Culture

For the average person, getting a cut or scrape on the foot may not be cause for immediate concern. However, for people with type 2 diabetes, these wounds can be life-threatening. According to a 2016 study, one-third of the cost of type 2 diabetes treatment is related to non-healing foot wounds and ulcers, which are the leading cause of amputation in the United States.

"This is a major clinical problem," says Katherine Gallagher, M.D., vascular surgeon and an Associate Professor in Michigan Medicine's Departments of Surgery and Microbiology/Immunology. "Most people don't realize that if someone has a major amputation due to a non-healing wound, they have only a 50 percent survival rate at three years, which is actually worse than most cancers."

In a new paper in the journal Immunity, Gallagher, first authors Andrew Kimball, M.D. and Frank Davis, M.D., and their colleagues describe for the first time an enzyme that seems to be critical for normal healing--and, in diabetes, appears to be missing. The discovery also hints at a possible treatment.

Steps to healing

It all starts with the immune system and cells called macrophages. During normal healing, an injury triggers the immune system to release monocytes in the blood which travel to the site of damaged tissue and become macrophages. At first, these macrophages create an inflammatory response to engulf and eliminate any bacteria or other pathogens. These same macrophages then change into a non-inflammatory repair mode to generate new tissue and promote healing. With diabetes, this conversion never takes place and inflammation persists.

Gallagher's team suspected that something environmental triggers epigenetic changes that prevents the macrophages from completing their job. "Type 2 diabetes typically develops over 20 to 30 years, and while genetics certainly play a role, we speculated that behaviors such as smoking or a long-term unhealthy diet were causing permanent epigenetic changes in the cells," she says. Epigenetics refers to changes in gene expression that do not come from changes from the underlying DNA sequence.

Using mice and human tissues, they discovered for the first time that an epigenetic enzyme called Setdb2 regulates the conversion of macrophages from an inflammatory type to a repair type. In diabetic mice, Setdb2 did not increase at the critical time and their wounds remained inflamed.

Potential treatment

Gallagher's team also found that Setdb2 appears to be a player in the metabolism of uric acid, known to be elevated in people with diabetes. People with high blood concentrations of uric acid can develop gout, which can cause painful inflamed joints. Gallagher and her team found that in normal healing, Setdb2 turns off xanthine oxidase, the enzyme that produces uric acid. In doing so, Setdb2 turns off inflammation.

To see whether blocking uric acid could help wound healing, the team administered allopurinol, a common drug used to treat gout and kidney stones, locally to wound sites in their diabetic mouse models.

"The drug seemed to improve healing," says Gallagher. "Our data looks very promising for using this as a local therapy."
Applying allopurinol directly to the wounds, she adds, could help avoid some of the toxic systemic side effects associated with the drug. The team hopes to eventually bring their findings to clinical trials, look for other inflammatory genes that may be targets, and explore ways of increasing Setdb2 for cell-based therapy.

The lab of Yongchao Ma, PhD, from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago, discovered how the genetic defect in fragile X syndrome - a type of autism - delays production of neurons (nerve cells) at a critical time in the embryo's brain development. In a study published in Cell Reports, Dr. Ma and colleagues describe a previously unknown regulatory mechanism controlling how stem cells differentiate into neurons. They identified early disruptions in this process in fragile X syndrome, the most common inherited intellectual disability in children.

"During embryonic brain development, the right neurons have to be produced at the right time and in the right numbers," says Dr. Ma, senior author and researcher at Lurie Children's, as well as Associate Professor of Pediatrics, Neurology and Physiology at Northwestern University Feinberg School of Medicine. "We focused on what happens in the stem cells that leads to slower production of neurons that are responsible for brain functions including learning and memory. Our discoveries shed light on the earliest stages of disease development and offer novel targets for potential treatments."

Other studies in fragile X development have focused on the interactions between mature neurons. Dr. Ma's study is the first to offer a new understanding of the disease at a stem cell level.

Fragile X syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females. It is caused by mutation in the gene called FMR1 that encodes a protein called FMRP. The genetic defect leads to reduced FMRP protein. Previously the function of FMRP protein during early brain development was not known.

Dr. Ma and colleagues discovered that within a stem cell, the FMRP protein plays a key role as a "reader" of a chemical tag (called m6A) on the RNA. This tag carries instructions on how to process the RNA. By reading these instructions, FMRP protein exports the RNAs from the nucleus to the cytoplasm of cells where the m6A-tagged RNAs will become proteins that control stem cell differentiation into neurons.

"We show how the reduced amount of FMRP protein in neural stem cell results in decreased nuclear export of m6A-tagged RNAs and ultimately, slower production of the neurons that are essential for healthy brain development," says first author Brittany Edens, graduate student in the Northwestern University Interdepartmental Neuroscience Program who works in Dr. Ma's lab. "Our findings also expand understanding of how the flow of genetic information form DNA to RNA to protein is regulated, which is a central question in biology."

"Currently we are exploring how to stimulate FMRP protein activity in the stem cell, in order to correct the timing of neuron production and ensure that the correct amount and types of neurons are available to the developing brain," says Dr. Ma. "There may be potential for gene therapy for fragile X syndrome."

Mammal brains -- including those of humans -- store and recall impressive amounts of information based on our good and bad decisions and interactions in an ever-changing world. Now, in a series of new experiments with mice, scientists at Johns Hopkins Medicine report they have added to evidence that such "decision-based" memories are stored in very particular parts of the brain.

"Figuring out where and how long animal brains store information about past choices can help us more broadly understand models of decision-making," says Jeremiah Cohen, Ph.D., assistant professor of neuroscience at the Johns Hopkins University School of Medicine. Eventually, he says, such models could lead to better treatments for addiction and other disorders marked by flawed or disordered decision-making.

A description of the studies was published July 4 in the journal Neuron.

For the experiments, Cohen and his colleagues at Johns Hopkins used various odors to train 36 mice to choose between two tubes that deliver water when licked and which were randomly controlled by a computer to turn the "faucets" on or off. When one tube was turned on, the other was turned off, and then, they'd switch. The experiment was designed to mimic how mice forage for water in the wild and learn where to return for the liquid.

The mice didn't know, with certainty, whether they would receive water when they made a particular choice, says Cohen. To find the water reward, they had to remember their recent choices and outcomes, he explains.

As expected, Cohen says, the mice more often explored and licked from water tubes that were turned on more frequently, maximizing the amount of water they received. Occasionally, they also explored water tubes that were turned off, licking them once in a while. When a tube with plentiful water was turned off, the mice switched to the other tube that was newly turned on, says Cohen. The scientists also found that the mice waited to make their water tube choices for up to half a minute.

Cohen says previous studies over the past decade have suggested that decision-based memories are stored in the prefrontal cortex -- the seat of complex behavior, personality and learning.

To figure out where in their brains the mice stored the water memories, a member of Cohen's team, Bilal Bari, attached microelectrodes to the brains to measure the firing rate of so-called "action potentials" crossing the membranes of more than 3,000 neurons in the prefrontal cortex.

According to Cohen, the firing rate of the neurons' action potentials in a mouse represents the internal cognitive estimate of the choice between the two water tube options -- basically, the mouse thinking about which tube to lick.

A baseline action potential rate in prefrontal cortex neurons is about two to 10 spikes per second. But when the mice were believed to be thinking about one tube choice versus the other, the scientists found action potential rates of an average of about 20 spikes per second in nearly 80% (2,401 of 3,073) of prefrontal cortex neurons.

They also found that the longer the mice took to decide between the two tubes, the action potential rate in prefrontal cortex neurons started to slow down. After 15 seconds without licking a tube, action potential rates were down to half their peak rate. "It's possible that the mouse is forgetting how valuable the particular environment is," says Cohen.

"These data give us a window into how neurons are storing these decision-based memories," says Cohen. "Not only can we see the changes in action potential firing rates, but we can quantify them too."

The researchers also measured where in the mouse brains the prefrontal cortex neurons extended to other parts of the brain, signaling structures elsewhere. They found increased electrical signaling to the dorsomedial striatum, a structure inside the basal ganglia, a region in the middle of the brain linked to movement.

Cohen says his team plans further study on where and how neurons connect from the prefrontal cortex to other parts of the brain that control movement. This information would likely shed light on how fast animals including humans learn from their experiences in the world. "We need to learn quickly in a volatile world, and figuring out more of how brains do that will offer insight into how such learning can be adjusted," Cohen says.

CHAMPAIGN, Ill. -- The anemonefish is a gender-bending marvel. It starts out as a male, but can switch to female when circumstances allow, for example, when the only female present dies or disappears. In a new study, researchers found that the male-to-female sex-change occurs first in the fish's brain and only later involves the gonads - sometimes after a delay of months or years. (Includes video).

"We discovered that when you pair two males together, they fight, and the winner becomes female," said University of Illinois psychology professor Justin Rhodes, a behavioral neuroscientist who led the research. "But the first thing that changes is the brain, in particular the part of the brain that controls the gonads."

The findings, reported in the journal Hormones and Behavior, describe the first known example of an animal undergoing a sex change in the brain before it occurs in the sex organs, the researchers said.

In anemonefish, females are dominant, Rhodes said. They pair up with a single male, the largest of the males available, to mate for life. Each mating pair makes its home in an anemone, "which is kind of like an upside-down jellyfish," Rhodes said. The anemone protects them from predators with its stinging tentacles. Anemonefish appear to be immune to the anemone's stings. The females lay eggs and the males fertilize them. After that, the mother defends the nest, protecting it from predators, and the father tends to the eggs.

"Anemonefish are completely dependent on the sea anemone for protection," Rhodes said. "Our species, Amphiprion ocellaris, will stay within a meter of the anemone at all times."

Sometimes, other nonreproductive male fish are allowed to also live on the same anemone with the mating pair. If, for some reason, the female disappears, her male mate begins - almost immediately - to take on female behaviors, such as aggressively defending the nest. And the next largest male moves in to become her mate.

But, at first, the fish that is behaving like a female has a male brain and gonads. Rhodes and his colleagues wanted to know whether the transition from male to reproductively viable female began first in the brain or gonads. They set up experiments in the laboratory where they paired male anemonefish together and tracked their development. In all, they followed 17 pairs of male anemonefish.

Within minutes or hours of being put together in a tank, one of the two males emerged as dominant, and began to behave as a female would, the researchers reported.

"We thought that once the fish figured out it was dominant, then immediately its gonads would start changing," Rhodes said. "In fact, that's not what happened. The gonads stayed male while the brain was changing."

The researchers focused on a brain structure that regulates gonad function. This structure, the preoptic area, is much bigger in females than in males, with roughly twice the number of neurons.

"We tracked changes in the preoptic area, changes in the gonads and in the blood hormones," Rhodes said. "We counted neurons in the preoptic area, took blood samples to look at the sex hormones, and examined the eggs to look at the proportion of eggs to testicular tissue in the gonads."

Within six months of being paired with another male, the dominant fish had grown its preoptic area to a size that made it indistinguishable from the same region in other female anemonefish brains.

"After six months, this part of the brain is completely changed from a male brain to a female brain," Rhodes said. "But the gonads have not yet changed, which means that they're still male gonads."

Any biologist who studies anemonefish would identify the fish at this stage as female, Rhodes said. "Also, if you ask other fish, they'll tell you it's a female."

Male anemonefish will not fight with a female, but females will fight each other to the death. This is exactly how the other fish responded to the dominant fish.

"It's a very clear demonstration that brain sex and gonadal sex can be uncoupled," Rhodes said. "Is it female or is it male? It's got a female brain, but its gonads are male."

Despite the researchers' expectations, the dominant fish appeared to be in no hurry to change their gonads to the fully female variety. Only three of the dominant fish in the 17 pairs actually transitioned all the way to reproductive females, with viable eggs in their gonads. One of the three laid eggs.

The rest of the pairs seemed to be in a holding pattern, with female brains and male gonads. The researchers followed them for three years, and the fish still hadn't made the full transition.

"We don't know exactly what they're waiting for," Rhodes said. "Maybe they're waiting to grow bigger, so they can produce more eggs. Maybe they don't have the right chemistry as a couple."

The global monsoon region, sprawling north and south from the Earth's equator, sustains nearly two-thirds of the world's population. It is characterized with abundant monsoon rainfall, a distinct wet-dry season contrast, and hence an active water cycle.

Future global warming would accelerate the water cycle over the entire global land monsoon region, meanwhile enlarge the wet-dry season contrast, according to a study recently published in Journal of Climate. The research reveals robust and coherent responses in the various aspects of water cycle to future warming over the populous global monsoon regions.

"The global monsoon regions deserve specific attention as they extensively affect the global water cycle," said Tianjun Zhou, the corresponding author on the paper. Zhou is a senior scientist at the State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics at the Institute of Atmospheric Physics and CAS Center for Excellence in Tibetan Plateau Earth Sciences in the Chinese Academy of Sciences. He is also a professor at the University of Chinese Academy of Sciences.

While there has been considerable research interest in the future changes in monsoon precipitation, limited attention has been paid to other aspects of the water cycle over the monsoon regions. Zhou and his team, using multi-model output from CMIP5, an archive of the state-of-the-art climate models, investigated and provided a comprehensive picture of water cycle changes over the monsoon regions, including both the atmospheric and surface water sectors, namely, precipitation, evaporation, surface fresh water fluxes, soil water, and total runoff (i.e., water flowing over and within the ground).

"Under future global warming, we will see an accelerated water cycle over the entire global monsoon region, as evidenced by the coherent increases in its various cycling fluxes, including the annual-mean precipitation, evaporation, total runoff and surface fresh water fluxes," Zhou introduced.

Moreover, the scientists found regional differences under the overall acceleration of water cycle. Specifically, the Northern Hemispheric African, South and East Asian monsoon regions will experience an intensified water cycle, while in the Northern Hemispheric American monsoon region, the water cycle would robustly be weakened. However, the changes in the Southern Hemispheric monsoon regions are largely uncertain.

"Apart from the spatial differences, the water cycle changes also vary with season," Zhou added. "The precipitation, runoff, and surface fresh water fluxes would increase most prominently in the wet season, but slightly reduce in the dry season. On one hand, this indicates an enlarged wet-dry season contrast in the monsoon regions. In terms of the human use of water resources, the changing seasonality can be described as 'wet season gets wetter, dry season gets drier'. On the other hand, there might be increasing flood risks in the wet season."

The water cycle includes both the cycling fluxes (i.e., movements) and reservoirs. The soil water, an important water reservoir in the Earth's surface, is also an indicator of agricultural drought. "The surface soil water would deplete all year round as a result of atmospheric warming. This could reduce crop yields and further threaten food security for the dense populations," Zhou added.

These results provide a broader understanding on the redistribution of freshwater resources across the globe induced by future changes in the monsoon system. Meanwhile, the authors are also calling for attention to the changing seasonality of the water cycle. "The seasonal changes are more remarkable and robust than the annual- mean changes," Zhou said. "We should be aware of and prepared for the potential additional flood and drought risks in the populous monsoon regions."

“Legacy” mercury pollution from decades ago and miles away is an important source of contamination in New Jersey Meadowlands waterways, according to a Rutgers-led study that could help guide cleanup efforts.

The study in the Journal of Hazardous Materials identified upper Berry’s Creek and its tributary, Peach Island Creek, in Bergen County, as major sources of mercury found throughout the Meadowlands coastal ecosystem. The two creeks are part of a Superfund site slated by the U.S. Environmental Protection Agency for a $332 million cleanup.

The researchers examined the degree to which old mercury contamination has been redistributed throughout the Hackensack River, the main waterway in Meadowlands, and the degree to which legacy pollution outweighs the mercury that may arrive from the atmosphere or other sources. Mercury, a toxic metal, causes neurological effects in wildlife and people.

“Our results will be useful to environmental managers at state and federal agencies overseeing cleanup efforts,” said lead author John Reinfelder, a professor in the Department of Environmental Sciences at Rutgers University–New Brunswick. “They are wrestling with deciding how much of the Meadowlands’ tidal waterways require remediation and the benchmark for how clean they need to be.”

Reinfelder and a U.S. Geological Survey scientist tracked mercury in the complex New Jersey Meadowlands ecosystem where water, sediment and contaminants are transported by tides, runoff and storm surges.

Old upstream sources of contamination comprised an estimated 21 percent to 82 percent of all sources of mercury, showing the impact on Meadowlands waterways more than 9 miles from the initial site of contamination, according to Reinfelder, who works in the School of Environmental and Biological Sciences.

Bottom Line: Imaging shows differences in the brains of U.S. government personnel who were potentially exposed to unusual audible and sensory phenomena (sound, pressure or vibration) while serving in Cuba when compared with brain images from a group of healthy individuals without such exposure, although the clinical importance of these brain differences is uncertain. A preliminary report published by JAMA in 2018 described neurological signs and symptoms experienced by some of these government workers. In this study, advanced magnetic resonance imaging (MRI) of the brain was done for 40 workers and 48 healthy individuals who were demographically similar for comparison to analyze three components (brain volume, microstructural tissue measures, and functional connectivity). Study authors report differences in whole brain white matter volume, regional gray and white matter volumes, cerebellar tissue microstructural integrity, and functional connectivity in the auditory and visuospatial subnetworks of the brain but not in the executive control subnetwork. There also were no significant differences in total whole brain gray matter volume. The findings suggest there may be differences in brain structure in several brain regions and in some functional brain networks. The current study has several limitations including that it cannot determine if the differences among patients are because of individual differences or differences in the level and degree of exposure to the reported sound, pressure or vibrations.

Authors: Ragini Verma, Ph.D., University of Pennsylvania, Philadelphia, and coauthors

(doi:10.1001/jama.2019.9269)

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

GAINESVILLE, Fla. --- Researchers picking through the contents of fossil clams from a Sarasota County quarry found dozens of tiny glass beads, likely the calling cards of an ancient meteorite.

Analysis of the beads suggests they are microtektites, particles that form when the explosive impact of an extraterrestrial object sends molten debris hurtling into the atmosphere where it cools and recrystallizes before falling back to Earth.

They are the first documented microtektites in Florida and possibly the first to be recovered from fossil shells.

Mike Meyer was a University of South Florida undergraduate when he discovered the microtektites during a 2006 summer fieldwork project led by Roger Portell, invertebrate paleontology collections director at the Florida Museum of Natural History.

As part of the project, students systematically collected fossils from the shell-packed walls of a quarry that offered a cross-section of the last few million years of Florida's geological history. They pried open fossil clams, washing the sediment trapped inside through very fine sieves. Meyer was looking for other tiny objects - the shells of single-celled organisms known as benthic foraminifera - when he noticed the translucent glassy balls, smaller than grains of salt.

"They really stood out," said Meyer, now an assistant professor of Earth systems science at Harrisburg University in Pennsylvania. "Sand grains are kind of lumpy, potato-shaped things. But I kept finding these tiny, perfect spheres."

After the fieldwork ended, his curiosity about the spheres persisted. But his emails to various researchers came up short: No one knew what they were. Meyer kept the spheres - 83 in total - in a small box for more than a decade.

"It wasn't until a couple years ago that I had some free time," he said. "I was like, 'Let me just start from scratch.'"

Meyer analyzed the elemental makeup and physical features of the spheres and compared them to microtektites, volcanic rock and byproducts of industrial processes, such as coal ash. His findings pointed to an extraterrestrial origin.

"It did blow my mind," he said.

He thinks the microtektites are the products of one or more small, previously unknown meteorite impacts, potentially on or near the Florida Platform, the plateau that undergirds the Florida Peninsula.

Initial results from an unpublished test suggest the spheres have traces of exotic metals, further evidence they are microtektites, Meyer said.

Most of them had been sealed inside fossil Mercenaria campechiensis or southern quahogs. Portell said that as clams die, fine sediment and particles wash inside. As more sediment settles on top of the clams over time, they close, becoming excellent long-term storage containers.

"Inside clams like these we can find whole crabs, sometimes fish skeletons," Portell said. "It's a nice way of preserving specimens."

During the 2006 fieldwork, the students recovered microtektites from four different depths in the quarry, which is "a little weird," Meyer said, since each layer represents a distinct period of time.

"It could be that they're from a single tektite bed that got washed out over millennia or it could be evidence for numerous impacts out on the Florida Platform that we just don't know about," he said.

The researchers plan to date the microtektites, but Portell's working guess is that they are "somewhere around 2 to 3 million years old."

One oddity is that they contain high amounts of sodium, a feature that sets them apart from other impact debris. Salt is highly volatile and generally boils off if thrust into the atmosphere at high speed, Meyer said.

"This high sodium content is intriguing because it suggests a very close location for the impact," Meyer said. "Or at the very least, whatever impact created it likely hit a very large reserve of rock salt or the ocean. A lot of those indicators point to something close to Florida."

Meyer and Portell suspect there are far more microtektites awaiting discovery in Florida and have asked amateur fossil collectors to keep an eye out for the tiny spheres.

But no one will be recovering microtektites from the original quarry any time soon. It's now part of a housing development.

"Such is the nature of Florida," Meyer said.

A study of dictators over the past 150 years shows they are rarely associated with strong economies, and quite often with weaker ones.

Autocratic leaders are often credited with purposefully delivering good economic outcomes, such as the late Lee Kuan-Yew, who is widely credited with Singapore's prosperity.

But new research published in the Leadership Quarterly journal by researchers from RMIT University and Victoria University in Melbourne, Australia, challenges that long-held assumption.

RMIT University economist Dr Ahmed Skali said robust analysis of data on economic growth, political regimes and political leaders from 1858 to 2010 found dictators rarely oversaw strong economies.

"In an era where voters are willingly trading their political freedoms in exchange for promises of strong economic performance to strongman figures like Donald Trump, Vladimir Putin or Recep Tayyip Erdogan, it's important to understand whether autocratic leaders do deliver economic growth," Skali said.

"Our empirical results show no evidence that autocratic leaders are successful at delivering economic growth in any systematic way."

Autocrats whose countries experienced larger than average economic growth were found only as frequently as you would predict based on chance alone.

In contrast, autocrats overseeing poor economic growth were found significantly more frequently than chance would predict.

"Taken together, these two results cast serious doubt on the view that autocratic leaders are successful at promoting economic growth," he said.

The study looked at other important outcomes beyond just economic growth.

"We also examined whether autocratic leaders were good at implementing measures which mainly benefit the less well-off in society, such as reducing unemployment or spending more on health and education. That was not the case," Skali said.

"We also looked further into whether growth-positive autocrats, although infrequent, really do deserve the credit for turning around their country's economic fate."

There was no evidence to suggest dictators had a positive influence over growth trajectories in the five or ten years after taking power.

"Therefore, it appears that even the rare growth-positive autocrats largely find themselves at the right place at the right time and "ride the wave" of pre-existing growth," Skali said.

The same analysis, carried out on dictators overseeing poor economies, to see if they had merely found themselves in the wrong place at the wrong time, found instead that economic growth dropped significantly after the entry into power of an economically 'bad' autocrat.

In short, dictators were shown to have little influence in driving economies up, but often more influence in driving them down.

How could we be so easily fooled into thinking otherwise?

Co-author and Victoria University behavioural economist Stephanie Rizio said humans were hard-wired to perceive agency: the tendency to ascribe conscious intentions to phenomena that are not guided by any such intents.

"In the wild, this is a successful evolutionary strategy, even if it leads to false positives," she explained.

"It is better to interpret rustling in a nearby bush as caused by a predator or an ill-intended rival tribesperson, and be incorrect, than to ascribe it to the wind and be incorrect. This tendency has remained with us into the present day."

As social primates, Rizio explained, we're also inclined to accept the authority of a single individual, the alpha primate.

"Perhaps this is why we routinely attribute group-level outcomes to the actions of leaders, even when leaders have no control over outcomes, which may lead us to be accepting of autocratic leadership styles," she said.

The leadership literature has recently shown that, in times of uncertainty, the order and predictability provided by a strongly hierarchical system can make the idea of autocratic leadership more attractive.

Skali said the research was not only interesting for economic development and political leadership theory, but also a timely question as the rise of 'strongman' figures is becoming more and more prevalent.

Cold Spring Harbor, NY -- Scientists haven't quite decoded how animals smell, but researchers at Cold Spring Harbor Laboratory (CSHL) found that it's different from previously thought.

To understand how the brain processes and interprets smells, CSHL neuroscientists Florin Albeanu, Alexei Koulakov and colleagues Honggoo Chae, Daniel Kepple, Walter Bast from CSHL, and Venkatesh Murthy from Harvard University, are putting past odor classifying models to the test, and they're discovering discrepancies.

Their results, published in the journal Nature Neuroscience, differ from other published studies that found predictable relations between molecular properties of odors and activity in the early stages of the olfactory system. The new research found that while there were some correlations between some molecular properties of odors and corresponding neuron activity response, they "held little predictive power when new odor pairs or shuffled properties were tested."

When it comes to smell, "we don't really know what the brain is looking for, and we don't know what physical or chemical features, if any, the brain extracts," Albeanu said.

Generally, scientists know that odor particles first enter through the nasal cavity, where odorant receptors expressed by olfactory receptor neurons in the sensory tissue bind to them. The olfactory bulb, a structure located in the forebrain of mammals, then processes information sent up from the receptors. Afterwards, the bulb sends out this information to several higher processing brain areas, including the cerebral cortex. There, the olfactory output messages are further analyzed and broadcast across the brain before they're conveyed back to the bulb in a feedback loop.

"Rich feedback makes the olfactory system somewhat different from the visual system," Koulakov said. "Olfactory experience is very subjective, perception of smells actually depends on the context, and on an individual's prior experience."

Factoring these in, Albeanu and Koulakov said it's probable that the entry-level of olfactory inputs and the further processed bulb outputs care about different aspects of smell.

The "rather unexpected" results of the new research, Koulakov said, are an exciting opportunity to build a more comprehensive and testable computational model for the odor space that captures the differences in informational relevance for scent features across the various levels of olfactory processing.

This paper is the first discovery to come out since the pair received the National Institutes of Health (NIH) Director's Transformative Research Award for an innovative neuroscience research project on the olfactory system in 2018. Albeanu views these findings as "an opening act" for continued research in this area.

A new study has found that an Inuit population in Canada's Arctic are genetically distinct from any known group, and certain genetic variants are correlated with brain aneurysm.

Geographically isolated populations often develop unique genetic traits that result from their successful adaptation to specific environments. Unfortunately, these adaptations sometimes predispose them to certain health issues if the environment is changed. The genetic background of these populations are often poorly understood because they live far from scientific research centres.

Canada's Inuit have higher prevalence of cardiovascular disorders, as well as increased incidence of brain aneurysms, than the general population. To learn about the possible genetic origin of these disorders, researchers at The Neuro (Montreal Neurological Institute and Hospital) of McGill University analyzed the genetic characteristics of 170 Inuit volunteers from Nunavik, a region of northern Quebec. This was done with approval from Nunavik Nutrition and Health Committee in Kuujjuaq, Nunavik.

Using exome sequencing and genome-wide genotyping, the researchers found several interesting traits among the Nunavik Inuit. They are a distinct genetic population, whose closest relatives are the Paleo-Eskimos, a people that inhabited the Arctic before the Inuit.

The Nunavik Inuit have distinct genetic signatures in pathways involving lipid metabolism and cell adhesion. These may be adaptations to adjust to the high-fat diet and extreme cold of the Canadian north.

One of these unique genetic variants correlates with a higher risk of brain aneurysm, also known as intracranial aneurysm, a weakening in the wall of a cerebral artery that causes ballooning. In serious cases the arterial wall may rupture, a potentially fatal condition known as a brain hemorrhage.

This study, published in the journal Proceedings of the National Academy of Sciences, is the first genetic study to highlight the genome-wide architecture of Nunavik Inuit with emphasis on natural selection in gene coding regions, from which may arise the genetic risk responsible for their predisposition to diseases such as intracranial aneurysm.

Non-European populations, particularly those isolated populations in remote areas of the world, are underrepresented, or not present at all, in genetics studies. Understanding the genetic makeup of non-European peoples, especially those isolated populations with unique genetic background, such as Nunavik Inuit, will improve our ability to deliver medical therapies tailored for them.

"In the case of the Nunavik Inuit, our results emphasize the need to provide effective neurological services," says Dr. Guy Rouleau, the study's senior author. "Future research will build on the findings to determine if these unique genetic traits increase risk of aneurysm, and if so, what interventions can be designed to reduce this risk. Thank you to the study participants and the Nunavik Nutrition and Health Committee for their collaboration and input."

Reports of racially motivated, fatal shootings by police officers have garnered extensive public attention and sparked activism across the nation. New research from Michigan State University and University of Maryland reveals findings that flip many of these reports on their heads - white police officers are not more likely to shoot minorities citizens than non-white officers.

"Until now, there's never been a systematic, nationwide study to determine the characteristics of police involved in fatal officer-involved shootings," said Joseph Cesario, co-author and professor of psychology at MSU. "There are so many examples of people saying that when black citizens are shot by police, it's white officers shooting them. In fact, our findings show no support for the idea that white officers are biased in shooting black citizens."

The findings - published in Proceedings of the National Academy of Sciences, or PNAS - are based on an independent database Cesario and his team created that catalogued each police shooting from 2015. The team - led also by co-author David Johnson from University of Maryland - contacted every police department that had a fatal police shooting to get the race, sex and years of experience for every officer involved in each incident. The team also leveraged data from police shooting databases by The Washington Post and The Guardian.

"We found that the race of the officer doesn't matter when it comes to predicting whether black or white citizens are shot," Cesario said. "If anything, black officers are more likely to shoot black citizens, but this is because black officers are drawn from the same population that they police. So, the more black citizens in a community, the more black police officers there are."

The data show that it's not racial bias on behalf of white officers relative to black officers when it comes to fatal shootings, and that's good news. The bad news, Cesario said, are that internal policy changes, such as diversifying police forces, may not reduce shootings of minority citizens.

Beyond officer race, the team drew other conclusions about details related to racial disparities in fatal officer shootings.

"Many people ask whether black or white citizens are more likely to be shot and why. We found that crime rates are the driving force behind fatal shootings," Cesario said. "Our data show that the rate of crime by each racial group predicts the likelihood of citizens from that racial group being shot. If you live in a county that has a lot of white people committing crimes, white people are more likely to be shot. If you live in a county that has a lot of black people committing crimes, black people are more likely to be shot. It is the best predictor we have of fatal police shootings."

By connecting the findings of police officer race, victim race and crime rates, the research suggests that the best way to understand police shootings isn't racial bias of the police officer; rather, by the exposure to police officers through crime.

The vast majority - between 90% and 95% - of the civilians shot by officers were actively attacking police or other citizens when they were shot. Ninety percent also were armed with a weapon when they were shot. The horrific cases of accidental shootings, like mistaking a cell phone for a gun, are rare, Cesario said.

"We hear about the really horrendous and tragic cases of police shootings for a reason: they're awful cases, they have major implications for police-community relations and so they should get attention," Cesario said. "But, this ends up skewing perceptions about police shootings and leads people to believe that all fatal shootings are similar to the ones we hear about. That's just not the case."

One thing that was surprising to the researchers, Cesario said, were the number of mental health cases that resulted in fatal officer shootings.

"It was truly striking and we didn't recognize just how many there were," he said. "This shows how underappreciated mental health is in the national discussion of fatal officer shootings."

Nearly 50% of all fatal shootings involving white civilians were because of mental health; it also accounted for nearly 20% of black civilians and 30% of Hispanics. These included two types of mental health cases: the first was "suicide by cop," in which civilians intentionally antagonize the police because they want an officer to kill themselves; the second was a result of mental disorders, such as when a civilian is suffering from schizophrenia and poses a threat to officers.

Although white officers are not more likely than black officers to shoot black citizens when looking at all fatal shootings, the data are too uncertain to draw firm conclusions once different subtypes of shootings, such as shootings of unarmed citizens, are examined. This is because these types of shootings are too rare for strong conclusions to be drawn.

Cesario said that better record keeping - such as the FBI's National Use-of-Force Data Collection, which launched in 2019 - will enable researchers to understand police shootings in finer detail.

Researchers at the Weizmann Institute of Science have shown in mice that intestinal microbes, collectively termed the gut microbiome, may affect the course of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. As reported today in Nature, progression of an ALS-like disease was slowed after the mice received certain strains of gut microbes or substances known to be secreted by these microbes. Preliminary results suggest that the findings on the regulatory function of the microbiome may be applicable to human patients with ALS.

"Our long-standing scientific and medical goal is to elucidate the impact of the microbiome on human health and disease, with the brain being a fascinating new frontier," says Prof. Eran Elinav of the Immunology Department. His team performed the study together with that of Prof. Eran Segal of the Computer Science and Applied Mathematics Department. Segal elaborates: "Given increasing evidence that microbiome affects brain function and disease, we wanted to study its potential role in ALS." The study was led by postdoctoral fellows Drs. Eran Blacher and Stavros Bashiardes, and by staff scientist Dr. Hagit Shapiro, all in the Elinav lab. They collaborated with Dr. Daphna Rothschild, a postdoctoral fellow in Eran Segal's lab, and Dr. Marc Gotkine, Head of the Motor Neuron Disease Clinic at Hadassah Medical Center, as well as with other scientists from Weizmann and elsewhere.

The scientists started out demonstrating in a series of experiments that the symptoms of an ALS-like disease in transgenic mice worsened after these mice were given broad-spectrum antibiotics to wipe out a substantial portion of their microbiome. In addition, the scientists found that growing these ALS-prone mice in germ-free conditions (in which, by definition, mice carry no microbiome of their own), is exceedingly difficult, as these mice had a hard time surviving in the sterile environment. Together, these results hinted at a potential link between alterations in the microbiome and accelerated disease progression in mice that were genetically susceptible to ALS.

Next, using advanced computational methods, the scientists characterized the composition and function of the microbiome in the ALS-prone mice, comparing them to regular mice. They identified 11 microbial strains that became altered in ALS-prone mice as the disease progressed or even before the mice developed overt ALS symptoms. When the scientists isolated these microbial strains and gave them one by one - in the form of probiotic-like supplements - to ALS-prone mice following antibiotic treatment, some of these strains had a clear negative impact on the ALS-like disease. But one strain, Akkermansia muciniphila, significantly slowed disease progression in the mice and prolonged their survival.

To reveal the mechanism by which Akkermansia may be producing its effect, the scientists examined thousands of small molecules secreted by the gut microbes. They zeroed in on one molecule called nicotinamide (NAM): Its levels in the blood and in the cerebrospinal fluid of ALS-prone mice were reduced following antibiotic treatment and increased after these mice were supplemented with Akkermansia, which was able to secrete this molecule. To confirm that NAM was indeed a microbiome-secreted molecule that could hinder the course of ALS, the scientists continuously infused the ALS-prone mice with NAM. The clinical condition of these mice improved significantly. A detailed study of gene expression in their brains suggested that NAM improved the functioning of their motor neurons.

The University of North Carolina at Charlotte-led archaeological dig on Jerusalem's Mount Zion has been going on for over a decade, looking at an area where there were no known ruins of major temples, churches or palaces, but nonetheless sacred land where three millennia of struggle and culture has long lain buried, evidence in layer upon layer of significant historical events.

Virtually every dig season, a significant discovery has been made at the site, adding real detail to the records of this globally-renowned city, giving new insights to what has often been imperfectly preserved in ancient histories. This year's findings are no different, confirming previously unverified details from nearly thousand-year-old historical accounts of the First Crusade - history that had never been confirmed regarding the five-week siege, conquest, sack and massacre of the Fatamid (Muslim)-controlled city in July of 1099.

The dig's archeological team --- co-directed by UNC Charlotte professor of history Shimon Gibson, Rafi Lewis, a faculty member at the University of Haifa and Ashkelon Academic College, and James Tabor, UNC Charlotte professor of religious studies -- has revealed the rumored, but never physically detected, moat-trench the Fatamid defenders dug along the city's southern wall to protect against siege engines - a defense that contemporary accounts claim helped stymie the southern assault.

Through stratigraphic evidence, the archaeologists have been able to confirm the 11th Century date of the 17-meter-wide by 4-meter-deep ditch, which abutted the Fatimid city wall (built in the same place as the current wall near the current Zion Gate), and have also found artifacts from the assault itself, including arrowheads, Crusader bronze cross pendants, and a spectacular piece of Muslim gold jewelry, which is probable booty from the conquest.

In past seasons, the team found remnants of a Fatamid city gate at the site, which, the archaeologists argue, makes the area a likely focal point for the Crusaders' main southern assault on the city wall. Despite reported attempts to fill the trench by the attacking forces, the southern assault was ultimately unsuccessful. The city's defenses were finally breached by a simultaneous operation from the north.

Near the trench, the archaeologists also unearthed an earthquake-damaged Fatamid structure, which was probably already a ruin at the time of the assault. The arrowheads, crosses and jewelry were found on the floor of the structure.

"There was, apparently, an extramural quarter of scattered buildings, outside the city to the south, and we excavated a building that was in a ruinous state, possibly damaged by the earthquake of 1033," Gibson said. "You can imagine the Crusaders coming at and attacking the city from the south and they find the ditch and this ruined building, and they made use of it for cover, and that explains some of the arrowheads because they would have been raining down upon them" Gibson speculated.

"This is enormously important for Crusader scholarship," said Lewis, an expert on medieval warfare, "because not only do we have the remains of the ditch that we only knew about from the sources but we also have the remains of the frontline battle itself."

The archaeology clarifies a historical picture that is mainly only known from contemporary chroniclers who had been considered questionable in their accuracy. By all accounts, the Crusader attack on the city of Jerusalem was a bloody one and took place on two sides of the city. While the principal forces broke into the city from the north, little has been known about the attack from the south.

Peter Tudebode, a contemporary chronicler, recounts that the Provencal forces led by Raymond de Saint Gille on the south side, positioned themselves somewhere on Mount Zion and proceeded to attack the wall. However, there was a ditch in front of the wall and they could not get their wooden siege tower up against the wall, and so Raymond asked his men, under cover of night, to fill in the ditch for payment of gold dinars. Though the siege tower was able to proceed, the southern assault still did not succeed because of the defenders aggressive counter-measures.

Until the current find, however, there was no evidence that a ditch, trench or moat ever existed, calling into question the reality of the accounts of the southern assault.

The Mount Zion dig team's discovery of the trench came through a puzzling observation made in earlier seasons at the site. "Just outside the city wall we noticed that, although the slope of the hill went down [from the wall], we found that the slope of a layer of fill was going in the opposite direction, dipping down [towards the wall]," Gibson noted. "That was our first clue - there was some feature that had been cut into the ground, which had been filled in later."

The fill provided the dating that explained what the structure was: "What was nice was that the ditch itself was sealed with a burnt layer that had coins in it from the time of King Baldwin III," Gibson said.

Baldwin III was an early crusader king who fought a civil war against his mother, in the course of which he burnt much of Jerusalem. Baldwin's fiery attack was known to be in 1153, about half a century after the conquest, thus dating the ditch as a landscape feature in the period before.

"The ditch got filled in and it disappeared - to such an extent that a lot of archaeologists who had been working at different points in time believed that maybe this ditch was a figment of the chroniclers' imaginations," Gibson said. "That's why this discovery is so important - for the first time, we can confirm details that appear in major historical texts."

The artifacts associated with the find provide some intriguing details about the historical moment of the First Crusade. In the ditch's fill the archaeologists found what might be a part of a battle standard made of metal, as well as pieces of Chinese celadon ware pottery, which show active trade with the far east during the Fatamid period.

The jewelry, which includes fine gold workmanship with pearls and colored beads, was found by staff archaeologists John Hutchins and Melanie Samed, and they carefully extracted it from the ruined house, where it had lain for 920 years. Gibson is fairly certain that it is booty from the sack or carried by the soldiers carrying out the attack, rather than a dropped domestic item, noting that looting was a real interest of the crusaders.

"It's large and valuable, not something you would lose, you see, " Gibson said. "This piece of jewelry may have been of Egyptian origin and it seems to have been used as an attachment for the ear, and because of its large size, perhaps also to hold a veil in position around a women's head." The Fatamid dynasty came from Egypt, and the gold work is a familiar Egyptian style of the period, with the use of gold and pearls in jewelry mentioned in documents from the Cairo Genizah.

Details bringing the moment of conquest to life are particularly important because the battle marks a critical moment in Jerusalem's history. The crusaders takeover is one of several catastrophic moments in Jerusalem's dramatic and violent history when the city was essentially wiped out and re-colonized by its conquerors.

"For three days, or perhaps even a week, the crusaders perpetrated every single atrocity under the sun - rape, pillage, murder," Gibson said. "The chroniclers talk about 'rivers of blood' running in the streets of the city, and it may not be an exaggeration. Terrible crimes were committed, and a lot of people died, Christians included. Local Christians were considered just as heretical as the Muslims and the Jews. They turned Jerusalem into a ghost town."

It is expected that further analysis of the artifacts will reveal further insights.

An effective drug to treat chronic heart failure may cost too much for senior citizens with a standard Medicare Part D drug plan, said a study co-authored by a John A. Burns School of Medicine (JABSOM) researcher at the University of Hawaii at Manoa.

The therapy is a combination of sacubitril/valsartan called Entresto®. Researchers found that, even with insurance, the cost to Medicare patients may be more than $1,600 a year.

"This drug is the standard of care for the people with significant congestive heart failure according to both the American Heart Association and American College of Cardiology guidelines, yet it's priced so high that, even with insurance, patients may not be able to afford it," said senior author Chien-Wen Tseng, HMSA Endowed Chair in Health Services and Quality Research at JABSOM and physician investigator with Honolulu's Pacific Health Research and Education Institute.

The study co-authors worry that, since Entresto® is a pricey, brand-name drug, such high copayments may result in patients not taking it at all. And that comes with a steep price.

"The science shows that this drug can help save lives," said Tseng, pointing to clinical studies showing the therapy has reduced deaths from heart failure by 20 percent. "We need to figure out a way to deal with its $5,000 price tag, and how folks on Medicare can afford to pay $1,600 each year in copayments to benefit from it."

Current laws prohibit the U.S. Department of Health and Human Services from negotiating drug prices with pharmaceutical companies on behalf of Medicare Part D beneficiaries. As a result, said lead researcher Colette DeJong of the University of California at San Francisco, "Paying $1,600 per year for a single drug could be a huge hardship for many older adults who lived on an average income of less than $25,000 in 2017. Changing the laws that prevent Medicare from negotiating drug prices on behalf of seniors and people living with disabilities would be one step toward curbing these skyrocketing out-of-pocket costs."