Removing the foreskin causes a significant shift in the bacterial community or microbiome of the penis, a new study has revealed.

Male circumcision reduces the abundance of bacteria living on the penis and might help explain why circumcision offers men some protection against HIV, according to a study led by the Translational Genomics Research Institute (TGen).
This international collaboration focused on 156 men in Rakai, Uganda - part of the world`s largest randomized-controlled trial on male circumcision.

Researchers showed that men who were circumcised as part of the study had 33.3 percent less bacteria on their penis than those who remained uncircumcised one year after the study began.

Researchers further showed that the decrease was primarily found in 12 types of bacteria, most of which were intolerant to oxygen.

Past studies have shown that circumcision reduces female-to-male HIV transmission, among other benefits.

This study suggests a possible mechanism for HIV protection - the shift in the number and type of bacteria living on the penis.

Further studies will have to be done to demonstrate that a change in the penis microbiome can help reduce the risk of HIV transmission, according to the authors.

At the same time, understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, especially for populations with high HIV prevalence and in places where male circumcision is culturally less acceptable, the study says.

"We know that male circumcision can prevent HIV and other diseases in heterosexual men, but it is important to know why," Dr. Lance Price, the Director of TGen Center for Microbiomics and Human Health and the study`s senior author said.

"We think that these dramatic changes in the penis microbiome may explain, at least in part, why male circumcision is protective," he said.

The study is published online in the journal mBio.

UC San Francisco scientists have revealed that specific DNA once dismissed as junk plays an important role in brain development and might be involved in several devastating neurological diseases.

Their discovery in mice is likely to further fuel a recent scramble by researchers to identify roles for long-neglected bits of DNA within the genomes of mice and humans alike.

While researchers have been busy exploring the roles of proteins encoded by the genes identified in various genome projects, most DNA is not in genes. This so-called junk DNA has largely been pushed aside and neglected in the wake of genomic gene discoveries, the UCSF scientists said.

In their own research, the UCSF team studies molecules called long noncoding RNA (lncRNA, often pronounced as "link" RNA), which are made from DNA templates in the same way as RNA from genes.

"The function of these mysterious RNA molecules in the brain is only beginning to be discovered," said Daniel Lim, MD, PhD, assistant professor of neurological surgery, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, and the senior author of the study.

Alexander Ramos, a student enrolled in the MD/PhD program at UCSF and first author of the study, conducted extensive computational analysis to establish guilt by association, linking lncRNAs within cells to the activation of genes.

Ramos looked specifically at patterns associated with particular developmental pathways or with the progression of certain diseases. He found an association between a set of 88 long noncoding RNAs and Huntington`s disease, a deadly neurodegenerative disorder. He also found weaker associations between specific groups of long noncoding RNAs and Alzheimer`s disease, convulsive seizures, major depressive disorder and various cancers.

Unlike messenger RNA, which is transcribed from the DNA in genes and guides the production of proteins, lncRNA molecules do not carry the blueprints for proteins. Because of this fact, they were long thought to not influence a cell`s fate or actions.

Nonetheless, lncRNAs also are transcribed from DNA in the same way as messenger RNA, and they, too, consist of unique sequences of nucleic acid building blocks.

Evidence indicates that lncRNAs can tether structural proteins to the DNA-containing chromosomes, and in so doing indirectly affect gene activation and cellular physiology without altering the genetic code. In other words, within the cell, lncRNA molecules act "epigenetically" - beyond genes - not through changes in DNA.

The brain cells that the scientists focused on the most give rise to various cell types of the central nervous system. They are found in a region of the brain called the subventricular zone, which directly overlies the striatum. This is the part of the brain where neurons are destroyed in Huntington`s disease, a condition triggered by a single genetic defect.

Ramos combined several advanced techniques for sequencing and analyzing DNA and RNA to identify where certain chemical changes happen to the chromosomes, and to identify lncRNAs on specific cell types found within the central nervous system. The research revealed roughly 2,000 such molecules that had not previously been described, out of about 9,000 thought to exist in mammals ranging from mice to humans.

In fact, the researchers generated far too much data to explore on their own. The UCSF scientists created a website through which their data can be used by others who want to study the role of lncRNAs in development and disease.

The study was published online in the journal Cell Stem Cell.

Scientists at The Scripps Research Institute (TSRI) have unravelled one of the major toxic mechanisms of Alzheimer`s disease.

The discoveries could lead to a much better understanding of the Alzheimer`s process and how to prevent it.

The findings showed that brain damage in Alzheimer`s disease is linked to the overactivation of an enzyme called AMPK. When the scientists blocked this enzyme in mouse models of the disease, neurons were protected from loss of synapses-neuron-to-neuron connection points-typical of the early phase of Alzheimer`s disease.

In addition to having implications for Alzheimer`s drug discovery, TSRI Professor Franck Polleux, who led the new study, noted the findings suggest the need for further safety studies on an existing drug, metformin. Metformin, a popular treatment for Type 2 Diabetes, causes AMPK activation.

Georges Mairet-Coello, a postdoctoral research associate in the Polleux lab, performed most of the experiments for the new study.

He began by confirming that amyloid beta, in the small-aggregate ("oligomer") form that is toxic to synapses, does indeed strongly activate AMPK; amyloid beta oligomers stimulate certain neuronal receptors, which in turn causes an influx of calcium ions into the neurons.

He found that this calcium influx triggers the activation of an enzyme called CAMKK2, which appears to be the main activator of AMPK in neurons.

The team then showed that this AMPK overactivation in neurons is the essential reason for amyloid beta`s synapse-harming effect. Normally, the addition of amyloid beta oligomers to a culture of neurons causes the swift disappearance of many of the neurons` dendritic spines-the rootlike, synapse-bearing input stalks that receive signals from other neurons.

With a variety of tests on mice, the scientists showed that amyloid beta oligomers can`t cause this dendritic spine loss unless AMPK overactivation occurs-and indeed AMPK overactivation on its own can cause the spine loss.

Next Mairet-Coello investigated the role of the tau protein. Ordinarily it serves as a structural element in neuronal axons, but in Alzheimer`s it somehow becomes hyperphosphorylated and drifts into other neuronal areas, including dendrites where its presence is associated with spine loss.
Recent studies have shown that amyloid beta`s toxicity to dendritic spines depends largely on the presence of tau, but just how the two Alzheimer`s proteins interact has been unclear.

The team took a cue from a 2004 study of Drosophila fruit flies, in which an AMPK-like enzyme`s phosphorylation of specific sites on the tau protein led to a cascade of further phosphorylations and the degeneration of nerve cells. The scientists confirmed that one of these sites, S262, is indeed phosphorylated by AMPK.

They then showed that this specific phosphorylation of tau accounts to a significant extent for amyloid beta`s synapse toxicity.

"Blocking the phosphorylation at S262, by using a mutant form of tau that can`t be phosphorylated at that site, prevented amyloid beta`s toxic effect on spine density," Mairet-Coello said.

The result suggests that amyloid beta contributes to Alzheimer`s via AMPK, mostly as an enabler of tau`s toxicity.

The findings were recently reported in the journal Neuron.

A group of researchers from the University of Oxford believe they have engineered a protein from flesh-eating bacteria that acts as a molecular `superglue` and could be used to help detect cancer cells.

"We`ve turned the tables and put one kind of flesh-eating bacterium to good use," said Mark Howarth, Ph.D., who led the research.

"We have engineered one of its proteins into a molecular superglue that adheres so tightly that the set-up we used to measure the strength actually broke. It resists high and low temperatures, acids and other harsh conditions and seals quickly.

"With this material we can lock proteins together in ways that could underpin better diagnostic tests - for early detection of cancer cells circulating in the blood, for instance. There are many uses in research, such as probing how the forces inside cells change the biochemistry and affect health and disease."

Howarth`s team at the University of Oxford in the United Kingdom genetically engineered the glue from a protein, FbaB, that helps Streptococcus pyogenes (S. pyogenes) bacteria infect cells. S. pyogenes is one of the microbes that can cause the rare necrotizing fasciitis, or flesh-eating bacteria syndrome, in which difficult-to-treat infections destroy body tissue.

They split FbaB into two parts, a larger protein and a smaller protein subunit, termed a peptide. Abbreviating S. pyogenes as "Spy," they named the small peptide "SpyTag" and the larger protein "SpyCatcher."

The gluing action occurs when SpyTag and SpyCatcher meet. They quickly lock together by forming one of the strongest possible chemical bonds. SpyCatcher and SpyTag can be attached to the millions of proteins in the human body and other living things, thus gluing proteins together.

One of the applications on the horizon involves testing the technology as a new way to detect "circulating tumor cells," or CTCs. Tumors shed these cells into the bloodstream, where they may act as seeds, spreading or metastasizing cancer from the original site to other parts of the body.

That spreading is the reason why cancer is such a serious health problem.

Howarth said that the Spy technology has advantages over other molecular gluing systems that are available. SpyCatcher and SpyTag, for instance, can glue two proteins together at any point in the protein.
"That flexibility allows us many different ways to label proteins and gives us new approaches to assemble proteins together for diagnostic tests," Howarth explained.

The study was recently presented at the 245th National Meeting and Exposition of the American Chemical Society.

Teenagers who increased the days on which they got just 20 minutes of exercise, equivalent to a short walk, were able to cut down on their smoking habit, according to a study.

It also found teenage smokers were more likely to quit altogether if they participated in a smoking cessation/fitness program-and they ramped up the days on which they got at least 30 minutes of physical activity.

"This study adds to evidence suggesting that exercise can help teenagers who are trying to quit smoking," said lead author Kimberly Horn, EdD, the Associate Dean for Research at the George Washington University School of Public Health and Health Services (SPHHS).

"Teens who boosted the number of days on which they engaged in at least 20 minutes of exercise, equivalent to a short walk, were more likely than their peers to resist lighting up a cigarette," the researcher stated.

Horn and her colleagues tracked 233 teenagers from 19 high schools in West Virginia, a state with among the highest smoking rates in the nation. The participants in the study were daily smokers with other risky behaviors.

That study found that an intensive smoking cessation intervention combined with a fitness program was the most successful way to help teenagers quit.

In the current study, Horn`s team looked to see if an increase in physical activity would help teens quit regardless of the type of intervention. In this study, as in the previous one, some teenagers went through an intensive anti-smoking program combined with a fitness intervention while others just got the smoking cessation program and still others listened to a short anti-smoking lecture.

Horn found that all of the teens increased their exercise activity to some degree-just by virtue of being in the study. However, teens who reported increasing the number of days in which they got just 20 minutes a day of exercise were able to significantly cut back on the cigarettes they smoked.

Horn`s previous study showed that the most powerful way for teens to quit smoking was if they participated in a program called Not-On-Tobacco; it was even more powerful for boys with an added fitness component. The researchers believe that the 20-minute threshold for changing smoking behavior deserves further study.

But Horn noted that the study has limitations.

"We don`t fully understand the clinical relevance of ramping up daily activity to 20 or 30 minutes a day with these teens. But we do know that even modest improvements in exercise may have health benefits. Our study supports the idea that encouraging one healthy behavior can serve to promote another, and it shows that teens, often viewed as resistant to behavior change, can tackle two health behaviors at once," she added.

And researchers still do not know the mechanism that might explain the findings. However, she says that physical activity is known to spur the release of the body`s feel-good chemicals called endorphins.

One possible explanation is that those substances might help teen smokers better deal with the cravings or weather the withdrawal symptoms that often lead to relapse, she said.

The study appeared online in the Journal of Adolescent Health, the official publication of the Society for Adolescent Medicine.