Culture

No NELL2, no sperm motility; novel protein is essential for male fertility

Newly produced spermatozoa within the testis are not fully functional until they mature in the epididymis, a duct that helps to transport and store sperm. Male infertility may arise from lack of communication between the testis and the epididymis and new research has uncovered a mechanism of this communication.

Dr. Martin Matzuk at Baylor College of Medicine, Dr. Masahito Ikawa with Osaka University and their colleagues have discovered a novel testicular luminal protein, NELL2, that triggers in the epididymis a chain of events that matures the sperm and enables each one to be motile in females.

Sperm production

Sperm are produced in the seminiferous tubules of the testis and move through the epididymis, a long, convoluted tube linked to the vas deferens, the duct that moves sperm from the testicle to the urethra. When the sperm enter the epididymis, they are not motile and are incapable of fertilization. However, in their passage through the epididymis, the sperm are provided an appropriate environment for maturation and storage pending ejaculation.

It has been hypothesized that proteins released by the testis earlier in this process could act on the epididymis to mature the sperm as they arrive in the epididymis.

"Until now the proteins working through the lumicrine system of signaling have remained elusive. While it was known that the orphan receptor tyrosine kinase ROS1 expressed in the initial segment of the epididymis is necessary for its differentiation, neither the testicular factors that regulate initial segment differentiation nor the process of sperm maturation had been fully understood," said Matzuk, professor and director of the Center for Drug Discovery at Baylor.

Identifying NELL2

The researchers zeroed in on NELL2, a protein factor secreted by testicular germ cells, as a possible lumicrine regulator of fertility.
"Using innovative genome editing technology, we generated knockout mice lacking the NELL2 gene and showed that these knockout males are sterile due to a defect in sperm motility," explains lead author Dr. Daiji Kiyozum. "Moreover, their infertility could be rescued with a germ-cell-specific transgene, thus excluding other sites of expression. We also illustrated lumicrine signaling by demonstrating tagged NELL2 in the epididymal lumen."

The research team observed that spermatogenesis proceeds normally in NELL2 knockout mouse testes but their epididymis was poorly differentiated, similar to Ros1 knockout mice. Following mating, neither NELL2 knockout nor Ros1 knockout spermatozoa can enter the uterine tubes or fertilize an egg. Further investigation showed that the Nell2 knockout epididymis is incapable of processing a specific sperm surface protein essential for male fertility.

Implications for male fertility?

Elaborating on their study, Ikawa and Matzuk, both senior authors, said, "We discovered a complicated cascade of events in which disruption of any point in this lumicrine pathway causes a male to be infertile. Our findings have important translational implications for diagnostic and therapeutic research in male infertility and male contraceptive development. This unique transluminal communication pathway between tissues and organs likely functions elsewhere in our bodies."

Credit: 
Baylor College of Medicine

Is COVID-19 widening the gender gap in academic medicine?

image: Reshma Jagsi, M.D., D.Phil.

Image: 
Michigan Medicine

ANN ARBOR, Michigan -- A new study finds that fewer women were first authors on COVID-19-related research papers published in the first half of this year. The difference was particularly striking during the first two months of the pandemic when schools closed and researchers were told to work remotely.

The findings suggest a worsening gender gap in academic medicine as previous research has shown women are underrepresented among authors of medical research. Other studies have shown female physician-scientists spend more time than their male colleagues on domestic tasks. Women are also more likely to serve on clinical and education tracks that were also upended when the pandemic struck.

"The coronavirus pandemic may be creating even greater challenges than before for women in academic medicine," says study author Reshma Jagsi, M.D., D.Phil., director of the Center for Bioethics and Social Sciences in Medicine at the University of Michigan. "We suspect school closures, limited child care and work-related service demands might have taken the greatest toll on early career women, especially during the height of the disruptions."

Researchers looked at 1,893 articles related to COVID-19 published between January and June whose first or last author had a U.S. affiliation. They compared that to 85,373 papers published in the same journals in 2019.

They found the share of women first authors dropped 14% for COVID-19 papers compared to papers published in 2019. They found the differences were most striking in March and April to compared to May. Looking only at March and April publications, the share of women first authors was 23% lower than for 2019 papers. Results were published in the journal eLife.

While the study does not assess the reasons for this drop, the authors suggest that during the initial shutdown and strict social distancing guidelines, women likely took on a greater share of child care and other domestic responsibilities, while also juggling major changes to their duties as educators and physicians.

"We know that diverse teams are important for solving complex problems like those related to COVID-19," Jagsi says. "It's critical in this time of crisis that we have policies that support the full inclusion of diverse scholars, including transforming attitudes about domestic expectations for women and resources to support all those balancing great demands both at home and at work."

Credit: 
Michigan Medicine - University of Michigan

Our itch to share helps spread COVID-19 misinformation

To stay current about the Covid-19 pandemic, people need to process health information when they read the news. Inevitably, that means people will be exposed to health misinformation, too, in the form of false content, often found online, about the illness.

Now a study co-authored by MIT scholars contains bad news and good news about Covid-19 misinformation -- and a new insight that may help reduce the problem.

The bad news is that when people are consuming news on social media, their inclination to share that news with others interferes with their ability to assess its accuracy. The study presented the same false news headlines about Covid-19 to two groups of people: One group was asked if they would share those stories on social media, and the other evaluated their accuracy. The participants were 32.4 percent more likely to say they would share the headlines than they were to say those headlines were accurate.

"There does appear to be a disconnect between accuracy judgments and sharing intentions," says MIT professor David Rand, co-author of a new paper detailing the findings. "People are much more discerning when you ask them to judge the accuracy, compared to when you ask them whether they would share something or not."

The good news: A little bit of reflection can go a long way. Participants who were more likely to think critically, or who had more scientific knowledge, were less likely to share misinformation. And when asked directly about accuracy, most participants did reasonably well at telling true news headlines from false ones.

Moreover, the study offers a solution for over-sharing: When participants were asked to rate the accuracy of a single non-Covid-19 story at the start of their news-viewing sessions, the quality of the Covid-19 news they shared increased significantly.

"The idea is, if you nudge them about accuracy at the outset, people are more likely to be thinking about the concept of accuracy when they later choose what to share. So then they take accuracy into account more when they make their sharing decisions," explains Rand, who is the Erwin H. Schell Associate Professor with joint appointments at the MIT Sloan School of Management and the Department of Brain and Cognitive Sciences.

The paper, "Fighting COVID-19 misinformation on social media: Experimental evidence for a scalable accuracy nudge intervention," appears in Psychological Science. Besides Rand, the authors are Gordon Pennycook, an assistant professor of behavioral science at the University of Regina; Jonathan McPhetres, a postdoc at MIT and the University of Regina who is starting a position in August as an assistant professor of psychology at Durham University; Yunhao Zhang, a PhD student at MIT Sloan; and Jackson G. Lu, the Mitsui Career Development Assistant Professor at MIT Sloan.

Thinking, fast and slow

To conduct the study, the researchers conducted two online experiments in March, with a total of roughly 1,700 U.S. participants between them, using the survey platform Lucid. Participants matched the nation's distribution of age, gender, ethnicity, and geographic region.

The first experiment had 853 participants, and used 15 true and 15 false news headlines about Covid-19, in the style of Facebook posts, with a headline, photo, and initial sentence from a story. The participants were split into two groups. One group was asked if the headlines were accurate; the second group was asked if they would consider sharing the posts on platforms such as Facebook and Twitter.

The first group correctly judged the stories' accuracy about two-thirds of the time. The second group might therefore be expected to share the stories at a similar rate. However, the participants in the second group shared about half of the true stories, and just under half of the false stories -- meaning their judgment about which stories to share was almost random in regard to accuracy.

The second study, with 856 participants, used the same group of headlines and again split the participants into two groups. The first group simply looked at the headlines and decided whether or not they would share them on social media.

But the second group of participants were asked to evaluate a non-Covid-19 headline before they made decisions about sharing the larger group of Covid-19 headlines. (Both studies were focused on headlines and the single sentence of text, since most people only read headlines on social media.) That extra step, of evaluating one non-Covid-19 headline, made a substantial difference. The "discernment" score of the second group -- the gap between the number of accurate and inaccurate stories they shared -- was almost three times larger than that of the first group.

The researchers evaluated additional factors that might explain tendencies in the responses of the participants. They gave all participants a six-item Cognitive Reflection Test (CRT), to evaluate their propensity to analyze information, rather than relying on gut instincts; evaluated how much scientific knowledge participants had; and looked at whether respondents were located close to Covid-19 outbreaks, among other things. They found that participants who scored higher on the CRT, and knew more about science, rated headlines more accurately and shared fewer false headlines.

Those findings suggest that the way people assess news stories has less to do with, say, preset partisan views about the news, and a bit more to do with their broader cognitive habits.

"A lot of people have a very cynical take on social media and our moment in history, that we're post-truth and no one cares about the truth any more," Pennycook says. "Our evidence suggests it's not that people don't care; it's more that they're distracted."

Something systemic about social media

The study follows others Rand and Pennycook have conducted about explicitly political news, which similarly suggest that cognitive habits, more so than partisan views, influence the way people judge the accuracy of news stories and lead to the sharing of misinformation. In this study, the scholars wanted to see if readers analyzed Covid-19 stories, and health information, differently than political information. But the results were generally similar to the political-news experiments the researchers have conducted.

"Our results suggest that the life-and-death stakes of Covid-19 do not make people suddenly take accuracy into [greater] account when they're deciding what to share," Lu says.

Indeed, Rand suggests, the very importance of Covid-19 as a subject may interfere with readers' ability to analyze it.

"Part of the issue with health and this pandemic is that it's very anxiety-inducing," Rand says. "Being emotionally aroused is another thing that makes you less likely to stop and think carefully."

Still, the central explanation, the scholars think, is simply the structure of social media, which encourages rapid browsing of news headlines, elevates splashy news items, and rewards users who post eye-catching news, by tending to give them more followers and retweets, even if those stories happen to be untrue.

"There is just something more systemic and fundamental about the social media context that distracts people from accuracy," Rand says. "I think part of it is that you're getting this instantaneous social feedback all the time. Every time you post something, you immediately get to see how many people liked it. And that really focuses your attention on: How many people are going to like this? Which is different from: How true is this?"

Credit: 
Massachusetts Institute of Technology

Trust me if you can

image: Victim of wind power plant

Image: 
Christian Voigt, IZW

Wind energy is considered to be one of the most promising forms of renewable energy. Yet, each year, wind turbines are responsible for the death of hundreds of thousands of airborne animals such as bats which die from collisions with turbine blades. To find a constructive way out of this "green-green" dilemma, companies building and running wind turbines might have to work together with environmental experts and conservationists. Yet a lack of trust between them is likely to hinder effective and creative collaboration. In an article published in Energy Reports, scientists of the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) show that shared values alone are not sufficient to build mutual trust between these groups, as beliefs and emotions hold a stronger sway for the collaboration. The authors argue that an improved awareness of each others' beliefs and emotions in relation to the construction and operation of wind turbines can benefit their work in this field and help find a way out of the dilemma.

Mitigating climate change by producing more renewable (green) energy, for instance through wind turbines, seems to be a good thing. So is the conservation of biological diversity through protecting airborne animals such as birds and bats. However, when bats and birds die from collisions with turbine blades a "green-green" dilemma arises that needs to be resolved. Parties involved in the planning and approval of wind turbine projects have contrasting views and interests. As both the mitigation of climate change and the protection of biodiversity have strong proponents with strong opinions, reaching a compromise between building and operating wind turbines and protecting e.g. bats is fraught with difficulties. If the relevant and often opposing stakeholders collaborate, their distinct views and expertise could contribute to the development of novel solutions to the conflict by helping to reconcile both goals. An example would be the avoidance of sensitive areas for the construction of wind turbines or the consistent alignment of wind turbine operating times with the activity rhythms of airborne wildlife. One crucial prerequisite for such cooperation is mutual trust.

A team of the Leibniz-IZW led by Dr Tanja Straka undertook a self-administered online survey to analyse how values, beliefs, and emotions towards wind turbines and bats affect trust between stakeholders involved in this "green-green" conflict in Germany. Overall, 537 representatives of six stakeholder groups participated in the survey: members of the wind energy sector, environmental consultants, conservation authorities, scientists, volunteers and employees of environmental NGOs.

The analysis of the responses showed that the members of all groups involved in wind energy projects share the same fundamental value of a sustainable use of nature. Yet, despite these shared values they have little trust in each other, suggesting that common values are not a good enough basis for mutual trust. The results of the investigation also demonstrated that a crucial basis for trust among stakeholders are shared beliefs and emotions towards wildlife conservation and green energy.

"Decision-making is seldom a purely rational process," argues Tanja Straka. The authors of the article, therefore, recommend having a closer look on the beliefs and emotions of the members of the stakeholder groups involved in wind energy projects. "When planning dialogues between stakeholder groups, creating a trustworthy ground for the participants to share and discuss their views should be as important as communicating evidence-based knowledge. Such an exchange can strengthen trust and foster cooperation between members of different groups, which could help improve bat conservation in wind turbines projects, ultimately faciltating the ecologically sustainable energy transition to renewable sources and protecting our biodiversity at the same time," adds PD Dr Christian Voigt, head of the Department of Evolutionary Ecology at the Leibniz-IZW.

Credit: 
Forschungsverbund Berlin

Dissecting fruit flies' varying responses to life-extension diet

image: A cartoon of an elderly fruit-fly enjoying his breakfast. The effects of calorie-restricted diets on fruit fly aging and lifespans is not uniform across different strains. A new study looks at small molecules involved in cell metabolism to see why this inconsistency occurs.

Image: 
Alice C. Gray

Changes in a few small molecules involved in a cell's metabolism seem to indicate whether a restricted "life extension" diet will actually extend, shorten, or have no effect on lifespan, a study of fruit flies has found.

The findings suggest that analyzing the level of small molecules in cells, an approach called metabolomics, may help us understand how calorie-restricted diets affect aging, and how genes, environment, and other factors influence an individual's response to calorie restriction.

"If we can use the metabolome to understand variation in something as complex as lifespan extension, we should be able to use it to understand many other differences we see across populations," said Kelly Jin, a computational biologist in pathology at the University of Washington (UW) School of Medicine. She was lead author on the new study.

A cell's metabolism involves basic chemical reactions that occur for the cell to develop, survive, and proliferate. The small molecules that participate in, and are generated by, these reactions are called metabolites. Metabolites include such things as amino acids that are the building blocks for proteins, sugars and fats that are broken down to generate energy, and products of those reactions. Collectively these molecules make up the metabolome.

In the new study, the UW researchers worked with collaborators at the Buck Institute for Research on Aging and others to understand how calorie-restricted diets may prolong life in different strains of flies.

Such diets can extend lifespans, according to previous studies of different species, including yeast, worms, fruit flies, and mice. Although low-calorie diets have not been shown to lengthen humans' lives, they have been shown to cause weight loss and improve such disease-risk factors as high blood pressure and elevated blood sugar and cholesterol.

The effects of these diets, however, are not uniform. A strain of fruit flies with one particular genetic makeup, or genotype, might see an increased lifespan while a strain with another genotype might see no effect or even a decrease in lifespan.

Clearly genetic differences between the strains are playing a role, but discerning which genetic differences are important is difficult: A fruit fly has about 14,000 genes, many of which are likely to influence lifespan.

A cell's metabolome, on the other hand, distills variation in the complex upstream processes, such as gene expression, gene transcription and protein synthesis, said Daniel Promislow, the paper's senior author. He is a UW School of Medicine professor of pathology and a professor of biology in the UW College of Arts & Sciences.

The complex interplay of these factors and factors in the environment ends up being filtered down to a much smaller number of metabolites, which are simpler to measure and closer to the trait you're studying," Promislow said.

The UW researchers compared the levels of 105 metabolites in fruit flies from 178 strains, which had been fed a normal diet or a restricted diet. They analyzed whether there was a relationship between the flies' diets, their metabolite levels, and changes in their lifespans.

"Dietary restriction dramatically remodeled the metabolome in consistent ways across all 178 fruit fly genotypes," Jin said. These included levels of some key amino acids used in the synthesis of proteins as well as metabolites involved in the alpha-ketoglutarate/glutamine pathway, a process involved in energy generation, among other things.

Genetic analysis was able to identify only one gene clearly associated with the fruit flies' lifespan response to diet restriction. So the researchers used a novel statistical tool, called network analysis, to link the metabolites to changes in lifespan, and then looked for genes linked to those metabolites.

With this approach they identified several genes that appeared to play a role, including one variant of a gene called CCHa2-R that codes for a neuropeptide receptor found in the brain and the gut and which is involved in nutrient sensing and satiety response.

"Our findings show how studying an organism's metabolome not only can help reveal the genetic variation behind complex traits, but also help explain the mechanisms that underlie variation seen in these traits," said Jin.

Credit: 
University of Washington School of Medicine/UW Medicine

Study says inhalers ok to use amid COVID-19 concerns

The benefits of using inhalers and nebulisers containing steroids outweigh the risks despite warnings to the contrary during the COVID-19 pandemic, a study by University of Huddersfield researchers has found.

A warning issued by WHO in March advised that steroids used in inhalers and nebulisers could have a negative effect on a user's immunity system, leaving them more susceptible to COVID-19. The concern was that regular steroid use could leave users vulnerable to contracting the virus, or developing a more severe version than non-users.

WHO's cautionary note caused worry for people with asthma or chronic obstructive pulmonary disease (COPD), leaving them unsure about whether they could keep using inhalers and nebulisers or not. The British Thoracic Society had reported that demand for inhalers had jumped by 400%, leading to shortages in the UK, following WHO's announcement.

However, Dr Hamid Merchant and Dr Syed Shahzad Hasan from the University of Huddersfield commissioned research into the use of steroids and risk of infections, especially viral infections of the upper respiratory tract. That included previous outbreaks of SARS, as well as the COVID-19 pandemic.

"It confused a lot of people," says Dr Hasan. "After the WHO advice, people thought that continuous use of steroids would leave them at a greater risk of contracting the virus or developing more than a mild version of CoViD-19."

Inhaled corticosteroids (ICS) and oral corticosteroids (OCS) are prescribed to help asthma sufferers and those with COPD, with inhalers used to prevent attacks.

The study has been published in Respiratory Medicine, having assessed evidence and findings from a range of bodies including the British Thoracic Society and the National Institute for Health and Care Excellence (NICE). The other authors in the study included Toby Capstick (a consultant pharmacist on respiratory medicine at Leeds Teaching Hospitals NHS Trust), Syed Tabish Zaidi (Associate Professor in Pharmacy at the University of Leeds) and Chia Siang Kow (a clinical pharmacist from Malaysia).

"We found there is strong evidence that the benefits of continuing with steroids outweighs the risk," declares Dr Merchant.

"There is a risk that the immune system goes down, and there is a chance of acquiring infections but the benefits of continuing with steroids throughout were higher than the risks. We concluded by saying that the patients should continue their regular medicines including steroids."

Credit: 
University of Huddersfield

Women who deliver by C-section are less likely to conceive subsequent children

HERSHEY, Pa. -- Women who deliver their first child by cesarean section (C-section) are less likely to conceive a second child than those who deliver vaginally, despite being just as likely to plan a subsequent pregnancy, according to Penn State College of Medicine researchers. The team followed more than 2,000 women for three years after they delivered their first child.

Kristen Kjerulff, professor of public health sciences, said that although previous studies showed that women who delivered by C-section were less likely to bear subsequent children, it was unclear to researchers whether this was due to maternal choice or a lower rate of conception.

The researchers followed women from before the birth of their first child and interviewed them every six months until three years after their first delivery. During each interview, they asked women to report how often they had unprotected intercourse in each of the previous six months.

Kjerulff and colleagues analyzed data from 2,021 women between the ages of 18 and 35 who provided data on unprotected intercourse and resulting conceptions for three years after their first birth. Nearly 600 of those women delivered their first child by C-section and those women were more likely to be older, overweight and obese, shorter, and more likely to have sought fertility advice, testing or treatment.

Approximately 69% of women who delivered by C-section conceived after unprotected intercourse compared to approximately 78% of women who delivered vaginally. Women who delivered by C-section also had a reduced likelihood of a live birth. The association remained after researchers accounted for maternal age, pre-pregnancy body mass index, time to conception of the first child, gestational weight gain, prior induced abortions, diabetes, hypertension, hospitalization during pregnancy and other factors.

Dr. Richard Legro, a coauthor of the manuscript published in JAMA Network Open and chair of the Department of Obstetrics and Gynecology at Penn State Health Milton S. Hershey Medical Center, says that controlling for intercourse was a key strength of the study and allowed the researchers to rule out trauma or lingering pain from C-section. Although the study didn't investigate the reasons for the decreased conception rate, he suspects there may be some physiological reasons.

"It's possible that pelvic or [fallopian] tubal scarring as a result of being exposed to open air and contaminants may affect subsequent attempts at getting pregnant," Legro said. "It is also possible that scar formation from the surgical wound in the uterus, though not in an area where pregnancies implant, may have lingering effects on the process of implantation."

Based on the findings from this study, Kjerulff and Legro recommend that women under 35 who fail to conceive after a year of unprotected intercourse following a C-section seek medical help. Legro noted the data from this study may be useful for physicians counseling women who elect to have C-sections.

"It's important that women who elect to have a C-section know that there is a chance they may have difficulty conceiving in the future," Legro said.

Credit: 
Penn State

Feeling with the heart

A person's sensitivity to external stimuli depends not only on the state of their nervous system, but also on their cardiac cycle. Usually we do not notice our heartbeat, paying attention to it only in unusual situations, such as in moments of excitement before a performance or while experiencing arrhythmia. The brain actively suppresses the perception of our heartbeat, but as a result, our perception of other sensory stimuli may also be affected. This conclusion was made in a paper by a team of scientists from the Max Planck Institute for Human Cognitive and Brain Sciences (Leipzig) with the participation of Vadim Nikulin, a leading researcher at the Institute of Cognitive Neurosciences at HSE University.

A cardiac cycle consists of two phases: systole and diastole. During systole, the heart muscles contract, and during diastole, they relax. It has been suggested earlier that a person is more susceptible to various stimuli during diastole and less sensitive during systole.

To find out what happens to the brain during different phases of the cardiac cycle, the scientists conducted an experiment by stimulating the fingers of 37 subjects with a barely perceptible electrical current. After each test, participants were asked if they felt any stimulation. At the same time, their brain and heart activity was monitored with EEG and ECG, respectively.

As expected, during systole, participants often did not notice the presence of stimuli. A decrease in sensitivity was accompanied by a change in brain activity. EEG recordings can show the P300 potential associated with the detection of the stimuli. During systole, this potential was less pronounced. Interestingly, the amplitude of the pre-stimulus heart-beat evoked potential correlated negatively with the detection and localization of somatosensory stimuli. Thus, the greater the potential caused by the heartbeat, the lower the potential of P300, and the more likely the subject would not sense the current.

Researchers believe that the brain predicts when the next contraction of the heart will occur, and suppresses the perception of stimuli more strongly in the systole phase, so that we are not distracted by our heart rhythm or confuse it with an external stimulus.

'These results are interesting since they show that our conscious perception of the external world can change within every heartbeat cycle, which is a rhythmic event that we mostly don't pay attention to,' says Esra Al, the lead author of the study. 'Therefore, these findings suggest that not only the brain but also the body plays an important role in shaping our consciousness.'

The results of the study may provide new insight into the understanding of neuronal processes associated with anxiety conditions. Such conditions are associated not only with a change in the heart rate, but also with a change in one's perception of their heartbeat.

Credit: 
National Research University Higher School of Economics

A new look at deep-sea microbes

image: Microbes found deeper in the ocean are believed to have slow population turnover rates and low amounts of available energy. However, microbial communities found deeper in seafloor sediments in and around hydrocarbon seepage sites have more energy available and higher population turnover rates than previously thought.

Image: 
Graphic by Jeffrey C. Chase

Microbial cells are found in abundance in marine sediments beneath the ocean and make up a significant amount of the total microbial biomass on the planet. Microbes found deeper in the ocean, such as in hydrocarbon seeps, are usually believed to have slow population turnover rates and low amounts of available energy, where the further down a microbe is found, the less energy it has available.

A new study published out of a collaboration with the University of Delaware and ExxonMobil Research and Engineering shows that perhaps the microbial communities found deeper in the seafloor sediments in and around hydrocarbon seepage sites have more energy available and higher population turnover rates than previously thought.

Using sediment samples collected by ExxonMobil researchers, UD professor Jennifer Biddle and her lab group -- including Rui Zhao, a postdoctoral researcher who is the first author on the paper; Kristin Yoshimura, who received her doctorate from UD; and Glenn Christman, a bioinformatician -- worked on a study in collaboration with Zara Summers, an ExxonMobil microbiologist. The study, recently published in Scientific Reports, looks at how microbial dynamics are influenced by hydrocarbon seepage sites in the Gulf of Mexico.

Biddle and her lab members received the frozen sediments, collected during a research cruise, from ExxonMobil and then extracted the DNA and sequenced it at the Delaware Biotechnology Institute (DBI).

The samples Biddle's lab group studied were ones collected from deeper in hydrocarbon seeps that usually get ignored.

"Most people only look at the top couple of centimeters of sediment at a seep, but this was actually looking 10-15 centimeters down," said Biddle associate professor in the School of Marine Science and Policy in UD's College of Earth, Ocean and Environment. "We then compared seepage areas to non-seepage areas, and the environment looked really different."

Inside the seep, the microbes potentially lead a fast, less efficient life while outside the seep, the microbes lead a slower but more efficient life. This could be attributed to what energy sources are available to them in their environment.

"Understanding deep water seep microbial ecology is an important part of understanding hydrocarbon-centric communities," said Summers.

Biddle said that microbes are always limited by something in the environment, such as how right now during the quarantine, we are limited by the amount of available toilet paper. "Outside of the seep, microbes are likely limited by carbon, whereas inside the seep, microbes are limited by nitrogen," said Biddle.

While the microbes found inside the seep seem to be racing to make more nitrogen to keep up and grow with their fellow microbes, outside of the seep, the researchers found a balance of carbon and nitrogen, with nitrogen actually being used by the microbes as an energy source.

"Usually, we don't think of nitrogen as being used for energy. It's used to make molecules, but something that was striking for me was thinking about nitrogen as a significant energy source," said Biddle.

This difference between the microbes found inside the seeps and those found outside the seeps could potentially mirror how microbes behave higher in the water column.

Previous research of water column microbes shows that there are different types of microbes: those that are less efficient and lead a more competition-based lifestyle where they don't use every single molecule as well as they could and those that are really streamlined, don't waste anything and are super-efficient.

"It makes me wonder if the microbes that are living at these seeps are potentially wasteful and they're fast growing but they're less efficient and the organisms outside of the seeps are a very different organism where they're way more efficient and way more streamlined," said Biddle, whose team has put in a proposal to go back out to sea to investigate further. "We want to look at these dynamics to determine if it still holds true that there is fast, less efficient life inside the seep and then slower, way more efficient life outside of the seep."

In addition, Biddle said this research showed that the deeper sediments in the seepages are most likely heavily impacted by the material coming up from the bottom, which means that the seep could be supporting a larger amount of biomass than previously thought.

"We often think about a seep supporting life like tube worms and the things that are at the expression of the sediment, but the fact that this could go for meters below them really changes the total biomass that the seep is supporting," said Biddle. "One of the big implications for the seepage sites with regards to the influence of these fluids coming up is that we don't know how deep it goes in terms of how much it changes the impact of subsurface life."

Summers added that these are interesting insights "when considering oil reservoir connectivity to, and influence on, hydrocarbon seeps."

Credit: 
University of Delaware

Bats offer clues to treating COVID-19

image: Bats--the only flying mammals--are highly mobile, constantly bringing new pathogens into their communities. According to University of Rochester biologists, that's one reason they have evolved to have immunity to so many viruses that plague humans, who have only recently (in evolutionary terms) come to be highly mobile and more likely to live in densely populated centers.

Image: 
Getty Images photo

Bats are often considered patient zero for many deadly viruses affecting humans, including Ebola, rabies, and, most recently, the SARS-CoV-2 strain of virus that causes coronavirus.

Although humans experience adverse symptoms when afflicted with these pathogens, bats are remarkably able to tolerate viruses, and, additionally, live much longer than similar-sized land mammals.

What are the secrets to their longevity and virus resistance?

According to researchers at the University of Rochester, bats' longevity and capacity to tolerate viruses may stem from their ability to control inflammation, which is a hallmark of disease and aging. In a review article published in the journal Cell Metabolism, the researchers--including Rochester biology professors Vera Gorbunova and Andrei Seluanov--outline the mechanisms underlying bats' unique abilities and how these mechanisms may hold clues to developing new treatments for diseases in humans.

WHY ARE BATS 'IMMUNE' TO VIRUSES?

The idea for the paper came about when Gorbunova and Seluanov, who are married, were in Singapore in March before COVID-19 travel bans began. When the virus started to spread and Singapore went into lockdown, they were quarantined at the home of their colleague Brian Kennedy, director of the Centre for Healthy Aging at the National University of Singapore and co-author of the paper.

The three scientists, all experts on longevity in mammals, got to talking about bats. SARS-CoV-2 is believed to have originated in bats before the virus was transmitted to humans. Although bats were carriers, they seemed to be unaffected by the virus. Another perplexing factor: generally, a species' lifespan correlates with its body mass; the smaller a species, the shorter its lifespan, and vice versa. Many bat species, however, have lifespans of 30 to 40 years, which is impressive for their size.

"We've been interested in longevity and disease resistance in bats for a while, but we didn't have the time to sit and think about it," says Gorbunova, the Doris Johns Cherry Professor of Biology at Rochester. "Being in quarantine gave us time to discuss this, and we realized there may be a very strong connection between bats' resistance to infectious diseases and their longevity. We also realized that bats can provide clues to human therapies used to fight diseases."

While there have been studies on the immune responses of bats and studies of bats' longevity, until their article, "no one has combined these two phenomena," Seluanov says.

Gorbunova and Seluanov have studied longevity and disease resistance in other exceptionally long-lived animals, including naked mole rats. One common theme in their research is that inflammation is a hallmark of the aging process and age-related diseases, including cancer, Alzheimer's, and cardiovascular disease. Viruses, including COVID-19, are one factor that can trigger inflammation.

"With COVID-19, the inflammation goes haywire, and it may be the inflammatory response that is killing the patient, more so than the virus itself," Gorbunova says. "The human immune system works like that: once we get infected, our body sounds an alarm and we develop a fever and inflammation. The goal is to kill the virus and fight infection, but it can also be a detrimental response as our bodies overreact to the threat."

Not so with bats. Unlike humans, bats have developed specific mechanisms that reduce viral replication and also dampen the immune response to a virus. The result is a beneficial balance: their immune systems control viruses but at the same time, do not mount a strong inflammatory response.

WHY DID BATS ACQUIRE A TOLERANCE FOR DISEASES?

According to the researchers, there are several factors that may contribute to bats having evolved to fight viruses and live long lives. One factor may be driven by flight. Bats are the only mammals with the ability to fly, which requires that they adapt to rapid increases in body temperature, sudden surges in metabolism, and molecular damage. These adaptations may also assist in disease resistance.

Another factor may be their environment. Many species of bats live in large, dense colonies, and hang close together on cave ceilings or in trees. Those conditions are ideal for transmitting viruses and other pathogens.

"Bats are constantly exposed to viruses," Seluanov says. "They are always flying out and bringing back something new to the cave or nest, and they transfer the virus because they live in such close proximity to each other."

Because bats are constantly exposed to viruses, their immune systems are in a perpetual arms race with pathogens: a pathogen will enter the organism, the immune system will evolve a mechanism to combat the pathogen, the pathogen will evolve again, and so on.

"Usually the strongest driver of new traits in evolution is an arms race with pathogens," Gorbunova says. "Dealing with all of these viruses may be shaping bats' immunity and longevity."

CAN HUMANS DEVELOP THE SAME DISEASE RESISTANCE AS BATS?

That's not an invitation for humans to toss their masks and crowd together in restaurants and movie theaters. Evolution takes place over thousands of years, rather than a few months. It has only been in recent history that a majority of the human population has begun living in close proximity in cities. Or that technology has enabled rapid mobility and travel across continents and around the globe. While humans may be developing social habits that parallel those of bats, we have not yet evolved bats' sophisticated mechanisms to combat viruses as they emerge and swiftly spread.

"The consequences may be that our bodies experience more inflammation," Gorbunova says.

The researchers also recognize that aging seems to play an adverse role in humans' reactions to COVID-19.

"COVID-19 has such a different pathogenesis in older people," Gorbunova says. "Age is one of the most critical factors between living and dying. We have to treat aging as a whole process instead of just treating individual symptoms."

The researchers anticipate that studying bats' immune systems will provide new targets for human therapies to fight diseases and aging. For example, bats have mutated or completely eliminated several genes involved in inflammation; scientists can develop drugs to inhibit these genes in humans. Gorbunova and Seluanov hope to start a new research program at Rochester to work toward that goal.

"Humans have two possible strategies if we want to prevent inflammation, live longer, and avoid the deadly effects of diseases like COVID-19," Gorbunova says. "One would be to not be exposed to any viruses, but that's not practical. The second would be to regulate our immune system more like a bat."

Credit: 
University of Rochester

Aquaculture's role in nutrition in the COVID-19 era

Aquaculture, the relatively young but fast-growing industry of farming of fish and other marine life, now produces around half of all seafood consumed by humans. A new paper from American University published today examines the economics of an aquaculture industry of the future that is simultaneously environmentally sustainable and nutritious for the nearly 1 billion people worldwide who depend on it for health and livelihoods.

Of the scenarios the paper discusses, included are two approaches that illustrate what aquaculture might look like if nations refocus inward for food and nutrition security in the COVID-19 era.

"Seafood is essential to meeting global food and nutrition security goals," said Jessica Gephart, the paper's primary author and an assistant professor of environmental science at American University. "Under what circumstances, and with what policies, can we maximize aquaculture for its nutrition benefits and sustainability for all who rely on seafood?"

This is a challenging question to answer, especially in the COVID-19 era. As the pandemic is still unfolding, the full scope of long-term damage to food systems is unknown, the paper notes. Yet, the aquaculture industry is suffering major setbacks, as some exports are being halted, workers are being laid off, demand has dramatically decreased, production units are incurring large losses and some countries are reconsidering their reliance on foreign seafood. The authors note that such setbacks "can be particularly long-lasting for a budding sector, with many young farms that potentially lack the capital to weather the storm and the political clout to secure sufficient recovery aid."

The demand for seafood is expected to increase significantly by 2050, the paper notes, if historical trends in income and population growth, urbanization, and diets are maintained. This has prompted researchers to contemplate the future role of aquaculture in meeting demand and supporting nutrition needs. "Nutrition sensitivity" refers to the multiple benefits derived from diverse foods, including improving nutrition, valuing the social significance of food, and supporting livelihoods.

For aquaculture, this means a food system that supports public health through production of diverse seafood, provides multiple, rich sources of essential nutrients, and supports equitable access to nutritious, safe, and culturally acceptable diets that meet food preferences for all populations, without compromising ecosystem functions, other food systems, and livelihoods.

The paper describes and discusses four possible scenarios for the future of the growth of aquaculture, with the first two outlining what an inward approach might look like. Elements of each of these scenarios exist in current production systems from around the world:

Growth-first, nationalistic approach. In this scenario, countries throughout the world turn inward for economic growth and focus on supporting national industries to meet seafood demand. Overall, diversity of seafood available in each country generally declines. Countries with mature aquaculture sectors that already supply a diversity of production technologies, species and product types will continue to meet some nutritional needs, but for a narrower range of consumers and at increased cost, and to a more limited extent.

Sustainable growth, localized approach. In this approach, countries throughout the world adopt sustainable local food production approaches focused on small-holder production. While some traditional production systems are highly productive, in general, global aquaculture production grows at a relatively slow rate - if at all - and total production is relatively low. Countries that have retained a cultural history of developing small-scale aquaculture will see an increase in these production systems, supported by government-backed schemes and extension services. When production is at the household scale, women are more likely to play a key role, increasing the likelihood that nutritional benefits flow directly to the most vulnerable.

Sustainable growth, globalized world. The world fully embraces the application of sustainable development principles, taking advantage of the benefits of globalized food systems while strengthening environmental governance. Global competition and high levels of technology transfer lead to relatively high global inland and marine seafood production. Favoring production of seafood in line with local environmental contexts, this world leads to moderate global species diversity. High global seafood production and low trade barriers enable low seafood prices, improving seafood access in urban areas and areas with transportation infrastructure connections and access to electricity for refrigeration.

Growth first, globalized world. In this scenario, the world moves toward further economic globalization and encourages boundless economic growth. Through genetic selection and modification, as well as technological innovations, the aquaculture industry develops intensive production systems with limited environmental regulation. Production systems rely on globalized supply chains, sourcing feed ingredients internationally, and taking advantage of low labor costs for processing. Through competition, massive production of only a few species results, which are highly traded and spread rapidly (akin to the dominance of four species in the meat market, led by chicken). Targeted policy interventions would be necessary to help nutritionally vulnerable populations.

Credit: 
American University

Teva presents latest data on AJOVY® ▼ (fremanezumab) at EHF Congress

AMSTERDAM, NETHERLANDS - Teva Pharmaceutical Europe B.V. has presented results from a pooled analysis of three randomized, double-blind, placebo-controlled Phase 3 studies assessing AJOVY® ▼ (fremanezumab), indicated for the preventative treatment of migraine in adults, which demonstrate clinically significant reductions in headache and migraine-related disability in the majority of patients studied.

The findings, presented at the 14th European Headache Federation (EHF) Congress, show that by comparison to placebo, individuals receiving fremanezumab treatment experienced a downward shift in disability severity, as defined by the validated HIT-6 and MIDAS assessment tools. At baseline, 87-89 per cent of patients had severe impact on HIT-6 and 74-75 per cent of patients had severe disability on MIDAS. In this analysis, the proportion of patients experiencing a downward shift of between 1 and 3 categories in severity of headache impact on HIT-6 was significantly greater than placebo with both doses of fremanezumab (47 to 50 per cent) versus placebo (33 per cent). Similarly, the number of patients experiencing a downward shift of 1, 2 or 3 grades in disability severity according to MIDAS scores was significantly greater with fremanezumab (55 to 58 per cent) versus placebo (40 per cent).

A parallel analysis assessed clinically meaningful improvements in HIT-6 and MIDAS scores in line with a recent American Headache Society (AHS) consensus statement. According to AHS, a ? 5 point reduction on HIT-6 is clinically meaningful, and this was achieved by 53-55 per cent of fremanezumab-treated patients versus 39 per cent of placebo patients. For MIDAS, AHS considers a ? 5 point reduction for patients with a baseline score of 11-20 or a ? 30% reduction for those with a baseline score > 20 to be clinically meaningful. The former was achieved by 70-71 per cent of fremanezumab treated patients versus 49 per cent of placebo patients, while the latter was achieved by 69-79 per cent of fremanezumab treated patients versus 58 per cent of placebo patients.

Collectively, the pooled analyses indicate that fremanezumab therapy in both quarterly and monthly regimens may result in clinically meaningful improvements particularly for patients with difficult-to-treat migraine, which can be debilitating and severely impact the quality of life for individuals.

"The personal impact of both episodic and chronic migraine cannot be underestimated," said Joshua M. Cohen, MD, MPH, FAHS, Sr. Director, Therapeutic Area Lead Migraine & Headache, Global Medical Affairs, Teva Pharmaceutical Europe B.V. "A continual need exists for new therapies which can help and support those affected and help individuals maintain a normal life where ability to work, be productive and look after families are not heavily compromised. These new analyses add to the positive data on fremanezumab and suggest it plays an important role in limiting and mitigating disability at several levels of severity, particularly for individuals who are finding their migraine difficult to treat and manage."

An additional study assessing long-term efficacy of fremanezumab in episodic and chronic migraine, also presented at the Congress, showed that over six to 15 months of long-term treatment, patients with difficult-to-treat migraine experienced progressive improvements in migraine days, with increasing numbers of patients achieving clinically meaningful response rates.

Migraine is a debilitating neurological disease that causes recurrent episodes of pain lasting 4-72 hours, often accompanied by nausea, vomiting, photophobia, phonophobia and a variety of other debilitating symptoms.

The pooled analyses follow primary results from the Phase FOCUS study in which fremanezumab was shown to significantly reduce the number of migraine and headache days of at least moderate severity as early as the first week of treatment in adult patients who had responded inadequately to two or more classes of migraine preventive therapy when compared to placebo. The proportion of patients experiencing a 50 percent or higher reduction of migraine days was also significantly greater than placebo. The incidence of adverse events (AEs) including AEs leading to treatment discontinuation and serious AEs was shown to be low and consistent with placebo.

The data presentations at EHF 2020 follow findings from the Teva-sponsored research project Beyond Migraine: The Real You survey of over 7,500 people living with the disease in Europe. The survey conducted across 10 European countries found that people living with migraine were struggling in how to better support themselves or advocate for improved disease management. The broader survey results went on to explore the often-devastating impact of migraine on all aspects of a patient's life, ranging from their relationships, work life, social life and education.

60% of people living with migraine indicated that migraine has negatively impacted their social life, their studies, work and career

40% of young people living with migraine indicate an impact on their education

Only 1 out of 8 were member of a patient support group

Of those patients who were receiving treatment from their HCP, almost 8 in 10 (77%) said that their treating doctor took their disease very seriously, but 30% felt their doctor was not sufficiently informed on the latest migraine treatments.2 One in 4 people said they would like to be more involved in decisions about their treatment.2

"While I have seen significant improvements in migraine management over recent decades, the survey data highlights the need for more work to be done to raise awareness, increase knowledge and continue to integrate a faster migraine diagnosis process" said Elena Ruiz de la Torre, Executive Director, European Migraine and Headache Alliance (EMHA).

Information for Europe about AJOVY® ▼ (fremanezumab) can be found here.

Adverse events should be reported.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events. Reporting forms and information can be found at https://www.hpra.ie. Adverse events should also be reported to Teva - please refer to local numbers.

AJOVY is available as a 225 mg/1.5 mL single dose injection in a prefilled syringe with two dosing options - 225 mg monthly administered as one subcutaneous injection, or 675 mg every three months (quarterly), which is administered as three subcutaneous injections. AJOVY can be administered in office by a healthcare professional or at home by a patient or caregiver. No starting dose is required to begin treatment. The AJOVY autoinjector has been approved by the FDA and is available in the U.S. In addition to the U.S., the AJOVY autoinjector has been approved by the EMA and is currently available in Germany and should soon be available in other select European markets.

Credit: 
Ketchum UK

Engineers design a reusable, silicone rubber face mask

image: Researchers at MIT and Brigham and Women's Hospital have designed a new silicone rubber face mask that they believe could stop viral particles as effectively as N95 masks. Unlike N95 masks, the new masks can be easily sterilized and used many times. This image shows photos of the mask (A and B) and the steps needed to clean and reuse the mask.

Image: 
MIT/Brigham and Women's Hospital

CAMBRIDGE, MA -- Researchers at MIT and Brigham and Women's Hospital have designed a new face mask that they believe could stop viral particles as effectively as N95 masks. Unlike N95 masks, the new masks were designed to be easily sterilized and used many times.

As the number of new Covid-19 cases in the United States continues to rise, there is still an urgent need for N95 masks for health care workers and others. The new mask is made of durable silicone rubber and can be manufactured using injection molding, which is widely used in factories around the world. The mask also includes an N95 filter, but it requires much less N95 material than a traditional N95 mask.

"One of the key things we recognized early on was that in order to help meet the demand, we needed to really restrict ourselves to methods that could scale," says Giovanni Traverso, an MIT assistant professor of mechanical engineering and a gastroenterologist at Brigham and Women's Hospital. "We also wanted to maximize the reusability of the system, and we wanted systems that could be sterilized in many different ways."

The team is now working on a second version of the mask, based on feedback from health care workers, and is working to establish a company to support scaled-up production and seek approval from the FDA and the National Institute for Occupational Safety and Health (NIOSH).

Traverso is the senior author of a paper describing the new masks, which appears today in the British Medical Journal Open. The lead authors of the study are James Byrne, a radiation oncologist at Brigham and Women's Hospital and research affiliate at MIT's Koch Institute for Integrative Cancer Research; Adam Wentworth, a research engineer at Brigham and Women's Hospital and a research affiliate at the Koch Institute; Peter Chai, an emergency medicine physician at Brigham and Women's Hospital; and Hen-Wei Huang, a research fellow at Brigham and Women's Hospital and a postdoc at the Koch Institute.

Easy sterilization

The N95 masks that health care workers wear to protect against exposure to SARS-CoV-2 and other viruses are made from polypropylene fibers that are specially designed to filter out tiny viral particles. Ideally, a health care worker would switch to a new mask each time they see a different patient, but shortages of these masks have forced doctors and nurses to wear them for longer than they are meant to be worn.

In recent months, many hospitals have begun sterilizing N95 masks with hydrogen peroxide vapor, which can be used up to 20 times on a single mask. However, this process requires specialized equipment that is not available everywhere, and even with this process, one mask can be worn for only a single day.

The MIT/BWH team set out to design a mask that could be safely sterilized and reused many times. They decide on silicone rubber -- the material that goes into silicone baking sheets, among other products -- because it is so durable. Liquid silicone rubber can be easily molded into any shape using injection molding, a highly automated process that generates products rapidly.

The masks are based on the shape of the 3M 1860 style of N95 masks, the type normally used at Brigham and Women's Hospital. Most of the mask is made of silicone rubber, and there is also space for one or two N95 filters. Those filters are designed to be replaced after every use, while the rest of the mask can be sterilized and reused.

"With this design, the filters can be popped in and then thrown away after use, and you're throwing away a lot less material than an N95 mask," Wentworth says.

The researchers tested several different sterilization methods on the silicone masks, including running them through an autoclave (steam sterilizer), putting them in an oven, and soaking them in bleach and in isopropyl alcohol. They found that after sterilization, the silicone material was undamaged.

Fit test

To test the comfort and fit of the masks, the researchers recruited about 20 health care workers from the emergency department and an oncology clinic at Brigham and Women's Hospital. They had each of the subjects perform the standard fit test that is required by the Occupational Safety and Health Administration (OSHA) for N95 masks. During this test, the subject puts the mask on and then performs a series of movements to see if the mask stays in place. A nebulized sugar solution is sprayed in the room, and if the subject can taste or smell it, it means the mask is not properly fitted.

All 20 subjects passed the fit test, and they reported that they were able to successfully insert and remove the N95 filter. When asked their preference between the new mask, a typical N95 mask, and a standard surgical mask, most either said they had no preference or preferred the new silicone mask, Byrne says. They also gave the new mask high ratings for fit and breathability.

The researchers are now working on a second version of the mask, which they hope to make more comfortable and durable. They also plan to do additional lab tests measuring the masks' ability to filter viral particles.

As many regions of the United States have seen a surge in Covid-19 cases over the past month, hospitals in those areas face the possibility of mask shortages. There is also a need for more masks in parts of the world that don't have the equipment needed for hydrogen peroxide sterilization.

"We know that Covid is really not going away until a vaccine is prevalent," Byrne says. "I think there's always going to be a need for masks, whether it be in the health care setting or in the general public."

Credit: 
Massachusetts Institute of Technology

Biologists trace plants' steady mitochondrial genomes to a gene found in viruses, bacteria

image: Arabidopsis plant that lacks functional copies of MSH1. Researchers investigated the role of this gene in mitochondrial genome stability.

Image: 
Dan Sloan/Colorado State University

One could say that mitochondria, the energy-producing organelles inside every human cell, dance to their own beat. After all, they have their own genome ­­- a set of DNA-containing chromosomes - completely separate from the genome of the cell's nucleus.

Mitochondria are essential to life because they power the cell's biochemical reactions, but they make a lot of missteps - that is, their genomes do. Human mitochondrial genomes are notoriously prone to mutation, which is why so many genetic disorders - from diabetes mellitus to mitochondrial myopathy - are linked to malfunctioning genes in this organelle.

Seeking to understand why human mitochondrial genomes mess up so much, Colorado State University biologist Dan Sloan thinks we have a lot to learn from our very distant evolutionary cousins - plants. Like us, plants maintain a separate mitochondrial genome, but unlike us, plant mitochondrial genomes have some of the slowest known mutation rates of any living thing - about one mutation at each DNA position in a billion years. Just how they keep their genetic sequences on lockdown, while we don't, has long been a mystery for many biologists.

Sloan is funded by a grant from the National Institutes of Health to investigate why plants have such stable mitochondrial genomes, and his lab has recently come across a tantalizing lead. They have traced this stability to a particular gene - MSH1 - that plants have but animals (including us) don't. Their experiments, described in Proceedings of the National Academy of Sciences, could lend insight into why animal mitochondrial genomes tend to mutate, possibly leading to breakthrough therapies to prevent such mutations.

"Understanding how some systems have been able to maintain these really accurate, low mutation rates, sets up the opportunity for understanding the flip side of the coin - how it is that humans suffer such high mitochondrial mutation rates," said Sloan, associate professor in the Department of Biology. "It's not as simple as just the nasty chemistry going on inside these mitochondrial compartments, as some have thought. It probably comes down to more differences between organisms' error correction machinery. That's one of the punchlines that comes out of this research."

The researchers tested several plant genes they thought might be responsible for mitochondrial genomic stability. They found that disrupting the MSH1 gene in a common plant, Arabidopsis thaliana, led to massive increases in frequency of point mutations and changes to the mitochondrial DNA. MSH1, it turns out, contains molecular features that may make it able to recognize mismatches of nucleotide base pairings during the process of DNA copying. They researchers plan to follow up on this hypothesis in later studies.

The MSH1 gene exists in plants, but not animals, which offers a good explanation for why human mitochondrial genomes mutate so often. The researchers then asked, where did this gene come from?

To find an answer, undergraduate researcher and paper co-author Connor King set out to explore the distribution of the gene across the tree of life. He computationally mined nucleotide and protein sequence repositories to find what species have the gene. He found evidence of the gene not only in plants but also in many lineages of complex organisms, including single-celled eukaryotic organisms, as well as some prokaryotic and viral species.

King's analysis raises the possibility that the gene came from so-called giant viruses that have genomes almost the size of bacteria, and are much more complex than typical viruses. They may have been shared with other organisms via an ancient horizontal gene transfer, in which one species transfers DNA into another.

"Connor's results pretty clearly tell us that this gene has been transferred around different parts of the tree of life," Sloan said. This insight would be consistent with the idea that some organisms manage to borrow machinery from viruses and replace it with their own.

The study was made possible by advanced DNA sequencing, in which huge amounts of DNA can be mined to find very rare mutations. A key enabling innovation was led by graduate student and co-author Gus Waneka, who customized a technique called duplex sequencing to increase its accuracy within the margin of error the team needed to draw their conclusions.

Credit: 
Colorado State University

Researchers explore new approaches to support work practices in homeless shelters

Researchers from Bentley University, in partnership with Pine Street Inn, New England's largest homeless shelter, have been exploring the ideas of process modeling to better understand and improve triage practices at homeless shelters. Conventional wisdom places the sequencing of standard tasks at the center of process models. In contrast, work in homeless shelters requires customizing work processes in response to individual guests.

By constructing a model of the triage work at the homeless shelters, the researchers demonstrate the need for this approach. The study illustrated challenges such as discretionary tasks and varying knowledge intensity, and explored an emerging technique that corresponds to the reality of triage work in the homeless shelters.

"A modeling approach that focused on the individual guests, providing options and tools to the employees and volunteers at the homeless shelter shows clear promise," says Dr. Sandeep Purao, a professor of information and process management and one of the lead researchers. A technique called CMMN (case management and modeling notation) has emerged over the last few years with industry backing and tool support that has the potential to support such work. "There are many approaches and tools that are developed in the for-profit domain that can be useful in humanitarian settings," says Dr. Monica Garfield, a computer information systems professor who also participated in the study.

The results of this work were published at the European Conference on Information Systems in June 2020. The team will continue the work by combining on-the-ground studies of work practices at homeless shelters and developing additional models and tools to support this work.

The work is important because homelessness continues to be a significant concern in the US. The 2019 Annual Homeless Assessment Report (AHAR) to Congress shows that 567,715 people - about 17 of every 10,000 - were experiencing homelessness across the United States. The homeless shelters represent the first line of defense for preventing homelessness. Understanding, improving and supporting work practices at the shelters can, therefore, have a direct impact on the problem.

Credit: 
Bentley University