Culture

Scripps Research scientists have developed a powerful new strategy for synthesizing molecular skeletons of chemicals used in drugs and other important products, a technique that provides unprecedented flexibility and control over chemical synthesis, according to a paper published July 30 in Nature.

The method, which combines two chemical reactions used to build molecular rings and link together sections of complex molecules, could speed the discovery of new drugs by offering the ability to simply and efficiently build a wide variety of molecular architectures. It also promises to provide a versatile option for synthesizing natural products from the ground up in the laboratory.

The Scripps team, led by Phil Baran, PhD, brought together two long-standing ways of constructing molecules, C-C cross coupling and cycloaddition, providing an elegant sequence of chemical reactions that harnessed the benefits of each method.

"Chemists have long had to choose between these two stalwart reaction classes, both presenting marked advantages, but also shortcomings," say Baran, holder of the Darlene Shiley Chair in Chemistry at Scripps Research. "Combining these two reactions solves this dichotomy by leveraging the strengths of both to provide a reliable and versatile strategy for producing complex molecules."

C-C cross coupling, a bond-forming method that is highly reliable and controllable, has long been the method of choice in the pharmaceutical industry for synthesizing the skeletons of drug candidates. However, the method is limited in its ability to construct complex three-dimensional architectures, resulting in a disproportionate number of flat drug molecules--a characteristic that potentially presents a hurdle to creating new drugs for increasingly difficult biological targets. Cycloaddition reactions, in contrast, offer the ability to build highly complex 3D shapes in a single step, but different types cycloaddition reactions required highly customized preparation, which limited their utility.

The compound epibatidine, a molecule studied as a potential pain medication, is an example of a complex molecule that has been synthesized using cycloaddition. The blood pressure medicine Cozaar, a drug much simpler in shape, was discovered and is manufactured using C-C cross coupling. Baran and his team sought to develop a way to build the skeletons of such molecules in a way that merged the complexity generating ability of cycloaddition with the reliability and versatility of C-C cross coupling.

To do this, they solved the conundrum of choosing one reaction over the other by using them together. Their new strategy overcomes a number of hurdles to synthesize molecules in a stepwise fashion, beginning by building a molecular scaffold using cycloaddition, setting its 3D shape and then use of C-C cross coupling to connect other molecular entities to the cycloaddition-built scaffold.

The Scripps team reports using their new method to construct more than 80 examples of complex molecules, including natural products (including epibatidine) and compounds currently produced at industrial scale but with different methods. In many cases, the technique offered advantages in terms of fewer steps, greater yield and the ability to produce a wider variety of forms of certain molecules.

The researcher was funded by LEO Pharma and the National Institutes of Health (Grant: GM-118176).

In addition to the Nature paper, Baran also penned an article providing context to the new technique in Accounts of Chemical Research.

Men who wear boxer shorts have higher sperm concentrations than men who wear tighter fitting underwear, according to new research published today (Wednesday) in Human Reproduction [1], one of the world's leading reproductive medicine journals.

The researchers also found that boxer shorts-wearing men had lower levels of follicle-stimulating hormone (FSH), compared to men who most frequently wore briefs, "bikinis" (very brief briefs), "jockeys" (underwear that finishes just above the knee) or other tight-fitting underwear. FSH stimulates sperm production and the researchers say that these findings suggest that it kicks into gear when it needs to compensate for testicular damage from increasing scrotal temperatures and decreasing sperm counts and concentration.

The study differs from previous research on this topic because it includes a larger number of men (656) than previous studies, and because it is the first to go beyond the traditional, narrow focus on semen quality and include information on a variety of indicators of testicular function, such as reproductive hormones and sperm DNA damage. These can help in understanding how choices of underwear affect the key regulator of sexual development and reproduction, the hypothalamic-pituitary-gonadal axis.

The researchers, led by Dr Lidia Mínguez-Alarcón, a research scientist at Harvard T.H. Chan School of Public Health (Boston, USA), recruited the male partners of couples who were seeking infertility treatment at the Massachusetts General Hospital between 2000 and 2017. The men were aged between 18 and 56, had an average body mass index (BMI) of 26, and had not had vasectomies. Each of them provided a semen sample and blood sample on the same day, and they answered a questionnaire that asked about the style of underwear they wore most frequently in the preceding three months.

Among the 656 men, 53% (345) reported that they usually wore boxer shorts. They tended to be younger, slimmer and more likely to take hot baths or Jacuzzis than the men who wore other, more tightly fitting underwear.

Men who primarily wore boxer shorts had a statistically significant 25% higher sperm concentration, 17% higher total sperm count, 33% more swimming sperm in a single ejaculate and 14% lower FSH levels than men who did not usually wear boxers, after adjusting for factors that might affect the results, such as BMI, physical activity, hot baths and Jacuzzis, smoking and the year the sample was taken [2]. In addition, more sperm were correctly shaped, although this result was not statistically significant.

The greatest difference in sperm concentration was found between men wearing boxer shorts most frequently and men wearing jockeys or briefs.

There were no significant differences in other reproductive hormones or damage to the DNA of the sperm. When the researchers adjusted their results to take account of reproductive hormones, apart from FSH, they found the adverse effect of tighter underwear on sperm quality remained. However, when they adjusted for FSH levels, the effect was no longer significant. This suggested to them that it was the damage to sperm concentrations and total sperm count associated with wearing tighter underwear that could be responsible for the changes in FSH levels.

Dr Mínguez-Alarcón said: "An important strength of this study is that we were able to investigate the potential relationship between the type of underwear worn and indicators of testicular function such as reproductive hormone levels and DNA damage, which were missing in all previous studies on the topic. Because of this, we were able to find a potential compensatory mechanism whereby decreased sperm production relating to the type of underwear signals to the hypothalamus to increase secretion of gonadotropin, a hormone that acts on the testes and that is reflected by the increased levels of FSH, to try to increase sperm production. This hypothesis requires confirmation by further research."

The researchers point out that it may not be possible to generalise the findings of their study to all men as the study focused on men attending a fertility centre. However, the men in this study tended to have good semen quality when compared to the World Health Organization's reference standards. It is also not possible to prove from these findings that the type of underwear causes the difference in semen quality and FSH levels, only that that there is an association between them. Other factors that might affect scrotal heat, such as type of trousers (e.g. skinny jeans) and underwear fabric, could also affect the results.

Dr Mínguez-Alarcón concluded: "Since men can modify the type of underwear they choose to wear, these results may be useful to improve men's testicular function."

Whereas ESO's Very Large Telescope (VLT) can observe very faint astronomical objects in great detail, when astronomers want to understand how the huge variety of galaxies come into being they must turn to a different sort of telescope with a much bigger field of view. The VLT Survey Telescope (VST) is such a telescope. It was designed to explore vast swathes of the pristine Chilean night skies, offering astronomers detailed astronomical surveys (https://www.eso.org/public/teles-instr/paranal-observatory/surveytelescopes/vst/surveys/ ) of the southern hemisphere.

The powerful surveying properties of the VST led an international team of astronomers to conduct the VST Early-type GAlaxy Survey (VEGAS) [1] to examine a collection of elliptical galaxies in the southern hemisphere [2]. Using the sensitive OmegaCAM detector at the heart of the VST [3], a team led by Marilena Spavone from INAF-Astronomical Observatory of Capodimonte in Naples, Italy, captured images of a wide variety of such galaxies in different environments.

One of these galaxies is NGC 5018, the milky-white galaxy near the centre of this image. It lies in the constellation of Virgo (The Virgin) and may at first resemble nothing but a diffuse blob. But, on closer inspection, a tenuous stream of stars and gas -- a tidal tail -- can be seen stretching outwards from this elliptical galaxy. Delicate galactic features such as tidal tails and stellar streams are hallmarks of galactic interactions, and provide vital clues to the structure and dynamics of galaxies.

As well as the many elliptical (and a few spiral) galaxies in this remarkable 400-megapixel image, a colourful variety of bright foreground stars in our own Milky Way Galaxy also pepper the image. These stellar interlopers, such as the vividly blue HD 114746 near the centre of the image, are not the intended subjects of this astronomical portrait, but happen to lie between the Earth and the distant galaxies under study. Less prominent, but no less fascinating, are the faint tracks left by asteroids in our own Solar System. Just below NGC 5018, the faint streak left by the asteroid 2001 TJ21 (110423) -- captured over several successive observations -- can be seen stretching across the image. Further to the right, another asteroid -- 2000 WU69 (98603) -- left its trace in this spectacular image.

While astronomers set out to investigate the delicate features of distant galaxies millions of light-years from Earth, in the process they also captured images of nearby stars hundreds of light-years away, and even the faint trails of asteroids only light-minutes away in our own Solar System. Even when studying the furthest reaches of the cosmos, the sensitivity of ESO telescopes and dark Chilean skies can offer entrancing observations much closer to home.

Alzheimer's disease is difficult to diagnose as well as treat, but researchers now have a promising new screening tool using the window to the brain: the eye.

A study of 3,877 randomly selected patients found a significant link between three degenerative eye diseases - age-related macular degeneration, diabetic retinopathy and glaucoma - and Alzheimer' disease.

The results offer physicians a new way to detect those at higher risk of this disorder, which causes memory loss and other symptoms of cognitive decline. .

The researchers, from the University of Washington School of Medicine, the Kaiser Permanente Washington Health Institute and the UW School of Nursing, reported their findings Aug. 8 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

"We don't mean people with these eye conditions will get Alzheimer's disease," said lead researcher Dr. Cecilia Lee, assistant professor of ophthalmology at the UW School of Medicine. "The main message from this study is that ophthalmologists should be more aware of the risks of developing dementia for people with these eye conditions and primary care doctors seeing patients with these eye conditions might be more careful on checking on possible dementia or memory loss."

The participants in the study were age 65 and older and did not have Alzheimer's disease at the time of enrollment. They were part of the Adult Changes in Thought database started in 1994 by Dr. Eric Larson, who is at Kaiser Permanente Washington Health Research Institute. Over the five-year study, 792 cases of Alzheimer's disease were diagnosed by a committee of dementia experts. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40 % to 50% greater risk of developing Alzheimer's disease compared to similar people without these eye conditions. Cataract diagnosis was not an Alzheimer's disease risk factor.

"What we found was not subtle," said Dr. Paul Crane, professor of medicine, Division of General Internal Medicine, at the UW School of Medicine. "This study solidifies that there are mechanistic things we can learn from the brain by looking at the eye."

More than 46 million older adults are affected by dementia worldwide and 131.5 million cases are expected by 2050, the researchers said. Alzheimer' disease is the most common dementia,and discovering risk factors may lead to early detection and preventive measures, they said in their paper.

Lee said anything happening in the eye may relate to what's happening in the brain, an extension of the central nervous system. The possible connections need more study. She said a better understanding of neurodegeneration in the eye and the brain could bring more success in diagnosing Alzheimer's early and developing better treatments.

The researchers said several factors suggest the effects they uncovered were specific to ophthalmic conditions and not merely age-related phenomenon.

Larson said for years Alzheimer's researchers were focused on amyloid buildup in brain tissue, but that hasn't brought much benefit to patients.

"This paper is pointing to a new area of opportunity," he said.

A new study shows that men only have to believe they've bested another man in competition to get raised testosterone levels and an inflated sense of their own value as a sexual prospect.

Scientists found that this hormonal and psychological shift made men more inclined to approach new potential partners.

The research team measured hormone levels, as well as self-perceived attractiveness and confidence in approaching women, in 38 men in their twenties before and after competing in head-to-head battles on rowing machines.

Unbeknownst to participants, the competitions in the study were rigged to randomly declare the winner, regardless of who was the stronger rower.

While previous studies have shown that winning can affect male hormones, it was not known whether this was down to the efforts it takes to win or the belief that one is victorious.

The latest study, led by biological anthropologists from the University of Cambridge and published today in the journal Human Nature, reveals that just being convinced you have won, or indeed lost, is enough to cause male hormonal fluctuations that can influence sexual behaviour.

Researchers say this is an example of "plasticity": the body adapting quickly - without altering genetic make-up - to suit a change in circumstance. In this case a perceived change in social status, due to the men believing they have defeated a rival.

The body attempts to take advantage of this apparent status improvement by inducing chemical and consequently behavioural changes that promote a "short-term" approach to reproductive success, say the researchers. Namely, more sex with new and different partners.

"Much of evolution consists of trade-offs in energy investment," said study lead author Dr Danny Longman, from Cambridge's Department of Archaeology.

"A common trade-off for males both across and within species is between mating strategies. One reproductive approach is short-term, investing time and energy in attracting and pursuing many mates, and fighting off competition. Another approach is long-term, investing energy in raising offspring with a single mate."

"We found that a perceived shift in social status can cause male physiology to adapt by preparing to shift mating strategies to optimise reproductive success."

Longman points out that in many animal populations, male social hierarchies correspond with reproductive success, and social status is determined by competition between males.

The study used a simple proxy for social and sexual competition by pitting athletic young men against each other to see who was the most powerful rower.

"Victory in a rowing contest strongly implies the possession of greater physical strength than the opponent, a trait found to be valued by women in our evolutionary past when choosing a mate," said Longman.

He took saliva samples to test hormone levels before and after the races. A number of psychological questionnaires were also administered, designed to gauge self-esteem, 'sociosexuality' (willingness to engage in casual sex), 'self-perceived mate value' and mating behaviour (e.g. the likelihood of approaching attractive women). Crucially, Longman and colleagues then manipulated the results of the races.

The men who believed they had won received an average testosterone increase of 4.92%, while those convinced they had lost dropped by an average of 7.24%. Overall, men who thought they were winners had testosterone levels 14.46% higher their deflated opponents.

The men who thought they had lost showed no difference in their perceived value as a mate or confidence approaching women. However, the men who felt like winners had a 'self-perceived mate value' that was 6.53% higher, on average, than their rivals, and were 11.29% more likely to approach attractive women in an effort to instigate sexual relations.

"The endocrine system that controls hormones is responsive to situational changes. Previous research has shown that testosterone is lower when men are in a committed relationship, or have children, to promote long-term mating strategies," said Longman.

"Our results show that both testosterone and its corresponding psychological effects can fluctuate quickly and opportunistically, shifting towards short-term mating in response to a perceived change in status that may increase mating value."

Male social status has less to do with physical strength in many modern societies, and Longman would be curious to see if similar results arise from intellectual challenges more familiar to the office-based culture many men now inhabit. There is always the issue of free will, however.

"Male physiology may shift to take advantage of certain situations, but ultimately a man's decisions are up to him."

ANN ARBOR, Mich. - New Medicaid rules in several states mean low-income people will have to work, or prove they're too unhealthy to work, to receive health coverage. Other states want permission to require the same, which could affect millions of Americans living in or near poverty.

Before these requirements get into full gear, a team of University of Michigan researchers is offering specific recommendations to help states ensure that work requirements don't harm the health of people enrolled in Medicaid.

The chance of such harm from losing Medicaid coverage forms the basis of a court case that has put Kentucky's Medicaid work requirement on hold and led to a public comment period that closes August 18.

The U-M team, which has studied Medicaid for years, published their recommendations in the New England Journal of Medicine. Their prior work on Michigan's Medicaid expansion showed that half of enrollees already work, and many others have health problems that limit their ability to work.

"We wanted to address the essential question: 'If we're going to have work requirements, then how can states implement them in the most humane way, so that the requirements focus on those who are more able to work and are less likely to experience worsening health if they lose coverage?'," asks John Z. Ayanian, M.D., M.P.P., lead author of the article and director of the U-M Institute for Healthcare Policy and Innovation. "We based our recommendations on the evidence we have about the current Medicaid expansion population. We hope state policymakers will take our recommendations into account as they seek to create reasonable, sustainable programs."

Ayanian and his co-authors are all general internal medicine physicians who provide primary care to patients at Michigan Medicine, U-M's academic medical center. Their recommendations focus in part on the new role that physicians would play in states that implement Medicaid work requirements.

The team recommends that states:

Focus on adults under age 50 who enrolled in Medicaid expansions. Compared to people over 50 and those under 50 whose health problem are serious enough to qualify them for traditional Medicaid, this population is less likely to suffer harm if the state bases their health insurance on their ability to work, or do another activity such as volunteering, attending school, undergoing addiction treatment or caring for a relative with a seriously illness or disability. That's because research has shown they are less likely to have chronic health conditions or limits on their everyday function that could get worse if they lose their health insurance because they don't meet a work requirement. The team notes that Arkansas, which implemented a Medicaid work requirement June 1, already follows this recommendation.

Give doctors clear guidance. While doctors already play a key role in some certifications related to their patients' disability status or ability to do certain jobs, Medicaid work requirements would ramp up that role to include many more patients. So, states should make it clear to physicians exactly what health conditions and functional limits will make someone exempt from a work requirement - or what limitations a person must have in order to require the level of caregiving that a family member could provide in order to meet their work requirement. In the latter case, the physician certifying a patient's level of disability or need for caregiving could affect the health insurance coverage for the patient's caregiver - someone not in their direct care. The new requirements may increase the workload for physicians and their staff appreciably.

Support work-related needs. Although the Medicaid system itself cannot pay using federal funds for services such as job training, help finding a job, or help getting to and from work or caring for children while a parent works, states that require work should connect Medicaid enrollees to such services, the team says. Such services would improve the odds that people covered by Medicaid will be able to find and keep jobs that will allow them to meet their state requirement, or even find a job that pays enough or provides health insurance benefits so that they no longer need Medicaid.

Make work reporting line up with today's work environment. As more workers have work patterns with hours that fluctuate week to week, have occasional gaps due to temporary jobs, or work that is concentrated in certain seasons, states should take this into account in their Medicaid reporting requirements, the team says. Requiring that participants report their work histories less frequently, covering a longer period of time, could smooth out these fluctuations and reduce the chance that a person who is making an effort to work will have to leave the Medicaid program.

Ayanian and co-authors Renuka Tipirneni, M.D., M.S., and Susan Goold, M.D., M.A., M.H.S.A., note that as work requirements become more widespread as part of ongoing or new Medicaid expansion programs, the details of implementation will become more important. All are faculty members in the Division of General Internal Medicine at the U-M Medical School, and members of IHPI.

"If the goal is to help people improve their economic standing in life and become self-sufficient, they'll need support to do so," says Ayanian, who also holds faculty appointments in the U-M Ford School of Public Policy and School of Public Health. "States should prevent potential harm that will arise if people with chronic conditions lose their Medicaid coverage, and therefore their access to health care providers and medications, especially if the economy changes."

Adds Goold, "If the goal is to provide a 'leg up' to economic self-sufficiency rather than a 'hand out,' providing health insurance through Medicaid is just one piece of providing such support. Child care, transportation, education and training, as well as health issues, present obstacles to self-sufficiency."

A study of 1.2 million people in the USA has found that people who exercise report having 1.5 fewer days of poor mental health a month, compared to people who do not exercise. The study found that team sports, cycling, aerobics and going to the gym are associated with the biggest reductions, according to the largest observational study of its kind published in The Lancet Psychiatry journal.

More exercise was not always better, and the study found that exercising for 45 minutes three to five times a week was associated with the biggest benefits.

The study included all types of physical activity, ranging from childcare, housework, lawn-mowing and fishing to cycling, going to the gym, running and skiing.

Exercise reduces the risk of cardiovascular disease, stroke, diabetes, and mortality from all causes, but its association with mental health remains unclear.

Previous research into the effect of exercise on mental health has conflicting results. While some evidence suggests that exercise may improve mental health, the relationship could go both ways - for example inactivity could be a symptom of and contributor to poor mental health, and being active could be a sign of or contribute to resilience. The authors note that their study cannot confirm cause and effect.

"Depression is the leading cause of disability worldwide, and there is an urgent need to find ways to improve mental health through population health campaigns," says Dr Adam Chekroud, Assistant Professor of Psychiatry at Yale University, and Chief Scientist at Spring Health, USA. "Exercise is associated with a lower mental health burden across people no matter their age, race, gender, household income and education level. Excitingly, the specifics of the regime, like the type, duration, and frequency, played an important role in this association. We are now using this to try and personalise exercise recommendations, and match people with a specific exercise regime that helps improve their mental health." [1]

In the study, the authors used data from 1.2 million adults across all 50 US states who completed the Behavioural Risk Factor Surveillance System survey in 2011, 2013, and 2015. This included demographic data, as well as information about their physical health, mental health, and health behaviours. The study did not take mental health disorders into account, other than depression.

Participants were asked to estimate how many days in the past 30 days they would rate their mental health as 'not good' based on stress, depression and emotional problems. They were also asked how often they took part in exercise in the past 30 days outside of their regular job, as well as how many times a week or month they did this exercise and for how long.

All results were adjusted for age, race, gender, marital status, income, education level, employment status, BMI, self-reported physical health and previous diagnosis of depression.

On average, participants experienced 3.4 days of poor mental health each month.

Compared to people who reported doing no exercise, people who exercised reported 1.5 fewer days of poor mental health each month - a reduction of 43.2% (2.0 days for people who exercised vs 3.4 days for people who did not exercise).

The reduction in number of poor mental health days was larger for people who had previously been diagnosed with depression, where exercise was associated with 3.75 fewer days of poor mental health compared with people who did not exercise - equivalent to a 34.5% reduction (7.1 days for people who exercised vs 10.9 days for people who did not exercise).

Overall, there were 75 types of exercise recorded and these were grouped into eight categories - aerobic and gym exercise, cycling, household, team sports, recreational activity [2], running and jogging, walking, and winter or water sports.

All types of exercise were associated with improved mental health, but the strongest associations for all participants were seen for team sports, cycling, aerobic and gym exercise (reduction in poor mental health days of 22.3%, 21.6%, and 20.1%, respectively).

Even completing household chores was associated with an improvement (reduction in poor mental health days of around 10%, or around half a day less each month).

The association between exercise and improved mental health (a 43.2% reduction in poor mental health) was larger than many modifiable social or demographic factors. For example, people with a college education had a 17.8% reduction in poor mental health days compared with people with no education, people with normal BMI had a 4% reduction compared with people who were obese, and people earning more than US$50,000 had a 17% reduction compared with people earning less than US$15,000.

How often and for how long people completed exercise was also an important factor. People who exercised between three and five times a week had better mental health than people who exercised less or more each week (associated with around 2.3 fewer days of poor mental health compared with people who exercised twice a month).

Exercising for 30-60 minutes was associated with the biggest reduction in poor mental health days (associated with around 2.1 fewer days of poor mental health compared with people who did not exercise). Small reductions were still seen for people who exercised more than 90 minutes a day, but exercising for more than three hours a day was associated with worse mental health than not exercising at all. The authors note that people doing extreme amounts of exercise might have obsessive characteristics which could place them at greater risk of poor mental health.

"Previously, people have believed that the more exercise you do, the better your mental health, but our study suggests that this is not the case. Doing exercise more than 23 times a month, or exercising for longer than 90 minute sessions is associated with worse mental health," continues Dr Chekroud. [1]

"Our finding that team sports are associated with the lowest mental health burden may indicate that social activities promote resilience and reduce depression by reducing social withdrawal and isolation, giving social sports an edge over other kinds." [1]

The study used people's self-reported assessment of their mental health and exercise levels so could be subject to bias. It also only asked participants about their main form of exercise so could underestimate the amount of exercise they do if they do more than one type.

Writing in a linked Comment, Dr Gary Cooney, Gartnavel Royal Hospital, UK, says: "There is gathering interest and momentum around research into exercise as a treatment for mental health disorders. The appeal is multifaceted: patients, particularly those reluctant to pursue medication or psychological approaches, are drawn to the self efficacy of exercise, the ability to attain a degree of agency in their own process of recovery. Mental health professionals, for their part, recognise the urgent need to address the comparatively poor physical health outcomes in the psychiatric patient population. With very high rates of physical comorbidity, and marked reductions in life expectancy, an intervention that might improve both mental and physical health is of particular clinical interest."

San Antonio, TX (August 8, 2018) - A new study at Texas Biomedical Research Institute is shedding light on the role of specific proteins that trigger a mechanism allowing Ebola virus to enter cells to establish replication. The work, published in a supplement to The Journal of Infectious Diseases, was led by Staff Scientist Olena Shtanko, Ph.D., in Texas Biomed's Biosafety Level 4 laboratory. The BSL4 is a high-containment facility that houses research on diseases for which there are no approved vaccines or cures.

The new outbreak of the deadly Ebola virus declared just last week in eastern Democratic Republic of Congo is believed to have claimed more than 30 victims so far, highlighting the continued urgency to find a way to stop the pathogen from killing the people it infects.

The cellular pathway under study is called autophagy, a word that literally means "self-eating." This ancient mechanism is switched on by cells to destroy invading foreign material or consume its own organelles and protein complexes in order to recycle nutrients and survive. Autophagy generally takes place inside the cell. Conducting in vitro work using live Ebola virus, Dr. Shtanko found that, surprisingly, this mechanism was clearly active near the surface of the cells and plays an essential role in facilitating virus uptake.

Ebola virus invades cells though macropinocytosis, a poorly understood process in which the cell surface remodels to form membrane extensions around virions (virus particles), eventually closing to bring them into the interior of the cell. "We were stunned to find that Ebola virus is using autophagy regulators right at the surface of the cell," Shtanko said. "Knowing that these mechanisms work together, we can start finding ways to regulate them."

The interplay between these two cellular processes could have implications for treatment of health conditions other than viruses. Shtanko believes that regulation of the autophagy proteins with a drug could help combat complex diseases where macropinocytosis is dysregulated such as in cancer and certain neurodegenerative disorders, including Alzheimer's.

"The work is a great example of serendipity," said Scientist Rob Davey, a co-author on the study. "Few would have thought that working on Ebola virus would reveal something truly new about how the cell works."

A study published today in the International Journal of Health Services finds that immigrants use far less health care than non-immigrants, and may actually subsidize the care of U.S. citizens. The findings by researchers at Harvard Medical School and Tufts University School of Medicine contradict recent claims by Pres. Trump and other political leaders that immigrants drive up U.S. medical costs.

Researchers examined all studies published since 2000 related to health care expenditures by immigrants. Compared to U.S.-born individuals, immigrants were found to have lower rates of utilization and lower per capita expenditures from private and public insurance sources; health expenditures were particularly low for undocumented immigrants. Across all age groups, immigrants' utilization was only one-half to two-thirds as high as that of the U.S.-born population. Immigrants also made larger out-of-pocket health care payments compared to those born in the U.S.

Researchers concluded that as a group, immigrants effectively subsidized private insurance and some public insurance programs such as Medicare because they constitute a low-risk pool that pays more into the system (by way of premiums and tax contributions) than is paid out for their care.

"Immigrants have been blamed for a range of problems plaguing the U.S., including health care costs," said study author Lila Flavin, a medical student at Tufts University School of Medicine. "But studies demonstrate that immigrants are propping up the Medicare Trust Fund by paying much more into Medicare than they will ever receive in benefits. Recent immigrants are substantially healthier than native-born Americans, which benefits the American health care economy. But to maintain their health over the long term, new immigrants -- and all Americans -- need access to good health care. Denying care to immigrants is a human rights violation that cannot be justified based on costs, and indeed may raise costs in the future."

Senior author Dr. J. Wesley Boyd, a psychiatrist at Cambridge Health Alliance and associate professor of psychiatry at Harvard Medical School and Harvard's Center for Bioethics added, "Our findings show that immigrants are clearly bringing down per capita health care costs and are likely subsidizing care for native-born Americans. Instead of attacking immigrants for driving up costs, we should recognize their proven economic contributions."

A new Biofuels, Bioproducts and Biorefining study has found that using ethanol from corncobs for energy production may help reduce greenhouse gas emissions in China, if used instead of starch-based ethanol.

China has committed to limiting its emissions by 2030, and biofuel is considered the key to lower emissions from transportation. The authors note that corncobs are abundant agriculture residues, and the government should provide stronger incentives to encourage the industry to invest in corncob ethanol.

"Our life-cycle assessment suggests that corncob ethanol emits about 50% less greenhouse gas than corn ethanol," said co-author Dr. Yu Wang, of Iowa State University.

US study confirms effectiveness of quadrivalent human papillomavirus (HPV) vaccine in women aged up to 20 years who receive all three doses, but more research is needed in women aged 21-26 years.

For women aged 14-20 years, catch-up HPV vaccination - offered if American women miss the recommended vaccination series at 11-12 years - is effective against the risk of important cervical precancers if women receive all three doses, according to a population case-control study of over 25000 people published in The Lancet Child & Adolescent Health journal.

The study analysed cases of CIN2+ or CIN3+ (cervical intraepithelial neoplasia - abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer) in a population of women and girls in California (USA).

In the USA, HPV vaccination is recommended for girls aged 11-12. For those who did not receive the vaccine at this age, catch-up vaccination is recommended for girls and women aged 13-26 years. The vaccine is approved as a three-dose series, and the US Centers for Disease Control and Prevention also allows for a two-dose series for girls aged 9-14.

However, rates of adolescent HPV vaccination are relatively low in the USA, with less than half of girls aged 13-17 years up to date with the HPV vaccine series. [1]

The findings of the new study suggest catch-up with the full three-dose series for girls and women who receive the first dose at age 14-20 years will offer significant protection. However, they find that more research is needed to confirm the effectiveness of catch-up vaccination in older women aged 21-26 years.

Importantly, the study looked at the effectiveness of the quadrivalent HPV vaccine, and not of the more recently introduced nonavalent HPV vaccine, which is anticipated to prevent more CIN2+ cases than the quadrivalent HPV vaccine. Therefore, further research, including in women aged over 21 years, will be important as new vaccines become more widely used.

The study included 4357 women with CIN2+ or CIN3+ who were aged 26 or younger when the quadrivalent HPV vaccine was introduced in 2006. For each case, five age-matched controls without CIN2+ or CIN3+ were randomly selected (21773). All women were enrolled at Kaiser Permanente North California. A total of 2837 women enrolled in the study had received at least one dose of the vaccine between 2006 and 2014.

The strongest protection against CIN2+ and CIN3+ was identified for women who had received at least three vaccine doses and had received their first dose aged 14-17 years, or aged 18-20 years. No significant protection was found in women who received their first dose aged 21 years or older, or who received fewer than the full three dose in the series.

"In comparison to other countries, HPV vaccine uptake in the US has been relatively low. Our findings show that girls and women who did not receive the full vaccine series at age 11-12 can still benefit from significant protection if they receive the full three doses of vaccine by the age of 20. The evidence suggests that protection is strongest the earlier the vaccine is initiated, and after the age of 21, the evidence of effectiveness is unclear. Further research in other settings, and using the recently introduced nonavalent vaccine, will now be needed to assess the effectiveness of vaccinating women aged 21-26 years," says lead author Michael J. Silverberg, a research scientist with Kaiser Permanente Northern California's Division of Research, Oakland (USA). [2]

The authors note that only 23 women were diagnosed with cervical cancer in the study, of which only 3 had had prior HPV vaccination. All three women had received at least three doses, and all were 21 or older at the age of the first dose. However, the small numbers limit the researchers' ability to quantify the effect of the HPV vaccine on cervical cancer incidence, rather than the composite outcomes of CIN2+ and CIN3+, which includes both cancer and precancerous lesions.

Additionally, the authors note that the study was conducted in a single health-care setting, meaning that it may only be generalizable to other integrated health care settings and insured women in the area, which may not represent the most at-risk populations. The study did not look at the effect of the HPV vaccine on other clinically important outcomes such as low-grade dysplasia (i.e., CIN1), persistent HPV infection, or genital warts.

Writing in a linked Comment, Sarah Dilley and Warner Huh, Division of Gynecologic Oncology, University of Alabama, Birmingham (USA) advise caution before abandoning the practice of catch-up vaccination in women aged over 21 years: "The results of this study confirm existing research which showed that the HPV vaccine is most effective when given at younger ages, but no benefit was found in patients older than 21 years. Efforts towards increasing HPV vaccine uptake should be focused on younger adolescents--with a priority on vaccinating children aged 11-12 years - and providing catch-up dosing for older adolescents. However, in the setting of low rates of HPV vaccination in the USA, the importance of catch-up dosing in young women should not be ignored. Given that prospective efficacy studies have shown benefits for catch-up vaccination up to at least age 26 years, more data is needed before abandoning this practice."

Forty-four planets in solar systems beyond our own have been unveiled in one go, dwarfing the usual number of confirmations from extrasolar surveys, which is typically a dozen or less. The findings will improve our models of solar systems and may help researchers investigate exoplanet atmospheres. Novel techniques developed to validate the find could hugely accelerate the confirmation of more extrasolar planet candidates.

An international team of astronomers pooled data from U.S. space agency NASA's Kepler and the European Space Agency (ESA)'s Gaia space telescopes, as well as ground-based telescopes in the U.S. Alongside John Livingston, lead author of the study and a graduate student at the University of Tokyo, the team's combined resources led to the confirmed existence of these 44 exoplanets and described various details about them.

A portion of the findings yield some surprising characteristics: "For example, four of the planets orbit their host stars in less than 24 hours," says Livingston. "In other words, a year on each of those planets is shorter than a day here on Earth." These contribute to a small but growing list of "ultrashort-period" planets, so it could turn out they're not as unusual as they might seem.

"It was also gratifying to verify so many small planets," continues Livingston. "Sixteen were in the same size class as Earth, one in particular turning out to be extremely small -- about the size of Venus -- which was a nice affirmation as it's close to the limit of what is possible to detect."

The source observations for this study were made by Kepler, and they would not have happened were it not for a fault in 2013, which prevented accurate control of the space telescope. "Two out of the four control-reaction wheels failed, which meant Kepler couldn't perform its original mission to stare at one specific patch of the sky," explains Professor Motohide Tamura of the University of Tokyo. "This led to its contingent mission, 'K2' -- our observations came from campaign 10 of this mission. We're lucky Kepler continues to function as well as it does."

The planets observed by K2 are known as transiting planets because their orbits bring them in front of their host stars, slightly reducing their brightness. However, other astrophysical phenomena can cause similar signals, so follow-up observations and detailed statistical analyses were performed to confirm the planetary nature of these signals. As part of his doctoral work, Livingston traveled to Kitt Peak observatory in the U.S. state of Arizona to obtain data from a special type of camera, known as a speckle interferometer installed on a large telescope there. These observations, along with follow-up observations from a telescope in the state of Texas, were necessary to characterize the host stars and rule out false positives. The combination of detailed analyses of data from these ground-based telescopes, K2 and Gaia enabled the precise determination of the planets' sizes and temperatures. The team's findings include 27 additional candidates that are likely to be real planets, which will be the subject of future research.

Scientists hope to understand what kinds of planets might be out there, but can only draw valid conclusions if there are enough planets for robust statistical analysis. The addition of a large number of new planets, therefore, leads directly to a better theoretical understanding of solar-system formation. The planets also provide good targets for detailed individual studies to yield measurements of planetary composition, interior structure and atmospheres -- in particular, the 18 planets in several multiplanet systems. "The investigation of other solar systems can help us understand how planets and even our own solar system formed," says Livingston. "The study of other worlds has much to teach us about our own."

Children with allergies have a lower risk of developing complicated appendicitis, according to a new study from Lund University and Skåne University Hospital in Sweden. The findings, now published in JAMA Pediatrics, could pave the way for new diagnostic tools in the future.

"In a study of all the children who underwent surgery for appendicitis in Lund, Sweden, over the span of a decade, we found that the most common form of allergy, such as allergy to pollen and animal fur, was associated with a three times lower risk of developing complicated appendicitis. The lower risk remained when we adjusted for other parameters known to increase the risk of serious appendicitis, such as lower age and long-lasting symptoms", says Martin Salö, a researcher at Lund University and physician at Skåne University Hospital.

Appendicitis is widespread among children and young people, and the condition is the most common cause of emergency abdominal surgery in the world.

One third of children affected have a more complicated form of appendicitis which requires a longer hospital stay and sometimes several surgeries. It is not yet clear why some children are affected by this more serious form of appendicitis, nor whether it is possible to prevent it.

One theory holds that complicated appendicitis depends on the body's immunological response differing to the response in cases of uncomplicated appendicitis. According to this theory, children with allergies have a lower risk of contracting complicated appendicitis, because their immunological response is different from that of non-allergic children. However, this had not been investigated more closely until now.

"The outcome of the study supports the theory that complicated appendicitis has a different immunological development compared to uncomplicated appendicitis. The results also provide clues that we hope can lead to the development of new diagnostic aids such as blood tests", concludes Martin Salö.

The study in brief:

The study included all children under the age of 15 who underwent surgery for appendicitis at Skåne University Hospital in Lund between 2007 and 2017. In total, 605 children were part of the study.

The researchers compared the outcomes for children with what is known as IgE-mediated allergy (102 children) with those for children without this allergy (503 children). Among the children with IgE-mediated allergy, 19.6% contracted more complicated appendicitis. In the group of children with no IgE-mediated allergy, 46.9% were affected.

Rates of dementia diagnosis are higher among black ethnic groups compared to white and Asian groups in the UK, a new UCL-led study has found.

The study, published in Clinical Epidemiology, is the first to compare incidence of dementia diagnosis by ethnicity in any nationally representative sample.

Researchers from UCL Psychiatry and the UCL Institute of Epidemiology & Health Care analysed data from 2,511,681 people, including 66,083 who had a dementia diagnosis, from The Health Improvement Network primary care database between 2007 and 2015.

They found that the incidence of dementia diagnosis was 25% higher among black women than white women, and 28% higher among black men than white men. Asian women and men were 18% and 12% less likely than white women and men, respectively, to have a dementia diagnosis.

More research is needed to understand why people in certain ethnic groups are more likely to develop dementia. It could be that factors such as level of formal education, financial deprivation, smoking, physical activity, mental health and some mid-life health outcomes, which all affect dementia risk, differ between the groups. Other research has found that South Asian people may have a lower genetic risk of getting dementia.

"Our new findings may reflect, for example, that there are inequalities in the care people receive to prevent and treat illnesses associated with dementia," said the study's lead author, Dr Claudia Cooper (UCL Psychiatry). "Or perhaps GPs or patients' families are reluctant to name dementia in communities where more stigma is associated with a dementia diagnosis."

The research team also compared the diagnosis rates to what could be expected in the different groups as predicted by prior research.

"What we found suggests that the rates of people receiving a diagnosis may be lower than the actual rates of dementia in certain groups, particularly among black men. It is concerning that black people appear to be more at risk of dementia but less likely to receive a timely diagnosis," added co-author Dr Tra My Pham (UCL Institute of Epidemiology & Health Care).

The researchers say they cannot yet explain the lower dementia rates they found among people of Asian descent.

"Perhaps British Asians do have a lower risk, or they may only be less likely to be diagnosed when they develop it. Rates of timely diagnosis in the UK have been improving, but it appears that not all groups of society are benefiting equally. It's important that messages that dementia is best diagnosed early are tailored to different groups. We've previously found that people's cultural background can influence how willing or unwilling they are to seek help," said Dr Cooper.

Wesley Dowridge, member of King's College London's Social Care Workforce Research Unit Service User and Carer Advisory Group, and study steering group member, commented: "As a black carer and one of the Windrush generation, these findings make me think about why black people I know have been reluctant to seek help for memory problems: worries about being treated fairly, or about being put in a care home. This study shows how important it is that messages about the benefits of timely dementia diagnoses reach everyone, especially people from minority ethnic groups who may be more at risk."

Co-author Professor Jill Manthorpe (King's College London), added that she hopes many people beyond academics and clinicians will take on board the study's findings. "Family and friends, as well as professionals such as nurses and social workers, have a key role to play in explaining the potential benefits of getting a timely diagnosis and in reducing the fears of talking about dementia. Faith and community groups can also play a part in making sure local dementia services are accessible to all."

CORVALLIS, Ore. - The compounds behind the perfumes and colognes you enjoy have been eliciting olfactory excitement since dinosaurs walked the Earth amid the first appearance of flowering plants, new research reveals.

Oregon State University entomologist George Poinar Jr. and his son Greg, a fragrance collector, found evidence that floral scents originated in primitive flowers as far back as 100 million years ago as pollinator attractants - a role they still play even though today's flowers also have colorful petals for luring pollinators.

"I bet some of the dinosaurs could have detected the scents of these early flowers," George Poinar said. "In fact, floral essences from these early flowers could even have attracted these giant reptiles."

The Poinars examined amber flowers from Burma, including the now extinct glandular laurel flower (Cascolaurus burmensis) and veined star flower (Tropidogyne pentaptera).

The research revealed that the flower-based chemical compounds that are the basis for the perfumes and colognes we use today have been providing olfactory excitement to pollinating insects and other animals since the mid-Cretaceous Period.

Without colorful petals, flowers from that period had to rely solely on scents to attract pollinators.

"You can't detect scents or analyze the chemical components of fossil flowers, but you can find the tissues responsible for the scents," said George Poinar, professor emeritus in the OSU College of Science.

The floral secretory tissues producing these scents include nectaries, glandular trichomes, eliaphores and osmophores.

Nectaries are glands that produce fragrances and sweet deposits that insects love. Glandular trichomes are hairs with cells that make and send out scented secretory products. Eliaphores are stalked aromatic oil glands. oOsmophores, also known as floral fragrance glands, are cell clusters specializing in scent emission.

The study also found that secretory tissues of these Cretaceous flowers are similar in structure to those of their modern descendants. That suggests modern and ancient flowers of the same lineages produced similar essences.

Some of flowers studied were even in the process of emitting compounds at the time they were engulfed by the tree resin that later became amber.

The study also included a milkweed flower (Discoflorus neotropicus) and an acacia flower (Senegalia eocaribbeansis) in 20- to 30-million-year-old Dominican Republic amber.

The anther glands on the fossil acacia flower were especially attractive to bees, one of which was fossilized while visiting the stamens. Today, honeybees are still visiting acacia flowers that have the same type of flora glands that existed in the ancient past.

"It's obvious flowers were producing scents to make themselves more attractive to pollinators long before humans began using perfumes to make themselves more appealing to other humans," George Poinar said.