Culture

Microbiomes can contain thousands of bacteria species, hinting at the complex ecosystem that houses the microbiome as well as the one contained within the microbiome. Yet, until now, researchers have been limited in the tools they have to precisely compare those microbiomes.

Now, a team based in China has published a comprehensive comparison method for microbiomes in the December 3 issue of Bioinformatics, a journal of the Oxford University Press.

The researchers focused on improving the current method of examining the so-called "shotgun metagenomes." When an environmental sample is processed, all of the genetic material present is cut apart into identifiable DNA samples. The DNA samples are processed to produce metagenomes of the species in the environmental sample - a combination of metadata and genomes.

A metagenome can contain genetic data from several types of organisms, indicating the evolutionary combinations that lead to that specific species. High populations of specific organisms have a higher representation of the DNA sample, but even minor species can be accounted for through this method.

"An accurate and reliable distance (or dissimilarity) among shotgun metagenomes is fundamental to understanding microbiomes; however, current methods may produce erroneous results, due to their incomprehensive consideration of microbial compositions in comparing metagenomes," said paper author SU Xiaoquan from the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS).

This incomprehensive consideration of microbial compositions includes discarding unclassified species or excluding evolutionary history or relationships among species.

To solve these problems, the researchers proposed the Dynamic Meta-Storms (DMS) algorithm. This method compares metagenomes - at the species level - for both their physical and genetic details, as well as their evolutionary relationships with other species.

"In addition, our new algorithm is also optimized for parallel computing: 20% faster than the currently most-used method and it also saves 40% memory," SU said. In 6.4 hours, the algorithm compared 100,000 metagenomes from 3,688 bacteria on a single computer node.

"The improved metagenomics comparison resolution and the high speed of the Dynamic Meta-Storms algorithm can be exploited to mine the massive quantity of metagenomes for classifying samples among various states, such as diagnosing the health status of a microbiome by comparing it to a reference database of diseased microbiomes," SU said.

The researchers made their tool available online for other scientists to use. They plan to continue improving the algorithm and working to identify metagenomes of microbiomes to better understand the evolutionary history of species.

There he is, standing upon his pedestal: David by Michelangelo. A world-?famous statue that nearly every child can recognise. But this David is just 1 millimeter tall, pedestal included, and is made not of marble like the 5.17-?meter original, but of pure copper.

It was created using 3D printing by Giorgio Ercolano from Exaddon, an offshoot of ETH spin-off Cytosurge, together with the team led by ETH Professor Tomaso Zambelli from the Laboratory of Biosensors and Bioelectronics. Zambelli and his team developed the 3D technique a few years ago. Scientists can use it to create metal structures at the nanometer and micrometer scale.

The core component of the process is a micropipette coupled to a cantilever; this makes it possible to monitor the force with which the point of the pipette touches the substrate. With this assembly, the researchers can electrochemically deposit dissolved metals onto an electrically conductive substrate with a high degree of precision. Thanks to the optical force measurement that automates the process, they can build minuscule metal structures layer by layer. Exaddon adopted this micrometal printing method and improved on it, particularly as regards its speed.

Making complicated geometries printable

Ercolano has now printed this micro-?David to highlight the technology's potential. Prior to that, the researchers had mostly created tiny columns or coils. "However, the process allows us to print structures or geometries of all levels of complexity," Ercolano says. The sculpture was printed in one go, without supports or templates, and didn't require any firing or tempering. Ercolano and his colleagues have just published their results in the journal Micromachines.

The data for the David sculpture is freely available on the internet. "I could even have printed the room that the statue is standing in - the data includes that as well!" says Ercolano with a laugh. But he chose to adjust the data set so he could reproduce David without the exhibition room.

Lower size limit set by resolution

Ercolano printed David in two sizes: first as a sculpture just 1 millimeter high, and then one ten times smaller. "The smaller figure is only as tall as the pedestal of the larger one," he says. But with structures that small, achieving the required resolution becomes problematic. Printed metallic micro-?objects typically starts at 1 micrometer (μm), and for more complex and detailed objects, sizes range from 100 μm to 1 mm. In terms of time, too, the 1 mm model is a world away from the one that is ten times smaller: the device needed 30 hours to create the "big" David but just 20 minutes for the smaller version.

Theoretically, the system can print objects up to 5 mm in size, but the printer cartridge contains only a microliter of "ink" - just about enough for manufacturing the larger David. But it is also enough "ink" to print hundreds or even thousands of tiny objects, which represents the real strength of the process. The principle works

Zambelli is very pleased with the result. "We're thrilled that a technology from our research lab has made its way into practical application," the ETH professor says, continuing: "An independent group was able to adopt our 3D printing technology and even improve upon it - which shows that it really works."

The printing process is of interest first and foremost to the electronics industry. With this method, manufacturers could connect computer chips together or precisely repair microelectronics systems. Although other metals can be printed, such as platinum, gold, nickel or silver, copper is in highest demand. "Nine out of ten enquiries are about copper," Ercolano says.

Painful inflammatory lesions of the skin and mucous membranes may occur in children who develop bacterial pneumonia. A research group at the University Children's Hospital Zurich has recently developed a new diagnostic blood test, which reliably diagnoses bacteria as the causative pathogen at an early stage, allowing more specific treatment and prediction about prognosis.

Rapidly dying mucous membrane cells in the mouth, eye and genital regions, and vesicles and blisters on the skin can be symptoms and signs of drug allergies or infections. The latter can be triggered by the bacterium Mycoplasma pneumoniae, which is a well-known cause of pneumonia in children. M. pneumoniae can also be found outside the lungs and trigger severe, painful skin and mucous membrane lesions.

Early and clear diagnosis of bacterial infections

The connection between a M. pneumoniae infection and inflammation of the skin and mucous membranes is difficult to prove, however: Routine diagnostic tests can detect M. pneumoniae, but do not answer the question of whether it is the cause of the infection or whether the bacteria has colonized only the nasopharyngeal cavity without any consequences.

A research group at the University Children's Hospital Zurich has therefore developed an ELISpot (Enzyme-Linked Immunospot) blood test, which can detect specific immune cells (B cells) within 24 hours. These immune cells are directed specifically against M. pneumoniae and only become active during an infection. "Early recognizing inflammatory lesions of the skin and mucous membranes as infection-triggered rather than drug-triggered enables more specific treatment, and most importantly, avoids restriction of possibly causative drugs," says Patrick Meyer Sauteur, Consultant in Pediatric Infectious Diseases and Hospital Epidemiology at the University Children's Hospital Zurich.

Severe skin and mucous membrane lesions as complication of pneumonia

The new ELISpot blood test has already been used in a childhood pneumonia study at the Children's Hospital Zurich, in which skin and mucous membrane lesions were the first time prospectively investigated. In one third of 152 children with pneumonia, M. pneumoniae was identified as cause of the infection. Skin and mucous membrane lesions were observed in 23 percent of these pneumonia cases caused by M. pneumoniae - three of the children had severe lesions, predominantly of the mucous membranes. In contrast, only three percent of children who had infections caused by other pathogens experienced skin and mucous membrane lesions.

The reason why infections with M. pneumoniae, in addition to respiratory disease, often lead to skin and mucous membrane lesions is not yet fully understood. The study showed that the immune system was much more activated in children who were infected with M. pneumoniae and had skin and mucosal lesions than in children with only respiratory tract disease due to M. pneumoniae. "This leads to an interesting conclusion: It may be not M. pneumoniae itself that causes the skin and mucous membrane lesions, but the immune system, which reacts to the bacteria," says Meyer Sauteur.

Immune response attacks not only the bacteria but also skin and mucous membranes

The group at the Children's Hospital is currently investigating which bacterial components trigger this distinct immune reaction and which structures of the skin and mucous membranes are targeted. Previous studies have shown that the surface of M. pneumoniae can be very similar to structures of various tissues in the body. It is therefore possible that the immune system attacks the human body as it cannot discriminate between bacterial and human tissue structures.

The new ELISpot blood test makes it possible to investigate the specific immune response in blood in detail and to make an exact diagnosis in patients with M. pneumoniae infections. "Our research has a direct impact on treatment management: In patients with M. pneumoniae infections, symptoms may be improved not only through treatment with antibiotics, but also with drugs that modulate the possibly disease-causing immune response," says the infectious disease specialist.

Researchers at the University of Helsinki, the University of Zurich and the University of Exeter have carried out modelling on how environmental factors affect the occurrence of human-pathogenic bacteria found in the sheep tick (Ixodes ricinus), a tick species common in Europe.

The researchers collected sheep ticks in the Swiss Alps from valleys up to the limit of their area of distribution, identifying all possible pathogenic bacteria living inside the ticks. A number of Borrelia species, which cause Lyme borreliosis, and Rickettsia species, which cause spotted fever, were found in the ticks.

According to the researchers, the modelling did not show any single environmental factor to clearly promote or impair the pathogens. Individual pathogens borne by ticks had different reactions to their environmental conditions, which makes it difficult to assess the impact of climate change.

"For example, temperature has a negligible effect on the kinds of pathogenic bacteria ticks have. More significant are factors related to the humidity of the surroundings, such as the aspect and slope of the sites. Borrelia afzelii is more common in slopes facing north, which are more humid than the hotter southern ones, while the Rickettsia species were more prevalent in steeper slopes that are also drier due to stronger water run-off," explains Tuomas Aivelo, a postdoctoral researcher at the Faculty of Biological and Environmental Sciences, University of Helsinki.

Collecting samples from different elevational gradients is a practical way of studying the effects of environmental conditions.

"Despite the short distances, ticks from varying habitats are easily comparable. A change of a single kilometre in the vertical is the equivalent of a roughly 1,000-kilometre transition between south and north. In the lowest reaches of the study area, the average temperature corresponds with a hotter than average Finnish summer day, whereas the summer temperatures in the upper reaches of the area over a kilometre higher resemble an average summer in central Finland."

The researchers found that the ticks were likely to be infected with many pathogens simultaneously. In other words, they may promote co-infection.

"On the other hand, ticks infected with Spiroplasma bacteria had much fewer human pathogens, such as Borrelia bacteria. A Spiroplasma infection is known to protect mosquitos against many parasites and pathogens, making a similar phenomenon possible also in ticks," Aivelo points out.

CHAPEL HILL, N.C. (December 19, 2019) - A new study that sought to find out whether serotonin reuptake inhibitors or trauma-focused psychotherapy is more effective in treating posttraumatic stress disorder (PTSD) concluded there is insufficient evidence at present to make that determination.

"Because of these findings, we recommend that, until we have evidence from head-to-head trials favoring one treatment or the other, clinicians should make shared decisions, with patients, about which treatment modality to use," said Jeffrey Sonis, MD, MPH, lead author of the study and an associate professor in the departments of social medicine and family medicine in the University of North Carolina School of Medicine. "These decisions should be based on patient preferences with regard to several treatment characteristics, such as the frequency of visits and time between treatment initiation and the onset of beneficial effects."

The systematic review and meta-analysis was led by Sonis and is published in the December 2019 issue of the journal Psychiatry Research. Joan M. Cook, PhD, of Yale University is co-author of the study.

Most guidelines for the treatment of PTSD in adults recommend that trauma-focused psychotherapy be used as a first-line treatment and medications be used as a second-line treatment, Sonis said. In other words, they recommend that psychotherapy should be offered, preferentially, to adults with PTSD, over medication. Those guidelines base those recommendations upon the fact that the effect sizes (the magnitude of the treatment effects) from randomized trials that compare psychotherapy to controls (such as wait-list controls) are substantially larger than the effect size from trials comparing medications to placebo.

However, comparing effect sizes based on indirect comparison is a flawed approach, Sonis said, because methodological differences between psychotherapy trials and medication trials are known to be associated with the effect size. For instance, blinding or masking, which is routine in medication trials but impossible in psychotherapy trials is known to be associated with smaller effect sizes. Other methodological differences are also associated with effect size and may explain the difference in effect sizes for psychotherapy and medication trials.

"We believe that only head-to-head randomized trials comparing psychotherapy directly to medications should be used to determine the relative effectiveness of psychotherapy and medications for treatment of PTSD," Sonis said. "There have been other meta-analyses of head-to-head randomize trials for treatment of PTSD previously but several head-to-head trials had been published since the last meta-analysis. Therefore, we conducted a meta-analysis exclusively consisting of head-to-head randomized trials."

"We found that the best estimate of the effect, comparing psychotherapy and medications, was that there was no difference between the two. However, the 95% confidence interval was very wide, indicating that true effect may favor psychotherapy or it may favor medications. We concluded that there is still insufficient evidence to determine whether psychotherapy or medications were more effective for treatment of PTSD in adults," Sonis said.

Until there is clear evidence from head-to-head trials favoring one treatment or the other, Sonis said, clinicians should make shared decisions, with patients, about which treatment modality to use, based not on comparative effectiveness (which is inconclusive) but on patient preferences regarding the following factors:

presumed mechanism of action

what is required of the patient

whether the patient will need to talk about the trauma
frequency of visits

time between treatment initiation and onset of beneficial effects

duration of benefit after treatment cessation

risk and adverse effects

"The bottom line is that while many researchers and clinicians believe that psychotherapy is more effective for treatment of PTSD than medications, our research shows that there is -- as of right now -- insufficient evidence from head-to-head trials to make that determination at this time," Sonis said. "Therefore, the choice of medication or psychotherapy as the initial treatment should be based on patient preferences for treatment characteristics and not on incorrect assumptions about which treatment is more effective."

New Rochelle, NY, December 18, 2019--Real transformation in healthcare through the adoption of artificial intelligence (AI), robotics, telecommunications, and other advanced technologies could provide significant improvements in healthcare quality, productivity, and access. The current status and future challenges and opportunities for integrating technology into consumer healthcare are discussed in a series of research and opinion articles published in a preview issue of Healthcare Transformation: Artificial Intelligence, Automation, and Robotics, a new peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The launch of the Journal coincides with the first day of the 2019 Partnership for Artificial Intelligence, Telemedicine & Robotics in Healthcare (PATH) Summit in Washington, DC.

Technology such as AI, mobile apps, and wearables have impacted people in areas such as ride sharing, shopping, and entertainment. How can technologies such as these and telehealth, "which have transformed other areas of individuals, families, and communities' lives, give people the tools to take charge of their health, and to manage their sicknesses?" asks Sharon Terry, Genetic Alliance (Washington, DC) in her Guest Opinion entitled "People at the Center." She emphasizes the need to keep people and their needs at the center as healthcare transformation through technology continues to evolve.

Ateev Mehrotra, MD, MPH, Harvard Medical School (Boston, MA) and colleagues from Harvard, McLean Hospital (Boston), RAND Corp. (Arlington, VA), and Beth Israel Deaconess Medical Center (Boston) coauthored the article entitled "Characteristics of Organizations that Provide Telemental Health." Using a random sample of Medicare beneficiaries, they identified the organizations that billed the largest number of telemental health visits. They found that five telemedicine companies provided nearly half (48.3%) of the telemental health visits. Most of the remaining visits were provided by private health clinics (24.3%) and community health centers (14.5%).

The Perspective article "Artificial Intelligence: Lessons Learned from Radiology." by Elizabeth Krupinski, PhD, Emory University (Atlanta, GA), discusses how AI can help medicine in general, and radiology more specifically. She focuses on AI and computer-aided detection and diagnosis of disease, and how AI can optimize advanced scanning modalities such as CT and MRI. Dr. Krupinski also describes how radiologists perceive AI, presents key challenges and opportunities for applying AI, and discusses where to learn more about AI and radiology.

"Technology can, when used appropriately and embedded within other transformations, result in real, significant, and lasting improvements in access, quality, and efficiencies," states Jonathan D. Linkous, MPA, FATA, Editor-in-Chief Healthcare Transformation and Co-Founder and CEO of PATH. "Amassing data alone is not a solution.," he says. "Real transformation is the challenge Healthcare Transformation and PATH hope to achieve."

Montreal, December 19 2019-- A team led by Professor Patrick Labonté at the Institut National de la Recherche Scientifique (INRS) in Montreal, Canada has identified the role of a key process in the replication cycle of the hepatitis D virus, an infection that is still very difficult to cure and affects 15 to 20 million people worldwide.

The hepatitis D virus (HVD) has a specific target: it infects only people carrying the hepatitis B virus (HBV). As with other co-infections, the combination of hepatitis B and D causes more liver damage than hepatitis B alone.

"HDV needs HBV to survive, it's like a parasite," says researcher Patrick Labonté who specializes in liver viruses (hepatitis). However, cure rates are low because treatments for hepatitis B are ineffective against HDV."

"It may seem contradictory since the virus cannot survive on its own," he adds. "In fact, drugs target a specific enzyme to control hepatitis B, but treatment does not completely eliminate the virus. The VHD survives normally and can continue its damage."

The challenge for Professor Labonté and his research team is thus to find a treatment that will fight both viruses and it seems they are on the right track.

In a study published recently in the Journal of Virology, the team showed that VHD was exploiting the same cellular protein as HBV, called ATG5, to promote its development, particularly its replication in the nucleus of the host cell. This protein is essential for what is called autophagy; a process that is used for cleaning cellular waste. In theory, autophagy should be able to destroy invaders, but most viruses, such as hepatitis C or influenza, have evolved to avoid this degradation and even use autophagy to their advantage.

"Several studies have looked at the role of autophagy in viruses, but it varies from one virus to another depending on its replication process. We are the first to determine the effect of the process on the hepatitis D virus," says Professor Labonté, who is also the study's corresponding author. He was not surprised that ATG5 protein benefits these two hepatitis viruses since they are closely linked.

Towards a Potential Treatment

With this common protein, the autophagic process could be a solution since it is essential to the life cycle of these viruses. However, the situation is not that simple. "If we block autophagy, then we are blocking an important function for all cells in the body. We do not know what the long-term effects might be. Autophagy should be inhibited in a targeted and temporary manner," warns Patrick Labonté;.

According to the World Health Organization, at least 5% of people with chronic HBV infection are also infected with HDV. HBV-HDV co-infection is the most severe form of chronic viral hepatitis because it progresses very quickly and can even be fatal. "Hepatitis B virus alone can cause cirrhosis or liver cancer. When combined with the hepatitis D virus, the development of these diseases happens more frequently and more rapidly," he says.

In the course of this research, Professor Labonté;'s team made an interesting discovery: some autophagy proteins travel outside their usual area. "Autophagy usually occurs in the cell's cytoplasm, but the process contributes to the replication of the HDV genome which takes place in the nucleus. Are there any autophagic proteins present in the nucleus in the case of an infection?", wonders the researcher. This is an area that the team is currently studying and will hopefully provide a more in-depth understanding of the role of autophagy in HDV.

Lung cancer is the leading cause of cancer deaths among all Kentuckians. Male Kentuckians have higher rates than females, with a disproportionate number residing in rural and medically underserved parts of the state.

According to a University of Kentucky study, worksite intervention may be key to connecting men in rural Kentucky with critical lung cancer prevention and control resources and services. A UK-led coalition is partnering with employers in Southern Kentucky to address this health disparity.

The UK College of Public Health, in coordination with the Kentucky Cancer Program at UK and the University of Louisville and the Kentucky Cancer Consortium, have created a worksite intervention on lung cancer, which targets work sites with predominantly male employees in eight rural and medically underserved counties in southern Kentucky. The counties include: Casey, Christian, Clay, Jackson, McCracken, Ohio, Perry and Warren.

The coalition was created in 2016, when the Centers for Disease Control and Prevention (CDC) designated a coalition based at the UK College of Public Health as a member of the SelfMade Health Network, a national network of dedicated professionals, organizations and communities seeking to eliminate tobacco-related health disparities in underserved or high-risk populations.

The first phase of funded research, which was recently published in the American Journal of Men's Health, included focus groups with community organizations in order to understand the resources and services available in each county, such as tobacco treatment, lung cancer screenings, smoke-free workplace policies and radon prevention.

"What we learned is that employers may be an effective way to reach men in rural Kentucky," said Jennifer Knight, an assistant professor in the UK College of Public Health Department of Health Management and Policy and principal investigator on the project. "Another important takeaway is community organizations and area employers are very interested in developing partnerships with one another."

While the first research phase was focused on how to create the partnerships, Knight says the coalition is now coordinating the worksite intervention.

After holding informational roundtables with work sites in each county, the group developed a resource kit for employers, who are currently testing them.

"When we take the time to do this kind of research in communities, we can learn a lot about what is needed and how we can contribute to improving the health of our communities," Knight said.

Scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory are exceptional in many respects. Working in collaboration with the Imperial College London, for example, they have conducted research on a phenomenon in information processing systems called “exceptional points.” This phenomenon has found applications in microwave, optical and mechanical technologies.

“Our team experimentally detected an exceptional surface, a continuous three-dimensional curving surface of exceptional points,” said Xufeng Zhang, who led this international research project and works as an assistant scientist at the Center for Nanoscale Materials (CNM) at Argonne, a DOE Office of Science User Facility. Past research by others had detected exception points, and subsequent researchers had plotted lines of measured exceptional points, but this is the first time researchers have plotted surfaces.

“Our original contribution is to have mapped three-dimensional surfaces of exceptional points based on experimental measurements, and the result is strikingly beautiful graphs.” — Xufeng Zhang, assistant scientist at the Center for Nanoscale Materials

“Think of two systems, each of which has its own loss of energy to the environment,” explained Zhang. “Also imagine that these systems are coupled so that they can exchange energy between them.”

When these systems are far apart, little interaction occurs between them, and energy-related calculations yield two independent solutions tied to their interactions with the environment alone. As they approach each other and interact together, the systems enter a transition phase where there is only one solution. That is considered an exceptional point. As the systems move even closer, the exceptional point vanishes, and the calculations yield pairs of “hybrid solutions,” a mixture of the solutions for each system.

A possible application of exceptional points is sensors with greatly enhanced sensitivity to disruptions such as slight fluctuations in a magnetic field. Another application is mode conversion, which allows, for example, the signals from the two parties in a telephone call to be kept in separate modes, thereby essentially eliminating any undesired interference.

“Our original contribution is to have mapped three-dimensional surfaces of exceptional points based on experimental measurements, and the result is strikingly beautiful graphs,” Zhang said. These exceptional surfaces themselves have what Zhang calls “exceptional saddle points,” the most exceptional point among all the other exceptional points on the surfaces. These saddle points have heightened desired behavior over the other exceptional points.

The team’s experimental apparatus combines two systems: a specialized printed circuit board that confines microwaves and a microscale magnetic sphere of yttrium iron garnet, which produces resonances called “magnons.”

“Magnons are quantized quasiparticles associated with spin waves, a collective excitation of the magnetic ordering in a crystal lattice,” Zhang explained. “What is important here is that changing the magnetization at one point in the lattice affects the neighboring sites like a wave rippling through the surface of a placid pond.”

The team used a magneto-electro-optical spectrometer at the CNM to measure the response to different tunings of the photon-magnon coupling strength and position in their apparatus, then plotted the results in three-dimensional graphs of an exceptional surface.

While highly abstract and mathematical, this pivotal discovery could have real world impact in information processing. As one of several possible examples, information transfer demands that noise not corrupt the zeros and ones being transmitted, and exceptional surface mapping could help provide much greater protection for this process.

“Our work also opens up exciting new possibilities for quantum information processing with highly desired functionalities,” Zhang noted.

Atomic-level studies of the architecture of tiny sodium channel proteins, critical to generating electrical signals that start off each beat of the heart, are imparting striking details about their function, malfunctions, disruption by many disease mutations, and response to medication.

This structural information could become the basis for developing better diagnostics and drugs for life-threatening heart rhythm problems, according to the researchers from the University of Washington School of Medicine working in this area.

Their latest findings appear Dec. 19 in Cell in the paper, "Structure of the Cardiac Sodium Channel." The senior authors are William Catterall and Ning Zheng, both UW School of Medicine professors of pharmacology. The first authors are Daohau Jiang and Hui Shi, UW postdoctoral fellows in pharmacology.

"The cardiac sodium channel not only initiates the heartbeat, mutations in it also cause deadly arrhythmias, and antiarrhythmic drugs act directly on it to control cardiac rhythms," explained Catterall.

The heart is both a plumbing and electrical marvel. For each heartbeat, electrical waves travel across a healthy heart in a pattern that controls its filling and pumping in a tightly coordinated manner. The rate at which the impulse is propagated through the heart tissue relies on actions taking place at the molecular level in tiny protein pores present in cardiac cell membranes.

Sodium ions - a type of charged particles -- pass through these protein passageways in the membrane boundary between the outside and inside of the cell.

Pufferfish harbor a toxin that acts on nerve and muscle, but not heart, sodium channels.

The activation and quick inactivation of these voltage-gated sodium channels are part of a series of electrical and physiological events that maintain a steady heartbeat.

"Sodium channels operate in concert with calcium channels and potassium channels to drive the heartbeat at a consistent frequency for our entire lives," Zheng noted.

When sodium channels don't work properly, the heart can be in trouble, even to the point of having dangerously fast and uncoordinated contractions that are life-threatening, the researchers explained.

Specifically, the NaV (Latin abbreviation for sodium, V for voltage) 1.5 channel has such an indispensable role that certain mutations in those channels can be fatal, because other sodium channels in the heart cannot compensate for their loss. These mutations can cause dangerous arrhythmias in adults and even sudden death in children and young athletes.

Fortunately, many heart rhythm disturbances can be treated with drugs that block cardiac sodium channels. For example, as UW Medicine physician Michael Lenaeus, a UW assistant professor of medicine, Division of General Internal Medicine, and a co-author of the study, noted, atrial fibrillation, or "A-fib," is increasingly prevalent among older Americans.

This condition can often be treated effectively with the drug flecainide. In their recent study, the researchers sought to learn, among other things, how drugs like flecainide act within the predominant form of sodium channels found in cardiac cells.

To obtain a high-resolution, 3-D map of the channels, the scientists used advanced cryo-electron microscopy at the new Beckman Center for Cryo-EM at the UW. They wanted to explore important structural features of these sodium channels and relate their configuration to their actions in normal physiological function, dysfunction, disease mutations, toxin sensitivity and the pharmacology of antiarrhythmic drugs.

According to the scientists, their experiments provide a blueprint for understanding many various aspects of cardiac sodium channels.

Among the key findings from this work were:

A description of some of the characteristics of the NaV1.5 channel that distinguish it from other sodium ion channels found in heart cells, as well as in nerve and muscle cells.

Structural insights into the mode of action of various arrhythmia mutations. There are many parts of the sodium channel protein that can be disrupted by mutations. Some mutations interfere with the activation or inactivation of the sodium channel. Others cause altered function by creating a channel protein hole that leaks sodium continuously. Still other mutations, found in Brugada syndrome, can impair or block the conductance of sodium ions.

Chemical insights into how the heart rhythm drug flecainide targets the inner pocket of the ion channel and plugs the central pore that conducts sodium ions.

The structural determinants that distinguish tetrodotoxin sensitive and insensitive sodium channels. Tetrodotoxin, the infamous, deadly poison in pufferfish, is a sodium channel blocker that has a high affinity for sodium channels in nerves and muscles, but not for those in heart cells.

A comparison of the conformation of an important component of the sodium ion channels that "senses" the voltage across the cell membrane and drives the channels from resting to activated states. After their rapid activation, cardiac sodium channels inactivate within 1 to 2 milliseconds, a timing that is essential to regular heart rhythm.

The researchers were able to determine how mutations can upset activation of the channel or even abolish its required rapid inactivation in a variety of ways.

In their conclusion, the researchers noted that, overall, the detailed, high-resolution structures they were able to obtain for the cardiac NaV1.5 channel allowed them to elucidate the molecular basis for several of its specific, distinctive, vital functions and to provide key chemical information for design and development of safer and more effective antiarrhythmic medications.

"Our high-resolution cryoEM structure of this iconic sodium channel gives new structure/function insights, reveals the molecular mechanisms of many inherited arrhythmias, and elucidates the exact binding site and blocking mode of the antiarrhythmic drug flecainide, which is used to treat atrial fibrillation, an increasingly prevalent problem in our aging population," Catterall said in summarizing the results.

A new computational model suggests that the food web of the human gut microbiome follows a hierarchical structure similar to that of larger-scale ecosystems. Tong Wang of the University of Illinois at Urbana-Champaign and colleagues present the model in PLOS Computational Biology.

In the human gut, hundreds of species of microbes exchange nutrients in a complex food web. Large-scale food webs, such as those of tropical forests, typically follow a hierarchy in which energy flows from plants, to herbivores, to carnivores. Wang and colleagues wondered if the gut microbiome could be considered to follow a similar hierarchy, from microbes that consume nutrients in food eaten by the human host, to those that eat nutrients produced by the first microbes, and so on.

To address this question, the researchers developed a computational model that uses the known species of microbes in a person's gut to predict microbial metabolites--the substances the microbes generate as part of their biological activities, and which may serve as nutrients for other gut microbes. The metabolite predictions generated by the model are in line with experimental data, providing support for its accuracy.

The new model indeed predicts a four-level hierarchy for the food web of the gut microbiome. This suggests that species composition systematically changes along the length of the gut. Near the entrance to the lower gut, one might find bacteria from the highest hierarchical level--those that consume nutrients in food eaten by the human. Near the end of the gut, one might find bacteria from the lowest level.

"There is a great premium on being able to predict metabolic profiles from species genomes, as our algorithm does," Wang says. "Metabolites are better than species composition for predicting important aspects of gut function, but genome sequencing is faster and cheaper than measuring metabolic profiles."

The researchers are now working to refine their model by using a machine-learning approach to infer important competitive relationships between gut microbes. Doing so could improve the model's accuracy, potentially reducing the need for expensive measurements of metabolic profiles in research on gut function.

An observational study of academic working hours has identified large differences in how researchers around the world manage their work-life balance.

QUT's Professor Adrian Barnett led the research which examined more than 49,000 manuscript and 76,000 peer review online submissions to The BMJ and The BMJ Open, measuring whether the submissions were made on weekends, national holidays or late at night.

The study is published in the Christmas edition of The BMJ (link), which is a special issue of light-hearted studies of health.

"Clear and consistent differences were seen between countries," Professor Barnett said.

"Chinese researchers most often worked at weekends and after midnight, whereas researchers in Scandinavian countries, which have a greater focus on work-life balance, were more likely to submit their papers during 9 to 5 on weekdays."

"The differences between countries suggest that a 'culture of overwork' is a literal thing, and not just a figure of speech," Professor Barnett said.

China, which is known to have a hard-working academic culture, was the notable leader on the table of weekend workers, both for submitting manuscripts and peer reviews to both journals in the study.

India, Denmark and Norway were the countries in which academics were least likely to work on weekends.

"Australian researchers were in the middle of the pack for most outcomes, and so were never the worst nor the best," Professor Barnett said

Professor Barnett said there were limitations to the study.

The study recorded when people submitted their papers but did not identify when the academics spent the hours in writing those papers. Other limitations included the possibility that some academics submitted their papers while travelling away from their usual time zones, and that the practices of health and medical researchers who write for BMJ may not be representative of all academics.

Fear, anger, sadness - while it is often assumed these emotion concepts are the same the world over, new research suggests there is greater cross-cultural variation in "how people think about emotions than is widely assumed", contributor Dr Joseph Watts says.

Dr Watts, a Research Fellow in the University of Otago's Religion Programme, is part of an international project on cross-cultural variation in emotion concepts.

The research team includes psychologists at the University of North Carolina at Chapel Hill in the US, and linguists at the Max Planck Institute for the Science of Human History in Germany; their findings have just been published in one of the world's top academic journals, Science.

The research combines wordlists from 2,474 languages in 20 major language families. Using a computational approach, the team identified patterns of "colexification" - a phenomenon in which languages use the same word to express semantically related concepts. Persian, for instance, uses the word-form ænduh to express both the concepts of grief and regret.

"This provides a new way of systematically identifying how people conceptualise emotions across thousands of different languages," Dr Watts says.

By building massive networks of colexification, the team found that there is substantial variation in how languages conceptualise emotion around the world. For example, Nakh-Dagestanian languages from the Caucasus view "grief" as similar to "fear" and "anxiety," but Tai-Kadai languages from Southeast Asia view "grief" as similar to "regret." This challenged common assumptions about the universal nature of emotion semantics.

However, variation in emotion semantics was not totally without structure. Language families in close geographic proximity were found to share more similar views of emotion than more distant language families. A likely reason for this is that common ancestry and historical contact between these groups has led to a shared understanding of emotion. This highlights the importance of culture in the way people think about emotions.

Emotion concepts were also found to be structured by whether they are pleasant vs. unpleasant to experience, and whether they are arousing versus calming to experience. This suggests that there are universal elements of emotion experience which may stem from universal biological processes.

Together, the findings of this research suggests that both biological and cultural evolutionary processes shape the way humans think about emotions.

Due to its scope, the research represents a departure for cross-cultural studies of emotion, which typically involve comparing only two cultures or focus on industrialised nations where it is easy to recruit human participants. The study examines common elements from languages worldwide to build large "associative networks" of meaning, and in doing so shows how new approaches in comparative linguistics can expand our understanding of human cognition.

Dr Watts plans to do more work on cross-cultural variation in mental state representations in the future. He recently received a Marsden Fast-Start grant to study cross-cultural variation in mental state vocabulary in the Pacific.

Brown algae are not just seaweed that floats in the ocean and tangles swimmers' feet - it also contains a secret. In its cell wall, brown algae hold polysaccharide alginate, one of the most abundant carbohydrates in the ocean. A major food source for several organisms, the alginate absorbs carbon dioxide and can be converted into ethanol.

Researchers from the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences are now studying the organisms to understand this mechanism, and they're making some discoveries along the way.

"The abundance of these seaweeds has made them an attractive and important source of renewable biomass for biofuel production," said JI Shiqi, research assistant professor in the Shandong Provincial Key Laboratory of Energy Genetics.

JI is part of an international team from China and the United Kingdom who is working to better understand how the alginate is processed into ethanol by organisms. By examining the enzymes that break down the alginate, the researchers may be able to harness the natural process to produce biofuel. During this process, they identified previously unknown enzymatic families that contribute to the bioconversion.

Their findings about the full structure of one such enzyme were published in Journal of Biological Chemistry on October 17.

The enzyme, called an alginate lyase, breaks down the alginate so it can be converted into other products. There are currently 37 identified lyase families that break down polysaccharides, which are structures that contain multiple sugars. Of those 37 families, nine specifically degrade alginates and seven of those nine have had their structures fully described.

JI and the team identified a new alginate lyase in a heat-loving bacterium that can directly utilize brown algae and ferment its components to ethanol with high-yield.

"The bacterium contains at least four alginate lyases, including a number of novel lyases that represent totally new polysaccharide lyase families," JI said.

The researchers focused on imaging the structure of one alginate lyase, dubbed "Dp0100," to better understand its molecular mechanisms in processing alginate into ethanol. The imaging study also led to a better understanding of the structure specificity, catalysis and evolution of alginate lyases with multiple domain sites, according to JI.

"While the mechanism of Dp0100's thermostability is not well understood yet, this research has furthered our understanding of the structure-function and evolutionary relationships within this important class of lyases," JI said.

The researchers will continue to study the alginate lyases, as well as pursue structural studies of other polysaccharide lyase families with the ultimate goal of determining the full function of alginate bioconversion.

Voters tend to believe that one political party's gain can only be obtained at another party's expense, according to a new study. Conservatives engage in so-called "zero-sum thinking" when the status quo is challenged, a finding that explains their tendency to uphold social hierarchies. Liberals, meanwhile, engage in zero-sum thinking when the status quo is upheld, leading them to question social hierarchies. The results illustrate how contrasting uses of zero-sum thinking contribute to political divides in the Unites States, suggesting policies may be more likely to attain bipartisan support if they are framed to emphasize the status quo when presented to conservative voters and if they are framed to challenge the status quo when presented to liberal voters. As examples of zero-sum thinking, some white Americans believe that anti-white prejudice stems from decreases in anti-black prejudice, and some American-born citizens worry that rising immigration threatens their own economic well-being. This thinking prevents "win-win" resolutions and reduces trust during political debates about who stands to win and who stands to lose from a proposed policy. To examine the effect of political ideology on zero-sum thinking, Shai Davidai et al. performed a series of six studies. They first analyzed World Value Survey data from 2,128 Americans, finding that the more strongly respondents identified as belonging to the right side of the political spectrum, the more they believed people can only get rich at the expense of others. Subsequent studies randomly assigned participants from Amazon's Mechanical Turk to positions that either challenged or maintained the status quo on issues including immigration and racial status inequality, finding across the board that conservatives engaged in zero-sum thinking only when an issue challenged the status quo, while liberals did the opposite.