Earth

A nuclear war that cooled Earth could worsen the impact of ocean acidification on corals, clams, oysters and other marine life with shells or skeletons, according to the first study of its kind.

"We found that the ocean's chemistry would change, with global cooling dissolving atmospheric carbon into the upper ocean and exacerbating the primary threat of ocean acidification," said co-author Alan Robock, a Distinguished Professor in the Department of Environmental Sciences in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick.

The study is published in the journal Geophysical Research Letters.

Scientists looked at how climate changes stemming from nuclear war would affect the oceans. They used a global climate model in which the climate reacted to soot (black carbon) in smoke that would be injected into the upper atmosphere from fires ignited by nuclear weapons. They considered a range of hypothetical nuclear wars, including a relatively small one between India and Pakistan and a large one between the United States and Russia.

Excess carbon dioxide from the burning of fossil fuels enters the ocean and reacts with water to form carbonic acid, which decreases ocean pH (makes it more acidic) and lowers levels of carbonate ions. Corals, clams, oysters and other marine organisms use carbonate ions to create their shells and skeletons, according to the National Oceanic and Atmospheric Administration. A more acidic ocean makes it harder to form and maintain shells and skeletons.

The massive amount of smoke from a nuclear conflict would block sunlight and cause global cooling. The cooling would temporarily boost the pH in the surface ocean over five years and briefly lessen the decline in pH from ocean acidification. But the cooling would also lead to lower levels of carbonate ions for about 10 years, challenging shell maintenance in marine organisms.

"We have known for a while that agriculture on land would be severely affected by climate change from nuclear war," Robock said. "A lingering question is whether the survivors could still get food from the sea. Our study is the first step in answering this question."

The next step is to combine projected changes in ocean chemistry with projected changes in temperature and salinity and assess their impacts on shellfish and fish stocks throughout the oceans, he said.

PULLMAN, Wash. - White-lipped peccaries have declined by as much as 87% to 90% from their historical range in Central America, signaling a population collapse of a key species in the region, according to a study published recently in the journal Biological Conservation. The research was conducted by a team of 50 scientists from 30 organizations including Washington State University, the Wildlife Conservation Society (WCS) and El Colegio de Frontera Sur.

A pig-like animal that is an important food source for large animal predators and humans alike, the white-lipped peccary (Tayassu pecari) also plays a critical ecological role by dispersing seeds and creating water holes that benefit other animals. The study found that current IUCN estimates underestimated the population decline. The study results are a 63% drop from the current IUCN range estimates for the region.

"White-lipped peccary populations are in more of a critical condition than previously thought," said lead author Dan Thornton of Washington State University. "While these results are sobering, they also offer a roadmap on how to conserve this iconic, ecologically important species."

The researchers say that human influence and loss of forest cover are the primary causes of the decline, and that peccaries now remain in increasingly threatened pockets of forest mostly found along transboundary areas. Outside of transboundary landscapes, remaining populations were generally scattered and isolated.

Due to their social behavior and anti-predatory defense of grouping together when threatened, white-lipped peccaries are highly sensitive to hunting. Their large area needs and reliance on widely dispersed fruit and water sources also makes this species highly vulnerable to forest loss and fragmentation.

The study found that the largest contiguous blocks of habitat for white-lipped peccaries occur in several major transboundary reserves. This includes the Maya Forest of Guatemala, Mexico and Belize, the Moskitia Forest complex of Honduras and Nicaragua, the Indio Maiz and Tortuguero National Park complex of Nicaragua and Costa Rica, and the Darien/Los Katios National Park complex between Panama and Colombia.

Although population estimates for white-lipped peccaries are difficult to calculate precisely, experts estimated that these same transboundary areas likely harbor the highest populations of remaining peccaries. For example, the entire Maya Forest, in Mexico, Belize, and Guatemala, hosts the largest white-lipped peccary population stronghold in Mesoamerica, with an estimated population of around 5000 individuals. The remote forests in the bi-national Moskitia, spanning Nicaragua and Honduras, may harbor around 3000 white-lipped peccaries.

Of particular concern to the plight of white-lipped peccaries in Mesoamerica is the status of the Maya Forest of Guatemala, Mexico, and Belize, the Moskitia Forest of Honduras and Nicaragua, and the Darien Forest in Panama and Colombia, all of which are under particularly grave threat from human activities. For example, in the past 15 years, wildlands (those areas with limited human influence) have been reduced by 30 percent in the Rio Platano/Bosawas complex and by 25 percent in the Maya Forest. Ninety percent of recent deforestation is due to cattle ranching, and these two forests are at imminent risk of losing their contiguity due to expansion of both sugar cane and cattle ranching.

"Based on this study, we believe that the white-lipped peccary should be uplisted to a higher category of threat in Mesoamerica from "Vulnerable" to "Endangered" in the IUCN Red List. We cannot afford to lose such an interesting species that has a unique social behavior of moving in large cohesive groups in a way that we still do not totally understand" said co-author Dr. Rafael Reyna of ECOSUR in Mexico and WCS Associate Researcher.

Mesoamerica's 5 Great Forests, spanning from Mexico to Colombia, and covering an area three times the size of Switzerland, are the most critical bastions for peccaries and other wildlife, and also provide services such as carbon sequestration, clean water, and food security to five million people. WCS is part of an alliance of countries, NGOs, Indigenous Peoples, and local communities committed to protect these remaining areas.

"Without Mesoamerica's five great forests, the white-lipped peccary will almost certainly go extinct in the region, with cascading impacts on forests, other wildlife, and people" said study co-author Jeremy Radachowsky, Director of WCS's Mesoamerica and Caribbean Program. "We must all work together to protect these incredibly important forests."

According to a new study, sleep problems among infants are very common and normally improve by the time the child reaches the age of two. The study was carried out by the Finnish Institute for Health and Welfare (THL) and the University of Turku.

The study found that large changes take place in the sleep of infants during their first two years: the time taken to fall asleep reduces to an average of 20 minutes by the age of 6 months, and by the age of two small children wake up are on average only once during the night.

At the same time, the total amount of time spent sleeping reduces to around 12 hours per day as daytime naps get shorter.

During the first two years, the child's sleep becomes more stable and more consistent.

However, there are large individual variations in the quality of sleep of babies and toddlers, and many parents are concerned about whether their child's sleeping patterns are normal or not. Around 40% of the parents of eight-month-old children who participated in the study said that they were concerned about their child's sleep.

The study was based on the CHILD-SLEEP and FinnBrain birth cohorts. In total, the cohorts contain data on approximately 5,700 Finnish children, and information provided by their parents.

Threshold values for good sleep

The primary goal of the study was to investigate how infants' sleep develops during their first two years.

"Up until now, we have not had any reference values for good infant sleep that are based on large data sets," says Research Manager Juulia Paavonen from THL.

"Now we know that the individual differences are very large, and that patterns relating to falling asleep, waking up, staying awake at night and sleeping rhythms often develop at different rates."

Secondly, the study sought to examine how large the individual differences in sleep among infants can be while still falling within the boundaries of normal child development. This would save parents from unnecessary worry and would help to focus interventions on genuine sleep disorders.

"Those children whose quality of sleep is clearly different from the average would probably benefit from situation assessment at, for example, the child welfare clinic. There are many tools available for reducing children's sleep problems," Paavonen says.

According to Paavonen, it is difficult to give a general recommendation on the total amount of sleep required, although sufficient sleep is certainly important for a child's well-being. The amount of sleep required depends on many factors.

"It is important to look at the child's well-being as a whole."

If it takes longer than 40 minutes for the 8-month-old child to fall asleep, it is best to discuss the matter in the child welfare clinic. The same applies if a 6-month-old child normally wakes at night three times or more, or if the child stays awake at night for particularly long periods, which would mean over 60 minutes for an 8-month-old baby, over 45 minutes for a 12-month-old, or over 30 minutes for an 18-month-old.

"If the parents are very concerned about their child or their own ability to cope, help should be sought even before these levels are reached," Paavonen emphasises.

The FinnBrain and CHILD-SLEEP cohort data is utilised by a wide consortium which includes the Finnish Institute of Health and Welfare, the Pirkanmaa Hospital District, the Universities of Helsinki, Turku, Tampere and Eastern Finland, and the Paediatric Research Center of the Helsinki and Uusimaa Hospital District.

Researchers created an algorithm that successfully predicted consumer purchases. The algorithm made use of data from the consumers' daily activity on social media. Brands could use this to analyze potential customers. The researchers' method combines powerful statistical modeling techniques with machine learning-based image recognition.

Associate Professor Toshihiko Yamasaki and his team from the Graduate School of Information Science and Technology at the University of Tokyo explore new and interesting ways to make use of data such as social media data. Some applications they develop are useful for entities like companies to improve their effectiveness in different ways, but in particular in how they reach and influence potential customers.

"I posed two questions to my team: 'Is it possible to calculate the similarity between different brands based on the way customers engage with them on social media?' And, 'If so, can brands use this information to improve the way they market themselves?'" said Yamasaki. "And with some time, effort and patience, they came back with a simple but confident answer: 'Yes!'"

But the way their team deduced this was anything but simple. The computational analysis of social media data is often called mining, as the term suggests it is a monumental and laborious task. For this reason, researchers in this field make use of various computational tools to analyze social media in ways that human beings cannot.

"In the past, many companies improved their marketing strategies with the use of customer surveys and projections based on their sales data," explained lead researcher Yiwei Zhang. "However, these are time-consuming and imprecise. Now we have access to and expertise in tools such as machine learning and complex statistical analysis."

The team began its work by gathering publicly available social media data from followers of selected brands. They used proven image recognition and machine-learning methods to analyze and categorize photos and hashtags relating to the brands' followers. This revealed patterns of behavior of consumers towards different brands. These patterns meant the researchers could calculate the similarity between different or even unrelated brands.

"We evaluated our proposed algorithm against purchase history and questionnaires, which are still useful to provide context to purchase information," continued Zhang. "The experimental results show that credit card or point card companies could predict customers' past purchasing behavior well. Our algorithm could accurately predict customers' willingness to try new brands."

This research could be extremely useful for new promotions of brands that make use of social media networks. It could also be used by shopping centers and malls to plan which stores they include or for stores themselves to choose which brands to stock. And the research could even help match brands with suitable social media influencers to help better advertise their products.

"To visualize what has not been visible before is always very interesting," concluded Yamasaki. "People might say that professionals already 'see' these kinds of patterns, but being able to show the similarity between brands numerically and objectively is a new innovation. Our algorithm is demonstrably more effective than judging these things based on intuition alone."

Tsukuba, Japan - Voluntary motor movements rely on the corticospinal tract (CST)--a group of neuronal fibers in mammals that connect each side of the brain to the opposite side of the spinal cord, and ultimately to muscles. It contains about 1 million fibers, the majority of which cross sides where the brain meets the spinal cord. This is why, for example, the left side of the brain controls your right hand. New experiments in mice by researchers at the University of Tsukuba have found that normal crossing of these fibers during development, and subsequent motor coordination during adulthood, rely on two key enzymes - Sulf1 and Sulf2.

During development, growing fibers made from neuronal axons are steered from the brain to their proper destinations by guidance molecules. Although the CST is the longest fiber tract and guidance molecules are particularly vital for its proper development, we still do not know all the key players. Researchers from the University of Tsukuba in Japan recently found that mouse embryos lacking Sulf1 and Sulf2 genes exhibit defects in axon guidance. Now, in work published in Frontiers in Molecular Neuroscience, the team has shown that Sulf1/Sulf2-deficient mice also show abnormal postnatal CST development.

"We tested this in a breed of mice that can survive Sulf1/Sulf2 knockout after birth. This let us examine postnatal development of the CST for the first time," study lead author Prof. Masayuki Masu says. "Sulf1/Sulf2 knockout resulted in anatomical abnormalities in the CST, especially at the pyramidal decussation and in the spinal cord projection. The mice showed abnormal motor function as a result."

Usually, most CST fibers cross sides at the bottom of the brainstem at the pyramidal decussation, named for the pyramid-shaped structures that they form there. These crossing fibers connect to muscles of the extremities, particularly the arms, legs, hands, and feet. The researchers found that many axons did not cross sides in the Sulf1/Sulf2 knockout mice, although they did end up in the equivalent muscles on the opposite side. The result was that both sides of the brain were connected to muscles on both sides of the body, and this reduced fine motor skills, but did not seem to affect gross movements.

"The anatomical anomalies seen in the mice were accompanied by impaired fine motor movement, such as skilled reaching and grasping," study co-author Prof. Akira Tamaoka says. "Stimulation of one side of the motor cortex evoked bilateral responses in the forelimb muscles. Under normal conditions, this should result in responses on just one side of the body. Knowing how abnormal CST development affects motor skills in mice could help us understand human motor disorders such as congenital mirror movement - in which voluntary movements of one side of the body are mirrored by involuntary movements of the other."

The results of this study indicate the importance of Sulf1 and Sulf2 and may provide some insight into how the left and right sides of our bodies are controlled by separate sides of the brain. Future work should investigate why eliminating Sulf1 and Sulf2 did not prevent all fiber crossings and whether any characteristics of abnormally uncrossed fibers can predict dexterity in mice or other animal models.

According to the statistics from World Health Organization (WHO), cardiovascular disease has become the leading cause of death worldwide, inducing almost 1/3 of death each year. Owing to its importance and promise in cardiovascular disease treatment, vascular regeneration has attracted global attentions in both academic and clinic. Within the vascular regeneration process, endothelium remodeling, which refers to the formation of a confluent vascular endothelial cell monolayer on the lumen, plays a vital role. However, rapid endothelialization confronts grand challenge using existing synthetic biomaterials or engineering methods as vascular endothelium remodeling is a complicated and dynamic process. Successful endothelium remodeling has become the key to the success of vascular remodeling.

Throughout the endothelialization process of native blood vessels, vascular endothelial cells and progenitor cells is first recruited/migrated to the regeneration sites, followed by the adhesion and spreading of vascular endothelial cells to form a confluent vascular endothelial cell monolayer. In human body, such process is implemented through extracellular matrix (ECM)-mediated stepwise modulation of vascular endothelial cell functions at different stages. Nevertheless, existing synthetic biomaterials usually exhibit static properties, which cannot offer dynamic and particularly on-demand inducements for manipulating specific vascular endothelial cell functions at different stages of endothelium remodeling.

To realize the on-demand manipulation of vascular endothelial cell functions for meeting the requirements of endothelium remodeling, in a research article recently published in the Beijing-based National Science Review, scientists at Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China demonstrate a remote-controlled "smart" platform that effectively directs programmed vascular endothelium remodeling in a temporally controllable manner. In this work, Co-authors Dr. Qilong Zhao (first author), Ms. Juan Wang (co-first author) and Dr. Xuemin Du (corresponding author) develop a bilayer platform with programable surface topographies using a shape-memory polymer and a photothermal agent, gold nanorods. The bilayer platform possesses originally stable anisotropic microgroove array topography at the physiological environment, which can significantly direct cell polarization and thereby enhance the collective migration of vascular endothelial cells. Upon 10-s near infrared (NIR) irradiation, the heat generated on the bottom layer can induce the change in the surface topographies of the platform from original anisotropic microgroove array to permanent isotropic micropillar array. Correspondingly, the focal adhesion and spreading of vascular endothelial cells can be subsequently promoted at the later stage of endothelialization by the platform with altering topographies. The platform with remote-controlled "smart" properties successfully promote different functions of vascular endothelial cell in turn, which mimics the dynamic ECM-mediated effects throughout the endothelialization process for the first time using synthetic biomaterials.

"Traditionally, biomaterials and tissue engineering scaffolds offer suitable platforms to support cell attachment and ingrowth. Nowadays, we aim to develop biomaterials with dynamic properties to actively modulate different cell functions in specific spatiotemporal manners, just like the native ECM in our bodies." Dr. Xuemin Du said, "We believe the biomaterials with dynamic properties will significantly contribute to the progresses of wound healing and complex tissue/organ regeneration".

The team was thus able to provide further evidence that there are interfaces between the nervous system and immune system. The researchers hope that the protagonists or antagonists of this signalling pathway may be suitable for therapeutic interventions. They report on this in the cover story in the journal Science Signaling on 4 February 2020.

Genes protect nerve cells against cell death

The Parkin gene protects nerve cells against functional impairment and cell death. It particularly ensures that mitochondria, cell organelles that are responsible for energy production, remain intact and that damaged mitochondria are removed. PACRG is located next to the Parkin gene in the genome. Both genes share what is called a promotor, which regulates the expression of the genes. Parkin and PACRG are thus expressed in a similar pattern.

"Little has been known about PACRG so far, so we investigated what functions this gene has," says Konstanze Winklhofer. Her team found that, unlike Parkin, PACRG has no influence on the elimination of damaged mitochondria, but, like parkin, is able to protect nerve cells from cell death.

Parkin and PACRG regulate a signalling pathway of the innate immune system

Further investigations into the mechanism of action showed that PACRG regulates a signalling pathway that is stimulated by tumour necrosis factor (TNF). This results in the activation of the transcription factor NF-κB, which ensures the increased formation of pro-survival proteins. Both Parkin and PACRG have an effect on an essential protein complex of this signalling pathway, called Lubac (linear ubiquitin chain assembly complex). Lubac is required for efficient signal transduction by modifying components of the NF-κB signalling pathway with linear ubiquitin chains.

The TNF-NF-κB signalling pathway not only regulates cell death but also plays an important role in the innate immune system. It prevents the spreading of certain bacteria that invade host cells, such as salmonella, linked to foodborne infections, or mycobacteria, which cause tuberculosis or leprosy. "Interestingly, sequence variations in the Parkin and PACRG genes have been described that lead to an increased susceptibility to these bacterial infections and are associated with severe courses of salmonella or mycobacterial infections," explains Konstanze Winklhofer. The current findings thus provide a plausible explanation for these observations and confirm that there are interfaces between the nervous system and immune system. Their protagonists or antagonists could be suitable targets for therapeutic interventions.

Philadelphia, February 5, 2020 - The Wilderness Medical Society (WMS) has released new clinical practice guidelines in a supplement to Wilderness & Environmental Medicine, published by Elsevier. This issue features updates to previously published clinical practice guidelines and newly developed guidelines on diabetes management and spinal immobilization in the wilderness setting.

These revised and new WMS clinical practice guidelines have been developed and guest-edited by Christopher Davis, MD, Department of Emergency Medicine-Wilderness and Environmental Medicine, University of Colorado School of Medicine, Aurora, CO, USA; Michael Caudell, MD, Department of Emergency Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA; and Tracy Cushing, MD, MPH, Department of Emergency Medicine, University of Colorado Hospital, Aurora, CO, USA. All recommendations are graded based upon the clinical strength of available evidence as outlined by the American College of Chest Physicians (ACCP).

"Clinical practice guidelines are increasingly necessary to help clinicians navigate and synthesize the expanding volume of available medical literature," explained Dr. Davis. "Our guidelines are continuously updated to reflect the most current literature and recommendations for wilderness medicine pathology and are uniquely interdisciplinary in their authorship. Our goal is to provide the most up-to-date and relevant clinical information to frontline providers in wilderness or austere environments."

"The WMS is committed to ensuring that each clinical practice guideline is developed by a working group representative of the best experts in the field and multidisciplinary in scope," added Dr. Davis. "As an interdisciplinary author group, the impact of these guidelines is far reaching both in terms of scope of practitioners and in breadth of information. These address unique pathology such as altitude illness that are not covered in other medical literature and sometimes provide the ONLY clinical practice guidelines for particular illnesses."

New clinical practice guidelines include:

Clinical practice guidelines for diabetes management

Athletes with both type 1 and type 2 diabetes are undertaking ever-expanding wilderness challenges. At least three individuals with diabetes have successfully reached the summit of Mount Everest. In a recent survey, people who self-identified as having diabetes represented seven percent of 3,000 surveyed ultramarathon runners. Both high and low blood sugar can be catastrophic in environments where there are limited resources, and glycemic control is more challenging in extreme conditions, needing additional monitoring, treatment adjustments, and careful planning beforehand.

The authors of a new guideline on diabetes management point out that there are so many variables that it is impossible to come up with a single set of guidelines. They recommend personalizing the medical care of each individual based on personal history and input, and advise adjusting insulin doses and diet plans according to the type and degree of activity that will be performed; an individual's baseline level of fitness; the individual's athletic and disease history; and the environment to which the athlete will be exposed. They also recommend that athletes with diabetes should carry a basic written plan developed with their endocrinologist describing their usual treatment regimen; a plan for basic adjustments in the back country; basics of hypo-/hyperglycemia management; and an emergency action plan.

Clinical practice guidelines for spinal cord protection

The low volume and quality of scientific evidence available does not support the current rationale for immobilizing a potential spine injury in the wilderness environment, according to the updated guideline on spinal injury care, suggesting that historic principles of out-of-hospital spinal injury care may have been more influenced by medicolegal implications and untested theory than by clinical or scientific evidence. The focus of this current guideline is to present an evidence-based approach to out-of-hospital care of an existing or potential spinal cord injury in wilderness environments that minimizes the possibility of neurologic deterioration or making the injury worse from the time of extrication to arrival at a medical facility. Current evidence suggests that rigid immobilization via collar or backboard can result in a worse patient outcome in both blunt and penetrating trauma. Instead, the guidelines propose that spinal motion restriction (SMR) may be the most appropriate mechanism currently available.

Other updated guidelines cover the prevention and treatment of acute altitude illness; prevention and treatment of frostbite; prevention and treatment of heat illness; prevention and treatment of drowning; water disinfection for wilderness, international travel, and austere conditions; and out-of-hospital evaluation and treatment of accidental hypothermia. They also highlight several important questions that remain to be addressed and could serve as a focus for future research, such as, the role of acetazolamide in preventing and treating high altitude cerebral edema; determining the optimal rate of ascent to prevent altitude illness; the role of staged ascent, preacclimatization, and hypoxic tents in altitude illness prevention; optimal methods of resuscitating hypothermic patients in cardiac arrest; and the use of technological innovations to allow access to wilderness pursuits such as big wall rock climbing and scuba diving that have historically been off limits to those with diabetes.

Dr. Cushing added a note of caution about the challenges faced in developing guidelines for illnesses encountered in the wilderness. "Wilderness recreation is increasingly popular. Accordingly, more individuals are at risk today than ever before. However, it is challenging to design and execute randomized clinical trials, as the illnesses we treat are not only rare, they also occur in challenging and remote environments."

"Previously published guidelines have been some of the most highly-cited articles in Wilderness & Environmental Medicine. It is our foremost goal to continue the tradition of bringing forward the best available data to the wilderness medical provider," concluded the guest editors.

An elaborate system of filaments, liquid droplet dynamics and protein connectors enables the repair of some damaged DNA in the nuclei of cells, researchers at the University of Toronto have found. The findings further challenge the belief that broken DNA floats aimlessly -- and highlight the value of cross-disciplinary research in biology and physics.

DNA repair helps ensure genome stability, which in turn allows cells to function and promotes health in all organisms. Double-strand DNA breaks are especially toxic to cells, and researchers had assumed for decades that these breaks floated inside cell nuclei without direction, until they trigger other cellular changes or happen on a fixer mechanism.

That thinking began to change in 2015, when Karim Mekhail and his lab showed that damaged DNA can be intentionally transported by motor protein 'ambulances' to DNA 'hospitals,' areas enriched with certain repair factors in the nuclei. The researchers later worked with U of T aerospace engineers to show that after a single double-strand break, DNA travels for repair via long 'autobahns' of thread-like microtubules, which are also moving.

In the current study, Mekhail and lead author Roxanne Oshidari looked at yeast cells with many DNA double-strand breaks, and showed that coordination between shorter types of microtubule filaments and liquid-like droplets composed of DNA repair proteins enables the creation and function of a DNA repair centre.

"The liquid droplets work with intranuclear microtubules to promote the clustering of damaged DNA sites," says Mekhail, an associate professor of laboratory medicine and pathobiology at U of T. "Repair proteins at these different sites assemble in droplets that fuse into a larger repair-centre droplet, through the action of the shorter nuclear microtubules."

This larger oil-like droplet then behaves like a spider, says Mekhail, shooting out a web of star-shaped filaments that tether to the longer autobahns along which damaged DNA can be transported to the DNA hospitals.

The journal Nature Communications published the findings today.

Mekhail turned to Nasser Ashgriz, a professor in U of T's department of mechanical and industrial engineering, to measure and understand the role of droplets in the repair process. "You couldn't ask for better expertise in fluid dynamics, and he was just across the road," Mekhail says of Ashgriz, who runs U of T's multi-phase flow and spray systems lab.

Mekhail brought a video of the droplets to Ashgriz, who projected it on a large screen in his office and confirmed that fluid dynamics appeared to be at play. But communication across the biology-physics divide was challenging. "Understanding what they do was very difficult in the beginning because our terminologies are totally different," says Ashgriz.

When he and Mekhail used plain language to describe how the droplets behaved, however, things started to make sense. "We focused on the physical aspects of the droplets," Ashgriz says. "The physics that cause their motion and dynamics became our common language."

After months of talks and experiments, computer simulations repeatedly predicted that the shorter filaments would move like pistons, lowering pressure in the nucleoplasm and creating a suction effect that leads to the fusion of droplets. Mekhail and his team confirmed that finding in their lab.

"Often when we dive deep in the specifics of a field, we get separated from one another," Ashgriz says. "Bringing together people with different views can really improve understanding, and this work was a good example -- with credit to Karim for his vision and initiative."

Mekhail and his team also uncovered further important properties of the repair droplets with U of T professors Hyun Kate Lee and Haley Wyatt in the department of biochemistry, in a process Mekhail likens to play with toys. They ran the droplets through many tests, bouncing them against each other and observing their behaviour, which turned out to be very similar in a petri dish and in cells.

The most surprising finding came after several cycles of droplet fusion, the researchers found. "It was very bizarre and totally unexpected, I still remember the day," Mekhail says. Oshidari observed that the larger droplets initiate an internal concentration of filament building blocks, forcing creation of a kind of self-interlocking brick road, which together with the spidery webs allow DNA to hook onto the longer autobahn filaments.

The complex process is easy to miss when looking at DNA damage sites, says Mekhail, largely because imaging in the field has become highly automated. Most software has been set up to see what has already been seen. "We can't rely on the old ways of observing," he says. "We need to update our software and also go back to looking with the human eye, guided by simulations when needed."

ANN ARBOR--It's 5 p.m. as you leave the parking garage at work, but you realize you have no idea which way to turn to travel home. You know where you are and what street your house is on--it's just that you can't remember how to get there.

This is what happens to patients with damage to a part of their brain called the retrosplenial cortex, a key region involved in the organ's inner compass. Despite its importance for navigation, the neurons and circuits it uses to help get people from the office to home remain understudied.

By recording signals from individual neurons in the mouse brain, researchers at the University of Michigan have identified a distinct excitatory neuron in the retrosplenial cortex. The properties of this neuron are ideally suited to encode direction-related information over long durations, like a compass.

"Regular neurons in the cortex are good at encoding directional information only when you are moving your head, but what happens when your head is still? You still need to know what direction you are facing so that you can use this information to plan your route," said Omar Ahmed, assistant professor of psychology, neuroscience and biomedical engineering, and lead author of the study published in the journal Cell Reports.

"You ideally need another kind of neuron--a neuron that can continuously encode your orientation over long durations even when your head is not moving."

Typical excitatory neurons slow down their firing rather quickly. In contrast, the newly identified neurons can continue firing their signals at high rates for extended periods of time--they are persistent and fast.

A second difference lies in their capacity to respond to inputs--these unique neurons, called low rheobase neurons--are hyperexcitable, which means they need little input to be activated.

"A simpler name for this small yet tenacious little neuron, as suggested by my classmate, would be 'The Little Neuron That Could,'" said Ellen Brennan, the graduate student who identified these unique neurons. "It's the perfect name because it highlights the persistence that makes them optimally suited to code continued direction. In comparison, the other typical excitatory neurons here are slow and stubborn."

"So the question was, can these low rheobase neurons process directional information better than typical excitatory neurons?" said Shyam Sudhakar, a postdoctoral fellow in the Ahmed lab who created computer models of these neurons to show that the answer is "yes."

"It's important for my brain to know when I change direction, but it's not good if all my brain detects is change," Brennan said. "A compass always has to know which way is north. It wouldn't be useful without that persistent sense of direction. That is exactly what the low rheobase neurons can provide."

Ahmed's lab is now focused on understanding how these unique neurons are altered in Alzheimer's model mice.

"The retrosplenial cortex is critical for spatial orientation, but is one of the earliest brain regions to show dysfunctional activity in Alzheimer's patients," Ahmed said. "This is probably why the vast majority of Alzheimer's patients suffer from spatial disorientation and get lost easily--because their retrosplenial cells are not working as they should.

"By understanding how retrosplenial cells encode compass-like information in healthy versus Alzheimer's brains, we hope to start working towards novel therapies."

WEST LAFAYETTE, Ind. - Foodborne illness hits about one in six people in the United States every year. The Centers for Disease Control and Prevention estimates that 48 million people in the U.S. get sick due to one or more of 31 recognized pathogens, including E. coli O157:H7, a particularly harsh strain of E. coli.

Researchers at Purdue University have been working to develop new technologies to help stop the spread of foodborne illnesses, which kill 3,000 people a year, by detecting them more efficiently. They have developed a bioluminescence-based assay coupled with a portable device that works with smartphones and laptops to do on-site testing for harmful E. coli in food samples.

The silicon photomultiplier (SiPM) device uses low light to from the bioluminescent assay to detect the presence of bacteria that cause foodborne illness in food samples. The Purdue team also created an electrical circuit with an amplifier, comparator and micro controller to send the data to laptops and smartphones via Bluetooth technology. They used 3D printing to design a portable cradle for the SiPM. The research is published in the January edition of Applied Optics.

"Our goal is to create technology and a process that allows for the cost-effective detection of the causes of foodborne illness using an easy, expedient and efficient process," said Euiwon Bae, a senior research scientist of mechanical engineering in Purdue's College of Engineering, who developed the technology along with Bruce Applegate, a professor of food science in Purdue's College of Agriculture. "This time frame allows for better integrated detection and quicker action to stop more people from getting sick."

To show the proof of concept, the Purdue team tested the device with artificially contaminated samples of ground beef from a local grocery store. They injected E. coli into the beef samples and then used their device to analyze the sample within 10 hours of inoculation.

The beef is rinsed and incubated with an enrichment liquid containing a modified phage, a virus for bacteria. The phage then infects harmful foodborne bacteria so that when a substrate is added, the bacteria emit light, which is detected by the SiPM. The device is able to count light pulses or photons.

"Our assay offers higher sensitivity, lower cost, better portability and other distinct advantages when compared to existing detection methods," Applegate said.

Baby diapers, contact lenses and gelatin dessert. While seemingly unrelated, these items have one thing in common -- they're made of highly absorbent substances called hydrogels that have versatile applications. Recently, a type of biodegradable hydrogel, dubbed microporous annealed particle (MAP) hydrogel, has gained much attention for its potential to deliver stem cells for body tissue repair. But it is currently unclear how these jelly-like materials affect the growth of their precious cellular cargo, thereby limiting its use in regenerative medicine.

In a new study published in the November issue of Acta Biomaterialia, researchers at Texas A&M University have shown that MAP hydrogels, programmed to biodegrade at an optimum pace, create a fertile environment for bone stem cells to thrive and proliferate vigorously. They found the space created by the withering of MAP hydrogels creates room for the stem cells to grow, spread and form intricate cellular networks.

"Our research now shows that stem cells flourish on degrading MAP hydrogels; they also remodel their local environment to better suit their needs," said Dr. Daniel Alge, assistant professor in the Department of Biomedical Engineering. "These results have important implications for developing MAP hydrogel-based delivery systems, particularly for regenerative medicine where we want to deliver cells that will replace damaged tissues with new and healthy ones."

MAP hydrogels are a newer breed of injectable hydrogels. These soft materials are interconnected chains of extremely small beads made of polyethylene glycol, a synthetic polymer. Although the microbeads cannot themselves cling to cells, they can be engineered to present cell-binding proteins that can then attach to receptor molecules on the stem cells' surface.

Once fastened onto the microbeads, the stem cells use the space between the spheres to grow and transform into specialized cells, like bone or skin cells. And so, when there is an injury, MAP hydrogels can be used to deliver these new cells to help tissues regenerate.

However, the health and behavior of stem cells within the MAP hydrogel environment has never been fully studied.

"MAP hydrogels have superior mechanical and biocompatible properties, so in principle, they are a great platform to grow and maintain stem cells," said Alge. "But people in the field really don't have a good understanding of how stem cells behave in these materials."

To address this question, the researchers studied the growth, spread and function of bone stem cells in MAP hydrogels. Alge and his team used three samples of MAP hydrogels that differed only in the speed at which they degraded, that is, either slow, fast or not at all.

First, for the stem cells to attach onto the MAP hydrogels, the researchers decorated the MAP hydrogels with a type of cell-binding protein. They then tracked the stem cells as they grew using a high-resolution, fluorescent microscope. The researchers also repeated the same experiment using another cell-binding protein to investigate if cell-binding proteins also affected stem cell development within the hydrogels.

To their surprise, Alge's team found that for both types of cell-binding proteins, the MAP hydrogels that degraded the fastest had the largest population of stem cells. Furthermore, the cells were changing the shape of the MAP hydrogel as they spread and claimed more territory.

"In the intact MAP hydrogel, we could still see the spherical microbeads and the material was quite undamaged," said Alge. "By contrast, the cells were making ridges and grooves in the degrading MAP hydrogels, dynamically remodeling their environment."

The researchers also found that as the stem cells grew, the quantity of bone proteins produced by the growing stem cells depended on which cell-binding protein was initially used in the MAP hydrogel.

Alge noted that the insight gained through their study will greatly inform further research and development in MAP hydrogels for stem-cell therapies.

"Although MAP hydrogel degradability profoundly affects the growth of the stem cells, we found that the interplay between the cell-binding proteins and the degradation is also important," he said. "As we, as a field, make strides toward developing new MAP hydrogels for tissue engineering, we must look at the effects of both degradability and cell-binding proteins to best utilize these materials for regenerative medicine."

It happens outside your window every time it rains: The soil gets wet and may form sticky mud. Then it dries. Later it might rain again. Each wetting and rewetting affects the structure and stability of the soil. These changes are taken into account when, for example, architects and engineers design, site, and construct buildings. But more broadly, the science of how particles stick together and then pull apart touches fields as diverse as natural hazards, crop fertilization, cement production, and pharmaceutical design.

Uniting these disparate fields, a team at the University of Pennsylvania has found that when particles are wet and then allowed to dry, the size of those particles has a lot to do with how strongly they stick together--and whether they stay together or fall apart the next time they are wetted.

What lends these sticky aggregates strength, the team found, are thin bridges formed when particles of the material are suspended in a liquid and then left to dry, leaving thin strands of particles that connect larger clumps. The strands, which the researchers call solid bridges, increase the aggregates' stability 10- to 100-fold.

The researchers reported their findings in the journal Proceedings of the National Academy of Sciences.

"This solid bridging phenomenon may be ubiquitous and important in understanding the strength and erodibility of natural soils," says Paulo Arratia, a fluid mechanics engineer in Penn's School of Engineering and Applied Science, and a coauthor on the study.

"We found that a particle's size can outweigh the contribution of its chemical properties when it comes to determining how strongly it sticks to other particles," adds Douglas Jerolmack, a geophysicist in the School of Arts and Sciences and the paper's corresponding author.

The research team was led by Ali Seiphoori, formerly a postdoc in Jerolmack's lab and now at MIT, and included physics postdoc Xiao-guang Ma. The current work spun out from investigations they had been pursuing in conjunction with Penn's Perelman School of Medicine on asbestos, specifically how its needle-like fibers stick to one other and to other materials to form aggregates. That got them thinking more generally about what determines the strength and stability of an aggregate.

The group took an experimental approach to answering this question by creating a simple model of particle aggregation. They suspended glass spheres of two sizes, 3 microns and 20 microns, in a droplet of water. (For reference, a human hair is roughly 50 to 100 microns in width.) As the water evaporated, the edges of the droplet retreated, dragging the particles inward. Eventually the shrinking water droplet transformed into multiple smaller droplets connected by a thin water bridge, known as a capillary bridge, before that too evaporated.

The team found that the extreme suction pressures caused by evaporation pulled the small particles so tightly together that they fused together in the capillary bridges, leaving behind solid bridges between the larger particles, to which they also bound, once the water evaporated completely.

When the team rewet the particles, applying water in a controlled flow, they found that aggregates composed solely of the 20 micron particles were much easier to disrupt and resuspend than those composed of either the smaller particles, or mixtures of small and larger particles.

"We found that if aggregates composed of only particles larger than 5 microns were rewet, they collapsed," Jerolmack says. "But under 5 microns, nothing happens, the aggregates were stable."

In further tests with mixtures of particles of four different sizes--more closely mimicking natural soil composition--the researchers found the same bridging affect occurring at different scales: The largest particles were bridged by the second largest, which were in turn bridged by the third largest, which themselves were stabilized by bridges of the smallest particles. Even mixtures that contained only a small fraction of smaller particles became more stable thanks to solid bridging.

How much more stable? To find out, Seiphoori painstakingly glued the probe of an atomic force microscope to a single particle, let it set, and then quantified the "pull-off force" required to remove that particle from the aggregate. Repeating this for particles in aggregates of both big and small particles, they found that particles were 10 to 100 times harder to pull off when they had formed a solid bridge structure than in other configurations.

To convince themselves that the same would be true with materials besides their experimental glass beads, they performed similar experiments using two types of clay that are both common components of natural soils. The principals held: the smaller clay particles and the presence of solid bridges made aggregates stable. And the reverse was also true: When clay particles smaller than 5 microns were removed from the suspensions, their resulting aggregates lost cohesion.

"Clay soils are thought to be fundamentally cohesive," says Jerolmack, "and that cohesiveness has usually been attributed to their charge or some other mineralogic property. But we found this very surprising thing that it doesn't seem to be the fundamental properties of clay that make it sticky, but rather the fact that clay particles tend to be very small. It's a brand new explanation for cohesion."

These new insights about the contribution of particle size to aggregate stability open up new possibilities for considering how to enhance stability of materials like soil or cement when desired. "You could envision stabilizing soils before a construction project by adding smaller particles that help bind the soil together," Jerolmack says.

In addition, the production of a variety of materials, from medical devices to LED screen coatings, relies on thin film deposition, which the researchers say might benefit from the controlled production of aggregates that they observed in their experiments.

WASHINGTON, February 4, 2020 -- Motor-related brain activity, particularly its accurate detection, quantification and classification capabilities, is of great interest to researchers. They are searching for a better way to help patients with cognitive or motor impairments or to improve neurorehabilitation for patients with nervous system injuries.

There is a close relationship between motor and cognitive activity of the human brain, and suppression of the specific rhythmic activity of neurons within the sensorimotor cortex of the brain -- known as the mu-rhythm (8 to 14 hertz) -- is a biological marker of motor-related brain activity. Studies indicate this feature of motor-related brain activity suffers from intra- and inter-subject variability when using traditional methods to explore it, such as time-frequency analysis, spatial filtering and machine learning.

In the journal Chaos, from AIP Publishing, Nikita Frolov and colleagues at Innopolis University in Russia are approaching the problem from a different angle to search for a more robust feature of brain activity associated with accomplishing motor tasks.

"We put forward the hypothesis that suppression of mu-oscillations will cause a reduction of measured brain activity signals and, consequently, reflects the simplification of underlying neuronal dynamics," said Frolov. "To address this issue, we applied recurrence quantification analysis, which is a powerful toolbox, to explore systems complexity through the analysis of its time series."

The group's work confirms, for the first time, the neuronal dynamics within the sensorimotor brain area underlying the motor functions of the human brain can be simplified.

"We demonstrated this using the RQA toolbox, which is fundamentally different from traditional methods for quantification of motor-related brain activity," Frolov said. "We also demonstrated that RQA measures of complexity are well suited to detect and classify motor tasks."

These results show potential for developing efficient methods for classifying brain states.

"By accurately introducing a state space, you can consider any natural system as a dynamical system. For the human brain, you can create state space by taking the measured signals of its activity as the state variables," Frolov said.

"In our study, we consider state space formed by the set of electroencephalograms (signals of electrical activity within the brain's cortical regions) recorded within the motor cortex. This allows us to introduce the 'state' of the cortical region of interest and to consider it as a dynamical system."

One of the applications of the group's work is "implementation of RQA-based analysis of electroencephalograms as a computational core of the brain-computer interfaces for online detection, quantification, and training of brain motor functions," Frolov said.

"This is relevant not only for the development of closed-loop interfaces for motor skills training during neurorehabilitation but also for the diagnosis of cognitive and motor impairments as well as age-related changes."

What The Study Did: Nearly 40 years of registry data for 7.3 million people living in Denmark were used to examine whether people diagnosed with neurological disorders, including  dementia, stroke, epilepsy, Parkinson disease and multiple sclerosis, die by suicide more often than others.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Annette Erlangsen, Ph.D., of the Danish Research Institute for Suicide Prevention in Copenhagen, Denmark, is the corresponding author.

(doi:10.1001/jama.2019.21834)

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