Culture

Firearm retailers around Washington state are willing to learn about suicide prevention and to train their employees in how to spot and act on suicide warning signs, a new University of Washington study finds.

With firearms the commonly used and most lethal means of suicide nationwide, the findings from the survey of nearly 200 independent firearm retailers across the state demonstrate the potential for key community members to be proactive in helping to prevent people from taking their own lives, said Thomas Walton, a UW doctoral candidate of social work at Forefront Suicide Prevention and lead author of the paper.

The study, believed to be first to look at what influences firearm retailers in suicide prevention efforts, also finds that a lack of awareness of the role of firearms in suicide, as well as a reluctance to talk to customers about personal issues, likely inhibit greater progress in suicide prevention.

"Suicide prevention hasn't been an area of focus in the firearm community, and it shows," Walton said. "But there's a definite willingness to pass on firearm safety information, and they want to be able to see how to integrate suicide prevention into talking about firearm safety."

The study was published online July 29 in the journal Suicide and Life-Threatening Behavior.

According to the Centers for Disease Control and Prevention, about half of all suicides in the United States from 1999 to 2017 (the most recent statistics available) involved a firearm. The percentage is even higher in veteran suicides.

In Washington, the data is similar: From 2013 to 2017, almost half of all suicides, and 67% of veteran suicides, involved a firearm, according to the state Department of Health. Beginning in 2017, the state Legislature helped fund Forefront's Safer Homes, Suicide Aware campaign, which offers training, outreach and locking devices for firearms and medications in communities with high rates of firearms ownership.

As part of its mission, the Safer Homes program has identified gun retailers as a key potential stakeholder in distributing information about suicide prevention. Other states, such as New Hampshire and Colorado have been working to engage firearm retailers in the issue; the UW study is the first aimed at understanding what influences such engagement.

The first step for UW researchers was surveying firearm retailers about their knowledge of suicide prevention and willingness to participate. Using records from the state Department of Licensing and the federal Bureau of Alcohol, Tobacco, Firearms and Explosives, Walton and Forefront director Jennifer Stuber were able to find email or mailing addresses for nearly 800 independent retailers around the state. The team created a 42-question survey that was available in print or online.

Big-box stores that sell guns were not included because of corporate policies governing store-level training and outreach.

The researchers also partnered with the Second Amendment Foundation and the owner of a Spokane gun shop, who together sent an introductory letter to the retailers explaining the survey.

In the end, 178 surveys were completed. Sixteen retailers contacted the researchers to refuse the survey, while 62 were minimally completed, and 33 were returned as undeliverable. The remaining 500 weren't returned.

"There are barriers to working with this population because of distrust and incomplete contact information," said Stuber, an associate professor in the UW School of Social Work. "But if you get the right messengers to get people to the table, there is clearly a willingness among retailers to be involved in the solutions."

The results can be grouped generally into three distinct types of questions: knowledge of suicide and how to prevent it; support for learning more; and a willingness to intervene directly with customers.

About half of the retailers who responded said they were familiar with warning signs of suicide, while nearly two-thirds of respondents said they wanted to know more about how firearm retailers can help prevent suicide. About 72% said they would provide free training to employees.

At the other end of the spectrum were beliefs about suicide and the retailer's role in talking with customers in crisis. Nearly three-quarters said asking customers about their mental health might offend them. About 45% said asking about personal issues is not their responsibility, and 66% agreed with the statement: "If a person wants to die by suicide, there is nothing I can do to stop them."

"It is critical to work on changing this common misperception that suicide is inevitable," Walton said. "For the vast majority of individuals, the desire to die by suicide is fleeting, so anything any of us can do to prevent or postpone a suicidal act is helping to save a life."

Survey results also indicated that the more a retailer knows about suicide, and the longer they have been in business, the more comfortable they are with ideas about training employees and talking with customers. For instance, retailers for whom a majority of sales come from firearms and ammunition were more likely to support education and outreach around suicide prevention. Those with longer tenure in the industry, the authors wrote, were also more supportive of suicide prevention efforts and thus could be tapped as leaders in any future effort among retailers.

"Notably, most firearm retailers lack awareness that suicide is the most common type of firearm fatality. Education about this fact is an important first step to increasing engagement in prevention efforts," Stuber said. "We are going to need out-of-the-box solutions to reach communities with high rates of firearm ownership to create compelling public health messages about suicide prevention."

What The Study Did: Giant cell arteritis is an inflammation of the blood vessels that typically occurs in adults over 50 and, if left untreated, can result in irreversible vision loss and death. This study examined whether occurrence of the disorder was associated with race.

Authors: Anna M. Gruener, B.M.B.S., M.Sc., F.R.C.Ophth, of the Nottingham University Hospitals National Health Service Trust in the United Kingdom, is the corresponding author.

(doi:10.1001/jamaophthalmol.2019.2919)

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

Identifying species among plants and animals has been a full-time occupation for some biologists, but the task is even more daunting for the myriad microbes that inhabit the planet. Now, MIT researchers have developed a simple measurement of gene flow that can define ecologically important populations among bacteria and archaea, including pinpointing populations associated with human diseases.

The gene flow metric separates co-existing microbes in genetically and ecologically distinct populations, Martin Polz, a professor of civil and environmental engineering at MIT, and colleagues write in the August 8 issue of Cell.

Polz and his colleagues also developed a method to identify parts of the genome in these populations that show different adaptations that can be mapped onto different environments. When they tested their approach on a gut bacterium, for instance, they were able to determine that different populations of the bacteria were associated with healthy individuals and patients with Crohn's disease.

Biologists often call a group of plants or animals a species if the group is reproductively isolated from others -- that is, individuals in the group can reproduce with each other, but they can't reproduce with others. As a result, members of a species share a set of genes that differs from other species. Much of evolutionary theory centers on species and populations, the representatives of a species in a particular area.

But microbes "defy the classic species concept for plants and animals," Polz explains. Microbes tend to reproduce asexually, simply splitting themselves in two rather than combining their genes with other individuals to produce offspring. Microbes are also notorious for "taking up DNA from environmental sources, such as viruses," he says. "Viruses can transfer DNA into microbial cells and that DNA can be incorporated into their genomes."

These processes make it difficult to sort coexisting microbes into distinct populations based on their genetic makeup. "If we can't identify those populations in microbes, we can't one-to-one apply all this rich ecological and evolutionary theory that has been developed for plants and animals to microbes," says Polz.

If researchers want to measure an ecosystem's resilience in the face of environmental change, for instance, they might look at how populations within species change over time. "If we don't know what a species is, it's very difficult to measure and assess these types of perturbations," he adds.

A yardstick for gene flow

Martin and his colleagues decided to look for another way to define ecologically meaningful populations in microbes. Led by microbiology graduate student Philip Arevalo, the researchers developed a metric of gene flow that they called PopCOGenT (Populations as Clusters Of Gene Transfer).

PopCOGenT measures recent gene flow or gene transfer between closely related genomes. In general, microbial genomes that have exchanged DNA recently should share longer and more frequent stretches of identical DNA than if individuals were just reproducing by splitting their DNA in two. Without this sort of recent exchange, the researchers suggested, the length of these shared stretches of identical DNA would shorten as mutations insert new "letters" into the stretch.

Two microbial strains that are not genetically identical to each other but share sizable "chunks" of identical DNA are probably exchanging more genetic material with each other than with other strains. This gene flow measurement can define distinct microbial populations, as the researchers discovered in their tests of three different kinds of bacteria.

In Vibrio bacteria, for instance, closely related populations may share some core gene sequences, but they appear completely isolated from each other when viewed through this measurement of recent gene flow, Polz and colleagues found.

Polz says that the PopCOGenT method may work better at defining microbial populations than previous studies because it focuses on recent gene flow among closely related organisms, rather than including gene flow events that may have happened thousands of years in the past.

The method also suggests that while microbes are constantly taking in different DNA from their environment that might obscure patterns of gene flow, "it may be that this divergent DNA is really removed by selection from populations very quickly," says Polz.

The reverse ecology approach

Microbiology graduate student David VanInsberghe then suggested a "reverse ecology" approach that could identify regions of the genome in these newly defined populations that show "selective sweeps" -- places where DNA variation is reduced or eliminated, likely as a result of strong natural selection for a particular beneficial genetic variant.

By identifying specific sweeps within populations, and mapping the distribution of these populations, the method can reveal possible adaptations that drive microbes to inhabit a particular environment or host -- without any prior knowledge of their environment. When the researchers tested this approach in the gut bacterium Ruminococcus gnavus, they uncovered separate populations of the microbe associated with healthy people and patients with Crohn's disease.

Polz says the reverse ecology method is likely to be applied in the near future to studying the full diversity of the bacteria that inhabit the human body. "There is a lot of interest in sequencing closely related organisms within the human microbiome and looking for health and disease associations, and the datasets are growing."

He hopes to use the approach to examine the "flexible genome" of microbes. Strains of E. coli bacteria, for instance, share about 40 percent of their genes in a "core genome," while the other 60 percent -- the flexible part -- varies between strains. "For me, it's one of the biggest questions in microbiology: Why are these genomes so diverse in gene content?" Polz explains. "Once we can define populations as evolutionary units, we can interpret gene frequencies in these populations in light of evolutionary processes."

Polz and colleagues' findings could increase estimates of microbe diversity, says Marx. "What I think is really cool about this approach from Martin's group is that they actually suggest that the complexity that we see is even more complex than we're giving it credit for. There may be even more types that are ecologically important out there, things that if they were plants and animals we would be calling them species."

CHICAGO--August 8, 2019--Viewing physical activity as an outlet for stress can increase college students' willingness to exercise. However, in order to maintain that routine, students need social support from family and friends, according to research published in The Journal of the American Osteopathic Association.

Researchers surveyed 135 college students, assessing their willingness to exercise for the recommended 150 minutes per week. Participants were asked to weigh pros, like improved energy and health against perceived disadvantages, like being tired and not having enough time for academics or leisure.

Once convinced that more exercise would benefit them, students were asked what they needed to get started. The single most significant factor was behavioral confidence, which involves visualization of future performance and external sources of confidence, like one's religious faith or an encouraging mentor.

"Physicians who want to encourage their patients to get more physical activity should suggest the techniques from this study," says Vinayak K. Nahar, MD, PhD, an assistant professor at the University of Mississippi Medical Center and co-author on this study. "Accessing internal and external sources of inspiration and resilience is an effective and sustainable model for positive change."

According to the survey, respondents indicated that sustaining the weekly 150 minutes of exercise would require the support of family and friends, as well as an emotional shift, in which students would use exercise as an outlet for stressors. Respondents also said social changes, like making friends who also exercise regularly would improve their ability to persist.

"Nearly half of all adults in the U.S. do not engage in the recommended 150 minutes of physical activity per week," says Manoj Sharma, MBBS, PhD, a professor of behavioral health at Jackson State University and lead researcher on this study. "This basic lack of exercise is tied to myriad health problems, so it is important to address it early."

Amyloid fibrils are a type of self-assembled proteins/peptides that take on a stacked sheet-like formation. Amyloid fibril aggregates are known to be a cause of several diseases--including Alzheimer's--and therefore, it is of immense scientific interest to understand how these aggregates can be broken. Some types of amyloid fibrils also play a role in regulation of gene expression in some organisms. It is also thought that the fiber-like formats appearing in these aggregates act as scaffolds on which to cultivate biomaterials. Therefore, a suitable technique for breakdown or "dissociation" of amyloid protein fibrils is critical from the perspective of medical treatment, modification of biological structures and functions, and even biomaterial engineering. A collaborative group of Japanese scientists from the IR Free Electron Laser Research Center at Tokyo University of Science and The Institute of Scientific and Industrial Research at Osaka University, consisting of Dr Takayasu Kawasaki, Prof Koichi Tsukiyama, and Asst Prof Akinori Irizawa, has now shown that a far-infrared (FIR) free-electron laser (FEL), called FIR-FEL, can be used to break down amyloid protein aggregates, which is a testament to the power of interdisciplinary scientific research. This study has been published recently in Scientific Reports. Kawasaki states, "We wanted to demonstrate the applicability of strong free-electron lasers in the life sciences, and this interdisciplinary research has made this possible."

Previous studies have investigated the dissociation of amyloid fibrils but with limited success and mixed results. Because their dissociation in water is difficult, physical methods of dissociation have been explored in the past. Lasers and electromagnetic radiation have been used for fabrication and structural/functional alteration of chemical and biological materials. Among lasers, the FIR-FEL has been studied very sparsely, although it has high penetration power and is absorbed well by biological systems. It is also used in tissue imaging, cancer diagnostics, and biophysics studies. Kawasaki explains, "Our study shows for the first time that FIR-FEL is also useful for breaking down the fibril aggregate structure of proteins."

For their study, the researchers used the 5-residue peptide DFKNF as the model because the link between its fibrillation and pathogenesis is already established. This peptide auto-assembles into a fibril sheet. They found that FIR-FEL damaged the rigid β-sheet conformation (one of the few structures that proteins assume) of the 5-residue peptide by creating small holes on the peptide film. The researchers found that FIR-FEL also disrupts the hydrogen bonds between adjacent β-sheets in the fibril and gives rise to free peptides. This is referred to as dissociation.

Kawasaki and team then checked for conformational changes in the peptide fibril after irradiation with FIR-FEL, by analyzing the ratios of 4 types of secondary structures of peptides (α-helix, β-sheet, β-turn, and other). They found that the proportion of the β-sheet conformation was drastically reduced, which suggests that the rigid sheet-like structure of the fibril was disrupted.

Kawasaki states that a previous study had also found mid-infrared (MIR)-FEL to be effective in this regard. "We compared the effects of MIR-FEL with those of FIR-FEL," says Kawasaki, "and we found that although MIR-FEL caused conformational changes in the fibril aggregates, it did not break down the fibrils as affectively as FIR-FEL did."

Using scanning electron microscopy and dye staining techniques, the researchers also confirmed that FIR-FEL causes morphological changes in the fibrils. Kawasaki says, "Because amyloid fibril peptides are involved in regulation of biological functions as well as pathologies, physical modification techniques (like FIR-FEL) could also be used to alter the biological functions of these macromolecules as needed."

As FIR-FEL is more effective than MIR-FEL, FIR-FEL can be used to destroy amyloid fibrils deep inside tissues, as in the case of Alzheimer's disease, whereas MIR-FEL can be used for removing dermal amyloids on the surface of the skin. Also, because fibril proteins act as scaffolds for biocompatible materials, FIR-FEL could be used in biomaterial engineering in regenerative medicine or Nano carrier drug-delivery systems.

To conclude, Kawasaki eloquently states, "For the first time in the world, we have found that a rigid aggregate of amyloid fibrils can be effectively broken down using a free-electron laser in the terahertz region (wavelength 50-100 micrometers). Our next step would be to understand how FIR-FEL affects different types of peptide fibrils. Our research can fuel the development of novel treatments for intractable diseases such as Alzheimer's. It could also aid the development of new methods for manipulating the structure of biocompatible materials."

In the depths of the sea, certain shark species transform the ocean's blue light into a bright green color that only other sharks can see--but how they biofluoresce has previously been unclear. In a study publishing August 8 in the journal iScience, researchers have identified what's responsible for the sharks' bright green hue: a previously unknown family of small-molecule metabolites. Not only is this mechanism of biofluorescence different from how most marine creatures glow, but it may also play other useful roles for the sharks, including helping them identify each other in the ocean and fight against microbial infections.

"Studying biofluorescence in the ocean is like a constantly evolving mystery novel, with new clues being provided as we move the research forward," says David Gruber, (@luminescentlabs) a professor at City University of New York and co-corresponding author of the study. "After we first reported that swell sharks were biofluorescent, my collaborators and I decided to dive deeper into this topic. We wanted to learn more about what their biofluorescence might mean to them."

Gruber, working with Jason Crawford, a professor at Yale University and the study's co-corresponding author, focused on two species of sharks--the swell shark and the chain catshark. They noticed that the sharks' skin had two tones--light and dark--and extracted chemicals from the two skin types. What they found was a type of fluorescent molecule that was only present in the light skin.

"The exciting part of this study is the description of an entirely new form of marine biofluorescence from sharks--one that is based on brominated tryptophan-kynurenine small-molecule metabolites," Gruber says.

These types of small-molecule metabolites are known to be fluorescent and activate pathways similar to those that, in other vertebrates, play a role in the central nervous system and immune system. But in the sharks, the novel small-molecule fluorescent variants account for the biophysical and spectral properties of their lighter skin. This mechanism is different from animals in the upper ocean, such as jellyfish and corals, that commonly use green fluorescent proteins as mechanisms to transform blue light into other colors, Gruber says.

"It's a completely different system for them to see each other that other animals cannot necessarily tap into. They have a completely different view of the world that they're in because of these biofluorescent properties that their skin exhibits and that their eyes can detect," Crawford says. "Imagine if I were bright green, but only you could see me as being bright green, but others could not."

The molecules also serve multiple other purposes, including to help the sharks identify each other in the ocean and potentially provide protection against microbial infections, Crawford says.

"It is also interesting that these biofluorescent molecules display antimicrobial properties. These catsharks live on the ocean bottom, yet we don't see any biofouling or growth, so this could help explain yet another amazing feature of shark skin," Gruber says. "This study opens new questions related to potential function of biofluorescence in central nervous system signaling, resilience to microbial infections, and photoprotection."

While the study focused on two biofluorescent shark species, Gruber and Crawford hope to more broadly explore the bioluminescent and biofluorescent properties of marine animals, which can ultimately lead to the development of new imaging techniques.

"If you can harness the abilities that marine animals have to make light, you can generate molecular systems for imaging in the lab or in medicine. Imaging is an incredibly important biomedical objective that these types of systems could help to propel into the future," Crawford says.

"Sharks are wonderful animals that have been around for over 400 million years. Sharks continually fascinate humans, and they hold so many mysteries and superpowers," Gruber says. "This study highlights yet another mystery of sharks, and it is my hope that this inspires us to learn more about their secrets and work to better protect them."

New software from Lancaster University cuts through hard-to-understand financial reports, to help investors and regulators.

Researchers have developed an app to dissect and analyse narrative aspects of companies' annual reports, documents aimed at shareholders, but also used by other stakeholders, including financial analysts, prospective investors, journalists and regulators.

Annual report narratives contain commentary on financial performance, as well as supplementary information on topics such as principal risks and corporate social responsibility policies - but management has a high level of discretion over their content and structure. As a result, investors can struggle to find and understand the information they require.

At present, there is no uniform structure to such documents, making comparison and large-scale analysis severely challenging. The Corporate Financial Information Environment - Final Report Structure Extractor (CFIE-FRSE) app aims to cut through hard-to-understand annual report language and help users identify unusual patterns in corporate reports that may help to distinguish long-term financial strength from inflated short-term profits.

The app aids regulators in seeing where businesses may be trying to conceal information and where they need to intervene. It also allows them to see where regulation is working and where it may need to change.

Professor Steve Young, Head of Accounting in Lancaster University Management School, said: "Annual reports are highly unstructured, and different companies report in different ways, which makes extracting content and comparing reports very difficult. Almost every document is different.

"Many reports are almost impossible for non-specialists - a group which includes many investors - to read, which is at odds with the trend towards a broader model of stakeholder reporting.

"We have designed an app to extract commentary from these documents and normalise it across firms - making comparisons much easier. The procedure provides a reliable means of capturing and classifying these narratives."

The interdisciplinary project has involved academics from Lancaster University Management School, the School of Computing and Communications, and the Department of Linguistics & English Language.

There has already been interest in CFIE-FRSE from investment and hedge-fund managers, who would gain a greater insight into the status and stability of companies, as well as regulators seeking to assess the effectiveness of regulation.

More than 26,000 documents published between 2003 and 2017 by companies listed on the London Stock Exchange have been analysed by the app and scored on features such as length, readability and sentiment. Because the CFIE-FRSE app detects report structure, scores are available for each section listed in the table of contents.

Dr Mahmoud El-Haj, Senior Research Associate in the School of Computing and Communications at Lancaster University, said: "The app uses heuristic approaches and rule-based decision making to automatically detect the structure of an annual report. This helps the software to extract sections' text by knowing their start and end pages.

"The app was trained to identify a set of common section titles (types) based on a training list of synonyms generated by accounting and finance experts. For example, the app is able to identify that the 'Letter to shareholders' in one company's report is the same as the 'Chairman's statement' in another company's report."

Analysis of the annual reports processed by the app reveals a number of interesting features and reporting trends. For example, average report length has more than doubled over the last decade to almost 34,000 words.

Average report readability - measured using an algorithm that penalises long sentences and complex words - is also poor; and there has been no noticeable improvement over the sample period. Long, unstructured documents containing complex language mean many retail investors and other non-specialist stakeholders struggle to understand the typical annual report.

Sentiment also varies dramatically across different sections within the same report. For example, sections where regulation and compliance shape content - such as governance statements and remuneration reports - are characterised by neutral language. In contrast, the tone of language is up to four times more positive in sections where directors have more reporting discretion and where performance is the primary focus.

Long considered an extreme reaction to fears of Armageddon and imminent nuclear disaster, 'preppers' in the US have traditionally been portrayed as motivated by extreme right-wing or apocalyptic views. New research from Dr Michael Mills, from the University of Kent, challenges this view.

Prepping, which involves stockpiling supplies including food, water, medicine and weapons, has been on the rise in the United States over the last decade. Many commentators and the mainstream media claim the rapid rise in the phenomenon after the election of President Barack Obama in 2008 was driven by an extreme political reaction to his presidency.

Research carried out by Dr Mills, Lecturer in Criminology in the School of Social Policy, Sociology and Social Research, included interviews with preppers based in 18 states to examine their motivations for hoarding items. It found that, though fear of President Obama and his political agenda played a role, those who engaged in the activity were motivated more by the general culture of fear that informs modern mainstream American society. Further, the research argues that a regular flow of recommendations from the US government on how to prepare for potential disasters, including, for example, advice to stockpile water, have, to an extent, helped fuel the growth of 'prepping'.

Dr Mills' research presents a more nuanced view of prepping, which has traditionally been portrayed as an apocalyptic belief in imminent disaster or the end of the world. Rather, modern preppers are responding to a general sense of fear and concern about risks including economic collapse, cyber-attacks, terrorism, pandemics and environmental disasters, causing them to seek self-sufficiency 'just in case' the worst should happen. Much of this fear is not derived from extreme ideologies, but nevertheless remains connected to established right-wing politics in America, which views Obama and other Democratic Party leaders exclusively through fear.

He said: 'Fear is now deeply entrenched in modern American culture and is the principal reason that so many citizens are engaging in 'prepping'. Many believe that the government's response in the event of a calamity, whether it's a natural disaster or an act of terrorism, simply won't be adequate to meet their needs. Many also believe that, under Democrat leadership, America becomes more vulnerable to terrorist attacks, financial collapse, and international hostility.

'While the media portrays 'preppers' as extremists, our view is much more nuanced. Rather than seeing prepping as an exception within America's right-wing political culture, we ought to see it as being reflective of increasingly established and popular outlooks.'

Suffering from tremor can be very frustrating and reduce the quality of life for many people. This includes people suffering from Parkinson's, multiple sclerosis or spinal cord injury and a relatively high fraction of the elderly. Today, there are no effective treatments for tremor, and thus, there is great potential in finding medications that can inhibit or completely suppress the tremor.

It is possible to test new medications for tremor in mouse models. Unfortunately, the equipment that measures the tremor in such tests is expensive and for that reason many scientists do not measure it. A single measuring device costs DKK 100,000-130,000. But now, brain researcher Eva Maria Meier Carlsen has invented an affordable solution to this problem.

'I thought it would be a pity if expensive equipment kept us from continuing our research to find treatments for tremor. That's why I set out to find an affordable and valid way to measure it, and I came up with the idea of ??using a smartphone as a measuring device', explains Eva Maria Meier Carlsen, who is a postdoc at the Department of Neuroscience.

Researchers Should Challenge the Conventions

In all its simplicity, the new method works by suspending a cage by means of rubber bands. A smartphone is mounted on the cage and - by means of its accelerometer - it measures the vibrations of the cage if the mouse trembles. The accelerometer is what can detect the movement of the smartphone, e.g. when taking pictures or playing games. With this method, researchers can relatively easily test whether medications will work to alleviate the tremor.

The brain researchers have repeated their tests with advanced and expensive equipment for measurement of tremor in collaboration with the company Saniona which, among other things, develops medications for the central nervous system. The smartphone method produced comparable results and may therefore be used by the research team itself and other researchers to prospectively look for treatments.

'It is a really good idea that Eva got, and our new study emphasises its validity. It is a good example of how we researchers sometimes have to challenge the conventions and invent new methods that are more accessible and can be used by more people', says the head of the research project Jean-François Perrier, Associate Professor at the Department of Neuroscience.

Already in Use

In connection with the new solution, the smartphone itself is the only significant cost. On the other hand, the expensive measurement technology costs more than DKK 100,000 for a single device. To make the solution even cheaper, there are also open source alternatives to the smartphone manufacturers, Eva Maria Meier Carlsen points out, such as the so-called single board computers which simply need to have an accelerometer mounted and installed.

The brain researchers are already using the new method to test medications for tremor in mice. They will also use the new affordable solution to test already approved medications that will have a much shorter path to the patients than brand new medications.

Your body is a wonderland. A wonderland teeming with trillions of bacteria, that is. But it's not as horrifying as it might sound. In fact, there's mounting evidence that many aspects of our health are closely intertwined with the composition and hardiness of our microscopic compatriots, though exactly how is still mostly unclear.

Now, researchers at the Stanford University School of Medicine have discovered that these microbial hitchhikers -- collectively known as the human microbiome -- are churning out tens of thousands of proteins so small that they've gone unnoticed in previous studies. The proteins belong to more than 4,000 new biological families predicted to be involved in, among other processes, the warfare waged among different bacterial strains as they vie for primacy in coveted biological niches, the cell-to-cell communication between microbes and their unwitting hosts, and the critical day-to-day housekeeping duties that keep the bacteria happy and healthy.

Because they are so small -- fewer than 50 amino acids in length -- it's likely the proteins fold into unique shapes that represent previously unidentified biological building blocks. If the shapes and functions of these proteins can be recreated in the lab, they could help researchers advance scientific understanding of how the microbiome affects human health and pave the way for new drug discovery.

A paper describing the research findings will be published Aug. 8 in Cell. Ami Bhatt, MD, PhD, assistant professor of medicine and of genetics, is the senior author. Postdoctoral scholar Hila Sberro, PhD, is the lead author.

'A clear blind spot'

"It's critically important to understand the interface between human cells and the microbiome," Bhatt said. "How do they communicate? How do strains of bacteria protect themselves from other strains? These functions are likely to be found in very small proteins, which may be more likely than larger proteins to be secreted outside the cell."

But the proteins' miniscule size had made it difficult to identify and study them using traditional methods.

"We've been more likely to make an error than to guess correctly when trying to predict which bacterial DNA sequences contain these very small genes," Bhatt said. "So until now, we've systematically ignored their existence. It's been a clear blind spot."

It might be intimidating for the uninitiated to think too deeply about the vast numbers of bacteria that live on and in each of us. They account for far more cells in and on the human body than actual human cells do. Yet these tiny passengers are rarely malicious. Instead, they help with our digestion, supplement our diet and generally keep us running at our peak. But in many cases, it's been difficult to pick apart the molecular minutiae behind this partnership.

Bhatt and her colleagues wondered if answers might be found in the small proteins they knew were likely to wiggle through the nets cast by other studies focusing on the microbiome. Small proteins, they reasoned, are more likely than their larger cousins to slip through the cell membrane to ferry messages -- or threats -- to neighboring host or bacterial cells. But how to identify and study these tiny Houdinis?

"The bacterial genome is like a book with long strings of letters, only some of which encode the information necessary to make proteins," Bhatt said. "Traditionally, we identify the presence of protein-coding genes within this book by searching for combinations of letters that indicate the 'start' and 'stop' signals that sandwich genes. This works well for larger proteins. But the smaller the protein, the more likely that this technique yields large numbers of false positives that muddy the results."

A big surprise

To tackle the problem, Sberro decided to compare potential small-protein-coding genes among many different microbes and samples. Those that were identified repeatedly in several species and samples were more likely to be true positives, she thought. When she applied the analysis to large data sets, Sberro found not the hundreds of genes she and Bhatt had expected, but tens of thousands. The proteins predicted to be encoded by the genes could be sorted into more than 4,000 related groups, or families, likely to be involved in key biological processes such as intercellular communication and warfare, as well as maintenance tasks necessary to keep the bacteria healthy.

"Honestly, we didn't know what to expect," Bhatt said. "We didn't have any intuition about this. The fact that she found thousands of new protein families definitely surprised us all."

The researchers confirmed the genes encoded true proteins by showing they are transcribed into RNA and shuttled to the ribosome for translation -- key steps in the protein-making pathway in all organisms. They are now working with collaborators to learn more about the proteins' functions and to identify those that might be important to the bacteria fighting for space in our teeming intestinal carpet. Such proteins might serve as new antibiotics or drugs for human use, they believe.

"Small proteins can be synthesized rapidly and could be used by the bacteria as biological switches to toggle between functional states or to trigger specific reactions in other cells," Bhatt said. "They are also easier to study and manipulate than larger proteins, which could facilitate drug development. We anticipate this to be a valuable new area of biology for study."

BOSTON - Huntington's disease (HD), an inherited and fatal disorder in which nerve cells in the brain break down over time, may become evident at any time in life but typically starts in a person's 30s or 40s. New research results published in the journal Cell, call into question an accepted theory about the timing of HD onset.

HD and a number of other neurodegenerative diseases are caused by inheritance of an expanded DNA segment of repeated CAG nucleotides that code for the amino acid glutamine. The age of onset of these diseases is negatively correlated with the length of the expanded CAG repeat and has been thought to result from increasing toxicity of the multiple glutamines--or polyglutamine--encoded by this CAG repeat in the DNA.

When James Gusella, PhD, Jong-Min Lee, PhD, and Marcy MacDonald, PhD, of the Molecular Neurogenetics Unit in the Center for Genomic Medicine at Massachusetts General Hospital (MGH), and their colleagues in the Genetic Modifiers of Huntington's Disease Consortium analyzed information on more than 9,000 individuals with HD, they found that the timing of HD onset was due to a property of the expanded CAG repeat in an individual's DNA, not due to the length of polyglutamine.

In addition, investigators found that multiple genes involved in DNA maintenance and repair can modify the timing of HD onset, making it either earlier or later than expected based upon the length of the inherited CAG repeat.

"Our data support the hypothesis that the critical property of the CAG repeat is its propensity to expand further as an individual ages, leading to longer and longer repeats in particular brain cells until a critical threshold length is reached and toxicity results," says Gusella, who is also a professor of neurogenetics at Harvard Medical School. "Our findings change the way researchers look at HD and other DNA repeat diseases by focusing attention early in the disease process on the DNA repeat itself rather than on the protein that it codes for. Rather than sharing a pathogenic process based upon polyglutamine toxicity, the 'polyglutamine diseases' instead share a DNA property that can be modified by processes that the cell uses to maintain the DNA."

The results indicate that either the CAG repeat itself or the DNA maintenance processes that modify its expansion in neurons may be potential targets for treatments that could delay or prevent the onset of HD and other repeat disorders. "A number of approaches are already being pursued to alter the length or purity of the HD CAG repeat and to develop drugs that inhibit or activate particular DNA maintenance proteins," says Gusella.

LA JOLLA, CA--As this year's Lassa fever outbreak in Nigeria is finally ebbing, the total tally came to more than 600 infected people, one-quarter of them dead. Thousands more die each year, uncounted in rural villages throughout West Africa. With an annual wave of infections and new viral strains emerging, it has never been more important to understand the characteristics of a broadly protective immune response in order to develop effective treatments, or better yet, a vaccine.

A new study, published in the August 8, 2019, issue of Cell by a team of researchers led by Instructor Kathryn Hastie, Ph.D., and Professor Erica Ollmann Saphire, Ph.D., at La Jolla Institute for Immunology (LJI), identified and then reverse engineered the molecular properties shared by antibodies that are particularly efficient at inactivating or "neutralizing" the virus. The team's findings also revealed that most neutralizing antibodies bind to the same spot on the surface of Lassa virus, providing a map for rational vaccine design.

"The beauty of structural biology is that it gives you the ability to dissect the molecular details at high resolution to explain precisely how something works," says structural immunologist Ollmann Saphire. "Once you do, you have a blueprint to engineer potent immunotherapeutics or a vaccine that elicits the desired immune response."

Identified 50 years ago and named for the town in Nigeria where the first known cases cropped up, Lassa virus is endemic in West Africa where it infects hundreds of thousands of people every year. For the majority of infected people, symptoms are mild and the infection mostly goes undiagnosed. But in 20 percent of patients, the disease causes a more serious illness including neurological symptoms and hemorrhage, which can result in multi-organ failure and death.

A deceptively simple virus, Lassa only carries four genes and displays a single protein, the so-called glycoprotein, on its surface. The surface glycoprotein is crucial for attachment and entry of Lassa virus into cells. "Because it is the only thing that the immune system sees, it is the main target for antibodies that prevent viral infection," says Hastie, who solved the structure of the Lassa glycoprotein in a groundbreaking effort only two years ago. Since then, the glycoprotein version engineered by the pair has become the international standard for testing candidate vaccines.

For the current study, Hastie compared the structure of three different neutralizing antibodies of varying potency--high, moderate and low--bound to the glycoprotein. The side-by-side comparison highlighted specific amino acid residues that drive high potency and enabled the researchers to precision-engineer mediocre antibodies to turn them into highly effective ones.

"Not only were we able to increase the antibody's potency, which means you can deliver much less antibody, we were also able to make it pan-Lassa. It can hit every Lassa virus lineage characterized so far," says Hastie.

But few naturally infected people generate neutralizing antibodies and current vaccine efforts focus on eliciting T cell immunity. "Historically, researchers have found that development of antibodies is not a good correlate of protection in natural Lassa infections," says Hastie. "It is actually very difficult to induce neutralizing antibodies."

The second part of the study explains why.

Before B cells can launch a full-blown antibody response against invading pathogens, their progenitors have undergo a tightly orchestrated, multi-step maturation process. Often compared to a miniaturized Darwinian struggle for survival, this process selectively promotes the proliferation of cells that produce high-affinity antibodies and weeds out those that produce less potent ones. The survivors undergo successive rounds of so called somatic hypermutation and selection, resulting in better and better antibodies during the course of an immune response.

Hastie and her colleagues found that in the absence of somatic hypermutation, early antibodies recognizing Lassa surface glycoprotein don't have high enough affinity to shove a couple of sugar chains out of the way that block access to the antibodies' binding site. When they removed the sugar chains, low affinity antibodies could bind and only needed a few hypermutations to get further to neutralization.

"Using these structures, we were able to identify which parts of the glycoprotein are actually hindering early antibody development," says Hastie. "It allowed us to give the immune system a leg up by crafting a glycoprotein that might be better at inducing those early antibodies to start the hypermutation process. When they encounter the native virus they have built up enough mutations to bind tightly enough to displace the glycans."

This kind of information is crucially important for international vaccine efforts currently underway by the Coalition for Epidemic Preparedness Innovations (CEPI), which has made Lassa fever a priority disease, and many others.

ANN ARBOR--In every tissue throughout our bodies, various cell types are communicating and coordinating their efforts to perform vital functions and maintain health.

In a new study led by the University of Michigan, researchers have now created a high-resolution picture of the cells at work inside a key hub of metabolism--the liver--and how individual cell types are reprogrammed in disease.

The findings, scheduled to publish Aug. 8 in the journal Molecular Cell, not only reveal a detailed map of cell-to-cell signaling in the liver, but also identify cellular changes that could potentially drive the progression of nonalcoholic steatohepatitis, or NASH, a severe form of fatty liver disease with no effective therapies.

Until recently, scientists could analyze what was occurring only across a mixture of cells in a specific organ or tissue. But they lacked the technology to decipher the distinct cells within that complex mixture and see how each type was involved in overall tissue health and function.

"That was one question we really wanted to address with this study: Can we have a high-definition picture of each cell type in the liver, what signaling molecules are being released by each of these different cell types and what they are capable of responding to?" said Jiandie Lin, senior study author and a professor at the U-M Life Sciences Institute. "Now, with the new single-cell RNA sequencing technology, we can do that."

Single-cell sequencing allows researchers to isolate cells from a tissue sample and then determine the precise order of nucleic acids--the molecules that make up DNA and RNA--within each cell. Researchers can use this information to discover new cell types and activities within the tissue.

Lin and his colleagues applied this new research tool to obtain a gene expression profile for individual liver cells. By comparing data from mouse and human livers, the researchers laid out a blueprint of the types of cells operating in the liver, which signals the cells produce and which cells receive those signals. The information provides unprecedented details that help create a high-definition map of cell signaling in the liver.

They also compared healthy livers with diseased livers to determine how cellular properties change in NASH livers. Patients with this severe form of fatty liver disease are more likely to experience cirrhosis and liver cancer. NASH is commonly associated with metabolic syndrome; however, the exact triggers that drive disease progression remain poorly understood.

"We wanted to decode what exactly is going on for each cell type during disease," said Lin, who is also a professor of cell and developmental biology at the U-M Medical School. "Can we uncover new biology, new disease mechanisms, maybe even new therapeutic targets using single-cell analysis?"

Using a mouse model of NASH, the researchers found that the abundance of cells within the liver changed with disease, but so did the properties of each cell type. In particular, cells called macrophages were present at substantially higher proportions in diseased livers and were more actively producing a protein called Trem2 (for "triggering receptors expressed on myeloid cells 2").

The emergence of Trem2-marked macrophages was also observed in the livers from a cohort of human NASH patients. What's more, the presence of Trem2 was also associated with disease severity--as the liver became more diseased, the cells produced more Trem2; as NASH improved, Trem2 levels decreased.

And the analysis of single cells also revealed new information about star-shaped cells, called hepatic stellate cells, that are known to contribute to liver fibrosis. In this new study, the researchers discovered that stellate cells are actively secreting various signaling molecules, dubbed "stellakines," and respond to hormones that typically act on blood vessels in the body.

"The findings on hepatic stellate cells really surprised us," said lead study author Xuelian Xiong. "And they highlight the power of single-cell biology in discovering new modes of cell communication and function."

Long-lived mushrooms that grow in 'fairy rings' accumulate surprisingly few mutations over time. This finding indicates that their protection against harmful mutations is well developed. The results, to be published in the esteemed journal Current Biology, are interesting in terms of both medicine and evolutionary biology.

In all living creatures, every cell contains DNA, which encodes the functions that the cell can perform. Changes in DNA, 'mutations', may cause loss of cell function, boosting the risk of disease. It is therefore important for the DNA to be kept intact over time. Whenever a cell divides, there is an increased risk of new mutations. Thus, organisms that are long-lived, and in which every cell can contribute DNA to the next generation, are particularly vulnerable to harmful mutations. In this study, researchers examined the speed and pattern of mutations in a species of long-lived fungus (Marasmius oreades, the Scotch bonnet or 'fairy ring mushroom') that forms 'fairy rings'.

Fairy rings can be found on lawns or in woodlands and forests. A darker circle in the vegetation under the mushrooms, or a circle of dead grass during dry periods, is sometimes distinguishable. Historically, fairy rings have been associated with various supernatural notions, such as traces of witches' cauldrons, dancing elves or other magical creatures. Nowadays, we know that a fairy ring is formed by the circular underground mycelium, the main body of a fungus (composed of a tangled web of threads called hyphae), which grows radially outwards from a starting point while, over time, dying away in the middle. Just as in most other species of fungi, every cell of the mycelium can form a fruiting body and give rise to a new generation of fungi.

In the current study, the researchers used fairy rings of Marasmius oreades, combined with whole genome DNA sequencing, to study mutations. The number of mutations proved to be strikingly small given the number of cell divisions that had taken place.

"In studying mutations, you often use cell lines at the lab, which isn't practical over long periods. In fairy rings, we can at one time-point study the emergence and accumulation of mutations over many years, and also in the organism's natural environment. Interestingly, we found far fewer mutations than we expected," says Markus Hiltunen, doctoral student and lead author of the study.

The results indicate that such long-lived fungi have a capacity to protect themselves against an accumulation of harmful mutations. In-depth study of the cell processes in these fungi can therefore provide important new knowledge about the challenges that need resolving to make their longevity attainable.

"The mechanism facilitating this protection is currently unknown, but leading candidates are extremely effective DNA repair systems or asymmetric DNA division during cell division, where mutated DNA may be left behind as the fungus grows outward. But this needs to be clarified in new studies," says Hanna Johannesson, who heads the research group at Uppsala University.

The study boosts knowledge about the challenges and solutions that are necessary for individuals to grow old and reproduce at an advanced age. This is relevant in areas including evolutionary biology and cancer research.

(WASHINGTON, August 8, 2019) -- New data suggest that people who have a parent, sibling, or child with blood cancer have a higher likelihood of being diagnosed with the disease. The study published online today in Blood offers the first evidence that such familial risks exist across the spectrum of hematologic malignancies.

Age of diagnosis, whether the relative is a parent, sibling, or child, and the number of affected first-degree relatives play a defining role in the relative risk of developing certain blood cancers, according to the study.

"This information improves our understanding of the causes of - and potential inherited predisposition to - blood cancers and should inform the identification and characterization of genetic risk factors for blood cancer, as well as how we best clinically manage patients and their relatives," said Amit Sud, MD, PhD, of The Institute of Cancer Research, London, and the study's lead author. "The results should also encourage conversations among families, clinicians, and patients about familial risk."

While earlier studies have demonstrated the increased risk of blood cancers in first-degree relatives of affected individuals, this is the largest and most comprehensive population-based evaluation to date.

Cases with a familial link represented 4.1 percent of all blood cancer diagnoses - higher than cancers of the nervous system, kidney and pancreas, but lower than those of the breast, colorectum, and prostate, which range from 8 to 15 percent, researchers report. Highest relative risks were seen for certain Hodgkin lymphoma (HL) subtypes, lymphoplasmacytic lymphoma, and mantle cell lymphoma. Markedly elevated familial risks were also observed for polycythemia vera, myelodysplasia and essential thrombocythemia.

While there are currently no definitive screening initiatives for blood cancers, a 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia recognized familial disease as an essential component of diagnosing certain subsets of blood cancers and underscores the need to further examine and understand familial risk. Developing definitive screening protocols based on evidence is an emerging area of research.

"We hope these robust data will be used to inform guidelines on genetic testing and screening. Certainly there are a number of individuals, such as those with a relative diagnosed at a young age and or with more than one affected first-degree relatives, for whom counseling, genetic testing, and surveillance may be appropriate," Dr. Sud said.

The present analysis drew from 16 million people in the Swedish Family-Cancer Database, ultimately including 153,115 patients with a confirmed blood cancer and 391,131 first-degree relatives, which allowed Dr. Sud and colleagues to fully characterize familial risk across all blood cancer types. For specific blood cancers such as chronic lymphocytic leukemia (CLL), the increase in risk is dependent on the age of the affected relative; whether it is a parent, sibling, or child; and the number of affected first-degree relatives. For example, for non-Hodgkin lymphoma, HL, and CLL, the risk was higher among those who had a sibling with the disease, whereas others blood cancers were more likely to occur if a parent had been diagnosed. Generally, the familial risk was more pronounced when relatives were diagnosed at younger ages. Dr. Sud added that the analysis also has potential implications for the selection of related stem-cell donors used for the treatment of these malignancies.

In addition to its size and long follow-up, another strength of the analysis is its use of registry data for which almost all blood cancer cases in the Swedish population had been recorded. Still, researchers say the findings may not be applicable to economically developing countries that tend to have different tumor incidence rates and potentially different environmental and genetic risk factors.