Earth

High levels of low-density lipoproteins, parcels of lipids and protein that carry cholesterol, are a leading risk factor for heart disease. Many cholesterol medications lower LDL, some of them by targeting the protein PCSK9. In the January issue of the Journal of Lipid Research, scientists at the University of California, San Francisco, report on an investigation into why experiments on PCSK9 give different results in a test tube and in liver cells. What they found may explain how a mutation in PCSK9 that has long puzzled scientists leads to heart disease.

Ordinarily, the LDL receptor on the surface of liver cells is responsible for suctioning low-density lipoprotein out of the blood. But after being torpedoed by PCSK9, LDL receptor is brought into the cells and broken down, making the liver less able to control LDL in the bloodstream.

"We have very effective and safe therapies at reducing PCSK9 function," said John Chorba, a cardiologist and researcher at UCSF. Perhaps you've heard of them: Praluent and Repatha are drugs that lower patients' cholesterol by blocking the interaction between PCSK9 and the LDL receptor. "But they're antibody-based approaches," Chorba said, "and are very expensive. Having a more thorough understanding of how PCSK9 works gives us new opportunities to develop drugs which could be more cost-effective."

Chorba, who splits his time between lab and clinic, worked with medical student Adri Galvan to better understand the biochemistry of the PCSK9/LDL receptor interaction. In a test tube, LDL particles block the interaction between the LDL receptor and PCSK9. This sounds like a good thing; the more LDL you have in circulation, the more you'd want the LDL receptor to work, and the less you would want PCSK9 to disrupt it.

But when Chorba and Galvan repeated the experiment in cells, the results showed that the relationship is a little more complicated. In cells, LDL does not seem to disrupt the interaction as effectively.

"That's when we really started to ask, what else is going on with these cells?" Galvan said. "What else is PCSK9 interacting with?"

Chorba said, "We thought there must be something (on the cells) that was attenuating that effect."

Around the same time that Chorba and Galvan were trying to determine what the mystery interactor might be, a Danish group at Aarhus University published its finding that heparan sulfate proteoglycans, extracellular proteins with a particular sugar chain attached, can help PCSK9 reach the LDL receptor.

Chorba and Galvan confirmed that in cells from which that sugar chain had been cleaved, the LDL receptor/PCSK9 interaction on the surface of cells could be disrupted by LDL, similar to what happened in a test tube.

This led them to a clue about how a long-known but poorly understood mutant form of PCSK9 might work. It's called the S127R mutation, because it changes the 127th amino acid in PCSK9, serine, into arginine. "S127R was the initial mutation discovered in PCSK9 as a cause of genetic familial hypercholesterolemia, but the way it worked has been unknown for years," Chorba explained.

S127R is a head-scratcher because the change in its amino-acid sequence disrupts PCSK9 maturation. You'd expect the change to reduce total PCSK9, which would reduce LDL, and that should be good for carriers of the gene. But instead, the mutant raises LDL cholesterol levels, putting patients at elevated risk of heart disease.

Chorba and Galvan found that while removing heparan sugar chains from cultured liver cells affected how the cells' LDL receptors bound to wild-type PCSK9, it affected their interaction with the mutant even more. That suggested that S127R PCSK9 might be interacting more strongly with HSPG--and offered a potential way for the mutant PCSK9 to interact more strongly with LDLR.

"I would imagine that S127R PCSK9 would be more likely to bind to the surface of (liver cells)," Chorba said. "So the local concentration of PCSK9 would be higher... and it would be more likely to run into an LDL receptor that would get internalized and degraded."

It remains to be seen whether this explanation holds up to further experimental scrutiny. If it does, then drugs that disrupt the PCSK9/heparin sulfate proteoglycan interaction, which a spinoff company from Aarhus University, called Draupnir Bio, is working to develop, could be especially effective for people with familial hypercholesterolemia who carry the S127 mutation.

A study carried out by researchers at Massachusetts General Hospital (MGH) and the Perelman School of Medicine at the University of Pennsylvania finds that low wages and poor benefits leave many female health care workers living below the poverty line. The report that will appear in the January issue of the American Journal of Public Health has been published online.

"Every day in the clinic and in the hospital, my colleagues who work in low-wage positions - as cleaners, dietary workers, medical assistants and nurse's aides - make vital contributions to the care of our patients." says Kathryn Himmelstein, MD, lead and corresponding author of the paper. "These workers should not have to go home to poverty or be unable to afford health care for themselves and their families." A resident in the MGH Department of Medicine and postdoctoral fellow at Harvard Medical School, Himmelstein initiated the study as a medical student at the University of Pennsylvania.

The authors note that more Americans are employed in health care than in any other industry, and three quarters of them are women. Their analysis of data from the 2017 Annual Social and Economic Supplement to the Current Population Survey, conducted by the U.S. Census Bureau and the Bureau of Labor Statistics, found that 18 percent of employed women responding to the 2017 survey and 23 percent of employed Black women work in health care, many of them in low-paying jobs.

Although the average hourly wage for female health care workers of more than $19/hour was higher than the average of around $16/hour for all other industries, it was almost 25 percent lower than the average for men working in health care. The data suggested that 34 percent of female health care workers, and nearly half of the Black and Latina women working in the health sector, earned less than $15/hour. While the largest number of health care workers making less than $15/hour were employed by hospitals, such workers made up a larger share of the total workforce in home health care and at nursing homes and other residential care facilities. Relatively few women and even fewer women of color worked as physicians or managers.

Projecting the survey's results across the entire U.S. population suggests that 5 percent of all women health care workers - including 10.6 percent of Black and 8.6 percent of Latina women health care workers - live in poverty, the authors note. Overall, 1.7 million women health care workers and their children lived below the poverty line in 2017, accounting for nearly 5 percent of all people living in poverty in the U.S. The researchers also found surprisingly high numbers of the female health care workers surveyed lack health insurance. Overall, 7 percent - projected to represent more than 1 million women nationwide - were uninsured, including more than 10 percent of Black and Latina women employed in health care.

The researchers also projected the potential impact of raising the minimum wage to $15/hour, a policy already implemented in several cities and some medical centers. They found that adopting such a policy nationwide would decrease poverty rates among female health care workers by up to 50 percent, while increasing U.S. health care costs by less than 1.5 percent.

Himmelstein says, "Public health experts have been urging hospitals and other health care providers to focus on the 'social determinants' of ill-health, and these institutions should start by addressing their own employment practices. But we shouldn't just leave that up to health care employers; lawmakers have a tremendous opportunity to lift millions of people out of poverty and promote racial and gender justice in health care employment by raising statutory minimum wages."

Senior author Atheendar Venkataramani, MD, PhD, assistant professor of Medical Ethics and Health Policy at the Perelman School of Medicine, adds, "Wage inequality in the health care sector reflects what we are seeing in other sectors of the economy in the United States. In that spirit, these findings should inform active debates around the role of new policies - for example, raising minimum wages, expanding the Earned Income Tax Credit or expanding access to higher education - that seek to address widening income inequality and diminishing opportunities for upward mobility."

Monoamine oxidase (MAO) inhibitors are potential drug candidates for treating neurological disorders such as anxiety, Alzheimer's disease and Parkinson's disease.

This review presents information about MAO inhibitory effects of the umbelliferone based derivatives. The potential antioxidant effects of the derivatives were evaluated by DPPH and H2O2 scavenging methods. The derivatives were screened for hMAO-A and hMAO-B inhibition through a series of different umbelliferone derivatives was designed and synthesized for experimental conditions. Through docking simulation, the mechanistic insight for enzyme- compound infractions was achieved. By two spectrophotometric titration methods, the antioxidant potential was dually assessed.

A remarkable hMAO-A inhibitory potential was exhibited by (7.473±0.035 μM and the selectivity index of 0.14) Compound 5 with bromo 5-bromo-isatin, revealing the impact of hybrid coumarin and 5- bromo-2-oxoindolin-3-yl ring with hydrazine linker on the hMAO-A active site. With an exceptional selectivity index of 8.55, compound 13 exhibited significant hMAO-B inhibition with an IC50 value of 10.32±0.044μM. Incorporation of 2-hydroxy-2-phenylacetate moiety on 2-oxo-2H-chromen ring led the important binding infractions within the hMAO active site.

A good correlation was revealed between experimental MAO inhibition and docking score by computational studies. Notably, the compounds with remarkable MAO inhibitory potential were also observed as potential antioxidants which have implications for therapy of neuropsychological and neurodegenerative diseases.

NEW YORK, December 31, 2018 - Researchers at the Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New York and at the City College of New York (CCNY) have developed a metamaterial that can transport sound in unusually robust ways along its edges and localize it at its corners.

According to a new paper published today in Nature Materials, the newly engineered material creates a robust acoustic structure that can control in unusual ways the propagation and localization of sound even when fabrication imperfections exist. This unique property may improve technologies that use sound waves, such as sonars and ultrasound devices, making them more resistant to defects.

The research is a collaboration between the labs of Alexander Khanikaev, a professor in the electrical engineering and physics departments at CCNY who is also affiliated with the ASRC, and of Andrea Alù, director of the ASRC's Photonics Initiative. Their advance is based on work that brought a field of mathematics called topology into the materials science world. Topology studies properties of an object that are not affected by continuous deformations. For instance, a donut is topologically equivalent to a plastic straw, as they both have one hole. One could be molded into the other by stretching and deforming the object, and without tearing it or adding new holes.

Using topological principles, researchers predicted and later discovered topological insulators--special materials that conduct electric currents only on their edges, not in the bulk. Their unusual conduction properties stem from the topology of their electronic band gap, and they are therefore unusually resistant to continuous changes, such as disorder, noise or imperfections.

"There has been a lot of interest in trying to extend these ideas from electric currents to other types of signal transport, in particular to the fields of topological photonics and topological acoustics," Alù says. "What we are doing is building special acoustic materials that can guide and localize sound in very unusual ways."

To design their novel acoustic metamaterial, the team 3D-printed a series of small trimers, arranged and connected in a triangular lattice. Each trimer unit consisted of three acoustic resonators. The rotational symmetry of the trimers, and the generalized chiral symmetry of the lattice, gave the structure unique acoustic properties that stem from the topology of their acoustic bandgap.

The acoustic modes of the resonators hybridized, giving rise to an acoustic band structure for the whole object. As a result, when sound is played at frequencies outside the band gap it can propagate through the bulk of the material. But when sound is played at frequencies inside the band gap, it can only travel along the triangle's edges or be localized at its corners. This property, Alù says, is not affected by disorder or fabrication errors.

"You could completely remove a corner, and whatever is left will form the lattice's new corner, and it will still work in a similar way, because of the robustness of these properties," Alù said

To break these properties, researchers had to reduce the symmetry of the material by, for example, changing the coupling between resonator units, which changes the topology of the band structure and thus changes the material's properties.

"We have been the first to build a topological metamaterial for sound supporting different forms of topological localization, along its edges and at its corners.", Khanikaev said. "We also demonstrated that advanced fabrication techniques based on 3D printed acoustic elements can realize geometries of arbitrary complexity in a simple and flexible platform, opening disruptive opportunities in the field of acoustic materials. We have been recently working on even more complex 3D metamaterial designs based on these techniques, which will further expand the properties of acoustic materials and expand capabilities of acoustic devices".

"We're showing, fundamentally, that it is possible to enable new forms of sound transport that are much more robust than what we are used to. These findings may find applications in ultrasound imaging, underwater acoustics and sonar technology," Alù said.

GAINESVILLE, Fla. --- A group of Florida Museum of Natural History scientists has issued a "call to action" to use big data to tackle longstanding questions about plant diversity and evolution and forecast how plant life will fare on an increasingly human-dominated planet.

In a commentary published today in Nature Plants, the scientists urged their colleagues to take advantage of massive, open-access data resources in their research and help grow these resources by filling in remaining data gaps.

"Using big data to address major biodiversity issues at the global scale has enormous practical implications, ranging from conservation efforts to predicting and buffering the impacts of climate change," said study author Doug Soltis, a Florida Museum curator and distinguished professor in the University of Florida department of biology. "The links between big data resources we see now were unimaginable just a decade ago. The time is ripe to leverage these tools and applications, not just for plants but for all groups of organisms."

Over several centuries, natural history museums have built collections of billions of specimens and their associated data, much of which is now available online. New technologies such as remote sensors and drones allow scientists to monitor plants and animals and transmit data in real time. And citizen scientists are contributing biological data by recording and reporting their observations via digital tools such as iNaturalist.

Together, these data resources provide scientists and conservationists with a wealth of information about the past, present and future of life on Earth. As these databases have grown, so have the computational tools needed not only to analyze but also link immense data sets.

Studies that previously focused on a handful of species or a single plant community can now expand to a global level, thanks to the development of databases such as GenBank, which stores DNA sequences, iDigBio, a University of Florida-led effort to digitize U.S. natural history collections, and the Global Biodiversity Information Facility, a repository of species' location information.

These resources can be valuable to a wide range of users, from scientists in pursuit of fundamental insights into plant evolution and ecology to land managers and policymakers looking to identify the regions most in need of conservation, said Julie Allen, co-lead author and an assistant professor in the University of Nevada-Reno department of biology.

If Earth's plant life were a medical patient, small-scale studies might examine the plant equivalent of a cold sore or an ingrown toenail. With big data, scientists can gain a clearer understanding of global plant health as a whole, make timely diagnoses and prescribe the right treatment plans.

Such plans are urgently needed, Allen said.

"We're in this exciting and terrifying time in which the unprecedented amount of data available to us intersects with global threats to biodiversity such as habitat loss and climate change," said Allen, a former Florida Museum postdoctoral researcher and UF doctoral graduate. "Understanding the processes that have shaped our world - how plants are doing, where they are now and why - can help us get a handle on how they might respond to future changes."

Why is it so vital to track these regional and global changes?

"We can't survive without plants," said co-lead author and museum research associate Ryan Folk. "A lot of groups evolved in the shadow of flowering plants. As these plants spread and diversified, so did ants, beetles, ferns and other organisms. They are the base layer to the diversity of life we see on the planet today."

In addition to using and growing plant data resources, the authors hope the scientific community will address one of the toughest remaining obstacles to using biological big data: getting databases to work smoothly with each other.

"This is still a huge limitation," Allen said. "The data in each system are often collected in completely different ways. Integrating these to connect in seamless ways is a major challenge."

Bottom Line: Children can exhibit physical aggression when they are very young but that behavior typically declines before and during elementary school. However, a small proportion of children have atypically high physical aggression problems into adolescence, which may put them at increased risk for violent crime, social maladjustment, and alcohol and drug abuse. This observational study of 2,223 boys and girls used information from mothers, teachers and the children to trace the development of physical aggression problems from infancy to adolescence. The analysis suggests the frequency of physical aggression increased from age 1½ to 3½ and then decreased until age 13. Trajectories for the development of physical aggression differed for boys and girls, and several risk factors were identified, including family characteristics when the child was an infant such as having parents with lower education and higher depression, lower socioeconomic status and a higher number of siblings. Interventions during pregnancy and early childhood may help to prevent high physical aggression in children in high-risk families.

Authors: Richard E. Tremblay, Ph.D., University of Montreal, Montreal, Quebec, Canada, and coauthors

To Learn More: The full study is available on the For The Media website.

(doi:10.1001/jamanetworkopen.2018.6364)

Editor's Note: The article contains funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Every month or two, a massive pulse of clouds, rainfall and wind moves eastward around the Earth near the equator, providing the tropics their famous thunderstorms.

This band of recurring weather, first described by scientists in 1971, is called the Madden-Julian Oscillation. It has profound effects on weather in distant places, including the United States. Atmospheric scientists have long studied how the Madden-Julian Oscillation modulates extreme weather events across the globe, from hurricanes to floods to droughts.

As human activities cause the Earth's temperature to increase, reliable, well-studied weather patterns like the Madden-Julian Oscillation will change too, say researchers at Colorado State University.

Eric Maloney, professor in the Department of Atmospheric Science, has led a new study published in Nature Climate Change that attributes future changes in the behavior of the Madden-Julian Oscillation to anthropogenic global warming. Maloney and co-authors used data from six existing climate models to synthesize current views of such changes projected for the years 2080-2100.

Their analysis reveals that while the Madden-Julian Oscillation's precipitation variations are likely to increase in intensity under a warmer climate, wind variations are likely to increase at a slower rate, or even decrease. That's in contrast to the conventional wisdom of a warming climate producing a more intense Madden-Julian Oscillation, and thus an across-the-board increase in extreme weather.

"In just looking at precipitation changes, the Madden-Julian Oscillation is supposed to increase in strength in a future climate," Maloney said. "But one of the interesting things from our study is that we don't think this can be generalized to wind as well."

Atmospheric science relies on weather patterns like the Madden-Julian Oscillation to inform weather prediction in other areas of Earth. For example, atmospheric rivers, which are plumes of high atmospheric water vapor that can cause severe flooding on the U.S. west coast, are strongly modulated by certain phases of the Madden-Julian Oscillation.

According to Maloney's work, the Madden-Julian Oscillation's impact on remote areas may gradually decrease. Degradation in the oscillation's wind signal may thus diminish meteorologists' ability to predict extreme weather events. In particular, preferential warming of the upper troposphere in a future, warmer climate is expected to reduce the strength of the Madden-Julian Oscillation circulation.

Maloney and colleagues hope to continue studying the Madden-Julian Oscillation using a broader set of climate models to be used in the next Intergovernmental Panel on Climate Change assessment.

Doctors at The Ohio State University Wexner Medical Center and College of Medicine are pioneering the use of primary targeted muscle reinnervation (TMR) to prevent or reduce debilitating phantom limb and stump pain in amputees.

Losing a limb due to trauma, cancer, or poor circulation can result in phantom limb and stump pain in upwards of 75 percent of amputees in the United States. Primary TMR - the rerouting of nerves cut during amputation into surrounding muscle - greatly reduces phantom limb and residual limb pain, as reported in recent publications by Dr. Ian Valerio, division chief of Burn, Wound and Trauma in Ohio State's Department of Plastic and Reconstructive Surgery, and Dr. J. Byers Bowen, a former resident who is now in private practice. Their latest work featured in the January 2019 issue of Plastic and Reconstructive Surgery describes how to perform this technique in below-the-knee amputations.

TMR was first developed to allow amputees better control of upper limb prosthetics. Traditionally doctors perform the surgery months or years after the initial amputation. When surgeons discovered the procedure also improves certain causes of pain, they started using it to treat disorganized nerve endings called symptomatic neuromas and/or phantom limb pain.

In this paper, Valerio and Bowen provide a detailed description of TMR in below-the-knee amputees and document the benefits of primary TMR for preventing pain.

"This paper provides a blueprint for improving patient outcomes and quality of life following amputation," said Dr. K. Craig Kent, dean of The Ohio State University College of Medicine.

Over the course of three years, the surgeons performed 22 TMR surgeries on below-the-knee amputees, 18 primary and four secondary. None of the patients have developed symptomatic neuromas and only 13 percent of patients who received primary TMR reported having pain six months later.

"A significant amount of pain in amputees is caused by disorganized nerve endings, i.e. symptomatic neuromas, in the residual limb. They form when nerves are severed and not addressed, thus they have nowhere to go," Valerio said. "Attaching those cut nerve endings to motor nerves in a nearby muscle allows the body to re-establish its neural circuitry. This alleviates phantom and residual limb pain by giving those severed nerves somewhere to go and something to do."

Valerio said patients who've had TMR significantly reduce or sometimes stop using narcotics and other nerve pain related medications, which can greatly improve their quality of life.

"TMR has been shown to reduce pain scores and multiple types of pain via a variety of validated pain surveys. These findings are the first to show that surgery can greatly reduce phantom and other types of limb pain directly," Valerio said.

Bowen added that upper extremity amputees are better able to use and control their prosthetics in addition to their improved pain outcomes. He said, "TMR allows for more individual muscle unit firings through the patient's thoughts. It provides for better intuitive control resulting in more refined functional movements and more degrees of motion by an advanced prosthetic."

The researchers believe primary TMR is a reliable technique to prevent the development of disorganized nerve endings and to reduce phantom and other limb pain in all types of amputations. When done at the time of initial amputation, there is minimal health risk and recovery is similar to that of traditional amputation surgery.

Surgeons perform TMR routinely at Ohio State, with primary TMR as the standard of care for most orthopedic-based traumatic and oncologic amputations. Valerio lectures and trains surgeons around the world on the primary TMR technique in an effort to make it a global best practice.

An amusing commercial shows someone having a bad day, and how that person's mood affects each person down the line, with more bad moods. This emotional "contagion" may be a real-world phenomenon, and it appears that what we experience online can have a similar effect. Examining over 2000 video blogs, or vlogs on YouTube, researchers from Tilburg University, Netherlands, found we mirror the emotions of those we see online and we seek out people who share our emotions.

The research appears in Social Psychological and Personality Science.

"Our research is a reminder that the people we encounter online influence our everyday emotions - being exposed to happy (or angry) people can make us more happy (or angry) ourselves." says Hannes Rosenbusch (Tilburg University). Rosenbusch is the lead author of the study.

Being affected by others' emotions is known as "contagion." People also seek out others like themselves, or in this case, people with similar outlooks and moods. In psychology, this is known as "homophily."

With almost 5 billion videos watched on YouTube daily, the researchers focused on vlogs and vloggers. Vloggers share emotions and experiences in their videos, providing a reliable source of data.

The researchers focused on studying more popular vlogs, with a minimum of 10,000 subscribers. Some of their sample vlogs had millions of subscribers.

To measure if people watching vlogs experienced emotional contagion or homophily, the team studied words and emotions expressed by the vloggers and analyzed the emotional language of online comments. They modeled the effect of both immediate (contagion) and sustained (homophily) emotional reactions (See Figure 1).

The team found evidence that there is both a sustained and an immediate effect that leads to YouTuber emotion correlating with audience emotion. When a YouTuber posts a video with a generally positive tone, the audience reacts with heightened positive emotions. The same is true for other emotional states.

They also note that this research looks at a complicated system: humans. The effects of video emotions on audience emotions probably comprises of a collection of mechanisms like contagion, empathy, and sympathy.

This study is the first to use a video-focused social media source like YouTube to explore contagion and homophily. Other researchers have found similar results looking at text-based social media sites like Twitter and Facebook.

"Our social life might move more and more to the online sphere, but our emotions and the way we behave towards one another will always be steered by basic psychological processes," summarizes Rosenbusch.

Anthony Evans and Marcel Zeelenberg are co-authors of this study.

New York, NY (December 27, 2018) -- In the largest population genomics investigation to date, a team of researchers at the Icahn School of Medicine at Mount Sinai, Stanford University, and the University of Colorado have discovered that kidney disease risk variants of the gene APOL1, previously known to affect African and African American populations, are also found at appreciable frequencies in Caribbean and Latin American populations. Because these populations are historically under-studied and under-tested in connection with APOL1, the gene's impact on these populations is currently unknown. The findings were described in a publication released today in The New England Journal of Medicine.

Risk variants in the APOL1 gene were first discovered in African Americans. Consequently, much of the research studies and clinical trials that followed have been heavily focused on self-reported African or African American populations. Knowing this, researchers in the study decided to link genetic and demographic data spanning more than 110 populations, leading to the discovery of APOL1 risk variants in other populations who share ancestry from Africa, such as those who are Hispanic or Latino.

"This finding is crucial in early detection of at-risk individuals who may not be indicated for genetic screening due to self-reporting of ethnic origins, but may still be at high risk due to the presence of APOL1 risk variants," said Girish Nadkarni, MD, Assistant Professor of Medicine (Nephrology) at the Icahn School of Medicine and first author of the study. "It is important to more fully understand the global distribution of these variants based on country of origin and genetic ancestry rather than self-reported race/ethnic group."

Knowing that the APOL1 risk is present in these populations could help physicians tailor treatment more closely to their needs, an example of the approach known as precision medicine. The team's data also provides a centralized resource to help the medical community better understand at-risk kidney disease populations worldwide.

"APOL1 is the poster child for precision medicine, as the risk variants have a large impact on lifetime risk for not only kidney disease, but also early onset hypertension and cardiovascular disease," said Eimear Kenny, PhD, Associate Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, Director of the Center for Genomic Health, and senior author of the publication. "Here at Mount Sinai, we are leading national efforts to learn about the impact of APOL1 risk variants in routine clinical settings, and the gene is currently under intense scrutiny as a therapeutic target and across diverse populations."

A class of drugs used to treat certain breast cancers could help to tackle lung cancers that have become resistant to targeted therapies, suggests a new study in mice from the Francis Crick Institute and the Institute of Cancer Research (ICR).

The research, published in Cell Reports, found that lung tumours in mice caused by mutations in a gene called EGFR shrunk significantly when a protein called p110α was blocked.

Drugs to block p110α are currently showing promise in clinical trials against certain breast cancers, so could be approved for clinical use in the near future. The new findings suggest that these drugs could potentially benefit patients with EGFR-mutant lung cancers whose tumours have become resistant to treatment.

"At the moment, patients with EGFR-mutant lung cancers are given targeted treatments that are very effective for the first few years," explains study leader Professor Julian Downward, who has labs at the Crick and the ICR. "These drugs are improving, but unfortunately after a couple of years the cancer usually becomes resistant and starts to grow and spread again. The second line of treatment is currently conventional chemotherapy, which is not targeted and has substantial side-effects.

"Our new study suggests that it would be worth investigating whether p110α inhibitors could be used as a second-line therapy. As our research is at such an early stage, more research in mice and patient cells would be needed before even considering clinical trials, but it opens up a promising avenue of investigation."

For this research, the team targeted a specific interaction between the RAS protein and p110α. The RAS gene is mutated in around one in five cancers, causing uncontrolled growth, and is a key focus of Julian's research. When they blocked this interaction in genetically modified mice with EGFR mutations, their tumours shrank significantly.

Before the intervention, the tumours filled around two thirds of the space inside the lung. When the interaction between RAS and p110α was genetically blocked, this shrank significantly to about a tenth of the space inside the lung. The intervention also had very few side-effects.

"As we wanted to pinpoint the specific interaction responsible, we used a genetic technique that would not be practical in a patient treatment," says Julian. "We're looking to develop ways to do this with drugs, as blocking this specific pathway would significantly reduce side-effects, but this work is many years from the clinic. In the medium-term, investigating existing drugs that inhibit p110α will be the next step. While these have side-effects, including temporary diabetes-like symptoms during treatment, they are still less toxic than chemotherapy."

On today's increasingly crowded globe, human migration can strain infrastructure and resources. Accurate data on migration flows could help governments plan for and respond to immigrants. Yet these figures, when available, tend to be spotty and error-ridden, even in the developed world. Researchers have developed approaches to estimate migration rates, but even the best of these rely on unrealistic assumptions about the mass movement of people and yield migration rates that can fall far below reality.

In a paper published the week of Dec. 24 in the Proceedings of the National Academy of Sciences, two scientists at the University of Washington unveiled a new statistical method for estimating migration flows between countries, using the so-called pseudo-Bayes approach. They show that rates of migration -- defined as an international move followed by a stay of at least one year -- are higher than previously thought, but also relatively stable, fluctuating between 1.1 and 1.3 percent of global population from 1990 to 2015. In addition, since 1990 approximately 45 percent of migrants have returned to their home countries, a much higher estimate than other methods.

These more accurate estimates of migration will ultimately help both migrants and the people who assist them, said senior author Adrian Raftery, a UW professor of statistics and sociology.

"Planning for migration is no simple task," said Raftery. "You need everything from medical infrastructure and trained personnel to elementary schools -- and governments rely on accurate demographic estimates to help them put the right plans and responses into place."

Countries collect migration data through immigration forms at ports of entry, but answers on these forms may contain mistakes, and often fail to collect the types of comprehensive information that demographers need to measure migration accurately. Census forms also tend to ask people where they were born, but usually not when they moved, information which does not accurately reflect the true level of movement.

"Migration is much more than the place you left and the place you ultimately settled in," said Raftery. "Researchers have tried for years to develop statistical methods that capture the comprehensive picture of human migration across the globe."

Raftery developed these new migration rate estimates along with his former doctoral student Jonathan Azose, a UW affiliate assistant professor of statistics and the paper's lead author. They applied the pseudo-Bayes method to migration estimates by incorporating elements of other methods, and calibrated their estimates against a relatively reliable model of migration among 31 European countries.

Azose and Raftery tested the accuracy of pseudo-Bayes against a set of reliable migration figures and discovered that its estimates were typically accurate to within a factor of three, better than many existing estimates.

"For the migration field, this level of accuracy is a significant improvement," said Azose. "Even when you look at data from European countries, it's not uncommon for a single migration flow to have estimates that differ by a factor of three or more depending on whether the sending or the receiving country collected the data."

They also discovered that, compared to other approaches, pseudo-Bayes can more accurately account for return migration, in which migrants go back to their home countries.

"Our estimate shows a higher global flow of migrants in large part because it indicates that return migration is much higher than previously thought," said Azose.

The researchers estimate significantly higher migration rates than prior methods -- between 67 million and 87 million migrants over each five-year period from 1990 to 2015. By comparison, one widely used alternative method, which only estimates the minimum rate of migration, calculates just 34 to 46 million migrants in each five-year period. In addition, while the total number of migrants estimated by pseudo-Bayes increased from 1990 to 2015, the migration rate over that period remained relatively stable as a proportion of global population -- between 1.1 and 1.3 percent.

Azose and Raftery also broke down migration rates by emigration, return migration and transit migration, in which migrants move between two countries that are not their countries of birth. In general, from 1990 to 2015, more than 60 percent of migration was emigration. Transit migration never topped 9 percent. Return migration accounted for 26 to 31 percent of migrants, more than twice the rate of other migration estimates. That high rate of return migration added up over time. From 1990 to 2015, approximately 45 percent of migrants ultimately returned to their home countries.

"We estimate a rate of return migration that is significantly higher than other methods, but it is also supported by history," said Raftery. "For example, during the Rwandan genocide in 1994, more than a million migrants left the country, but most returned within three years after the conflict ended."

The top migration rates that they observed more recently between countries were consistent with ongoing world events. Migration out of Syria, for example, accounted for two of the top three emigration flows from 2010 to 2015.

The researchers would like to refine their method by differentiating between refugees, which are counted by their method, and other types of migrants. In addition, they would like to incorporate data from non-governmental sources, such as social media records, to improve the accuracy of their estimates, as well as develop approaches to forecast future migration.

DURHAM, N.C. -- A new study from Duke University and Fudan University in China is the first to estimate how much Chinese residential electricity consumption would increase due to climate change. It's a lot.

By the end of the 21st century, each degree Celsius increase in global mean surface temperature (GMST) would raise average Chinese residential electricity use by about 9 percent.

Peak electricity use will rise 36 percent for every increased degree Celsius.

By 2099, scientists estimate mean surface temperature will be 2-5 C hotter than today. If consumption patterns remained similar to today, average residential electricity demand in China would rise by 18 percent at the low end and as much as 55 percent at the high end. Peak usage would rise by a minimum of 72 percent.

This finding has important implications for energy grid planning, but even without climate change, average household electricity consumption in China is projected to double by 2040 due to rising incomes.

The study, "Climate Change and Residential Electricity Consumption in the Yangtze River Delta, China," by Yating Li, William A. Pizer, and Libo Wu, appears the week of December 24 in the Proceedings of the National Academy of Sciences.

"Our findings contribute solid evidence supporting China's low-carbon policy by showing how important increasing demand from the residential sector will be," said Libo Wu, a professor and director of the Center for Energy Economics and Strategies Studies at Fudan.

To examine how customers responded to daily temperature changes, the authors analyzed data from more than 800,000 residential customers in the Pudong district of Shanghai between 2014 and 2016. They combined these data on consumer behavior with a variety of detailed climate model simulations to construct the relationship between projected mean global temperature change at the end of the century and localized projected impacts in China.

"This state-of-the-art approach has been applied to communities in the United States, but this is the first application in China," said Billy Pizer, a professor in Duke's Sanford School of Public Policy and Duke Kunshan University in Jiangsu Province, China. Most previous studies of these impacts have been done in Western countries.

Although residential usage accounts for just one-fourth of total electricity consumption in Shanghai, researchers focused on homes because they are very responsive to temperature fluctuations. During extreme heat days (around August 1) and extreme cold days (around February 1), home usage increases more dramatically in response to temperatures than commercial or industrial usage, and drives peak consumption during these times.

For temperatures above 25 C (77 F), the authors found residential daily electricity consumption increased sharply -- 14.5 percent for every 1 C increase in daily temperature. For example, compared with a comfortable 20 C day, when electricity consumption is the lowest, a 32 C day led to a 174-percent increase in daily electricity consumption.

In the comfortable range between 13 C and 25 C (55 to 77 F), temperature change did not trigger residents to adjust their thermostats. When temperatures dipped below 13 C, electricity use increased with each 1 C drop, but more moderately.

The study found that high-income Chinese used more electricity during the winter. However, the response to hot summer days was similar for all income groups in Shanghai -- everyone reached for the air conditioning.

"If we consider that more provinces would become 'Shanghai' as incomes rise, our results may ultimately be more broadly applicable," said Yating Li, a Duke PhD candidate in environmental policy.

The authors believe the results can be applied to other urban areas in the Yangtze River Delta, which have similar climate and economic conditions. This metropolitan region includes Jiangsu, Zhejiang and Anhui provinces, roughly one-fifth of China's urban population and one-fourth of economic output of China (GDP).

Researchers applied a machine learning technique that could potentially translate patterns of activity in fear-processing brain regions into scores on questionnaires used to assess a patient's fear of pain. This neuroscientific approach, reported in eNeuro, may help reconcile self-reported emotions and their neural underpinnings.

Pain-related fear is typically assessed with various questionnaires, often used interchangeably, that ask patients how they feel about their clinical pain. However, it is unclear to what extent these self-reports measure fear and anxiety, which are known to involve different brain regions, and perhaps other psychological constructs.

Michael Meier and colleagues from Petra Schweinhardts' lab at the Balgrist University Hospital in Zurich, Switzerland, addressed this ambiguity by imaging the brains of patients with low back pain as they watched video clips evoking harmful (bending) and harmless (walking) activities for the back. Participants' brain activity was predictive of their scores on the various questionnaires. Importantly, different questionnaires were associated with distinct patterns of neural activity. These results suggest similar questionnaires may measure different emotional states.

An international team of scientists including an employee of I.M. Sechenov First Moscow State Medical University (MSMU) developed a device for mixing chemical and biological reaction feeds. The team managed to increase the mixing efficiency up to 90%. The new device will be used in biological and chemical experiments. The article of the scientists was published in the RSC Advances journal.

Small mixing devices are used in biological and chemical research in the course of experiments. For example, in biology such mixers are used for analysis, purification, and synthesis of DNA, as well as for the delivery of medicinal drugs. In chemistry they are necessary for carrying out reactions.

There are two types of mixing devices - active and passive ones. In the first group the principle of operation is based on the use of external forces, such as magnetic fields, heat, acoustic fluctuations, and so on, that accelerate the mixing process. However, due to complicated construction they have reduced reliability and service life. Therefore, the second type of mixing devices that uses only the energy of flow movement is considered more prospective. Passive mixers create a turbulent flow - the flow of liquid that causes it to exchange substance between its layers. The efficiency of this method directly depends on a mixer's geometry. As a rule, it consists of one or several metal plates placed one after another in a small tube. Each plate has a considerable number of holes of different shapes and sizes. They direct the flows of liquid and secure their efficient mixing.

A team of sciences from Iran, Australia, and Russia used existing mathematical models of liquid mixing and developed five different variants of passive mixers. Each has its own unique geometry and mixing characteristics. After that the scientists added them one by one into one system named a hybrid micro mixer.

The new mixing device consists of six consequent metal plates with holes of different shapes. By changing the combinations of elements, the researchers created a micro mixer that secures almost 100% mixing of two liquids with low viscosity and 90% - with high viscosity.

"Micro mixers can be used in medical, chemical, and biological research. We've created a hybrid micro mixer and compared it with other mixing devices by mixing efficiency. Our device turned out to be applicable to a wide range of biological studies. The suggested micro mixer has different construction elements that helped us combine the mixing methods. It secures high process efficiency and is designed to replace the existing models of passive micro mixers," said Majid Warkiani, a co-author of the work and a research associate of the laboratory of nanotheranostics at MSMU and of the Institute of Biomedical Materials and Devices, University of Technology Sydney.