Women Tend to Have Better Sense of Touch Due to Smaller Finger Size

People who have smaller fingers have a finer sense of touch, according to new research in the Dec. 16 issue of The Journal of Neuroscience. This finding explains why women tend to have better tactile acuity than men, because women on average have smaller fingers.

"Neuroscientists have long known that some people have a better sense of touch than others, but the reasons for this difference have been mysterious," said Daniel Goldreich, PhD, of McMaster University in Ontario, one of the study's authors. "Our discovery reveals that one important factor in the sense of touch is finger size."

To learn why the sexes have different finger sensitivity, the authors first measured index fingertip size in 100 university students. Each student's tactile acuity was then tested by pressing progressively narrower parallel grooves against a stationary fingertip -- the tactile equivalent of the optometrist's eye chart. The authors found that people with smaller fingers could discern tighter grooves.

"The difference between the sexes appears to be entirely due to the relative size of the person's fingertips," said Ethan Lerner, MD, PhD, of Massachusetts General Hospital, who is unaffiliated with the study. "So, a man with fingertips that are smaller than a woman's will be more sensitive to touch than the woman."

The authors also explored why more petite fingers are more acute. Tinier digits likely have more closely spaced sensory receptors, the authors concluded. Several types of sensory receptors line the skin's interior and each detect a specific kind of outside stimulation. Some receptors, named Merkel cells, respond to static indentations (like pressing parallel grooves), while others capture vibrations or movement.

When the skin is stimulated, activated receptors signal the central nervous system, where the brain processes the information and generates a picture of what a surface "feels" like. Much like pixels in a photograph, each skin receptor sends an aspect of the tactile image to the brain -- more receptors per inch supply a clearer image.

To find out whether receptors are more densely packed in smaller fingers, the authors measured the distance between sweat pores in some of the students, because Merkel cells cluster around the bases of sweat pores. People with smaller fingers had greater sweat pore density, which means their receptors are probably more closely spaced.

"Previous studies from other laboratories suggested that individuals of the same age have about the same number of vibration receptors in their fingertips. Smaller fingers would then have more closely spaced vibration receptors," Goldreich said. "Our results suggest that this same relationship between finger size and receptor spacing occurs for the Merkel cells."

Whether the total number of Merkel cell clusters remains fixed in adults and how the sense of touch fluctuates in children as they age is still unknown. Goldreich and his colleagues plan to determine how tactile acuity changes as a finger grows and receptors grow farther apart.

The research was supported by the National Eye Institute and the Natural Sciences and Engineering Research Council in Canada.

Courtesy: Science Daily

Microcephaly Genes Associated With Human Brain Size

A group of Norwegian and American researchers have shown that common variations in genes associated with microcephaly -- a neuro-developmental disorder in which brain size is dramatically reduced -- may explain differences in brain size in healthy individuals as well as in patients with neurological and psychiatric disorders.

The study, which involved collaboration between researchers from the University of Oslo, the University of California, San Diego and Scripps Translational Science Institute in La Jolla, California, will be published online the week of December 21 in the Proceedings of the National Academy of Science.

In relation to body size, brain size has expanded dramatically throughout primate and human evolution. In fact, in proportion to body size, the brain of modern humans is three times larger than that of non-human primates. The cerebral cortex in particular has undergone a dramatic increase in surface area during the course of primate evolution.

The microcephaly genes have been hot candidates for a role in the evolutionary expansion of the human brain because mutations in these genes can reduce brain size by about two-thirds, to a size roughly comparable to our early hominid ancestors. There is also evidence that four of the genes -- MCPH1, ASPM, CDK5RAP2 and CENPJ -- have evolved rapidly and have been subject to strong selective pressure in recent human evolution.

"It is obvious that such anatomical changes must have a basis in genetic alterations, said Lars M. Rimol, a research fellow at the University of Oslo. "Until now, little has been known about the molecular processes involved in this evolution and their genetic underpinnings. Now we have a piece of that genetic puzzle."

Several previous MRI studies have attempted to demonstrate a link between single polymorphisms (an inherited genetic variation that is found in more than one percent of the population) in these genes and brain size in healthy human adults, all of them unsuccessful. According to the research team, the success of the current study is likely due to two unique characteristics: first, by using a whole genome scan, the scientists could access an unprecedented number of polymorphisms, including non-coding regions outside of the gene itself; second, they were able to estimate cortical surface area, using software that reconstructs the cortical surface, based on volumetric MR scans, allowing for highly precise measurements of cortical thickness and areal expansion.

The software was developed by Anders Dale, PhD, professor of Radiology and Neurosciences at the UC San Diego School of Medicine, who headed the American branch of the research team. "The most statistically significant associations were consistently found with the areal expansion measure, which has implications also for future studies," said Dale.

The initial discovery was made in a sample of 289 psychiatric patients and controls from the Norwegian Thematically Organized Psychosis research project (TOP), led by Ole Andreassen from the University of Oslo, principal investigator of the Norwegian branch of the international research team. The most significant findings were then replicated in a sample of 655 healthy and demented patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the largest Alzheimer's disease study ever funded by the National Institutes of Health. The Norwegian sample was ethnically homogenous; the ADNI sample was ethnically diverse. According to the researchers, the fact that reported associations were found across two independent studies, including healthy controls and various patient groups, shows that these effects are likely to be independent of population or disease.

Highly significant associations were found between cortical surface area and polymorphisms in possible regulatory regions near the gene CDK5RAP2. This gene codes for a protein involved in cell-cycle regulation in neuronal progenitor cells -- cells that migrate to the cerebral cortex during the second trimester of gestation and eventually become fully functioning neurons. The cerebral cortex is the outer layer of the brain, often referred to as "gray matter." The most highly developed part of the human brain, the cerebral cortex is responsible for higher cognitive functions, such as thinking, perceiving, producing and understanding language, some of which is considered uniquely human.

Similar but less significant findings were made for polymorphisms in two other microcephaly genes, known as MCPH1 and ASPM. All findings were exclusive to either males or females but the functional significance of this sex-segregated effect is unclear.

"One particularly interesting feature of this new discovery is that the strongest links with cortical area were found in regulatory regions, rather than coding regions of the genes," said Andreassen. "One upshot of this may be that in order to further understand the molecular and evolutionary processes that have determined human brain size, we need to focus on regulatory processes rather than further functional characterization of the proteins of these genes. This has huge implications for future research on the link between genetics and brain morphology."

Additional contributors include Ingrid Agartz, Srdjan Djurovic, Andrew A. Brown, Anna K. Khäler,Morten Mattingsdal, Lavinia Athanasiu, Kjetil Sundet and Ingrid Melle of the University of Oslo, Norway; J. Cooper Roddey and Eric Halgren of UC San Diego; Alexander H. Joyner, of UC San Diego and Scripps Translational Science Institute;,and Nicholas J. Schork of Scripps Translational Science Institute.

Funding for this study was provided in part by the National Institutes of Health, Eastern Norway Health Authority and Research Council of Norway, and by the National Institute of Aging of the National Institutes of Health.

Exposure to Young Triggers New Neuron Creation in Females Exhibiting Maternal Behavior

Maternal behavior itself can trigger the development of new neurons in the maternal brain independent of whether the female was pregnant or has nursed, according to a study released by researchers at Tufts University's Cummings School of Veterinary Medicine. These findings performed in adult, virgin rats were published in Brain Research Bulletin.

In the study, virgin, or nulliparous, rats were exposed to foster pups each day until they began to exhibit maternal behavior, including crouching over the young, grouping them, or retrieving them back to the nest. Data from the study showed that the nulliparous rats exposed to pups have increased numbers of new neurons.

The research was undertaken by Cummings School Department of Biomedical Sciences researchers Miyako Furuta and Robert Bridges, who is the head of the Cummings School's reproduction and neurobiology section.

Previous research has found that exposure to young can stimulate maternal behavior not only in rats, but also mice, hamsters, monkeys, and even humans. Increased creation of new neurons, or neurogenesis, has also been shown during pregnancy and lactation in rodents and associated with maternal behavior, but studies analyzing neurogenesis in nulliparous animals exhibiting maternal behavior had not been done. The area of the brain that was the focus of the present study was the subventricular region -- a region involved in the production of cells that affect odor recognition and possibly recognition of young. Bridges and Furuta found increased numbers of new neurons in the subventricular zone in adult, nulliparous rats that behaved maternally compared with numbers in subjects that either were not exposed to young or exposed to young, but did not behave maternally.

What stimulates increased new neuron production in the nulliparous mothers is not known. One possibility is that the hormone prolactin, which stimulates both the onset of maternal behavior as well as production of neurons during pregnancy, may play a role in the production of new neurons in nulliparous females exhibiting maternal behavior. However, this possibility remains to be investigated. A second possibility is that stimulation received from the young themselves may, in fact, play a crucial role in stimulating maternal neuron production.

"As with all scientific studies, these findings trigger more questions than answers," said Dr. Robert Bridges, section head of reproduction and neurobiology at Tufts University's Cummings School of Veterinary Medicine. "Next, we hope to determine what role this neurogenesis plays in terms of the female's behavior and physiological processes. Where do these new cells migrate to within the brain and what do they do? For example, do they affect how a female subsequently perceives her young through recognition of baby odors? These are the questions we hope to answer."

The study was funded by a National Institutes of Health grant.

Journal Reference:

1. Furuta et al. Effects of maternal behavior induction and pup exposure on neurogenesis in adult, virgin female rats. Brain Research Bulletin, 2009; 80 (6): 408 DOI: 10.1016/j.brainresbull.2009.08.011

Crystallographer faked data

A protein researcher at the University of Alabama at Birmingham (UAB) has been found guilty of falsifying data that he used to construct 12 fraudulent protein structures that made it into the scientific literature and an international archive of protein structures.

After investigating the misconduct -- with the help of a committee of independent protein scientists -- the university has asked that the structures be removed from the database and that ten research papers, authored by former UAB researcher H.M. Krishna Murthy over the past decade, be retracted from the literature.

"What we know is that when Dr. Murthy was asked to provide the data behind the structures, there was not sufficient material presented to allow the expert panel to determine the source of the error," Richard Marchase, UAB's vice president for research and economic development, told The Scientist.

The UAB investigation concluded that the structures Murthy proposed violated basic physical and chemical laws, making their existence virtually impossible. "There were just many aspects of the proposed structures that didn't appear to be at all plausible given the physical laws of how proteins come together," added Marchase, who is also UAB's scientific integrity officer.

"I think [Murthy] deserves tarring and feathering," Gert Vriend, a bioinformatician at Radboud University Nijmegen Medical Centre in The Netherlands, told The Scientist.

Murthy, whose UAB contract at the school's Center for Biophysical Sciences and Engineering expired in February of this year with the university opting not to renew it, "has always denied any misconduct," according to Marchase. Murthy could not be reached for comment by email, and UAB is unaware of his current whereabouts.

According to Marchase, the university informed the Office of Research Integrity (ORI) of the U.S. Department of Health & Human Services that UAB was investigating Murthy's suspect structures, and presumably the ORI will now initiate their own investigation of Murthy. But the agency is not talking about the Murthy case yet. "We can neither confirm nor deny that we have such a case," wrote an ORI spokesperson in an email to The Scientist.

Murthy's fraud was uncovered when European crystallographers who were working on some of the same structures that Murthy was claiming to solve raised red flags. Piet Gros, a crystallographer at Utrecht University in The Netherlands, was alerted to potential problems with Murthy's structures by one of his grad students. Gros's lab published a structure for the immune protein C3b in a 2006 issue of Nature. Along with the Gros group's paper, two other papers on the structure of C3b were published in the issue. One was from Murthy's group at UAB and the other from researchers at the biotech company Genentech.

"We noticed quite quickly that there was a problem with the crystal lattice in the Murthy structure," Gros told The Scientist. "There were huge gaps between layers of molecules. That was a huge red flag."

Gros said that he contacted Murthy about the abnormalities, but the UAB researcher brushed aside his concerns. "Basically we were not satisfied with his answers to the questions," Gros said. "He could not give an explanation to us."

Gros and his colleagues began looking into more of Murthy's structures and noticing other "abnormal features." After unsuccessfully trying to get answers from Murthy, they had independent colleagues, including Vriend, analyze the structures and wrote a letter to Nature and to UAB detailing their findings.

Using sophisticated validation software, Gros and his colleagues uncovered several problems with more of Murthy structures. There were unexplained gaps in the packing pattern of amino acids in the structures and contacts between atoms that were unrealistic, and "there was no solvent in the data," according to Gros. "There are things which are physically impossible," he said.

Though the problems with Murthy's data seem glaring, uncovering the fraud required intricate analysis by protein experts. "The structure [of C3b] was strange, but it did require an expert to read from the numbers that something was worrisome," said Vriend.

Murthy was able to publish fraudulent data on 12 protein structure over the span of 10 years in several different journals, such as Nature, Proceedings of the National Academy of Science, Biochemistry, and Cell. At the beginning of this month, the Journal of Biological Chemistry (JBC) retracted one paper that Murthy published in 1999 on the structure of a domain in the dengue virus. According to Marchase, "Another journal is likely to retract but has not yet," but he declined to say which one.

Officials at the Protein Data Bank (PDB), which archives thousands of protein crystal structures from the literature, have removed the structure (dengue virus NS3 serine protease) reported in the JBC paper from its database, and "will make the remaining 11 entries obsolete if and when the corresponding papers are retracted," according to a PDB statement.

Vriend and Gros said that one good thing to come out of the Murthy fraud case is that journals and the protein structure archives are rethinking the process whereby they validate submitted crystal structures. "This appears to be an extremely rare case," Gros said. "But the [validation] process has to be improved. People are discussing processes of doing this better, and I think that will happen, and it's a good thing."

Vriend agreed, adding that the analysis of Murthy's fraud demonstrated the importance of carefully validating proposed crystal structures for proteins. "Protein structures are so important for so many fields in science that they must be right."

Correction (18th December): In the original version of this story, Murthy was said to have been the recipient of five NIH grants this year. The NIH's Research Portfolio Online Reporting Tool, inaccurately lists the UAB email and name of H.M. Krishna Murthy under grants won by Krishna K. Murthy of the Southwest Foundation for Biomedical Research in Texas. Krishna K. Murthy was not involved in any way with the fraud perpetrated by H.M Krishna Murthy, and the subject of this story was not awarded any NIH grants in 2009. The Scientist regrets the error.

The five hottest biology papers of 2009

Which papers made the biggest splash this year? ScienceWatch, a website that tracks and analyzes trends in basic science research, compiles bimonthly lists of the 10 most cited papers. From those lists, The Scientist pulled the five papers in biology published in the last two years which were some of the most cited papers in 2009. The two topics that dominate the top five papers this year: genomics and stem cells.

5. A M. Wernig, et al., "In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state," Nature 448: 318-24, 2007.
Citations this year: 237
Total citations to date: 512
Findings: Scientists successfully performed somatic-cell nuclear transfer (SCNT), producing stem cell lines and cloned animals for the first time using fertilized mouse eggs. This paper consistently ranked in the top 10 most cited papers in 2009, according to ScienceWatch.

4. E. Birney, et al., "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project, "Nature, 447: 799-816, 2007.
Citations this year: 267
Total citations to date: 618
Findings: The ENCODE project -- ENCODE stands for the ENCyclopedia Of DNA Elements -- set out to identify all functional elements in the human genome. After examining one percent of the genome, the paper revealed several new insights about how information encoded in the DNA comes to life in a cell.

3. A. Barski, et al., "High-resolution profiling of histone methylations in the human genome," Cell, 129: 823-37, 2007.
Citations this year: 299
Total citations to date:: 560
Findings: This study looked at how histone modifications influence gene expression in more detail than previous attempts. Using a powerful sequencing tool called Solexa 1G, the researchers mapped more than 20 million DNA sequences associated with specific forms of histones, finding there were differences in methylation patterns between stem cells and differentiated T cells.

2. K.A. Frazer, et al., "A second generation human haplotype map of over 3.1 million SNPs," Nature, 449: 854-61, 2007.
Citations this year: 389
Total citations to date: 588
Findings: Since the sequencing of the human genome in 2003, the International HapMap Project has explored single nucleotide polymorphisms (SNPs) -- differences in a single letter of the DNA -- to study how these small variations affect the development of diseases and the body's response to pathogens and drugs. HapMap I, the original report, placed one SNP at roughly every 5,000 DNA letters. The newest map, featured in this paper, sequenced an additional 2 million SNPs, increasing the map's resolution to one SNP per kilobase. The additional detail allows scientists to more closely investigate patterns in SNP differences, especially in hotspot regions, or concentrated stretches of DNA.

1. K. Takahashi, et al., "Induction of pluripotent stem cells from adult human fibroblasts by defined factors," Cell, 131: 861-72, 2007.
Citations this year: 520
Total citations to date: 886
Findings: This work from Shinya Yamanaka's lab in Japan was the first to demonstrate that induced pluripotent stem (iPS) cells can be generated from adult human dermal fibroblasts. Previous efforts by the team showed that iPS cells could be derived from mouse somatic cells. This paper was an easy top pick, receiving the most citations this year, according to ScienceWatch.

The top 5 people of 2009

From budgets padded with stimulus funding to advancements in stem cell legislation, 2009 has been an all around big year for research. But in The Scientist's mind, a few individuals have stuck out in terms of their contributions, support, and leadership in the life sciences.

Here are our picks for the top five most influential people of the year, presented in alphabetical order:
Francis Collins

Unless you have been living under a rock this year, you know that Collins was appointed director of the National Institutes of Health in August. The geneticist accepted the position after 15 years at the helm of the National Human Genome Research Institute, during which time he helped finish the Human Genome Project ahead of schedule and under budget. Since taking control of the NIH, Collins has been pushing an agenda focused on personalized medicine and stem cell research, backing the efforts by approving 40 new human embryonic stem cell lines as eligible for federal funding. Collins has also found time to be a much more public figure than previous NIH directors, taking time out to rock with Aerosmith's Joe Perry and joke around with Stephen Colbert.

Sheng Ding

For the first time, Ding and colleagues at the Scripps Research Institute induced pluripotency in mouse embryonic cells using only recombinant proteins, avoiding gene manipulation altogether, publishing the research in Cell Stem Cell. The technology, which was named The Scientist's top life science tool of 2009, is being used by Fate Therapeutics, a company cofounded by Ding in 2007, to interrogate stem cell biology in an effort to enable new drug discovery. Ding was also featured in our pages as Scientist to Watch in November.

Bart Gordon

As Chairman of the House Committee on Science and Technology, the 13th term Democrat from Tennessee played a key role in ensuring science got a major boost from stimulus funding. Gordon also authored bills to further nanotechnology research and commercialization (H.R. 554, passed February 11), require that the President create a national water strategy (H.R. 1145, passed April 23), and improve science, technology, engineering, and math (STEM) education programs (H.R. 1709, passed June 8). Gordon also helped allocate $400 million in stimulus funding to start the Department of Energy's Advanced Research Projects Agency -- Energy, which funds high risk, high reward energy research. Although the Congressman announced he won't be running for re-election next year, science sure was lucky to have him around in 2009.

Henry Gustav Molaison

Known to scientists for most of his life only as H.M., Molaison is recognized as one of the most important patients in the history of brain science. After undergoing experimental surgery in 1953 to correct a seizure disorder, which included removing two slivers of brain tissue and cutting into the hippocampus, Molaison lost the ability to form new memories. For the next 55 years, he helped transform scientists' understanding of memory, including the identification of two different systems of remembrance -- declarative (names and faces, for example) and motor learning. Molaison died in December 2008 at the age of 82, but not before agreeing to donate his brain to research. This year, scientists at the University of California, San Diego, began slicing the organ into approximately 2,600 fragments in an effort to correlate individual brain structures with specific functions.

Erika Sasaki

Sasaki, from the Central Institute for Experimental Animals in Kawasaki, Japan, led the team of researchers that successfully generated the world's first transgenic primates capable of passing on a foreign gene to their offspring. The research, published in Nature, brings scientists one step closer to being able to use primates as models for studying human neurological and behavioral conditions, such as Parkinson's, Huntington's and amyotrophic lateral sclerosis. The team injected viral vectors with a green fluorescence protein transgene into embryos of marmosets. Out of 80 transgenic embryos planted into 50 surrogate mothers, five offspring survived, all of which expressed the glowing transgene.

Parasite Evades Death By Promoting Host Cell Survival

The parasite Trypanosoma cruzi (or T. cruzi), which causes Chagas' disease, will go to great lengths to evade death once it has infected human host cells, researchers have discovered. In a study published in the November 17 online issue of Science Signaling, the researchers describe how a protein called parasite-derived neurotrophic factor (PDNF) prolongs the life of the T. cruzi parasite by activating anti-apoptotic (or anti-cell-death) molecules in the host cell. These protective mechanisms help to explain how host cells continue to survive despite being exploited by T. cruzi parasites.

"We asked ourselves, 'How is it possible that the host cells stay alive for so long with thousands of T. cruzi parasites consuming the host cell's vital resources?' We discovered that PDNF on the surface of the T. cruzi parasite essentially inhibits cell death signals and activates cell-protective mechanisms, ensuring T. cruzi sufficient time to develop and reproduce in the host cell," says senior author Mercio Perrin, MD, PhD, professor in the pathology department at Tufts University School of Medicine (TUSM) and member of the immunology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

Taking a multi-faceted approach, the researchers used bioinformatics, immunochemistry, intracellular colocalization microscopy, and in vitro enzymatic techniques to study T. cruzi's survival in the host. Perrin and co-author Marina Chuenkova, PhD, a research instructor in the pathology department at TUSM and the Sackler School, demonstrated that PDNF is a substrate and activator of Akt kinase, an enzyme that promotes cell survival by inhibiting "cell death" proteins.

"Further investigation showed that within T. cruzi-infected cells, PDNF also activates increased production of Akt, prolonging its protective effects," says Chuenkova. "Akt is a key regulator of diverse cellular processes, and supports cell survival not only by inhibiting apoptotic molecules, but additionally by increasing nutrient uptake and metabolism," she continued.

"In short, the T. cruzi parasite has a means of establishing life insurance once it has invaded the host. If we can fully understand the mechanisms behind this protection, we can begin to explore ways to undermine it with treatment," said Perrin.

Chagas' disease, typically transmitted to humans by blood-feeding insects, infects an estimated 8 to 11 million people throughout Mexico, and Central and South America. Although it is still rare in the United States, according to the Centers for Disease Control and Prevention (CDC), there are 300,000 people with Chagas' disease living in the United States, most of whom acquired the disease while living in other countries.

The acute phase of Chagas' disease can result in fever or swelling at the site of the insect bite, but many people do not experience symptoms at all. If left untreated, the disease enters an indeterminate phase in which no symptoms are present. During this phase, many people are not aware that they are infected, but approximately 30 percent will eventually develop life-threatening complications of the disease, including enlargement of the digestive tract and/or heart.

This study was funded by grants from the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health.

Chuenkova MV and PereiraPerrin M. Science Signaling. 2009. (November 17); 2(97), ra74. "Trypanosoma cruzi targets Akt in host cells as an intracellular antiapoptotic strategy." Published online November 17, 2009, doi: 10.1126/scisignal.2000374

About Tufts University School of Medicine

Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. The Sackler School undertakes research that is consistently rated among the highest in the nation for its impact on the advancement of medical science.

Source: Tufts University

Tiny RNA Has Big Impact On Lung Cancer Tumors

Researchers from Yale University and Mirna Therapeutics, Inc., reversed the growth of lung tumors in mice using a naturally occurring tumor suppressor microRNA. The study reveals that a tiny bit of RNA may one day play a big role in cancer treatment, and provides hope for future patients battling one of the most prevalent and difficult to treat cancers.

"This is the first time anybody has shown a positive effect of microRNAs in shrinking lung cancer," said Frank Slack, Ph.D., co-senior author of the paper, researcher at the Yale Cancer Center and professor of molecular, cellular & developmental biology.

The tumors in mice with non-small cell lung cancer shrank after the Yale team delivered an intranasal dose containing a type of micro-RNA called let-7, the authors reported in the Dec. 7 issue of the journal Oncogene. MicroRNAs are small bits of genetic material most often associated with transmission of information encoded in DNA. However in the past decade microRNAs have been shown to play crucial roles in gene regulation and/or gene silencing

The Yale team also found that mice without let-7 developed cancer, supporting their hypothesis that the microRNA acts as a tumor suppressor. The tumors in mice that received let-7 were not eliminated, but reduced by 66 percent, the study showed. The team is currently studying whether let-7 therapy in combination with chemotherapy and radiation can induce full remission.

Slack noted let-7 is absent in many cancers and acts upon a gene known to play a role in about a quarter of all human cancers.

"We hope it will be valuable in the treatment of many other forms of cancer," he said.

The research was conducted as part of collaboration between Yale and Mirna Therapeutics Inc, a biotechnology company in Austin, Texas. Joanne B. Weidhaas, MD/Ph.D. of Yale and Andreas G. Bader, Ph.D. of Mirna were co-senior authors of the paper. Other Yale authors on the paper are first author Phong Trang, Pedro P. Medina and Robert Homer; other Mirna authors are Jason F. Wiggins, Lynnsie Ruffino, Kevin Kelnar, Michael Omotola and David Brown, Ph.D.

Funding for the work came from the National Institutes of Health, Connecticut Department of Health, The Hope Funds for Cancer Research and Mirna Therapeutics, Inc.

Source:
Bill Hathaway
Yale University

Scientists Hear Cell Conversation For First Time

A cutting edge technique that allows scientists to monitor communication between cells could transform the way laboratory medical experiments are conducted. The method is likely to make laboratory studies of cancers and other human diseases, and assessment of new drugs to target them, more accurate.

The study was completed by Dr Rune Linding, head of the Cellular and Molecular Logic Team at The Institute of Cancer Research (ICR) in the UK, along with UK and Canadian-based colleagues. The research is published in the latest edition of the journal Science.

Dr Linding says that understanding communication between cells is crucial, as many cancers and other diseases are caused by a breakdown in communications systems.

"Organs and tissues are composed of many different cell types with distinct roles to play," Dr Linding says. "To function properly, the cells must communicate with each other, which they do through a network of specialised proteins known as signalling molecules. When cells are unable to send or receive the correct signals, they can behave abnormally and this can lead to disease."

Until now, scientists have generally studied cell communication by taking a single population of cells, adding a molecule to stimulate the cells and measuring the level of signalling molecules produced. But this technique does not take into account that cells respond to the signals they receive and feedback to each other, like a conversation between people.

"In our latest study, we have developed a way to more accurately replicate what's happening in the body - before scientists could only hear a monologue, but now for the first time we can assess the outcome of a conversation," Dr Linding says.

The new method involves growing cells in media containing labelled amino acids (the fundamental building blocks of proteins) that are incorporated into the cells' proteins. Two cell types, grown with different labels, are then combined for a short time to allow them to talk to each other, and then the cells are broken open so the proteins produced can be examined. A technique called mass spectrometry is then used to measure the level of each label, showing from which cell type the proteins originated.

The team then looked for genes that were involved in the conversation. They tested about 10 per cent of all human genes by blocking them within the cells one by one, using small interfering RNA molecules, and measured whether the cells behaved differently. Information about the proteins and genes was used to make a computer model of the signalling networks involved - effectively highlighting the important points in the conversation.

The research team first used this technique to study a key communications system known as EphB2, which is used to position cells precisely within the body and is important for maintaining boundaries between tissues. Cancer cells need to cross tissue boundaries to spread throughout the body, so a mutation in this system can promote metastasis.

Co-author Dr Claus Jørgensen from The Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Canada says: "Many types of cancers - including colorectal cancer, lung, prostate and breast cancer and glioma - have an abnormality in the Eph communications system, and it may also play a role in other diseases. However, until now it has not been possible to study this network during cell-to-cell contact, the most crucial time".

"Our study identified several new molecules involved in this system, knowledge that may play a role in future network biology-based drug development at the ICR. Perhaps most importantly, we found that the two cell types we studied responded differently to the conversation, which shows that previous experiments on just one cell type could well be inaccurate. This means that if you want to measure how cells will respond to signals - including signals that trigger cancer, or signals from drugs - you need to look at how they will respond when they are with other cell populations, not just one cell type alone."

Co-author Dr Tony Pawson, also from The Samuel Lunenfeld Research Institute, says: "This technique, which lets us consider two cell populations at once, is a major step towards more accurate laboratory research. We will adopt this approach to study how distinct cell populations talk to one another in diseases like cancer; the next stage is to find a way to take even more cell types and molecules into account. We can't mimic what goes on in the body yet, but we are getting closer."

Funding for this project came from the ICR, the Medical Research Council, Genome Canada through the Ontario Genomics Institute, a Terry Fox Programme grant from the Canadian Cancer Society, the Canadian Institutes for Health Research, the Canada Foundation for Innovation, the Human Frontiers Science Program and The Lundbeck Foundation.

Source
The Institute of Cancer Research

EMBL Scientists Uncover The Gene Responsible For Keeping Females Female

Is it a boy or a girl? Expecting parents may be accustomed to this question, but contrary to what they may think, the answer doesn't depend solely on their child's sex chromosomes. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany and the Medical Research Council's National Institute for Medical Research (NIMR) at Mill Hill, UK discovered that if a specific gene located on a non-sex chromosome is turned off, cells in the ovaries of adult female mice turn into cells typically found in testes. Their study, published in Cell, challenges the long-held assumption that the development of female traits is a default pathway. At the same time, it grants a valuable insight into how sex determination evolved.

In humans and most other mammals, an individual's sex is determined by its sex chromosomes: females have two X chromosomes, males have one X and one Y. Scientists had long assumed that the female pathway - the development of ovaries and all the other traits that make a female - was a kind of default: if it had a gene called Sry, which is located on the Y chromosome, an embryo would develop into a male, if not, then the result would be a female. But in adult animals it is the male pathway that needs to be actively suppressed, as Mathias Treier and his team at EMBL discovered.

A gene called Foxl2, which is located on an autosome - a chromosome other than the sex chromosomes - and therefore present in both sexes, was known to play an important role in the female pathway, but its precise function remained elusive. To elucidate the matter, Treier and colleagues ablated, or 'turned off', this gene in the ovaries of adult female mice.

"We were surprised by the results," says Treier, "We expected the mice to stop producing oocytes, but what happened was much more dramatic: somatic cells which support the developing egg took on the characteristics of the cells which usually support developing sperm, and the gender-specific hormone-producing cells also switched from a female to a male cell type."

Thus, the scientists discovered that Foxl2 plays a crucial role in keeping female mice female.

Teaming up with the group of Robin Lovell-Badge at the NIMR, they were able to decipher together the underlying molecular mechanism. They showed that FOXL2 and estrogen receptor act together by repressing a DNA element called TESCO that Lovell-Badge's group had previously identified to regulate expression of the testes-promoting gene Sox9. Sox9 was known to function in the embryo to make the early gonads become testes rather than ovaries, but the new studies suggest that it can perform the same task in the adult. FOXL2 is therefore critical to keep Sox9 turned off in ovaries throughout life.

"As most vertebrates have Foxl2, estrogen receptors and Sox9," Lovell-Badge explains, "this mechanism for maintaining female traits probably appeared early on in the evolution of vertebrates, while Sry and the mammalian Y chromosome are relatively new inventions."

These findings will have wide-ranging implications for reproductive medicine and may, for instance, help to treat sex differentiation disorders in children, for example where XY individuals develop as females or XX as males, and understand the masculinising effects of menopause on some women.

The study is discussed by author Mathias Treier in an online video in Cell's 'PaperFlicks' series, which is also available on YouTube.

Source: Sonia Furtado
European Molecular Biology Laboratory

Novel Detection Method Unmasks Circulating Breast Cancer Cells

Circulating metastatic breast cancer cells can lose their epithelial receptors, a process that enables them to travel through the bloodstream undetected, according to research from The University of Texas M. D. Anderson Cancer Center.

The findings were presented at the CTRC-AACR San Antonio Breast Cancer Symposium.

Levels of these circulating tumor cells (CTCs) - which are shed from a primary tumor or its metastases - have been used to monitor and tailor cancer therapy and to predict a patient's prognosis. CTCs that have undergone epithelial-mesenchymal transition (EMT), however, evade current detection methods and lose their traditional prognostic and therapeutic value. Those cancer cells also become more resistant to chemotherapy and radiation therapy. Finding a reliable method to detect these stealth breast cancer cells may reveal additional therapeutic targets that could help eradicate micrometastatic disease in patients with breast cancer or other epithelial tumors.

EMT and the Invasion-Metastasis Cascade

EMT is a process in which cancer cells undergo transdifferentiation (transformation into a different type of cell). "The carcinoma cells activate a transdifferentiation program in order to acquire the ability to execute the multiple steps necessary for the invasion-metastasis cascade," said the study's first author Michal Mego, M.D., Ph.D., formerly a fellow at M. D. Anderson. "During EMT, epithelial cells acquire a mesenchymal appearance with increased motility and invasiveness."

The researchers hypothesized that these changes render the EMT-CTCs undetectable by current detection assays, such as CellSearch (Veridex). The cells' acquired resistance to chemotherapy and radiotherapy also suggested that EMT-CTCs are tumor-initiating cells and are responsible for tumor dissemination. Moreover, the researchers had found subgroups of high-risk patients with brain metastases, triple receptor-negative disease, or inflammatory breast cancer whose blood tests did not reveal elevated levels of CTCs, further supporting their hypothesis.

Detecting CTCs Through EMT Gene Expression

The researchers then set out to develop a detection method that could identify EMT-CTCs in the peripheral blood of breast cancer patients. They took approximately 5 mL of peripheral blood from 27 patients ranging in age from 34 - 72 years, with a median age of 54. Sixteen of the women had metastatic disease, 19 had inflammatory breast cancer, and 12 had primary, non-inflammatory breast cancer.

"Using magnetic beads coated with monoclonal antibodies capable of capturing the majority of hematopoietic cells in peripheral blood, we obtained a fraction of cells enriched for CTCs," said Mego, who is now a scientist at the National Cancer Institute in the Slovak Republic. "Next we isolated RNA from these cells to detect genes that are involved in epithelial-mesenchymal transition, using molecular biology technology, such as the polymerase chain reaction."

Five EMT genes were identified: TWIST1, SNAIL1, SLUG, ZEB1, and FOXC2. At least one of these genes was over-expressed in 21 percent of the patients. Over-expression of EMT genes was more common among women with triple receptor-negative breast cancer than among those without this high-risk signature. The researchers found no correlation between EMT gene expression and CTC count as measured by CellSearch or the carcinoma-associated antigen known as Ep-CAM (epithelial cell adhesion molecule).

"We found that current CTC detection methods underestimate the most important subpopulation of CTCs involved in tumor dissemination-those with tumor-initiating properties," said James Reuben, Ph.D., professor in M. D. Anderson's Department of Hematopathology, the study's senior author. "A novel detection method such as ours that is capable of detecting CTCs after EMT could add important new prognostic information and could be useful for monitoring treatment efficacy in real time."

The M. D. Anderson and the Slovak National Cancer Institute teams have initiated a confirmatory study among patients with metastatic breast cancer, prostate cancer, or colon cancer. They also have initiated studies designed to identify therapeutic targets on EMT-CTCs. In addition to Mego and Reuben, other authors on the M. D. Anderson study include: Massimo Cristofanilli, M.D., Eleni Andreopoulou, M.D., and Summer Jackson, all of the Department of Breast Medical Oncology; Hui Gao, Ph.D. Changping Li, M.D., Sanda Tin, M.D. and Evan Cohen, all of the Department of Hematopathology; and Sendurai Mani, Ph.D., Department of Molecular Pathology.

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For six of the past eight years, including 2009, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Source: University of Texas M. D. Anderson Cancer Center

Those extra helpings of gravy and dessert at the holiday table are even less of a help to your waistline than previously thought. According to a new research report recently appearing online in The FASEB Journal, a diet that is high in fat and in sugar actually switches on genes that ultimately cause our bodies to store too much fat.

This means these foods hit you with a double-whammy as the already difficult task of converting high-fat and high-sugar foods to energy is made even harder because these foods also turn our bodies into "supersized fat-storing" machines.

In the research report, scientists show that foods high in fat and sugar stimulate a known opioid receptor, called the kappa opioid receptor, which plays a role in fat metabolism. When this receptor is stimulated, it causes our bodies to hold on to far more fat than our bodies would do otherwise.

According to Traci Ann Czyzyk-Morgan, one of the researchers involved in the work, "the data presented here support the hypothesis that overactivation of kappa opioid receptors contribute to the development of obesity specifically during prolonged consumption of high-fat, calorically dense diets."

To make this discovery, Czyzyk-Morgan and her colleagues conducted tests in two groups of mice. One group had the kappa opioid receptor genetically deactivated ("knocked out") and the other group was normal. Both groups were given a high fat, high sucrose, energy dense diet for 16 weeks. While the control group of mice gained significant weight and fat mass on this diet, the mice with the deactivated receptor remained lean. In addition to having reduced fat stores, the mice with the deactivated receptor also showed a reduced ability to store incoming nutrients.

Although more work is necessary to examine what the exact effects would be in humans, this research may help address the growing obesity problem worldwide in both the short-term and long-term. Most immediately, this research provides more proof that high-fat and high-sugar diets should be avoided. In the long-term, however, this research is even more significant, as it provides a new drug target for developing therapies for preventing obesity and helping obese people slim down.

"In times when food was scarce and starvation an ever-present threat, an adaptation that allows our bodies to store as much energy as possible during plentiful times was probably a lifesaver," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "By taking that opioid receptor off the table, researchers may have found a way to keep us from eating ourselves to death."

Journal Reference:

1. Traci A. Czyzyk, Ruben Nogueiras, John F. Lockwood, Jamie H. McKinzie, Tamer Coskun, John E. Pintar, Craig Hammond, Matthias H. Tschöp, and Michael A. Statnick. κ-Opioid receptors control the metabolic response to a high-energy diet in mice. The FASEB Journal, 2009; DOI: 10.1096/fj.09-143610

New Mechanism of Blocking HIV-1 from Entering Cells Identified

Publishing in PLoS Pathogens, researchers at from the Kimmel Cancer Center at Jefferson have found a novel mechanism by which drugs block HIV-1 from entering host cells.

Cellular invasion by HIV-1 requires the concerted action of two proteins on the viral surface: gp120 and gp41. The function of gp41 is to get the viral contents into the interior of the host cells. This requires the association of two distinct regions of gp41 called N-HR and C-HR. Anti-HIV-1 agents known as fusion inhibitors target the N-HR or C-HR and disrupt their association, which prevents the virus from entering into the host cell. One drug that works like this is Fuzeon (Roche), and there are other agents in the pipeline.

But blocking the N-HR/C-HR association is not only mechanism by which fusion inhibitors prevent HIV-1 entry, according to Michael Root, M.D., Ph.D., assistant professor of Biochemistry and Molecular Biology at Jefferson Medical College of Thomas Jefferson University. The inhibitors also induce irreversible deactivation of gp41.

"After these drugs bind, they seem to shuttle gp41 into a dead conformation from which the protein cannot recover," Dr. Root said. "Importantly, the speed of this drug-induced deactivation greatly influences how potent a drug is at preventing HIV-1 infection."

When the inhibitors bind to the gp41 C-HR, the protein rapidly deactivates before inhibitors have time to dissociate. But when the inhibitors bind to the gp41 N-HR, deactivation takes a very long time, and many inhibitors can readily unbind. To potently inhibit HIV-1 entry, a C-HR targeting fusion inhibitor can have a relatively low affinity, but an N-HR targeting fusion inhibitor must bind extremely tightly.

A major drawback to using Fuzeon and related drugs that target N-HR is the rapid emergence of HIV-1 strains resistant to the drugs. Dr. Root's study suggests that the resistance phenomenon is related to the slow speed of gp41 deactivation induced by these fusion inhibitors. HIV-1 appears to have more difficulty developing resistance to drugs that can remain bound to gp41 for much longer than gp41 takes to deactivate, even if the drugs are no more potent than Fuzeon against the original HIV-1 strain. Armed with this knowledge, Dr. Root and his team have developed a new strategy to improve the antiviral activities of N-HR-targeting fusion inhibitors.

These unexpected properties of HIV-1 fusion inhibitors are a consequence of the short time interval these drugs have to work. The N-HR and C-HR are only accessible to drug binding in a short-lived "intermediate state" that occurs right before N-HR/C-HR association. Most pharmaceutical agents bind targets that exist for long times, but a growing class of drugs target similar, short-lived intermediate states. These drugs include local anesthetics, antibiotics and immunosuppressive agents used in clinical practice. The results of this study might also be extended to understand the activities and limitations of these drugs.

How Did Flowering Plants Evolve to Dominate Earth?

To Charles Darwin it was an 'abominable mystery' and it is a question which has continued to vex evolutionists to this day: when did flowering plants evolve and how did they come to dominate plant life on earth? A new study in Ecology Letters reveals the evolutionary trigger which led to early flowering plants gaining a major competitive advantage over rival species, leading to their subsequent boom and abundance.

The study, by Dr Tim Brodribb and Dr Taylor Field of the University of Tasmania and University of Tennessee, used plant physiology to reveal how flowering plants, including crops, were able to dominate land by evolving more efficient hydraulics, or 'leaf plumbing', to increase rates of photosynthesis.

"Flowering plants are the most abundant and ecologically successful group of plants on earth," said Brodribb. "One reason for this dominance is the relatively high photosynthetic capacity of their leaves, but when and how this increased photosynthetic capacity evolved has been a mystery."

Using measurements of leaf vein density and a linked hydraulic-photosynthesis model, Brodribb and Field reconstructed the evolution of leaf hydraulic capacity in seed plants. Their results revealed that an evolutionary transformation in the plumbing of angiosperm leaves pushed photosynthetic capacity to new heights.

The reason for the success of this evolutionary step is that under relatively low atmospheric C0₂ conditions, like those existing at present, water transport efficiency and photosynthetic performance are tightly linked. Therefore adaptations that increase water transport will enhance maximum photosynthesis, exerting substantial evolutionary leverage over competing species.

The evolution of dense leaf venation in flowering plants, around 140-100 million years ago, was an event with profound significance for the continued evolution of flowering plants. This step provided a 'cretaceous productivity stimulus package' which reverberated across the biosphere and led to these plants playing the fundamental role in the biological and atmospheric functions of the earth.

"Without this hydraulic system we predict leaf photosynthesis would be two-fold lower then present," concludes Brodribb. "So it is significant to note that without this evolutionary step land plants would not have the physical capacity to drive the high productivity that underpins modern terrestrial biology and human civilisation."

Courtesy: ScienceDaily

Naked Mole Rats May Hold Clues to Surviving Stroke

Blind, nearly hairless, and looking something like toothy, plump, pink fingers, naked mole rats may rank among nature's most maligned creatures, but their unusual physiology endears them to scientists.

Two University of Illinois at Chicago researchers report in the Dec. 9 issue of NeuroReport (now online) that adult naked mole rat brain tissue can withstand extreme hypoxia, or oxygen deprivation, for periods exceeding a half-hour -- much longer than brain tissue from other mammals.

The findings may yield clues for better treatment of brain injuries associated with heart attack, stroke and accidents where the brain is starved of vital oxygen.

John Larson, associate professor of physiology in psychiatry, and Thomas Park, professor of biological sciences, studied African naked mole rats -- small rodents that live about six feet underground in big colonies of up to 300 members. The living is tight and the breathing even worse, with the limited air supply high in carbon dioxide and low in oxygen.

The air they breathe is so foul it would be fatal or lead to irreversible brain damage in any other mammal, Larson and Park said.

But naked mole rats studied were found to show systemic hypoxia adaptations, such as in the lungs and blood, as well as neuron adaptations that allow brain cells to function at oxygen and carbon dioxide levels that other mammals cannot tolerate.

"In the most extreme cases, naked mole rat neurons maintain function more than six times longer than mouse neurons after the onset of oxygen deprivation," said Larson.

"We also find it very intriguing that naked mole rat neurons exhibit some electrophysiological properties that suggest that neurons in these animals retain immature characteristics."

All mammal fetuses live in a low-oxygen environment in the womb, and human infants continue to show brain resistance to oxygen deprivation for a brief time into early childhood. But naked mole rats, unlike other mammals, retain this ability into adulthood.

"We believe that the extreme resistance to oxygen deprivation is a result of evolutionary adaptations for surviving in a chronically low-oxygen environment," said Park.

"The trick now will be to learn how naked mole rats have been able to retain infant-like brain protection from low oxygen, so we can use this information to help people who experience temporary loss of oxygen to the brain in situations like heart attacks, stroke or drowning," he said.

Larson said study of the naked mole rat's brain may yield clues for learning the mechanisms that allow longer neuronal survival after such accidents or medical emergencies, which may suggest ways to avoid permanent human brain damage.

Courtesy: ScienceDaily

Some Germs Are Good for You: Surface Bacteria Maintain Skin's Healthy Balance

On the skin's surface, bacteria are abundant, diverse and constant, but inflammation is undesirable. Research at the University of California, San Diego School of Medicine now shows that the normal bacteria living on the skin surface trigger a pathway that prevents excessive inflammation after injury.

"These germs are actually good for us," said Richard L. Gallo, MD, PhD, professor of medicine and pediatrics, chief of UCSD's Division of Dermatology and the Dermatology section of the Veterans Affairs San Diego Healthcare System.

The study, to be published in the advance on-line edition of Nature Medicine on November 22, was done in mice and in human cell cultures, primarily performed by post-doctoral fellow Yu Ping Lai .

"The exciting implications of Dr. Lai's work is that it provides a molecular basis to understand the 'hygiene hypothesis' and has uncovered elements of the wound repair response that were previously unknown. This may help us devise new therapeutic approaches for inflammatory skin diseases," said Gallo.

The so-called "hygiene hypothesis," first introduced in the late 1980s, suggests that a lack of early childhood exposure to infectious agents and microorganisms increases an individuals susceptibility to disease by changing how the immune system reacts to such "bacterial invaders." The hypothesis was first developed to explain why allergies like hay fever and eczema were less common in children from large families, who were presumably exposed to more infectious agents than others. It is also used to explain the higher incidence of allergic diseases in industrialized countries.

The skin's normal microflora -- the microscopic and usually harmless bacteria that live on the skin -- includes certain staphylococcal bacterial species that will induce an inflammatory response when they are introduced below the skin's surface, but do not initiate inflammation when present on the epidermis, or outer layer of skin.

In this study, Lai, Gallo and colleagues reveal a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. Such inhibition is mediated by a molecule called staphylococcal lipoteichoic acid (LTA) which acts on keratinocytes -- the primary cell types found on the epidermis.

The researchers also found that Toll-like receptor 3 (TLR3) activation is required for normal inflammation after skin injury.

"Keratinocytes require TLR3 to mount a normal inflammatory response to injury, and this response is kept from becoming too aggressive by staphylococcal LTA," said Gallo. "To our knowledge, these findings show for the first time that the skin epithelium requires TLR3 for normal inflammation after wounding and that the microflora helps to modulate this response."

Additional contributors to the paper include Yuping Lai, Anna Di Nardo, Teruaki Nakatsuji, Anna L Cogen, Chun-Ming Huang and Katherine A. Radek, UCSD Division of Dermatology and the VA San Diego Healthcare System; Anke Leichtle and Allen F. Ryan, UCSD Department of Surgery/Otolaryngology and the VA San Diego Healthcare System; Yan Yang and Zi-Rong Wu, School of Life Science, East China Normal University, Shanghai; Lora V Hooper, Howard Hughes Medical Institute and University of Texas Southwestern Medical Center, Dallas; and Richard R Schmidt and Sonja von Aulock, University of Konstanz, Germany.

The study was funded by grants from the National Institutes of Health, and a US Veterans Administration Merit Award.

Courtesy: ScienceDaily

Can Meditation Curb Heart Attacks?

When Julia Banks was almost 70, she took up transcendental meditation. She had clogged arteries, high blood pressure and too much weight around the middle, and she enrolled in a clinical trial testing the benefits of meditation.

Now Mrs. Banks, 79, of Milwaukee, meditates twice a day, every day, for 20 minutes each time, setting aside what she calls “a little time for myself.”

“You never think you’ve got that time to spare, but you take that time for yourself and you get the relaxation you need,” said Mrs. Banks, who survived a major heart attack and a lengthy hospitalization after coronary artery bypass surgery six years ago.

“You have things on your mind, but you just blot it out and do the meditation, and you find yourself being more graceful in your own life,” she said. “You find out problems you thought you had don’t exist — they were just things you focused on.”

Could the mental relaxation have real physiological benefits? For Mrs. Banks, the study suggests, it may have. She has gotten her blood pressure under control, though she still takes medication for it, and has lost about 75 pounds.

Findings from the study were presented this week at an American Heart Association meeting in Orlando, Fla. They suggest that transcendental meditation may have real therapeutic value for high-risk people, like Mrs. Banks, with established coronary artery disease.

After following about 200 patients for an average of five years, researchers said, the high-risk patients who meditated cut their risk of heart attacks, strokes and deaths from all causes roughly in half compared with a group of similar patients who were given more conventional education about healthy diet and lifestyle.

Among the roughly 100 patients who meditated, there were 20 heart attacks, strokes and deaths; in the comparison group, there were 32. The meditators tended to remain disease-free longer and also reduced their systolic blood pressure by five millimeters of mercury, on average.

“We found reduced blood pressure that was significant – that was probably one important mediator,” said Dr. Robert Schneider, director of the Institute for Natural Medicine and Prevention, a research institute based at the Maharishi University of Management in Fairfield, Iowa, who presented the findings. The study was conducted at the Medical College of Wisconsin in Milwaukee, in collaboration with the institute.

An earlier study of high-risk Milwaukee residents, many of them overweight or obese, also found transcendental meditation, along with conventional medications, could help reduce blood pressure. Most of those in the study had only high-school educations or less, about 40 percent smoked and roughly half had incomes of less than $10,000 a year.

The participants found transcendental meditation easy to learn and practice, Dr. Schneider said.

“Fortunately, it does not require any particular education and doesn’t conflict with lifestyle philosophy or beliefs; it’s a straightforward technique for getting deep rest to the mind and body,” he said, adding that he believes the technique “helps to reset the body’s own self-repair and homeostatic mechanism.”

Dr. Schneider said other benefits of meditation might follow from stress reduction, which could cause changes in the brain that cut stress hormones like cortisol and dampen the inflammatory processes associated with atherosclerosis.

“What is it about stress that causes cardiovascular disease?” said Dr. Theodore Kotchen, associate dean for clinical research at the Medical College of Wisconsin. “Hormones, neural hormones, cortisol, catecholamines — all tend to be elevated in stress. Could they in some way be contributing to cardiovascular disease? Could a reduction in these hormones with meditation be contributing to reduction in disease? We can only speculate.”

Another recent study focusing on transcendental meditation, published in The American Journal of Hypertension, focused on a young healthy population. It found that stressed-out college students improved their mood through T.M., and those at risk for hypertension were able to reduce their blood pressure. Dr. Schneider was also involved in that study, which was carried out at American University in Washington and included 298 students randomly assigned to either a meditation group or a waiting list.

Students who were at risk of hypertension and practiced meditation reduced systolic blood pressure by 6.3 millimeters of mercury and their diastolic pressure by 4 millimeters of mercury on average.

Courtesy:Newyork times

Termites Create Sustainable Monoculture Fungus Farming

Food production of modern human societies is mostly based on large-scale monoculture crops, but it now appears that advanced insect societies have the same practice. Our societies took just ten thousand years of (mainly cultural) evolution to adopt this habit and we are far from convinced that it is sustainable. Farming ants and termites had tens of millions of years to evolve their fungus farming systems and here monocultures are apparently evolutionary stable.

In a study published in the journal Science, researchers from the Laboratory of Genetics of Wageningen University and the Centre for Social Evolution at the University of Copenhagen take significant steps to resolve this puzzle.

The fungus-growing termites of the old-world tropics build impressive mounds consisting of thousands of workers and soldiers. These societies domesticated African Termitomyces mushrooms more than 30 million years ago and became obligatorily dependent on farming their own fungal food in their often gigantic nest mounds. The termite fungus-farming symbiosis had a single African rain-forest origin and now comprises ca 330 species. It is of major ecological importance for decomposition and mineralcycling.

A colony-founding termite queen and king normally do not acquire their first garden until they have raised the first workers. These helpers collect Termitomyces spores while foraging, together with the plant material that they defecate in the nest to establish a garden substrate. These spores are amply available because the fungus gardens produce large mushrooms once a year on top of the termite mounds.

However, this farming practice offers a paradox: Evolutionary theory predicts that symbioses with multiple lineages per colony should be unstable, because these genotypes can be expected to compete for making mushrooms rather than collaborate to serve the termite farmers.

The new study shows that a very special mechanism is in place to prevent this from happening. All colonies from which multiple fungal samples were genetically analyzed contained only a single fungal genotype in spite of gardens having been initiated from at least two and probably many more genetically different spores.

Duur Aanen, Koos Boomsma and their respective colleagues in Wageningen and Copenhagen show that genotypes that happen to be common in a garden, become even more common at the expense of rarer genotypes. This happens not because common genotypes are better direct competitors, but because they have a higher chance of having an identical genotype as neighbor. Every time this happens, such genetically identical mycelia merge, which enhances the efficiency by which they produce asexual spores that the termites eat and deposit in new garden material of the colony. This process of positive reinforcement makes every colony end up with a life-time commitment to a single fungal symbiont in spite of the population at large having many fungal genotypes.

Shifting Vaccine for Flu to Elderly

Federal health officials are trying to shift supplies of the seasonal flu vaccine away from chain pharmacies and supermarkets to nursing homes, hoping to counter a shortage that threatens to cause a wave of deaths this winter among the nation’s most vulnerable population.

The extent of the shortage is still unclear, but Janice Zalen, director of special programs for the American Health Care Association, which represents 11,000 nursing homes and assisted-living facilities, called it “a very big problem.”

Ms. Zalen said that of 1,000 nursing home managers who responded to a survey of the association’s 11,000 members, 800 reported they could not get enough vaccine.

Dr. Carol Friedman, head of adult immunization at the Centers for Disease Control and Prevention, said she did not have a figure for the size of the shortage, but added, “It’s a problem, and it’s all over the country.”

Mary Hahn, who manages six Ohio nursing homes with 800 beds, said she could not get vaccine for any of her patients.

“It’s just so disheartening, because we’re having to leave people unprotected,” she said. “You see people get flus and get sent to the hospital because they really can’t fight it off.”

A nationwide shortage of the seasonal flu vaccine has been reported for several weeks, but nursing homes and their suppliers have grown more alarmed in recent days. Of the 36,000 Americans who die of seasonal flu in the average year, more than 90 percent are 65 or older, and nursing home outbreaks are particularly deadly. By contrast, the swine flu epidemic has been most deadly among younger people.

The nursing homes’ predicament has been caused by a confluence of factors. Because of the swine flu pandemic, far more people than usual are seeking vaccination, Dr. Friedman said — even though the seasonal vaccine does not protect against swine flu.

The five companies licensed to make flu shots for the United States originally planned to make only slightly more than the 118 million they made in 2008. Then, production problems caused GlaxoSmithKline to cut its run by half; Novartis’s shrank by 10 percent. Then all five companies had to switch over early to making swine flu vaccine.

So the total supply of vaccine is about 114 million doses, of which about 95 million have been shipped.

At the same time, reports of price gouging have grown more frequent. That also happened in 2004, when sterility problems at a British plant cut the American flu vaccine supply in half; prices shot up as high as $90 a dose, from the normal level of $8 to $9.

Gouging is illegal in about half the states, but each state varies in how big a price increase constitutes gouging and as to whether an emergency must have been declared for the law to kick in.

“To pursue a case, we need to show it’s not just a couple of dollars but is very significant,” said Attorney General Richard Blumenthal of Connecticut, who has opened an investigation.

Criminal charges are less likely than a civil suit, Mr. Blumenthal said. But he added that if distributors were “masquerading or fraudulently claiming to have vaccine,” that could end in a criminal charge. While he had suspicions, he said, “we don’t have hard evidence yet.”

Dr. Friedman said that once the agency became aware of the shortage at nursing homes, “we began working with the manufacturers to see if they could redirect some of their vaccine.”

“Several big-box retailers and pharmacies volunteered to go into the long-term-care facilities and set up flu clinics,” she said.

Dr. Friedman said she knew of one major supplier to nursing homes that received 100,000 fewer doses from the vaccine makers than it had ordered. Her agency began acting as a broker among the homes, vaccine distributors and other customers. Since then, she said, that supplier has found about 50,000 more doses.

“That’s definitely not going to close the gap,” she said, “but it will help.”

Also, both she and Ms. Zalen said, pharmacy and supermarket chains like Walgreen’s and Safeway that bought millions of doses to sell for $25 to $30 have offered to give shots in nursing homes. They do not charge but get Medicare reimbursements, which vary by state but run up to $25.

By contrast, Bob McKay, chief of sales for PharMerica, one of the two largest wholesale pharmacies supplying nursing homes, said he had received 95 percent of the 300,000 doses he ordered and “the voids are getting filled in” at the nursing homes he supplies.

“We’re not hearing rage and craziness out there,” Mr. McKay said. “If a lot of homes were still short, they’d be beating our doors down.”

But he said he had asked some not to buy shots for their staffs. Flu experts say that in nursing homes, vaccination of staff members is just as important as patient vaccination.

Prices offered to PharMerica for the extra doses they needed were “in the $15-$16 range,” Mr. McKay said. “That’s more than we’d normally pay, but not price-gouging.”

Jim Mathews, an executive at Hometown Pharmacy, a smaller wholesale pharmaceutical company supplying Michigan nursing homes, said that late last month he found himself 3,000 doses short; his usual supplier, which charges $6.75 per dose, was out of stock. He called the C.D.C. for advice, was directed to a Web page listing other suppliers and contacted all 10. Only one had vaccine, and it sent him a fax in broken English asking for $57 to $59 per dose.

Mr. Mathews said he reported that to local law enforcement officials, but he is more worried about the patients who will not get shots.

“When I first recognized the potential death toll from this shortage, there was time to prioritize the remaining supply for the most vulnerable elderly,” he said. “Now I’m afraid it’s too late. From what I see, the seasonal flu vaccine shortage is going to cost more lives than the H1N1 shortage is.”

Dr. Friedman, of the C.D.C., said she had heard of “about 15” price-gouging complaints.

Dr. Lillian Overman, an internist in East Hartford, Conn., was one of the first to alert Mr. Blumenthal, the state’s attorney general, about gouging accusations. On Oct. 26, her office manager began looking for vaccine, for which she normally pays $8.50 a dose. A saleswoman at ABO Pharmaceuticals in San Diego wanted $60 per dose, she said.

“That’s just prohibitive,” a frustrated Dr. Overman said. “If I’d known there would be a shortage, I would have called in my most vulnerable patients first.”

Mark Nemeth, an ABO sales manager, denied that anyone there had asked for $60.

“I can guarantee you without a shadow of a doubt, we would never have offered it at that price,” he said; the company is asking “in the ballpark of $12 to $14” for its remaining supplies.

Courtesy: Newyorktimes

New Synthetic Molecules Trigger Immune Response To HIV And Prostate Cancer

Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in theJournal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.

The molecules -- called "antibody-recruiting molecule targeting HIV" (ARM-H) and "antibody-recruiting molecule targeting prostate cancer" (ARM-P) -- work by binding simultaneously to an antibody already present in the bloodstream and to proteins on HIV, HIV-infected cells or cancer cells. By coating these pathogens in antibodies, the molecules flag them as a threat and trigger the body's own immune response. In the case of ARM-H, by binding to proteins on the outside of the virus, they also prevent healthy human cells from being infected.

"Instead of trying to kill the pathogens directly, these molecules manipulate our immune system to do something it wouldn't ordinarily do," said David Spiegel, Ph.D., M.D., assistant professor of chemistry and the corresponding author of both papers.

Because both HIV and cancer have methods for evading the body's immune system, treatments and vaccinations for the two diseases have proven difficult. Current treatment options for HIV and prostate cancer -- including antiviral drugs, radiation and chemotherapy -- involve severe side effects and are often ineffective against advanced cases. While there are some antibody drugs available, they are difficult to produce in large quantities and are costly. They also must be injected and are accompanied by severe side effects of their own.

By contrast, the ARM-H and ARM-P molecules, which the team has begun testing in mice, are structurally simple, inexpensive to produce, and could in theory be taken in pill form, Spiegel said. And because they are unlikely to target essential biological processes in the body, the side effects could be smaller, he noted.

"This is an entirely new approach to treating these two diseases, which are extraordinarily important in terms of their impact on human health," Spiegel said.

HIV is a global pandemic that affects 33 million people worldwide, while prostate cancer is the second leading cause of cancer-related death among American men, with one out of every six American men expected to develop the disease.

Funding for this research was provided by the National Institutes of Health.

Courtesy: ScienceDaily

Seafloor Fossils Provide Clues To Climate Change

Deep under the sea, a fossil the size of a sand grain is nestled among a billion of its closest dead relatives. Known as foraminifera, these complex little shells of calcium carbonate can tell you the sea level, temperature, and ocean conditions of Earth millions of years ago. That is, if you know what to look for.

Assistant Professor of Earth and Environmental Sciences at Rensselaer Polytechnic Institute Miriam Katz has spent the past two decades studying these ancient, deep-sea fossils to reconstruct the climates of Earth up to 250 million years ago. Through ice ages and greenhouse climates, Katz has been able to piece together oxygen, carbon, and faunal data to paint a portrait of how, when, and why our climate has changed so drastically over geologic history. In addition, her investigations into the deep past of Earth have important implications for understanding and tracking the potential drastic repercussions of modern, human-induced climate change.

"There is a saying among scientists in my field that 'the past is a window on the future,' " Katz said. "By reconstructing the climates of the past, particularly those where we see massive and rapid changes in the climate, we can provide a science-based means to explore or predict possible system responses to the current climate change."

While her work requires a lot of time in the laboratory, Katz has spent nearly two years at sea on seven different ocean voyages around the world to drill for foraminifera as part of the Integrated Ocean Drilling Program (IODP), an international marine research effort that explores the Earth's history and structure by looking at seafloor sediments and rocks. During each two-month IODP excursion, Katz and the other scientists on board never set foot on land and spend hours poking through the millions of layers of sediment, trapped gases, fossils, and trace elements found in huge cores drilled from deep under the seafloor.

Just a few inches in diameter, each core is painstakingly drilled and removed from the seafloor. From top to bottom, the core provides a reverse chronology of the various organisms, sediments, and elements that were found on Earth throughout history. Unlike cores from sedimentary layers from the continents that are quickly destroyed by the forces of plate tectonics, wind, and water, these rarely disturbed ocean sediment cores can provide records up to 180 million years ago as new layers of sediment bury and preserve those of the past.

Katz is most interested in the foraminifera found in the cores. The foraminifera she studies live on or just below the seafloor. When they die, their hard shells are incorporated in the surrounding sediments and buried over time in a nearly uniform layer.

The assemblages of foraminifera in each layer can provide valuable information on the climate of that time. "Some species are only found in certain environments, such as in warm water or in shallow, tidal areas," Katz said. "By piecing together the species assemblages that are found in a given area during the given time period, we can reconstruct the sea level and ocean and climate conditions of that period based on our knowledge of each foraminiferal species."

In addition to the specific type of foraminifera seen in each layer, valuable information can also be gathered by looking at variations in the chemical structure of the fossilized calcium carbonate (CaCO3) shell seen in the various layers. During their life, the foraminiferal shells are formed from the elements found in the seas that they lived in. The ratios of various isotopes of the elements carbon and oxygen found in foraminiferal shells at different times in Earth's history provide important information needed to reconstruct the climate and ocean waters that surrounded them during their short lives millions of years ago.

In the case of oxygen (O), the ratio between isotopes 18O and 16O tells scientists how much water is trapped in glacial ice, providing important clues about temperature and the size of the ancient continental ice sheets. Carbon (C) in the shells can be analyzed for either 12C or 13C isotopes. Plants prefer to incorporate lighter 12C during photosynthesis, increasing the ratio of 13C to 12C in foraminifera when plant and algae production is high. This carbon data provides clues on the types and amounts of vegetation at various times as well as ocean circulation, according to Katz.

Gathering this information from cores has allowed Katz to develop important theories on one of the most recent and dramatic climate change events that has occurred in recent geologic history -- the transition from the greenhouse climate of the Eocene epoch to the "icehouse" or glacial conditions of the Oligocene epoch approximately 33.5 million years ago.

"The boundary between the late Eocene to the early Oligocene is a striking example of rapid climate change that we can look to in Earth's past," Katz said. "Information from this period can provide us with important information on how rapid changes in temperature can significantly impact ice volume, sea level, and the evolution of life on Earth."

Katz has used oxygen and carbon isotopes as well as the ratio of magnesium to calcium within foraminifera from this period to reconstruct the changes that occurred as the climate rapidly cooled. Along with her research colleagues, she has shown that ice sheets at the end of the transition were approximately 25 percent larger than today, causing a decrease in sea level of approximately 105 meters.

Her research also reaches even further back to reconstruct conditions earlier in Earth's history. In particular, she took part in a study of atmospheric oxygen and carbon dioxide concentrations since the Jurassic period 205 million years ago. The group has found that oxygen levels doubled in the short period of time from the Jurassic period to the Eocene epoch (~150 million years ago), providing a climate with just enough oxygen for placental mammals to develop.