Culture

Infectious proteins called prions cause a group of related, fatal and incurable neurodegenerative disorders, including bovine spongiform encephalopathy or Mad Cow disease and Creutzfeldt-Jakob disease, both of which affect humans.

Chronic wasting disease or CWD, also caused by prions, has reached the point of a global epidemic among deer, elk and members of the deer family. The latest estimates show 26 states and three Canadian provinces have reported the disease in animals on farms and those who are free-ranging. CWD was inadvertently introduced in South Korea in the 1990s and has also recently been identified in Norway, Finland and Sweden.

Scientists' efforts to more fully conduct research have been hindered due to the constraints of studying this disease in deer and elk; this type of research is challenging, costly and requires large laboratory spaces.

But that may now change. Researchers at Colorado State University, led by Professor Glenn Telling, have developed a new gene-targeted approach to study chronic wasting disease in mice, allowing opportunities for research that has not previously existed.

"It's a real breakthrough in the field," said Telling, director of the Prion Research Center at CSU. The study was published May 29 in the Proceedings of the National Academy of Sciences.

The research team also detected a difference in prion strain properties in deer and elk, which is significant because these properties control the ability of whether prions can transmit a disease between species.

Telling said that development of the new mouse model has been in the works for years. The scientists replaced the gene that encodes the prion protein in the mouse and replaced it with an exact replica of the code from either deer or elk.

Through this work, the research team learned that the gene-targeted mice displayed different strains of chronic wasting disease. This is akin to the different strains of viruses that exist for conditions like influenza and herpes, Telling said.

Researchers had not previously been able to detect these different strains in mouse models, even though deer and elk spread different strains of CWD.

Using this new research model, Telling said that scientists can more readily study the routes used by prions to access the central nervous system and spread disease, known as peripheral pathogenesis.

Understanding the number of strains of CWD that exist in the world is incredibly important for animal and human health.

"Ultimately, we want to understand whether or not human beings exposed to CWD prions will contract a new form of human prion disease," Telling said. "We still don't understand the potential for prions to transmit disease from one species to another."

The research team is already working on a gene-targeted model to study the potential for CWD transmission to human beings.

A scorpion native to Eastern Mexico may have more than just toxin in its sting. Researchers at Stanford University and in Mexico have found that the venom also contains two color-changing compounds that could help fight bacterial infections.

The team not only isolated the compounds in the scorpion's venom, but also synthesized them in the lab and verified that the lab-made versions killed staphylococcus and drug-resistant tuberculosis bacteria in tissue samples and in mice.

The findings, published in the June 10 issue of the journal Proceedings of the National Academy of Sciences, highlight the potential pharmacological treasures awaiting discovery in the toxins of scorpions, snakes, snails and other poisonous creatures.

"By volume, scorpion venom is one of the most precious materials in the world. It would costs $39 million to produce a gallon of it," said study senior author Richard Zare, who led the Stanford group. "If you depended only on scorpions to produce it, nobody could afford it, so it's important to identify what the critical ingredients are and be able to synthesize them."

Milking scorpions

Zare worked with his colleagues in Mexico, including Lourival Possani, a professor of molecular medicine at the National University of Mexico, whose students caught specimens of the scorpion Diplocentrus melici for study.

"The collection of this species of scorpion is difficult because during the winter and dry seasons, the scorpion is buried," Possani said. "We can only find it in the rainy season."

For the past 45 years, Possani has focused on identifying compounds with pharmacological potential in scorpion venom. His group has previously uncovered potent antibiotics, insecticides and anti-malarial agents hidden in the arachnid's poison.

When the Mexican researchers milked the venom of D. melici - a process that involves stimulating the tail with mild electrical pulses - they noticed that the venom changed color, from clear to brownish, when it was exposed to air.

When Possani and his lab investigated this unusual color-change, they found two chemical compounds that they believed were responsible. One of the compounds turned red when exposed to air, while the other turned blue.

To find out more about each compound, Possani reached out to Zare's group at Stanford, which has a reputation for identifying and synthesizing chemicals.

Using only a tiny sample of the venom, Stanford postdoctoral researchers Shibdas Banerjee and Gnanamani Elumalai were able to work out the molecular structure of the two compounds. "We only had 0.5 microliters of the venom to work with," said Zare, who is the Marguerite Blake Wilbur Professor in Natural Science at Stanford's School of Humanities and Sciences. "This is ten times less than the amount of blood a mosquito will suck in a single serving."

Using clues gleaned from running the compounds through various chemical analysis techniques, the Stanford scientists concluded that the color-changing ingredients in the venom were two previously unknown benzoquinones - a class of ring-like molecules known to have antimicrobial properties.

The benzoquinones in the scorpion venom appeared to be nearly identical to one another. "The two compounds are structurally related, but whereas the red one has an oxygen atom on one of its branches, the blue one has a sulfur atom," Banerjee said.

The group confirmed the compounds' structures when, through much trial and error, they learned how to synthesize them. "Many of the reactions you write on paper that appear to work don't actually work when you try them in the lab, so you need to be patient and have many different ideas," said Stanford MD-PhD graduate student Shyam Sathyamoorthi, who led the synthesis efforts.

Drug potential

Zare's lab sent a batch of the newly synthesized benzoquinones to Rogelio Hernández-Pando, a pathologist at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City, whose group tested the lab-made compounds for biological activity.

Hernández-Pando's group found that the red benzoquinone was particularly effective at killing the highly infectious staphylococcus bacteria, while the blue one was lethal to both normal and multi-drug-resistant strains of tuberculosis-causing bacteria.

"We found that these compounds killed bacteria, but then the question became 'Will it kill you, too?'" Zare said. "And the answer is no: Hernández-Pando's group showed that the blue compound kills tuberculosis bacteria but leaves the lining of the lungs in mice intact."

Possani said the antimicrobial properties of the compounds might not have been discovered if Zare's group had not figured out how to synthesize it, thus allowing it to be produced in larger quantities. "The amount of venom components we can get from the animals is extremely low," Possani said. "The synthesis of the compounds was decisive for the success of this work."

The Stanford and Mexican scientists are planning further collaborations to determine whether the isolated venom compounds can be transformed into drugs and also why they're present in the venom in the first place.

"These compounds might not be the poisonous component of the venom," Zare said. "We have no idea why the scorpion makes these compounds. There are more mysteries."

Corruption affects all of us. It impedes equitable development, destabilizes societies, and undermines the institutions and values of democracy. It is viewed by many as one of the world's greatest problems. According to the Gallup Poll, a majority of people even place its negative impacts ahead of global problems like climate change, poverty, and terrorism.

Corruption comes in various guises, including favoritism, clientelism (the exchange of goods and services for political support), and embezzlement of public funds. In their study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), researchers from IIASA, the University of Vienna, and two Japanese universities focused specifically on one form of corruption, namely bribery in public institutions. They used a broad definition of public institutions that also included agencies run by officials such as soccer referees, journalists, or executives of nongovernmental organizations (NGOs) - in other words, all public officials that wield power based on social trust.

The team analyzed a basic model of bribery using evolutionary game theory - a framework originally developed to describe biological evolution and increasingly used to analyze social evolution. By adopting this viewpoint, the researchers explain, they posit that socioeconomic role-players are guided by self-interest. Their goal was to create a minimal model capturing key dynamics that would be relevant for many specific systems. In particular, they wanted to show that the adaptation of individual agents to a prevailing social situation leads to sustained or damped cycles that reflect the waxing and waning of institutional corruption in conjunction with the waning and waxing of cooperation within the society.

This can be illustrated by the following situation. Public institutions are generally supposed to function as guardians of the community. These institutions are however managed by individuals who are not exempt from selfish motives, which necessitates that communities relying on the protection afforded by these institutions hold the institutions accountable - in other words, they have to "guard the guardians". Putting anti-corruption measures in place to implement this vigilance is usually a costly affair. When these measures are neglected, corruption can spread, leading to a loss of trust and a breakdown in cooperation. Such a crisis may prompt stakeholders to reinvigorate their efforts to monitor the institution and only invest in it when they can again trust that it is sufficiently reliable - this can curb corruption and bolster economic activity. As soon as cooperation and honesty however again become commonplace, efforts to watch the integrity of the institution become less critical and may therefore become neglected again, thus initiating another cycle in the process.

According to the researchers, this feedback cycle occurs because successful anti-corruption measures create conditions under which cutting back on their costs seems rationally warranted. That is to say, successful anti-corruption measures undermine their own success.

"Anti-corruption measures suffer from an inherent instability that must be recognized and remedied before measures have a chance to be successful in the long term. Transparency about the integrity of institutions is key to fighting corruption, and costly vigilance against corruption must be maintained even when corruption levels appear to be low," explains IIASA researcher Ulf Dieckmann, one of the authors of the study.

The team hopes that their analysis will help guide the design of anti-corruption measures and serve as a springboard for future game-theoretical investigations of this important topic.

Analysis of the first fully-sequenced genome of the Siberian hamster shows how these small, seasonal breeders adapt their bodies and energy usage to survive the winter.

The research, published this week in the Proceedings of the National Academy of Sciences, also includes transcriptome analysis of gene expression in the brain during both summer and winter conditions, which reveals the cascade of signals that prepare the hamster for winter, triggered by decreasing day length.

The Siberian hamster (Phodopus sungorus) is a model organism for studying seasonal biological rhythms. They breed during the spring and early summer, but as fall approaches and day length shortens, their bodies change dramatically. The hamsters lose almost half their body weight, mostly through fat, and limit food intake by 30 to 40%. They don't hibernate, but modestly reduce their body temperature during the daytime to conserve energy. Their fur thickens and changes color to stark white, and they become infertile until they begin reversing course to prepare for the next breeding season.

The new study shows that shifting day length alone was enough to trigger these changes, regardless of temperature or how much food is available.

"We hope this will be a tool for discovery and more research on a really interesting biological puzzle, which is how organisms navigate the energetic landscape of nature over the course of a year," said Brian Prendergast, PhD, professor of psychology at the University of Chicago and one of the authors of the study.

The research is a collaborative project with senior author Tyler Stevenson, PhD, a former postdoctoral fellow in Prendergast's lab now on the faculty at the University of Glasgow. Stevenson worked with Riyue Bao, PhD, from the UChicago Center for Research Informatics bioinformatics group, to assemble and analyze the hamster genome and transcriptome, or the RNA molecules expressed by its genes, to understand the activity of these genes in the brain under both summer and winter conditions.

'Simply a matter of connecting the dots'

The researchers focused on activity in the hypothalamus, part of the brain that initiates a number of important metabolic processes like releasing hormones, providing signals to the thyroid, and controlling body temperature, hunger and sleep. Modern science has a pretty good understanding of how these processes maintain weight in the short-term through appetite, food intake and energy expenditure. For the new study, the researchers wanted to see how animals like the Siberian hamster maintain weight long-term in an annual cycle.

Stevenson and Bao worked together to interpret the data about how genes were expressed, looking for differences between samples taken from hamsters during the summer and winter periods. Once Bao spotted those differences and identified which biological processes might be affected, she turned to Stevenson for validation.

"Our collaboration is quite dynamic, like a two-way street," Bao said. "I would pass the data to him and ask if a certain pathway made sense. Then he might recognize a certain RNA molecule or candidate gene and ask for more information."

They narrowed in on a gene called pomc. For years, scientists have speculated that it is involved in long-term regulation of weight and energy balance in many animals, but, "It was the steps that control pomc expression that had been the mystery," Stevenson said. "The studies we designed served to fill the gaps and it was simply a matter of connecting the dots."

That chain of events begins with thyroid hormone, which is called T4. The T4 hormone is readily available in the bloodstream, and when the amount of daylight begins to increase in the spring, the hamster produces enzymes called deiodinases. These enzymes remove an iodine molecule from T4 and turn it into a more potent hormone called T3 that controls the activity of pomc.

During the summer, increased T3 production allows the hamsters to become fertile, and also ramps up pomc activity, causing them to gain weight. As the days shorten in the fall, T3 production decreases, shutting down reproduction for the upcoming winter. Lowered T3 also downregulates--or switches off--pomc, resulting in dramatic weight loss.

Stevenson also compared the genome of the Siberian hamster to other small mammals like mice and voles. He noticed a lot of differences between animals in the sequence patterns, or motifs, in the promoter region of the pomcgene. This section of DNA at the beginning of the gene sequence plays an important role in how it's transcribed into RNA, and ultimately how the gene functions. The Siberian hamster shares the same motif with other seasonal breeders, suggesting that it's key to how pomcis expressed to manage the summer-winter adaptations.

"All animals show a level of seasonal biology, humans included. What our findings show, in hamsters, is that thyroid hormones acting in the brain where pomc is expressed provides the long-term regulation of energy balance," Stevenson said.

"What is completely fascinating is that this process evolved in some animals, like hamsters and voles, and not in others, like sheep or humans. This tells us that a large degree of genome variability exists across animals and indicates a strong species-specific control of long-term energy balance," he said.

'A wonderful puzzle'

In a separate set of experiments, the researchers also restricted the amount of food for the hamsters. While this caused some changes in brain chemistry, it didn't have an effect on pomcexpression. Only long-term changes to day length had an effect on pomc.

Prendergast says patterns like this make the Siberian hamster interesting not just in how it manages seasonal adaptations but in managing body weight in general.

"Researchers who study obesity should pay attention to this model because this is an animal that becomes reversibly obese. Then it can lose almost half its body weight on cue when the day length says it's time to lose weight," he said. "They're a wonderful puzzle for understanding all of these processes."

New research from Washington University in St. Louis reveals the molecular machinery behind the high-intensity sweetness of the stevia plant. The results could be used to engineer new non-caloric products without the aftertaste that many associate with sweetener marketed as Stevia.

Although the genes and proteins in the biochemical pathway responsible for stevia synthesis are almost completely known, this is the first time that the three-dimensional structure of the proteins that make rebaudioside A -- or 'RebA,' the major ingredient in the product Stevia -- has been published, according to the authors of a new paper in the Proceedings of the National Academy of Sciences.

"If someone is diabetic or obese and needs to remove sugar from their diet, they can turn to artificial sweeteners made from chemical synthesis (aspartame, saccharin, etc), but all of these have 'off-tastes' not associated with sugar, and some have their own health issues," said Joseph Jez, professor of biology in Arts & Sciences and lead author of the new study.

"Stevias and their related molecules occur naturally in plants and are more than 200 times sweeter than sugar," he said. "They've been consumed for centuries in Central and South America, and are safe for consumers. Many major food and beverage companies are looking ahead and aiming to reduce sugar/calories in various projects over the next few years in response to consumer demands worldwide."

Researchers determined the structure of the RebA protein by x-ray crystallography. Their analysis shows how RebA is synthesized by a key plant enzyme and how the chemical structure needed for that high-intensity sweetness is built biochemically.

To make something 200 times sweeter than a single glucose molecule, the plant enzyme decorates a core terpene scaffold with three special sugars.

That extra-sweet taste from the stevia plant comes with an unwanted flavor downside, however.

"For me, the sweetness of Stevia comes with an aftertaste of licked aluminum foil," Jez said. Many consumers experience this slightly metallic aftertaste.

"The taste is particular to the predominant molecules in the plant leaf: the stevioside and RebA," he said. "It is their chemical structure that hits the taste receptors on the tongue that trigger 'sweet,' but they also hit other taste receptors that trigger the other tastes."

"RebA is abundant in the stevia plant and was the first product made from the plant because it was easy to purify in bulk. Call this 'Stevia 1.0'," Jez said. "But in the leaf are other related compounds with different structures that hit the 'sweet' without the aftertaste. Those are 'Stevia 2.0,' and they will be big."

There are many ways that the newly published protein structure information could be used to help improve sweeteners.

"One could use the snapshot of the protein that makes RebA to guide protein engineering efforts to tailor the types and/or pattern of sugars in the stevias," Jez said. "This could be used to explore the chemical space between 'sweet' and 'yuck'."

"There are also molecules in other plants that are not 'stevias' but can deliver intense sweetness," he said. "We could use the information of how the stevia plant does it as a way of finding those details."

Legalizing medical marijuana does not reduce the rate of fatal opioid overdoses, according to researchers at the Stanford University School of Medicine.

The finding contradicts a 2014 study that legal-pot advocates, public officials and even physicians have touted as a reason to legalize marijuana. That study found lower rates of fatal opioid overdoses in the states that had legalized marijuana for medical purposes than in states where marijuana remained illegal.

The Stanford study, which revisited the issue after many more states had legalized medical marijuana, found no evidence of a connection between opioid deaths and the availability of medical cannabis, said Keith Humphreys, PhD, professor of psychiatry and behavioral sciences.

"If you think opening a bunch of dispensaries is going to reduce opioid deaths, you'll be disappointed," Humphreys said. "We don't think cannabis is killing people, but we don't think it's saving people."

A paper describing the new study will be published online June 10 in Proceedings of the National Academy of Sciences. Humphreys is the senior author. The lead author is postdoctoral scholar Chelsea Shover, PhD.

Medical pot now legal in 47 states

In 1996, California became the first state to legalize medical marijuana. By 2010, 13 states, most of them in the West, had legalized medical marijuana. Today, 47 states permit some version of medical pot.

For the new study, the Stanford researchers used the same method employed in the 2014 study to evaluate the connection between legalized medical marijuana and fatal opioid overdoses. They confirmed the findings from the 2014 study, but when they looked at opioid deaths up to 2017 -- by which point most states had legalized some form of medical marijuana, if not recreational marijuana -- they found that the opposite was true: States with legal medical marijuana had a higher rate of deaths due to opioid overdose.

After the 2014 study was released, medical marijuana proponents and some public officials interpreted the results to mean that, given access to legalized pot, people would turn to it rather than opioids for pain relief or recreation. Yet when the Stanford researchers compared states that have more restrictive medical marijuana laws with those that allow recreational marijuana, they found no correlation between opioid overdose mortality and the level of restriction.

"Accounting for different types of laws didn't change the bottom line," Shover said.

Also, given that only 2.5% of the U.S. population uses medical marijuana, it's unlikely that use could affect mortality statistics, the researchers said.

'Something else about those states'

Humphreys said the results of the 2014 study may have reflected policies and conditions in states that legalized medical marijuana early. Those states tended to be wealthier and more politically liberal, with greater access to addiction treatment and to naloxone, which reverses the effects of opioids and can prevent overdose fatalities. The states that legalized pot early also incarcerate fewer people for drug use, Humphreys added. When people are released from prison, where they lack access to drugs and lose tolerance to them, they may try to use the same levels as they did before they were incarcerated, leading to overdose.

The finding of lower death rates "wasn't about the cannabis," Humphreys said. "It was something else about those states."

Humphreys and Shover said they believe that medical marijuana provides benefits and that research into its effectiveness should continue.

"There are valid reasons to pursue medical cannabis policies, but this doesn't seem to be one of them," Shover said. "I urge researchers and policymakers to focus on other ways to reduce mortality due to opioid overdoses."

PITTSBURGH (June 10, 2019) ... Mastering a new skill - whether a sport, an instrument, or a craft - takes time and training. While it is understood that a healthy brain is capable of learning these new skills, how the brain changes in order to develop new behaviors is a relative mystery. More precise knowledge of this underlying neural circuitry may eventually improve the quality of life for individuals who have suffered brain injury by enabling them to more easily relearn everyday tasks.

Researchers from the University of Pittsburgh and Carnegie Mellon University recently published an article in PNAS (DOI: 10.1073/pnas.1820296116) that reveals what happens in the brain as learners progress from novice to expert. They discovered that new neural activity patterns emerge with long-term learning and established a causal link between these patterns and new behavioral abilities.

The research was performed as part of the Center for the Neural Basis of Cognition, a cross-institutional research and education program that leverages the strengths of Pitt in basic and clinical neuroscience and bioengineering, with those of CMU in cognitive and computational neuroscience.

The project was jointly mentored by Aaron Batista, associate professor of bioengineering at Pitt; Byron Yu, associate professor of electrical and computer engineering and biomedical engineering at CMU; and Steven Chase, associate professor of biomedical engineering and the Neuroscience Institute at CMU. The work was led by Pitt bioengineering postdoctoral associate Emily Oby.

"We used a brain-computer interface (BCI), which creates a direct connection between our subject's neural activity and the movement of a computer cursor," said Oby. "We recorded the activity of around 90 neural units in the arm region of the primary motor cortex of Rhesus monkeys as they performed a task that required them to move the cursor to align with targets on the monitor."

To determine whether the monkeys would form new neural patterns as they learned, the research group encouraged the animals to attempt a new BCI skill and then compared those recordings to the pre-existing neural patterns.

"We first presented the monkey with what we call an 'intuitive mapping' from their neural activity to the cursor that worked with how their neurons naturally fire and which didn't require any learning," said Oby. "We then induced learning by introducing a skill in the form of a novel mapping that required the subject to learn what neural patterns they need to produce in order to move the cursor."

Like learning most skills, the group's BCI task took several sessions of practice and a bit of coaching along the way.

"We discovered that after a week, our subject was able to learn how to control the cursor," said Batista. "This is striking because by construction, we knew from the outset that they did not have the neural activity patterns required to perform this skill. Sure enough, when we looked at the neural activity again after learning we saw that new patterns of neural activity had appeared, and these new patterns are what enabled the monkey to perform the task."

These findings suggest that the process for humans to master a new skill might also involve the generation of new neural activity patterns.

"Though we are looking at this one specific task in animal subjects, we believe that this is perhaps how the brain learns many new things," said Yu. "Consider learning the finger dexterity required to play a complex piece on the piano. Prior to practice, your brain might not yet be capable of generating the appropriate activity patterns to produce the desired finger movements."

"We think that extended practice builds new synaptic connectivity that leads directly to the development of new patterns of activity that enable new abilities," said Chase. "We think this work applies to anybody who wants to learn - whether it be a paralyzed individual learning to use a brain-computer interface or a stroke survivor who wants to regain normal motor function. If we can look directly at the brain during motor learning, we believe we can design neurofeedback strategies that facilitate the process that leads to the formation of new neural activity patterns."

The Metropolitan Museum of Art (The Met) and The University of New Mexico (UNM) today announced the groundbreaking findings of a two-year study of the plasmonic properties of daguerreotypes.

Using atomic force microscopy and scanning electron microscopy, together with numerical calculations, the team of scientists from The Met and UNM, in collaboration with Century Darkroom, Toronto was able to determine how the light scattered by the metallic nanoparticles on the surface of a daguerreotype determines the characteristics of its image, such as shade and color.

The pioneering research-- recently published in the journal PNAS--not only provides an in-depth understanding of these 19th century photographs that are crucial for their preservation, but also introduces new possible approaches for color printing where nanostructures are directly manufactured by light.

"We are thrilled by these findings that help us better understand the fascinating properties of daguerreotypes and shed light on how to continue to advance the preservation of these incredible works of art," said Silvia A. Centeno, Research Scientist in the Department of Scientific Research at The Metropolitan Museum of Art.

"The team at the University of New Mexico embarked on this study to achieve a better understanding of the mechanisms that give rise to the optical response of daguerreotypes and to contribute to the development of protocols for preserving these fragile artifacts," said Alejandro Manjavacas from the Department of Physics and Astronomy at The University of New Mexico. "Thanks to the fantastic teamwork between scientists from both the cultural and scientific communities we were able to accomplish what we set out to do."

Unlike other types of photographs, daguerreotypes rely on light scattering by metallic nanoparticles to create images that project off a reflective silver substrate. These early photographs can be recognized as the first examples of plasmonic color printing, an emerging research field that exploits the interactions between light and metallic nanostructures to produce vivid colors.

The image tones of a daguerreotype are dynamic and unique in that they can change with the viewing angle and, for the first time, this effect is explained by the authors, who found that the morphology and size of nanoparticles determines how these will scatter thus creating the visual outcome of the daguerreotype. Studies of the image properties of daguerreotypes serve to inform the development of preservation protocols, as well as novel approaches to future color printing technologies inspired by past ones.

A new study from Professor Doug VanderLaan's lab in UTM's Department of Psychology looking at biological mechanisms that are often thought to influence male sexual orientation was published in the latest edition of PNAS.

"Studying individual differences in gender and sexual orientation provides insight into how early-life biology shapes the brain and behaviour," says the developmental psychology researcher.

VanderLaan's study assessed whether biomarkers--markers of early-life biological processes--work in conjunction with each other to contribute to male same-sex sexual orientation or influence sexual orientation independently of one another.

"The biomarkers have all tended to be studied on their own before. But our study considers whether there is some interaction or association between these influences," says VanderLaan.

The biomarkers VanderLaan examined included participants' number of older brothers, rate of left- versus right-handedness, and the presence of gay and/or bisexual male relatives in their families. VanderLaan's group used latent profile analysis (LPA), a statistical technique, to help identify whether these biomarkers cluster together in the same individuals or are present in only particular subgroups of men.

The study found evidence for at least four different subgroups: men with elevated numbers of older brothers, men with a greater degree of non-right-handedness, men with elevated gay and/or bisexual male relatives, and men with low levels of these biomarkers.

VanderLaan's study concluded that the biomarkers likely reflect different subgroups of men. Participants who belonged to the subgroups that showed biomarkers were more likely to report same-sex attractions than the subgroup that showed low levels of these biomarkers.

"These findings likely reflect the existence of subgroups of same-sex attracted men who owe their sexual orientation to different developmental processes," VanderLaan says.

The study also found differences between the subgroups on measures of psychological characteristics that previous research had suggested were associated with male sexual orientation. The subgroup without these biomarkers conformed the most to masculine gender roles, whereas the subgroup with greater numbers of older brothers among their siblings scored higher on measures of feminine gender role expression and agreeableness. These patterns suggest the biological processes associated with each biomarker might have unique influences on psychological development.

"Our study illustrates the value of LPA for studying individual differences in people," says VanderLaan.

"The findings also suggest that there are multiple and distinct pathways influencing same-sex sexual orientation in men and we will further pursue these pathways in other studies."

TORONTO, ON (Canada) - If you've ever come out of a bad relationship and decided you need to date someone different from your usual "type," you're not alone.

However, new research by social psychologists at the University of Toronto (U of T) suggests that might be easier said than done. A study published today in Proceedings of the National Academy of Sciences shows people often look for love with the same type of person over and over again.

"It's common that when a relationship ends, people attribute the breakup to their ex-partner's personality and decide they need to date a different type of person," says lead author Yoobin Park, a PhD student in the Department of Psychology in the Faculty of Arts & Science at U of T. "Our research suggests there's a strong tendency to nevertheless continue to date a similar personality."

Using data from an ongoing multi-year study on couples and families across several age groups, Park and co-author Geoff MacDonald, a professor in the Department of Psychology at U of T, compared the personalities of current and past partners of 332 people. Their primary finding was the existence of a significant consistency in the personalities of an individual's romantic partners.

"The effect is more than just a tendency to date someone similar to yourself," says Park.

Participants in the study along with a sample of current and past partners, assessed their own personality traits related to agreeableness, conscientiousness, extraversion, neuroticism, and openness to experience. They were polled on how much they identified with a series of statements such as, "I am usually modest and reserved", "I am interested in many different kinds of things" and "I make plans and carry them out". Respondents were asked to rate their disagreement or agreement with each statement on a five-point scale.

Park and MacDonald's analysis of the responses showed that overall, the current partners of individuals described themselves in ways that were similar to past partners.

"The degree of consistency from one relationship to the next suggests that people may indeed have a 'type'," says MacDonald. "And though our data do not make clear why people's partners exhibit similar personalities, it is noteworthy that we found partner similarity above and beyond similarity to oneself."

By examining first-person testimonials of someone's partners rather than relying on someone's own description of them, the work accounts for biases found in other studies.

"Our study was particularly rigorous because we didn't just rely on one person recalling their various partners' personalities," said Park. "We had reports from the partners themselves in real time."

The researchers say the findings offer ways to keep relationships healthy and couples happy.

"In every relationship, people learn strategies for working with their partner's personality," says Park. "If your new partner's personality resembles your ex-partner's personality, transferring the skills you learned might be an effective way to start a new relationship on a good footing."

On the other hand, Park says the strategies people learn to manage their partner's personality can also be negative, and that more research is needed to determine how much meeting someone similar to an ex-partner is a plus, and how much it's a minus when moving to a new relationship.

"So, if you find you're having the same issues in relationship after relationship," says Park, "you may want to think about how gravitating toward the same personality traits in a partner is contributing to the consistency in your problems."

The data for the research comes from the German Family Panel study launched in 2008, an ongoing longitudinal study on couple and family dynamics with a nationally representative sample of adolescents, young adults, and midlife individuals in Germany.

CORVALLIS, Ore. - The vast subtropical "gyres" - large systems of rotating currents in the middle of the oceans - cover 40 percent of the Earth's surface and have long been considered biological deserts with stratified waters that contain very little nutrients to sustain life.

These regions also are thought to be remarkably stable, yet scientists have documented one anomaly in the North Pacific Subtropical Gyre ecosystem that has puzzled oceanographers for years: The region's chemistry changes periodically, especially levels of phosphorous and iron, affecting the overall nutrient composition and ultimately its biological productivity.

In a new study published this week in Proceedings of the National Academy of Sciences, researchers document what induces these variations: changes in the amount of iron that is deposited into the ocean via dust from Asia.

"We now know that these areas that were thought to be barren and stable are actually quite dynamic," said Ricardo Letelier, an Oregon State University biogeochemist and ecologist, who in collaboration with David Karl at the University of Hawaii led this study. "Since these areas cover so much of the Earth's surface, we need to know more about how they work in order to better predict how the system will respond to climate variations in the future."

The study focused on the North Pacific Subtropical Gyre, and used three decades of observation data from Station ALOHA by the Hawaii Ocean Time-series program, which is funded by the National Science Foundation.

The surface layer of the North Pacific gyre is characterized by very clear waters with hardly any nutrients. The extraordinary optical clarity of these waters allows sunlight to penetrate deep into the water column and support photosynthetic activity below 100 meters (or 328 feet).

Typically, the ocean's upper water column is fertilized by nutrient-rich water mixing from the deep, but these waters are very stratified and little mixing takes place. Deeper water (hundreds to thousands of meters below the surface) is enriched in nutrients through the decomposition of the remains of small organisms that grew and harvested the scarce nutrients in the surface layers before sinking toward the seafloor.

Both phosphorous and iron are key components for life and the researchers noticed that the levels of those nutrients in North Pacific gyre surface waters changed significantly during the three decades of the study.

Letelier said the team was able to relate these changes to the iron input from Asian dust - a combination of the desertification of that continent, with combustion, especially wildfires and factory output and the wind patterns across the North Pacific ocean - that accounted for the variance and provided varying amounts of nutrients to sustain life.

And a key to that variance is the Pacific Decadal Oscillation, an ocean-atmosphere relationship that varies between weak and strong phases of atmospheric pressure in the northeast Pacific. In years when the low pressure weakens, winds from Asia become stronger, move more southward, and bring more dust, fertilizing the ocean surrounding Station ALOHA. When the pressure strengthens, the opposite takes place.

Strong winds can bring significant amounts of iron, allowing organisms to grow and utilize all the phosphorus in the upper layers of the ocean. However, because most of the iron is not soluble, deep waters are enriched in phosphorus relative to iron. Hence, when winds are weaker, there is little iron input to fertilize and remove any excess phosphorus in the upper layers that may be introduced through deep water mixing.

"Sometimes there are periods of 5-6 years of phosphorus enrichment, and then there are periods when it switches over," Letelier said. "From 2000 to 2007, there was almost no phosphorus. We have seen some changes in the function of the ecosystem, but we haven't yet seen significant changes in the biological composition. They may be coming; it's too early to tell."

As the Artic warms, the scientists say they expect to see long-term changes in wind patterns across the North Pacific. In addition, the evolution of land use and pollution driven by anthropogenic activity in Asia will affect the sources and magnitude of iron and other nutrients carried by wind across the ocean.

How these changes will affect the transport of iron-rich dust into the eastern Pacific and affect the productivity in this vast oceanic region remains an open question.

Sexually active Australian secondary students tend to engage in responsible sexual behaviour but there is still room to improve knowledge and education for this group, according to a nationwide survey conducted by La Trobe University.

The sixth National Survey of Australian Secondary Students and Sexual Health, conducted in 2018 and released today, found 47 per cent of Year 10-12 students taking the survey had engaged in sexual intercourse. Of sexually active respondents, 76 per cent had sex at home; 65 per cent with a boyfriend or girlfriend; 62 percent often or always used a condom; and 86 per cent with somebody about the same age.

Lead researcher at La Trobe University's Australian Research Centre in Sex, Health and Society Dr Christopher Fisher said the survey asked 6327 Year 10-12 students in Government, Catholic and Independent schools from each state and territory, about their sexual behaviour and knowledge of sexually transmitted infections.

"Overall, young Australians have good knowledge of sexual health, are behaving responsibly and are actively seeking out trusted, reliable sources of information," Dr Fisher said.

He said more work is needed to help improve this age group's level of knowledge of HPV (the human papillomavirus) and viral hepatitis; to decrease reports of unwanted sexual behaviour; and to further increase rates of condom use.

"This survey has evolved over time and is a key tool to support and inform policies around sexual health education and disease prevention, but I hope our report helps bring awareness to the wider community as well," Dr Fisher said.

The survey, which started in 1992 and occurs every five years, is funded by the Commonwealth Department of Health. Dr Fisher said Australia is one of the few countries conducting such a study, making it significant internationally

"There are many positive findings, including that those young people who are not yet sexually active don't feel pressured to start having sex until they're ready. Also, young people turn to a wide variety of sources of information to educate themselves about sexual health in addition to getting sexual health information in the school system. GPs are the most trusted source of information by far followed by female friends and mothers," Dr Fisher said.

The survey's findings included:

Knowledge and Education

- 80 per cent answered questions about HIV correctly indicating a generally high awareness, largely unchanged since 2013 but down from 92 per cent in 1992

- 93 per cent believed they were at low or no risk of HIV infection, slightly up from 2013 at 95 percent

- 87 per cent did not believe they were likely to get an STI, largely unchanged since 1992

- 79 per cent accessed information about sexual health online almost doubled from 2013 at 44 per cent

- The most trusted source of sexual health information was GPs (89 per cent), followed by their mother (60 per cent)

- 71 per cent were confident talking about sexual health with female friends

- 84 per cent received Relationships and Sexual Education at school, similar to 2013

Behaviours

- Overall, 47 per cent had had intercourse, including 34 per cent of Year 10s, 46 per cent of Year 11s and 56 per cent of Year 12s

- 76 per cent of sexually active students had sex at home or their partner's home

- 77 per cent discussed sexual health before having sex

- 62 per cent of sexually active students had only one partner in the past year

- 53 per cent had not yet had sexual intercourse

- 89 per cent of those not yet sexually active did not regret their decision not to have sex yet

- 35 per cent of students indicated attraction to same or multiple genders

Media Contact: Kathryn Powley - k.powley@latrobe.edu.au +61 3 9479 3491 | +61 456 764 371

CORVALLIS, Ore. - Large-scale land transactions in which nations sell huge, publicly owned parcels to foreign and domestic corporations negatively affect local women more than men, a new study by Oregon State University shows.

The findings are important because the transactions, also known as land grabs, are occurring at a pace and scale that are unprecedented - at least 45 million hectares, and possibly as many as 200 million, have changed hands over the past decade, mainly in lower-income countries, OSU College of Forestry researcher Reem Hajjar said.

"Governments try to frame it as development of marginal or underutilized land," said Hajjar, assistant professor of forest ecosystems and society. "They say 'we're going to boost production, we're going to feed the country.' What we find is that these large-scale land transactions actually take food away from their own countrymen and women because the most successful transactions end up going to cash crops for export, like mango and sugar, resulting in poorer nutrition in the local area."

The large-scale land transactions, known as LSLTs, are not always for agricultural reasons. Tourism, commercial forestry, mining and even "green grabs" or "blue grabs" - land and water resources being acquired for environmental purposes - are other motivators for transactions that change residents' tenure over land and forests - the right to access, benefit from and/or control land-related resources.

In many places local communities have insecure tenure rights, meaning their customary or traditional rights over lands may not be recognized by statute, making it easier for governments to appropriate and sell off those lands to corporations.

Hajjar, collaborating with researchers at the University of Michigan, Arizona State University, the University of Copenhagen, and the Ethiopian Environment and Forest Research Institute, analyzed four LSLTs in western Ethiopia. They found that women in communities that lost access to lands suffered effects that were "more adverse and more severe" compared to the effects on men.

Big transactions tended to cause three main changes in land ownership and use in the study areas: Relocation and decrease in size of individually held private lands, where villagers plant crops for subsistence and to sell; loss of communal grazing lands; and loss of forests, either through deforestation by the investor or through the resettlement of villagers and their agricultural lands into forested areas. Compensation to villagers who lost land often didn't materialize.

Post-transaction, both women and men were left with few choices beyond working as day laborers on investors' lands to generate income to buy food they were no longer able to grow themselves, Hajjar said.

"People were transformed from being mostly self-sufficient, small-scale agriculture entrepreneurs into wage laborers," she said. "And jobs that were promised on the transacted lands were usually less abundant and less permanent than expected. Many husbands had to find work in town, leaving women to handle agricultural tasks on the increasingly small parcels of land the households still owned."

Women were also still expected to fulfill all of their previous domestic responsibilities, such as collecting firewood - which had to be done at sites significantly farther away following the land transactions - cooking, cleaning, and caring for children.

"With the men gone, women now raise children alone, adding to their daily labor burden," Hajjar said. "Female-headed households are particularly affected since the older male children leave home in search of work. The decrease in household-owned land that stems from the large-scale land transactions has shifted household labor in a way that has increased the burden on women, who have to work both as wage laborers while also juggling a bigger workload at home."

Women also bore the brunt of the transactions' impacts on community members' physical health.

"The subsequent decreases in food availability hit women harder because they're primarily responsible for providing food for their household," Hajjar said. "Women will often respond to shortages by eating less to ensure men and children are fed. Loss of communal grazing lands often meant that households would go with less meat and dairy products since they couldn't support livestock on remaining lands."

Evidence for the ancient, 1.2 billion years old, meteorite strike, was first discovered in 2008 near Ullapool, NW Scotland by scientists from Oxford and Aberdeen Universities. The thickness and extent of the debris deposit they found suggested the impact crater - made by a meteorite estimated at 1km wide - was close to the coast, but its precise location remained a mystery.

In a paper published today in Journal of the Geological Society, a team led by Dr Ken Amor from the Department of Earth Sciences at Oxford University, show how they have identified the crater location 15-20km west of a remote part of the Scottish coastline. It is buried beneath both water and younger rocks in the Minch Basin.

Dr Ken Amor said: 'The material excavated during a giant meteorite impact is rarely preserved on Earth, because it is rapidly eroded, so this is a really exciting discovery. It was purely by chance this one landed in an ancient rift valley where fresh sediment quickly covered the debris to preserve it.

'The next step will be a detailed geophysical survey in our target area of the Minch Basin.'

Using a combination of field observations, the distribution of broken rock fragments known as basement clasts and the alignment of magnetic particles, the team was able to gauge the direction the meteorite material took at several locations, and plotted the likely source of the crater.

Dr Ken Amor said: 'It would have been quite a spectacle when this large meteorite struck a barren landscape, spreading dust and rock debris over a wide area.'

1.2 billion years ago most of life on Earth was still in the oceans and there were no plants on the land. At that time Scotland would have been quite close to the equator and in a semi-arid environment. The landscape would have looked a bit like Mars when it had water at the surface.

Earth and other planets may have suffered a higher rate of meteorite impacts in the distant past, as they collided with debris left over from the formation of the early solar system.

However, there is a possibility that a similar event will happen in the future given the number of asteroid and comet fragments floating around in the solar system. Much smaller impacts, where the meteorite is only a few meters across are thought to be relatively common perhaps occurring about once every 25 years on average.

It is thought that collisions with an object about 1 km (as in this instance) across occur between once every 100,000 years to once every one million years - but estimates vary.

One of the reasons for this is that our terrestrial record of large impacts is poorly known because craters are obliterated by erosion, burial and plate tectonics.

The following papers will be presented at the ADA conference in San Francisco and published simultaneously in either The Lancet or The Lancet Diabetes & Endocrinology journals. All papers are under embargo until the stated time. Contact details for corresponding authors are provided in the Articles and linked Comments. Funding information is listed on the first page of each Article.

Embargo: 16.45hrs [UK time] / 8.45am [San Francisco time] Saturday 8th June 2019
The Lancet: Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial

Once the embargo lifts, please use this link as the one above will be deactivated: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31271-1/fulltext

Embargo: 16.45hrs [UK time] / 8.45am [San Francisco time] Sunday 9th June 2019
The Lancet Diabetes and Endocrinology: Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes (DUAL VIII): a multicentre, open-label, phase 3b, randomised controlled trial

Once the embargo lifts, please use this link as the one above will be deactivated: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30184-6/fulltext

Embargo: 20.00hrs [UK time] / 12.00 (midday) [San Francisco time] Sunday 9th June 2019
The Lancet Diabetes and Endocrinology: Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial

Once the embargo lifts, please use this link as the one above will be deactivated: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30192-5/fulltext

Embargo: 20.00hrs [UK time] / 12.00 (Midday) [San Francisco time] Sunday 9th June 2019
The Lancet Diabetes and Endocrinology: Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial

Once the embargo lifts, please use this link as the one above will be deactivated: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30194-9/fulltext

Embargo: 22.15hrs [UK time] / 2.15pm [San Francisco time] Sunday 9th June 2019
The Lancet Diabetes and Endocrinology: Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial

Once the embargo lifts, please use this link as the one above will be deactivated: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30180-9fulltext **Please note this hyperlink will go live after the embargo lifts on the morning of Monday 10th June UK time**

Embargo: 00.30hrs [UK time] Monday 10th June / 16.30pm [San Francisco time] Sunday 9th June 2019
The Lancet: Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial

Once the embargo lifts, please use this link as the one above will be deactivated: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext

Embargo: 00.30hrs [UK time] Monday 10th June / 16.30pm [San Francisco time] Sunday 9th June 2019
The Lancet: Dulaglutide and renal outcomes in type 2 diabetes:an exploratory analysis of the REWIND randomised, placebo-controlled trial

Once the embargo lifts, please use this link as the one above will be deactivated: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31150-X/fulltext