Culture

Heavy water tastes sweet

image: Differences between the behavior of the transmembrane part of the human sweet taste receptor in H2O vs D2O base on analysis of three independent microsecond trajectories.

Image: 
Carmelo Tempra / IOCB Prague

Ordinary pure water has no distinct taste, but how about heavy water - does it taste sweet, as anecdotal evidence going back to 1930s may have indicated? And if yes - why, when D2O is chemically practically identical to H2O, of which it is a stable naturally-occurring isotope? These questions arose shortly after heavy water was isolated almost 100 years ago, but they had not been satisfactorily answered until now. Now, researchers Pavel Jungwirth and Phil Mason with students Carmelo Tempra and Victor Cruces Chamorro at the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague), together with the group of Masha Niv at the Hebrew University and Maik Behrens at the Technical University of Munich, found answers to these questions using molecular dynamics simulations, cell-based experiments, mouse models, and human subjects. In their research article published in Communications Biology, they show conclusively that, unlike ordinary water, heavy water tastes sweet to humans but not to mice, with this effect being mediated by the human sweet taste receptor.

Heavy water (D2O) differs from normal water (H2O) by an H-D isotopic substitution only, and as such, should not be chemically distinct. Leaving aside a trivial 10% change in density due to the doubled mass of D compared to H, differences in properties of D2O vs H2O, such as pH or melting and boiling points, are indeed very small. These differences are solely due to nuclear quantum effects, namely, changes in zero-point vibrations, which lead to a slightly stronger hydrogen bonding in D2O than in H2O.

"Despite the fact that the two isotopes are nominally chemically identical, we have shown conclusively that humans can distinguish by taste (which is based on chemical sensing) between H2O and D2O, with the latter having a distinct sweet taste," commented Pavel Jungwirth on the principal result of their study. In their work, the authors complement taste experiments on human subjects with tests on mice and on HEK 293T cells transfected with the human sweet taste receptor TAS1R2/TAS1R3, and with molecular modelling. The results consistently point to the fact that the sweet taste of heavy water is mediated in humans by the TAS1R2/TAS1R3 receptor. Future studies should be able to elucidate the precise sites and mechanisms of action, as well as the reason why D2O activates TAS1R2/TAS1R3 in particular, resulting in a sweet (but not other) taste.

While clearly not a practical sweetener, heavy water provides a glimpse into the wide-open chemical space of sweet molecules. Since heavy water has been used in medical procedures, the finding that it can elicit responses of the sweet taste receptor, which is located not only on the tongue but also in other tissues of the human body, represents an important information for clinicians and their patients. Moreover, due to wide application of D2O in chemical structure determination, chemists will benefit from being aware of the present observations.

Finally, it is worth mentioning that 86 years ago, Science published a short letter by H. C. Urey, Nobelist for the discovery of deuterium (H. C. Urey & G. Failla, Science, 81, 273, 1935. http://doi.org/10.1126/science.81.2098.273-a), stating authoritatively that D2O is undistinguishable from H2O by taste, which had a strong albeit misleading effect on the ongoing discussion about the subject.

"Our study thus resolves an old controversy concerning the sweet taste of heavy water using state-of-the-art experimental and computer modelling approaches, demonstrating that a small nuclear quantum effect can have a pronounced influence on such a basic biological function as taste recognition," concludes Pavel Jungwirth.

Credit: 
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

South Korea data helps create framework to identify COVID-19 vulnerable areas worldwide

image: TTUHSC's Yoonjung Lee, Pharm.D., Ph.D., joined a group of researchers who developed a framework to identify pockets of COVID-19-vulnerable populations through the use of socioeconomic status and epidemiological determinants.

Image: 
TTUHSC

Though the U.S. and South Korea recorded their first official COVID-19 case on the same day, January 20, 2020, there were notable differences in how each country would ultimately address what has become the world's most severe pandemic since 1918.

Yoonjung Lee, Pharm.D., Ph.D., a pharmacy preceptor and pharmaceutical sciences researcher at the Texas Tech University Health Sciences Center (TTUHSC) Jerry H. Hodge School of Pharmacy, said she was surprised at how South Korea effectively managed the pandemic without the business shutdowns and lockdowns that occurred in China, the U.S. and many European countries.

"I am amazed at how the Korean government had prompt and effective public health interventions to not only address COVID-19, but also to address COVID-19-vulnerable populations simultaneously," Lee said. "That could be why the incidences of COVID-19 cases drastically decreased toward the late phase of our study."

The study Lee referred to is one that she and a group of researchers recently conducted to develop a methodological framework for identifying pockets of COVID-19-vulnerable populations through the use of socioeconomic status (SES) and epidemiological determinants. They then applied data taken from South Korea's response to COVID-19 to operationalize and demonstrate the value of the framework.

Other members of the research team included Principal Investigator David O. Carpenter, M.D., and primary author Bayarmagnai Weinstein, M.D., MPH, from the University of Albany; Alan R da Silva, Ph.D., (University of Brasília); Dimitrios E. Kouzoukas, Ph.D., (Edward Hines, Jr. VA Hospital); Tanima Bose, Ph.D., (Ludwig-Maximilian University of Munich); Gwang-Jin Kim, Ph.D., (University of Freiburg-Germany); Paola A. Correa, Ph.D., (Howard Hughes Medical Institute); Santhi Pondugula, Ph.D., (University of Florida); and Jihoo Kim, M.S., (Hanyang University-Seoul).

Their study, "Precision Mapping of COVID-19 Vulnerable Locales by Epidemiological and Socioeconomic Risk Factors, Developed Using South Korean Data," was published Jan. 12 in the International Journal of Environmental Research and Public Health.

In previous research conducted during and after more recent, and less severe pandemics such as SARS (Severe Acute Respiratory Syndrome), swine flu (H1N1) and MERS (Middle East Respiratory Syndrome), investigators had defined a gap in how these illnesses were detected and treated among differing populations. Those populations considered to be socioeconomically disadvantaged seemed to bear the brunt of the diseases while those populations considered to be more affluent and educated were significantly less affected.

Because of these earlier studies, Lee said the research team believed there was the potential to reduce the outbreak of COVID-19 by utilizing targeted interventions. However, those earlier studies focused solely on socioeconomic handpicked by their investigators. More recent studies also had provided COVID-19 risk factors but none had identified COVID-19-vulnerable locales associated with SES and epidemiological factors specific enough to the virus.

"Indeed, the previous studies used SES variables based on researchers' preferences, irrespective of their COVID-19 relevance. Consequently, the SES measures across these studies were incomparable, limiting their usefulness," she added.

Lee said her group's COVID-19 study identified and used seven specific socioeconomic and epidemiologic factors: health care access, health behavior, crowding, area morbidity, education, difficulty to social distancing and population mobility.

To ensure they captured information about the study population's socioeconomic and population health that was as complete as possible, Lee said the team applied Coleman's Foundations of Social Theory, which combines the observed social actions of individuals with the rational concept of economists that contends individuals acts independently of one another and for their own self-interest.

"Coleman's Social Theory guided us to collect data in each of three fundamental domains -- material, human and social capitals -- that concertedly characterize each geographic unit's SES and area-health status in the study," Lee explained.

Lee said the team further filtered the study's variables by utilizing Blumenshine's conceptual mechanistic framework, which describes the potential causes of disparities in the U.S. during an influenza or respiratory infection pandemic. It attributes those disparities to varying levels of exposure to the virus, differences in susceptibility to the disease and distinct variations in access to health care.

"That directed us to causally relevant variables to COVID-19, as they determine the likelihood of being exposed to the virus agent, of contracting the disease upon exposure and of receiving timely and effective treatment after the disease has developed," Lee said.

Integrating Coleman's Foundations of Social Theory and Blumenshine's mechanistic framework helped the research team formulate a universal SES definition and select SES indicators that were mechanistically and casually relevant to COVID-19 health outcomes. The development of this methodological framework made this research unique because it allowed the team to identify COVID-19-vulnerable locales through their associated SES and epidemiological determinants.

"Through this approach, we could have universal SES variables with acceptable generalizability and methodological capacity," Lee said. "Consequently, this helped make our study's regression model stronger and more accurate by using SES variables that were relevant to COVID-19."

Lee said the significance of the research is that it provides a methodological framework and precision mapping method that is globally replicable for COVID-19 and future pandemics because it provides robust SES measurements based on the established theories for reducing bias from arbitrary data selections. In fact, she contended, the novelty of the work speaks to the integrity of the study's design and the statistical methodology of the research.

"Firstly, the combined use of global and spatial statistical methods increased the accuracy as global models verified the geographical model," Lee said. "Secondly, we collaborated in this study with Alan da Silva, who developed the negative binomial extension of the geographically weighted regression. His application of this method eliminated the tool's erroneous use while also optimizing the model to study the data. Lastly, our study showed the progression of the COVID-19 epidemic over three consecutive time-periods, which was a novel approach at the time of the study."

In using the South Korea data, the study showed the risk of COVID-19 increased with higher area morbidity, risky health behaviors, crowding and population mobility. Other factors that influenced risk included education, lower social distancing and the ability to access health. Yet, Lee said, falling COVID-19 risks and spatial shifts over three consecutive time periods (early-phase, middle-phase and late-phase) reflected effective public health interventions in South Korea.

"This finding can be different if other data is used, though the South Korean data, based on our knowledge, was the most detailed and publicly available data with open access, which was the reason why we used South Korean data in our study," Lee said. "Therefore, as depicted in our study, it is crucial to identify COVID-19-vulnerable locales associated with SES and COVID-19 specific epidemiological factors and then to target prompt and effective public health interventions toward these locales for effective pandemic control."

Credit: 
Texas Tech University Health Sciences Center

The incredible bacterial 'homing missiles' that scientists want to harness

image: An illustration of tailocins, and their altruistic action painted by author Vivek Mutalik's daughter, Antara.

Image: 
Antara Mutalik

Imagine there are arrows that are lethal when fired on your enemies yet harmless if they fall on your friends. It's easy to see how these would be an amazing advantage in warfare, if they were real. However, something just like these arrows does indeed exist, and they are used in warfare ... just on a different scale.

These weapons are called tailocins, and the reality is almost stranger than fiction.

"Tailocins are extremely strong protein nanomachines made by bacteria," explained Vivek Mutalik, a research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) who studies tailocins and phages, the bacteria-infecting viruses that tailocins appear to be remnants of. "They look like phages but they don't have the capsid, which is the 'head' of the phage that contains the viral DNA and replication machinery. So, they're like a spring-powered needle that goes and sits on the target cell, then appears to poke all the way through the cell membrane making a hole to the cytoplasm, so the cell loses its ions and contents and collapses."

A wide variety of bacteria are capable of producing tailocins, and seem to do so under stress conditions. Because the tailocins are only lethal to specific strains - so specific, in fact, that they have earned the nickname "bacterial homing missiles" - tailocins appear to be a tool used by bacteria to compete with their rivals. Due to their similarity with phages, scientists believe that the tailocins are produced by DNA that was originally inserted into bacterial genomes during viral infections (viruses give their hosts instructions to make more of themselves), and over evolutionary time, the bacteria discarded the parts of the phage DNA that weren't beneficial but kept the parts that could be co-opted for their own benefit.

But, unlike most abilities that are selected through evolution, tailocins do not save the individual. According to Mutalik, bacteria are killed if they produce tailocins, just as they would be if they were infected by true phage virus, because the pointed nanomachines erupt through the membrane to exit the producing cell much like replicated viral particles. But once released, the tailocins only target certain strains, sparing the other cells of the host lineage.

"They benefit kin but the individual is sacrificed, which is a type of altruistic behavior. But we don't yet understand how this phenomenon happens in nature," said Mutalik. Scientists also don't know precisely how the stabbing needle plunger of the tailocin functions.

These topics, and tailocins as a whole, are an area of hot research due to the many possible applications. Mutalik and his colleagues in Berkeley Lab's Biosciences Area along with collaborators at UC Berkeley are interested in harnessing tailocins to better study microbiomes. Other groups are keen to use tailocins as an alternative to traditional antibiotics -which indiscriminately wipe out beneficial strains alongside the bad and are increasingly ineffective due to the evolution of drug-resistance traits.

In their most recent paper, the collaborative Berkeley team explored the genetic basis and physical mechanisms governing how tailocins attack specific strains, and looked at genetic similarities and differences between tailocin producers and their target strains.

After examining 12 strains of soil bacteria known to use tailocins, the biologists found evidence that differences in the lipopolysaccharides - fat- and sugar-based molecules - attached to the outer membranes could determine whether or not a strain is targeted by a particular tailocin.

"The bacteria we studied live in a challenging, resource-poor environment, so we're interested to see how they might be using tailocins to fight for survival," said Adam Arkin, co-lead author and a senior faculty scientist in the Biosciences Area and technical co-manager of the Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) Scientific Focus Area. Arkin noted that although scientists can easily induce bacteria to produce tailocins in the lab (and can easily insert the genes into culturable strains for mass production, which will be handy if we want to make tailocins into medicines) there are still a lot of unanswered questions about how bacteria deploy tailocins in their natural environment, as well as how - and why - particular strains are targeted with an assassin's precision.

"Once we understand the targeting mechanisms, we can start using these tailocins ourselves," Arkin added. "The potential for medicine is obviously huge, but it would also be incredible for the kind of science we do, which is studying how environmental microbes interact and the roles of these interactions in important ecological processes, like carbon sequestration and nitrogen processing."

Currently, it's very difficult to figure out what each microbe in a community is doing, as scientists can't easily add and subtract strains and observe the outcome. With properly harnessed tailocins, these experiments could be done easily.

Mutalik, Arkin, and their colleagues are also conducting follow-up studies aiming to reveal tailocins' mechanisms of action. They plan to use the advanced imaging facilities at Berkeley Lab to take atomic-level snapshots of the entire process, from the moment the tailocin binds to the target cell all the way to cell deflation. Essentially, they'll be filming frames of a microscopic slasher movie.

Credit: 
DOE/Lawrence Berkeley National Laboratory

AI-powered symptom checkers can help healthcare systems deal with the COVID-19 burden

AI-powered symptom checkers can potentially reduce the number of people going to in-person clinics during the pandemic, but first, researchers say, people need to know they exist.

COVID symptom checkers are digital self-assessment tools that use AI to help users identify their level of COVID-19 risk and assess whether they need to seek urgent care based on their reported symptoms. These tools also aim to provide reassurance to people who are experiencing symptoms that are not COVID-19 related.

Most platforms, like Babylon and Isabel, are public-facing tools, but the University of California, San Francisco (UCSF) has one of the first COVID-19 symptom checkers that is fully integrated with the users' medical records, allowing for immediate appointment scheduling.

A mixed-methods study at the University of Waterloo found that 18- to 34-year-old young adults, typically the first age group to adopt new technologies, were unaware of the existence of these platforms.

"Young adults are usually eager adopters of technology, so we were a little surprised by this finding," said lead researcher Stephanie Aboueid, a PhD candidate in the School of Public Health and Health Systems. "Symptom checkers have the potential to reduce the burden on health-care systems and the risk of person-to-person infection, so we wanted to find out how to improve these platforms so more people use them."

Of the 22 university students interviewed in winter and spring of 2020, nine of them did not know the tools exist. The researchers also conducted a survey on general symptom checkers in winter 2021, and data suggested 88 per cent (1,365 out of 1,545) of participants did not use one in the past year.

Findings from the smaller qualitative study suggest that three-quarters of those who had used government-issued symptom checkers were satisfied with them. Those who used non-government symptom checkers found the experience suboptimal, citing a lack of trust and credibility.

"One of the findings was that users wanted more personalization and were less trusting of tools that gave the same results to everyone," Aboueid said. "The UCSF system was able to reduce the number of visits while taking into account underlying conditions along with the symptom checks and booking follow-up appointments when needed."

Besides more personalization, the researchers found that other improvements to existing symptom checkers include providing users more information about the creators of the platform, providing more explanation of the symptoms in lay language, more language options and the option to get tested at a nearby location.

Credit: 
University of Waterloo

Characteristics of multisystem inflammatory syndrome in children during COVID-19

What The Study Did: The clinical and other characteristics of multisystem inflammatory syndrome in children in the United States, a condition that occurs in association with the COVID-19 pandemic, are described in this study.

Authors: Ermias D. Belay, M.D., of the Centers for Disease Control and Prevention in Atlanta, 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/jamapediatrics.2021.0630)

Editor's Note: The article includes conflict of interest 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.

Credit: 
JAMA Network

Gut microbiome plays role in autism

Washington, D.C. - April 6, 2021 - A new study has demonstrated that autism spectrum disorder is related to changes in the gut microbiome. The findings are published this week in mSystems, an open-access journal of the American Society for Microbiology.

"Longitudinally, we were able to see that within an individual, changes in the microbiome were associated with changes in behavior," said principal study investigator Catherine Lozupone, PhD, a microbiologist in the Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado. "If we are going to understand the link between the gut microbiome and autism, we need more collaborative efforts across different regions and centers to get really thorough generalizable information about this relationship."

In the new study, researchers compared the gut microbiome composition between individuals with autism spectrum disorder and neurotypical controls in Arizona and Colorado using standardized DNA extraction and sequencing methods. The researchers found that the gut microbiome composition differed between individuals in Arizona and those in Colorado and gastrointestinal symptoms were significantly higher in those with autism compared with those without autism in Arizona but not Colorado. Gut microbiome composition was significantly associated with autism while controlling for study-site location but not when controlling for gastrointestinal symptoms.

The researchers also longitudinally evaluated the gut microbiome's relationship to autism behavioral severity, diet, and gastrointestinal symptoms in the individuals from Colorado. "We reached out to study participants every three months or so and had them fill out a number of checklists, one being the aberrant behavior checklist which looks at behaviors that are associated like inappropriate speech and repetitive motions," said Dr. Lozupone. "A food frequency questionnaire asked participants what they were eating in the past week. We also asked what types of GI symptoms participants were experiencing. We obtained fecal samples to look at the microbiome. We collected all this data to see how it related to each other."

In the longitudinal analysis, the researchers found that difference in levels of lethargy/social withdrawal measured in individuals at different time points correlated with the degree of change in gut microbiome composition and that a worsening of inappropriate speech between time points was associated with decreased gut microbiome diversity.

"We need more research, but our work shows that the gut microbiome is playing a role in the provocation of symptoms in kids with autism spectrum disorder," said Dr. Lozupone.

"This further supports the fact that the gut microbiome could be a valuable therapeutic target for children with autism spectrum disorders. I know that some labs have been exploring things like fecal microbiome transplant in these children and having some promising results."

Further work to tease out the mechanisms at play could lead to new therapies for children with autism.

Credit: 
American Society for Microbiology

Young people with autism improved their communication with their families during lockdown

The period with the strictest lockdown conditions and quarantining posed additional problems for young people with autism spectrum disorder (ASD) and their families, given that their routines were suddenly disrupted. Routines form an essential aspect of their everyday life and life structure. However, their response and adaptation to this new situation was better than expected in aspects like communication and interaction with their families.

A study conducted by researchers from the Universitat Oberta de Catalunya, the University of Perugia and the ABAULA Occupational Therapy and Child and Adolescent Psychology Centre in Girona studied the behaviour of young people who suffer autism spectrum disorder during the strictest lockdown period (March, April, May and June 2020) to lay the foundations for future support more in line with their actual needs.

According to the authors of the study, most of the families that participated in the study observed a change in the emotional state of their child with ASD. Specifically, parents stressed that during lockdown their children were happier, calmer and more placid than they were before it. To a great extent, they benefitted from the increase in the amount of time they spent with their families and the routines they adopted.

"Families stressed that children and adolescents with ASD adapted to the situation much better than they expected. In fact, following an initial period of complexity, they improved in aspects such as communication, relationships and emotional responses and they even participated more often in routines proposed by their families", highlighted Cristina Mumbardó Adam, an affiliated member of the UOC's Cognition and Language Research Group (GRECIL), a Disability and Quality of Life: Educational Aspects (DISQUAVI) researcher and the lead author of this study.

In this sense, the authors relate that, in the European context, normal working hours do not necessarily make it easy for families to spend more quality time with their children, given that long working days make it hard to strike a work-life balance. However, the timetable flexibility brought in with the pandemic has provided families with more time to look after, grow with, teach and make progress with their children.

Care and technological support

In spite of these results, families with these children in their care also stressed that they suffered greater difficulties at the start of the quarantine. This was not just due to the disruption of their habits, but also because their care and educational resources were not prepared for this new situation.

"Families lamented the lack of support from their schools, which, like all schools, had to reorganize, which took some time to achieve. However, families did highly appreciate having more time to spend with their children, to get to know them better and be able to broaden their range of interests", highlighted Mumbardó. The expert also stated that education centres and professionals "did everything they could during the quarantine to reach all their students" although the situation has shown that "it is clear that new measures are necessary to face such challenges."

Moreover, the experts also assessed the adaptation and response of youth with ASD to processes they were less familiar with, such as the use of new technologies to stay in contact, especially video calls.

They found that these youngsters also respond well to new remote communication channels. For example, seeing their family members, teachers and friends on video calls made during lockdown increased their well-being and calmness.

"Technology was of great help and although sometimes they did not know how to use these new means of communicating with someone, just being able to see a grandparent, classmates and other family members made them happier and calmer", said the researcher.

However, the authors point out that due to the variability of symptoms associated with ASD, the results are applicable to these families, but not necessarily to other family units.

Lack of social understanding

Additionally, the quarantine and lockdown situation also highlighted the lack of social understanding suffered by people with autism spectrum disorder and their families. This situation was especially evident at the specific times during the pandemic when the social groups with the greatest difficulties were allowed to go outside.

In this context, some families were rebuked by their neighbours for apparently not respecting the lockdown and they were unwilling to stigmatize their children by making them wear items like blue scarves as a means of identification. "This unpleasant situation was experienced by a lot of people who had the right to go outside because they needed to and it was very hard on many families", stated Mumbardó.

Finally, the experts explained that future research in this area must focus on benefits and the development of policies to ensure the well-being and academic performance of children with ASD who attend inclusive schools.

"Policymakers and stakeholders should take this study into account in any future decision-making processes related to the Covid-19 pandemic", concluded the authors.

Credit: 
Universitat Oberta de Catalunya (UOC)

A new material enables the usage of 'calcium' for batteries

image: Calcium battery employing new fluorine-free electrolyte using hydrogen cluster with high conductivity and high electrochemical stability againstlectrodes.

Image: 
Kazuaki Kisu and Shin-ichi Orimo

Scientists from Tohoku University have developed a new fluorine-free calcium (Ca) electrolyte based on a hydrogen (monocarborane) cluster that could potentially realize rechargeable Ca batteries.

The researchers say the new material, achieved by designing the coordination structure of Ca cation with a weakly coordinating anion and mixed solvents, shows markedly improved electrochemical performances such as high conductivity and high electrochemical stabilities.

Current lithium-ion (Li-ion) batteries have some drawbacks. They are approaching their demand limits of theoretical energy density and cost, and lithium is not naturally plentiful.

Calcium, however, is the fifth most abundant element in Earth's crust and its metal anode has low reduction potential (-2.87 V vs. standard hydrogen electrode (SHE)) and volumetric capacities of 2072 mAh cm-3, giving it comparable cell voltage and energy density to those of Li. Calcium batteries are therefore cost effective and possess high battery performance, making them a suitable substitute for Li-batteries.

Still, many challenges remain before Ca batteries can be realized due to a lack of suitable electrolytes which possess reductive/oxidative stabilities and high ionic conductivities. Moreover, realizing a fluorine-free system is desirable for practical Ca electrolytes because a fluorine-containing electrolyte intrinsically induces CaF2 formation on the electrode, which hinders Ca diffusion as well as the Ca plating and stripping processes.

The Tohoku University research team, which was led by Kazuaki Kisu and Shin-ichi Orimo from the Advanced Institute for Materials Research (AIMR), utilized the hydrogen cluster anion because of its high reductive and oxidative stability, which allows for a wide potential window and demonstrates excellent stability against metal anodes such as Li, Na, and Mg.

"A design that incorporates a hydrogen cluster into a Ca electrolyte had not been proposed yet," said Kisu. "We were pleased that this turned out suitable for a Ca battery."

The team, which also included Kim Sangryun from the Institute of Materials Research and Kun Zhao and Andreas Züttel from École Polytechnique Fédérale de Lausanne (EPFL) as part of Tohoku University's Core Research Cluster for Materials Science, envisions this new Ca electrolyte with robust electrochemical performances to be a breakthrough for Ca batteries.

"We expect the development of a promising electrolyte candidate based on complex hydrides compatible with Ca batteries will create future opportunities for exploring other related complex hydride compounds such as multivalent electrolytes," added Kisu.

Credit: 
Tohoku University

Maternal stress in conception linked to higher chance of female foetus

image: The UGR research team that conducted this study

Image: 
university of granada

A total of 108 women participated in the research from the first weeks of pregnancy to delivery, having recorded their stress levels before, during, and after conception (via the concentration of cortisol in hair) and performed different psychological tests

A study carried out by scientists from the University of Granada (UGR) has revealed that women who experience stress both before becoming pregnant and during conception are almost twice as likely to have a girl as a boy.

Researchers from the Mind, Brain and Behaviour Research Centre (CIMCYC), the Department of Pharmacology (Faculty of Pharmacy), and the Faculty of Psychology have analysed the levels of cortisol (a steroid hormone that is released in response to stress) in the hair of pregnant women in the period spanning from before conception to week 9 of pregnancy, to determine whether there was any link with the sex of the baby.

A total of 108 women were monitored from the first weeks of pregnancy through to delivery, to record their stress levels before, during, and after conception via the concentration of cortisol in their hair and various psychological tests. The measurement of cortisol in hair samples taken approximately in week 8-10 of pregnancy showed the concentration of cortisol in the pregnant woman for the previous three months (one month per centimetre of hair growth), meaning that it covered the period preceding and after conception. Subsequently, the UGR scientists recorded different variables relating to the birth and the sex of the baby.

María Isabel Peralta Ramírez, the main author of this work and researcher at the UGR's Department of Personality, Evaluation and Psychological Treatment explains: "The results we found were surprising, as they showed that the women who had given birth to girls presented higher concentrations of hair cortisol in the weeks before, during, and after the point of conception than those who had boys." In fact, these cortisol concentrations in the hair of mothers who subsequently had girls were almost double those who had boys.

Consequences of stress

There is ample scientific evidence demonstrating the impact of stress on the mother in the processes of pregnancy, birth, and even infant neurodevelopment. "Specifically, our research group has shown in numerous publications how psychological stress in the mother generates a greater number of psychopathological symptoms during pregnancy, postpartum depression, a greater likelihood of assisted delivery, an increase in the time taken for lactation to commence (lactogenesis), or inferior neurodevelopment of the baby six months after birth," says Peralta.

All of the existing research tells us about the effect of stress when pregnancy has already occurred. However, few studies have shown the link between stress and the mother-to-be before or during the conception of the baby, the present study being a rare exception. Its findings were recently published in the prestigious Journal of Developmental Origins of Health and Disease.

One possible explanation for the results would be that the activation of the "stress system"--the hypothalamus-pituitary-adrenal gland system--which involves an increase in cortisol secretion, modifies the concentrations of sex hormones at the time of conception. However, the mechanisms underlying this modification are not clear, because, on the one hand, there is evidence that testosterone could influence the determination of the baby's sex, since the higher the levels of prenatal stress, the higher the levels of female testosterone.

On the other hand, there is scientific evidence that sperm carrying the X chromosome (which determines that the baby will be female) perform better at passing through the cervical mucus in circumstances of adversity. Therefore, due to the hormonal changes associated with stress in the mother, these sperm are more likely to be successful in reaching the egg than sperm carrying the Y chromosome (which determines that the baby will be male).

"There are other possible hypotheses that attempt to explain this phenomenon. Among the strongest theories is the idea that there are more terminations of male foetuses on medical grounds during the first weeks of gestation in situations of severe maternal stress. That said, in light of the design of these studies, it is recommended that the results are corroborated in greater depth," observes Peralta.

The effect of stress on the foetus

What does appear to be clear-- and this has been shown in several studies--is that foetuses are vulnerable to the effect of stress, since it plays a key role in their development. An example of this is the proven fact that male (XY) foetuses mature more slowly than female (XX) foetuses; they tend to be associated with more complications in pregnancy and premature delivery; and, at birth, they are more likely to have shorter telomeres. This renders XY foetuses more vulnerable to adverse prenatal environments, suggesting that women who experience high levels of stress around the time of conception may be less likely to give birth to a boy.

Credit: 
University of Granada

New wasp species discovered in Norway

image: There are a total of over 2,500 described golden wasp species, with 40 recorded in Norway.

Image: 
Photo: Arnstein Staverløkk, NINA, CC BY3.

Cuckoo wasps - also called emerald wasps - are some of the most beautiful insects we have, with colourful exteriors that shine like jewels. However, these beauties have also created a lot of headaches.

"Normally we distinguish insects from each other by their appearance, but cuckoo wasps are so similar to each other that it makes it difficult," says Frode Ødegaard.

Ødegaard is an insect researcher at the NTNU (Norwegian University of Science and Technology) University Museum and belongs to the European research group that has now described thia recent contribution to species diversity. The new species is very rare, and is only a single specimen has been found on the Lista peninsula in Agder county in Norway.

For more than 200 years, insect researchers have struggled to sort cuckoo wasps into the right "species boxes," and to determine which characteristics are variations within a species and which are species-specific differences.

In the last 10 years, DNA barcoding has brought about a major breakthrough by making it possible to distinguish different species of cuckoo wasps from each other by looking at the differences in their genetic material.

"But it's not always that easy, either. In this case, we had two cuckoo wasps with microscopic differences in appearance and very small differences in DNA," Ødegaard says.

"The next step was to look at the language of each of the wasps to find out if they belonged to different species," he says.

Insects communicate with each other through pheromones - in other words, they have a chemical language. Very closely related species often have completely different languages to prevent them from interbreeding.

The cuckoo wasp is an insect with above-average linguistic abilities. They are parasites, which means that they behave like cuckoos and lay their eggs in the nests of other bees and wasps. The larvae grow quickly and hatch before the host's eggs. Then they eat the eggs, the larvae and the food supply that the host has arranged in the nest.

"When you live as a parasite, it's important not to be discovered, and therefore the cuckoo wasp has also learned the language of its host," says Ødegaard.

By conducting an ever-so-small language study, the researchers were able to discover that the two almost identical cuckoo wasps did indeed belong to different species. They use different hosts - and that means that they also speak completely different languages.

"The evolutionary development associated with sponging off another species happens very fast. That's why you can have two species that are really similar genetically but still belong to different species," says Ødegaard.

When a new species is described it has to be given a name, and Frode Ødegaard had the good fortune to receive the honour of naming the newcomer.

"A naming competition was announced among researchers in Europe who work with cuckoo wasps, and then the proposals that came in were voted on. It turned out my proposal actually got the most votes!" Ødegaard says.

"As mentioned, the new wasp is very similar to another species called Chrysis brevitarsis, so the new species was named Chrysis parabrevitarsis, which means 'the one standing next to brevitarsis'."

Ødegaard was also responsible for giving the species its slightly simpler Norwegian name of sporegullveps. He makes no secret of the fact that he found it great to be able to name a new species.

"In a way, you place yourself in the perspective of eternity, because that species will always have that name. There's something very fundamental about it."

The only known specimen of this cuckoo wasp has been captured and pinned in an insect collection. So it may seem both morally reprehensible and unnecessary that this one lone individual was stuck onto a needle.

"Even with today's advanced methods, using live animals for studies like this isn't possible, but collecting individual specimens fortunately has no impact on the population," Ødegaard says.

"The insects have enormous reproductive potential, and the size and quality of the habitats are what determine the viability of the population, not whether any specimens are eaten by birds or collected by an insect researcher."

He adds that the collected insects are absolutely crucial for researchers to be able to map and describe their diversity and thus take care of viable populations for posterity.

Credit: 
Norwegian University of Science and Technology

Rising Sika deer populations linked to bovine TB infections

image: New research suggests Ireland's increasing populations of Sika deer may be linked to local outbreaks of TB infection in cattle. Although TB infection rates have decreased in general in recent decades, county-level data shows a correlation between higher Sika numbers and higher local TB infections - with County Wicklow a particular hotspot.

Image: 
Benjamin Lecomte

New research suggests Ireland's increasing populations of Sika deer may be linked to local outbreaks of TB infection in cattle.

Although TB infection rates have decreased in general in recent decades, county-level data shows a correlation between higher Sika numbers and higher local TB infections - with County Wicklow a particular hotspot.

The research, conducted by researchers from Trinity College Dublin and the National Parks and Wildlife Service and supported by the Department of Agriculture, Food and the Marine, has major implications for controlling TB. It has just been published in the journal, Frontiers in Veterinary Science.

First author of the journal article, Dr David Kelly, from Trinity's School of Natural Sciences, said:

"Irish farmers have been aware of the effects of bovine TB for well over 70 years. Its incidence has steadily diminished in Ireland, from 3% in 1960 to 0.3% some 50 years later. In the mid-1980s it became clear European badgers were a TB wildlife host. Since then, badger populations have been controlled around farms with TB outbreaks whenever those outbreaks cannot be linked to cattle.

In recent years, however, it has become clear that controlling TB in badger populations cannot rely on culling alone. Along with this change in thinking, there has been a steady shift away from culling and towards badger vaccination. Unfortunately, while the management of one TB wildlife host has made great advances, another wildlife TB host has appeared on the radar: deer."

The number of deer in Ireland has been rising steadily during the 21st century, and studies in Europe and the USA have shown that deer, at higher densities, can sustain TB in their herds. Indeed, recent research has identified Sika deer in County Wicklow as one such maintenance host of TB.

The researchers behind the current study used county-level population densities (taken between 2000 and 2018) to track the three known maintenance hosts of TB in Ireland: cattle, badgers, and Sika deer.

They then considered how variations in local densities compared with the variation in bovine TB infection across the country (and also at county-level).

Dr Kelly said:

"Our analyses show that while there have been general reductions in TB infection, there is a correlation between increasing Sika deer density and higher local TB infection. This pattern has emerged in recent years and has major implications for TB control within Ireland.

"Now, when attempting to manage TB in wildlife, Sika deer will need to be considered as well as badgers. Our analyses suggest Sika deer are currently of greatest concern in County Wicklow but if numbers continue to rise in other counties they may also pose problems elsewhere."

Credit: 
Trinity College Dublin

LSU Health New Orleans study discovers source of Zika neurodevelopmental defects

New Orleans, LA - A study led by Edward Wojcik, PhD, Associate Professor of Biochemistry & Molecular Biology at LSU Health New Orleans School of Medicine, identified how microcephaly (abnormally small heads) and blindness may develop in Zika-infected fetuses, as well as a new way to potentially prevent these neurodevelopmental defects. The results are published online in iScience, available here.

The mechanism by which Zika virus disrupts neuronal development and results in congenital Zika syndrome was unknown. Because of similarities between Zika syndrome and a recognized congenital genetic disease (Kinesin-5) known to cause microcephaly and retinopathies in developing infants, the research team studied both, looking for similarities. They discovered a direct link, the first molecular and cellular evidence supporting a direct connection between the two.

"We had a hunch that the microcephaly and blindness that results from Kinesin-5 genetic disease could be linked to Zika infection, and the hunch paid off," notes Dr. Wojcik. "Our experiments identify a molecular motor as a target for degradation by an encoded Zika virus protein (Zika protease). The molecular motor is Kinesin-5, and it is required for cell division in humans. Our data identify Kinesin-5 as a target for the virus and links the infection to microcephaly."

The researchers observed that Zika protease cuts Kinesin-5 during cell division, disrupting the process and causing a loss of function. They also suggest a way to prevent it.

The Zika protease can degrade only a target protein it can reach. Since the protease is part of the endoplasmic reticulum (ER) membrane, only target proteins that come in direct contact with the ER can be degraded. In this way, the protease acts in a spatially restricted manner in the cell; target proteins are degraded only in certain regions of the cell volume and not in others. So, the research team proposes a drug that would affect only the Zika protease instead of drugs that would affect all target proteins in a cell.

"We predict and hope that potential drugs that inhibit Zika protease may be effective in preventing microcephaly and blindness from developing within Zika-infected fetuses," Dr. Wojcik concludes.

Credit: 
Louisiana State University Health Sciences Center

Seismic coda used to locate and define damage from explosions

Comparison of coda waves, the scattered waves that arrive after the direct waves of a seismic event, can be used to determine the relative locations of two underground explosions, according to a new study published in the open-access journal The Seismic Record.

The technique, called coda wave interferometry, was tested on explosions conducted as part of the Source Physics Experiment (SPE). Lawrence Livermore National Laboratory researchers Sean Ford and Bill Walter report that coda wave interferometry can also put a limit on the extent of damage caused by an explosion.

The findings suggest the technique could be used to improve the estimates of the relative locations of larger explosions, such as the series of announced nuclear tests conducted by the Democratic People's Republic of Korea over the past two decades.

"Based on the size and frequency scaling that we were able to employ in the paper and successes at SPE," said Ford, "a conclusion point is that this technique could be used for larger explosions at larger separations recorded at more distant stations" such as those used to monitor North Korean testing.

Unlike the direct and strong P- and S-seismic waves produced by an earthquake or explosion event, coda waves arrive later and are more sensitive to scattering by the rock that they pass through. Any changes in the scattering structure--from rocks pushed or crushed by an explosion, for example--"will show up in how these later arriving waves have bounced around in that medium over a greater duration," Ford explained.

In the new study, Ford and Walter used data from the SPE, an ongoing multi-institutional project involving Lawrence Livermore, Los Alamos and Sandia National Laboratories at the former Nevada nuclear test site. The SPE conducts chemical explosions to better understand the seismic waves they produce and to refine explosion detection techniques, using the analyses to improve monitoring of global nuclear explosions.

The researchers used coda wave interferometry to determine the known relative location of two chemical explosions that took place during Phase I of the SPE. The first explosion, SPE-1, was equivalent to 87.9 kilograms of TNT. The second explosion, SPE-2, was equivalent to 997 kilograms of TNT.

Their analysis concluded that the two explosions were located between 6 and 18 meters apart, and most likely 9.2 meters apart. The known separation between the two explosions is about 9.4 meters apart.

Previous research by seismologists David Robinson and coworkers, showed that coda wave interferometry could precisely locate earthquakes separated by hundreds of meters. "We were confident that the approach would work for chemical explosions, but the question for us was whether it could work for such small and closely located explosions," said Ford.

Ford and Walter also used the technique to better characterize the underground damage caused by SPE-2, comparing its coda waves with those produced by the 905-kilogram TNT equivalent SPE-3 that was later detonated in the same spot as SPE-2.

The details of the damage "can't be seen from the direct waves arriving at the [1-kilometer or more] distant stations that we're used to, so we thought perhaps we could see it in these more sensitive scattered waves, the coda waves," Ford explained

Based on the analysis, the damage caused by SPE-2 must have been confined to a spherical region with a radius less than 10 meters, the researchers concluded.

"We thought there would be much more damage, or at least more of an effect on the outgoing waves, but now there is evidence against that hypothesis, so this points us in other directions to explain the observed P- and S-waves," Ford said.

The study is the first research paper published in The Seismic Record, a new short-form, open-access journal from the Seismological Society of America.

Credit: 
Seismological Society of America

Small cell lung cancer: Scientists identify two new approaches for therapy

image: Small cell lung cancer cells in culture (blue), non-endocrine cells are stained red.

Image: 
Christina Bebber

Using samples of small cell lung tumours, a research team led by biologist Dr Silvia von Karstedt has discovered two new ways to induce tumour cell death. One of two subsets of tumour cells can be targeted by activating ferroptosis: iron-dependent cell death caused by oxidative stress. In the second subtype, oxidative stress - and hence cell death - can also be induced in a different way. Both types of cell death must be triggered simultaneously by drugs to kill the majority of the tumour mass. The results of the study have been published in Nature Communications.

Despite many advances in treatment, a diagnosis of small cell lung cancer means a particularly poor prognosis. In Germany, up to 8000 new cases of small cell lung cancer (SCLC) are diagnosed each year. At the time of diagnosis, cancer has already found many loopholes to escape the body's immune system. 'Traditional' cell death mechanisms, such as regulated cell death by apoptosis, are usually already inactivated at this stage. That way, tumour cells can continue to divide and spread almost unperturbed.

A high cell division rate is characteristic of small cell lung cancer, which initially promises a good response to chemotherapy. 'Unfortunately, in many cases the success of chemotherapy is short-lived because tumour cells rapidly develop resistance to therapy. In addition, a tumour consists not only of one, but of several cell types - the so-called subtypes - each of which uses unique strategies to escape lethal therapy,' said von Karstedt, research group leader at the CECAD Cluster of Excellence for Aging Research, the Department of Translational Genomics at the University of Cologne and the Center for Molecular Medicine Cologne (CMMC). This is where her research comes in. The biologist explores which cell death mechanisms are already inactivated in cancer cells and which ones can still be targeted by therapies to kill the tumour.

The research team used patient samples taken at the time of diagnosis, thus depicting the treatment-naïve tumour. To find out which pathways of cell death are still available, the scientists compared gene activity between patient cells taken inside and outside the tumour. Signalling pathways important for traditional cell death mechanisms were already switched off inside the tumour at this early stage, before therapy. In contrast, genes important for the activation of iron-dependent cell death by oxidative damage (ferroptosis) were strongly activated in the cancer cells.

Put in simple terms, small cell lung cancer cells can be divided into two subtypes: neuroendocrine cells and non-neuroendocrine cells. In the neuroendocrine cell subtype, more genes are active which are otherwise typically found in nerve cells that produce hormones. Cells belonging to the other subtype do not have this property and are therefore grouped as non-neuroendocrine cells. 'Several experiments showed that cells of the non-neuroendocrine type can be killed using buthionine sulfoximine, which induces ferroptosis. In cells belonging to the neuroendocrine subtype, we found that they protect themselves from oxidative stress - and thus cell death - by producing antioxidants. However, by adding the antioxidant inhibitor Auranofin, we were able to kill these cells as well,' explains doctoral researcher Christina Bebber, the lead author of the paper.

Regarding a possible application of these findings to the therapy of small cell lung cancer, the biologists made an important observation: When targeting just one of the two pathways - i.e., either activating ferroptosis or inhibiting antioxidant production - in a tumour consisting of cells of both subtypes, cancer cells were able to evade the lethal therapy. They did so by adjusting their gene expression to switch to the subtype that could resist the respective single pathway-targeting treatment. 'When we applied a combination therapy, we took away this route of escape. What is also special about the study is that we used drugs that have already been tested in extensive clinical trials or even approved for the treatment of other diseases,' von Karstedt explained. Buthionine sulfoximine, which triggers ferroptosis, is already in clinical trials for cancer treatment. The gold salt Auranofin, which blocks the production of protective antioxidants in cancer cells, has been in use for decades to treat rheumatoid arthritis.

Future clinical studies using this combined therapy will clarify to what extent this targeted therapy option will improve the prognosis of small cell lung cancer patients.

Credit: 
University of Cologne

Being top baboon costs males their longevity

image: Male baboons maintain their pecking order in the troop with physical displays of aggression. A new study shows that the guys at the top will age faster as a result of constantly having to defend their higher status.

Image: 
Elizabeth Archie

DURHAM, N.C. -- Some guys have it all: the muscle, the power, the high social status, the accelerated aging.

But wait. Faster aging? Who wants that? For male baboons, it's the price they pay to be at the top.

New research appearing April 6 in eLife by Jenny Tung, associate professor of evolutionary anthropology and biology at Duke University, and her colleagues shows that male baboons that climb the social ladder age faster than males with lower social standing. If a male drops in social status, his estimated rate of aging drops as well.

Using blood samples from 245 wild baboons in the Amboseli ecosystem in Kenya, the team analyzed chemical modifications to DNA known as DNA methylation marks.

"These marks change with age in a clock-like fashion," Tung said. "However, environmental stressors can make the clock tick faster." This would make an individual appear older than they really are, and, research in humans suggests, can put them at a higher risk of aging-related disease.

Since this cohort of baboons is one of the most intensively studied wild mammal populations in the world, the researchers already knew not only each baboon's age, but also the environment in which they grew up, their exposure to early life adversity, and a great deal about their adult environment, especially the aspects that predict how long they live and how many offspring they leave behind.

"We used DNA methylation to compare the baboons known ages to their 'biological ages,'" said Jordan Anderson, a graduate student in the Tung lab who co-led the work. These methylation markers are found across the genome, so the team first needed to measure a large number of these sites - about 400,000 of them - and then, through statistical methods and models, whittle the number of sites down to about 500 that best predicted age.

Interestingly, for males, early life adversity didn't affect how fast their biological clocks tick.

Adult social status was the strongest factor that affected aging. "Male baboons who compete successfully for high social status appear to age faster," Tung said. "We repeatedly sampled some of these males and were able to show that the clock can speed up or slow down as males move up or down the social ladder."

This is contrary to what we see in humans. Typically, high social status in humans predicts better health, not worse. The most wealthy and powerful humans have access to and can afford the best houses, schools, healthcare and more. Those who live in poverty and have lower socioeconomic status are at increased risk and have higher rates of disease, cancer and all-cause mortality.

Male baboons, though, have to fight for their social status. Because of this, it's common to see male-male competition on a regular basis, where baboon observers can see a clear winner and a clear loser.

To maintain their social status, males at the top regularly have to hold their ground and defend themselves physically. Because of this, male baboons at the top tend to have more muscle mass and better body condition than lower ranking baboons. But as their physicality starts to diminish with age, a new, younger, stronger male may overcome them for the top spot.

High ranking males also spend a lot of time mate-guarding females. Around ovulation, they follow females closely and ward off other males. Mate-guarding constrains a male's other activities, and Tung and her team think it is likely to be energetically costly -- perhaps helping to explain their accelerated aging result.

So why do these males work so hard to achieve a high stress social status? It's simple: to have offspring.

"If male baboons are going to have babies, they need to achieve high rank," Tung said. "They will have very little chance to leave offspring if they don't achieve high rank, which creates a powerful evolutionary motivation."

This study highlights one way that the social environment can influence aging. "Our research shows that the manner in which social status is attained and maintained is crucial to understanding its consequences," Tung said.

Credit: 
Duke University