Culture

For a caterpillar, a green leaf can make a nice meal. But to the plant itself, it's an attack. And very hungry caterpillars can do a lot of damage as they eat their way through life.

Plants can fight back, unleashing an array of chemical defenses to discourage wayward foragers -- from releasing chemicals that attract caterpillar predators to secreting compounds that make the plant taste so foul that desperate caterpillars resort to cannibalism. But scientists know little about how plants detect these attacks and marshal defenses.

In a paper published Nov. 23 in the Proceedings of the National Academy of Sciences, a team led by scientists at the University of Washington and the University of California, San Diego reports that cowpeas -- a type of bean plant -- harbor receptors on the surface of their cells that can detect a compound in caterpillar saliva and initiate anti-herbivore defenses.

"Despite chemical controls, crop yield losses to pests and disease generally range from 20-30% worldwide. Yet many varieties are naturally resistant or immune to specific pests," said lead author Adam Steinbrenner, a UW assistant professor of biology. "Our findings are the first to identify an immune recognition mechanism that sounds the alarm against chewing insects."

The receptor is a protein known by the acronym INR. The team showed that, in response to both leaf wounds and the presence of a protein fragment specific to caterpillar saliva, the cowpea's INR protein boosts the production of ethylene, a hormone that plants often produce in response to munching by herbivores and other types of environmental stress. The protein fragment in caterpillar spit that elicited this response, Vu-IN, is actually a fragment of a cowpea protein, which gets broken down by the caterpillar as it dines on cowpea leaves.

Researchers have fewer methods to study cowpeas compared to other plants. So to learn more cellular details about INR's function, they popped the gene for INR into tobacco plants. These tobacco plants, when exposed to Vu-IN, increased production of ethylene as well as reactive oxygen species, another anti-herbivore defense that consists of chemically reactive forms of oxygen. In addition, the team's experiments showed that a tobacco-eating caterpillar -- the beet armyworm -- munched less on INR-harboring tobacco plants than plants without INR.

The research shows that plants like the cowpea sound the alarm only after their cells detect specific molecules associated with herbivory. Vu-IN is a trigger for cowpea defenses. Other plants likely have different molecular triggers for their own defensive systems, the researchers believe.

Understanding how plants activate their immune systems could help scientists develop more effective strategies to defend crop plants against hungry insects.

LA JOLLA, CA--As the consumer genetics industry rapidly expands, more and more people are turning to DNA-based services to learn their risk of developing a wide range of diseases.

However, the risk scores from these genetic tests are not always as precise as they could be, according to a new study from Scripps Research. The scientists, whose research appears in the journal Genome Medicine, examine many approaches to calculating the scores and recommend that personal genomics organizations adopt standards that will raise the bar for accuracy.

"Polygenic risk scores can be incredibly useful and affordable tools to guide preventative health decisions," says the study's senior author Ali Torkamani, PhD, director of Genomics and Genome Informatics at Scripps Research Translational Institute and Associate Professor of Integrative Structural and Computational Biology at Scripps Research. "Given the increasing utility of these scores, it's important to remove variability as much as possible and ensure the data is updated regularly to reflect new knowledge from genomic studies."

Companies such as 23andMe and Ancestry--along with dozens of others--need only a small sample of a person's saliva to generate estimations known as "polygenic risk scores," which are determined by comparing snippets of an individual's DNA with findings from large-scale genome studies. Examining these small segments of genomic variation, known as SNPs, is faster and far more economical than sequencing a person's entire genome. But one drawback is that the results can sometimes vary unexpectedly.

Torkamani notes that in most cases, the degree of fluctuation in a risk score is small and doesn't change the overall interpretation of the result; most individuals remain in the same risk category. Also, fluctuations are especially minor at the extremes of the risk distribution, where disease risk implications are most critical. Yet any variation can lead to a loss of consumer confidence in these important scores, and that can undermine preventative health. And in some rare cases, the scores can fluctuate substantially.

For their study, Torkamani and his team used various methods of calculating polygenic risk scores for conditions including coronary artery disease, atrial fibrillation, type 2 diabetes, Alzheimer's disease, glaucoma and breast cancer. They found that regardless of the method used, the computational algorithms are prone to introduce random variability for individuals due to how the calculations incorporate data from population-level genetic studies.

To reduce variability in individual polygenic risk scores, the team recommends running the algorithms multiple times, which would help smooth out random imperfections. By paying attention to variable elements in a score calculation, actions can be taken to either eliminate those elements or create an average, Torkamani explains.

"While we identified some clear challenges in applying population genetics tools to individual-level genetic analysis, we also see ways to overcome these issues to produce results that will inspire confidence," he says.

He and his team decided to pursue the study after making updates to different project they developed called MyGeneRank, which predicts risk of heart disease and other conditions by looking at specific genetic markers. They sought to identify a computational process that would lead to the greatest degree of stability and accuracy in the face of a score that is expected to evolve over time as new data becomes available.

The recommendations put forth in the new study could help personal genomics companies improve the quality of the scores they deliver to customers--and ultimately, encourage more individuals take smart preventative health actions based on what they learn in genotyping reports.

LA JOLLA, CA--A new study on Alzheimer's disease by Scripps Research scientists has revealed a previously unknown biochemical cascade in the brain that leads to the destruction of synapses, the connections between nerve cells that are responsible for memory and cognition.

The findings present a fresh angle for discovering drugs that treat Alzheimer's disease, which affects roughly 50 million people worldwide. The study, led by Scripps Research Professor and Step Family Foundation Endowed Chair Stuart Lipton, MD, PhD, appears in the journal Science.

This newly-discovered series of abnormal chemical events, termed "protein transnitrosylation reactions," contribute to synapse loss, the main driver of memory loss and cognitive decline in Alzheimer's.

Lipton, who is also a clinical neurologist, explains that most recent attempts to develop Alzheimer's treatments have targeted the sticky protein known as beta amyloid that accumulates in the brain of patients, disrupting cell communication and causing inflammation. However, for a variety of reasons, these attempts have failed in clinical trials.

"This work gives us new hope for better therapeutic targets, as the reactions we discovered are downstream of amyloid action," Lipton says. "We've opened up a whole new avenue for drug development."

Lipton is no stranger to drug development for Alzheimer's and Parkinson's diseases. Drugs developed in and patented by his laboratory have led to four FDA-approved medicines for these diseases, including the widely prescribed drug, memantine (Namenda®). "Much better drugs are needed, however," Lipton says.

A chemistry success story

In the new study, Lipton and his team used physical chemistry techniques to quantify how electrons participate in chemical reactions, as they suspected unknown processes may be taking place in the brain. Through this, they uncovered the entirely new series of biochemical events in nerve cells affected by Alzheimer's.

They found that small clumps of beta amyloid protein trigger excessive neuron activity and inflammation, leading to the destructive series of transnitrosylation reactions.

The process begins with excessive levels of nitrogen (N) and oxygen (O) atoms joining together as an "NO group," which is then transferred to a protein building block called cysteine to regulate the activity of the protein. A series of these aberrant protein reactions cuts off energy to the brain's nerve cells by disrupting their mitochondria--organelles that generate power for the cell's biochemical reactions. This eventually leads to loss of synapses connecting the nerve cells.

"We were able to show that these reactions occur in brains of Alzheimer's patients, and when we prevented these reactions in the brains of animal models of the disease, we protected the synapses," Lipton says. "Our findings suggest that it may be possible to intercede to reverse synapse damage in spite of plaques and tangles," he added, referring to "plaques" of beta amyloid and "tangles" of misfolded tau protein, both of which are characteristic of Alzheimer's disease.

He notes that while normal levels of NO foster memory and learning, excessive levels can build up as we age and become harmful to synapses.

"With this new knowledge, we may be able to restore synaptic connections in Alzheimer's patients after extensive plaques and tangles have formed in their brains," adds Tomohiro Nakamura, PhD, senior staff scientist in the Lipton laboratory group and first author of the study.

Revealing secret connections

Lipton says that one of the team's most incredible findings was that the three enzymes discovered to pass NO to each other along a concerted chain of events, resulting in energy failure, were previously not thought to be even remotely related to one another. Each of the enzymes is important in its own right in a completely disparate normal biochemical pathway, and yet they interact under disease conditions in a novel manner to trigger intense neuronal stress and synapse damage.

"This type of hidden or 'ghost' pathway may only become evident under disease conditions and may represent an important fundamental tenet of why we did not understand the disease process previously," Lipton says. "If we do not know about a pathway, scientists cannot study its contribution to disease or develop drugs to treat it."

While many molecular biochemical pathways have been discovered, an over-reliance on this existing body of evidence can actually impede discovery of disease processes, he adds.

"Hence, the most important aspect of the work is that we have to be on our guard to look for new pathways and new relationships of existing enzymes in order to understand and treat neurodegenerative disorders such as Alzheimer's," Lipton says.

Many everyday foods--from yogurt and other fermented foods to fresh fruits and vegetables--contain live microorganisms. And although humans have consumed these safe and potentially beneficial bacteria in their daily diets for millennia, live microbes have received much less attention than other components of the diet. With a rising global awareness of the importance of gut health, many people believe intake of live microbes is health-promoting, but so far it has not been possible for experts to create a guideline on how many we should be consuming on a daily basis.

A group of seven interdisciplinary scientists recently published a review paper in The Journal of Nutrition, titled: Should There Be a Recommended Daily Intake of Microbes? They explain that only weak evidence to date confirms the link between live microbes and better human health, highlighting specific gaps in the research and laying out a plan for quantifying the relationship between consumption of live microbes and health outcomes across populations.

In the review, the authors outline why this scientific endeavour is worthwhile, but far from straightforward. Challenges include the scant records on consumption of microbes in past human populations; frequent mis-reporting of dietary intakes in current nutrition research; and the complex biology of the digestive tract, which makes the mechanisms of microbial health benefits difficult to discover.

"People frequently hear that they should keep adding 'good microbes' to their gut microbiomes," says Dr. Mary Ellen Sanders, co-author of the paper and Executive Science Officer of the International Scientific Association for Probiotics and Prebiotics (ISAPP). "This makes intuitive sense, but it's important to build up the scientific evidence for the idea rather than just assume this is true. Our paper is a call for scientists around the world to start building the evidence base in a rigorous way."

The publication builds on a discussion group held at the 2019 ISAPP annual meeting in Belgium, which aimed to explore evidence that live microbes in general - and not only the bacterial strains that have special status as probiotics - form an essential part of the human diet.

"Currently, food guides around the world do not recommend daily intake of live microbes," says Sanders. "Although continual doses of live microbes may not be critical for our survival, by ignoring them we may be missing out on an important opportunity to support the health of different populations."

What The Study Did: State crisis standards of care (CSC) guidelines in the U.S. allocate scarce health care resources among patients, and this study examined the implications of these guidelines for patients with cancer, including allocation methods, cancer-related categorical exclusions and deprioritizations, and provisions for blood products and palliative care.

Authors: Gregory A. Abel, M.D., M.P.H., of the Dana-Farber Cancer Institute in Boston, is the corresponding author.

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

(doi:10.1001/jamaoncol.2020.6159)

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

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Children grow taller in rural households where their mothers are supported to grow their own food - according to new research from the University of East Anglia (UEA).

The research, which looked at households in low- and middle-income countries, showed growing their own food helped mothers to prevent stunting, wasting and underweight in their children. Their children's food was more varied, meaning they had access to different classes of food nutrients.

The study, 'Impact of home food production on nutritional blindness, stunting, wasting, underweight and mortality in children: a systematic review and meta-analysis of controlled trials', is published today in the journal Critical Reviews in Food Science and Nutrition.

The team from the Norwich Medical School and the School of International Development at UEA analysed studies that introduced women to home farming in African and Asian countries including Nigeria, Ghana, India, Cambodia, Mozambique, Uganda, Kenya and Burkina Faso. The home farming included growing brightly coloured Vitamin A-rich fruit and vegetables such as sweet potatoes, and sometimes also included chicken farming.

The health of these women's children was assessed over the next year or more. The children of the women who were introduced to home farming did better than children of other women, in that they were less likely to suffer from wasting, stunting and underweight.

No studies, however, reported on children's eye health. The researchers concluded that high-quality trials are needed to assess the impact of home food production on nutritional blindness in children, especially in rural areas.

Xerophthalmia is abnormal dryness and inflammation of the eye, leading to irreversible blindness, and is predominantly caused by an insufficient intake of Vitamin A. Vitamin A supplementation prevents children from dying and improves their health in other ways, such as reducing the risk from measles. Many countries run Vitamin A supplementation programmes for children, but these often leave out children in rural areas.

Approximately 250 million preschool children are still Vitamin A deficient, according to the World Health Organization. Vitamin A deficiency is the main global cause of preventable childhood blindness with about 2.8 million preschool-age children at risk of blindness. Vitamin A deficiency also increases the risk of mortality from other childhood diseases, such as diarrhoea and measles, and plays a significant role in normal immune function. It remains one of the most prevalent micronutrient deficiencies globally.

Mrs Chizoba Bassey, a postgraduate researcher in UEA's Norwich Medical School, led the team conducting the systematic review.

Mrs Bassey said: "Well-evidenced interventions such as Vitamin A supplementation programmes should be adopted and expanded to children at greatest risk to prevent nutritional blindness.

"Currently there is not enough evidence of the effects of home gardening on xerophthalmia, night blindness or mortality in children, but the evidence from our research shows that if women take up home gardening the risk of stunting, wasting and underweight in their children is reduced.

"The introduction of home food production may be appropriate in areas where nutritional blindness, underweight, stunting and wasting are prevalent and where more intensive nutritional support, such as Vitamin A supplementation programmes, are not available."

Home farming may help to achieve sustainability in controlling Vitamin A deficiency and can complement Vitamin A supplementation programmes where they are available.

Allowing families to choose schools that are more suited to their children may play a key role in improving student mental health, including reducing adolescent suicide rates, suggests new research published in the peer-reviewed journal School Effectiveness and School Improvement.

The study is the first of its kind to examine the relationship between U.S. school choice policies and teen suicide and mental health issues.

U.S. states are expanding private school options through charter schools--which are publicly funded but granted charters to operate outside many of the regulations of regular neighbourhood schools--and voucher programs for students to attend a private school of choice. More than 6% (over 3.1 million) of all public school students attend charter schools, and over 5.7 million students attend private schools [1]. However, little is known about whether these choices affect students' mental health.

The U.S. National Institute of Mental Health estimates that around half of teenagers (aged 13-18 years) will experience a mental health disorder in their lifetime. Between 2007 and 2015, suicide rates doubled among girls aged 15-19 years, and rose by 30% in boys of the same age. Suicide is the second leading cause of death in Americans aged 15-34 years old, and the third in those aged 10-14 years.

To examine the relationship between school choice and adolescent suicide and the impact of private schooling on adult mental health, researchers analysed public and private school data from 49 states between 1976 and 2016, coupled with nationally representative data from 4,353 students participating in the 1997-1998 cohort of the National Longitudinal Survey of Youth (who were followed up for around 15 years).

The findings suggest that states adopting voucher and charter school choice laws witnessed declines in suicide rates among young people, even after accounting for demographic (e.g., age, race) and economic (e.g., unemployment rate, percentage of state below poverty line) factors. The researchers estimate that the effect of the charter school law translated to around a 10% decline in the suicide rate among 15 to 19-year-olds.

Further analyses of survey data suggest that private schooling was associated with better mental health in adulthood, even after controlling for important sociodemographic and health factors including gender, parental education level, household income, race, and measures of mental health near the start of the study.

Compared with public schools, individuals attending private school were about 2 percentage points less likely to report having a mental health condition at around 30 years old, and to be treated for a mental illness.

"Our findings raise the question of whether increased school choice could improve students short- and long-term mental health", says Professor Angela Dills from Western Carolina University, NC, USA who co-led the research. "It's likely that private schools face stronger competitive pressures to provide a safer school environment and improve mental health if they want to remain open. Public schools, on the other hand, are more likely to be burdened with government regulations that make it difficult for them to control discipline policy and create strong school cultures."

According to co-lead author Corey DeAngelis from the Reason Foundation in Washington, DC, USA: "Our results suggest that expanding school choice could help address the roots of the student mental health problem. Unfortunately, many students are stuck in unhealthy or unsafe school environments, which can have extremely harmful effects on their mental health. With further research the mechanisms that promote mental health in charter schools and private schools could be identified."

Published today in The Lancet Public Health, a study by researchers at King's College London research team detail the modelling behind the ZOE COVID Symptom Study App.

They found that self-reported data from over 2.8 million volunteer users of the app living in England, including more than 120 million daily assessments logged by those users, can be used to provide accurate estimates of COVID-19 prevalence and incidence, and timely identification of regional infection hotspots.

Joint first author Dr Mark Graham from King's College London said: "The data accurately predicted many of the hotspots that were significantly affected by the second wave, including detecting Leicester in June which then became the first region to be placed under local lockdown. In mid-July they detected many regions around Manchester, which was also placed under local restrictions in late July. The data will also likely prove valuable for detecting regional hotspots if we experience a third wave after lockdown is eased.

"The reduced reliance on PCR tests means this could be a cost-effective, complementary and rapid way for governments to monitor the spread of COVID-19 and identify potential areas of concern. Detection of hotspots should encourage additional testing capacity to be focused on these regions, to ensure as many new cases are captured as possible and onwards transmission chains broken."

The study's joint first author Thomas Varsavsky from King's College London said: "We also found that regions where more tests are being carried out have better agreement with our predictions of incidence. We hope that this can inform policy makers about which areas would benefit from additional testing, thus detecting hotspots earlier."

Researchers found that one advantage of the app is the data is released every day, while ONS is released weekly and REACT every few weeks - this means that the app team might be able to pick up changes in incidence or prevalence earliest with their data.

"Our results show that a mobile-based approach detects similar incidence and prevalence to the more traditional but less cost effective ONS/REACT-1 approaches, which is encouraging," Dr Graham said. "To make better public health decisions, the ZOE Covid Symptom Study data should be seen as a complementary data source to ONS and REACT. Like all the surveys, our sample is not fully representative of the population, and while the team seek to address this with our modelling, the results need to be interpreted with this in mind."

Professor Sebastien Ourselin, lead senior author from King's College London said: "Using the data from the ZOE COVID Symptom Study App as an adjunct to other sources of information means that we can equip communities with the most up to date and reliable information with which the best actions can be taken to tackle the pandemic. Earlier identification of hotspots, more information on prevalence and incidents builds a stronger defence in conjunction with the latest data being released."

A new study by Johns Hopkins Medicine researchers of adults hospitalized for the eating disorder anorexia nervosa has strengthened the case for promoting rapid weight gain as part of overall efforts for a comprehensive treatment plan. The study findings, after analyzing data regarding 149 adult inpatients with anorexia nervosa in the Johns Hopkins Eating Disorders Program, stand in contrast to long held beliefs that patients would not tolerate a faster weight gain plan because it would be too traumatic.

In a report on the work published online Oct. 7 in the International Journal of Eating Disorders, researchers say a majority of patients not only tolerated the regimen, they also met their weight gain goals in weeks rather than months, they would recommend the program to others and they would be willing to repeat it, if needed.

A form of self-starvation, anorexia nervosa is a serious psychiatric disorder in which people feel fat or fear gaining weight despite being very underweight. Over time, people with anorexia experience physical, psychological and social complications with a high risk of long-term consequences that can include heart, kidney and liver damage, bone loss, depression and self-harm. Anorexia has one of the highest mortality rates of any psychiatric condition.

The investigators say their findings also suggest that inpatient eating disorder programs that focus on rapid weight gain can minimize a patient's time away from home, work and family, help curb treatment costs by reducing lengths of stay in a hospital or residential treatment program and be rated helpful by most patients.

"Treating anorexia is expensive due to the high cost of inpatient and residential treatment, and the cost of health care is important to both patients and health systems," says Angela Guarda, M.D., director of the Eating Disorders Program at The Johns Hopkins Hospital. Guarda is also the Stephen and Jean Robinson Associate Professor of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. "Our findings suggest that a meal-based nutritional approach that emphasizes faster weight gain coupled with different types of behavioral therapy and meal support is well tolerated and achieves weight restoration in a majority of patients."

Earlier work by Guarda and others countered the belief that patients with anorexia need to gain weight slowly to avoid a potentially life threatening condition called re-feeding syndrome, which is a metabolic imbalance that can occur when severely malnourished people take in too much food or drink. Despite these safety studies, clinicians are still reluctant to implement rapid re-feeding strategies, combined with behavioral treatment approaches, because they fear that patients won't endure them. With the new study, Guarda and her team sought the patients' perception of the Johns Hopkins rapid re-feeding program.

For the study, researchers analyzed information gathered on 134 women and 15 men, averaging 35 years of age, who were treated and discharged from the integrated inpatient-partial hospitalization eating disorders program at The Johns Hopkins Hospital between February 2014 and June 2017. They were underweight when admitted to the program and placed on a regimen emphasizing faster weight gain, balanced meals and behavioral therapies designed to prevent relapses. The program aims to normalize eating and weight control behaviors, encourage healthier eating habits and help patients overcome their anxieties about eating a variety of foods.

More than 70% of the patients in the study reached a healthy body mass index (BMI). BMI is a measure of body fat based on height and weight. For most adults, a healthy BMI is between 18.5 and 24.9. Patients in the study achieved an average BMI of at least 19, which is within the healthy range, compared to an average of 16.1 at the beginning of the program. The average hospital stay was just 39 days, and patients gained 4 pounds per week on average -- "close to twice what many intensive treatment programs achieve, which means half as much hospital time is needed to reach a healthy weight," says Guarda.

Upon hospital discharge, patients were invited to complete an anonymous questionnaire to rate their satisfaction with the treatment. Some 107 participants (72%) completed the questionnaire. Overall, 71% of respondents said they would come back if they needed help with their eating disorder in the future, while 83% would recommend the program to others.

Like faster weight gain, Guarda explains, behavioral management is often criticized by clinicians as poorly tolerable by patients. However, the program's focus on behavior change was rated good or very good by 83% of the patients.

Participants also rated the degree to which they felt included in the treatment (78%), and their level of satisfaction with staff members (clinical nurses: 96%, occupational therapists: 99%, dietitians: 45%, social workers: 75%). Satisfaction with intervention factors (group therapies: 79%, family meetings and education: 63%) and environmental factors (comfort of units: 50%, presentation/taste of food: 36%) was also assessed.

"Our program is solely meal-based and does not employ tube feeding," says Guarda. Occupational therapists and nursing and dietician staff members assist patients in preparing and portioning meals, and in eating food prepared by others in cafeteria and restaurant settings. "We want to help our patients translate what they're learning here to a more real world environment so they can stay healthy once back at home."

According to Guarda, most patients go to inpatient programs like the one at Johns Hopkins under pressure from family members, employers or a significant other, and they are often anxious and apprehensive about entering treatment. "At the beginning, they often don't see the need to be here," she says, "but these results show that for most patients, their overall perception is positive by the end of treatment."

Guarda says she's encouraged that the field of anorexia nervosa is gradually moving toward greater and more uniform accountability about outcomes. "The standard of care should be based on evidence. Uniform, transparent reporting of weight and behavioral outcomes by treatment programs is needed so that patients, their families and referring clinicians can be more informed about treatment programs," she says.

According to the National Eating Disorders Association, 0.9% of women and 0.3% of men will develop anorexia during their lifetime.

A team of Johns Hopkins University researchers has developed a new software that could revolutionize how DNA is sequenced, making it far faster and less expensive to map anything from yeast genomes to cancer genes.

The software, detailed in a paper published in Nature Biotechnology, can be used with portable sequencing devices to accelerate the ability to conduct genetic tests and deliver diagnoses outside of labs. The new technology targets, collects and sequences specific genes without sample preparation and without having to map surrounding genetic material like standard methods require.

"I think this will forever change how DNA sequencing is done," said Michael C. Schatz, a Bloomberg Distinguished Associate Professor of Computer Science and Biology and senior author of the paper.

The new process shrinks the time it takes to profile gene mutations, from 15 days or more to just three. That allows scientists to understand and diagnosis conditions almost immediately, while saving time and money by eliminating preparation and additional analysis.

"In cancer genomics there are a few dozen genes known to increase cancer risk, but with a standard sequencing run, you would have to sequence the whole genome just to read off those few genes," Schatz said, adding that adaptive sequencing allows researchers to "pick and choose which molecules we want to read and which can be skipped."

To provide a sense of how much this invention speeds up sequencing, Schatz relates it to finding a movie on Netflix. The older, standard method of sequencing would require someone to watch every second of every movie on Netflix to find what they want. Instead, adaptive sequencing eliminates hours of watching irrelevant content by quickly recognizing unwanted movies and skipping to the next entry.

The open-source software's algorithm was written by lead author Sam Kovaka, a Johns Hopkins doctoral student. Its acronymic name, UNCALLED, stands for a Utility for Nanopore Current Alignment to Large Expanses of DNA.

It took two years to code, develop and test the software, and another year to refine it enough to produce results worthy of publication, Kovaka said.

"UNCALLED allows for unprecedented flexibility in targeted sequencing," he added. "The fact that it's purely software-based means researchers can target any genomic region with no added cost compared to a normal sequencing run, and they can easily change targets just by running a different command."

The process identifies DNA molecules as they pass through tiny electrified holes, or "nanopores," inside devices called nanopore sequencers, which are smart phone-sized versions of the bulky machines used in labs. The software reads the data and checks it against a specified genome's reference sequence within a fraction of a second. Desired molecules are allowed to pass through the pore to be fully mapped. But if an undesirable molecule is detected, the software reverses the voltage in the nanopore, physically ejecting the molecule to make room for the next.

"It's like a nightclub doorman allowing desired guests on a list to enter while rejecting the rest with a Taser," Schatz explains.

The research team performed two demonstrations of UNCALLED.

The first showed that the software was able to enhance the sequencing of 148 genes known to increase cancer risk by quickly and accurately profiling all of their variants with just a single run through a portable sequencer. The software made it possible to catalogue in real time dozens of complex structural mutations in the cancer genes that a standard run would have missed.

Then the team demonstrated how the software could selectively sequence certain species collected from an environment, such as microbes living on skin or those in pond water. By rejecting molecules from known microbes (such as E. coli), the software was able to efficiently sequence the remaining molecules, which revealed a less-understood yeast genome.

UNCALLED can operate on standard hardware used for nanopore sequencing without requiring special reagents or accelerators. The selection of genes or genomes to sequence is controlled entirely in the software and can be changed at any time.

As medical research progresses, traditional treatment protocols are being rapidly exhausted. New approaches to treat diseases that do not respond to conventional drugs are the need of the hour. In search for these approaches, science has turned to a wide range of potential answers, including artificial nucleic acids. Artificial or xeno nucleic acids are similar to naturally occurring nucleic acids (think DNA and RNA) -- but are produced entirely in the laboratory.

Xeno nucleic acids are essential for the development of nucleic acid-based drugs. To be effective, they need to be able to stably bind to natural RNA (a cellular single-stranded version of the DNA, which is essential for all body processes). However, it is unclear how, if at all, RNA hybridizes with these xeno nucleic acids. A new study by researchers from Japan sheds light on this mechanism, opening doors to the development of potentially revolutionary nucleic acid-based drugs.

In their experimental study published in Communications Chemistry, the team of the researchers was able to determine three-dimensional structures of RNA hybridization with the artificial nucleic acids serinol nucleic acid (SNA) or L-threoninol nucleic acid (L-aTNA), two of the few xeno nucleic acids capable of binding and forming duplexes with natural RNA effectively. This study was the outcome of collaboration among researchers at the Graduate School of Engineering of Nagoya University, the Graduate School of Pharmaceutical Sciences of Nagoya City University, the Exploratory Research Center on Life and Living Systems (ExCELLS) of the National Institutes of Natural Sciences, and the Graduate School of Engineering of Osaka University.

Natural nucleic acids like DNA and RNA have a sugar-phosphate "backbone" and nitrogen-based components; while the nitrogen-based components in SNA and L-aTNA remain the same, they have an amino acid-based backbone instead. SNA and L-aTNA have advantages over other artificial nucleic acids because of their simple structure, easy synthesis, excellent water solubility, and high nuclease resistance. These characteristics make them more suitable for developing nucleic acid drugs. "Since SNA and L-aTNA can bind to natural nucleic acids, we wanted to know what the key to stabilize the duplex structure between SNA or L-aTNA and RNA," states Dr. Yukiko Kamiya, the lead scientist on the study, "and therefore, we started to work on determining the three-dimensional structure."

They found that intra-molecular (within-molecule) interactions are important for keeping the helical (twisted) double-stranded structures formed of acyclic nucleic acids and RNA stable. While helical structures of natural nucleic acids are A-type, meaning that they twist towards the right, these synthetic duplex structures seemed to align in a perpendicular pattern, resulting in larger areas between each turn of the helix. In addition, they obtained triple-stranded structures consisting of L-aTNA or SNA and RNA, through "Hoogsteen base pair" interactions, as shown in Figure 1.

These findings question a lot of things we have so far believed to be fundamental in biology. Ribose, the sugar in the backbone of natural nucleic acids, doesn't seem to be necessary for forming a stable duplex, contrary to the currently accepted knowledge. Then why did nature select ribose? "This is perhaps better answered through future studies looking at the helical structure," says Dr. Kamiya.

For now, her team is happy that their findings open up more drug development avenues. "The structural understanding of these duplexes can help us come up with novel designs of nucleic acid-based drugs. We hope that through these findings, the development of nucleic acid drugs will accelerate," she says.

These insights, of course, go beyond medical applications. Nucleic acids are the blueprints of the "construction" of all living organisms, but we realize that many of their secrets are still uncovered. These findings shed light on a small but significant chapter of nucleic acids.

New Curtin University research has found southern Australian long-finned pilot whales are able to mimic the calls of its natural predator and food rival - the killer whale, as a possible ploy to outsmart it.

The study is the first published research analysing the calls of long-finned pilot whales in the Southern Hemisphere, which were recorded in the Great Australian Bight, off WA and SA, between 2013 and 2017.

The research, published in Scientific Reports, also found evidence of 'duetting', which is common in birds and primates but very rarely reported in aquatic mammals, and which suggests the whale's sophisticated acoustic communication system is more complex than previously thought.

Lead author Rachael Courts from Curtin's Centre for Marine Science and Technology said the study of long-finned pilot whales off southern Australia showed what appeared to be mimicry of a call of the Australian killer whale.

"This mimicry may be a clever strategy employed by the whales in order to disguise themselves from predators including killer whales. It may also allow them to scavenge food remnants from killer whales, undetected," Ms Courts said.

"Duetting refers to coordinated and patterned singing by two animals and is related to social bonding and coordination of behaviour.

"Some long-finned pilot whale calls were found to be remarkably similar to those of the same species in the Northern Hemisphere, which is surprising as non-equatorial aquatic mammals such as these are not expected to cross the equator for large-scale migrations, meaning the last contact the two hemispheres' populations could have had would have been more than 10,000 years ago.

"Our findings therefore raise the question of how far these two populations' home ranges really extend and now that we have some of their call repertoire documented, we can monitor home ranges with remote underwater sound recorders such as those used by many countries, including Australia."

Professor Christine Erbe, Director of Curtin's Centre for Marine Science and Technology, said the research was not only the first to be published on the calls of long-finned pilot whales off southern Australia but also the first in the entire Southern Hemisphere. Previous studies have only focussed on waters off the US, Canada and Europe.

"Our research discovered three unique vocalisations recorded from southern Australian long-finned pilot whales, which have not been reported for the species," Professor Erbe said.

"These were very complex multi-component calls much like killer whale calls, but given this is the first southern hemisphere study, we don't know how common the calls might be in other Southern Hemisphere pilot whales. This aspect could be the focus of future research."

A team of scientists from Hokkaido University has suggested that marimo maintain their characteristic spherical shape due to the rarity of the formation of reproductive cells.

The marimo is the aggregative form of the freshwater alga Aegagropila linnaei. In Japan, Lake Akan in Hokkaido is the best known habitat of the marimo. It is so emblematic of the lake and surrounding region that it has been designated as a special national monument. However, due to decades of deforestation and pollution, the marimo populations in Lake Akan have steeply dropped and have not recovered, despite a number of protective measures.

In the current study, Professor Isamu Wakana and Professor Masashi Ohara of Hokkaido University have discovered that A. linnaei rarely produces its reproductive cells, called zoospores, suggesting that such rarity contributes to the formation of the characteristic spherical appearance of marimo. Their findings, published in the journal Aquatic Botany, contribute to the ongoing efforts to understand the reproduction of the marimo and, hence, its conservation.

A. linnaei is a filamentous alga commonly found in two forms: free-floating and epilithic (attached to rocks); the extremely rare third form, spherical aggregates called marimo, is known from only two locations in the world: Lake Akan, Japan, and Lake Myvatn, Iceland. The means by which this alga transitions between the three forms is still under investigation. In this study, the scientists decided to investigate the reproductive behavior of the marimo and examine if it had any relation to the forms of A. linnaei.

All three forms of A. linnaei are found in Lake Akan. Between May and October in 2017 and 2018, the scientists sampled five different locations across the lake: Churui and Kinetanpe for aggregative forms, Takiguchi for free-floating forms, and Jyagaiwa and Shurikomabetsu for epilithic forms. The number of zoospores (the reproductive cells) from fifty filaments of each of the different forms were counted.

The formation of zoospores with four flagella (spores) was observed, for the first time, in epilithic and aggregate forms from mid-August to early-September. However, the level of formation was very low (maximum 1.3%), particularly in aggregative forms. Zoospore formation was not observed in the free-floating forms.

A. linnaei has been known to produce zoospores (with two flagella) very rarely under cultured condition, but the current study has verified that zoospore (with four flagella) formation occurs regularly in summer in the natural environment, albeit at a very low level. Since the formation of zoospore can lead to fragmentation of aggregates, the low percentages of produced zoospores appear to maintain the aggregative form, the marimo. This is a breakthrough in the understanding of the formation of marimo. However, this work was unable to verify the presence of zoospores with two flagella; confirming their formation and their role in the life cycle are vital.

Isamu Wakana is an acknowledged expert on the subject of marimo. He is currently a Technical Committee Member of the Kushiro International Wetland Centre, where his expertise is critical to the conservation of marimo in Lake Akan.

The Bolson tortoise (Bolson Gopherus flavomarginatus) is the largest land reptile in North America. It lives mainly in dry areas, in particular, in the Chihuahua desert in northern Mexico. In recent decades, its numbers have fallen by 50%, driving the International Union for Conservation of Nature to include it on its red list and it has been classified as endangered. Land tortoises are prone to suffering from a wide range of diseases that can deplete their numbers even more, therefore understanding potential pathogenic organisms could help in advancing conservation strategies.

This was the task set for a research team made up of members from different universities and Mexican entities, including Zoology Professor Francisco Sánchez Tortosa from the University of Córdoba, given his knowledge and experience in conservation biology. Specifically, in this research study, published in Biology, the bacteria present in Ornithodoros turicata ticks were analyzed. These ticks are parasites on tortoises and can transmit diseases to them.

In order to carry out the research, 45 Bolson tortoises were captured at the Mapimí Biosphere Reserve in Mexico, out of which 11 had ticks on their shell or their skin. 17 adult ticks were collected to analyze the bacteria they carried, by means of next generation sequencing.

In the analyses, a large number of potentially pathogenic bacteria was found. This could be due to the large variety of guests found on these kinds of ticks that act as hosts. These live in the big burrows built by the tortoises and used by other animal species such as rodents, birds and other reptiles, that they are parasites on as well.

Among the most numerous bacteria detected are Proteobacteria, Actinobacteria and Firmicutes. Of these, two documented bacteria were registered as pathogens, Mycoplasma spp and Pasteurella testudinis. In addition, A. marginale pathogenic bovine bacteria and A. kovis pathogenic ovine bacteria were detected, as well as A. phagocytophilum, Coxiella burnetii and Neoehrlichia sp zoonoctic bacteria.

According to Professor Francisco Sánchez Tortosa, these results could be interpreted in two ways. On the one hand, this research could lead us to believe that these ticks, and in turn these tortoises, carry diseases that could spread to other animal species, such as livestock, and ultimately, to humans. "That would be an erroneous and catastrophic interpretation as it could lead to a campaign against it that could end in this species's extinction", he asserts.

On the other hand, his vision is more optimistic. "Jumps from one species to another are very uncommon. Now we have this information, but these pathogens have been living with all the other fauna for thousands of years and nothing has ever happened. If we were to perform this research with other animal species, we would surely find similar results. This research is simply a tool in order for us to better understand natural processes and help conserve this species of tortoise, not the other way around", he explains.

The tortoises with parasites did not show evident signs of disease, so further research is needed to understand the tortoises' defense mechanisms against diseases that can be transmitted by ticks, and their characteristics as guests.

A study by University of Tartu researchers indicates that the sensitivity of tests used to detect viral antibodies in a blood sample may differ significantly. The combination of several tests may give the best result.

At the onset of COVID-19 symptoms, first, the nasopharyngeal swab is taken to verify the presence of the virus. But if the aim is to determine whether an asymptomatic person has been in contact with the virus or, vice versa, to know which acute disease the person recently suffered from, a test detecting antibodies in a blood sample comes helpful.

Antibodies are produced in the human body as a counteraction to viral proteins to prevent the virus from replicating and spreading in the body. Usually, it takes a couple of weeks after infection for the antibodies to emerge. Different parts of the virus induce the development of different antibodies. In the case of coronavirus, for instance, there can be antibodies against the spike protein of the virus, against the proteins of the receptor binding domains as well as against the nucleocapsid.

Different types of antibodies are produced, but the IgG antibodies stay in the body for the longest. "When we ever suffer from a disease, usually the IgG antibodies are the ones to stay in our body," explained Epp Sepp, Senior Research Fellow in Medical Microbiology at the University of Tartu, one of the authors of the article published in Plos One.

One use for tests detecting viral antibodies in a blood sample is in large studies trying to ascertain the percentage of the population that has been exposed to the virus. This was also done in spring in the pilot seroepidemiological study in Estonia led by the University of Tartu.

To detect antiviral antibodies, tests are used that detect the presence of antibodies to different proteins or their combinations. There are now hundreds of coronavirus antibody tests, which, unfortunately, are not universally suitable for all patients.

Test sensitivity varies significantly

The study was conducted in cooperation between the University of Tartu, Synlab and Kuressaare Hospital in Saaremaa (Saaremaa is the island in Estonia with the biggest corona outbreak during the first virus wave - editor remark). In the study nine coronavirus antibody tests that were most widely used during the outbreak in spring were analysed. Seven of them were by major producers and two were laboratory tests developed at the University of Tartu by the research group led by Professor Pärt Peterson.

The study involved 97 patients from Saaremaa with a confirmed case of COVID-19. The IgG antibodies to coronavirus were determined by nine tests and the test results were compared based on the patients' symptoms (cough, headache, tiredness, difficulty breathing, diarrhoea, etc.) and the time between the onset of the disease and the antibody test. The majority of studied patients had COVID-19 symptoms, except for about one fifth of them.

The study revealed that in general, the sensitivity of the tests was lower than the producers had stated. As was expected, the rapid test included in the study at the request of the Health Board had the lowest sensitivity.

In half of the patients, all nine antibody tests gave a positive result. In two patients, none of the tests detected coronavirus antibodies. This implies that antiviral antibodies might not even emerge in some COVID-19 patients. For the rest of the patients, the test results varied. Analysis of the correlation of the results indicated that in some patients, the prevailing antibodies were those against the nucleocapsid while in others antibodies against the spike protein prevailed.

Finding a reliable combination is crucial

Some tests worked equally well for asymptomatic patients and those with many symptoms. In the case of some tests, the results were highly dependent on the time of taking the sample and the number of symptoms. For instance, for some tests, the positivity rate in asymptomatic COVID-19 cases was about two times lower than in polysymptomatic ones. The best diagnostic sensitivity in detecting antibodies was achieved by combining several antibody tests, for instance, a test detecting antibodies to the spike protein with the test detecting antibodies to the nucleocapsid.

"In the everyday work of Synlab, we are using the Abbott test that is sensitive to antibodies to the nucleocapsid. If that gives a borderline negative result in a patient, we will analyse this sample again using another test sensitive to antibodies to the spike protein. If the result is positive, we will trust that. My experience has shown that antibodies to the nucleocapsid disappear faster and antibodies to the spike protein last for longer," explained the lead author of the study Paul Naaber, Senior Research Fellow in Medical Microbiology at the University of Tartu.

According to researchers, there is no one perfect test that works well in all cases. To get the most reliable result, the tests may need to be combined. "This is a very important piece of knowledge for planning major seroepidemiological studies. Our analysis showed that had we relied solely on the information written on the package by the producer, the studies in which the tests were used could have led to a completely different result. In spring, only a few published studies had compared tests, so we took it upon ourselves. Objective measurements indicate that test sensitivity may be significantly lower than stated on the package," Naaber explained.