January-October 2014 temperatures highest on record

The global average temperature over land and ocean surfaces for January to October 2014 was the highest on record, according to NOAA. October was the hottest since records began in 1880.

The global average temperature over land and ocean surfaces for January to October 2014 was the highest on record, according to the U.S. National Oceanic and Atmospheric Administration (NOAA). It said October was the hottest since records began in 1880.

NOAA said the combined global land and ocean average surface temperature for the January-October period was 0.68°C (1.22°F) above the 20th century average of 14.1°C (57.4°F). For October, it was 0.74°C (1.33°F) above the 20th century average of 14.0°C (57.1°F).

The high October temperature was driven by warmth across the globe over both the land and ocean surfaces and was fairly evenly distributed between the Northern and Southern Hemispheres. The Southern Hemisphere had its hottest October on record and the Northern Hemisphere its third warmest.

October marked the third consecutive month and fifth of the past six with a record high global temperature for its respective month (July was fourth highest).

The Tokyo Climate Center, which is a WMO Regional Climate Centre, also reported that October was the hottest on record. The record was also confirmed by data from NASA's Goddard Institute for Space Studies.

WMO uses a combination of datasets to compile its annual Statement on the Status of the Global Climate. Additional information is drawn from the ERA-Interim reanalysis-based data set maintained by the European Centre for Medium-Range Weather Forecasts.

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Gut microbiota influences blood-brain barrier permeability

A new study in mice, conducted by researchers at Sweden's Karolinska Institutet together with colleagues in Singapore and the United States, shows that our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood. According to the authors, the findings provide experimental evidence that our indigenous microbes contribute to the mechanism that closes the blood-brain barrier before birth. The results also support previous observations that gut microbiota can impact brain development and function.

The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream. In the current study, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by gut microbes -- which therefore play an important role in the protection of the brain.

The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.

"We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus," says first author Dr. Viorica Braniste at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. "In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma."

The team also showed that the increased 'leakiness' of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this 'leakiness' could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. The precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria.

According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life.

"These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology," says Professor Sven Pettersson, the principal investigator at the Department of Microbiology, Tumor and Cell Biology. "Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome. This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier."

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Another human footprint in the ocean: Rising anthropogenic nitrate levels in North Pacific Ocean

Human-induced changes to Earth's carbon cycle -- for example, rising atmospheric carbon dioxide and ocean acidification -- have been observed for decades. However, a study published this week in Science showed human activities, in particular industrial and agricultural processes, have also had significant impacts on the upper ocean nitrogen cycle.

The rate of deposition of reactive nitrogen (i.e., nitrogen oxides from fossil fuel burning and ammonia compounds from fertilizer use) from the atmosphere to the open ocean has more than doubled globally over the last 100 years. This anthropogenic addition of nitrogen has reached a magnitude comparable to about half of global ocean nitrogen fixation (the natural process by which atmospheric nitrogen gas becomes a useful nutrient for organisms). David Karl, Professor of Oceanography and Director of the Daniel K. Inouye Center for Microbial Oceanography at the University of Hawai'i, teamed up with researchers from Korea, Switzerland and the U.S. National Oceanic and Atmospheric Administration to assess changes in nitrate concentration between the 1960s and 2000s across the open North Pacific Ocean.

Their analysis, which could discern human-derived nitrogen from natural nitrogen fixation, revealed that the oceanic nitrate concentration increased significantly over the last 30 years in surface waters of the North Pacific due largely to the enhanced deposition of nitrogen from the atmosphere.

"This is a sobering result, one that I would not have predicted," said Karl. "The North Pacific is so vast it is hard to imagine that humans could impact the natural nitrogen cycle."

The researchers used ocean data in conjunction with the state-of-the-art Earth System Model to reconstruct the history of the oceanic nitrate concentration and make predictions about the future state of the North Pacific Ocean. Their assessment revealed a consistent picture of increasing nitrate concentrations, the magnitude and pattern of which can only be explained by the observed increase in atmospheric nitrogen deposition.

Enhanced nitrogen deposition has several potential ecological ramifications. Because biological activity is limited by nitrate availability in the North Pacific Ocean, the input of new nitrogen from the atmosphere may increase photosysnthesis in the sunlit layers and export of carbon-rich organic material out of the surface ocean into the deep.

"The burgeoning human population needs energy and food -- unfortunately, nitrogen pollution is an unintended consequence and not even the open ocean is immune from our daily industrial activities," said Karl.

Given the likelihood that the magnitude of atmospheric nitrogen deposition will continue to increase in the future, the North Pacific Ocean could rapidly switch to having surplus nitrate. Thus, past and future increases in atmospheric nitrogen deposition have the potential to alter the base of the marine food web; and, in the long term, the structure of the ecosystem.

In particular, the shift in nutrient availability could favor marine organisms that thrive under the high nitrate and low phosphorus conditions. If similar trends are confirmed in the Atlantic and Indian Oceans, it would constitute another example of a global-scale alteration of Earth system. Further, the findings of this study of the North Pacific highlight the need for greater controls on the emission of nitrogen compounds during combustion and agricultural processes.

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'Eye of Sauron' provides new way of measuring distances to galaxies

This image shows the spiral galaxy NGC 4151.

A team of scientists, led by Dr Sebastian Hoenig from the University of Southampton, have developed a new way of measuring precise distances to galaxies tens of millions of light years away, using the W. M. Keck Observatory near the summit of Mauna Kea in Hawaii.

The method is similar to what land surveyors use on Earth, by measuring the physical and angular, or 'apparent', size of a standard ruler in the galaxy, to calibrate the distance from this information.

The research, which is published in the journal Nature, was used to identify the accurate distance of the nearby NGC4151 galaxy, which wasn't previously available. The galaxy NGC 4151, which is dubbed the 'Eye of Sauron' by astronomers for its similarity to the film depiction of the eye of the character in The Lord of the Rings, is important for accurately measuring black hole masses.

Recently reported distances range from 4 to 29 megaparsecs, but using this new method the researchers calculated the distance of 19 megaparsecs to the supermassive black hole.

Indeed, as in the famous saga, a ring plays a crucial role in this new measurement. All big galaxies in the universe host a supermassive black hole in their centre and in about a tenth of all galaxies, these supermassive black holes are growing by swallowing huge amounts of gas and dust from their surrounding environments. In this process, the material heats up and becomes very bright -- becoming the most energetic sources of emission in the universe known as active galactic nuclei (AGN).

The hot dust forms a ring around the supermassive black hole and emits infrared radiation, which the researchers used as the ruler. However, the apparent size of this ring is so small that the observations were carried out using infrared interferometry to combine W. M. Keck Observatory's twin 10-meter telescopes, to achieve the resolution power of an 85m telescope.

To measure the physical size of the dusty ring, the researchers measured the time delay between the emission of light from very close to the black hole and the infrared emission. This delay is the distance the light has to travel (at the speed-of-light) from close to the black hole out to the hot dust.

By combining this physical size of the dust ring with the apparent size measured with the data from the Keck interferometer, the researchers were able to determine a distance to the galaxy NGC 4151.

Dr Hoenig says: "One of the key findings is that the distance determined in this new fashion is quite precise -- with only about 10 per cent uncertainty. In fact, if the current result for NGC 4151 holds for other objects, it can potentially beat any other current methods to reach the same precision to determine distances for remote galaxies directly based on simple geometrical principles. Moreover, it can be readily used on many more sources than the current most precise method."

"Such distances are key in pinning down the cosmological parameters that characterise our universe or for accurately measuring black hole masses. Indeed, NGC 4151 is a crucial anchor to calibrate various techniques to estimate black hole masses. Our new distance implies that these masses may have been systematically underestimated by 40 per cent."

Dr Hoenig, together with colleagues in Denmark and Japan, is currently setting up a new program to extend their work to many more AGN. The goal is to establish precise distances to a dozen galaxies in this new way and use them to constrain cosmological parameters to within a few per cent. In combination with other measurements, this will provide a better understanding of the history of expansion of our universe.

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Most American presidents destined to fade from nation's memory, study suggests

American presidents spend their time in office trying to carve out a prominent place in the nation's collective memory, but most are destined to be forgotten within 50-to-100 years of their serving as president, suggests a study on presidential name recall released today by the journal Science. "By the year 2060, Americans will probably remember as much about the 39th and 40th presidents, Jimmy Carter and Ronald Reagan, as they now remember about our 13th president, Millard Fillmore," predicts study co-author Henry L. Roediger III, PhD, a human memory expert at Washington University in St. Louis.

Roediger, the James S. McDonnell Distinguished University Professor in Arts & Sciences, has been testing the ability of undergraduate college students to remember the names of presidents since 1973, when he first administered the test to undergraduates while a psychology graduate student at Yale University.

His current study, co-authored with Washington University graduate student K. Andrew DeSoto, compares results from the presidential-recall tests Roediger has given to three generations of undergraduate college students (1974, 1991 and 2009) and a similar test offered online to 577 adults ages 18-69 in 2014.

While Roediger's early research used the presidential-recall test to study patterns of remembering and forgetting in individual test takers, the new study was able to uncover how Americans forget presidents from our historical or popular memory over time.

In each test, participants were provided a numbered list with blank spaces and asked to fill in the names of all presidents they could remember in the order in which they served. If they could remember names but not the order, they were instructed to guess or to put the names off to the side. Thus, the results could be scored for recall of presidents with or without regard to correct order.

Findings showed several consistent patterns in how we have forgotten past presidents and offer a formula to predict the rate at which current presidents are likely to be forgotten by future generations.

Among the six presidents who were serving or had served most recently when the test was first given in 1973, Harry S. Truman, Lyndon B. Johnson and Gerald R. Ford are now fading fast from historical memory, whereas John F. Kennedy has been better retained. The study estimates that Truman will be forgotten by three-fourths of college students by 2040, 87 years after his leaving office, bringing him down to the level of presidents such as Zachary Taylor and William McKinley.

The current data do not permit assessment of forgetting rates of the most recent presidents, and do not specify why some relatively recent presidents are forgotten more rapidly than others, Roediger said.

"Kennedy was president less than three years, but is today remembered much better than Lyndon Johnson," Roediger said. "One idea is that his assassination made him memorable, but of course that does not apply to James Garfield or William McKinley, who were also assassinated and are remembered relatively poorly.

"Kennedy may be well recalled because his brothers and other family members were (and are) active in politics and help to keep his memory alive," Roediger speculated.

HIllary Clinton, if elected in 2016, has the potential to be much better remembered than her husband, because her presidency would represent a unique first in American history. Barack Obama may be well remembered for the same reason, Roediger said.

The rate at which college students forgot the order of recent presidents remained remarkably consistent over time and across different groups of college students. In 1974, nearly all college students recalled Johnson and his ordinal position (36), but by 1991, the proportion remembering him dropped to 53 percent and by 2009, it plummeted to 20 percent.

When asked to name the presidents in the order they served, we as a nation do fairly well at naming the last few presidents, but our recall abilities then fall off quickly, with less than 20 percent able to remember more than the last eight or nine presidents in order, the study finds.

While Americans who were tested could name the nation's first president (George Washington) and do reasonably well at naming the next three or four presidents in order, the recall success rate for early presidents also drops off sharply, with fewer than 25 percent of Americans able to recall more than the first five presidents in order.

"Out of the 150 college students we tested in 2009, only four of them were able to recall virtually every president and place each in the correct position," DeSoto said. "It's possible that these individuals used a mnemonic like a song or rhyme that they learned for the purpose of remembering the presidents."

With a few interesting exceptions, the vast majority of presidents in the middle of pack -- from No. 8, Martin Van Buren, to No. 30, Calvin Coolidge -- already are largely forgotten by the average American, the study finds.

The probability that anyone who took the test could recall both the name and the order of most presidents in this middle range is quite low, and this level of poor recall for the middle presidents has generally held true in testing across all generations for nearly four decades.

A notable exception in this middle wasteland of presidential recall is Abraham Lincoln and his two immediate successors, Andrew Johnson and Ulysses S. Grant.

"Clearly, Lincoln and his successors are well remembered because of their association with the American Civil War and the ending of slavery, but it is notable that many students and adults also often know that Lincoln was the 16th president," Roediger said.

Other pre-Coolidge presidents who were remembered reasonably well in the free recall portion of the test are Theodore Roosevelt (26), William Howard Taft (27) and Woodrow Wilson (28), a showing that could be related to their favorable rankings by historians and ongoing mentions in popular culture and news media, the researchers suggest.

Roediger's prediction about the memorability of Reagan and other recent presidents hinges on two core principles of human memory that are confirmed by this study and related research.

First, when presented with information in a long list, we tend to best remember items that are presented at the beginning and end of the list. Second, items presented in the middle of a long list are better remembered when they are somehow distinctive and different from other items in the list.

America's memory for Johnson and Reagan, like that for most presidents, is destined to fade along a quick and predictable trajectory as new elections inexorably push them and their memories further down the list of the most recent and currently best-remembered presidents, the study suggests.

While most collective memory research conducted thus far has explored how we as a nation remember historic events, such as the Holocaust or the 9/11 terror attacks, this study is among the first to focus on how we forget salient events of the past over generations and to obtain estimates of rate of forgetting over time.

"Our results show that memories of famous historical people and events can be studied objectively," Roediger said. "The great stability in how these presidents are remembered across generations suggests that we as a nation share a seemingly permanent form of collective memory."

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Notre Dame biologist leads sequencing of the genomes of malaria-carrying mosquitoes

Nora Besansky, O'Hara Professor of Biological Sciences at the University of Notre Dame and a member of the University's Eck Institute for Global Health, has led an international team of scientists in sequencing the genomes of 16 Anopheles mosquito species from around the world. Anopheles mosquitoes are responsible for transmitting human malaria parasites that cause an estimated 200 million cases and more than 600 thousand deaths each year. However, of the almost 500 different Anopheles species, only a few dozen can carry the parasite and only a handful of species are responsible for the vast majority of transmissions. Besansky and her fellow researchers investigated the genetic differences between the deadly parasite-transmitting species and their harmless (but still annoying) cousins.

Two papers published in today's (Nov. 27) editions of Science Express, an electronic publication of the journal Science in advance of print, describe detailed genomic comparisons of these mosquitoes and the deadliest of them all, Anopheles gambiae. These results offer new insights into how these species are related to each other and how the dynamic evolution of their genomes may contribute to their flexibility to adapt to new environments and to seek out human blood. These newly sequenced genomes represent a substantial contribution to the scientific resources that will advance our understanding of the diverse biological characteristics of mosquitoes, and help to eliminate diseases that have a major impact on global public health.

Malaria parasites are transmitted to humans by only a few dozen of the many hundreds of species of Anopheles mosquitoes, and of these, only a handful are highly efficient disease-vectors. Thus, although about half the world's human population is at risk of malaria, most fatalities occur in sub-Saharan Africa, home of the major vector species, Anopheles gambiae. Variation in the ability of different Anopheles species to transmit malaria -- known as "vectorial capacity" -- are determined by many factors, including feeding and breeding preferences, as well as their immune responses to infections. Much of our understanding of many such processes derives from the sequencing of the Anopheles gambiae genome in 2002, which was led by Notre Dame researchers and which has since facilitated many large-scale functional studies that have offered numerous insights into how this mosquito became highly specialized in order to live amongst and feed upon humans.

Until now, the lack of such genomic resources for other Anopheles limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquito's ability to transmit parasites. To address these questions, researchers sequenced the genomes of 16 Anopheles species.

"We selected species from Africa, Asia, Europe, and Latin America that represent a range of evolutionary distances from Anopheles gambiae, a variety of ecological conditions, and varying degrees of vectorial capacity," Besansky said.

DNA sequencing and assembly efforts at the Broad Institute were funded by NHGRI and led by Daniel Neafsey, with samples obtained from mosquito colonies maintained through BEI Resources at the United States Centres for Disease Control and Prevention, and wild-caught or laboratory-reared mosquitoes from scientists in Africa, India, Iran, Melanesia and Southeast Asia.

"Getting enough high-quality DNA samples for all species was a challenging process and we had to design and apply novel strategies to overcome the difficulties associated with high levels of DNA sequence variations, especially from the wild-caught sample," Neafsey said.

With genome sequencing complete, scientists from around the world contributed their expertise to examine genes involved in different aspects of mosquito biology including reproductive processes, immune responses, insecticide resistance, and chemosensory mechanisms. These detailed studies involving so many species were facilitated by large-scale computational evolutionary genomic analyses led by Robert Waterhouse from the University of Geneva Medical School and the Swiss Institute of Bioinformatics.

The researchers carried out interspecies gene comparisons with the Anopheles and other insects, to identify equivalent genes in each species and highlight potentially important differences.

"We used similarities to genes from Anopheles gambiae and other well-studied organisms such as the fruit fly to learn about the possible functions of the thousands of new genes found in each of the Anopheles genomes," Waterhouse said.

Examining gene evolution across the Anopheles revealed high rates of gene gain and loss, about five times higher than in fruit flies. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely-related species.

"These dynamic changes," Neafsey said, "may offer clues to understanding the diversification of Anopheles mosquitoes; why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans."

The newly available genome sequences also provided conclusive evidence of the true relations amongst several species that are very closely related to Anopheles gambiae but nevertheless show quite different traits that affect their vectorial capacity.

"The question of the true species phylogeny has been a highly contentious issue in the field," Besansky said. "Our results show that the most efficient vectors are not necessarily the most closely-related species, and that traits enhancing vectorial capacity may be gained by gene flow between species."

This study substantially improves our understanding of the process of gene flow between closely related species -- a process believed to have occurred from Neanderthals to the ancestors of modern humans -- and how it may affect the evolution of common and distinct biological characteristics of mosquitoes such as ecological flexibility and vectorial capacity.

These two very different evolutionary timescales -- spanning all the Anopheles or focusing on the subset of very closely-related species -- offer distinct insights into the processes that have moulded these mosquito genomes into their present-day forms. Their dynamic evolutionary profiles may represent the genomic signatures of an inherent evolvability that has allowed Anopheles mosquitoes to quickly exploit new human-generated habitats and become the greatest scourge of humankind.

Besansky's research focuses primarily on African vectors of human malaria: the anopheline mosquitoes known as Anopheles gambiae and Anopheles funestus.

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Mindfulness treatment as effective as CBT for depression, anxiety

Group mindfulness treatment is as effective as individual cognitive behavioral therapy (CBT) in patients with depression and anxiety, according to a new study from Lund University in Sweden and Region Skåne. This is the first randomized study to compare group mindfulness treatment and individual cognitive behavioral therapy in patients with depression and anxiety in primary health care.

The researchers, led by Professor Jan Sundquist, ran the study at 16 primary health care centres in Skåne, a county in southern Sweden. They trained two mindfulness instructors, from different occupational groups, at each primary health care centre during a 6-day training course.

In spring 2012, patients with depression, anxiety or reactions to severe stress were randomized to either structured group mindfulness treatment with approximately 10 patients per group, or regular treatment (mainly individual CBT). Patients also received a private training programme and were asked to record their exercises in a diary. The treatment lasted 8 weeks. General practitioner and mindfulness instructor Ola Schenström designed the mindfulness training programme and model for training instructors.

A total of 215 patients were included in the study. Before and after treatment, the patients in the mindfulness and regular treatment groups answered questionnaires that estimated the severity of their depression and anxiety. Self-reported symptoms of depression and anxiety decreased in both groups during the 8-week treatment period. There was no statistical difference between the two treatments.

"The study's results indicate that group mindfulness treatment, conducted by certified instructors in primary health care, is as effective a treatment method as individual CBT for treating depression and anxiety," says Jan Sundquist. "This means that group mindfulness treatment should be considered as an alternative to individual psychotherapy, especially at primary health care centres that can't offer everyone individual therapy."

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Protein elevated in blood predicts post-concussion symptom severity in professional athletes

New Penn Medicine research has found that elevated levels in the blood of the brain-enriched protein calpain-cleaved αII-spectrin N-terminal fragment, known as SNTF, shortly after sports-related concussion can predict the severity of post-concussion symptoms in professional athletes. The complete findings were released today in the Journal of Neurotrauma.

This new study builds on previous research from this group showing that elevated blood levels of SNTF on the day of a mild traumatic brain injury treated in the emergency room predicted those patients who would go on to suffer diffuse axonal injury and long-term cognitive dysfunction.

"We extended this biomarker research to the domain of professional sports to test its merit as an objective and rapid way to determine players' severity of brain injury," says lead author, Robert Siman, PhD, Research Professor of Neurosurgery at Penn. "This blood test may aid neurobiologically-informed decisions on suitability for return to play following a sports-related concussion."

The study, conducted in collaboration with Henrik Zetterberg, MD, PhD and Kai Blennow, MD, PhD, of the Sahgrenska Academy at University of Gothenburg, Sweden, and their colleagues, enrolled 288 players in the top Swedish professional ice hockey league. Each of the 28 players who suffered a concussion during the first half of the 2012-2013 season received serial blood draws and was evaluated daily for symptom resolution using the latest guidelines for treatment of sports concussions. Eight of the concussed players were symptom-free within a few days of their injury, but 20 of the players had persistent post-concussion symptoms requiring they be withheld from play six days or longer. An additional 45 players were evaluated during the preseason, 17 of whom were also tested before and after a concussion-free training game.

Compared to those players who were not concussed, or whose concussion symptoms resolved rapidly, the researchers found an increase in the blood SNTF concentration from one hour up to 144 hours post-concussion in those players experiencing persisting post-concussion symptoms. SNTF is a protein that is present at undetectable levels in healthy human brains, but is produced under conditions where nerve cells are traumatized and begin to die. Concussions that lead to lasting brain dysfunction cause SNTF to accumulate in vulnerable long axon tracts of the brain, and its blood elevation is a measure of this diffuse axonal injury.

"These results show that SNTF has promise as a blood biomarker for sports-related concussion and beyond. High blood levels of SNTF appear to identify acute brain damage that corresponds with persisting symptoms after concussion. These observations lend further support to the growing awareness that concussion is not trivial, since it can induce permanent brain damage in some individuals," agree Siman and senior author, Douglas H. Smith, MD, professor of Neurosurgery and director of the Center for Brain Injury and Repair at Penn.

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New substance overcomes treatment-restistance in leukemia

Haematologists from Goethe University Frankfurt, working with a Russian pharmaceutical company, have developed a new active substance that effectively combats the most aggressive forms of Philadelphia chromosome-positive leukemia.

The chances of patients with Philadelphia chromosome-positive leukemia (Ph+) being cured has greatly increased in recent years. Nevertheless, a high percentage of patients have developed resistance to available medication. But now, haematologists from Goethe University Frankfurt, working with a Russian pharmaceutical company, have developed a new active substance that effectively combats the most aggressive forms of Philadelphia chromosome-positive leukemia, both in vitro and in vivo. They have reported this in the current edition of the specialist journal 'Leukemia'.

Patients with the Philadelphia chromosome develop chronic myelogenous leukemia (CML) or acute lymphatic leukemia (Ph+ ALL). These are the first types of leukemia that are able to be treated due to the development of targeted molecular therapy. Selective kinase inhibitor active substances act directly on the cancer-inducing gene BCR/ABL. However, after a while, the treatment becomes ineffective for many patients -- either due to BCR/ABL mutations or due to other mechanisms that are as yet unknown. At present, there is only one substance, Ponatinib, which is able to overcome nearly all clinical resistance. Unfortunately, Ponatinib can only be used with extreme caution due to some of its life-threatening side-effects.
Moscow-based company Fusion Pharma has developed an innovative kinase inhibitor, PF-114 with the aim of having the same effect on Ph+ leukemia as Ponatinib, but with reduced side-effects. In the current edition of 'Leukemia', the team led by Dr. Afsar Mian, Professor. Oliver Ottoman and lecturer Dr. Martin Ruthardt from the Haematology Department of Medical Clinic II, have reported that PF-114 is as effective as Ponatinib against resistant Ph+ leukemia.

"These results provide the basis for the administration of PF-114 in treatment-resistant patients with Ph+ leukemia. The favourable efficacy and good side effect profile now need to be further tested on patients in clinical phase I studies," explained Dr. Ruthardt. "PF-114 would not have reached this level of development without our colleagues in Frankfurt. On the basis of this data, in the first half of 2015, we will be able to start international phase I studies," explains Dr. Ghermes Chilov, CEO of Fusion Pharma, the company that financed the project.

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Love at first smell: Can birds choose mates by their odors?

Mate choice is often the most important decision in the lives of humans and animals. Scientists at the Konrad Lorenz Institute of Ethology at the Vetmeduni Vienna have found the first evidence that birds may choose their mate through odor. The researchers compared the preen gland chemicals of black-legged kittiwakes with genes that play a role in immunity. Kittiwakes that smell similarly to each other also have similar genes for immunity. Since the birds prefer to mate with unrelated mates, the scientists have now found the likely mechanism by which they recognize relatedness. The scientists published their findings in Nature's Scientific Reports.

It has long been understood that reproducing with close relatives may have profoundly negative effects on offspring. It is therefore not surprising that biologists have discovered in some species that breeding individuals have evolved ways to detect their genetic similarity with those of prospective partners. Over 20 years ago it was discovered that female mice were able to choose unrelated over related males as mates. Females achieved this by comparing the smell of the urine of each male and comparing it with their own odors. Amazingly, the urine odors reflected the genetic composition of each mouse. More specifically, the odors were correlated with a special group of genes called the "major histocompatiabilty complex," or MHC, which helps individuals resist diseases. Thus, by pairing with MHC-dissimilar mates, breeders produce offspring with a more diverse collection of disease-resistant genes.

This discovery in mice was followed by similar findings in other mammals. More recently it has been shown that birds in several species also avoid breeding with MHC-similar mates. This poses a mystery. Whereas smell is a very well developed sense in mammals, it has long been thought that birds lack such keen olfactory abilities. Although a growing body of research is showing that birds can discriminate odors more than previously thought, none had shown that birds can do as mammals and use odor to compare their MHC composition with that of prospective mates. This mystery appears to have been solved by a group of researchers from Austria and France. Team leader Richard H. Wagner and behavioral geneticist Wouter van Dongen of the Konrad Lorenz Institute of Ethology, a part of the Veterinary Medicine University Vienna, have been collabortating with French colleagues on a long-term study of a cliff-nesting gull, the black-legged kittiwake, breeding in Anchorage Bay, Alaska.

When birds groom themselves with their bills, they spread chemical compounds from their preen glands throughout their plumage. These chemicals produce odors that appear to be unique to each individual, providing an olfactory fingerprint. The team suspected that, just as in mammals, these odors may be used by kittiwakes to assess their relatedness to other individuals.

To test this idea, the researchers collected both DNA samples and preen gland odor samples from nesting kittiwakes. The project then entailed two kinds of laboratory work: while Sarah Leclaire at the University of Toulouse conducted the analyses of the preen gland chemicals to characterise the odor signatures of each individual, van Dongen analyzed the MHC of the kittiwakes in the Vienna lab. The team had previously discovered that kittiwakes avoided pairing with relatives, but the mechanism by which the birds recognized their relatedness to each other had remained unknown until now. Their new finding is that individual kittiwakes that smell similarly to each other (i.e. have similar preen gland chemicals) also have similar MHC genes. Closer relatives therefore have more similar odors than distantly related individuals. This suggests that birds may be able to compare their own odor with those of potential mates, and to choose unrelated individuals as breeding partners. Quips ornithologist Wagner, "the more research that is performed on smell, the more it appears that anything mammals can do, birds can do too." The new findings, moreover, open the door for further work linking mate choice and disease-resistance in birds.

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Genomes of malaria-carrying mosquitoes sequenced

Anopheles mosquito.

Nora Besansky, O'Hara Professor of Biological Sciences at the University of Notre Dame and a member of the University's Eck Institute for Global Health, has led an international team of scientists in sequencing the genomes of 16 Anopheles mosquito species from around the world.

Anopheles mosquitoes are responsible for transmitting human malaria parasites that cause an estimated 200 million cases and more than 600 thousand deaths each year. However, of the almost 500 different Anopheles species, only a few dozen can carry the parasite and only a handful of species are responsible for the vast majority of transmissions. Besansky and her fellow researchers investigated the genetic differences between the deadly parasite-transmitting species and their harmless (but still annoying) cousins.

Two papers published in today's (Nov. 27) editions of Science Express, an electronic publication of the journal Science in advance of print, describe detailed genomic comparisons of these mosquitoes and the deadliest of them all, Anopheles gambiae. These results offer new insights into how these species are related to each other and how the dynamic evolution of their genomes may contribute to their flexibility to adapt to new environments and to seek out human blood. These newly sequenced genomes represent a substantial contribution to the scientific resources that will advance our understanding of the diverse biological characteristics of mosquitoes, and help to eliminate diseases that have a major impact on global public health.

Malaria parasites are transmitted to humans by only a few dozen of the many hundreds of species of Anopheles mosquitoes, and of these, only a handful are highly efficient disease-vectors. Thus, although about half the world's human population is at risk of malaria, most fatalities occur in sub-Saharan Africa, home of the major vector species, Anopheles gambiae. Variation in the ability of different Anopheles species to transmit malaria -- known as "vectorial capacity" -- are determined by many factors, including feeding and breeding preferences, as well as their immune responses to infections. Much of our understanding of many such processes derives from the sequencing of the Anopheles gambiae genome in 2002, which was led by Notre Dame researchers and which has since facilitated many large-scale functional studies that have offered numerous insights into how this mosquito became highly specialized in order to live amongst and feed upon humans.

Until now, the lack of such genomic resources for other Anopheles limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquito's ability to transmit parasites. To address these questions, researchers sequenced the genomes of 16 Anopheles species.

"We selected species from Africa, Asia, Europe, and Latin America that represent a range of evolutionary distances from Anopheles gambiae, a variety of ecological conditions, and varying degrees of vectorial capacity," Besansky said.

DNA sequencing and assembly efforts at the Broad Institute were funded by NHGRI and led by Daniel Neafsey, with samples obtained from mosquito colonies maintained through BEI Resources at the United States Centres for Disease Control and Prevention, and wild-caught or laboratory-reared mosquitoes from scientists in Africa, India, Iran, Melanesia and Southeast Asia.

"Getting enough high-quality DNA samples for all species was a challenging process and we had to design and apply novel strategies to overcome the difficulties associated with high levels of DNA sequence variations, especially from the wild-caught sample," Neafsey said.

With genome sequencing complete, scientists from around the world contributed their expertise to examine genes involved in different aspects of mosquito biology including reproductive processes, immune responses, insecticide resistance, and chemosensory mechanisms. These detailed studies involving so many species were facilitated by large-scale computational evolutionary genomic analyses led by Robert Waterhouse from the University of Geneva Medical School and the Swiss Institute of Bioinformatics.

The researchers carried out interspecies gene comparisons with the Anopheles and other insects, to identify equivalent genes in each species and highlight potentially important differences.

"We used similarities to genes from Anopheles gambiae and other well-studied organisms such as the fruit fly to learn about the possible functions of the thousands of new genes found in each of the Anopheles genomes," Waterhouse said.
Examining gene evolution across the Anopheles revealed high rates of gene gain and loss, about five times higher than in fruit flies. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely-related species.

"These dynamic changes," Neafsey said, "may offer clues to understanding the diversification of Anopheles mosquitoes; why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans."

The newly available genome sequences also provided conclusive evidence of the true relations amongst several species that are very closely related to Anopheles gambiae but nevertheless show quite different traits that affect their vectorial capacity.

"The question of the true species phylogeny has been a highly contentious issue in the field," Besansky said. "Our results show that the most efficient vectors are not necessarily the most closely-related species, and that traits enhancing vectorial capacity may be gained by gene flow between species."

This study substantially improves our understanding of the process of gene flow between closely related species -- a process believed to have occurred from Neanderthals to the ancestors of modern humans -- and how it may affect the evolution of common and distinct biological characteristics of mosquitoes such as ecological flexibility and vectorial capacity.

These two very different evolutionary timescales -- spanning all the Anopheles or focusing on the subset of very closely-related species -- offer distinct insights into the processes that have moulded these mosquito genomes into their present-day forms. Their dynamic evolutionary profiles may represent the genomic signatures of an inherent evolvability that has allowed Anopheles mosquitoes to quickly exploit new human-generated habitats and become the greatest scourge of humankind.

Besansky's research focuses primarily on African vectors of human malaria: the anopheline mosquitoes known as Anopheles gambiae and Anopheles funestus.

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Fragile X study offers hope of new autism treatment

People affected by a common inherited form of autism could be helped by a drug that is being tested as a treatment for cancer, according to researchers from the University of Edinburgh and McGill University.

Fragile X Syndrome is the most common genetic cause of autism spectrum disorders. It affects around 1 in 4,000 boys and 1 in 6,000 girls. Currently, there is no cure.

The scientists, who have identified a chemical pathway that goes awry in the brains of Fragile X patients, say a cancer drug candidate could reverse their behavioural symptoms. The researchers have found that a naturally occurring anti-fungal called cercosporamide can block the pathway and improve sociability in mice with the condition.

The team identified a key molecule -- eIF4E -- that drives excess protein production in the brains of Fragile X patients. This can cause behavioural symptoms that include learning difficulties. It can also lead to more serious intellectual disabilities, delays in speech and language development and problems with social interactions.

"We found that eIF4E regulates the production of an enzyme called MMP-9, which breaks down and re-orders the connections between brain cells called synapses," says Nahum Sonenberg, McGill professor in the Faculty of Medicine and the Goodman Cancer Research Centre and co-author of the study, "Excess MMP-9 disrupts communication between brain cells, leading to changes in behaviour."

The team found that treatment with cercosporamide blocks the activity of eIF4E, and therefore reduces the amounts of MMP-9, and reverses the behavioural symptoms in mice with a version of Fragile X Syndrome. The new findings suggest that it could have a use as a treatment for patients with Fragile X Syndrome. The study is published in the journal Cell Reports.

Findings open door to targeted treatments

McGill post-doctoral student and a co-first author of the study Arkady Khoutorsky said that "the enzyme MMP-9 has been implicated before in Fragile X Syndrome. What's new in our research is the demonstration that the symptoms of the disease can be controlled by manipulating eIF4E activity with available drug candidates."
"Our findings open the door to targeted treatments for Fragile X Syndrome," says Christos Gkogkas, of the University of Edinburgh's Patrick Wild Centre for Research into Autism, Fragile X Syndrome and Intellectual Disabilities. "By designing treatments that block just this pathway, it is hoped that we can limit the potential side-effects and develop therapies that are more efficient than general treatment approaches."

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Experimental Ebola vaccine appears safe, prompts immune response

An experimental vaccine to prevent Ebola virus disease was well-tolerated and produced immune system responses in all 20 healthy adults who received it in a Phase 1 clinical trial conducted by researchers from the National Institutes of Health. The candidate vaccine, which was co-developed by the NIH's National Institute of Allergy and Infectious Diseases (NIAID) and GlaxoSmithKline (GSK), was tested at the NIH Clinical Center in Bethesda, Maryland. The interim results are reported online in advance of print in the New England Journal of Medicine.

"The unprecedented scale of the current Ebola outbreak in West Africa has intensified efforts to develop safe and effective vaccines, which may play a role in bringing this epidemic to an end and undoubtedly will be critically important in preventing future large outbreaks," said NIAID Director Anthony S. Fauci, M.D. "Based on these positive results from the first human trial of this candidate vaccine, we are continuing our accelerated plan for larger trials to determine if the vaccine is efficacious in preventing Ebola infection."

The candidate NIAID/GSK Ebola vaccine was developed collaboratively by scientists at the NIAID Vaccine Research Center (VRC) and at Okairos, a biotechnology company acquired by GSK. It contains segments of Ebola virus genetic material from two virus species, Sudan and Zaire. The Ebola virus genetic material is delivered by a carrier virus (chimpanzee-derived adenovirus 3 or cAd 3) that causes a common cold in chimpanzees but causes no illness in humans. The candidate vaccine does not contain Ebola virus and cannot cause Ebola virus disease.

The trial enrolled volunteers between the ages of 18 and 50. Ten volunteers received an intramuscular injection of vaccine at a lower dose and 10 received the same vaccine at a higher dose. At two weeks and four weeks following vaccination, the researchers tested the volunteers' blood to determine if anti-Ebola antibodies were generated. All 20 volunteers developed such antibodies within four weeks of receiving the vaccine. Antibody levels were higher in those who received the higher dose vaccine.

The investigators also analyzed the research participants' blood to learn whether the vaccine prompted production of immune system cells called T cells. A recent study by VRC scientist Nancy J. Sullivan, Ph.D., and colleagues showed that non-human primates inoculated with the candidate NIAID/GSK vaccine developed both antibody and T-cell responses, and that these were sufficient to protect vaccinated animals from disease when they were later exposed to high levels of Ebola virus.

The experimental NIAID/GSK vaccine did induce a T-cell response in many of the volunteers, including production of CD8 T cells, which may be an important part of immune protection against Ebola viruses. Four weeks after vaccination, CD8 T cells were detected in two volunteers who had received the lower dose vaccine and in seven of those who had received the higher dose.

"We know from previous studies in non-human primates that CD8 T cells played a crucial role in protecting animals that had been vaccinated with this NIAID/GSK vaccine and then exposed to otherwise lethal amounts of Ebola virus," said Julie E. Ledgerwood, D.O., a VRC researcher and the trial's principal investigator. "The size and quality of the CD8 T cell response we saw in this trial are similar to that observed in non-human primates vaccinated with the candidate vaccine."

There were no serious adverse effects observed in any of the volunteers, although two people who received the higher dose vaccine did develop a briefly lasting fever within a day of vaccination.

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Bioengineering study finds two-cell mouse embryos already 'talking' about their future

Bioengineers at the University of California, San Diego have discovered that mouse embryos are contemplating their cellular fates in the earliest stages after fertilization when the embryo has only two to four cells, a discovery that could upend the scientific consensus about when embryonic cells begin differentiating into cell types. Their research, which used single-cell RNA sequencing to look at every gene in the mouse genome, was published recently in the journal Genome Research. In addition, this group published a paper on analysis of "time-course"single-cell data which is taken at precise stages of embryonic development in the journal of Proceedings of the National Academy of Sciences.

"Until recently, we haven't had the technology to look at cells this closely," said Sheng Zhong, a bioengineering professor at UC San Diego Jacobs School of Engineering, who led the research. "Using single-cell RNA-sequencing, we were able to measure every gene in the mouse genome at multiple stages of development to find differences in gene expression at precise stages."

The findings reveal cellular activity that could provide insight into where normal developmental processes break down, leading to early miscarriages and birth defects.

The researchers discovered that a handful of genes are clearly signaling to each other at the two-cell and four-cell stage, which happens within days after an egg has been fertilized by sperm and before the embryo has implanted into the uterus. Among the identified genes are several genes belonging to the WNT signaling pathway, well-known for their role in cell-cell communications.

The prevailing view until now has been that mammalian embryos start differentiating into cell types after they have proliferated into large enough numbers to form subgroups. According to the co-authors Fernando Biase and Xiaoyi Cao, when the first cell fate decision is made is an open question. The first major task for an embryo is to decide which cells will begin forming the fetus, and which will form the placenta.

The research was funded by the National Institutes of Health (DP2OD007417) and the March of Dimes Foundation.

Zhong's research in the field of systems or network biology applies engineering principals to understand how biological systems function. For example, they developed analytical methods to predict personal phenotypes, which refer to the physical description of an individual ranging from eye and hair color to health and disposition, using an individual's personal genome and epigenome. Epigenome refers to the chemical compounds in DNA that regulate gene expression and vary from person to person. Predicting phenotypes with genome and epigenome is an emerging area of research in the field of personalized medicine that scientists believe could provide new ways to predict and treat genetic disorders.

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Invisible shield found thousands of miles above Earth blocks 'killer electrons'

A team led by the University of Colorado Boulder has discovered an invisible shield some 7,200 miles above Earth that blocks so-called "killer electrons," which whip around the planet at near-light speed and have been known to threaten astronauts, fry satellites and degrade space systems during intense solar storms.

The barrier to the particle motion was discovered in the Van Allen radiation belts, two doughnut-shaped rings above Earth that are filled with high-energy electrons and protons, said Distinguished Professor Daniel Baker, director of CU-Boulder's Laboratory for Atmospheric and Space Physics (LASP). Held in place by Earth's magnetic field, the Van Allen radiation belts periodically swell and shrink in response to incoming energy disturbances from the sun.

As the first significant discovery of the space age, the Van Allen radiation belts were detected in 1958 by Professor James Van Allen and his team at the University of Iowa and were found to be composed of an inner and outer belt extending up to 25,000 miles above Earth's surface. In 2013, Baker -- who received his doctorate under Van Allen -- led a team that used the twin Van Allen Probes launched by NASA in 2012 to discover a third, transient "storage ring" between the inner and outer Van Allen radiation belts that seems to come and go with the intensity of space weather.

The latest mystery revolves around an "extremely sharp" boundary at the inner edge of the outer belt at roughly 7,200 miles in altitude that appears to block the ultrafast electrons from breeching the shield and moving deeper towards Earth's atmosphere.

"It's almost like theses electrons are running into a glass wall in space," said Baker, the study's lead author. "Somewhat like the shields created by force fields on Star Trek that were used to repel alien weapons, we are seeing an invisible shield blocking these electrons. It's an extremely puzzling phenomenon."

A paper on the subject was published in the Nov. 27 issue of Nature.

The team originally thought the highly charged electrons, which are looping around Earth at more than 100,000 miles per second, would slowly drift downward into the upper atmosphere and gradually be wiped out by interactions with air molecules. But the impenetrable barrier seen by the twin Van Allen belt spacecraft stops the electrons before they get that far, said Baker.

The group looked at a number of scenarios that could create and maintain such a barrier. The team wondered if it might have to do with Earth's magnetic field lines, which trap and control protons and electrons, bouncing them between Earth's poles like beads on a string. The also looked at whether radio signals from human transmitters on Earth could be scattering the charged electrons at the barrier, preventing their downward motion. Neither explanation held scientific water, Baker said.

"Nature abhors strong gradients and generally finds ways to smooth them out, so we would expect some of the relativistic electrons to move inward and some outward," said Baker. "It's not obvious how the slow, gradual processes that should be involved in motion of these particles can conspire to create such a sharp, persistent boundary at this location in space."

Another scenario is that the giant cloud of cold, electrically charged gas called the plasmasphere, which begins about 600 miles above Earth and stretches thousands of miles into the outer Van Allen belt, is scattering the electrons at the boundary with low frequency, electromagnetic waves that create a plasmapheric "hiss," said Baker. The hiss sounds like white noise when played over a speaker, he said.

While Baker said plasmaspheric hiss may play a role in the puzzling space barrier, he believes there is more to the story. "I think the key here is to keep observing the region in exquisite detail, which we can do because of the powerful instruments on the Van Allen probes. If the sun really blasts Earth's magnetosphere with a coronal mass ejection (CME), I suspect it will breach the shield for a period of time," said Baker, also a faculty member in the astrophysical and planetary sciences department.

"It's like looking at the phenomenon with new eyes, with a new set of instrumentation, which give us the detail to say, 'Yes, there is this hard, fast boundary,'" said John Foster, associate director of MIT's Haystack Observatory and a study co-author.

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DNA survives critical entry into Earth's atmosphere

This image shows the launch of the rocket TEXUS-49 from the Esrange Space Center in Kiruna, North Sweden.

The genetic material DNA can survive a flight through space and re-entry into Earth's atmosphere -- and still pass on genetic information. A team of scientists from UZH obtained these astonishing results during an experiment on the TEXUS-49 research rocket mission.

Applied to the outer shell of the payload section of a rocket using pipettes, small, double-stranded DNA molecules flew into space from Earth and back again. After the launch, space flight, re-entry into Earth's atmosphere and landing, the so-called plasmid DNA molecules were still found on all the application points on the rocket from the TEXUS-49 mission. And this was not the only surprise: For the most part, the DNA salvaged was even still able to transfer genetic information to bacterial and connective tissue cells. "This study provides experimental evidence that the DNA's genetic information is essentially capable of surviving the extreme conditions of space and the re-entry into Earth's dense atmosphere," says study head Professor Oliver Ullrich from the University of Zurich's Institute of Anatomy.

Spontaneous second mission

The experiment called DARE (DNA atmospheric re-entry experiment) resulted from a spontaneous idea: UZH scientists Dr. Cora Thiel and Professor Ullrich were conducting experiments on the TEXUS-49 mission to study the role of gravity in the regulation of gene expression in human cells using remote-controlled hardware inside the rocket's payload. During the mission preparations, they began to wonder whether the outer structure of the rocket might also be suitable for stability tests on so-called biosignatures. "Biosignatures are molecules that can prove the existence of past or present extraterrestrial life," explains Dr. Thiel. And so the two UZH researchers launched a small second mission at the European rocket station Esrange in Kiruna, north of the Arctic Circle.

DNA survives the most extreme conditions

The quickly conceived additional experiment was originally supposed to be a pretest to check the stability of biomarkers during spaceflight and re-entry into the atmosphere. Dr. Thiel did not expect the results it produced: "We were completely surprised to find so much intact and functionally active DNA." The study reveals that genetic information from the DNA can essentially withstand the most extreme conditions.
Various scientists believe that DNA could certainly reach us from outer space as Earth is not insulated: in extraterrestrial material made of dust and meteorites, for instance, around 100 tons of which hits our planet every day.
This extraordinary stability of DNA under space conditions also needs to be factored into the interpretion of results in the search for extraterrestrial life: "The results show that it is by no means unlikely that, despite all the safety precautions, space ships could also carry terrestrial DNA to their landing site. We need to have this under control in the search for extraterrestrial life," points out Ullrich.

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'Scary' centipede's genes reveal how life evolved on our planet

Centipedes, those many-legged creatures that startle us in our homes and gardens, have been genetically sequenced for the first time. In a new study in the journal PLoS Biology, an international team of over 100 scientists today reveals how this humble arthropod's DNA gave them new insight into how life developed on our planet.

Centipedes are members of the arthropods, a group with numerous species including insects, spiders and other animals. Until now, the only class of arthropods not represented by a sequenced genome was the myriapods, which include centipedes and millipedes. For this study, the researchers sequenced the genome of the centipede Strigamia maritima, because its primitive features can help us understand more complex arthropods.

According to Prof. Ariel Chipman, senior co-author of the study and project leader at the Hebrew University of Jerusalem's Alexander Silberman Institute of Life Science, the genetic data reveal how creatures transitioned from their original dwelling-place in the sea to living on land.

"The use of different evolutionary solutions to similar problems shows that myriapods and insects adapted to dry land independently of each other," said Chipman. "For example, comparing the centipede and insect genomes shows that they independently evolved different solutions to the same problem shared by all land-dwelling creatures -- that of living in dry air."

According to Chipman, the study found that despite being closely related to insects, the centipede lacks the olfactory gene family used by insects to smell the air, and thus developed its own air-sniffing ability by expanding other gene families not present in insects.

In addition, Chipman said, this specific group of centipedes live underground and have lost their eyes, together with almost all vision genes and genes involved in the body's internal clock. They maintain enhanced sensory capabilities enabling them to recognize their environment and capture prey.

Published in the latest edition of PLoS Biology, the research is a collaborative effort by over 100 scientists from 50 institutions. Thousands of human-hours went into looking at specific genes in the centipede genome, with each researcher looking at a limited set of genes or at specific structural characteristics to address specific questions.

Other leaders of the international research effort include Dr. Stephen Richards, Baylor College of Medicine; Dr. David Ferrier, University of St. Andrews; and Prof. Michael Akam of Cambridge University. The research paper is titled "The First Myriapod Genome Sequence Reveals Conservative Arthropod Gene Content and Genome Organisation in the Centipede Strigamia maritima."

While early studies of genomics focused on humans, as sequencing equipment and expertise became more readily available, researchers expanded into animals directly relevant to human wellbeing. In the latest research, genomic sequencing has become more broad-based, investigating the workings of the world around us.

In explaining the purpose of the research, Hebrew University's Chipman said: "If we have a better understanding of the biological world around us, how it operates, and how it came to be as it is, we will ultimately have a better understanding of ourselves."

According to Chipman, the research will have applications for other researchers ranging from conservation to dealing with crop pests.

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Vegetable oil ingredient key to destroying gastric disease bacteria

The bacterium Helicobacter pylori is strongly associated with gastric ulcers and cancer. To combat the infection, researchers at University of California, San Diego School of Medicine and Jacobs School of Engineering developed LipoLLA, a therapeutic nanoparticle that contains linolenic acid, a component in vegetable oils. In mice, LipoLLA was safe and more effective against H. pylori infection than standard antibiotic treatments.

The results are published online Nov. 24 in the Proceedings of the National Academy of Sciences.

"Current H. pylori treatments are facing a major challenge -- antibiotic resistance," said Liangfang Zhang, PhD, professor in the UC San Diego Moores Cancer Center and Department of Nanoengineering. "Our goal was to develop a nanotherapeutic that can tolerate the harsh gastric environment, kill H. pylori and avoid resistance." Zhang and Marygorret Obonyo, PhD, assistant professor in the Moores Cancer Center and Department of Medicine, are co-senior authors of the study.

LipoLLA is a lipid (fat) particle that contains linolenic acid. When LipoLLA encounters H. pylori, it fuses with the bacterial membrane. Then the particle's linolenic acid payload spills out, disrupting the membrane and killing the bacteria.

Zhang, Obonyo and their team labeled LipoLLA particles with fluorescent markers, fed them to mice and watched as the particles distributed themselves in the stomach lining -- and stayed there. After treatment, they measured bacterial load in the stomach and markers of inflammation. Compared to standard antibiotic therapies, LipoLLA was more effective at getting rid of H. pylori. What's more, LipoLLA was not toxic to the mice and the bacteria did not develop resistance to the therapy.

"This is the first step to verify that we can make this therapeutic nanoparticle and demonstrate that it works to reduce H. pylori colonization. We're now working to further enhance the particle, making it more stable and more effective," Zhang said.

Co-authors include Soracha Thamphiwatana, and Weiwei Gao, UC San Diego.
This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK095168), part of the National Institutes of Health.

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Long-term testosterone therapy does not increase risk of prostate cancer

Testosterone (T) therapy is routinely used in men with hypogonadism, a condition in which diminished function of the gonads occurs. Although there is no evidence that T therapy increases the risk of prostate cancer (PCa), there are still concerns and a paucity of long-term data. In a new study in The Journal of Urology^®, investigators examined three parallel, prospective, ongoing, cumulative registry studies of over 1,000 men. Their analysis showed that long-term T therapy in hypogonadal men is safe and does not increase the risk of PCa.

Lead investigator Ahmad Haider, MD, PhD, urologist, Bremerhaven, Germany, states, "Although considerable evidence exists indicating no relationship between testosterone and increased risk of developing PCa, decades of physician training with the notion that testosterone is fuel for PCa made it difficult to dispel such fallacy and the myth continued to persist. Nevertheless, in the absence of long-term follow-up data demonstrating reduced risk of PCa in hypogonadal men who are receiving T therapy, considerable skepticism remains throughout the medical community and this is an expected natural and acceptable path of medical and scientific discourse. In view of the current evidence, clinicians are compelled to think this over and cannot justify withholding T therapy in hypogonadal men, also in men who have been successfully treated for PCa."

A total of 1,023 patients on T therapy were followed for up to 17 years with a median follow-up of approximately 5 years. Two study cohorts of 261 (cohort 1) and 340 (cohort 2) men were treated by urologists since 2004 and a third cohort of 422 men was treated at an academic andrology center since 1996. Hypogonadism was diagnosed if testosterone was ≤12 nmol/L and if other symptoms were present, such as erectile dysfunction, fatigue, depression, or unfavorable changes in body composition (gaining of fat mass and waist circumference despite physical activity). If no contraindications were present, all were started on T therapy.

There were six (2.3%) diagnoses of PCa in cohort 1, there were five (1.5%) diagnoses of PCa in cohort 2, and all biopsies were negative in cohort 3. PCa incidence per 10,000 patient-years in cohorts 1 and 2 was 54.4 and 30.7, respectively, which is lower than 116 reported by the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) and 96.6 reported by the ERSPC ( European Randomized Study of Screening for Prostate Cancer).

Investigators stress that if guidelines for T therapy are properly applied, it is safe in hypogonadal men.

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Mere expectation of treatment can improve brain activity in Parkinson's patients

Learning-related brain activity in Parkinson's patients improves as much in response to a placebo treatment as to real medication, according to a new study by researchers at the University of Colorado Boulder and Columbia University.

Past research has shown that while Parkinson's disease is a neurological reality, the brain systems involved may also be affected by a patient's expectations about treatment. The new study, published in the journal Nature Neuroscience, explains how the placebo treatment -- when patients believe they have received medication when they have not -- works in people with Parkinson's disease by activating dopamine-rich areas in the brain.

"The findings highlight the power of expectations to drive changes in the brain," said Tor Wager, an associate professor of psychology and neuroscience at CU-Boulder and a co-author of the study. "The research highlights important links between psychology and medicine."

Parkinson's patients have difficulty with "reward learning," the brain's ability to associate actions with rewards and make motivated decisions to pursue positive outcomes. Reward learning is supported by neurons that emit dopamine when an action, like pushing a particular button, leads to a reward, like receiving money.

Reward learning is impaired in Parkinson's patients because the disease causes the neurons that release dopamine to die. Parkinson's patients can be treated for this condition with a medication that increases the dopamine in the brain, L-dopa.

For the new study, the research team -- which also includes Columbia University researchers Liane Schmidt, Erin Kendall Braun and Daphna Shohamy -- used functional Magnetic Resonance Imaging (fMRI) to scan the brains of 18 Parkinson's patients as they played a computer game that measures reward learning. In the game, participants discover through trial and error which of two symbols is more likely to lead to a better outcome, in this case a small monetary reward or simply not losing any money.

The Parkinson's patients played the game three times: when they were not taking any medication, when they took real medication (dissolved in orange juice), and when they took a placebo, which consisted of drinking orange juice that they thought contained their medication. The researchers found that the dopamine-rich areas of the brain associated with reward learning -- the striatum and the ventromedial prefrontal cortex -- became equally active when patients took either the real medication or the placebo treatment.

"This finding demonstrates a link between brain dopamine, expectation and learning," Wager said. "Recognizing that expectation and positive emotions matter has the potential to improve the quality of life for Parkinson's patients, and may also offer clues to how placebos may be effective in treating other types of diseases."

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Endangered species success: Idaho salmon regaining fitness advantage

Endangered Snake River sockeye salmon are regaining the fitness of their wild ancestors, with naturally spawned juvenile sockeye migrating to the ocean and returning as adults at a much higher rate than others released from hatcheries, according to a newly published analysis. The analysis indicates that the program to save the species has succeeded and is now shifting to rebuilding populations in the wild.

Biologists believe the increased return rate of sockeye spawned naturally by hatchery-produced parents is high enough for the species to eventually sustain itself in the wild again.

"This is a real American endangered species success story," said Will Stelle, Administrator of NOAA Fisheries' West Coast Region. "With only a handful of remaining fish, biologists brought the best genetic science to bear and the region lent its lasting support. Now there is real potential that this species will be self-sustaining again. The sockeye didn't give up hope and neither did we."

Biologists Paul Kline of the Idaho Department of Fish and Game and Thomas Flagg of NOAA Fisheries' Northwest Fisheries Science Center report the results in the November issue of Fisheries, the magazine of the American Fisheries Society.

These findings demonstrate that the program to save Snake River sockeye can indeed reverse the so-called "extinction vortex," where too few individuals remain for the species to sustain itself. Some thought that Snake River sockeye had entered that vortex in the 1990s, highlighted in 1992 when the sole returning male Redfish Lake sockeye, known as "Lonesome Larry" captured national attention.

NOAA Fisheries earlier this year released a proposed recovery plan for Snake River sockeye, which calls for an average of 1,000 naturally spawned sockeye returning to Redfish Lake each year, with similar targets for other lakes in Idaho's Sawtooth Valley. About 460 naturally spawned sockeye returned to Redfish Lake this year -- the most since the program began -- out of an overall record return of about 1,600.

The article in Fisheries recounts the 20-year history of the scientific program to save the Snake River sockeye. The program began with 16 remaining adult sockeye -- 11 males and five females -- taken into captivity from 1991 to 1998. Through advanced aquaculture techniques, the program has retained about 95 percent of the species' remaining genetic variability, while boosting surviving offspring about 2,000 percent beyond what could be expected in the wild.

Without such advances, the scientists write, "extinction would have been all but certain."

The program funded by the Bonneville Power Administration has released more than 3.8 million sockeye eggs and fish into lakes and streams in the Sawtooth Valley, and tracks the fish that return from the ocean. Hatchery fish returning as adults have also begun spawning again in Redfish Lake, increasingly producing naturally spawned offspring that are now also returning.

A new analysis of those returns shows that the naturally spawned sockeye are returning at rates up to three times higher than those released from hatcheries as smolts, and more than 10 times greater than those released as even younger pre-smolts.

The higher returns indicate the naturally spawned fish are regaining the fitness the species needs to better survive their 900-mile migration to the ocean, their years at sea, and the return trip to Redfish Lake. A salmon population must produce at least one returning offspring per adult to sustain itself.

Naturally spawned sockeye have returned at more than twice that rate in some years, indicating that under the right conditions they can not only sustain the species but add to it.

The results also suggest that hatchery-produced sockeye may regain the fitness advantages they need to sustain their species in the wild much faster than had been previously estimated, the scientists reported. Biologists caution that the current results span only three years so far, but indicate that fitness -- and, in turn, survival -- can improve in as little as only one generation in the wild.

"We hoped we could get returns equivalent to what you'd expect to see from a hatchery," said Flagg, manager of the NOAA Fisheries Northwest Fisheries' Science Center's Manchester Research Station. "We've seen the population respond even better than that, which bodes well for the idea that the lakes can produce the juveniles you'd want to see to get to recovery."

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Trojan horse tactic gives parasites edge over immune systems

Illustration of parasitic worm (stock image). Scientists have shown that parasites are able to secrete tiny sealed packages of genetic material into the cells of their victims, in order to suppress the immune response to infection.

Parasites use Trojan horse subterfuge to suppress the immunity of their victims when causing infection, according to a study.

The finding, which shows a new trick parasites can play, paves the way to possible treatments for infectious diseases and allergies.

Scientists have shown that parasites are able to secrete tiny sealed packages of genetic material into the cells of their victims, in order to suppress the immune response to infection.

The packages, known as vesicles, mimic those that are produced naturally in most organisms to carry out everyday functions such as transporting nutrients and chemical messages to and from cells. The parasite uses vesicles to hide its material inside a seemingly friendly exterior, like a Trojan horse.

The study, carried out on a parasite found in mice, showed that the material in the packages is able to interact with the mouse's own genes. It manipulates the cell's machinery to suppress products linked to immunity, so reducing resistance to infection.

Researchers say the discovery could inform new strategies for treating diseases caused by parasitic worms, which affect hundreds of millions of people and animals. The findings also offer a possible way to treat allergies, such as hayfever, because the immune mechanism that parasites block is also linked to allergic reactions.

The genetic material from the parasites can also be detected in human blood, suggesting that this could be used as a test to detect infection in people.

Ongoing studies are looking into whether other parasites and viruses use this same strategy. The study, published in Nature Communications, was funded by the Wellcome Trust.

Dr Amy Buck, of the University of Edinburgh's School of Biological Sciences, who led the study, said: "We can see for the first time that parasites can use packages to sneak their material into the cells of other organisms. We now can develop ways to target this with implications for the billions of people and animals at risk of infectious diseases and allergy."

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Many animals steal defenses from bacteria: Microbe toxin genes have jumped to ticks, mites and other animals

This is a tick resting on a blade of grass. Some species of ticks are among the many animals that have incorporated bacterial toxin genes into their genomes.

It's a dog eat dog world, and bacteria have been living in it for a long time. It's of no surprise that bacteria have a sophisticated arsenal to compete with each other for valuable resources in the environment. In 2010, work led by University of Washington Department of Microbiology Associate Professor Joseph Mougous uncovered a weaponry system used in this warfare between bacteria. The combatants inject deadly toxins into rival cells.

Now, in a surprising twist, Mougous and colleagues have found that many animals have taken a page from the bacterial playbook. They steal these toxins to fight unwanted microbes growing in or on them. The researchers describe their findings in a report to be published online Nov. 24 in the journal Nature.

The animal toxins were serendipitously discovered when the Mougous group was working with evolutionary biologist Harmit Malik at Fred Hutchinson Cancer Research Center in Seattle to find more bacterial competition toxins.

"When we started digging into genome databases, we were surprised to find that toxin genes we thought were present only in bacteria were also in several animals," explained co-author Matt Daugherty, a postdoctoral fellow in the Malik lab. "We immediately started wondering why they were there."

Their analyses revealed that these genes had jumped from bacteria into animals. These genes had become permanently incorporated into the genomes of these animals through a process known as horizontal gene transfer. While such transfer events are common between microbes, very few genes have been reported to jump from bacteria to more complex organisms.

The organisms carrying the bacterial toxins were incredibly diverse and included several species of ticks and mites. The team of scientists immediately recognized the potential medical importance of the toxin in one organism in particular -- the deer tick, infamous for its ability to transmit Lyme disease.

"We were excited to see this in the deer tick, given the increasing prevalence of Lyme disease in North America. Lyme disease is caused by a bacterium, so we speculated that the transferred antibacterial toxin might affect how the tick interacts with the Lyme disease agent," said co-author Seemay Chou, a postdoctoral researcher in the Mougous group.

Ticks carry pathogens in their guts and transmit them through their saliva when they feed on animals. The toxin was abundant in both of these sites in the tick. The researchers observed that, when they used genetic strategies to reduce production of the toxin in ticks, levels of the Lyme disease pathogen rose significantly.

"We are now following up on these results by looking into how these toxins influence Lyme disease transmission," said Chou.

How the toxins function in organisms other than ticks remains to be explored. The researchers now are looking at the possibility that other bacterial toxins have been repurposed by animals for antibacterial defense.

"Given the rate by which we are discovering new toxins, it would not surprise me at all if we find more that have been horizontally transferred" noted Mougous.

The Nature paper is titled, "Transferred interbacterial antagonism genes augment eukaryotic innate immune function."

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