SUNDAY - December 2, 2007----------------------------------------------News Archive/Return to Today's News Alerts

Autumn and Winter Babies Like Sports

Children who are good at sports are more likely to be born in the autumn and winter months, according to one of the largest studies of early childhood.

The findings are the latest to emerge from Children of the 90s, which has followed the health and development of 14,000 children since before their births in the early 1990s.

Researchers at Bristol University found that children born in the spring were the most sluggish. Those born in the summer were 4.5% more active than the norms, while those delivered in the autumn and winter months were 9% more active.

The researchers asked 5,451 children aged 11 to 12 to wear a device around their waist that recorded, minute by minute, their levels of activity for a week. The device also logged the intensity and frequency of physical activity.

Researchers then compared the children's activity levels with an array of other factors such as their birth date, how active their mother was during and after pregnancy and whether they had sib

Calum Mattocks, the study leader, said a biological explanation was unlikely. He suspected a link to when children begin school: "If you're born later in the school year, you're likely to be smaller than your peers and that could disadvantage you in sports and other activities, such as playing." Older children were likely to be bigger and stronger than classmates and more likely to do better in sports, perhaps motivating them to stay interested in exercise as they grew up, he added.

"Previous studies have indicated that children born late in the school year may be at a disadvantage academically. Our findings show that this may also be true of physical activity, which could impact on future health. If teachers are aware of this, they can try to make it possible for the younger children to achieve at an appropriate level. This could help them stay motivated, before they decide they're 'no good at games'," said Mattocks.

Having at least one physically active parent led to children being on average 4% more active; an older sibling improved activity levels by a similar amount.

A weak link was found between watching television and activity levels later in life. Children who watched a lot of TV between the ages of three and four were less than 1% less active than others by the time they reached 11.

Published December, 2007 in the BMJ - British Medical Journal.


Hotspots Found For Chromosome Gene-Swapping

It appears that crossovers and double-strand DNA breaks are not occurring randomly on yeast chromosomes during meiosis as thought, according to research in the laboratory of Whitehead Fellow Andreas Hochwagen. Instead, their proximity to the chromosome’s telomere affects these crossovers.

Chromosome abnormalities and birth defects are the result of faulty crossovers.

Meiosis is a type of cell division that produces cells with only one copy of each chromosome - spores in yeast, and eggs and sperm in higher organisms.

During meiosis, chromosome pairs line up in the middle of the cell. Then they are pulled apart, with exact copies of each ending up at opposite sides of the cell. To ensure that they align properly in the middle of the cell, chromosomes crossover - or swap certain sections of genes.

Without crossovers, chromosomes could misalign and both copies of a chromosome might end up in one cell. When this happens, the cells die or produce severe genetic problems, such as Down syndrome.

Before a crossover can occur, both strands of a chromosome’s DNA helix must be broken. About half of these double-strand DNA breaks (DSBs) are processed to form crossovers, and the rest are resealed to restore the original chromosomes.

The final number of crossovers is relatively small and scientists have long wondered how cells ensure that even the smallest chromosomes make at least one crossover. Indeed, in almost half of Down’s Syndrome cases, chromosome 21, one of the smallest human chromosomes, failes to form a crossover in one of the parents.

Hannah Blitzblau, graduate student at MIT, suggests that part of the answer lies in where DSBs are formed.

Blitzblau has shown that DSBs are not scattered randomly throughout the chromosomes, but occur most frequently in a specific band near telomeres, the end caps of chromosomes. When telomeres are manually engineered into the central part of a chromosome, this DSB “hotspot” effect is still seen the same distance from the new telomere location.

“This is a simple mechanism for making sure that all chromosomes, even the shortest ones, have the crossovers required for meiosis,” says Blitzblau. “If the breaks occurred randomly, the smallest chromosomes often wouldn’t have any crossovers.”

In addition, Blitzblau showed that DSBs occur at high rates around the central part of the chromosome called the centromere. It was previously thought that DSBs and crossovers rarely occurred in this region.

“This is incredibly surprising,” says Hochwagen. “The chromosomes start the crossover process in the centromeres, but divert and reseal the breaks instead.”

Some earlier research into crossovers had been done in mutant yeast strains. But the Whitehead researchers say that their current work in non-mutant yeast is a more accurate representation of normal processes.

This research will help scientists understand chromosome events leading to infertility and birth defects.

Published November 30, 2007 in the journal Genes & Development.


How Our Ancestors Were Like Gorillas

Research published this week shows that some of our closest extinct relatives had more in common with gorillas than we thought.

Dr Charles Lockwood, UCL Department of Anthropology and lead author, said: “When we examined fossils from 1.5 to 2 million years ago we found that in one of our close relatives the males continued to grow well into adulthood, just as they do in gorillas. This resulted in a much bigger size difference between males and females than we see today.

“It’s common knowledge that boys mature later than girls, but in humans the difference is actually much less than in some other primates. Male gorillas continue to grow long after their wisdom teeth have come through, and they don't reach what is referred to as dominant "silverback" status until many years after the females have already started to have offspring.”

Jacopo Moggi-Cecchi, based at the University of Florence and an expert on fossil teeth, participated in the study and says: "It takes large samples of fossils to ask questions about variation and growth, and it's really a tribute to fieldworkers such as Robert Broom and Bob Brain [who worked at Swartkrans] that this research could even take place. It's also an example of why we need to continue to look for fossils after we think we know what a species is – more specimens allow us to answer more interesting questions. Even isolated teeth can give us new insights into what variation means.”

Another point to be made by the researchers, is that not all fossil hominin samples show the same patterns of growth. It is quite possible that further work will reveal even more diversity in social structure between our extinct human ancestors - the same way that differences exist between today's chimpanzees and bonobos.


Published October, 2007 by the Natural History Museum, London The Human Story: Where We Come From and How We Evolved.

SATURDAY - December 1, 2007----------------------------------------------News Archive/Return to Today's News Alerts

Reducing Seizures in Pregnant Women With Epilepsy

New research shows that monitoring the level in the blood of the popular epilespy drug lamotrigine, helps reduce the increased seizure activity and improve the overall health of pregnant women and their fetuses.

Lamotrigine is popular because of its mild risk of birth defects. But it has been linked to increased seizure activity in up to 75 percent of pregnancies.

“This is important data considering current treatment guidelines do not address how to dose epilepsy drugs once women become pregnant,” said study author Page B. Pennell, MD, with Emory University School of Medicine in Atlanta, GA, and member of the American Academy of Neurology.

For the study, 53 women taking lamotrigine underwent therapeutic drug monitoring every one to three months throughout their pregnancies.

Researchers measured seizure activity and the amount of lamotrigine in the blood since past studies have shown lamotrigine levels significantly drop during pregnancy, causing seizures to worsen.

In the current study, the clearance of lamotrigine increased by 89 percent in the third trimester compared to non-pregnant levels. Dosages were adjusted depending on the lamotrigine blood levels with the goal of maintaining each patient’s target concentration determined by pre-pregnancy information.

The study found that although 39 percent of women reported an increase in seizure activity during their pregnancy, 33 percent actually reported a decrease in seizures and 28 percent no change. The health of the babies born was similar to that found in women who do not have epilepsy.

“This type of drug monitoring is relatively easy since pregnant women can give blood for lamotrigine testing during their regular visits with their obstetrician or neurologist,” said Pennell. “It’s really a benefit for both mothers and babies.”

Interestingly, the study also found the amount of lamotrigine leaving the blood during pregnancy was higher in white women compared to African American women.

Published online November 28, 2007 in the journal Neurology.


Reversing Ageing Skin in Mice - With a Patch

Blocking the effects of a single gene can reverse skin ageing in mice, finds a new study which switches off a key protein in the skin.

However, the protein switched off also plays an important role in the immune response. Therefore, scientists caution that the technique might cause side-effects and is unlikely to be used to erase wrinkles in people until more investigation reveals its risks.

Lead researcher, Dr Howard Chang, from the Stanford School of Medicine in California, said the findings supported a theory that ageing is the result of specific genetic changes rather than accumulated wear and tear.

Chang's group used a technology called microarray analysis to get a picture of which of the 20,000 genes in the entire mouse genome are most active in the skin at different ages. They found a particular gene, called NF-Kappa-B, activates a number of genes in the skin – especially in old age. The needed a way to switch off the NF-Kappa-B protein produced by this gene. So they genetically engineered mice with a molecule that travels to the cell nucleus and disables the NF-Kappa-B protein. But the molecule can only do this in the presence of a specific drug called 4-hydroxytamoxifen.

The team applied skin patches containing the drug on the backs of 2-year-old mice – near the upper age limit of the rodent – and monitored what happened. They also applied a patch containing only ethanol as a control, refreshing the patches daily for two weeks.

There were no marked changes in the area of the skin under the control patch over this period. But the experimental treatment patch produced about a 75% increase in the thickness of the skin.

This change is significant because, while mice do not get wrinkles as humans do, rodents' skin does become thin in old age – possibly as a result of the failure of new cell growth and the breakdown of supporting collagen proteins.

Published November 30, 2007 in the journal Genes & Development.


Pedophilia May Be the Result of Faulty Brain Wiring

Pedophilia might be the result of faulty connections in the brain, according to new research released by the Centre for Addiction and Mental Health (CAMH).

The study used MRIs and a sophisticated computer analysis technique to compare a group of pedophiles with a group of non-sexual criminals. The pedophiles had significantly less of a substance called “white matter.” which is responsible for wiring the different parts of the brain together.

The study, published in the Journal of Psychiatric Research, challenges the commonly held belief that pedophilia is brought on by childhood trauma or abuse. This finding is the strongest evidence yet that pedophilia is instead the result of a problem in brain development.

Previous research from this team has strongly hinted that the key to understanding pedophilia might be in how the brain develops. Pedophiles have lower IQs, are three times more likely to be left-handed, and even tend to be physically shorter than non-pedophiles.

“There is nothing in this research that says pedophiles shouldn’t be held criminally responsible for their actions,” said Dr. James Cantor, CAMH Psychologist and lead scientist of the study, “Not being able to choose your sexual interests doesn’t mean you can’t choose what you do.”

This discovery suggests that much more research attention should be paid to how the brain governs sexual interests. Such information could potentially yield strategies for preventing the development of pedophilia.


Published December, 2007 in the Journal of Psychiatric Research.


FRIDAY - November 30, 2007------------------------------------------------News Archive/Return to Today's News Alerts

Cancer Fighter Gene P53 May Help Embryo to Implant

A protein known primarily for its role in fighting cancer also helps embryos implant in the womb, according to a study in mice. The find may explain why some women have difficulty becoming pregnant.

The p53 protein is known for its anticancer performance, it repairs DNA damage and initiates cell death to prevent the formation of tumors. Mutations in the p53 gene can lead to cancer. What p53 does under normal conditions is a mystery, however.

Last year, researchers led by reproductive endocrinologist Carolyn Coulam of the Rinehart Center for Reproductive Medicine in Evanston, Illinois, found an association between women carrying variations of p53 having problems conceiving, but why was unclear.

A team led by p53 co-discoverer and cancer biologist Arnold Levine of the Institute for Advanced Study in Princeton, New Jersey, has noticed a link between p53 and fertility in past experiments. The presence or absence of the gene seemed to have an effect on whether female mice became pregnant.

The team dug deeper, comparing mice bred to lack p53 with normal mice, and found the normal mice all became pregnant after breeding with litters of five to six pups, but just 63% of the mice lacking p53 became pregnant and their litters were only one or two pups. In another strain lacking p53, only 27% of the mice conceived and birthed pups.

Because the p53 protein fights cancer by regulating certain genes, the researchers thought maybe p53 regulates certain genes in reproduction. A scan of possible target genes identified the leukemia inhibitory factor (LIF) gene. LIF codes for a protein of the same name which helps embryos implant in the womb, as well as snuffing out certain leukemia cells.

More experiments confirmed that p53 regulates LIF. Female mice lacking the p53 gene had lower levels of LIF in their uteri, and fewer embryo implantation sites. Giving LIF to these mice reversed their fertility problems, improving their pregnancy rate to 100% and increased their litter size. And it did not adversly effect mice with the p53 gene.

Coulam says this new role for p53 may explain infertility cases where the embryo fails to implant.

It also suggests a new role for cancer-treating drugs that target p53, adds developmental biologist Colin Stewart of the Institute of Medical Biology in Singapore. "Some of these drugs may turn out to be useful in helping women conceive by improving the function of p53 in the uterus. … Others may turn out to be possible contraceptives by blocking p53's function in the uterus."

Published online November 29, 2007 in the journal Nature.


'Supermouse' Created That Beats Cancer

Mice created with a gene making them almost invulnerable to cancer may help us create safer and more effective treatments for humans.

The new breed were created with a more active "Par-4" gene, and did not develop tumours, even living longer!

Par-4 was was originally discovered in the early 1990s working inside human prostate cancers. It is believed to have a role in "programmed cell death"- apoptosis - the body's own system for rooting out and destroying damaged or faulty cells.

A Kentucky team of scientists used an existing mouse breed known to be more vulnerable to cancers to test whether Par-4 could be used to fight cancers. They introduced the gene to mouse eggs, and it became active in both the resulting pups - and those pups own offspring.

Dr Vivek Rangnekar, who led the research, said that the gene offered the potential, unlike most other cancer treatments, of destroying cancer cells without harming normal cells.

"When a cancer patient goes to the clinic, they undergo chemotherapy or radiation and there are potential side effects associated with these treatments. We are thinking of this as a holistic approach that not only would get rid of the tumour, but not harm the organism as a whole."

“A spokesman for Cancer Research UK said: "Although at an early stage, research like this allows us to understand more about the faulty genes involved in cancer and throws open new avenues to explore for cancer treatment.

"It's important to remember that this work has only been done using genetically engineered mice, and more research is needed before we'll know if it can be translated to humans."

Published November 28, 2007 in the journal Cancer Research.


Mature Heart Cell Potential in Embryonic Stem Cells

In a new study, UC Davis researchers report the first functional evidence that heart cells derived from human embryonic stem cells exhibit one of the most critical properties of mature adult heart cells, an important biological process called excitation-contraction coupling.

The finding gives scientists hope that these cells can one day be coaxed into becoming functionally viable cells safe for transplantation into the damaged hearts of patients with end-stage disease, potentially avoiding the necessity of a heart transplant. Currently, there are nearly 3,000 people on heart transplant lists around the nation, including more than 300 in California.

UC Davis research scientist Ronald Li and his colleagues write that they observed cells that had begun the maturation process toward becoming heart cells.

Li took human embryonic stem cells and grew them in cultures, allowing them to differentiate, or develop, into heart cells. Once they had these tiny, pulsing masses, the investigators energized the cells with small amounts of electrical current and chemicals, including caffeine. They then measured how the amount of intracellular calcium changed and looked for the presence of proteins and cellular structures known to be involved in excitation-contraction coupling.

According to Li, the fact that different cell lines exhibit different potentials for differentiation and maturation underscores the need to develop new and additional stem cell lines in order to advance critical research into potential therapies for patients.

Li’s study is a first step toward deriving cardiomyocytes with fully functional contractile properties from human embryonic stem cells. With heart transplants being the current treatment of last resort due to severe shortages of donor organs and the complexity of transplantation, the long term goal of researchers like Li is to come up with alternatives that are both safe and effective.

“Our latest study gives us great hope of eventually achieving a breakthrough where stem cell therapy could be used in the types of cases that today require a heart transplant,” concluded Li.

Published December, 2007 in the journal Stem Cells.


THURSDAY - November 29, 2007--------------------------------------------News Archive/Return to Today's News Alerts

Diet May Influence The Sex Of Your Baby

A mother’s diet in the run-up to conception could influence the sex of her child, suggests a study in mice. The research shows that mice given drugs to lower their blood-sugar levels produced significantly more female than male pups.

The findings mimic traditional beliefs that eating certain foods can influence the sex of offspring.

Conventional wisdom tells us the father’s sperm is the main determinant of the sex of a child. But increasingly scientists have found hints that maternal factors might have an influence too. For example, earlier work has suggested that single mothers are more likely to give birth to daughters.

Elissa Cameron at the University of Pretoria in South Africa and her colleagues wanted to study how changes in diet might influence sex ratios – the proportion of males to females in a population. To do this, they altered the levels of blood-sugar in female mice during conception, by feeding the mice a steroid called dexamethasone (DEX), which inhibits the transport of glucose into the bloodstream.

The scientists gave 20 female mice water dosed with DEX for the first three days that the females were exposed to males. Afterwards, the mice were given plain water. Cameron’s team measured the blood-sugar levels of these mice, as well as that of 20 control females several times during the experiment.

The average blood-glucose levels in mice that received DEX dropped from 6.47 to 5.24 millimoles/litre. And the team found that 53% of the pups born to the control females mice were male, but only 41% of those born to the mice receiving DEX were male.

Exactly how a drop in blood sugar causes more female births remains unclear. But the opposite also seems to work. A previous study involving diabetic mice, found that rodents with high blood-sugar levels produced more male offspring than expected.

Biologists have theorised that mothers may give birth to more female offspring during times of stress or ill health, because it confers an evolutionary advantage. If the stressed mother gave birth to a weak male, he is unlikely to mate. But if the child was female, no matter how weak, she would likely bear more children.

“It does seem that sugar levels could act as an indicator of whether a mother is in a good state or bad state,” says Ruth Mace at the University College London, UK. Mace previously published a study that found mothers with more muscle mass are more likely to give birth to sons during food shortages.

The idea of diet influencing sex ratio is already part of traditional wisdom. Folklore says that mothers should eat more red meat and salty snacks if they want a boy, and fish, vegetables, chocolates and sweets if they want a girl. “This is interesting, since meat raises blood sugar for a sustained period of time, whereas sugar-based snacks raise blood sugar very high, but for a short amount of time, followed by a slump in blood glucose,” says Cameron.

Published online November 28, 2007 in the journal Proceedings of the Royal Society.

Shinya Yamanaka - Stem Cell Pioneer - Says Embryonic Research Still Needed

Shinya Yamanaka, the Japanese scientist who produced stem cells from skin, says controversial research on human embryos must continue for now, as it will take time to put the new breakthrough into practical use.

"It was a breakthrough. It allowed us to see a goal. But the goal is far off in the distance," Shinya Yamanaka, the leader of the Kyoto University research team, told AFP in an interview. His team's work, verified by US researcher James Thomson of the University of Wisconsin at Madison, has generated stem cells from human skin.

"Before our success in the human skin research, we had to do research on animals because it is extremely hard to obtain human embryonic stem cells for research purposes," Yamanaka said.

Research involving embryonic stem cells - which can develop into various organs or nerves - is seen as having the potential to save lives by helping find cures for diseases such as cancer and diabetes.

Japan, the largest spender on scientific research after the United States, has fewer taboos about embryonic research. However, all projects in Japan need approval from a government panel on bioethics, which has restrictions including a prohibition on attempts at human cloning. Many women are also hesitant to donate eggs.

Yamanaka's team generated versatile iPS (induced Pluripotent Stem) cells, which, like embryonic stem cells, can develop into various organs and tissues. The researchers last year generated the world's first iPS cell by introducing four genes into mice skin. In the breakthrough project, they succeeded in generating the human iPS cells by putting the same four genes into human skin cells.

“This alternative way of developing stem cells, however, holds the risk of causing cancer because it uses a retrovirus - seen as having a carcinogenic quality - to make the skin cell function as a stem cell. In addition, one of the four genes is a cancer gene.

"We have to test the safety of the alternative stem cells first, including the risk of cancer," said Yamanaka.

Reported November 28, 2007 in the online newspaper The Raw Story.


Protein Injections Can Delay Symptoms Of Lou Gehrig's Disease

A research team from Wake Forest University School of Medicine is the first to show that injections of a protein normally found in human cells can increase lifespan and delay the onset of symptoms in mice with ALS (amyotrophic lateral sclerosis), or Lou Gehrig's disease.

The researchers found treatments of recombinant heat shock protein 70 (Hsp70) increased total lifespan by 10 percent - significantly more than Riluzole®, the only ALS treatment approved by the U.S. Food and Drug Administration. They cautioned, however, that while the research suggests a new treatment approach for ALS, it is not ready for studies in patients.

"This is another piece in the puzzle of what causes ALS and how to best treat it," said David Gifondorwa, lead author and a Ph.D. candidate at Wake Forest. "It's possible that one day a treatment based on this finding could be part of a 'cocktail' for attacking the disease from different fronts."

ALS is a disease that causes death of motor neurons, the nerve cells that control muscles. There are two sets of motor neurons affected in ALS: upper motor neurons that are located in the brain and brainstem, and lower motor neurons that are located in the spinal cord but send out nerve fibers, or "transmission lines," to connect with muscles. The study focused on the lower motor neurons. Previous research by Wake Forest and others had shown that before the motor neuron dies, it first detaches, or denervates, from the muscle.

"Our hope is that the results of our study will help steer thinking into focusing on what happens at the junction of nerve and muscle. It is possible that if we can develop treatments to maintain the contact of nerves and muscle, we can maintain the health of the motor neurons longer" says Carol Milligan, Ph.D., senior researcher.

The mice in the study got injections with Hsp70 three times a week beginning 50 days after birth. Lifespan increased by 10 days in the Hsp70 treated mice, compared to one day in the Riluzole group. Ten days represents about 10 percent increase in the lifespan of the mouse model of ALS. In humans, Riluzole increases lifespan by only about 60 days.

Published November 28, 2007 in the Journal of Neuroscience.


WEDNESDAY - November 28, 2007-----------------------------------------News Archive/Return to Today's News Alerts

Radiation Exposure of Pregnant Women More than Doubles in 10 Years

The past decade has seen an unprecedented increase in the use of radiologic exams on pregnant women, according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA).

"Through medical imaging examinations, we are exposing pregnant women to twice the amount of radiation as we did 10 years ago," said Elizabeth Lazarus, M.D., assistant professor of diagnostic imaging at the Warren Alpert School of Medicine at Brown University in Providence, R.I. "Overall, the levels of radiation to which we are exposing pregnant women are low, but they do carry a slight risk of harm to the developing fetus."

The researchers conducted a retrospective review of selected imaging examinations -- nuclear medicine, computed tomography (CT) and plain-film x-rays -- performed at Brown to determine how often these imaging exams were utilized in pregnant women and the estimated resulting radiation dose to the fetus. Data were compiled for the years 1997 through 2006 and compared to the number of infant deliveries per year.

The investigators found that from 1997 to 2006, the number of imaging studies performed on pregnant women increased by 121 percent. The greatest increases were in the number of CT exams, which deliver more radiation than many other radiologic procedures. An abdominal CT exposes the patient to a radiation amount more than twice that of an x-ray of the lower gastrointestinal tract. An abdominal ultrasound exposes the patient to no ionizing radiation.

CT is not routinely used in pregnancy, but pregnant women may undergo CT to detect suspected life-threatening conditions such as bleeding in the brain, blood clots in the lungs or appendicitis. Since CT exposes the developing fetus to radiation, concerns are often raised regarding overuse. The majority of CT examinations (approximately 75 percent) analyzed in the study were performed in areas of the mother''s body separate from the uterus, so the fetus was not exposed to any direct radiation. Even low levels of radiation have been shown to carry a small risk of harm to a developing fetus.

"While performing CT exams during pregnancy is still uncommon, we found that pregnant women are being recommended for CT more often over the last 10 years," Dr. Lazarus said.

The researchers evaluated 5,235 examinations on 3,249 patients. During the 10 years of the study, the number of patients imaged per year increased from 231 to 447, and the number of exams per year increased from 325 to 730. This represented an 89 percent increase in patients and a 121 percent increase in examinations over the course of the study. During the same 10 years, the number of deliveries only increased from 8,661 to 9,261, a rise of only 7 percent or less than 1 percent annually.

Use of plain-film x-rays increased an average of 7 percent per year, and the number of nuclear medicine examinations rose by approximately 12 percent annually. CT examinations increased by approximately 25 percent per year. The average estimated fetal radiation exposure for CT was 0.69 rads, compared to 0.04 rads for nuclear medicine and 0.0015 rads for plain-film x-rays.

Other studies have shown that use of high-tech modalities, such as CT and magnetic resonance imaging (MRI), has increased in all patient populations throughout the United States. According to Dr. Lazarus, some of this increase is due to the development of new imaging techniques to better diagnose abnormalities, and some is due to motivation by hospitals and insurers to make fast diagnoses to shorten hospital stays and improve patient care.

Dr. Lazarus cautions healthcare consumers to be aware of this trend. "I want to assure patients that CT can be a safe, effective test for pregnant patients," she said. "However, there are alternatives that should at least be explored. Pregnant patients should ask their doctors about other imaging or diagnostic tests that may not expose the fetus to radiation."

Published online November 27, 2007 as meeting notes from the Radiological Society of North America.

How Mitochondria Enact Cell Apotois - or Cell 'Suicide'

Mitochondria straddle the fence between life and death. These tiny bags of enzymes inside cells consist of a smooth, continuous outer membrane and a second, inner membrane that is arranged in tubules or in folds that form plate-like double membranes.

When mitochondria use the enzymes located on these membranes to extract energy from food molecules like glucose, they keep the cell alive. When they activate a series of biochemical events called apoptosis, they cause the cell to self-destruct.

Apoptosis helps the developing embryo sculpt organs out of masses of cells and eliminates abnormal cells from the body. Some cancer drugs work by forcing the cell to undergo apoptosis.

So the study of mitochondria—especially their role in cell death—is a hot area of research worldwide.

One of the most cited authors of scientific papers on apoptosis is Douglas Green, PhD, Immunology chair. Green and former St. Jude employee Cristina Munoz-Pinedo contributed to a report in the September issue of Nature Cell Biology that takes the study of apoptosis deep into the mitochondria with photos and videos that show exactly what happens to this structure during the early states of apoptosis.

Two key events in apoptosis are the release of a protein called cytochrome c from the mitochondria and the subsequent loss of the membrane potential across the outer mitochondrial membrane. Membrane potential is voltage that exists across a membrane; voltage refers to the difference in electric charge on either side of a membrane.

The multi-institutional team first examined the structure of mitochondria at specific stages of apoptosis in cells treated with the cancer drug etoposide. They tagged cytochrome c with a fluorescent chemical to track its movement out of mitochondria and used a special chemical to help them to identify which mitochondria retained their membrane potential and which lost it.

The researchers observed that apoptosis caused by treatment with etoposide occurred in three stages:

1) before the release of cytochrome c and before loss of membrane potential;

2) after release of cytochrome c but before loss of membrane potential; and

3) after both release of cytochrome c and loss of membrane potential.

Next, the researchers used electron microscopy to identify five changes in shape that occur during the three stages of apoptosis as the mitochondria swell and the inner membrane structures become distorted. The team also created 3-D images of the insides of these five changes using a technique called electron microscope tomography. Similar to a CT scan, this technique makes images that represent a series of “slices” through the mitochrondria. The individual slices are then reconstructed into 3-D views of the specimen.

The images showed that late in the course of apoptosis, after the release of cytochrome c and the loss of the membrane potential, the inner mitochondrial membrane undergoes dramatic remodeling, changing from neat plates of folds into many small, separate sacs.

“The photos and movies of apoptosis we produced in this study are particularly informative and should significantly improve our understanding of this important event,” Green said.

Published November 2, 2007 in the journal Nature Cell Biology.


Think of Your Body As a Superorganism

The armies of bacteria that sneak into our bodies the moment we are born must be the original illegal immigrants, uninvited but necessary guests. A few miscreants, though, will kill us if we let them stay. How do we separate friend from foe? Wouldn’t it be safer just to nuke them all?

In the course of a century, scientists have run through many of the same slogans politicians have. The pioneering immunologist Elie Metchnikoff, winner of a 1908 Nobel Prize, thought the only good germ was a dead one: he “viewed bacteria as the worst sort of parasites,” says Jessica Snyder Sachs in her capable book, "Good Germs, Bad Germs" Health and Survival in a Bacterial World.

The results speak for themselves. It turns out that the indiscriminate killing of harmless microbes damages the body in complex ways we are only beginning to understand. Meanwhile, the bad germs are pretty much unstoppable. A few have proved susceptible to vaccines, but under attack the rest simply become hardened and infinitely resourceful, forcing a continuous escalation of weaponry on our part - as well as theirs.

We host more bacteria than we ever realized: new DNA technology has found hundreds of previously unrecognized species in the traditional stomping grounds of mouth and intestine, and traces of bacteria even in tissues previously thought to be sterile. Further, our indwelling organisms apparently communicate constantly with one another, both within individual colonies and also among species. Powerful antibiotics introduced into this complex environment cause mayhem, much like a series of bombs tossed into a market square.

In addition, many scientists now subscribe to the theory that the creation of an unnaturally microbe-free environment is at least partly responsible for the modern explosion of allergic and autoimmune diseases. Without routine early exposure to a wide array of microbes, the immune system may become jumpy and frightened, overreacting violently to harmless substances like pollen, peanuts or even the body’s own cells.

Ms. Sachs gives the last word to Joshua Lederberg, the Nobel-winning molecular biologist: “It would broaden our horizons if we started thinking of a human as more than a single organism. It is a superorganism that includes much more than our human cells.”

In other words, perhaps we should stop trying to live within an inviolate fortress. The melting pot may prove as happy an image for the body human as it is for the body politic.

Published November 27, 2007 in the New York Times.


TUESDAY - November 27, 2007---------------------------------------------News Archive/Return to Today's News Alerts

Genital Herpes Has Mysteries for Physicians and Patients

Neither patients nor the physicians they consult seem to be well informed about genital herpes, with diverging opinions about how the infection is transmitted and treated, a survey has revealed.

The general knowledge of family physicians and patients about genital herpes is "disappointing," Barbara Romanowski, M.D., of the University of Alberta, and colleagues reported online in Sexually Transmitted Infections.

Of special concern, physicians and patients underestimated the risk of transmission during periods of asymptomatic viral shedding. Patients estimated that a mean of 51% of patients are infected by a partner who does not have an outbreak at the time of contact, and doctors estimated that a mean 45% of cases are transmitted during periods of asymptomatic shedding (P<0.001).

The actual figure reported in the literature is 70%, the authors said.

When patients were asked to indicate the possible sources of infection from a list of options, virtually all cited sexual contact (99%). However, some also considered toilet seats (19%), blood transfusions (18%), shaking hands (8%), and swimming pools or baths (6%) as potential sources.

"Overall, only 65% got it right, identifying sexual transmission as the sole means of transmission.

Only 40% of patients were aware that daily antiviral therapy was available to reduce the risk of transmission, while the most compelling reason for a high interest in suppressive therapy for 62% of the patients was to reduce the frequency and severity of outbreaks rather than transmission risk.

Although physicians believe they are providing patients with choices on disease management, the message fails to reach many of their patients. Doctors must ensure that they are accurate and complete in their knowledge of genital herpes and adapt their communication style so that choices in disease management are truly shared with patients.

The challenge will be to educate both groups, with the goal of achieving optimal genital herpes management and standard of care as the norm, not the exception, Dr. Romanowski concluded.

Published November, 2007 in the journal Sexually Transmitted Infections.


'Cocktail' of Compounds Improves Brain Function in Rodents

MIT researchers have shown that a cocktail containing three compounds normally in the blood stream promotes growth of new brain connections and improves cognitive function in rodents. The treatment is now being tested in Alzheimer's patients and could hold promise for other brain diseases and injuries.

The mixture, which includes a type of omega-3 fatty acid, is part of a new approach to attacking Alzheimer's. That approach focuses on correcting the loss of synapses, or connections between neurons, which characterizes the disease.

"It's been very frustrating," said Richard Wurtman, the Cecil H. Green Distinguished Professor of Neuropharmacology and senior author of a paper on the new work published in the November issue of Brain Research. "Nobody has demonstrated that if you prevent formation of the amyloid, people get better."

Synapses, where information is passed between neurons, play a critical role in learning and memory. Messages travel from a presynaptic neuron to a postsynaptic cell.

In the Brain Research paper, the MIT team reported that rodents given a cocktail of DHA (a type of omega-3 fatty acid), uridine and choline showed a greatly increased concentration of dendritic spines, which receive messages in the postsynaptic neuron. That indicates that synapse regeneration has occurred, which is unusual, Wurtman said.

Synapse regrowth could also prove an effective treatment for other brain diseases, such as Parkinson's, or for brain injuries, he said.

The researchers found that rodents who received the DHA treatment performed much better on tests of cognitive ability (specifically, navigating a water maze). Sarah Holguin, an MIT graduate student in brain and cognitive sciences, presented those results at the Society for Neuroscience annual meeting earlier this month.

Some of the rats in the studies received all three compounds and some received only one. The improvements in synapse growth and cognitive ability were greatest in the rats given all three.

Omega-3 fatty acids are not produced in the body but are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Choline can be synthesized in the body and obtained through the diet; it is found in meats, nuts and eggs. Uridine cannot be obtained from food sources, but is a component of human breast milk and can be produced in the body.

The cocktail of compounds is now in clinical studies in Europe.

Published November, 2007 in the journal Brain Reseach.


Copper's Role in Alzheimer's Identified

A team of U.S. researchers has identified a mechanism by which copper might contribute to the development of Alzheimer's disease.

Scientists of the University of Rochester discovered copper damages a protein called LRP that transports a substance called amyloid beta from the brain. Amyloid beta accumulates in the brains of people with Alzheimer's.

Although metals have long been thought to contribute to Alzheimer's, the researchers said their discovery marks the first time a mechanism for a specific metal's role in the disease has been identified.

The study was conducted in mice, as well as on cells from brains of people who died from Alzheimer's disease. The team found mice drinking water with trace levels of copper had one-third fewer LRP molecules in their brains' blood vessels, and one-third more amyloid beta in their brains than control mice after 10 weeks.

In human cells, the team discovered copper damages the protein LRP to such an extent that it stops working. Fewer LRP molecules lead to higher levels of amyloid beta, a substance that ultimately kills brain cells.

Presented November 6, 2007 in San Diego during the 37th annual meeting of the Society for Neuroscience.

MONDAY - November 26, 2007----------------------------------------------News Archive/Return to Today's News Alerts

Can Babies Judge Good and Bad Behavior Around Them?

Babies are good judges of character long before they learn to speak, according to a new study. Infants as young as six months preferred characters which helped rather than hindered others in a simple puppet show.

Researchers say the findings reveal that humans begin making social evaluations far earlier than previously thought.

"This is the very first experiment in anywhere near this age that shows babies develop preferences for individuals based on their actions," says Karen Wynn at Yale University in New Haven, Connecticut, US, who led the study.

Wynn and her colleagues studied the reactions of infants to a sketch in which a brightly coloured wooden block with goggly eyes attempts to climb up a hill. Much like in a puppet show, the infant could not see the person behind a curtain who controlled the character's movement with a wooden stick.

After the show, the researchers brought out the helper block and the hinderer block on a platter and placed it in front of the infants. A colleague who did not see the skit, and did not know the role of each block in the performance, recorded how the babies interacted with the objects.

"Wynn says that the infants are very willing to reach out for one of the blocks, an action that indicated their preference: "They're very cooperative in grabbing things." She says that all 12 of the six-month-olds preferred the helper block. Similarly, 14 out of the 16 infants aged 10 months reached for the helper block.

She believes the results from her study indicate that babies have a preference for helpful individuals about a year earlier than previously thought. "They are an unbiased third party and they are not at all shy about rendering a judgement on social actions," she says, adding that this tendency appears early in development because it is a strongly advantageous trait later in life.

Legerstee hopes the experiment will be repeated using another skit involving human actors rather than wooden blocks. By altering the people who play the role of helpers and hinderers the scientists can control for confounding factors, such as babies preferences for attractive people.

Published November, 2007 in the journal Nature.


Fountain of Youth for Fat Mice?

A molecule found in grapes and red wine increased the survival rate of fat mice by 30%, according to a new study. The finding comes as scientists hunt ever harder for a holy grail in anti-aging research: An easy-to-take therapy that mimics the long-life benefits of slashing calories, without the unpleasant nature of that drastic diet. It's not clear yet that this treatment is a magic chalice, but the study suggests that the molecule, called resveratrol, is a potent protector of health and life in mammals.

Resveratrol is an antioxidant, a substance that can protect against tissue damage. In the last few years, a team at Harvard Medical School led by molecular biologist David Sinclair has given resveratrol to yeast, flies, and worms, and in every case, the molecule has stretched lifespan (ScienceNOW, 14 July 2004). That's the same outcome scientists have observed for decades in calorie-restricted species (ScienceNOW, 18 January). Researchers have also found that calorie restriction makes a gene called SIR2, or SIRT1 in mammals, more active, which in turn somehow affects metabolism. Sinclair and some others suspect that resveratrol also acts directly or indirectly through SIR2, much like calorie restriction, although other scientists say that hasn't yet been proven.

Following their studies in other species, Sinclair and his colleagues set out to test resveratrol's effects on mice. They studied 1-year-old male mice in three groups of 55 animals each: One was put on a standard diet, a second was fed a high-calorie, high-fat diet, and a third got that same high-calorie diet with daily doses of resveratrol. At 2 years of age, 58% of the animals in the second group were dead of natural causes. In the other two groups, only 42% of the animals had died.

The scientists also found other benefits in the resveratrol group. The motor skills of the animals treated with resveratrol improved as they aged, and they were indistinguishable from the mice on a normal diet. Perhaps most notably, their livers remained healthy, unlike those of obese animals who didn't get resveratrol, the team reports online today in Nature. "The obese mice lived as long and were much more similar to the lean animals," says Sinclair, who has co-founded a company that's designing resveratrol-based treatments. Sinclair is also testing the effects of resveratrol in lean mice and comparing them to calorie-restricted animals.

The results are exciting, says Matt Kaeberlein, a molecular biologist at the University of Washington in Seattle. But he notes that the mice used in the study were inbred, causing them to suffer from just a handful of diseases that typically kill them. It's far from clear whether resveratrol is targeting only those problems or has broader effects, he says. "There's clearly a beneficial effect" of resveratrol, says Cynthia Kenyon, a molecular geneticist at the University of California, San Francisco. She believes it's worth launching a clinical trial testing resveratrol in obese individuals, or those with type 2 diabetes.

Published June, 2006 in the journal Nature
Read more on the scientists behind reseveratrol, October 2007, in Technology Review by MIT.


Materialism in Children and Adolescents Linked to Self-Esteem

In one of the first studies to focus on the development of materialism among children, Deborah Roedder John, a professor of marketing at the University of Minnesota’s Carlson School of Management, reveals that a young person’s level of materialism is directly connected to their self-esteem.

In her recent paper, John and co-author Lan Nguyen Chaplin, assistant professor of marketing at the University of Illinois and Carlson alum, report the results of two studies conducted with children in three age groups.

In the first study, they found that materialism increases from middle childhood (8 and 9 years old) to early adolescence (12 and 13 years old) but then declines by the end of high school (16 to18 years old). This mirrors patterns in self-esteem, which instead decreases in early adolescence but increases in late adolescence.

“The level of materialism in teens is directly driven by self-esteem,” said John. “When self-esteem drops as children enter adolescence, materialism peaks. Then by late adolescence, when self-esteem rebounds, their materialism drops.”

In a second study, John and Chaplin boosted self-esteem by giving children positive information about peer acceptance. Children were given paper plates with positive descriptors about them, such as smart and fun, which were provided by their peers in a summer camp setting. This seemingly small gesture drastically reduced the high levels of materialism found among 12 to13 year-olds and the moderate levels of materialism found among 16 to 18 year-olds.

"Particularly relevant,” said John, “is the fact that by simply increasing self-esteem in teens, we see a decreased focus on material goods that parallels that of young children. While peers and marketing can certainly influence teens, materialism is directly connected to self-esteem.”

For parents interested in instilling positive values in their children and teens, the message is clear: encouraging a sense of self-worth among young people can reduce the emphasis on material goods. In other words, more self-esteem, fewer $150 athletic shoes and $250 purses.


Published December 2007, Journal of Consumer Research.