Culture

In mammalian adult brains, neural stem cells are only present in few specific parts, so called niches. Only these niches are capable of generating new neurons. For the first time, researchers defined the proteome of these niches, the entire set of expressed proteins, and compared it to other regions of the brain. The findings help to identify key regulators for neurogenesis, an important step towards activating neurogenesis after brain injuries.

What distinguishes neural stem cell niches from other parts of the brain? Why do only these niches contain neural stem cells and the rest of the brain does not? So far, we did not know what gives the niches their special function. Also, little was known about factors allowing the integration of new neurons into existing networks in the adult brain. A comparison of the proteome of neural stem cell niches and the region in which new neurons integrate with the remaining part of the brain, aimed to shed light about the unique niche environment allowing neurogenesis in the otherwise non-permissive adult mammalian brain.

Defining the niche characteristics

In a first step, Magdalena Götz and her team characterized the proteome of these specific brain regions. They used the largest neural stem cell niche in the subependymal zone of the brain and the olfactory bulb as this is the region where newly-generated neurons from the subependymal zone migrate, differentiate and integrate. They then compared this proteome to the cerebral cortex, an area where neither neurogenesis nor integration of new neurons occurs as in most parts of the adult mammalian brain. As a result, the team found that the proteome of the neurogenic niche evokes a niche-specific extracellular matrix architecture. One of the most important characteristics was the high solubility of the extracellular matrix. Other characteristic proteins however, such as those of the multifunctional enzyme transglutaminase 2, are hardly soluble meaning strongly cross-linked. Using pharmacological inhibitors as well as genetic experiments, the team was able to show that transglutaminase 2 is crucial for the regulation of neurogenesis. Furthermore, due to its cross-linking properties, the enzyme may contribute to the unique stiffness of the neural stem cell niche in otherwise soft brain tissue.

Turning the injured brain region into a neural stem cell niche

Having established the differences between the proteome of a neurogenic and a non-neurogenic site is a key step. It could help to find ways to convert the one to the other. Equally important for future cell replacement therapies is the generation of a beneficial environment for the integration of new neurons in the cerebral cortex by activating factors from the olfactory bulb, an area where new neurons are constantly being integrated. Next, the researchers want to compare these proteomes to the environment after brain injury. Their aim is to create new neurons after brain injury by turning the injured region into a neurogenic stem cell niche. Injured tissue demonstrates alternative phenotypes, that may create additional barriers for activating neurogenesis: "One of our collaborators at the University of Cambridge showed that scar tissue in the brain is particularly soft - a trait that is hostile to the function of neurogenesis. Overcoming this hurdle and generating a beneficial environment for repair will be the next steps of our research", says Götz.

From plastics to pesticides, it seems like every week delivers fresh news about the dangers of endocrine disruptors--chemicals in the environment that alter the body's hormones and can lead to reproductive, developmental, neurologic and immune problems and cancer.

Industry regulation and individual consumer choice can reduce exposure to such chemicals, but there are few options to counteract damage that has already occurred.

Now new research conducted in worms suggests a path toward changing that.

A naturally occurring antioxidant known as Coenzyme Q10, or CoQ10, reversed most of the reproductive harms caused by exposure to the plasticizer BPA (bisphenol A) in Caenorhabditis elegans worms, according to a study led by the lab of Monica Colaiácovo, professor of genetics in the Blavatnik Institute at Harvard Medical School.

The findings, published Feb. 6 in Genetics, provide the first evidence that at least some BPA-induced fertility damage can be undone.

"Chemicals are so prevalent in our environment that it was critical for us to focus first on identifying which ones are toxic and how they may affect human reproductive health," said Colaiácovo, senior author of the study.

"Now, as we continue to screen for and study how chemicals affect reproductive health, we can also ask the next really important question: Given that we're all exposed, how can we mitigate those effects in order to improve fertility and have healthier births?"

CoQ10 is produced by the body and can be found in many foods, particularly meat and fish. It is also available in over-the-counter dietary supplements, but those are neither regulated nor FDA-approved for any health conditions, and they occasionally cause side effects.

Although CoQ10 is already being recommended in some fertility clinics in the U.S. and Canada, the research team cautions that their findings must be replicated in further animal studies and in human clinical trials before the enzyme is prescribed for BPA-induced fertility damage.

Colaiácovo's lab has documented the reproductive repercussions of many environmental chemicals in worms, including BPA.

When work from her lab and others suggested that BPA hampers reproductive health in part by causing oxidative damage, "it made sense to look at antioxidants" for help, she said.

The team started with CoQ10 because it's readily available in stores, inexpensive and relatively safe, so if it proved effective in animal models, it would be well positioned for testing in people, said Colaiácovo.

The Kaneka Corporation, an international chemical manufacturer, provided the compound for the study. It did not contribute funding. None of the study authors stand to benefit financially from increased sales of CoQ10, Colaiácovo confirmed.

The researchers exposed groups of C. elegans worms to BPA, CoQ10 and a solvent called DMSO, alone and in various combinations. The timing of BPA and CoQ10 exposures were designed to approximate those in humans, and BPA levels detected inside the worms were proportional to the amounts found in the general human population.

The researchers found that CoQ10 improved or reversed multiple types of damage caused by BPA. Worms treated with the antioxidant had lower rates of egg cell death, fewer double-strand DNA breaks and fewer chromosome abnormalities during egg cell division, and lower levels of oxidative stress in egg cells. Early embryos also had fewer instances of abnormal chromosome numbers and other defects.

In humans, these types of abnormalities can lead to infertility, miscarriage and birth defects.

"CoQ10 rescued a lot of the defects we'd reported before," said Colaiácovo. "It's exciting to consider that we could be looking at a simple, low-cost intervention."

C. elegans has proved a useful model organism for studying countless aspects of basic biology. Many of the reproductive abnormalities caused by exposure to environmental toxins observed in worms are also seen in mammals from mice to primates, said Colaiácovo, boosting hope that the CoQ10 findings will similarly translate.

Nevertheless, humans are not big worms, and people should not rush out and start taking CoQ10 as an anti-BPA agent without consulting a doctor, the study authors said.

For one thing, the researchers used "very pure," quality controlled CoQ10, while store-bought supplements vary in CoQ10 content and do not always contain the amounts stated on labels, previous analyses have found.

"Our study underscores the need for tighter regulation and dedicated research on the biological effects of supplements," said Colaiácovo.

For Colaiácovo, the findings offer a glimmer of hope amid a flood of concerning findings.

"When we uncover evidence of toxicity from yet another chemical, often there is a feeling of 'Here we go again,'" she said. "But it's important to see what we can learn from it. I want us to figure out solutions."

Survival may more than double for adults with glioblastoma, the most common and deadly type of brain tumor, if neurosurgeons remove the surrounding tissue as aggressively as they remove the cancerous core of the tumor.

This discovery, reported in a retrospective study headed by researchers at UC San Francisco, is welcome news for those in the glioblastoma community, which celebrated its last breakthrough in 2005 with the introduction of the chemotherapy drug temozolomide.

Removing the "non-contrast-enhancing tumor" -- so called because it does not light up on MRI when a contrast agent is injected into the vein -- represents a paradigm shift for neurosurgeons, according to senior author and neurosurgeon Mitchel Berger, MD, director of the UCSF Brain Tumor Center.

"Traditionally, the goal of neurosurgeons has been to achieve total resection, the complete removal of contrast-enhancing tumor," said Berger, who is also affiliated with the UCSF Weill Institute for Neurosciences. "This study shows that we have to recalibrate the way we have been doing things and, when safe, include non-contrast-enhancing tumor to achieve maximal resection."

Mutant Tumor Type Indicative of Longer Life

Some 22,850 Americans are diagnosed each year with glioblastoma -- one of the most relentless adult cancers and one that may be best known for claiming the lives of senators John McCain and Edward Kennedy, and the son of Vice President Joe Biden. The average survival for the 91 percent of glioblastoma patients whose tumor is characterized by IDH-wild-type mutations is 1.2 years, according to a 2019 study. However, the remaining 9 percent have a type of glioblastoma classified as IDH mutant, with average survival of 3.6 years.

In their study, which publishes in JAMA Oncology on Feb. 6, 2020, the researchers tracked the outcomes of 761 newly diagnosed patients at UCSF who had been treated from 1997 through 2017. The patients, whose average age was 60, were divided into four groups with varying risk based on age, treatment protocols, and extent of resections of both contrast-enhancing and non-contrast-enhancing tumor.

They identified a group of 62 patients whose average survival was 37.3 months (3.1 years). These patients had IDH-mutant tumors, or were under 65 with IDH-wild-type tumors and had undergone both radiation and chemotherapy with temozolomide in virtually all cases. Each had resections with a median of 100 percent of contrast-enhancing tumor and a median of 90 percent of non-contrast-enhancing tumor.

In comparison, their counterparts -- 212 patients under 65 who had received the same therapies, but had more modest resections of the non-enhancing tumor -- survived only 16.5 months (1.4 years) on average, or about half as long. These results were verified with patient cohorts at the Mayo Clinic and the Cleveland Clinic's Ohio Brain Tumor Study.

Resecting Non-Enhancing Tumor Evens Survival Between Tumor Types

Among the group of longer-surviving patients, those with IDH-wild-type tumor did approximately as well as those with the IDH-mutant variant when a portion of the non-contrast enhancing tumor was removed, the authors noted. "The difference was that the patients with IDH-wild-type tumor declined more rapidly after the three-year mark," said first author Annette Molinaro, PhD, from the UCSF Department of Neurological Surgery, and the Department of Epidemiology and Biostatistics.

The researchers caution that maximal resection should only be achieved when it can be safely performed using techniques such as intraoperative brain mapping. This means that areas of the brain responsible for speech, motor, sensory and cognition are tested during surgery to ensure that these functional areas are preserved.

"There is a survival benefit for maximal resection for patients with glioblastoma, but as surgeons we must remove them in a manner that limits injury to the rest of the brain," said co-author and neurosurgeon Shawn Hervey-Jumper, MD, of the UCSF Brain Tumor Center and of the Weill Institute for Neurosciences.

Brain Mapping Is Critical for Aggressive Surgery

"Although these data show a survival benefit associated with maximal resection, it remains critically important that we do our best to remove tumor in a manner that will not harm the patient," Hervey-Jumper said, noting that about 80 percent of medical centers do not offer brain mapping.

While maximal resection of both enhancing and non-enhancing tumor should always be considered, Molinaro said that we are a long way from achieving a cure for glioblastoma.

"It's a complex tumor to treat for a number of reasons," she said. "One challenge is that the blood-brain barrier -- the network of blood vessels that acts as the brain's gatekeeper -- effectively blocks many cancer agents from reaching their target. Another challenge is that these are heterogenous tumors driven by multiple mutations -- if you target one mutation, others will thrive."

Materials called perovskites show strong potential for a new generation of solar cells, but they've had trouble gaining traction in a market dominated by silicon-based solar cells. Now, a study by researchers at MIT and elsewhere outlines a roadmap for how this promising technology could move from the laboratory to a significant place in the global solar market.

The "technoeconomic" analysis shows that by starting with higher-value niche markets and gradually expanding, solar panel manufacturers could avoid the very steep initial capital costs that would be required to make perovskite-based panels directly competitive with silicon for large utility-scale installations at the outset. Rather than making a prohibitively expensive initial investment, of hundreds of millions or even billions of dollars, to build a plant for utility-scale production, the team found that starting with more specialized applications could be accomplished for more realistic initial capital investment on the order of $40 million.

The results are described in a paper in the journal Joule by MIT postdoc Ian Mathews, research scientist Marius Peters, professor of mechanical engineering Tonio Buonassisi, and five others at MIT, Wellesley College, and Swift Solar Inc.

Solar cells based on perovskites -- a broad category of compounds characterized by a certain arrangement of their molecular structure -- could provide dramatic improvements in solar installations. Their constituent materials are inexpensive, and they could be manufactured in a roll-to-roll process like printing a newspaper, and printed onto lightweight and flexible backing material. This could greatly reduce costs associated with transportation and installation, although they still require further work to improve their durability. Other promising new solar cell materials are also under development in labs around the world, but none has yet made inroads in the marketplace.

"There have been a lot of new solar cell materials and companies launched over the years," says Mathews, "and yet, despite that, silicon remains the dominant material in the industry and has been for decades."

Why is that the case? "People have always said that one of the things that holds new technologies back is that the expense of constructing large factories to actually produce these systems at scale is just too much," he says. "It's difficult for a startup to cross what's called 'the valley of death,' to raise the tens of millions of dollars required to get to the scale where this technology might be profitable in the wider solar energy industry."

But there are a variety of more specialized solar cell applications where the special qualities of perovskite-based solar cells, such as their light weight, flexibility, and potential for transparency, would provide a significant advantage, Mathews says. By focusing on these markets initially, a startup solar company could build up to scale gradually, leveraging the profits from the premium products to expand its production capabilities over time.

Describing the literature on perovskite-based solar cells being developed in various labs, he says, "They're claiming very low costs. But they're claiming it once your factory reaches a certain scale. And I thought, we've seen this before -- people claim a new photovoltaic material is going to be cheaper than all the rest and better than all the rest. That's great, except we need to have a plan as to how we actually get the material and the technology to scale."

As a starting point, he says, "We took the approach that I haven't really seen anyone else take: Let's actually model the cost to manufacture these modules as a function of scale. So if you just have 10 people in a small factory, how much do you need to sell your solar panels at in order to be profitable? And once you reach scale, how cheap will your product become?"

The analysis confirmed that trying to leap directly into the marketplace for rooftop solar or utility-scale solar installations would require very large upfront capital investment, he says. But "we looked at the prices people might get in the internet of things, or the market in building-integrated photovoltaics. People usually pay a higher price in these markets because they're more of a specialized product. They'll pay a little more if your product is flexible or if the module fits into a building envelope." Other potential niche markets include self-powered microelectronics devices.

Such applications would make the entry into the market feasible without needing massive capital investments. "If you do that, the amount you need to invest in your company is much, much less, on the order of a few million dollars instead of tens or hundreds of millions of dollars, and that allows you to more quickly develop a profitable company," he says.

"It's a way for them to prove their technology, both technically and by actually building and selling a product and making sure it survives in the field," Mathews says, "and also, just to prove that you can manufacture at a certain price point."

Already, there are a handful of startup companies working to try to bring perovskite solar cells to market, he points out, although none of them yet has an actual product for sale. The companies have taken different approaches, and some seem to be embarking on the kind of step-by-step growth approach outlined by this research, he says. "Probably the company that's raised the most money is a company called Oxford PV, and they're looking at tandem cells," which incorporate both silicon and perovskite cells to improve overall efficiency. Another company is one started by Joel Jean PhD '17 (who is also a co-author of this paper) and others, called Swift Solar, which is working on flexible perovskites. And there's a company called Saule Technologies, working on printable perovskites.

Mathews says the kind of technoeconomic analysis the team used in its study could be applied to a wide variety of other new energy-related technologies, including rechargeable batteries and other storage systems, or other types of new solar cell materials.

"There are many scientific papers and academic studies that look at how much it will cost to manufacture a technology once it's at scale," he says. "But very few people actually look at how much does it cost at very small scale, and what are the factors affecting economies of scale? And I think that can be done for many technologies, and it would help us accelerate how we get innovations from lab to market."

The situation is extraordinary: there have only ever been four declarations of public health emergencies of international concern in the past and now there are two at the same time. Whilst the risks associated with the novel coronavirus are still unclear, people in the Democratic Republic of the Congo are still battling with an outbreak of the deadly Ebola virus which has been ongoing since 2018 and has already claimed over 2000 lives. One issue is the precise characterisation of the pathogen because the ebolaviruses, like lots of viruses, appear in various genetic forms. Only the analysis of its genetic material provides the information necessary to develop specific tests for diagnosis and decide on efficient measures for controlling the outbreak. A German Center for Infection Research (DZIF) team at Charité - Universitätsmedizin Berlin has now developed a test which accelerates the process of identifying the genetic makeup of the virus.

There have been multiple Ebola outbreaks in the last decades. Since 2013, at least eight countries have been affected and 30,000 people have contracted the virus. The origin of these outbreaks is often unclear and they are caused by various ebolavirus variants. "At the moment, it often takes months to develop the right tools to fully characterise the genetic material of the ebolavirus causing an outbreak" explains Professor Jan Felix Drexler, a scientist at the German Center for Infection Research (DZIF) and Charité. "However, this knowledge is crucial for developing specific diagnostic tests, identifying transmission chains and eventually controlling the outbreak."

The scientists in Professor Drexler's team have now developed a test which provides information about the genetic material of new ebolaviruses regardless of the species or the variant, that is, of the genetic makeup. The test is based on the commonly used polymerase chain reaction (PCR), using which the genetic material can be amplified in a manner that allows precise sequencing. The new test is compatible with various technical procedures such as high-throughput sequencing. It has been tested with four different ebolavirus species.

"In cases in which different regions and countries are affected by outbreaks of this kind in particular, it is necessary to establish whether the case in question relates to the spread of a previously known variant of the virus or a new outbreak," explains the virologist. This is exactly what the new test can now determine in one process. "Both in the current outbreak in the Democratic Republic of the Congo and in future outbreaks, we may now be able to characterise the trigger more quickly and take appropriate effective measures to end the outbreak," says the scientist.

Hip replacements, severe burns, spinal cord injuries, blast injuries, traumatic brain injuries--these seemingly disparate traumas can each lead to a painful complication during the healing process called heterotopic ossification. Heterotopic ossification is abnormal bone formation within muscle and soft tissues, an unfortunately common phenomenon that typically occurs weeks after an injury or surgery. Patients with heterotopic ossification experience decreased range of motion, swelling and pain.

Currently, "there's no way to prevent it and once it's formed, there's no way to reverse it," says Benjamin Levi, M.D., Director of the Burn/Wound/Regeneration Medicine Laboratory and Center for Basic and Translational Research in Michigan Medicine's Department of Surgery. And while experts suspected that heterotopic ossification was somehow linked to inflammation, new U-M research explains how this happens on a cellular scale--and suggests a way it can be stopped.

To help explain how the healing process goes awry in heterotopic ossification, the research team, led by Levi, Michael Sorkin, M.D. and Amanda Huber, Ph.D., of the Department of Surgery's section of plastic surgery, took a closer look at the inflammation process in mice. Using tissue from injury sites in mouse models of heterotopic ossification, they used single cell RNA sequencing to characterize the types of cells present. They confirmed that macrophages were among the first responders and might be behind aberrant healing.

Macrophages are white blood cells whose normal job is to find and destroy pathogens. Upon closer examination, the Michigan team found that macrophages are more complex than previously thought--and don't always do what they are supposed to do.

"Macrophages are a heterogenous population, some that are helpful with healing and some that are not," explains Levi. "People think of macrophages as binary (M1 vs. M2). Yet we've shown that there are many different macrophage phenotypes or states that are present during abnormal wound healing."

Specifically, during heterotopic ossification formation, the increased presence of macrophages that express TGF-beta leads to an errant signal being sent to bone forming stem cells.

For now, the only way to treat heterotopic ossification is to wait for it to stop growing and cut it out which never completely restores joint function. This new research suggests that there may be a way to treat it at the cellular level. Working with the lab led by Stephen Kunkel, Ph.D. of the Department of Pathology, the team demonstrated that an activating peptide to CD47, p7N3 could alter TGF-beta expressing macrophages, reducing their ability to send signals to bone-forming stem cells that lead to heterotopic ossification.

"During abnormal wound healing, we think there is some signal that continues to be present at an injury site even after the injury should have resolved," says Levi. Beyond heterotopic ossification, Levi says the study's findings can likely be translated to other types of abnormal wound healing like muscle fibrosis.

The team hopes to eventually develop translational therapies that target this pathway and further characterize not just the inflammatory cells but the stem cells responsible for the abnormal bone formation.

An international study, in which the University of Granada (UGR) participated, has confirmed that intergroup contact between advantaged groups (ethnic majorities and cis-heterosexuals) and disadvantaged groups (ethnic minorities and sexual minorities) is not always positive as a strategy for reducing prejudice toward disadvantaged groups, contrary to the view traditionally defended in the Social Psychology field.

The research, published recently by the journal Nature Human Behavior, notes that, for minority groups, this contact seems to be negatively related to support for social change toward greater equality.

The team led by Tabea Hässler and Johannes Ullrich of the University of Zurich (Switzerland) coordinated an international study conducted jointly by academics from 69 countries, in which data was collected from advantaged groups (ethnic majorities and cis-heterosexuals) and disadvantaged groups (ethnic minorities and sexual minorities). By means of international coordination, data was obtained from a total of 12,997 people from different groups and countries.

The results show that, for people who belong to a majority (for example, heterosexuals), contact with a minority group (for example, LGTBI people) fosters support for social equality. The greater the degree of contact, the greater the support for disadvantaged groups.

By contrast, for minority groups, intergroup contact and support for social change toward greater equality appear to be negatively associated. That is, intergroup contact in this case makes people who belong to minorities less supportive of equality (even though, a priori, equality is something that benefits them as a group).

Mario Sainz Martínez of the UGR's Mind, Brain and Behaviour Research Centre (CIMCYC) and Professor at the School of Psychology of the University of Monterrey (Nuevo León, Mexico) is one of the researchers on the project. He notes that, despite the differences between countries and between groups, "in general, our results show that, indeed, intergroup contact, in certain situations, can have negative consequences for disadvantaged groups, as it can encourage people in minorities to form attitudes against equality and against their rights as a collective."

Social implications of the study

Even where there are important variations in this effect, depending on how the intergroup contact and support for social change are operationalised, these results are relevant for research in Social Psychology, since they raise important questions regarding the type of strategies (for example, cooperation or confrontation) necessary to achieve greater support for pro-social-equality policies and actions.

The authors of this paper argue that, on occasion, intergroup contact between minority and majority groups may lead to attempts to rationalise the existence of economic inequalities, unequal access to resources and education, and so on. "For example, contact between people who are residents of a given country and immigrants does not necessarily lead to more favourable attitudes toward migrants or favour their integration in society. Sometimes, this contact actually serves to reinforce stereotypes or conflictive situations," concludes the UGR researcher.

PHILADELPHIA - Like buoys bobbing on the ocean, many receptors float on the surface of a cell's membrane with a part sticking above the water and another underwater, inside the cell's cytoplasm. But for cells to function, these receptors must be docked at specific regions of the cell. Most research has focused on the 'underwater' portions. That's where the cell's molecular machines swarm and interact with a receptor's underwater tails, with those interactions then fueling signals that dive deep into the nucleus, changing the cell's course.

New work by a team of Thomas Jefferson University researchers reveals new activity above the surface, in brain-cell receptors that govern learning and chronic pain. In the study, the authors show that the 'above water' portion of proteins can help dock the proteins at synapses, where neurons mediate flow of information throughout the brain. This discovery opens the possibility of using this docking site as a target to develop treatments for chronic pain and other diseases more effectively. The study was published January 29th in Nature Communications.

"The extracellular spaces - the parts 'above the water' - have been largely overlooked," says senior author Matthew Dalva, PhD, professor and vice chair of the Department of Neuroscience and director of the Jefferson Synaptic Biology Center in the Vickie & Jack Institute for Neuroscience - Jefferson Health. Dr. Dalva and his team looked at the NMDAR receptor on brain cells and pinpointed the spot where this receptor interacts with a neighbor to initiate signaling. "When trying to develop new therapy, finding the bullseye is half the problem," says Dr. Dalva.

Finding a key interaction that sits above the cell's surface, could make it more accessible to therapeutics. "The kinds of receptor interactions we're talking about are different than when a receptor binds to its ligand outside of the cell, which is well documented," says Dr. Dalva. "Here we're describing the kinds of biochemical exchanges - kinase phosphorylation fueled by free-floating ATP - that we thought, until recently, were exclusive to the inside of cells."

The researchers focused on the synaptic protein called NMDA-type glutamate receptors (NMDARs), which help regulate the strength of synaptic connections between neurons. It's important that the synapse connects strongly, but not too strongly, in order to prevent creating an overly excitable connection.

A key mechanism controlling synaptic strength is the increase in NMDAR function due to direct molecular interaction with another synaptic protein called the EphB receptor tyrosine kinase. Dr. Dalva and colleagues had previously shown that the phosphorylation of EphB on the "outside" or extracellular portion of the molecule can lead to a direct interaction with NMDARs. And that chemical exchange causes the receptors to cluster and drive neuronal plasticity and chronic pain (PlosBiology 2017). Their new work identifies a specific region of the NMDAR or bullseye, necessary for these proteins to interact.

This specific bullseye could have important medical implications, as disruption of the EphB-NMDAR interaction has been associated with Alzheimer's, and in chronic pain can be due to too much of this interaction. As a trans-synaptic organizer and NMDAR binding protein, the EphB receptor is a key regulator of these events.

However, despite discovery of this interaction over a decade ago, the exact spot where NMDAR interacts with EphB has been a mystery. Here, the researchers demonstrate that specific amino acids in the hinge region of the NDMAR are required to interact with EphB2. Importantly, the amino acids in the hinge region are required for proper NDMAR mobility and stabilization at the synapse.

"There is growing evidence that extracellular interactions may play key regulatory roles in diseases ranging from pain to cancer and even malaria," says Dr. Dalva. "As we begin to define what these exchanges look like, we'll be able to study them, understand their contribution to disease and potentially use them to find better medical interventions."

In the future, robots could take blood samples, benefiting patients and healthcare workers alike.

A Rutgers-led team has created a blood-sampling robot that performed as well or better than people, according to the first human clinical trial of an automated blood drawing and testing device.

The device provides quick results and would allow healthcare professionals to spend more time treating patients in hospitals and other settings.

The results, published in the journal Technology, were comparable to or exceeded clinical standards, with an overall success rate of 87% for the 31 participants whose blood was drawn. For the 25 people whose veins were easy to access, the success rate was 97%.

The device includes an ultrasound image-guided robot that draws blood from veins. A fully integrated device, which includes a module that handles samples and a centrifuge-based blood analyzer, could be used at bedsides and in ambulances, emergency rooms, clinics, doctors’ offices and hospitals.

Venipuncture, which involves inserting a needle into a vein to get a blood sample or perform IV therapy, is the world’s most common clinical procedure, with more than 1.4 billion performed yearly in the United States. But clinicians fail in 27% of patients without visible veins, 40% of patients without palpable veins and 60% of emaciated patients, according to previous studies.

Repeated failures to start an IV line boost the likelihood of phlebitis, thrombosis and infections, and may require targeting large veins in the body or arteries – at much greater cost and risk. As a result, venipuncture is among the leading causes of injury to patients and clinicians. Moreover, a hard time accessing veins can increase procedure time by up to an hour, requires more staff and costs more than $4 billion a year in the United States, according to estimates.

“A device like ours could help clinicians get blood samples quickly, safely and reliably, preventing unnecessary complications and pain in patients from multiple needle insertion attempts,” said lead author Josh Leipheimer, a biomedical engineering doctoral student in the Yarmush lab in the biomedical engineering department in the School of Engineering at Rutgers University–New Brunswick.

In the future, the device could be used in such procedures as IV catheterization, central venous access, dialysis and placing arterial lines. Next steps include refining the device to improve success rates in patients with difficult veins to access. Data from this study will be used to enhance artificial intelligence in the robot to improve its performance.

Rutgers co-authors include Max L. Balter and Alvin I. Chen, who both graduated with doctorates; Enrique J. Pantin at Rutgers Robert Wood Johnson Medical School; Professor Kristen S. Labazzo; and principal investigator Martin L. Yarmush, the Paul and Mary Monroe Endowed Chair and Distinguished Professor in the Department of Biomedical Engineering. A researcher at Icahn School of Medicine at Mount Sinai Hospital also contributed to the study.

Journal

TECHNOLOGY

DOI

10.1142/S2339547819500067

BINGHAMTON, N.Y. - Easter Island society did not collapse prior to European contact and its people continued to build its iconic moai statues for much longer than previously believed, according to a team of researchers including faculty at Binghamton University, State University of New York.

The island of Rapa Nui is well-known for its elaborate ritual architecture, particularly its numerous statues (moai) and the monumental platforms that supported them (ahu). A widely-held narrative posits that construction of these monuments ceased sometime around 1600, following a major societal collapse.

"Our research flies in the face of this narrative," said Carl Lipo, an anthropologist at Binghamton University. "We know, of course, that if we are right, we really need to challenge ourselves (and the archaeological record) to validate our arguments. In this case, we thought to look carefully at the tempo of construction events associated with large platforms."

The researchers, led by the University of Oregon's Robert J. DiNapoli, examined radiocarbon dates, relative architectural stratigraphy and ethnohistoric accounts to quantify the onset, rate and end of monument construction as a means of testing the collapse hypothesis.

"Archaeologists assign ages to the archaeological record by getting what are known as radiocarbon dates," said Lipo. "These dates represent the amount of time since some organisms (a bush, tree, etc.) died. Assembling groups of these dates together to look at patterns requires some sophisticated statistical analyses that have only recently been available to archaeologists. In this paper, we use these tools to provide the first-ever look at the history of platform construction on Easter Island."

The researchers found that construction of these statues began soon after colonization and increased rapidly, sometime between the early-14th and mid-15th centuries, with a steady rate of construction events that continued beyond European contact in 1722.

"What we found is that once people started to build monuments shortly after arrival to the island, they continued this construction well into the period after Europeans arrived," said Lipo. "This would not have been the case had there been some pre-contact "collapse"-- indeed, we should have seen all construction stop well before 1722. The lack of such a pattern supports our claims and directly falsifies those who continue to support the 'collapse' account.

"Once Europeans arrive on the island, there are many documented tragic events due to disease, murder, slave raiding and other conflicts," he added. "These events are entirely extrinsic to the islanders and have, undoubtedly, devastating effects. Yet, the Rapa Nui people -- following practices that provided them great stability and success over hundreds of years -- continued their traditions in the face of tremendous odds. The degree to which their cultural heritage was passed on - and is still present today through language, arts and cultural practices -- is quite notable and impressive. I think this degree of resilience has been overlooked due to the "collapse" narrative, and deserves recognition."

The researchers believe that their model-based approach to test hypotheses regarding the chronology of collapse can be extended to other case studies around the world where similar debates remain difficult to resolve.

Half of female Spanish researchers believe that being a woman makes your career more difficult. Furthermore, 70% of female scientists think that there are not enough female researchers in leadership roles in Spain. This is according to a report on gender equality in research published by the Society of Spanish Researchers in the United Kingdom in collaboration with the Cotec Foundation. In an attempt to mitigate this inequality, companies and institutions across Europe are implementing gender equality measures in R&D, the outcome of which is not normally evaluated from a scientific perspective.

In light of the situation, the Universitat Oberta de Catalunya (UOC) and Arhaus University in Denmark have participated in a study led by the German research organization Fraunhofer, which analysed 19 interventions of this nature in six European countries (including Spain). The research has shown that more resources are needed and that all employees need greater gender competence for these R&D equality measures to be effective.

"One of institutions' main areas for improvement is the level of gender competence throughout the institution, from employees without management responsibilities, through to middle management and senior decision-makers," said Rachel Palmén. Palmén is a member of the Gender and ICT research group at the UOC's Internet Interdisciplinary Institute (IN3), and the study's principal investigator.

The study, which has been published in the journal Evaluation and Program Planning, analyses different gender equality initiatives in sectors such as higher education, business and government administration. It focuses on the countries of Austria, Denmark, Germany, Hungary, Spain and Sweden, analysing their interventions on a regional, national and institutional level.

The study's results highlight the need to invest more resources into devising equality measures

In each of the 19 case studies, the scientists carried out document analysis and conducted between four and twelve interviews with those in charge of gender policy, those affected by the measures and other employees, both male and female.

The study, which is part of the EFFORTI project, then used the data to analyse how gender quality measures are implemented in relation to eight parameters: if they were coherent with the outlined objectives, if they had changed over time, who assumed responsibility, their relationship with decision-making organisms, what fixed procedures were in place, which factors inhibited their implementation, which factors favoured their implementation and if the obstacles that did exist could be overcome.

Palmén and her team were able to deduce that, in Spain, far fewer resources are dedicated to gender equality measures in R&D than in other countries such as Austria, Germany or other Nordic countries. She said that "in the Spanish case studies we see a constant lack of resources for this type of intervention, although expectations of real change remain high, leading to unrealistic expectations of what can actually be achieved".

Despite this lack of resources, it seems Spain has one of the most advanced legislative frameworks for gender equality in R&D. "This country has a wealth of experience in devising gender equality plans and is home to some of the most well-known experts in this area in Europe," Palmén said.

More than just figures: reducing gender bias

The research highlights a widespread notion that gender equality simply means having the same number of women and men in a company or institution. "It's much more than that: it also involves thinking about how institutional processes and procedures can promote or reduce gender bias," said Palmén.

In the specific case of the R&D sector, the measures must go beyond just achieving institutional change and consider that the gender dimension should be integrated into research and innovation. "Gender equality interventions in R&D are complex and any evaluation of these measures must take this complexity into account," Palmén said.

In many workplaces, standing desks and walking meetings are addressing the health dangers of sitting too long each day, but for universities, the natural question is how to make such adjustments for classrooms.

The question appealed to emerita dance professor Angelia Leung from the UCLA Department of World Arts & Cultures/Dance. Sitting too long was never an issue for Leung's students. But for most college students, desk time is more common than dance time. In an unusual collaboration between the arts and sciences, Leung partnered with Burt Cowgill, an assistant adjunct professor with the UCLA Fielding School of Public Health, to find ways to help students stand up.

The team's research, published in the Journal of American College Health on Feb. 6, hit upon solutions that students and faculty can agree on. However, all the solutions, the researchers said, would work best if joined with an effort to raise awareness about the health risks of extended sitting, aimed at shifting cultural expectations and norms about classroom etiquette.

Studies have linked prolonged sitting with health concerns such as heart disease, cancer, depression, diabetes and obesity. Research shows that breaking up long periods of sitting with movement at least once an hour reduces those risks, while regular exercise at other times of day does not. Despite those risks, the UCLA research found that more than half of students interviewed considered it socially unacceptable to stand up and stretch in the middle of class, and nearly two-thirds felt the same about doing so during smaller discussion sections.

"A cultural change has to take place -- that it's OK to take a stretch break, to stand up during a lecture, to fidget when needed -- it's 'good' for health's sake," Leung said. "My students have an advantage because dance classes naturally involve movement, but we can extend these benefits to any class on campus with something as simple as short stretching breaks -- no dancing required."

Some of the recommendations are simple: Take hourly breaks to stand and stretch during long classes; include more small-group activities that require moving to switch desks; and create more open classrooms with space to walk without squeezing past fellow students and room to install standing desk areas.

To overcome social stigma, the researchers emphasized that professors and instructors will have to take the lead in offering group breaks at specific times rather than suggesting students can get up any time they wish. They also recommended that professors encourage students to get up and move during their breaks; and suggested that university administrators establish policies that call for building more open classrooms and adding features such as adjustable desks.

The research was funded by the Semel Healthy Campus Initiative Center at UCLA, a campuswide effort to make the healthy choice the easy choice, and to promote wellness through education and research. For the study, moderators conducted eight focus-group interviews and guided discussions with 66 UCLA students, roughly half undergraduates and half graduate students. The researchers also interviewed eight faculty members. The researchers looked at how much students and faculty knew about the health risks of sitting, investigated whether the participants could avoid prolonged sitting in class, and gathered ideas for feasible solutions.

"We need to change the way we teach so that we can offer more standing breaks, create opportunities for in-class movement, and even change the built environment so that there's more room for moving around," Cowgill said.

But even though the study found that students and faculty were broadly supportive of making changes, Cowgill said he doubts people will, ahem, stand up against the status quo if there isn't also an effort to raise awareness about the health risks. Social norms and the physical classroom environment are barriers, but awareness is the biggest obstacle.

Cowgill said he was surprised to learn that many of the participants were not aware of the health problems that prolonged sitting can cause, even for people who are otherwise active. "Many people thought they would be fine if they also squeezed in a 30-minute jog, and that's just not what research shows us."

The researchers expect the study will shed light on misconceptions about the health risks of extended sitting, and help faculty and students learn the ways they can work together to stand up and stretch.

Rural areas have been hit hard by the opioid crisis, but few studies have been done to understand how to improve access to treatment and reduce the overdose death rate in these communities, according to a new study by Rutgers University, the University of Michigan, and Wayne State University.

The study appears in The American Journal of Drug and Alcohol Abuse.

The researchers analyzed previous studies on treatment around opioid use disorder (OUD) in rural areas of the United States and identified a number of barriers to treatment. They found that earlier research consistently showed there are far fewer medication providers and treatment resources in rural areas. People living in rural communities are also more likely to face burdensome travel distances when seeking help.

More surprisingly, they found a lack of overall research.

"We saw multiple gaps in terms of research in rural settings even though these communities surpassed the urban overdose-death rate in 2015," said Jamey Lister, lead author and an assistant professor at Rutgers School of Social Work. "Primarily, there are no long-term studies of treatment outcomes for rural patients, no attention to racial minorities in rural settings, limited attention to rural treatment barriers in the Midwest and no studies that asked rural patients for their perspectives on medication treatment."

After reviewing the literature, the Rutgers, UM, and Wayne State researchers made a number of recommendations, including:

Making medication treatment more accessible, with an expansion of telemedicine by creating policy that exempts rural patients from in-person visits when starting treatment and reimbursing telemedicine for publicly insured patients.

Encouraging low-cost options such as technology-assisted treatment and peer recovery specialists to address other psychosocial problems.

Subsidizing transportation through policies offering reimbursement for mileage, non-emergency medical shuttles and ride-sharing, especially for people whose methadone or buprenorphine treatments require frequent clinic visits.

Promoting legislation that allows pharmacies to dispense medication treatment such as in Australia, Canada and the United Kingdom.

Having doctors and hospitals encourage healthcare providers to complete training about administering medication, and building relationships with other specialists delivering treatment.

The researchers' recommendations involve coordination between stakeholders, including academics, healthcare systems, policymakers and community advocates, said Lister, whose expertise includes access and quality of treatment for people with addiction.

He will be discussing their recommendations and building coalitions with rural advocates and policymakers at the National Rural Health Association's Rural Health Policy Institute in February.

Vaccine responses in the developing immune systems of children may depend on factors such as age, location and anemia status, according to a study comparing samples from 1,119 Dutch children to 171 children in sub-Saharan Africa who took part in a malaria vaccine trial. By casting light on how geography shapes immune responses in children, the findings could help health authorities conduct more effective vaccination campaigns in developing countries. Children in low-income countries are highly susceptible to both vaccine-preventable diseases and infections such as malaria that have historically lacked a vaccine. However, some immunizations do not work as well in children as in adults, partly because scientists don't fully understand how age, nutrition and genetics influence the developing immune system. Danika Hill and colleagues examined blood samples from 55 children in Tanzania and 116 children in Mozambique under the age of five who had taken part in a phase 3 trial for RTS,S (MosquirixTM) - one of the first vaccines for malaria licensed in Europe. They found that the composition of immune cells in the children evolved over the 32-month trial, and in some cases matured more quickly when compared with samples from Dutch children collected during a previous study. Furthermore, children in Mozambique showed a stronger antibody response to the malaria vaccine compared with Tanzanian children, hinting that geography within continents also influences immune dynamics. One key finding was that children in Tanzania and Mozambique with anemia showed weaker immune responses to the vaccine and lower frequencies of B cells, which, through follow-up studies in the lab, the authors tied to a lack of bioavailable iron. They say their results could explain the poor vaccination outcomes observed in anemic children and iron-deficient adults, but add that further studies should dissect the influence of iron deficiency.

COLUMBIA, Mo. - Retailers and brands such as Kohl's, Nike, Target, Tommy Hilfiger and Zappos have recently launched adaptive apparel lines, and economists have predicted that the U.S. adaptive clothing market could grow to $54.8 billion by 2023. However, brands should consider the language they use when marketing products to this group of consumers, according to a new study from the University of Missouri. Researchers say that "adaptive" makes the apparel seem separate from the market.

"Terms such as 'adaptive apparel' are popular with companies," said Kerri McBee Black, instructor of textile and apparel management. "However, calling an item of clothing adaptive can alienate and exclude people living with disabilities. Like all consumers, this population wants to feel embraced by a brand, not excluded as someone different."

McBee-Black and co-author Jung Ha Brookshire surveyed how four terms -- adaptive apparel, functional apparel, universal design and inclusive design -- were used in apparel research and in the marketplace. They found that, for consumers with disabilities, the term adaptive could be interpreted as apparel that focused on their disability and not on their apparel needs and wants. They also found that while adaptive apparel was the term most commonly used in the marketplace, universal design and inclusive design were rarely used, although these are terms seen as less stigmatizing to people living with disability.

"Adaptive is the popular terminology but very non-inclusive of the disabled community," McBee Black said. "Perhaps the adaptiveness of the products should be communicated using a more inclusive tone. This would allow consumers to see adaptive apparel as useful for anyone and not just apparel designed for wheelchair users. Using inclusive descriptors within marketing and communications strategies benefits all consumers, including those with disabilities."

McBee-Black hopes her research on apparel and people living with disabilities will bring about change for consumers, brands, educators and even policymakers.

"Currently, the Americans with Disabilities Act focuses primarily on the built-environment," McBee Black said. "Including language about inclusive or universally designed products used in everyday life, like apparel, could help remove the barriers to social participation, including workforce participation that many people living with disabilities face. It also might drive apparel brands to consider a more inclusive approach in their designs."

The researchers suggest that apparel brands need to invest their time into understanding how the words used to describe the apparel they are marketing to consumers with disabilities.