Culture

The survival of the heavily exploited Asian Houbara depends on the regulation of trapping and hunting, according to research led by the University of East Anglia (UEA).

New findings published today reveal that trying to stabilise populations solely through captive breeding will require the release of such large numbers it will inevitably compromise wild populations.

The Asian Houbara, a large, spectacular bird that breeds from the Middle East through Asia, is of major cultural and political significance because of Arab falconry, with hunting influencing international diplomacy. The species is threatened by uncontrolled hunting and poaching, which has caused its decline in the Middle East and Central Asia since the 1960s.

Attempts to conserve the species while also supporting the ancient tradition of Arabian falconry have focused on releasing captive-bred birds in increasing numbers. But research published today in the journal Biological Conservation shows that the species in Uzbekistan is declining by more than 9 per cent each year, and that the number of captive-bred birds needed to be released annually just to stabilise this population would be 1.5 times larger than the wild population itself.

Although captive-breeding can help rescue species from extinction, it bears many risks [see Notes to editors], and such mass-scale releases may compromise the fitness of wild populations. Sustainable hunting and conservation instead needs an integrated approach that also includes controls on hunting, according to Prof Paul Dolman, professor of conservation ecology in UEA's School of Environmental Sciences.

Prof Dolman said: "While captive-breeding can be a valuable conservation tool, over-reliance on it without tackling the unsustainable scale of hunting and trapping cannot save the houbara and may in itself become an additional threat.

"Developing a truly sustainable model of hunting requires international cooperation between falconers and the countries with houbara, to regulate hunting and trapping using sound biological evidence."

The study comes from a long-term collaboration between the Emirates Bird Breeding Centre for Conservation (EBBCC), BirdLife International and UEA. The research aims to develop a sustainable future for the wild Asian Houbara populations that also preserves traditional Arab falconry, with sustainable hunting strategies based on robust transparent scientific evidence. The work was conducted with permission from the State Committee for Nature Conservation of the Republic of Uzbekistan.

The study used data collected over seven years of desert fieldwork in Uzbekistan and satellite-tracking wild and released birds, to understand the houbara's breeding productivity, survival and population trend. The researchers predict numbers to be declining at 9.4 per cent each year, driven by unsustainable levels of hunting and trapping on the wintering grounds in Iran, Afghanistan and Pakistan.

Captive-bred birds survive worse than young wild birds, and to stabilise the population in the 14,300 km2 study area and compensate for a modest hunting quota within Uzbekistan, would require releasing one-and-a half times the wild population number each year. To put this in context, 7200 captive-bred birds would have to be released into a population of 4700 birds every spring just to keep the population from decreasing. Apart from the huge expense this would risk domestication of the wild breeding stock, making it less fit than its wild ancestors.

However, the UEA team also showed that regulating hunting and trapping can substantially reduce the numbers of captive-bred birds that need to be released. This integrated approach will be vital if hunting is to become sustainable.

Prof Nigel Collar, Leventis Fellow at BirdLife International, honorary professor at UEA, and chair of the IUCN Bustard Specialist Group, was a close collaborator in the study.

Prof Collar said: "Bustards in Asia are disproportionately in trouble. The current reliance on captive-breeding diverts resources and attention away from other key conservation needs for the Asian Houbara, such as tackling illicit trade for falcon training, establishing safe havens along the flyways and reducing threats from power lines. A holistic, multi-faceted approach to houbara conservation is now absolutely essential."

Dr Robert Burnside, a senior researcher on the project from UEA's School of Environmental Sciences, said: "The Asian Houbara is a fascinating bird that has evolved to live and be successful in one of the toughest terrestrial environments on the planet.

"The vast desert environment and the cryptic colour and behaviour of the houbara make it extremely difficult to study. We could not have done this research without the advanced satellite-tracking technology we used to follow more than 100 houbara during their breeding and migration. We were able to determine whether birds that died succumbed to hunting, trapping, collisions with power lines or natural causes. On several occasions, local hunters took the transmitter of a hunted bird back to their homes, as the satellite imagery showed."

Use of practitioner-led complementary and alternative medicine (CAM), such as acupuncture, massage, osteopathy and chiropractic treatment, rose from 12 per cent of the population in 2005 to 16 per cent of the population in 2015, according to a survey led by researchers at the University of Bristol's Centre for Academic Primary Care. However, access to these treatments was unequal, with women, those who are better off and those in the south of England more likely to use CAM.

The survey, funded by the National Institute for Health Research, undertaken by Ipsos MORI and published in BJGP Open today [14 November], asked adults in England about their CAM use in the last 12 months. Out of a representative sample of 4,862 respondents aged 15 and over, 766 (16 per cent) said they had seen a CAM practitioner.

More women than men and more people in higher socioeconomic groups (A-C) than in lower socioeconomic groups (D-E) used CAM. CAM use was almost twice as high in the south of England compared with the North and Midlands.

The majority of CAM users either paid for treatment themselves or had it paid for by friends or family (67 per cent). Most CAM users self-referred (either found the practitioners themselves or through a recommendation from a friend or family) (70 per cent). A small proportion were referred by their GP (17 per cent) or other health professional (four per cent) and more of these were from lower socioeconomic groups.

The main reasons for CAM use were for musculoskeletal problems, particularly back pain (38 per cent), and other musculoskeletal pain (neck pain, shoulder pain or knee pain) (22 per cent). Mental health accounted for 12 per cent of CAM use, including for minor depression, anxiety or stress (seven per cent) and sleep problems, tiredness or fatigue (four per cent).

CAM use was fairly evenly spread across all age groups.

Professor Debbie Sharp, from the Centre for Academic Primary Care and lead author of the study, said: "This survey shows that CAM is widely used by the general population, especially for musculoskeletal and mental health problems, with a slight increase in use since 2005. Access, however, is unequal and most people who see a CAM practitioner are better off and pay for it themselves. We also asked about people's willingness to pay for CAM and found, unsurprisingly, that it seemed to be based on ability to pay. However, 13 per cent of non-CAM users said they would be willing to part-pay if the NHS or other organisations paid the rest."

Dr Ava Lorenc, co-author from the Centre for Academic Primary Care, added:

"Current UK health policy advocates patient-centred care and has a focus on prevention and patient self-management. Greater integration of CAM services into NHS primary care could address the inequality in access that we found, for example, through social prescribing. This survey was part of a wider scoping study for a trial to test the effectiveness of CAM for people with both musculoskeletal and mental health problems, which we hope will add to the evidence-base for CAM."

Researchers from the University of Granada (UGR) belonging to the Mind, Brain and Behavior Research Center (CIMCYC, from its name in Spanish) and the Faculty of Business and Economics have proven that adolescents who suffer from obesity feel less food enjoyment than those who have a normal weight. In addition, their work reveals that even trivial restrictions on food intake (that is, temporary diets) are associated with a reduction in pleasure.

For this work, published in the journal Food Quality and Preference, a large sample of 552 adolescents between 11 and 17 years old from several high schools in Granada has had their emotional reactions analyzed during the visualization of images of sweet foods.

Thus, the researchers observed that those adolescents who reported different types of dietary restrictions (different types of diet, dieting very often, skipping breakfast, eating less frequently, etc.), along with those who were obese and those who had unhealthy behaviors unrelated to food (such as smoking or having insufficient sleep), felt less pleasure, attraction and desire to eat the highly palatable foods they were looking at (images of sweets, donuts, ice-creams, chocolate crêpes, etc.).

As explained by Laura Miccoli, main author of this study, "adolescence, typically associated with greater body dissatisfaction, is a key stage for the development of risky eating behaviors, related both to uncontrolled restrictions on food intake -which may lead to to the development of eating disorders- and with the stabilization of overweight and obesity." Hence the importance of studies that approach both food-related disorders from an integrative perspective.

A pioneering study

Not in vain, the research led by the UGR is the first study that has examined the adolescents' emotions toward sweet food cues based on a constellation of risk behaviors, related to both obesity and eating disorders.

In the light of the results obtained, the UGR scientists point out that those adolescents who feel more pleasure or enjoyment when eating "have a healthy relationship with food, and this pleasure may be a possible protective factor against eating and weight-related disorders."

Therefore, "consistent with recent prevention strategies, it is important to change the perspective on the enjoyment of food with respect to the prevention of obesity, banishing the idea that we should avoid the pleasure of eating. On the contrary: we should take advantage of it, and make food enjoyment -the 'slow food movement'- a tool for healthy eating," Miccoli points out.

Dublin, Ireland: An antibody that binds simultaneously to two distinct regions of the HER2 receptor to block the growth of cancer cells has shown promising signs of anti-tumour activity in a number of cancers including those of the gullet (oesophagus), stomach and bowel.

Results from the phase I clinical trial of the drug, called ZW25, had been presented earlier this year [1], but updated results, focusing on patients with oesophageal, stomach, bowel and several other cancers driven by HER2, were presented today (Wednesday) at the 30th EORTC-NCI-AACR [2] Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland.

HER2, a member of the human epidermal growth factor receptor family, is best known for the role it plays in breast cancer. Trastuzumab (Herceptin) is an effective treatment for HER2?positive breast cancers. Stomach cancers that are driven by HER2 also respond well to trastuzumab, but if the cancer returns in these patients, there are no further approved HER2?targeted agents. Unfortunately, for patients with other HER2?driven cancers, there are currently no approved HER2?targeted agents.

Dr Murali Beeram, a medical oncologist and clinical investigator at the START Center for Cancer Care, San Antonio, USA, told the Symposium that as of 16 October a total of 24 patients, who had received several previous therapies (an average of four) but whose cancers had returned, have been given between one and ten cycles of ZW25 since joining the phase I trial, which started in September 2016 (either 10 mg/kg weekly or 20 mg/kg every other week). All had HER2 positive cancers, including cancers of the oesophagus and stomach (gastroesophageal) (10 patients), bowel (5), gall bladder (3), bile duct (1), cervix (1), endometrial (1) fallopian tube (1), skin (adnexal) (1), and parotid gland (1), and eight of these patients remain in the trial.

The latest results in 17 patients with responses available for evaluation show that 13 experienced shrinkage of their tumour. The median time the patients survived without their disease progressing was 6.21 months. Side effects have been mostly mild or moderate with the most common being diarrhoea or a reaction to the infusion of the drug.

Dr Beeram said: "As a clinician, I am excited by the single agent anti-tumour activity and tolerability we are seeing with ZW25, particularly in these patents with advanced HER2?expressing cancers that have progressed after multiple prior therapies, including HER2?targeted agents. In fact, trastuzumab is the only HER2?targeted therapy approved for gastric cancer and there are no approved HER2-targeted therapies for other types of cancer that are driven by the HER2 receptor. ZW25 has been well tolerated to date, which should allow it to be used in combination with other agents for potentially even better responses."

ZW25 is an antibody that can simultaneously bind two distinct regions of the HER2 receptor, a protein that promotes the growth of cancer cells. Dr Beeram explained: "This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, increased binding, and removal of HER2 protein from the cancer cell surface; it also stimulates the immune system to attack the cancer cells. This has led to encouraging anti-tumour activity in patients whose tumours have stopped responding to approved therapies, and who are in desperate need of new medicines that provide anti-tumour activity without excessive toxic side effects. The impressive activity of ZW25, combined with its tolerability, is notable and should be investigated further."

In addition to the cancers already mentioned, a number of others also are driven by the HER2 protein; they include cancers of the womb, ovaries, lung and bladder. Zymeworks, the company that developed ZW25, has expanded the study and a phase II/III study for patients with oesophageal, stomach, and other cancers is planned for next year. In addition, studies are planned to investigate ZW25 in combination with other anti-cancer drugs in patients with cancers that have an overabundance of HER2 receptors and copies of the HER2 gene, and also in those with fewer HER2 receptors and gene copies.

Co-chair of the EORTC-NCI-AACR Symposium, Professor Antoni Ribas from the University of California Los Angeles, who was not involved in the research, commented: "Although these are early results on a small number of patients, they suggest that this new HER2 targeted antibody can have an effect on difficult-to-treat cancers that have either failed to respond to previous therapies or have recurred. We look forward to further results from this study, as well as the further studies that are planned."

With the Christmas party season fast approaching, there will be plenty of opportunity to re-live the familiar, and excruciatingly-awkward, social situation of not being able to remember an acquaintance's name.

This cringe-worthy experience leads many of us to believe we are terrible at remembering names.

However, new research has revealed this intuition is misleading; we are actually better at remembering names than faces.

The authors of the study, from the University of York, suggest that when we castigate ourselves for forgetting someone's name we are placing unfair demands on our brains.

Remembering a person's face in this situation relies on recognition, but remembering their name is a matter of recall, and it is already well-established that human beings are much better at the former than the latter.

The researchers also point out that we only become aware that we have forgotten a name when we have already recognised the face.

We rarely have to confront the problem of knowing a name, but not a face - remaining blissfully unaware of the countless faces we should recognise, but walk straight past on the street.

For the study, the researchers designed a "fair test", pitting names against faces on a level playing field.

They set up an experiment to place equal demands on the ability of participants to remember faces and names by testing both in a game of recognition.

The results showed participants scored consistently higher at remembering names than faces - recognising as little as 64% of faces and up to 83% of names in the tests.

Dr Rob Jenkins, from the Department of Psychology at the University of York, said: "Our study suggests that, while many people may be bad at remembering names, they are likely to be even worse at remembering faces. This will surprise many people as it contradicts our intuitive understanding.

"Our life experiences with names and faces have misled us about how our minds work, but if we eliminate the double standards we are placing on memory, we start to see a different picture."

For the study, participants were given an allotted period of time to memorise unknown faces and names and then tested on which ones they thought they had seen before.

The researchers then repeated the test, but this time they complicated the experiment by showing participants different images of the same faces and the names in different typefaces. This was to make the test as realistic as possible, as real faces appear slightly differently, due to factors such as lighting and hairstyle, each time you see them.

On average, participants recognised 73% of faces when shown the same photo and 64% when shown a different photo. On the other hand, they recognised 85% of names presented in the same format and 83% in different fonts and sizes.

When the researchers presented faces and names of famous people, participants achieved a much more balanced score - recognising a more or less the same number of faces as they did names.

The results show that we are particularly bad at recognising unknown faces, but even with faces and names we have encountered before, we still don't perform better at recognising faces than names at any point.
Dr Jenkins added: "Knowing someone's face, but not remembering their name is an everyday phenomenon.

Our knee-jerk reaction to it is to say that names must be harder to memorise than faces, but researchers have never been able to come up with a convincing explanation as to why that might be. This study suggests a resolution to that problem by showing that it is actually a red herring in the first place."

I recognise your name, but I can't remember your face: an advantage for names in recognition memory is published in the Quarterly Journal of Experimental Psychology.

Scientists at the University of Cambridge have completed the world's largest ever study of typical sex differences and autistic traits. They tested and confirmed two long-standing psychological theories: the Empathizing-Systemizing theory of sex differences and the Extreme Male Brain theory of autism.

Working with the television production company Channel 4, they tested over half a million people, including over 36,000 autistic people. The results are published today in the Proceedings of the National Academy of Sciences.

The Empathizing-Systemizing theory predicts that women, on average, will score higher than men on tests of empathy, the ability to recognize what another person is thinking or feeling, and to respond to their state of mind with an appropriate emotion. Similarly, it predicts that men, on average, will score higher on tests of systemizing, the drive to analyse or build rule-based systems.

The Extreme Male Brain theory predicts that autistic people, on average, will show a masculinised shift on these two dimensions: namely, that they will score lower than the typical population on tests of empathy and will score the same as if not higher than the typical population on tests of systemizing.

Whereas both theories have been confirmed in previous studies of relatively modest samples, the new findings come from a massive sample of 671,606 people, which included 36,648 autistic people. They were replicated in a second sample of 14,354 people. In this new study, the scientists used very brief 10-item measures of empathy, systemizing, and autistic traits.

Using these short measures, the team identified that in the typical population, women, on average, scored higher than men on empathy, and men, on average, scored higher than women on systemizing and autistic traits. These sex differences were reduced in autistic people. On all these measures, autistic people's scores, on average, were 'masculinized': that is, they had higher scores on systemizing and autistic traits and lower scores on empathy, compared to the typical population.

The team also calculated the difference (or 'd-score') between each individual's score on the systemizing and empathy tests. A high d-score means a person's systemizing is higher than their empathy, and a low d-score means their empathy is higher than their systemizing.

They found that in the typical population, men, on average, had a shift towards a high d-score, whereas women, on average, had a shift towards a low d-score. Autistic individuals, on average, had a shift towards an even higher d-score than typical males. Strikingly, d-scores accounted for 19 times more of the variance in autistic traits than other variables, including sex.

Finally, men, on average, had higher autistic trait scores than women. Those working in STEM (Science, Technology, Engineering and Mathematics), on average, had higher systemizing and autistic traits scores than those in non-STEM occupations. And conversely, those working in non-STEM occupations, on average, had had higher empathy scores than those working in STEM.

In the paper, the authors discuss how it is important to bear in mind that differences observed in this study apply only to group averages, not to individuals. They underline that these data say nothing about an individual based on their gender, autism diagnosis, or occupation. To do that would constitute stereotyping and discrimination, which the authors strongly oppose.

Further, the authors reiterate that the two theories are applicable to only two dimensions of typical sex differences: empathy and systemizing. They do not apply to all sex differences, such as aggression, and to extrapolate the theories beyond these two dimensions would be a misinterpretation.

Finally, the authors highlight that although autistic people on average struggle with 'cognitive' empathy - recognizing other people's thoughts and feelings - they nevertheless have intact 'affective' empathy - they care about others. It is a common misunderstanding that autistic people struggle with all forms of empathy, which is untrue.

Dr Varun Warrier, from the Cambridge team, said: "These sex differences in the typical population are very clear. We know from related studies that individual differences in empathy and systemizing are partly genetic, partly influenced by our prenatal hormonal exposure, and partly due to environmental experience. We need to investigate the extent to which these observed sex differences are due to each of these factors, and how these interact."

Dr David Greenberg, from the Cambridge team, said: "Big data is important to draw conclusions that are replicable and robust. This is an example of how scientists can work with the media to achieve big data science."

Dr Carrie Allison, from the Cambridge team, said: "We are grateful to both the general public and to the autism community for participating in this research. The next step must be to consider the relevance of these findings for education, and support where needed."

Professor Simon Baron-Cohen, Director of the Autism Research Centre at Cambridge who proposed these two theories nearly two decades ago, said: "This research provides strong support for both theories. This study also pinpoints some of the qualities autistic people bring to neurodiversity. They are, on average, strong systemizers, meaning they have excellent pattern-recognition skills, excellent attention to detail, and an aptitude in understanding how things work. We must support their talents so they achieve their potential - and society benefits too."

The first study to disentangle the effect of forest trails from the presence of humans shows the number of birds, as well as bird species, is lower when trails are used on a more regular basis. This is also the case when trails have been used for many years, suggesting that forest birds do not get used to this recreational activity. Published in Frontiers in Ecology and Evolution, the finding suggests the physical presence of trails has less of an impact on forest birds than how frequently these recreational paths are used by people. To minimize the impact on these forest creatures, people should avoid roaming from designated pathways.

"We show that forest birds are quite distinctly affected by people and that this avoidance behavior did not disappear even after years of use by humans. This suggests not all birds habituate to humans and that a long-lasting effect remains," says Dr Yves Bötsch, lead author of this study, based at the Swiss Ornithological Institute, Sempach, Switzerland and affiliated with Institute of Evolutionary Biology and Environmental Studies, University Zurich, Switzerland. "This is important to show because pressure on natural habitats and nature protection areas is getting stronger and access bans are often ignored."

Many outdoor activities rely on infrastructure, with roads and trails being most common. Previous research has shown that trails cause habitat loss and fragmentation, where larger areas of habitat are dissected into smaller pieces thereby separating wildlife populations. However it has been difficult to say for certain whether it is the presence of trails or humans that have the most impact on forest birds.

Bötsch explains, "Previous studies provide conflicting results about the effects of trails on birds, with some studies showing negative effects while others do not. We thought differences in the intensity of human use may cause this discrepancy, which motivated us to disentangle the effect of trails from the presence of humans."

The researchers visited four forests with a similar habitat, such as the types of trees, but which differed in the levels of recreation. They recorded all birds heard and seen at points near to the trails, as well as within the forest itself, and found that a lower number of birds were recorded in the forests used more frequently by humans. In addition, they noticed certain species were more affected than others.

"Species with a high sensitivity, measured by flight initiation distance (the distance at which a bird exposed to an approaching human flies away), showed stronger trail avoidance, even in rarely frequented forests. These sensitive species were raptors, such as the common buzzard and Eurasian sparrowhawk, as well as pigeons and woodpeckers," says Bötsch.

He continues, "Generally it is assumed that hiking in nature does not harm wildlife. But our study shows even in forests that have been used recreationally for decades, birds have not habituated to people enough to outweigh the negative impact of human disturbance."

Bötsch concludes with some advice, which may help to minimize the adverse effects on forest birds by people who use forests recreationally.

"We believe protected areas with forbidden access are necessary and important, and that new trails into remote forest areas should not be promoted. Visitors to existing forest trails should be encouraged to adhere to a "stay on trail" rule and refrain from roaming from designated pathways."

A new survey finds that most family medicine and general internal medicine clinicians are willing to provide routine care for transgender patients. In a survey of primary care clinicians in an integrated Midwest health system, 86 percent of respondents (n=140) were willing to provide routine care to transgender patients and 79 percent were willing to provide Pap tests to transgender men. Willingness to provide routine care decreased with age. Willingness to provide Pap tests was higher among family physicians, those who had met a transgender person, and those who measured lower on a transphobia scale. These findings, according to the authors, underscore the importance of integrating personal exposure to transgender individuals into medical education.

New research led by academics at the University of Bristol has discovered that the scales on moth wings vibrate and can absorb the sound frequencies used by bats for echolocation (biological sonar). The finding could help researchers develop bioinspired thin and lightweight resonant sound absorbers.

Bats exert high predation pressure on nocturnal insects, such as moths. In defence against bat echolocation, the thin layer of tiny scales on moth wings has long been assumed to absorb ultrasound therefore creating acoustic camouflage.

The paper, published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) today [Monday 12 November], has revealed a biomechanical mechanism that creates acoustic camouflage by resonant sound absorption.

Numerical and experimental results both show that an example scale of the Cabbage tree emperor moth (Bunaea alcinoe) exhibits its first three resonances in the typical echolocation frequency range of bats. Numerical modelling has confirmed that these resonances can cause absorption of up to 50 per cent of the sound energy at the corresponding frequencies, and act as effective ultrathin sound absorbers that creates acoustic camouflage.

Dr Zhiyuan Shen, Research Associate: Diffraction of Life project in the School of Biological Sciences, and lead author, said: "Man-made sound absorbers can become much thinner when they are based on resonant processes. The resonant mechanism we have discovered has the potential to inspire a new concept of ultra-thin acoustic absorbers."

Dr Marc Holderied, Reader in Biological Sciences in the School of Biological Sciences, and co-author, added: "Our next steps will be to quantify to what degree the ultrasonic reflection and absorption coefficients of moth wings confirm such ultrasonic absorber functionality and investigate how the naturally narrowband resonant absorption of individual scales can create broadband overall absorption of a layer of scales."

In a new study that one scientist called jaw-dropping, a joint UCLA/Caltech team has shown that it is possible to obtain the structures of small molecules, such as certain hormones and medications, in as little as 30 minutes. That's hours and even days less than was possible before.

The team used a technique called micro-electron diffraction (MicroED), which had been used in the past to learn the 3-D structures of larger molecules, specifically proteins. In this new study, the researchers show that the technique can be applied to small molecules, and that the process requires much less preparation time than expected. Unlike related techniques--some of which involve growing crystals the size of salt grains--this method, as the new study demonstrates, can work with run-of-the-mill starting samples, sometimes even powders scraped from the side of a beaker.

"We took the lowest-brow samples you can get and obtained the highest-quality structures in barely any time," says Caltech professor of chemistry Brian Stoltz, who is a co-author on the new study, published in the journal ACS Central Science. "When I first saw the results, my jaw hit the floor." Initially released on the pre-print server Chemrxiv in mid-October, the article has been viewed more than 35,000 times.

The reason the method works so well on small-molecule samples is that while the samples may appear to be simple powders, they actually contain tiny crystals, each roughly a billion times smaller than a speck of dust. Researchers knew about these hidden microcrystals before, but did not realize they could readily reveal the crystals' molecular structures using MicroED. "I don't think people realized how common these microcrystals are in the powdery samples," says Stoltz. "This is like science fiction. I didn't think this would happen in my lifetime--that you could see structures from powders."

The results have implications for chemists wishing to determine the structures of small molecules, which are defined as those weighing less than about 900 daltons. (A dalton is about the weight of a hydrogen atom.) These tiny compounds include certain chemicals found in nature, some biological substances like hormones, and a number of therapeutic drugs. Possible applications of the MicroED structure-finding methodology include drug discovery, crime lab analysis, medical testing, and more. For instance, Stoltz says, the method might be of use in testing for the latest performance-enhancing drugs in athletes, where only trace amounts of a chemical may be present.

"The slowest step in making new molecules is determining the structure of the product. That may no longer be the case, as this technique promises to revolutionize organic chemistry," says Robert Grubbs, Caltech's Victor and Elizabeth Atkins Professor of Chemistry and a winner of the 2005 Nobel Prize in Chemistry, who was not involved in the research. "The last big break in structure determination before this was nuclear magnetic resonance spectroscopy, which was introduced by Jack Roberts at Caltech in the late '60s."

Like other synthetic chemists, Stoltz and his team spend their time trying to figure out how to assemble chemicals in the lab from basic starting materials. Their lab focuses on such natural small molecules as the fungus-derived beta-lactam family of compounds, which are related to penicillins. To build these chemicals, they need to determine the structures of the molecules in their reactions--both the intermediate molecules and the final products--to see if they are on the right track.

One technique for doing so is X-ray crystallography, in which a chemical sample is hit with X-rays that diffract off its atoms; the pattern of those diffracting X-rays reveals the 3-D structure of the targeted chemical. Often, this method is used to solve the structures of really big molecules, such as complex membrane proteins, but it can also be applied to small molecules. The challenge is that to perform this method a chemist must create good-sized chunks of crystal from a sample, which isn't always easy. "I spent months once trying to get the right crystals for one of my samples," says Stoltz.

Another reliable method is NMR (nuclear magnetic resonance), which doesn't require crystals but does require a relatively large amount of a sample, which can be hard to amass. Also, NMR provides only indirect structural information.

Before now, MicroED--which is similar to X-ray crystallography but uses electrons instead of X-rays--was mainly used on crystallized proteins and not on small molecules. Co-author Tamir Gonen, an electron crystallography expert at UCLA who began developing the MicroED technique for proteins while at the Howard Hughes Medical Institute in Virginia, said that he only started thinking about using the method on small molecules after moving to UCLA and teaming up with Caltech.

"Tamir had been using this technique on proteins, and just happened to mention that they can sometimes get it to work using only powdery samples of proteins," says Hosea Nelson (PhD '13), an assistant professor of chemistry and biochemistry at UCLA. "My mind was blown by this, that you didn't have to grow crystals, and that's around the time that the team started to realize that we could apply this method to a whole new class of molecules with wide-reaching implications for all types of chemistry."

The team tested several samples of varying qualities, without ever attempting to crystallize them, and were able to determine their structures thanks to the samples' ample microcrystals. They succeeded in getting structures for ground-up samples of the brand-name drugs Tylenol and Advil, and they were able to identify distinct structures from a powdered mixture of four chemicals.

The UCLA/Caltech team says it hopes this method will become routine in chemistry labs in the future.

"In our labs, we have students and postdocs making totally new and unique molecular entities every day," says Stoltz. "Now we have the power to rapidly figure out what they are. This is going to change synthetic chemistry."

The escape response to evade perceived threats is a fundamental behavior seen throughout the animal kingdom, and laboratory studies have identified specialized neural circuits that control this behavior. Understanding how these neural circuits operate in complex natural settings, however, has been a challenge.

A new study led by researchers at UC Santa Cruz and NOAA Fisheries overcame this challenge using a clever experimental design to record and analyze escape responses in coral reef fish. The results, published November 12 in Proceedings of the National Academy of Sciences, reveal how a sequence of well-defined decision rules generates evasion behavior in a wide range of coral reef fish species.

"We took an approach used in laboratory studies into a complex, natural environment and found that the same behavioral mechanisms seem to apply. A set of simple rules are combined in different ways to generate a rich suite of behaviors to accomplish this fundamental goal: to avoid being killed," said first author Andrew Hein, an assistant researcher at the UC Santa Cruz Institute of Marine Sciences and research ecologist at the NOAA Fisheries Lab in Santa Cruz.

The coral reef fish in the study feed on algae in shallow reef flats, where they are vulnerable to predators such as moray eels and reef sharks. To simulate a threat, the researchers employed a widely used visual stimulus called the looming stimulus, a black dot that grows in size slowly and then rapidly, creating the illusion of a rapidly approaching object. A waterproof tablet computer deployed on a coral reef in Mo'orea, French Polynesia, played the looming stimulus, while video cameras recorded the responses of fish that swam into the area in front of the tablet.

The researchers then used computer vision technology to analyze the video. Automated tracking and a method known as "ray casting," originally developed by video game designers, allowed them to reconstruct what each fish was seeing as it decided whether or not to flee from the threat. They found that fish initiated escape maneuvers in response to the perceived size and expansion rate of the threat stimulus using a decision rule that matched the dynamics of known loom-sensitive neural circuits.

"This same behavioral circuit that neuroscientists identified in lab studies seems to be operating in the more complex natural environment," Hein said. "But we also found something new: the sensitivity to the looming stimulus gets tuned up or down depending on the locations of other fish. If an individual is the closest one to the stimulus, it is much more likely to flee than if there is another fish between it and the threat."

A third factor in the escape response was the location of a safe place to shelter, offered by a mounding coral alongside the experimental area. The initial response to the stimulus is to quickly turn away from the threat, but almost immediately the fish then began turning toward the shelter and swam directly toward it.

"When you look at the paths they take, it looks like spaghetti--they're all different--but the analysis shows they're all generated by the same simple set of behavioral rules," Hein said.

All vertebrates need muscles to function; they are the most abundant tissue in the human body and are integral to movement.

In a recent article published in Nature Communications, an international team of researchers discovered two proteins essential to the development of skeletal muscle. This research, led by Jean-François Côté, a professor at the Montreal Clinical Research Institute (IRCM) and the Faculty of Medicine at Université de Montréal, could lead to a better understanding of rare muscular diseases and the development of new treatments.

From nuclear fusion to cell fusion

Skeletal muscles are attached to our bones and enable our bodies to move. Whether in a developing embryo or a professional athlete, the same sequence leads to their formation.

"In vertebrates, cells derived from stem cells, called myoblasts, first align with each other and come so close as to eventually touch and compress their cell membranes," explained the study's lead author Jean-François Côté, Director of the IRCM's Cytoskeleton Organization and Cell Migration Research Unit.

Ultimately, myoblasts merge to create one large cell. This phenomenon, called "cell fusion", is very particular. "Cell fusion involves just a few tissues, including the development of the placenta and the remodeling of our bones," Côté said.

The 'dance' of the muscle cells

To develop and also repair muscle, myoblasts have to perform their movements very carefully. No false move is permissible, otherwise there will be defects. In their study, Côté and his team describe their discovery of two proteins - ClqL4 and Stabilin-2 - that regulate this singular choreography.

Indeed, ClqL4 and Stabilin-2 ensure successful completion of this delicate sequence. They slow down and trigger cell fusion respectively at key moments. Their role is crucial: if the "metronome" of myoblasts is interrupted, the muscles will not be the right size, and their function will be affected. This is what happens in muscle diseases characterized by a weakness that makes certain movements difficult.

The discovery of the proteins is the culmination of an international collaboration between teams from Montreal, Japan, the United States and South Korea. "Our second author, Viviane Tran, one of my doctoral students, spent time in Tokyo to conduct important experiments in the lab of Michisuke Yuzaki, one of our collaborators," Côté noted.

The IRCM researchers have already embarked on the follow-up study. They want to determine whether the results of their research could become a therapeutic target for rare muscle diseases such as myopathies and muscular dystrophies.

Dublin, Ireland: Treatment with capivasertib, a drug designed to work against a particular gene mutation found in some tumours, shows signs of being effective in a trial of 35 patients presented today (Tuesday) at the 30th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland.

The phase 2 trial (EAY131-Y) is part of a larger USA study, called NCI-MATCH (EAY131) [2], that aims to determine whether cancer patients can be treated successfully by selecting therapies that target gene abnormalities found in their tumours, rather than by cancer type.

Researchers say their results provide further evidence that the approach of tailoring treatment according to tumour genes could offer more effective treatments for individual patients in the future. The more traditional approach is to treat patients based on what has worked in the past for other patients with the same type of cancer.

The research was presented by Dr Kevin Kalinsky, Assistant Professor of Medicine, New York Presbyterian-Columbia University Irving Medical Centre, USA. He explained: "Capivasertib can be taken by mouth and it's a type of drug called an AKT inhibitor. This means it binds to a molecule called AKT that has mutated a change that plays a role in helping cancer cells grow. In a prior phase 2 study, capivasertib has shown potential in treating an aggressive form of breast cancer.

"In this trial, we wanted to see if capivasertib could be used in patients with any type of cancer whose tumours have the mutation that leads the AKT molecule to become over-active and make the cancer grow."

Patients were selected by having the cells from their tumours tested. Each of the 35 patients in the trial was carrying the AKT mutation in the cells of their tumour. Although this mutation occurs in several different types of cancer, overall it is rare. Researchers found the mutation in 1.3% of patients (70 of 5548) tested centrally in the NCI-MATCH trial.

In all patients on the EAY131-Y study, the cancer had spread to other parts of the body, and most had already received three or more previous treatments. The patients were treated with capivasertib, taken by mouth twice a day, in weekly cycles of four days with treatment and three days without treatment.

Patients' tumours were measured by imaging, such as CT scans, before and after treatment. In the best confirmed responses, the tumour reduced in size in eight patients (23%), and in 16 patients (46%) the tumour did not grow but did not shrink either. In three patients (9%), the tumour grew.

Researchers observed the following side effects from the drug, saying that physicians should carefully manage these in patients being treated with capivasertib: high blood sugar, fatigue, diarrhoea, nausea, vomiting, and skin rash.

Dr Kalinsky said: "Overall, 23% of the patients in our trial experienced a positive response, which was defined as tumour shrinkage from before they started capivasertib. We determined in advance that if 16% of patients experienced this response from the treatment, it would be a signal to move the drug on to a larger trial. This is a positive finding in a trial with patients whose cancers continued to grow despite previous treatments."

Researchers estimate that, six months after the treatment, the percentage of patients alive and without their tumours growing was 52%.

"This study is a limited but important piece of evidence. More trials are needed to learn the benefit in each tumour type and to understand why some patients did not have a response while others had a prolonged time without tumour growth," Dr Kalinsky added.

Professor Charles Swanton of the Francis Crick Institute, London, UK, is scientific co-chair of the EORTC-NCI-AACR Symposium and was not involved in the research. He said: "Although we understand more than ever about the role of genes in different cancers, there is still a lack of evidence on using this knowledge to guide treatments and improve patient survival. Outside of a trial setting, this approach is not widely available.

"This study is a small but important piece of evidence and it's part of a larger study that will help us move towards more personalised cancer treatments.

"This trial approach is particularly important for those with rarer cancers where we know less about which treatments are most effective and conducting patient trials is difficult."

Researchers at University of California San Diego School of Medicine, Scripps Institution of Oceanography, and international collaborators have evidence that Kawasaki Disease (KD) does not have a single cause. By studying weather patterns and geographical distributions of patients in San Diego, the research team determined that this inflammatory disease likely has multiple environmental triggers influenced by a combination of temperature, precipitation and wind patterns. Results will be published in the November 12 online edition of Scientific Reports.

"We are seeing firsthand evidence of these weather patterns in San Diego, where eight children have recently been diagnosed with Kawasaki Disease. Recent low pressure systems in San Diego have been associated with two distinct clusters of the disease," said Jane C. Burns, MD, pediatrician at Rady Children's Hospital-San Diego and director of the Kawasaki Disease Research Center at UC San Diego School of Medicine. "Our research is pointing towards an association between the large-scale environment, what's going on with our climate on a large scale, and the occurrence of these clusters."

Kawasaki disease is the most common acquired heart disease in children. Untreated, roughly one-quarter of children with KD develop coronary artery aneurysms -- balloon-like bulges of heart vessels -- that may ultimately result in heart attacks, congestive heart failure or sudden death.

Burns and her team examined 1,164 cases of KD treated at Rady Children's Hospital over 15 years. Noticeable clusters of KD cases were often associated with distinct atmospheric patterns that are suspected to transport or concentrate agents that result in KD. Days preceding and during the KD clusters exhibited higher than average atmospheric pressure and warmer conditions in Southern California, along with a high pressure feature south of the Aleutian Islands.

"For the first time, we have evidence that there is more than one trigger for Kawasaki Disease. Up until now, scientists have been looking for one 'thing' that triggers KD," said Burns. "Now we see that there are distinct clusters of the disease with different patterns suggesting varying causes."

Gene expression analysis further revealed distinct groups of KD patients based on their gene expression pattern, and that the different groups were associated with certain clinical characteristics.

"Our data suggest that one or more environmental triggers exist, and that episodic exposures are influenced at least in part by regional weather conditions. We propose that characterization of the environmental factors that trigger KD in genetically susceptible children should focus on aerosols inhaled by patients who share common disease characteristics," said Burns who has studied KD for more than 35 years.

Although KD is estimated to affect fewer than 6,000 children in the U.S. each year, the incidence is rising in San Diego County. While the average incidence per 100,000 children less than 5 years of age residing in San Diego County was approximately 10 for the decade of the 1990s, the estimate from 2006 to 2015 was 25.5. This increase may be attributed to the efforts of the KD team at Rady Children's Hospital to teach local physicians how to diagnose KD. Or it may be due to increasing exposure to the environmental triggers of the disease.

Prevalence rates of KD are increasing among children in Asia. Japan has the highest incidence rate, with more than 16,000 new cases per year. One in every 60 boys and one in every 75 girls in Japan will develop KD during childhood.

Incidence rates in the U.S. are approximately 19 to 25 cases per 100,000 children under age 5 -- but are higher in children of Asian descent. Predictive models estimate that by 2030, 1 in every 1,600 American adults will have been affected by the disease.

Boston, Mass. -- Bacteria are present in just about every breath of air we take in. How the airway protects itself from infection from these bacteria has largely remained a mystery -- until now. When bacteria are inhaled, exosomes, or tiny fluid-filled sacs, are immediately secreted from cells which directly attack the bacteria and also shuttle protective antimicrobial proteins from the front of the nose to the back along the airway, protecting other cells against the bacteria before it gets too far into the body.

A research team from Massachusetts Eye and Ear describes this newly discovered mechanism in a report published online today in the Journal of Allergy and Clinical Immunology (JACI). The findings shed new light on our immune systems -- and also pave the way for drug delivery techniques to be developed that harness this natural transportation process from one group of cells to another.

"Similar to kicking a hornets nest, the nose releases billions of exosomes into the mucus at the first sign bacteria, killing the bacteria and arming cells throughout the airway with a natural, potent defense" said senior author Benjamin Bleier, MD, a sinus surgeon at Massachusetts Eye and Ear and associate professor of otolaryngology at Harvard Medical School. "It's almost like this swarm of exosomes vaccinates cells further down the airway against a microbe before they even have a chance to see it."

The JACI study was motivated by a perplexing previous finding from Dr. Bleier's lab a few years ago. In studies of sinus inflammation, researchers found that proteins in the cells of the nasal cavity were also present in patients' nasal mucus. The team wanted to know why and how these proteins were moving from the cells into the nasal mucus, hypothesizing that exosomes had something to do with that process.

The new findings described in the JACI study shed light on this process. When cells at the front of the nose detect a bacterial molecule, they trigger a receptor called TLR4, which stimulates exosome release. When that happens, an innate immune response occurs within 5 minutes. First, it doubles the number of exosomes that are released into the nose. Second, within those exosomes, a protective enzyme, nitric oxide synthase, also doubles in amount. As a well-known antimicrobial molecule, nitric oxide potently arms each exosome to defend against bacteria.

The exosome "swarm" process gets an assist from another natural mechanism of the nose -- mucocilliary clearance. Mucocilliary clearance sweeps the activated exosomes over to the back of the nose, along with information from cells that have already been alerted to the presence of bacteria. This process prepares the cells in the back of the nose to immediately fight off the bacteria, arming them with defensive molecules and proteins.

In their experiments described in the JACI report, Dr. Bleier's team sampled patients' mucus and grew up their own cells in culture. They then simulated an exposure to bacteria and measured both the number and composition of the released exosomes. They found a doubling of both the number of exosomes and of antibacterial molecules after stimulation. The team then confirmed this finding in live patients and further showed that these stimulated exosomes were as effective as antibiotics at killing the bacteria. Finally, the team showed that the exosomes were rapidly taken up by other epithelial cells, where they were able to "donate" their antimicrobial molecules.

Along with this new understanding of the innate immune system, the authors on the JACI paper suggest that their findings may have implications for new methods of delivering drugs through the airway to be developed. More specifically, as natural transporters, exosomes could be used to transfer inhaled packets of therapeutics to cells along the upper airway -- and possibly even into the lower airways and lungs.

"The nose provides a unique opportunity to directly study the immune system of the entire human airway -- including the lungs," said Dr. Bleier.