Culture

DNA only persists through replication - naturally or synthetically. While humans need the genetic material to be reproduced in order to replace old or damaged cells, the ability to replicate DNA in a laboratory setting can provide researchers insights into the mechanisms of disease or the platform to develop treatments.  

Moreover, large-scale synthesis of DNA via such replication is a cornerstone of synthetic biology. However, just like the way we write or type an article, this DNA "writing" process is error prone, which has become a serious problem in large-scale DNA synthesis.

Now, a team of researchers from the Chinese Academy of Science (CAS) has developed a more efficient and cost-effective way to accurately synthesize DNA than traditionally used methods. They published their results on March 5, 2020 in ACS Synthetic Biology.  

"In synthetic biology, genes, gene networks and even entire genomes are synthesized to create new functions," said ZHANG Jia, paper first-author and a researcher from Single-Cell Center, Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT), CAS.  

The synthetization process involves assembling DNA in liquid or on a microchip outfitted to intentionally pair specific genetic fragments. The problem, according to ZHANG, is that the fragments frequently mismatch and produce significant errors. Current methods to reduce these errors involve a protein called MutS, which is attracted to mismatched genetic fragments. The protein acts as a flag on the errors, allowing scientists to identify and remove them.  

This process is costly and time-consuming, however. One major reason is that, the key error-correcting enzyme of eMutS, a protein derived from E. coli and binds errors with high accuracy, is fragile and does not last long.  

"To tackle this challenge, we have developed a simple, effective and cost-efficient error-correction system that is readily applicable in gene synthesis workflow," ZHANG said. 

The CAS team began by treating eMutS with chemical stabilizers in the form of a kind of molecular glue called disulfide bonds. With a strong chemical structure, the introduced bonds, plus improvements in enzyme production and storage, extended the life of the proteins from seven to 63 days. Preparing the proteins for the error-removal process can take a significant amount of time, so this remarkable increase in enzyme durability means that researchers can go from preparing proteins once a week to once every two months. In industry-scale DNA synthesis workflows, this means significant reduction in operation, labor and time costs. 

Furthermore, using the newly durable eMutS protein,  86.4% of the synthetic DNA fragments are completely free of errors - a nearly seven-fold increase in accuracy from the commercial enzyme systems currently on the market, according to ZHANG.  

"This system's high fidelity, simple operation and low cost in error correction address one of the key challenges in DNA synthesis and could have implications for broad applications in synthetic biology, including industrial applications," said XU Jian, senior author of the study and Director of Single-Cell Center, QIBEBT, CAS.  

The team plans to continue improving the shelf-life of the proteins while also further increasing the accuracy of error removal in DNA synthesis.  

Silkworms are useful for more than just making strong and absorbent strings of silky thread for the textiles industry. A group of KAUST scientists has now coaxed these grub-like insects into making the human form of E-selectin, a critical adhesion molecule involved in inflammation, cancer and other disease processes.

Working with collaborators at Kyushu University in Japan, biochemist Jasmeen Merzaban and her team engineered silkworms to produce different variants of E-selectin. They then studied how the various adhesion proteins interacted with cells, discovering that there is more to E-selectin's molecular stickiness than how its terminal binding domain interacts with target molecules.

For the first time, they have shown that critical for binding is the connecting arm of E-selectin --a repetitive region of variable length (known as the short consensus repeat domain) that extends the protein's hand to grab cells out of flow.

Longer armed E-selectins are better at tethering blood stem cells, Merzaban and her colleagues report. But the speed with which E-selectin grabs the cells seems controlled only by the protein's hand and wrist--the lectin and the epidermal growth-factor-like domains, respectively.

The findings shed light on the natural trafficking of blood components into and out of tissues. They might also explain how rogue cancer cells in the blood get captured at distant organs to seed new tumors throughout the body.

"Evaluating the ability of components of the E-selectin molecule to block adhesion interactions based on our work could generate results with therapeutic implications," Merzaban says.

She and members of her are currently exploring the potential for lab-grown E-selectin proteins to serve as decoys in the body. These molecules should get between cancer cells and natural E-selectins found in blood vessels or in the bone marrow, and thereby reduce the rate of metastasis, the main cause of cancer-related death, or prevent tumor cells from hiding away in organs where they are protected from chemotherapy.

To manufacture more E-selectin, the team will again rear huge numbers of transgenic creamy white silkworms. Other options for large-scale protein production abound, including the use of Chinese hamster ovary cells and bacterial culture systems. But rodent cells can be expensive and inefficient in making recombinant proteins and bacteria cannot always faithfully replicate aspects of mammalian protein biology.

"The silkworm expression system presents the advantage of producing functional mammalian proteins at large scale with high yields at low cost," says Fajr Aleisa, the first author of the study and a former Ph.D. student in Merzaban's lab group.

Eating more protein at breakfast or lunchtime could help older people maintain muscle mass with advancing age - but most people eat proteins fairly unevenly throughout the day, new research at the University of Birmingham has found.

The body's mechanisms for producing new muscle require regular stimulation to function efficiently - this stimulation happens when we eat protein. The mechanisms are less efficient in older people, so they need to eat more protein to get the same response as younger people.

But just eating more protein is not enough, though - older people also need to spread that intake evenly across all their meals to ensure they maximise the benefits of protein for muscle mass.

Researchers in the School of Sport, Exercise and Rehabilitation Sciences at the University of Birmingham, studied the dietary intake of young, middle-aged and old-aged individuals with a particular focus on the amount, pattern and source of protein consumed.

Their results showed that, while the majority of individuals across all three groups met or exceeded current national guidelines (RDA) for protein intake, the protein intake and distribution across daily meals and snacks were very varied.

The study involved 120 participants divided into three age groups. In the first, participants had an average age of 23; in the second an average age of 51; and in the third an average age of 77. All participants were asked to complete a food diary over a three-day period, weighing out every single food item consumed.

Researchers looked for patterns in the dietary behaviour of participants. In particular, they evaluated the protein intake across the different age groups and found 18 different patterns of protein intake throughout the day, showing a wide variety of eating habits.

Most noticeably, the team found that old people, compared to young and middle-aged individuals, people were more likely to eat a lower-quality protein source, such as bread, at lunchtime.

The results offer compelling evidence for revised nutritional guidelines that could help older people adopt habits that spread consumption of good quality proteins across all their meals.

"We know that older people show a blunted response to muscle building when consuming a certain amount of protein. Therefore, older individuals need to eat more protein to get the same muscle building response as younger and middle-aged people," explains Dr Benoit Smeuninx, first author on the study. "another way to help muscles make better use of dietary protein is to perform regular exercise".

"Most people are reaching the Recommended Daily Allowance of protein, but our results show that a one-size-fits-all guideline for protein intake isn't appropriate across all age groups. Simply saying older people should eat more protein isn't really enough either. We need a more sophisticated and individualised approach that can help people understand when and how much protein to consume to support muscle mass."

Future areas for research include studying how protein needs in hospitalised individuals could aid the maintenance of muscle mass, and to further elucidate the interaction between physical activity protein consumption in the fight against age-related muscle loss.

Many genetic and breeding studies have shown that point mutations and indels (insertions and deletions) can alter elite traits in crop plants. Although nuclease-initiated homology-directed repair (HDR) can generate such changes, it is limited by its low efficiency. Base editors are robust tools for creating base transitions, but not transversions, insertions or deletions. Thus, there is a pressing need for new genome engineering approaches in plants.

David R. Liu and his colleagues at Harvard University developed a new genome editing approach, prime editing, which uses engineered Cas9 nickase (H840A)-reverse transcriptase (RT) fusion proteins paired with a prime editing guide RNA (pegRNA) that encodes the desired edit in human cells.

Recently, a research team led by Prof. GAO Caixia of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences reported the optimization of a prime editing system (PPE system) for creating desired point mutations, insertions and deletions in two major cereal crops, namely, rice and wheat. The main components of a PPE system are a Cas9 nickase-RT fusion protein and a pegRNA.

Using the PPE system, these researchers produced all 12 kinds of single base substitutions, as well as multiple point mutations and small DNA insertions and deletions at 9 rice and seven wheat sites in protoplasts, with efficiencies up to 19.2%. The efficiency of PPE was strongly affected by the length of the primer binding site (PBS) and RT template.

Although byproducts (off-target effects) were generated by the PPE system, they can be reduced by optimizing RT template length. Moreover, using a PPE system optimized for plants, they found that the original RT could be replaced by CaMV-RT (from the cauliflower mosaic virus) and retron-derived RT (from E. coli BL21). Prime editing efficiency was also improved at some targets by using their PPE-Ribozyme (PPE-R) and by incubating at 37 ?.

Furthermore, GAO and her collaborators were able to create stable mutant rice plants carrying G-to-T point mutations, multinucleotide substitutions, and a number of desired 6-nt deletions, with a mutant production efficiency approaching 22%. It is noteworthy that these three types of mutation are very difficult to produce with current editing tools.

"Although the efficiency of the PPE system is lower than that of base editors, it is still an appealing new tool for creating all 12 types of single-point mutation, mixtures of different substitutions, and insertions and deletions. The system thus has great potential for plant breeding and functional genomics research," said Dr. GAO.

Advances in materials, microfabrication and medical imaging are accelerating the pace of innovation in implantable neuroprosthetics. These soft, biocompatible devices, which rely on the electrical stimulation of the nervous system, have shown enormous potential in improving quality of life for patients with a range of conditions such as paralysis and deafness. Despite their promise, most of these groundbreaking discoveries never make it out of the lab.

Few discoveries make it to market

Researchers tend to underestimate the amount of engineering and development work needed to get a discovery out of the lab and into clinical use. "These discoveries can be so far ahead of the curve that finding an industry partner willing to do the development work is practically impossible," says Stéphanie Lacour, who heads EPFL's Laboratory for Soft Bioelectronic Interfaces (LSBI).

There is often a disconnect between the evaluation of new implantable devices and the physical and biological reality of healthcare practice. "With a new soft, implantable interface, you have to go through extra validation steps that don't apply to conventional implants," adds Lacour.

The EPFL team has developed an experimental protocol for testing, optimizing and validating soft, personalized implants such as the devices developed by researchers at the LSBI. The method, which should help facilitate the transition from lab to market, is described in a paper published in the journal Advanced Materials.

A four-step process

The first step is to develop a personalized, anatomically accurate, biophysical prototype of the tissue into which the device will be implanted. This process is made possible by medical imaging data and 3D printing techniques. "This means that, for each patient, we reproduce the precise structure of the tissue that will ultimately host the implant," explains Giuseppe Schiavone, a scientist at the LSBI.

Next, the fabrication process is optimized to make sure it is both reliable and reproducible. The soft implant is inserted into the tissue prototype, which is then placed in an environment that replicates the biophysical conditions inside the human body. Using a biomimetic platform developed in the lab, the researchers apply mechanical stimuli to the implant and the surrounding tissue to mimic the dynamic in vivo environment and to validate the device's biocompatibility and therapeutic efficacy. The platform also ages the implant physically and electrochemically under near-realistic conditions.

Fine-tuning through tests

"With this method, we're able to test implants more quickly, realistically and cheaply without the need for surgical procedures," adds Schiavone. "And because we evaluate the device at each stage of the process, we can fine-tune and improve it on the fly with minimal disruption." According to Schiavone, a lack of standardized validation processes for soft, biocompatible implants means that research teams currently devise their own protocols.

Researchers at the LSBI worked with the group of Marco Capogrosso at the University of Fribourg and EPFL and Lausanne University Hospital (CHUV) teams led by Grégoire Courtine and Jocelyne Bloch to test the protocol on e-dura, an EPFL-developed neuromodulation device implanted in the epidural space of the spinal cord.

Although these new soft, implantable devices are not yet ready to proceed to clinical trial, the paper's authors hope that their work will encourage other researchers to apply translational principles and support further advances in medtech innovation.

CHAMPAIGN, Ill. -- Two brain-signaling molecules control how anemonefish dads care for their young and respond to nest intruders, researchers report in a new study. Because there are many similarities in brain structure between fish and humans, the findings offer insight into the fundamental nature of parental care, the scientists say.

"One of the benefits of studying fish is that their behaviors are simpler," said Ross DeAngelis, a former graduate student who conducted the work in the laboratory of Justin Rhodes, a professor of psychology at the University of Illinois at Urbana-Champaign. "By exploring these systems, we can understand the broader implications on vertebrate behavior."

Anemonefish live in pairs on sea anemones in the wild. Female anemonefish are more aggressive than their mates and help protect the nest from intruders. Fathers have a more nurturing role. See video.

"Male anemonefish are spectacular fathers," said Rhodes, who led the research. "They nourish the eggs by fanning them to provide oxygen and clear debris, and they nip at the eggs to clean them. When a predator is around, they switch their behavior to become aggressive - they try to bite and fight the predators away."

Previous research focused on only one facet of parental care: either nourishment or defense. The new study aims to understand both aspects together in the presence of intruders.

Two hormones play a role in guiding the trade-off between caring for one's offspring and defending them. Arginine vasotocin increases aggression, while isotocin boosts egg care. Their effects on parental behavior in the presence of intruders was previously unknown.

The researchers used inhibitory compounds, known as antagonists, to block the binding of arginine vasotocin or isotocin to their receptors in the brain. They injected these compounds into the abdomens of the fish. From there, the antagonists were carried to the brain through the blood.

"Blocking arginine vasotocin reduced aggression and increased parental care in male anemonefish," DeAngelis said. "This is an unusual result because they are such good dads - we didn't think it was possible for them to be even better."

Blocking isotocin had the opposite effect. It increased aggression, and the fish spent less time nipping and fanning their eggs, DeAngelis said.

"The results are similar to what we see in humans," Rhodes said. "Oxytocin, which is the human version of isotocin, is known to be important for nurturing. Arginine vasopressin, which is the human version of arginine vasotocin, plays a role in social and affiliative behavior in the slightly different context of mating."

The two hormones have very similar structures and bind to similar receptors in the brain, so the researchers cannot be certain that the antagonist for one isn't also affecting the other. They also have not yet determined how the hormones specifically modify brain-signaling.

"Individuals across the animal kingdom have to make decisions on how to maximize their fitness, and most of those decisions are based on environmental context," DeAngelis said. "It is interesting to see that the neurochemical pathways can be modulated by the current social context."

Scientists from the University of Sheffield have discovered a pulsating ancient star in a double star system, which will allow them to access important information on the history of how stars like our Sun evolve and eventually die.

The discovery of the first ever pulsating white dwarf star in an eclipsing binary by physicists at Sheffield means the team can see how binary evolution has affected the internal structure of a white dwarf in detail for the first time.

An eclipsing binary, or double star system, is made up of two stars orbiting each other and periodically passing in front of each other as seen from the Earth.

White dwarf stars are the burnt out cores left behind when a star like the Sun dies. This particular white dwarf could provide key insights into the structure, evolution and death of these stars for the first time.

Most white dwarfs are thought to be made primarily of carbon and oxygen, but this particular white dwarf is made mostly of helium. The team think this is a result of its binary companion cutting off its evolution early, before it got a chance to fuse the helium into carbon and oxygen.

The pulsations from this star were discovered using HiPERCAM, a revolutionary high-speed camera developed by a team led by Professor Vik Dhillon from the University of Sheffield's Department of Physics and Astronomy.

HiPERCAM can take one picture every millisecond simultaneously in five different colours and is mounted on the 10.4m Gran Telescopio Canarias (GTC), the world's largest optical telescope on La Palma. This allowed the researchers to detect the rapid and subtle pulsations from this particular white dwarf.

The pulsations of the white dwarf star and the eclipsing binary system allowed the team to investigate the structure of it using two techniques, asteroseismology and eclipse studies.
Asteroseismology involves measuring how fast sound waves travel through the white dwarf.

Dr Steven Parsons, from the University of Sheffield's Department of Physics and Astronomy, who led the study said: "Determining what a white dwarf is made of is not straightforward because these objects have about half of the mass of the Sun, packed into something about the size of the Earth. This means that gravity is extremely strong on a white dwarf, around one million times larger than here on Earth, so on the surface of a white dwarf an average person would weigh about 60,000,000kg. The gravity causes all of the heavy elements in the white dwarf to sink to the centre, leaving only the lightest elements at the surface and so the true composition of it remains hidden underneath.

"This pulsating white dwarf we discovered is extremely important since we can use the binary motion and the eclipse to independently measure the mass and radius of this white dwarf, which helps us determine what it is made of. Even more interestingly, the two stars in this binary system have interacted with each other in the past, transferring material back and forth between them. We can see how this binary evolution has affected the internal structure of the white dwarf, something that we've not been able to do before for these kinds of binary systems."

The next step of the research is to continue observing the white dwarf to record as many pulsations as possible using HiPERCAM and the Hubble Space Telescope.

A good indicator of dysregulation in live cells is a change in their RNA expression. MicroRNA (miRNA), a special type of RNA, is considered a biomarker for carcinogenic cells. A team of scientists from China has found a way to amplify miRNA in live tumor cells for bioimaging. As they report in the journal Angewandte Chemie, their assay is based on a robust cellular autocatalytic biocircuit triggered by synthetic DNA and nanoparticles.

Diagnosing cancer before a tumor becomes visible has been one of the long-standing goals in medicine. One of the biomarkers for carcinogenicity in a cell is its RNA expression pattern or, more precisely, the change in RNA expression, which causes metabolic degeneration. There are many types of RNA, among which a short noncoding RNA called miRNA promotes or impedes the translation of nucleus-encoded genetic information into protein. Accordingly, the detection of a changed miRNA expression profile is thought to be a reliable indication of the degeneration of a cell.

However, the detection of a particular miRNA is difficult because it is present in the cell only in tiny amounts and must by amplified and connected to a signaling entity, such as a fluorescence dye, for visualization. A team of scientists at Wuhan University, China, led by Fuan Wang, have discovered a suitable amplification-detection mechanism for miRNA, which relies on an autocatalytic biocircuit activated by synthetic DNA, leading to a strong fluorescence signal that flags tumor cells.

RNA is usually synthesized in the nucleus of the cell and transported to the cytoplasm where it conveys genetic information. However, when synthetic DNA is present in the cytoplasm, RNA can bind to a matching nucleotide sequence of the DNA strand; a fact that is exploited in, for example, antiretroviral treatment to silence viral RNA expression. Wang and his coworkers did the opposite. By matching synthetic DNA strands with miRNA, they triggered an autocatalytic amplification circuit--called autocatalytic DNAzyme biocircuit--to form DNA-miRNA assemblies. These assemblies grew further to form DNAzyme nanowires that carry the fluorescence dyes.

After administering the DNAzyme detection kit, the authors observed bright fluorescence in a mouse model at the location where a tumor was developing.

To make the DNAzyme enter the tumor cells, the authors used nanoparticles--tiny parcels that can deliver drugs and other molecular freight to the cells--made of manganese dioxide with a honeycomb-like structure. According to the authors, this composition and architecture has the advantage that the nanoparticle can be readily activated by glutathione, which is a chemical found in abundance in tumor cells. Another advantage is that the released manganese ions would sustain the autocatalytic DNAzyme biocircuit, the authors write.

The scientists emphasize that their self-enhanced bioimaging system could be developed as a powerful tool to visualize tumor cells with biomarkers. This is especially promising as many different miRNAs can be selectively targeted to investigate different cancers or other cell dysfunction.

(New York, March 16) A new CUNY Graduate School of Public Health and Health Policy (CUNY SPH) survey released today found that 60% of New York State residents believe their chances of contracting the novel Coronavirus are low or very low. The survey of 1000 New York households, conducted between March 13-15, 2020 and considered accurate within a range of 3%, also found that more than half (55%) of all respondents live in households with one or more members over age 60, the highest risk age group for Coronavirus infection. However, just more than one-fourth (27%) of them believed that they were living with someone who has a high chance of becoming sick. In general, a bare majority of New Yorkers (51%) said they have some knowledge of Coronavirus, while 34% believed they know a lot about it.

A substantial majority of New York residents believe that current policies help in containing the virus, including closing schools and universities (68%), limiting travel to and from certain countries (69%), and two weeks of quarantine for people exposed to the virus (71%).

Messages about ways to prevent the spread of the virus have led many residents to change their plans and routines in the past week. Almost one-fourth (24%) of respondents reported they did not attend an event they had paid for due to concerns about the virus, and almost two in five respondents (39%) decided to stay home instead of going to work or changed existing travel plans (40%). Almost three in five (57%) said they had stayed at home instead of going to a restaurant or movie, and almost two-thirds (64%) say they have avoided shaking hands or hugging. The single recommendation that most respondents reported following regarded handwashing. Nine out of ten (88%) of New Yorkers reporting they increased the frequency of which they wash their hands or used hand sanitizer.

Almost three New Yorkers in ten (29%) rated television news ranked as the most trusted source of information about Coronavirus, followed by the CDC at 26%, and the WHO at 15%. Only 7% of respondents reported that President Trump was their most trusted source of information.

While an equally low percentage of respondents said social media were their most trusted information source, most people (51%) reported that they do share information on Coronavirus on these platforms at least once a day. Three in ten (30%) said they have passed along information on social media about Coronavirus without knowing it was accurate. The most frequently used online media sources respondents reported using were news media posts (36%), followed by friends (27%) and the government (20%).

"We conducted this survey and will update it regularly over the course of this public health crisis as a part of our unique mission within the City's largest public university," said CUNY SPH Dean Ayman El Mohandes. "Working together promoting evidence-based communication with innovative approaches for individual and community action, we can and will help address the threat of COVID-19."

The complete survey results and related commentary can be found at https://sph.cuny.edu/research/covid-19-tracking-survey/week-1/ and at JHC Impact, an initiative of the Journal of Health Communication: International Perspectives.

The CUNY SPH survey was conducted by Emerson College Polling from March 13-15, 2020. The sample for the NY Statewide results, n=1,000, with a Credibility Interval (CI) similar to a poll's margin of error (MOE) of +/- 3 percentage points. The data sets were weighted by gender, age, ethnicity, education and region based on the 2018 1-year American Community Survey model. It is important to remember that subsets based on gender, age, ethnicity and region carry with them higher margins of error, as the sample size is reduced. Data was collected using an Interactive Voice Response (IVR) system of landlines (n=477), SMS-to-online (n=360) and an online panel provided by MTurk and Survey Monkey (n=166).

The CUNY Graduate School of Public Health and Health Policy (CUNY SPH) is committed to teaching, research and service that creates a healthier New York City and helps promote equitable, efficient and evidence-based solutions to pressing health problems facing cities around the world.

Toxic personality is a term used to describe people who behave greedily, immodestly and unfairly and take the truth very lightly. Dr. Mareike Kholin, Bastian Kückelhaus and Prof. Dr. Gerhard Blickle from the Department of Psychology at the University of Bonn found out why such people can still succeed in their careers. The trick that leads to the top is social skill. The results are presented online in advance in the journal "Personality and Individual Differences". The print version will be published in April.

Social skills are in themselves a good thing in the workplace. They can open locked doors and help to cope with daily stress. But they can also be used to deceive others, abuse trust or construct a façade of harmlessness beyond which actually lurks deceitfulness. Dr. Mareike Kholin and the research team determined that toxic personalities who are considered socially adept by their colleagues were considered more capable by their superiors and occupy a higher hierarchical position. "We have to get used to the idea that social skills can be a double-edged sword," says Kholin.

In personality tests, "toxic" persons have low scores in the categories "honesty" and "modesty". "Such personalities tend to focus on themselves all the time," says Blickle. "Good social skills enable them to deceive others." On the other hand, those who are distinctly honest and modest are a real joy for their team: Such individuals behave fairly and allow colleagues to share in their successes.

Low values for the characteristics "honesty" and "modesty"

Psychologists from the University of Bonn investigated the phenomenon by interviewing various work teams: First the participants completed an anonymous online survey and assessed themselves on the characteristics "honesty" and "modesty", among others. Then colleagues provided information on the social skills of the participant. The participant's supervisor then gave an appraisal of his work performance. The researchers were able to collect data from a total of 203 of such "trios" of employees, colleagues and superiors.

The results showed that workers with low values for honesty and modesty can nonetheless succeed in their careers if they balance the toxic parts of their personality with social skills. Bastian Kückelhaus: "Trickery, disguise and deception are the dark side of social skills."

How can toxic personalities be assessed more accurately?

But how can companies and teams respond to these findings? "In order to slow down the ascent of toxic personalities, more attention should be paid to actual performance and less to the good impression when selecting staff and making assessments," advises Prof. Blickle. This is particularly difficult in activities where it is important to impress and arouse interest, such as in sales or leadership positions. "Here, it makes sense for instance to also look at the sickness and notice rate of employees, or customer loyalty," Blickle adds.

KNOXVILLE --The best bargains for conserving some of the world's most vulnerable salamanders and other vertebrate species can be found in Central Texas and the Appalachians, according to new conservation tools developed at the National Institute for Mathematical and Biological Synthesis (NIMBioS) at the University of Tennessee, Knoxville.

The study involves a suite of computer algorithms that surf across many different kinds of data to create maps of top priorities and projections of what species would benefit the most from increases in conservation dollars.

An interdisciplinary team of computer programmers, biodiversity data scientists, conservation decision makers, economists, and others from around the globe convened at NIMBioS to develop the optimization tool, which was published in the journal Ecological Applications.

The study is available at https://doi.org/10.1002/eap.2118

Determining where the best protection payoffs are to be found has traditionally been a challenge for conservation, especially when budgets are stretched thin.

"The challenge for conservation practitioners is how to best combine many really disparate kinds of data and do so in a way that lets them compare possible options for protection--the goal being to find opportunities where conservation efforts offer the greatest bang for the buck," said the study's lead author, UT Professor of Ecology and Evolutionary Biology Paul Armsworth.

The algorithm considers data including land acquisition costs, future development patterns, budget allocations for conservation, and the presence of threatened species.

The new approach could prove valuable to conservation and natural resource managers looking to optimize conservation dollars.

"It's basically a giant bargain-hunting formula for biodiversity conservation," said Joe Fargione, science director for the North American region at the Nature Conservancy, a leading conservation organization. "The authors are finding important bargains--places where the most good for the most species can be done, sometimes at very low cost."

When comparing many possible scenarios and models, the researchers found that some priority areas for protection arose repeatedly. In the United States, those appeared to be in counties around Austin, Texas, and parts of the southern Appalachians.

The unique geology and complex groundwater systems around Austin provide habitats for highly specialized species. Many salamander species found there occur nowhere else in the world, with some receiving protection under the US Endangered Species Act because of their vulnerability to extinction.

The ancient mountains of southern Appalachian Mountains provided a refuge for species through past Ice Ages. The rich topography and diversity of habitats in the region provide a global hotspot for many different groups of species.

"Both areas offer very good deals if you only have a limited budget to work with and are trying to protect vulnerable species. Adding more protection into these places wouldn't be too expensive. And these habitats could be in trouble in the future if additional protection isn't undertaken," Armsworth said.

Crick and Imperial researchers have found that a key antibiotic widely used to treat drug-resistant tuberculosis does not work as expected - a finding which could be used to develop new drugs. The study was part-funded by the Francis Crick Institute and the Wellcome Trust.

The research, published in Nature Chemical Biology, found that contrary to current understanding, an antibiotic used to treat tuberculosis is unable to permanently prevent one of the enzymes it targets from functioning. By uncovering how this enzyme is re-activated, the research could lead to the development of improved versions of the drug which could be used against antibiotic resistant bacteria.

For more than 50 years, the antibiotic D-cycloserine has been used to treat cases of TB that are resistant to first-line drugs. It had been thought that this drug in part worked by irreversibly preventing an enzyme, alanine racemase, from helping to build TB bacteria's cell walls.

However, this study found that despite being exposed to D-cycloserine, about 10% of the alanine racemase enzyme was later able to function effectively again. This enzyme is capable of regaining activity by inactivating the drug, in a process called hydrolysis. This change means the modified drug can no longer bind to and block the enzyme.

The drug however can still treat TB because it also inhibits another enzyme involved in building TB cell walls, D-Ala:D-Ala ligase.

"You could say that alanine racemase acts like Dr Jekyll and Mr Hyde. When first exposed to the drug, it's Dr Jekyll, as it is a good target for the drug, and this stops the bacteria for a time. However, over time it turns into Mr Hyde, as it stops the drug from targeting it and so it can function again. If it weren't for the drug also blocking a separate target, it would be ineffective against TB," says Luiz Pedro Carvalho, group leader in the Mycobacterial Metabolism and Antibiotic Research Laboratory at the Crick.

These findings could lead to the development of new drugs. One new route, for example, would be to develop similar molecules that cannot be hydrolysed and therefore would irreversibly inhibit alanine racemase. Various bacteria have the same enzyme or a version of it, so such drugs could provide a new way to treat these diseases.

"For decades, it's been thought this drug worked in one way, that its action could not be reversed, so it's rather incredible that we've found it gets inactivated by one of its targets," further explains Luiz Pedro Carvalho. "The fact this has been missed for so long demonstrates how important it is to work with the right protein derived from the organism you want to understand."

Cesira de Chiara, principal laboratory research scientist in Luiz's lab, says: "The key here is that tuberculosis takes a relatively long time to replicate, about 20 hours, so there's enough time for this enzyme to be inhibited and then re-activated. Previous studies missed this re-activation as they haven't studied the process of inactivation of the enzyme by the drug over such a long period.

"If we could create a tweaked version of this drug that can permanently block this family of enzymes, we could further improve its effectiveness against the raising threat of antibiotic resistant bacteria, perhaps reducing the doses and, with them, the risk of potentially toxic side-effects."

Philadelphia, March 16, 2020 - An e-cigarette carried in the left breast shirt pocket of a patient with an implantable cardioverter-defibrillator (ICD) caused magnetic reversion, interrupting the ICD's ability to detect and treat dangerous heart rhythm problems, clinicians report in HeartRhythm Case Reports, published by Elsevier. The patient was not aware that the e-cigarette has an integrated magnetic component, and it had suspended detection of heart rhythm problems by the ICD four times before he reported it to his healthcare team.

"To our knowledge this is the first reported case of magnetic reversion of an ICD by an e-cigarette," stated senior investigator Usha B. Tedrow, MD, MPH, and lead authors Julie B. Shea, MS, RNCS, Martin Aguilar, MD, and William Sauer, MD, from the Cardiovascular Arrhythmia Service at Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. "Given the increasing use of e-cigarettes worldwide, recognition of this potentially serious interaction appears clinically important."

A 48-year-old male with an ICD reported that he heard his device "beep" several times, both at home and at his office. There were no adverse symptoms associated with the beeping, and remote monitoring found the device was working normally. The patient denied any magnetic exposure, but data provided by the ICD manufacturer found four instances of magnet interactions with the device, corresponding with when the patient heard the tone.

Upon further questioning, the patient recalled using his e-cigarette (JUUL vape device), which he frequently stored in his left breast pocket, overlying the ICD. When the healthcare team held the device up to his ICD, it triggered the steady magnet tone. The patient was educated about the importance of keeping any type of magnet away from his ICD. JUUL's website does recommend keeping e-cigarettes away from key cards, credit cards, and other items with magnetic strips, as well as pacemakers.

"Magnets are ubiquitous in commercially-available electronic devices. They can be integrated in ways that are difficult to recognize. Although manufacturers are not routinely required to specify the strength of the magnetic fields and safety information for interference with medical-grade devices, the general recommendation is that any portable electronic or magnetic device be kept at least six to 12 inches away from an implant," noted Dr. Tedrow and Ms. Shea.

There are commercially available magnetic field meters, and even several smartphone applications, that can be used to estimate the strength of a magnet. Practically speaking, most cardiac implantable devices have a magnetic exposure upper limit of 10G, and manufacturers typically recommend a 2:1 safety margin for safe clinical operation. "As such, finding the distance at which the magnetic field is 5G or less would, in principle, provide adequate clearance for safe clinical operation of cardiac implantable devices," Dr. Aguilar added.

"Practitioners should remain vigilant regarding the use of new technology by their ICD patients. In our case, there was no adverse effect from the interaction of the e-cigarette with the device, but if it had happened during a tachycardia episode, it could have had serious, perhaps even fatal consequences," cautioned Dr. Tedrow and Ms. Shea.

Finally, some good news has emerged about the novel coronavirus that has spread to about 50 countries across the world. Chinese professors report in the journal Frontiers in Pediatrics that it doesn't appear that the viral infection is transmittable from pregnant mothers to newborns at birth.

The study is the second out of China within the last month to confirm that mothers infected with coronavirus disease 2019 (COVID-19) during pregnancy did not infect their babies.

All four mothers in the current study, which focused on the health of the newborns, gave birth at Wuhan's Union Hospital while infected. Wuhan in Hubei Province is believed to be the epicenter of the current outbreak that has sickened more than 100,000 people worldwide and killed more than 3,400 -- most of them in China.

None of the infants developed any serious symptoms associated with COVID-19 such as fever or cough, though all were initially isolated in neonatal intensive care units and fed formula. Three of the four tested negative for the respiratory infection following a throat swab, while the fourth child's mother declined permission for the test.

One newborn did experience a minor breathing issue for three days that was treated by non-invasive mechanical ventilation. Two babies, including the one with a respiratory problem, did have body rashes that eventually disappeared on their own.

It's impossible to conclude whether there's a connection between these other medical issues and COVID-19. "We are not sure the rash was due to the mother's COVID-19 infection," said study co-author Dr. Yalan Liu at Huazhong University of Science and Technology. She also works in the Department of Pediatric at Union Hospital.

All four infants remain healthy, and their mothers also fully recovered.

In the previous retrospective study on nine pregnant mothers infected with COVID-19, researchers also found no evidence that the viral infection can pass to the child. All nine births were done by cesarean section. Three of the four pregnancies in the current study were also brought to term by C-section.

"To avoid infections caused by perinatal and postnatal transmission, our obstetricians think that C-section may be safer," Liu said. "Only one pregnant mother adopted vaginal delivery because of the onset of the labor process. The baby was normal. Maybe vaginal delivery is OK. It needs further study."

In previous coronavirus outbreaks, scientists found no evidence of viral transmission from mother to child, but SARS and MERS were both associated with "critical maternal illness, spontaneous abortion, or even maternal death," according to Liu.

Globally, an estimated 3.4 percent of reported COVID-19 cases have died, according to the latest data from the World Health Organization. In comparison, seasonal flu generally kills far fewer than 1 percent of those infected. However, COVID-19 does not appear to spread as easily as influenza. Note that transmission and fatality rates are currently subject to change and revision as more research is done on the virus.

The authors said further investigations into other aspects of potential COVID-19 infection in newborns and children are needed. For example, the sensitivity of the current diagnostic test for detecting the virus is about 71 percent, so they suggest evaluating its reliability in children.

Toward that end, the researchers are collecting additional samples from the newborns, including placenta, amniotic fluid, neonatal blood and gastric fluid, among others, to detect possible receptors for the virus.

ANN ARBOR, Mich. -- Experts recommend starting conversations about inappropriate touching during the preschool years, but less than half of parents of preschoolers in a national poll say they've begun that discussion.

Meanwhile, one in four parents of elementary school-age children say they have not yet begun talking about inappropriate touching, according to the C.S. Mott Children's Hospital National Poll on Children's Health at the University of Michigan.

The report is based on responses from 1,106 parents who had at least one child age 2-9 years.

"This is a conversation parents should be having multiple times in age-appropriate ways," says Mott Poll co-director Sarah Clark.

Three in five parents agree that the preschool years is the right time to talk about inappropriate touching. But among parents of preschoolers who have not talked about it, 71% believe their child is too young.

Many parents also say they want more help navigating the conversation - but two in five say they haven't received any information on how to talk with their child about inappropriate touching. Just a quarter of parents have received such information from a health care provider.

"Many parents have not gotten any information about how to talk with children about inappropriate touching. Without practical tips or suggestions, parents may be at a loss for how to begin."

Clark notes that parents may start this process during the preschool years by teaching the anatomically correct names for body parts and explaining what parts are private.

Among parents of elementary school-age children who have not talked about inappropriate touching, the most common reason was just not getting around to it (39%). Another 18% said that discussions are unnecessary because inappropriate touching of children rarely happens.

"Parents shouldn't disregard the reality of child sexual abuse," Clark says. "Statistics show that up to 1 in 4 girls and 1 in 6 boys will be sexually abused before the age of 18."

Other common reasons for not talking about inappropriate touching with school-age children include feeling the child is still too young (36%), not wanting to scare the child (21%), and not knowing how to bring it up (18%).

"It's clear that this is a challenging area for many parents. However, it's essential to help children understand the difference between appropriate and inappropriate touching, and that they should tell mom or dad if any inappropriate touching occurs. Failure to do so leaves children unequipped to deal with one of the gravest dangers of childhood."

In addition to discussions, Clark says parents should think about family rules that can reinforce the concept of personal boundaries. For example, parents shouldn't force children to accept hugs, kisses or other physical contact from anybody, including family members and friends.

Sixty percent of parents said they'd like their child's school to teach students about the topic, and 76% want the school to provide information for parents.

"In the past, talking about appropriate vs inappropriate touching was probably something that parents would want to keep in the family," says Clark. "However, it's clear that parents want information and resources on how best to approach this sensitive topic. Schools and child health providers have a substantial role in helping families recognize and confront child sexual abuse."