "I think this is going to be a fairly complex thing to work out," Reeves says, adding that Ets2 encodes a transcription factor that influences the activity of at least 200 other genes.
The counterintuitive finding that a gene that promotes cancer in some situations may repress it in others could have important implications for understanding, and ultimately treating, cancer in the general population, says geneticist David Threadgill of the University of North Carolina, Chapel Hill. "I think we have to reevaluate how we look at a lot of these cancer-associated genes."
Published January, 2008 in the journal Nature
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Stem Cell Shots Rescue Terminally Ill Children
Children who had seemed doomed to die within weeks may have been rescued by injections of stem cells originally extracted from healthy bone marrow donors.
The children all had graft-versus-host [GVH] disease, a condition in which bone marrow transplants aimed at treating diseases such as leukaemia end up attacking the child instead. Between 30 and 60 per cent of children receiving such transplants develop the condition. While the majority of cases are mild and can be resolved with immunosuppressive drugs, a minority of patients do not respond to treatment and die within three months from liver failure, diarrhoea and bleeding in the gut.
Osiris Therapeutics of Columbia, Maryland, teamed up with Vinod Prasad at Duke University Medical Center in Durham, North Carolina, to offer injections of mesenchymal stem cells, isolated from the bone marrow of healthy donors, to 12 children aged four months to 15 years who had not responded to conventional treatment.
In 2001, Osiris and the Dana Farber Cancer Institute in Boston had shown that mesenchymal stem cells [MSCs] from the bone marrow of adults do not carry the markers on their surface that lead to rejection. White blood cells causing the inflammation associated with graft-versus-host disease were pacified when exposed to the transferred mesenchymal cells. The cells were so good at evading rejection that transplanting them from pigs to rats did not trigger a response, according to unpublished work by Ray Chiu of McGill University in Montreal.
Five of the 12 children who received the stem cell injections, are still alive after eight months. However, seven children died but not from GVH. They suffered from infections or organ failure caused by their cancers. Yet each displayed no GVH prior to their deaths. Osiris wants to begin a much larger trial to see if the results are repeatable.
Published January 6, 2008 in the journal New Scientist
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Laser Procedure May Treat Vasa Previa Pregnancies
A University of South Florida fetal surgeon at Tampa General Hospital successfully treated in utero a rare but potentially devastating condition in which placental blood vessels block the birth canal and can rupture during labor, leaving the baby without vital blood and oxygen. If undiagnosed, the condition known as vasa previa is frequently deadly for newborns.
Ruben Quintero, MD, professor and director of the Division of Maternal-Fetal Medicine at USF Health, used a laser to seal off the abnormally positioned fetal blood vessels connecting the two parts of a bilobed placenta. The procedure essentially removed the unprotected vessels crossing the cervical entrance to the birth canal beneath the baby, so that the vessels would not tear or break and cause rapid fetal hemorrhage.
“This is the first time laser therapy has been used to correct vasa previa,” said Dr. Quintero, a pioneer in the field of minimally-invasive fetal surgery. “Patients have described this prenatal condition as a ticking time bomb waiting to go off. A patient with vasa previa lives with the constant worry that if her water breaks at any time, she may lose the pregnancy.”
Vasa previa occurs in about 1 in every 2,000 to 5,000 pregnancies. Despite advances in medical technology, the condition often goes undetected until it is too late and then an emergency caesarian section and aggressive resuscitation is required to save the baby. Vasa previa has a high death rate if it’s not caught before labor, because many babies lose most or all of their blood supply within a few minutes when their mother’s water breaks. A color Doppler ultrasound showing blood flow in the womb can help detect vasa previa, but unless a woman is identified as having a high-risk pregnancy, she typically does not get this more sophisticated test during pregnancy
Published December, 2007 in the Journal of Maternal-Fetal and Neonatal Medicine
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MONDAY - December 24, 2007-----------------------------------------------News Archive/Return to Today's News Alerts
Breakthrough of the Year - Human Genetic Variation
In 2007, researchers were dazzled by the degree to which genomes differ from one human to another and began to understand the role of these variations in disease and personal traits. Science and its publisher, the American Association for the Advancement of Science - AAAS, the nonprofit science society, recognize “Human Genetic Variation” as the Breakthrough of the Year, and identify nine other of the year’s most significant scientific accomplishments in their 21 December issue.
“For years we've been hearing about how similar people are to one another and even to other apes,” said Robert Coontz, deputy news editor for physical sciences who managed the selection process. “In 2007, advances on several fronts drove home for the first time how much DNA differs from person to person, too. It’s a huge conceptual leap that will affect everything from how doctors treat diseases to how we see ourselves and protect our privacy.”
The genomes of several individuals have already been sequenced. As technologies advance, many of us will have some, perhaps all, of our own genomes sequenced and will be able to learn the diseases for which we are at risk.
Since the sequencing of the human genome, biologists have been charting minute variations as small as one base, called single-nucleotide polymorphisms (SNPs). These variations were key to a dozen research projects in 2007 called genome-wide association studies in which researchers compared the DNA of thousands of individuals with and without a disease to determine which small genetic variants pose risks. This information can help lead researchers to disease-related genes, as in the case of several type 2 diabetes genes found this year.
In 2007, biologists also learned that within DNA’s billions of bases, thousands to millions of them can get lost, added or copied in ways that can change genetic activity within a few generations. The effects of these “copy number variants” have been shown in populations with high-starch diets, as they have more copies of a gene for digesting starch than members of societies of hunter gatherers. Geneticists who studied the genomes of children with and without autism have found a new DNA modification that leads to increased risk for autism.
Genomes can differ in many other ways. Bits of DNA ranging from a few to many thousands, even millions, of bases can get lost, added, or turned around in an individual's genome. Such revisions can change the number of copies of a gene or piece of regulatory DNA or jam two genes together, changing the genes'products or shutting them down. This year marked a tipping point, as researchers became aware that these changes, which can alter a genome in just a few generations, affect more bases than SNPs.
In one study, geneticists discovered 3600 so-called copy number variants among 95 individuals studied. Quite a few overlapped genes, including some implicated in our individuality--blood type, smell, hearing, taste, and metabolism, for example. Individual genomes differed in size by as many as 9 million bases. This fall, another group performed an extensive analysis using a technique, called paired-end mapping, that can quickly uncover even smaller structural variations.
These differences matter. One survey concluded that in some populations almost 20% of differences in gene activity are due to copy-number variants; SNPs account for the rest. People with high-starch diets--such as in Japan--have extra copies of a gene for a starch-digesting protein compared with members of hunting-gathering societies. By scanning the genomes of autistic and healthy children and their parents for copy-number variation, other geneticists have found that newly appeared DNA alterations pose a risk for autism.
New technologies that are slashing the costs of sequencing and genome analyses will make possible the simultaneous genome-wide search for SNPs and other DNA alterations in individuals. Already, the unexpected variation within one individual's published genome has revealed that we have yet to fully comprehend the degree to which our DNA differs from one person to the next. Such structural and genetic variety is truly the spice of our individuality.
Other Observations in 2007 Regarding Fertility and Infertility:
One serving a day of a low- or nonfat dairy product increased the risk of ovulatory infertility by 11%. But adding one serving per day of a full-fat dairy product, particularly whole milk, decreased it by 22%.
One or two servings a day of whole milk or other full-fat dairy foods. The idea is to balance the ratio of male to female hormones - not pack on pounds which disrupt the balance of hormones needed for reproduction.
Take a multivitamin. Though American women of childbearing age are advised to consume 400 micrograms of folic acid per day to prevent neural tube birth defects, the nurses study found that ovulation and conception improve with consumption of at least 700 micrograms per day.
Women who regularly took an iron supplement of at least 40 milligrams a day were 40% less likely to have trouble getting pregnant. But this was only true of women who got the iron from fruits, vegetables, beans and supplements. Those who consumed iron from mostly meat, which contains a different form of iron than that found in other food sources, weren't protected from ovulatory infertility. Previous research suggests that a woman's eggs and the embryo need iron to function properly.
"It's incredible that some of the simplest interventions - simple in theory at least - may in fact be the most effective," says Adamson, a reproductive endocrinologist in San Jose. "It's really important for women to understand that there are a lot of things they do to ensure the best reproductive outcome for themselves."
Published November, 2007 in the journal Obstetrics & Gynecology
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