Male Menopause Affects More Than Five Million Men

While most frequently associated with women's health, age-related hormone changes, often dubbed menopause, can occur in men as well, causing symptoms of fatigue, mood swings, decreased desire for sex, hair loss, lack of concentration and weight gain. Experts estimate that more than 5 million men are affected, yet worry the number may be considerably higher since symptoms are frequently ignored.

Male hypogonadism, as it's referred to in the medical community, occurs when the testicles do not produce enough testosterone, the hormone that plays a key role in masculine growth and development. When hormone levels drop, men can experience significant mental and physical changes.

"This is a highly prevalent disorder," said Robert Brannigan, MD, urologist at Northwestern Memorial Hospital. "Unfortunately, we estimate that 95 percent of cases are undiagnosed and therefore untreated. When ignored, symptoms can seriously disrupt one's quality of life."

"My body was telling me that something wasn't right. I was always tired, it didn't matter how much sleep I got, I constantly wanted to take a nap," said Michael Andruzzi, a 40 year old man diagnosed with male hypogonadism and a patient at Northwestern Memorial.

Brannigan explains hormone variations are a normal aspect of getting older. "In females, ovulation comes to an end and hormone production declines in a relatively quick period of time, whereas men experience hormone shifts more slowly, with testosterone levels dropping around one percent each year beginning in a man's late thirties," adds Brannigan, who is also an associate professor of urology at the Northwestern University Feinberg School of Medicine.

Brannigan goes on to explain that by age seventy, the reduction in a male's testosterone level could be as high as fifty percent or more compared to baseline levels, but notes that aging men are not the only ones at risk. A number of genetic causes can impact males from birth and are usually diagnosed with failure to progress normally through puberty during the teenage years.

Treatment options for male hypogonadism include hormone replacement therapy (HRT) via absorbable pellet implants, topical gels, patches, and injections. Through HRT, doctors can restore sexual function and muscle strength. In addition, men often experience an increase in energy and an improved overall sense of well-being.

"Once I began treatment, I felt better very quickly," said Andruzzi. "My energy level shot back up; I regained strength and felt I could concentrate much better."

"We are seeing more men affected by male hypogonadism than we saw ten years ago," said Brannigan. "However, many men continue to suffer in silence due to a lack of awareness surrounding the disorder. Because male hypogonadism can significantly impact the quality of one's life, it's important that men pay attention to their body and openly discuss symptoms with their physician in order to prevent overlooking the cause and avoid missing an opportunity for appropriate therapy."

Although research to determine the exact association continues, doctors also warn that male hypogonadism has been linked to chronic medical conditions such as high cholesterol, diabetes and cardiovascular disease. It's also closely associated with infertility.

"This disorder is not something that should be ignored," said Brannigan, who is working to educate patients and physicians about the symptoms and treatments available in order to ensure therapies are made available to men in need.

Male hypogonadism is most commonly diagnosed through a simple blood test. Brannigan notes hormone replacement therapy is not appropriate for all patients especially those with history of prostate and breast cancer and men trying to conceive. He suggests consulting your doctor if you are experiencing symptoms.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Northwestern Memorial Hospital.

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New Understanding of the 'Flight-or-Fight' Response

New research in the Journal of General Physiology helps explain how the body's "flight-or-fight" response is mediated. The study may provide new answers to the question of how the heart pacemaker -- the sinoatrial (SA) node -- is regulated.

When the body goes into "flight-or-flight" response as a reaction to stress, the increased firing rate of the SA node increases the heart rate and cardiac output to deliver more oxygen and nutrients to peripheral tissues, especially skeletal muscles. There has been much debate recently about whether HCN channels or intracellular calcium oscillations are the main regulators of heart rate.

Now, Catherine Proenza and co-workers (University of Colorado) lend new support to the HCN channels theory. The team shows that HCN channels in SA nodal cells are modulated by protein kinase A (PKA) and suggest that this modulation of HCN channels contributes to the increased firing rate of nodal cells.

According to Peter Larsson (University of Miami) in a Commentary accompanying the paper, the results might reduce some of the confusion in the field, providing a missing piece to the puzzle in explaining how the SA node mediates pacemaking in the heart.

Journal References:

1. Z. Liao, D. Lockhead, E. D. Larson, C. Proenza. Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node. The Journal of General Physiology, 2010; DOI: 10.1085/jgp.201010488
2. H. P. Larsson. How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle. The Journal of General Physiology, 2010; DOI: 10.1085/jgp.201010506

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Widespread Floating Plastic Debris Found in the Western North Atlantic Ocean

Despite growing awareness of the problem of plastic pollution in the world's oceans, little solid scientific information existed to illustrate the nature and scope of the issue. Now, a team of researchers from Sea Education Association (SEA), Woods Hole Oceanographic Institution (WHOI), and the University of Hawaii (UH) published a study of plastic marine debris based on data collected over 22 years by undergraduate students in the latest issue of the journal Science.

A previously undefined expanse of the western North Atlantic has been found to contain high concentrations of plastic debris, comparable to those observed in the region of the Pacific commonly referred to as the "Great Pacific Garbage Patch."

More than 64,000 individual plastic pieces were collected at 6100 locations that were sampled yearly over the course of the study. A surface plankton net was used to collect plastic debris as well as biological organisms at each station. The highest concentrations of plastic were observed in a region centered at 32°N (roughly the latitude of Atlanta, GA) and extending from 22-38°N latitude. Numerical model simulations by Nikolai Maximenko (UH) explain why surface currents cause the plastic to accumulate in this region.

Said SEA scientist Kara Lavender Law, the Science paper's lead author, "Not only does this important data set provide the first rigorous scientific estimate of the extent and amount of floating plastic at an ocean-basin scale, but the data also confirm that basic ocean physics explains why the plastic accumulates in this region so far from shore."

One surprising finding is that the concentration of floating plastic debris has not increased during the 22-year period of the study, despite the fact that the plastic disposal has increased substantially. The whereabouts of the "missing plastic" is unknown.

Says SEA Dean Paul Joyce, "The analysis presented in this Science article provides a robust scientific description of the extent of plastic pollution to date, which can be used to make better management and policy decisions, and to inform popular perceptions of this issue."

A companion study published in Marine Pollution Bulletin details the characteristics of the plastic debris collected in these tows. Most of the plastic is millimeters in size and consists of polyethylene or polypropylene, materials that float in seawater. There is evidence that biological growth may alter the physical characteristics of the plastic over time, perhaps causing it to sink.

"I think some of the big questions are colonization: who actually lives on these pieces of plastic?" said Chris Reddy of WHOI, who was co-author on both papers. "To what extent are ocean currents moving the small life on these plastic particles around the ocean?"

Data continue to be collected onboard SEA's sailing research vessels in both the Atlantic and Pacific Oceans by undergraduate students in the SEA Semester program. A dedicated research cruise, Plastics at SEA: North Atlantic Expedition, recently investigated the eastern boundary of the Atlantic accumulation zone.

"The several thousand SEA Semester undergraduate students who helped collect and count plastic debris over the decades have been essential contributors to this work," said SEA president John Bullard. "They have gained a much fuller understanding of the oceans and the role humans play both in the present and its future."

The work was funded by the National Science Foundation.

Journal Reference:

1. Kara Lavender Law, Skye Moret-Ferguson, Nikolai A. Maximenko, Giora Proskurowski, Emily E. Peacock, Jan Hafner, and Christopher M. Reddy. Plastic Accumulation in the North Atlantic Subtropical Gyre. Science, 2010; DOI: 10.1126/science.1192321

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Scientists Clarify Structural Basis for Biosynthesis of Mysterious 21st Amino Acid

Researchers at the RIKEN Systems and Structural Biology Center and the University of Tokyo have clarified the structural basis for the biosynthesis of selenocysteine (Sec), an amino acid whose encoding mechanism offers clues about the origins of the genetic alphabet. The findings deepen our understanding of protein synthesis and lay the groundwork for advances in protein design.

One of the most remarkable aspects of translation, the process whereby genetic information is converted into proteins in cells, is its universality: nucleotide triplets ("codons") encode a set of twenty amino acids that form the building blocks for all living organisms. Selenocysteine, the "21^st amino acid" whose antioxidant properties help prevent cellular damage, is a rare exception to this rule. Structurally similar to the amino acid serine (Ser) but with an oxygen atom replaced by the micronutrient selenium (Se), selenocysteine is synthesized through a complex juggling of the cell's translational machinery whose mechanisms remain poorly understood.

Central to this multi-step process is a Sec-specific transfer RNA (tRNA^Sec) with an unusual structure that enables it to hijack the "stop codon" UGA to allow incorporation of selenocysteine during protein synthesis. In earlier work, the researchers identified features of tRNA^Sec that differentiate it from other tRNA, notably the peculiar structure of a domain called the D-arm, which appeared to act as an identification marker for recognition by the selenocysteine synthesis machinery. This time, the team analyzed the D-arm's role in the interaction of tRNA^Sec with O-phosphoseryl-tRNA kinase (PSTK), a protein whose selective phosphorylation is essential for selenocysteine encoding.

Using X-ray crystallography, the team showed for the first time that it is the unique structure of the tRNA^Sec D-arm which enables PSTK to distinguish tRNA^Sec from other tRNA. Reported in the August 13 issue of Molecular Cell (online August 12), the discovery clarifies a pivotal step in selenocysteine biosynthesis, shedding new light on the mysterious 21^st amino acid and the elaborate process by which it is created.

Journal Reference:

1. Shiho Chiba, Yuzuru Itoh, Shun-ichi Sekine and Shigeyuki Yokoyama. Structural Basis for the Major Role of O-Phosphoseryl-tRNA Kinase in the UGA-Specific Encoding of Selenocysteine. Molecular Cell, 2010; 39: 1-11 DOI: 10.1016/j.molcel.2010.07.018

Courtesy: ScienceDaily

Single Neurons Can Detect Sequences

Single neurons in the brain are surprisingly good at distinguishing different sequences of incoming information according to new research by UCL neuroscientists.

The study, published August 12 in Science and carried out by researchers based at the Wolfson Institute for Biomedical Research at UCL, shows that single neurons, and indeed even single dendrites, the tiny receiving elements of neurons, can very effectively distinguish between different temporal sequences of incoming information.

This challenges the widely held view that this kind of processing in the brain requires large numbers of neurons working together, as well as demonstrating how the basic components of the brain are exceptionally powerful computing devices in their own right.

First author Tiago Branco said: "In everyday life, we constantly need to use information about sequences of events in order to understand the world around us. For example, language, a collection of different sequences of similar letters or sounds assembled into sentences, is only given meaning by the order in which these sounds or letters are assembled.

"The brain is remarkably good at processing sequences of information from the outside world. For example, modern computers will still struggle to decode a rapidly spoken sequence of words that a 5 year-old child will have no trouble understanding. How the brain does so well at distinguishing one sequence of events from another is not well understood but, until now, the general belief has been that this job is done by large numbers of neurons working in concert with each other."

Using a mouse model, the researchers studied neurons in areas of the brain which are responsible for processing sensory input from the eyes and the face. To probe how these neurons respond to variation in the order of a number of inputs, they used a laser to activate inputs on the dendrites in precisely defined patterns and recorded the resulting electrical responses of the neurons.

Surprisingly, they found that each sequence produced a different response, even when it was delivered to a single dendrite. Furthermore, using theoretical modelling, they were able to show that the likelihood that two sequences can be distinguished from each other is remarkably high.

Senior author Professor Michael Hausser commented: "This research indicates that single neurons are reliable decoders of temporal sequences of inputs, and that they can play a significant role in sorting and interpreting the enormous barrage of inputs received by the brain.

"This new property of neurons and dendrites adds an important new element to the "toolkit" for computation in the brain. This feature is likely to be widespread across many brain areas and indeed many different animal species, including humans."

Funding for this study was provided by the Gatsby Charitable Foundation and the Wellcome Trust.

Journal Reference:

1. Tiago Branco, Beverley A. Clark, and Michael Hausser. Dendritic discrimination of temporal input sequences in cortical neurons. Science, August 12 2010 DOI: 10.1126/science.1189664

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Dangerous Bacterium Hosts Genetic Remnant of Life's Distant Past

Within a dangerous stomach bacterium, Yale University researchers have discovered an ancient but functioning genetic remnant from a time before DNA existed, they report in the August 13 issue of the journal Science.

To the surprise of researchers, this RNA complex seems to play a critical role in the ability of the organism to infect human cells, a job carried out almost exclusively by proteins produced from DNA's instruction manual.

"What these cells are doing is using ancient RNA technology to control modern gene expression," said Ron Breaker, the Henry Ford II Professor of Molecular, Cellular and Developmental Biology at Yale, investigator for the Howard Hughes Medical Institute and senior author of the study.

In old textbooks, RNA was viewed simply as the chemical intermediary between DNA's instruction manual and the creation of proteins. However, Breaker's lab has identified the existence and function of riboswitches, or RNA structures that have the ability to detect molecules and control gene expression -- an ability once believed to be possessed solely by proteins. Breaker and many other scientists now believe the first forms of life depended upon such RNA machines, which would have had to find ways to interact and carry out many of the functions proteins do today.

The new paper describes the complex interactions of two small RNA molecules and two larger RNA molecules that together influence the function of a self-splicing ribozyme, a structure many biologists had believed had no role other than to reproduce itself. The new study, however, suggests that in the pathogenic stomach bacterium Clostridium difficile, this RNA structure acts as a sort of sensor to help regulate the expression of genes, probably to help the bacterium manipulate human cells.

"They were though to be molecular parasites, but it is clear they are being harnessed by cells to do some good for the organism," Breaker said.

This is the sort of RNA structure would have been needed for life exist before the evolution of double-stranded DNA, with its instruction book for proteins that carry out almost all of life's functions today. If proteins are necessary to carry out life's functions, scientists need to explain how life arise without DNA's recipe. The answer to the chicken or egg question is RNA machines such as the one identified in the new study, Breaker said.

"A lot of sophisticated RNA gadgetry has gone extinct but this study shows that RNA has more of the power needed to carry out complex biochemistry," Breaker said. "It makes the spontaneous emergence of life on earth much more palatable."

Journal Reference:

1. Elaine R. Lee, Jenny L. Baker, Zasha Weinberg, Narasimhan Sudarsan, and Ronald R. Breaker. An Allosteric Self-Splicing Ribozyme Triggered by a Bacterial Second Messenger. Science, 13 August 2010: 845-848

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Turning Scar Tissue Into a Beating Heart

Cell biologists often seem like modern-day alchemists. Instead of turning lead or straw into gold, they're looking for ways to turn one kind of cell into another, potentially more useful, cell. Now, one research team has found a way to turn a very common heart cell into a cell missing in injured hearts.

A healthy heart is a mix of several kinds of cells, including cardiomyocytes, the muscle cells that beat, and cardiac fibroblasts, which provide structural support and help keep all the heart cells working together. When a mammalian heart is injured, for example by a heart attack, it forms scar tissue dominated by fibroblasts instead of cardiomyocytes. As a result, the heart doesn't fully recover its pumping capacity. Developmental biologist Deepak Srivastava and cardiovascular researcher Masaki Ieda of the Gladstone Institute of Cardiovascular Disease in San Francisco, California, and their colleagues wondered whether some cellular alchemy could prompt the fibroblasts to turn into cardiomyocytes.

The researchers used a technique called cellular reprogramming, which others had shown can turn one cell type into another. They inserted into mouse cardiac fibroblasts extra copies of more than a dozen genes known to play a role in heart development and watched to see whether any of the cells took on characteristics of cardiomyocytes. After several rounds of tests, the scientists identified a trio of genes that together did the trick. The team inserted extra copies of the three genes into cardiac fibroblasts growing in the lab, and after 2 weeks about 20% of them took on characteristics of cardiomyocytes, expressing typical genes for the muscle cells. After growing for a month, the reprogrammed cells began to contract, like beating heart cells, the researchers report in the 6 August issue of Cell. The reprogrammed cells look and act convincingly like bona fide cardiomyocytes, says Christine Mummery, a developmental biologist not involved with the research who studies cardiac stem cells at Leiden University Medical Center in the Netherlands.

Whether these cells could actually help repair a damaged heart remains an open question, however. Transplants of heart muscle cells created from embryonic stem cells haven't worked as hoped so far—the new cells don't seem to fully integrate into the heart tissue. Ideally, Srivastava says, researchers will find small molecules that can replace the three-gene cocktail. Such molecules could be applied directly to an injured heart and turn fibroblasts into cardiomyocytes. That might lead to more effective repair, he suggests. Mummery agrees. Reprogramming cells directly in the heart "would be potentially much more interesting" than transplantation, she says. The most important question now, she says, is whether the same alchemy will work on human heart cells.

Courtesy: Science.com

How Viruses Jump from Hosts: Secrets of Rabies Transmission in Bats Discovered

HIV-AIDS. SARS. Ebola. Bird Flu. Swine Flu. Rabies. These are emerging infectious diseases where the viruses have jumped from one animal species into another and now infect humans. This is a phenomenon known as cross-species transmission (CST) and scientists are working to determine what drives it.

Gary McCracken, a professor at the University of Tennessee, Knoxville, and department head in Ecology and Evolutionary Biology, is one of those scientists and has made a groundbreaking discovery into how viruses jump from host to host.

His article will appear in the Aug. 6 edition of Science and will be featured on the issue's cover.

It has been a long-held belief that rapid mutation is the main factor that allows viruses to overcome host-specific barriers in cellular, molecular or immunological defenses. Therefore, it has been argued that viruses emerge primarily between species with high contact rates.

McCracken and his colleagues now report that CST may have less to do with virus mutation and contact rates and more to do with host similarity.

"That innate similarity in the defenses of closely related species may favor virus exchange by making it easier for natural selection to favor a virus' ability to infect new hosts," McCracken explained.

McCracken performed his research with former UT Knoxville Ph.D. student Amy Turmelle who now works with the Centers for Disease Control (CDC) and Maarten J. Vonhof, a former post-doctoral scholar at UT Knoxville, who is now with Western Michigan University. Other colleagues include CDC Rabies Team Members Ivan Kuzmin, Charles Rupprecht and Daniel Streicker, who is also with the University of Georgia.

The team made their discovery by analyzing hundreds of rabies viruses in 23 species of bats. In the United States, there are at least 45 different species of bats and many different strains of rabies. Not coincidentally, the CDC collects rabid bats after humans or their pets or livestock may have been exposed to the virus -- adding nearly 2,000 bats annually to its database. McCracken and his colleagues used this database to document the cases in which a rabies virus jumped from one species of bat to another. They verified the cases by genotyping both the viruses and the bats.

The researchers documented over 200 examples of CSTs and analyzed the best explanations for CSTs, such as geographic range, behavior, ecology and genetic relatedness. The study found that the majority of viruses from cross-species infections were tightly nested among genetically similar bat species.

"It turns out, the most important factor in cross-species transmission is how closely related the bat species are," McCracken said. "Our study demonstrates that rapid evolution can be insufficient to overcome phylogenetic barriers at two crucial stages of viral emergence: initial infection and sustained transmission."

This discovery may have significant implications for public health authorities as they try to track where the next infectious disease will emerge. The team's research provides a model for how such diseases transfer from host to host.

"Although CST events are the source of infectious diseases that kill millions of people each year, the natural reservoirs of viruses in wild animals and how they cross species barriers are poorly known and difficult to observe. In this study, rabies in bats serves as a model to understand events that are critical to public health concerns worldwide," McCracken said.

Journal Reference:

1. Daniel G. Streicker, Amy S. Turmelle, Maarten J. Vonhof, Ivan V. Kuzmin, Gary F. McCracken, and Charles E. Rupprecht. Host Phylogeny Constrains Cross-Species Emergence and Establishments of Rabies Virus in Bats. Science, Vol. 329. no. 5992, pp. 676 - 679 DOI: 10.1126/science.1188836

Courtesy: ScienceDaily

Artificial Bee Eye Gives Insight Into Insects’ Visual World

Despite their tiny brains, bees have remarkable navigation capabilities based on their vision. Now scientists have recreated a light-weight imaging system mimicking a honeybee's field of view, which could change the way we build mobile robots and small flying vehicles.

New research published Aug. 6 in IOP Publishing's Bioinspiration & Biomimetics, describes how the researchers from the Center of Excellence 'Cognitive Interaction Technology' at Bielefeld University, Germany, have built an artificial bee eye, complete with fully functional camera, to shed light on the insects' complex sensing, processing and navigational skills.

Consisting of a light-weight mirror-lens combination attached to a USB video camera, the artificial eye manages to achieve a field of vision comparable to that of a bee. In combining a curved reflective surface that is built into acrylic glass with lenses covering the frontal field, the bee eye camera has allowed the researchers to take unique images showing the world from an insect's viewpoint.

In the future, the researchers hope to include UV to fully reflect a bee's colour vision, which is important to honeybees for flower recognition and discrimination and also polarisation vision, which bees use for orientation. They also hope to incorporate models of the subsequent neural processing stages.

As the researchers write, "Despite the discussed limitations of our model of the spatial resolution of the honeybees compound eyes, we are confident that it is useful for many purposes, e.g. for the simulation of bee-like agents in virtual environments and, in combination with presented imaging system, for testing bee-inspired visual navigation strategies on mobile robots."

Journal Reference:

1. W Stürzl et al. Mimicking Honeybee Eyes with a 280◦ FOV Catadioptric Imaging System. Bioinspiration & Biomimetics, 2010; [link]

Courtesy: ScienceDaily

Next Generation Sequencing Establishes Genetic Link Between Two Rare Diseases

Scientists have successfully used "next generation sequencing" to identify mutations that may cause a rare and mysterious genetic disorder. The research, published on July 29th in the American Journal of Human Genetics, demonstrates that sequencing an affected individual's entire "exome"; that is, all of the genes that carry instructions for producing proteins, can reveal critical genes that when mutant, cause inherited disorders.

Perrault syndrome is a recessive disorder that is associated with hearing loss in both boys and girls, and failure of ovarian function in girls. Some individuals with Perrault syndrome also have neurological symptoms. Prior to the current study, no genes for Perrault syndrome had been identified.

A research group led by Mary-Claire King, PhD, from the University of Washington in Seattle studied the genetics of Perrault syndrome in a small family, originally of Irish and Italian ancestry, that included two sisters with well-characterized Perrault syndrome.

"Because the family is small and not consanguineous (both parents descended from a common ancestor), standard genetic mapping techniques would not have been informative in identifying the responsible gene," explains Dr. King. "Instead, we attempted to identify the gene responsible for Perrault syndrome in this family through the use of whole exome sequencing." The exome can be thought of as a kind of genetic blueprint for the synthesis of proteins.

After sequencing the entire exome of one of the sisters, the researchers identified a single gene (HSD17B4) that exhibited two rare functional variants. This gene encodes D-bifunctional protein (DBP), a multifunctional enzyme involved in lipid metabolism. Underscoring the genetic diversity of the disease, the researchers went on to show that six other families with Perrault syndrome had normal HSD17B4.

"Other mutations in HSD17B4 are known to cause a very severe congenital syndrome called DBP deficiency that is generally fatal within the first two years of life," says Dr. King. "No girls with DBP deficiency have been reported to survive past puberty, so ovarian abnormalities have not previously been known to be associated with this illness. The few reported long term survivors of DBP deficiency exhibit hearing loss and neurological dysfunction."

Taken together, the findings indicate that Perrault syndrome and DBP deficiency share some clinical symptoms and that very mild cases of DBP deficiency may be under-diagnosed. "Our research also demonstrates that whole exome sequencing can reveal critical genes in small nonconsanguinous families," concludes Dr. King.

The researchers include Sarah B. Pierce, University of Washington, Seattle, WA; Tom Walsh, University of Washington, Seattle, WA; Karen M. Chisholm, University of Washington, Seattle, WA; Ming K. Lee, University of Washington, Seattle, WA; Anne M. Thornton, University of Washington, Seattle, WA; Agata Fiumara, University of Catania, Catania, Italy; John M. Opitz, University of Utah School of Medicine, Salt Lake City, UT; Ephrat Levy-Lahad, Shaare Zedek Medical Center, Jerusalem, Israel, Hebrew University Medical School, Jerusalem, Israel; Rachel E. Klevit, University of Washington, Seattle WA; and Mary-Claire King, University of Washington, Seattle, WA.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Cell Press, via EurekAlert!, a service of AAAS.

Courtesy: ScienceDaily

Mechanism Uncovered Behind Salmonella Virulence and Drug Susceptibility

Researchers have discovered a novel mechanism in Salmonella that affects its virulence and its susceptibility to antibiotics by changing its production of proteins in a previously unheard of manner. This allows Salmonella to selectively change its levels of certain proteins to respond to inhospitable conditions.

Although the mechanism had not been recognized before, the scientists were intrigued to find evidence of a similar mechanism in all five kingdoms of life -- animals, plants, fungi, protista, and monera.

The findings were published July 29 in Molecular Cell. The senior author of the study is Dr. Ferric C. Fang, professor of microbiology, laboratory medicine, and medicine at the University of Washington (UW). Fang also directs the Clinical Microbiology Laboratory at Harborview Medical Center in Seattle. The lead author is William Wiley Navarre, who began the study as a postdoctoral fellow in the Fang lab and is now an assistant professor at the University of Toronto.

Salmonella enters the gut when people eat contaminated food, and can sometimes spread to other parts of the body. Illness outbreaks and grocery recalls related to Salmonella are often in the news. Babies, young children, the elderly, and people with cancer or HIV are especially prone to severe illness from Salmonella.

Salmonella is adaptable and can withstand many of the body's attempts to fight it. The bacteria live and multiply in a special compartment inside the cells of an infected person or animal. Salmonella can alter its physiology as it moves from a free-swimming life to its residence in a host cell. Salmonella's metabolism also changes over time to make use of the nutrients available in the host cell, and to survive damage from the build-up of oxidants and nitric oxide in the infected cell.

While screening mutant Salmonella that were resistant to a form of nitric oxide that normally stops the bacteria from dividing, Navarre, Fang and their research collaborators found mutations in two little-known genes. These are the closely linked poxA and yjeK genes. In a number of bacteria, these two genes are associated with a third gene that encodes the Bacterial Elongation Factor P, which is involved in protein production.

The researchers discovered that these three genes operate in a common pathway that is critical for the ability of the Salmonella bacteria to cause disease and resist several classes of antibiotics. Salmonella with mutations in either the poxA gene or the yjeK genes, the study noted, appear to be nearly identical and show similar changes in proteins involved in metabolism. Strains with mutations in both genes resemble the single mutant strains, an observation that suggests the two genes work in the same pathway.

The mutant strains exhibited many abnormalities under stressful conditions.

"The wide spectrum of compounds that dramatically inhibited the growth of these mutant strains suggest that the defect lies in a general stress response," the researchers noted. The mutant bacteria measurably differed from the wild-type Salmonella under 300 different conditions. In addition, their aberrant production of virulence factors reduces their ability to survive in the host.

The researchers' analysis also suggests that the way poxA and yjeK modify the bacterial protein elongation factor is essential in the production of proteins that allow the bacteria to use alternative energy sources when they are deprived of nutrients, as occurs after they enter host cells.

Unexpectedly the researchers found that the Salmonella with mutations in poxA and yjeK continued to respire inappropriately under nutrient-poor conditions in which wild-type Salmonella cease respiration.

Perhaps the mutant strains don't know when to quit. Wild-type Salmonella might enter a state of suspended animation to weather harsh conditions, whereas the mutants fail to respond properly to environmental stress. The fact that the mutants continue to respire when they are in dire straits might lead to the production of toxic oxygen-containing compounds.

"This might explain," the authors suggested, "why the mutants are broadly sensitive to a large number of unrelated compounds and cellular stresses."

The researchers also noticed a resemblance between the astounding manner in which the poxA gene modifies the bacterial elongation factor to regulate stress resistance, and the way a similarly acting factor is regulated in plant and animal cells.

During the manufacture of a protein, transfer RNA, also called tRNA, normally places an amino acid at the end of a growing chain of protein building blocks. A certain type of enzyme normally hands the tRNA the amino acid for it to place. However, in this study, researchers have shown for the first time that the poxA enzyme steps in and directly attaches an amino acid to the Elongation Factor P protein, rather than to the tRNA.

Fang said, "Sometimes it seems as if the most basic discoveries in biology have already been made. It was fun and unexpected to learn something new about a process as fundamental as protein synthesis."

"This is an interesting illustration of molecular evolution," Fang continued. "This essential, but previously unrecognized mechanism, for regulating the production of proteins appears to have been conserved over evolutionary time and continues to take place in cells belonging to all five kingdoms of life."

Future studies in his lab will address the specific reasons behind the defective stress response in poxA- and yjeK-deficient bacteria and the explanation for its different effects on the amounts of individual proteins. The lab will also look further into the roles of the normal poxA and yjeK proteins, the intriguing way in which the bacterial elongation protein is modified, the apparent universality of this protein-modifying mechanism in living cells and its conservation throughout the course of evolution.

This research was supported by grants from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Navarre also received support from the Damon-Runyon Cancer Foundation and the Canadian Institutes of Health Research.

In addition to Navarre and Fang, the scientists on the study are Shicong Zou, Jinglin Lucy Xie, and Runjan Kumar, all from the Department of Molecular Genetics at the University of Toronto; Herve Roy and Michael Ibba from the Department of Microbiology at The Ohio State University; Alexei Savchenko, Alexander Singer, and Elena Edvokimova from the Banting and Best Institute for Medical Research in Toronto; and Lynne R. Prost from the UW Department of Microbiology.

Journal Reference:

1. William Wiley Navarre, S. Betty Zou, Hervé Roy, Jinglin Lucy Xie, Alexei Savchenko, Alexander Singer, Elena Edvokimova, Lynne R. Prost, Runjun Kumar, Michael Ibba, Ferric C. Fang. PoxA, YjeK, and Elongation Factor P Coordinately Modulate Virulence and Drug Resistance in Salmonella enterica. Molecular Cell, 2010; DOI: 10.1016/j.molcel.2010.06.021

Courtesy: ScienceDaily

Male Modesty Not Appreciated by Female or Male Interviewers, Study Suggests

Macho, macho man. I’ve got to be, a macho man. Macho, macho man. I’ve got to be a macho! — The Village People

It's more than 30 years since that Disco Era anthem first blared though dance club speakers and into America's consciousness, but does the message still sing true for the 2lst century male? Does he still got to be a macho man? Are there penalties for not being macho enough?

Corinne A. Moss-Racusin, a doctoral candidate in Rutgers' Department of Psychology, explored the consequences for men (and women) when they acted modestly in job interviews. She co-authored, with graduate fellow Julie E. Phelan and Professor Laurie A. Rudman, "When Men Break the Gender Rules: Status Incongruity and Backlash Against Modest Men" in the journal Psychology of Men and Masculinity.

According to Moss-Racusin, the applicants in the staged interviews were judged equally competent, but the "modest" males were less liked, a sign of social backlash. Modesty was viewed as a sign of weakness, a low-status character trait for males that could adversely affect their employability or earnings potential. Modesty in women, however, was not viewed negatively nor was it linked to status.

"For men and women, there are things they must and must not be," Moss-Racusin says. "Women must be communal and other-oriented, but they must not be dominant. Historically and cross-culturally, men have been stereotyped as more agentic, that is, more independent and self-focused than women."

In the study, 132 female and 100 male student volunteers (who earned partial academic credit for their psychology course) viewed videotaped, 15-minute job interviews of either males or females. All the applicants were paid actors rehearsed to deliver similar, "modest" responses for the gender-neutral position that required strong technical abilities and social skills.

The researchers sought to determine which gender stereotype promote backlash. "Women are allowed to be weak while this trait is strongly prohibited in men," Moss-Racusin said. "By contrast, dominance is reserved for men and prohibited for women. Thus, gender stereotypes are comprised of four sets of rules and expectations for behavior consist of both 'shoulds' and 'should nots' for each gender."

The researchers' prediction that modest male applicants would face hiring discrimination was not supported, however, and she speculates that because men's status is higher than women's, meek men are afforded the benefit of the doubt and are less likely to encounter hiring discrimination than dominant women.

Journal Reference:

1. Moss-Racusin et al. When men break the gender rules: Status incongruity and backlash against modest men.. Psychology of Men & Masculinity, 2010; 11 (2): 140 DOI: 10.1037/a0018093

Courtesy: ScienceDaily