Brain

Researchers perform experiments that can add or subtract a single quantum of sound--with surprising results when applied to noisy sound fields.

Quantum mechanics tells us that physical objects can have both wave and particle properties. For instance, a single particle--or quantum--of light is known as a photon, and, in a similar fashion, a single quantum of sound is known as a phonon, which can be thought of as the smallest unit of sound energy.

A team of researchers spanning Imperial College London, University of Oxford, the Niels Bohr Institute, University of Bath, and the Australian National University have performed an experiment that can add or subtract a single phonon to a high-frequency sound field using interactions with laser light.

The team's findings aid the development of future quantum technologies, such as hardware components in a future 'quantum internet', and help pave the way for tests of quantum mechanics on a more macroscopic scale. The details of their research are published today in the prestigious journal Physical Review Letters.

To add or subtract a single quantum of sound, the team experimentally implement a technique proposed in 2013 that exploits correlations between photons and phonons created inside a resonator. More specifically, laser light is injected into a crystalline microresonator that supports both the light and the high-frequency sound waves.

The two types of waves then couple to one another via an electromagnetic interaction that creates light at a new frequency. Then, to subtract a single phonon, the team detect a single photon that has been up-shifted in frequency. "Detecting a single photon gives us an event-ready signal that we have subtracted a single phonon," says lead author of the project Georg Enzian.

When the experiment is performed at a finite temperature, the sound field has random fluctuations from thermal noise. Thus, at any one time, the exact number of sound quanta present is unknown but on average there will be n phonons initially.

What happens now when you add or subtract a single phonon? At first thought, you may expect this would simply change the average to n + 1 or n - 1, respectively, however the actual outcome defies this intuition. Indeed, quite counterintuitively, when you subtract a single phonon, the average number of phonons actually goes up to 2n.

This surprising result where the mean number of quanta doubles has been observed for all-optical photon-subtraction experiments and is observed for the first time outside of optics here. "One way to think of the experiment is to imagine a claw machine that you often see in video arcades, except that you can't see how many toys there are inside the machine. Before you agree to play, you've been told that on average there are n toys inside but the exact number changes randomly each time you play. Then, immediately after a successful grab with the claw, the average number of toys actually goes up to 2n," describes Michael Vanner, Principal Investigator of the Quantum Measurement Lab at Imperial College London.

It's important to note that this result certainly does not violate energy conservation and comes about due to the statistics of thermal phonons.

The team's results, combined with their recent experiment that reported strong coupling between light and sound in a microresonator, open a new path for quantum science and technology with sound waves.

Cancer is the second leading cause of death in the world. The number of deaths and incidences is increasing each year. The metal-based anticancer drugs were used clinically worldwide, but suffer from poor selectivity, serious side effects and drug resistance. Tumor-targeting drug development is the basis for precise cancer treatment.

Recently, Professor Hongke Liu of Nanjing Normal University, Professor Jing Zhao and Academician Zijian Guo of Nanjing University have made breakthrough achievements in anticancer drug development. They proposed a "bio-orthogonally catalyzed lethality" (BCL) strategy (Figure 1) and published their results in "National Science Review" (National Science Review, NSR). The BCL strategy uses tumors as manufacturing factories to generate a highly potential tumor-targeted drug Ru-rhein, which can selectively kill cancer cells and tumors in tumor-bearing mice, while no toxicity on normal cells. BCL strategy generates targeting drugs from non-toxic compounds within the tumor, not only avoiding the decomposition and inactivation of the drug during transportation and storage, but also reducing the serious side effects caused by interacting with biologically active molecules during treatment.

The copper content in tumor cells is much higher than that in normal cells. The targeting drug Ru-rhein is generated from two non-toxic compounds Ru-N3 and rhein-alkyn within tumor with a yield of more than 80%, by using the endogenous copper-catalyzed bioorthogonal reactions. However, the above-mentioned reactions hardly occur in normal tissues. Thus tumor targeting and selectivity of Ru-rhein is realized by BCL strategy. Ru-rhein exhibits high anti-cancer activity, especially towards lung cancer cell A549, almost as toxic as cisplatin, while it is non-toxic to normal lung cell HLF and might be used as a candidate drug for clinical development (Figure 2). Ru-rhein targets the mitochondria of tumor cells and causes autophagic cell death through the mitochondrial pathway.

A mouse model was used to validate the BCL strategy. Compared with the control group, tumor growth of the tumor-bearing mice injected with Ru-N3 and rhein-alkyn was significantly inhibited, and other organs were almost undamaged (Figure 3). The generality of the BCL strategy was demonstrated in the generation of osmium and iridium-based metallodrugs within tumor cells.

The BCL method provides a general strategy for precise diseases treatment, and also reveals that tumor can provide copper species that efficiently catalyze orthogonal reactions. This research was funded by the National Natural Science Foundation of China. Dr. Xuling Xue, a postdoctoral fellow at Nanjing Normal University, is the first author of the paper.

Solar-driven photoelectrochemical (PEC) water splitting is an attractive approach to convert solar energy into chemical energy. Among many photoelectrode materials, crystalline silicon (c-Si) has drawn considerable attention because of its earth abundance, narrow bandgap, and suitable band edge position for hydrogen evolution reaction (HER). However, c-Si suffers from low photovoltage generated from the solid-liquid junction.

Various strategies, such as the construction of p-n homojunctions, metal-insulator-semiconductor (MIS) junctions and p-n heterojunctions, have been adopted to obtain high photovoltage. The MIS junctions have been the focus of attention in PEC water splitting due to their simple fabrication and the potential to achieve higher efficiencies than p-n junctions. However, there are very limited Si-based MIS photocathodes reported with efficiency exceeding 5%, much lower than that of p-n junction photocathode (10%).

One of the major challenges of p-Si MIS photocathodes for higher efficiency is the parasitic light absorption from HER catalysts such as Pt, Ni-Mo, etc. Traditional MIS photocathodes are fabricated from p-Si, where the photogenerated minority carriers (electrons) drive the reduction reaction at the front surface. This could be translated into the fact that the catalyst must be placed at the same side of MIS junction. Thus, the parasitic light absorption from catalysts will severely limit the photocurrent density. The metal layers in MIS junction also cause optical loss. Another limiting factor is the lack of low work function metals to form a large band offset with p-Si in MIS junction, resulting in a low photovoltage.

In a research article published in National Science Review, scientists at Tianjin University present a unique illumination-reaction decoupled MIS photocathode fabricated from n-Si, which surmounts the challenges that seriously impede the development of p-Si MIS photocathode.

Different from previous works that employ minority carriers to drive the surface reduction reaction, the majority carriers (electrons) of n-Si MIS photocathode are used in this work. Upon this simple, unconventional yet effective modification, the MIS junction and catalyst can be placed on the opposite sides of n-Si, which avoids the light-shielding problem of catalyst.

Moreover, this MIS photocathode constructed from n-Si addresses the drawback of lacking metallic materials with suitable work function to generate a large band offset for p-Si MIS photocathode. By using indium tin oxide (ITO) with a high transmittance as the high work function metallic material for n-Si MIS photocathode, the trade-off between metal coverage and light absorption confronted by high work function metals is further eliminated.

As a result, this illumination-reaction decoupled n-Si MIS photocathode exhibits a light absorption higher than 90%, a photovoltage up to 570 mV, and a recorded efficiency of 10.3%, exceeding traditional p-Si MIS photocathodes.

This facile strategy exhibits a potential to inspire the rational design of solar powered photoelectrochemical systems that use catalysts with poor light transmittance, a step forward towards future large-scale commercialization of solar water splitting.

Becoming a parent often brings great joy, but not always. Parenthood also entails challenges, stress and, for some people, it can trigger depression. A new study from Lund University in Sweden shows that male postnatal depression is more common in men who are insecure in their relationship with their partner.

Depression affects around 10-12 per cent of new mothers, and at least 8 per cent of new fathers. The figures are even higher when looking at depressive symptoms; as many as one in five new fathers experience troublesome symptoms, according to the new study conducted by Elia Psouni, registered psychologist and associate professor of psychology at Lund University in Sweden, and Anna Eichbichler, clinical psychologist.

The study focused on reasons behind the fathers' depressive symptoms. Affected men often have a negative view of themselves and are worried about being inadequate in their intimate relationships; a concern that may be based on childhood experiences with their own parents.

"Having a negative view of oneself, one's own characteristics and abilities, while valuing other people highly often leads to a constant worry about not being good enough, about disappointing others and - potentially - losing them", says Elia Psouni.

The study also attempted to determine what specific aspect of low self-esteem in intimate relationships triggered the depression. Is it a question of relationship difficulties in general, or stress about not being good enough as a parent? The answers showed it was the latter.

"Low self-confidence in close relationships seems to trigger parental stress, which in turn triggers the symptoms of depression", says Psouni.

This is the second study in which Psouni and her colleagues show that over one in five fathers of children aged 1-18 months experience debilitating symptoms of depression. The study also revealed that men whose female partners suffered from postpartum depression were over-represented, and that very few of them were in contact with a professional to get help.

"The study shows beyond doubt that parents affect one another and reveals the importance of monitoring how parents in various relationships and family constellations manage and fare over a long period", says Psouni.

She and her colleagues are now conducting a longitudinal project that will monitor families over time to generate knowledge about the wellbeing and development of children and parents in various family constellations.

Metals such as gold or platinum are often used as catalysts. In the catalytic converters of vehicles, for example, platinum nanoparticles convert poisonous carbon monoxide into non-toxic CO2. Because platinum and other catalytically active metals are expensive and rare, the nanoparticles involved have been made smaller and smaller over time.

"Single-atom" catalysts are the logical end point of this downsizing: The metal is no longer present as particles, but as individual atoms that are anchored on the surface of a cheaper support material. Individual atoms can no longer be described using the rules developed from larger pieces of metal, so the rules used to predict which metals will be good catalysts must be revamped - this has now been achieved at TU Wien. As it turns out, single atom catalysts based on much cheaper materials might be even more effective. These results have now been published in the journal Science.

Smaller is sometimes better

Only the outer atoms of the piece of metal can play a role in chemical processes - after all, the atoms inside never come into contact with the environment. In order to save material, it is therefore best to use tiny metal particles instead of large lumps, so that a greater proportion of the atoms reside at the surface. If we go to the ultimate limit and use individual atoms, every single atom is chemically active. Over the last decade the field of "single atom" catalysis has grown dramatically, achieving great success.

Wrong model, right solution

"The reasons why some precious metals are good catalysts was already researched in the 1970s," says Prof. Gareth Parkinson from the Institute for Applied Physics at TU Wien. "For example, Gerhard Ertl was awarded the Chemistry Nobel Prize in 2007 for providing atomic-scale insights into catalysis."

In a piece of metal, an electron can no longer be assigned to a specific atom; the electronic states result from the interaction of many atoms. "For individual atoms, the old models are no longer applicable" says Gareth Parkinson. "Individual atoms do not share electrons like a metal, so the electron bands, whose energy was key to explaining catalysis, simply do not exist in this case."

Gareth Parkinson and his team have therefore been intensively investigating the atomic mechanisms behind this single-atom catalysis in recent years. "In many cases the metals that we think of as good catalysts remain good catalysts in the form of individual atoms" says Gareth Parkinson. "In both cases it is the same electrons, the so-called d electrons, that are responsible for this."

Customized properties through tailored surfaces

Entirely new possibilities arise in single-atom catalysis that are not available when using ordinary metal particles: "Depending on the surface on which we place the metal atoms and which atomic bonds they form, we can change the reactivity of the atoms", explains Parkinson.

In some cases, particularly expensive metals like platinum are no longer necessarily the best choice. "Individual nickel atoms show great promise for carbon monoxide oxidation. If we understand the atomic mechanisms of single atom catalysis, we have a lot more leeway to influence the chemical processes," says Parkinson.

Eight different metals were precisely analyzed in this way at TU Wien - the results fit perfectly with the theoretical models that have now been developed in a collaboration with Prof. Cesare Franchini at the University of Vienna.

"Catalysts are very important in many areas, especially when it comes to chemical reactions that play a major role in attempts to develop a renewable energy economy," emphasizes Gareth Parkinson. "Our new approach shows that it doesn't always have to be platinum." The decisive factor is the local environment of the atoms - and if you choose it correctly, you can develop better catalysts and at the same time save resources and costs.

An adverse upbringing often impairs people's circumstances and health in their adult years, especially for couples who have both had similar experiences. This is shown by a new study, carried out by Uppsala University researchers, in which 818 mothers and their partners filled in a questionnaire one year after having a child together. The study is now published in the scientific journal PLOS ONE.

"When we studied couples where both partners stated they'd had a hard time as children, the connection between negative childhood experience and a relatively unfavourable living situation in adulthood became especially clear," says Per Kristiansson, a specialist doctor in general medicine, senior lecturer at Uppsala University's Department of Public Health and Caring Sciences and the study's principal author.

Adverse childhood experiences (ACEs) have serious lifelong repercussions. Previous international studies (eg Felitti et al 1998, Hughes et al 2017, Merrick et al 2018) have shown that they entail a greater risk of falling ill, and of dying prematurely, from a range of common diseases and conditions. These include severe mental ill-health, cancer, cardiovascular disease and diabetes. The more numerous the ACEs, the higher the risk of negative consequences.

The present study is distinguished by the unusually large number of respondent couples. A total of 818 (1636 individuals, comprising 818 mothers and their 818 partners, 3 of whom were women) took part, submitting answers to the questionnaire, one year after having a child together.

The ACEs the researchers focused on were both mental and physical abuse and neglect; sexual assault; and problematic situations in the family like criminal behaviour, substance abuse, violence, mental disorders and separations.

Individual ACEs were common among all respondents, and 11 per cent of the women and 9 per cent of their partners reported having four or more such experiences. In 2 per cent of the couples, both individuals recounted at least four ACEs. If one person in a couple had undergone them, the other was more likely to have done so as well.

The greater the number of ACEs for the woman, the partner and the couple together, the worse their adult prospects turned out to be. Several couples who had experienced many problems in childhood had strikingly more problems in adulthood than the others. This group of respondents, compared with the couples who described their childhood as problem-free, were characterised by the following to a larger extent:

low educational attainment

low income

poor couple relationships

overweight

smoking habits to a larger extent

low sense of coherence (SOC)

poor self-assessed health

high stress level

very high frequency of anxiety and depression.

Kristiansson explains: "The fact that ACEs in early life can have such grave consequences is connected with the severe, toxic stress that affects children's central nervous system and other organs while they are growing up. 'Toxic stress' means strong, frequent and lasting activation of the body's stress-response system (Shonkoff et al 2009). This indicates that ACEs have a far-reaching negative impact on people's lives and health up to an advanced age, and may also affect the next generation."

Previous studies (Shonkoff et al 2009, Heckman 2006) show, he points out, that combating toxic stress in the early years brings gains for society: it improves student performance, boosts economic productivity and enhances citizens' sense of responsibility.

"That's why we hope our results will prompt public agencies - especially healthcare and social services, but also civil society - to take the initiative in detecting, supporting and providing treatment for families and individuals affected by adverse childhood experiences."

PHILADELPHIA -- (Jan. 21, 2021) -- Researchers at The Wistar Institute have discovered a new enzymatic function of the Epstein-Barr Virus (EBV) protein EBNA1, a critical factor in EBV's ability to transform human cells and cause cancer. Published in Cell, this study provides new indications for inhibiting EBNA1 function, opening up fresh avenues for development of therapies to treat EBV-associated cancers.

EBV establishes life-long, latent infection in B lymphocytes, which can contribute to development of different cancer types, including Burkitt's lymphoma, nasopharyngeal carcinoma (NPC) and Hodgkin's lymphoma.

The Epstein-Barr Nuclear Antigen 1 (EBNA1) serves as an attractive therapeutic target for these cancers because it is expressed in all EBV-associated tumors, performs essential activities for tumorigenesis and there are no similar proteins in the human body.

"We discovered an enzymatic activity of EBNA1 that was never described before, despite the intense research efforts to characterize this protein," said Paul M. Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor, leader of the Gene Expression & Regulation Program at Wistar, and corresponding author of the study. "We found that EBNA1 has the cryptic ability to cross-link and nick a single strand of DNA at the terminal stage of DNA replication. This may have important implications for other viral and cellular DNA binding proteins that have similar cryptic enzyme-like activities."

Lieberman and colleagues also found that one specific EBNA1 amino acid called Y518 is essential for this process to occur and, consequently, for viral DNA persistence in the infected cells.

They created a mutant EBNA1 protein in which the critical amino acid was substituted with another and showed that this mutant could not form covalent binding with DNA and perform the endonuclease activity responsible for generating single strand cuts.

In latently infected cells, the EBV genome is maintained as a circular DNA molecule, or episome, that is replicated by cellular enzymes along with the cell's chromosomes. When the cell divides, the two episomal genomes segregate into the two daughter cells.

While it was known that EBNA1 mediates replication and partitioning of the episome during division of the host cell, the exact mechanism was not clear. The new study sheds light on the process and describes how the newly discovered enzymatic activity of EBNA1 is required to complete replication of the viral genome and maintenance of the episomal form.

"Our findings suggest that one could create small molecules to 'trap' the protein bound to DNA and potentially block replication termination and episome maintenance, similar to known inhibitors of topoisomerases," said Jayaraju Dheekollu, Ph.D., first author on the study and staff scientist in the Lieberman Lab. "Such inhibitors may be used to inhibit EBV-induced transformation and treat EBV-associated malignancies."

Suppose Smokey the Bear were to go on a tear and start setting forest fires instead of putting them out. That roughly describes the behavior of certain cells of our immune system that become increasingly irascible as we grow older. Instead of stamping out embers, they stoke the flames of chronic inflammation.

Biologists have long theorized that reducing this inflammation could slow the aging process and delay the onset of age-associated conditions, such as heart disease, Alzheimer's disease, cancer and frailty, and perhaps even forestall the gradual loss of mental acuity that happens to nearly everyone.

Yet the question of what, exactly, causes particular cells of the immune system to kick into inflammatory overdrive has lacked a definitive answer.

Now, Stanford Medicine researchers think they have one. If their findings in old mice and in human cell cultures apply to actual humans, they could presage the pharmaceutically managed recovery of older people's mental abilities.

In a study to be published Jan. 21 in Nature, the investigators pin the blame on a set of immune cells called myeloid cells. Katrin Andreasson, MD, professor of neurology and neurological sciences, is the study's senior author. Its lead author is MD-PhD student Paras Minhas.

Myeloid cells, which are found in the brain, the circulatory system and the body's peripheral tissues, are part soldier and part park ranger. When not fighting off infectious intruders, they keep busy cleaning up debris, such as dead cells and clumps of aggregated proteins; provide nutrient snacks to other cells; and serve as sentinels watching for signs of invading pathogens.

But as we age, myeloid cells begin neglecting their normal, health-protecting functions and adopting an agenda of endless warfare with a nonexistent enemy, inflicting collateral damage to innocent tissues in the process.

An effective blockade

In the study, blocking the interaction of a particular hormone and a receptor that abounds on myeloid cells was enough to restore the youthful metabolism and placid temperament of mouse and human myeloid cells in a dish and in living mice. This blockade also reversed age-related mental decline in older mice, restoring their recall and navigation skills to those exhibited by young mice.

"If you adjust the immune system, you can de-age the brain," Andreasson said. Her team's experiments in human cells suggest that similar rejuvenation may be possible in people, she said.

Myeloid cells are the body's main source of PGE2, a hormone that belongs to the family known as prostaglandins. PGE2 does many different things in the body -- some good, some not always so good -- for example, promoting inflammation. What PGE2 does depends on which cells, and which of several different varieties of receptor on those cells' surfaces, the hormone lands on.

One receptor type for PGE2 is EP2. This receptor is found on immune cells and is especially abundant on myeloid cells. It initiates inflammatory activity inside the cells after binding to PGE2.

Andreasson's team cultured macrophages, a class of myeloid cells situated in tissues throughout the body, from people older than 65 and compared them with macrophages from people younger than 35. They also looked at macrophages of young versus old mice.

'A double-whammy'

Older mouse and human macrophages, they observed, not only produced much more PGE2 than younger ones but also had far greater numbers of EP2 on their surfaces. Andreasson and her colleagues also confirmed significant increases of PGE2 levels in the blood and brains of old mice.

"It's a double-whammy -- a positive feedback loop," Andreasson said. The resulting exponential increase in PGE2-EP2 binding amps up intracellular processes associated with inflammation in the myeloid cells.

The investigators showed, in both human and mouse myeloid cells, how this inflammatory hyperdrive sets in: The vastly increased PGE2-EP2 binding in myeloid cells of older individuals alters energy production within these cells by rerouting glucose -- which fuels energy production in the cell -- from consumption to storage.

The researchers found that myeloid cells undergo an increasing propensity, driven by age-associated increased PGE2-EP2 binding, to hoard glucose by converting this energy source into long glucose chains called glycogen (the animal equivalent of starch) instead of "spending" it on energy production. That hoarding, and the cells' subsequent chronically energy-depleted state, drives them into an inflammatory rage, wreaking havoc on aging tissues.

"This powerful pathway drives aging," she said. "And it can be downshifted."

The Stanford scientists showed this by blocking the hormone-receptor reaction on myeloid-cell surfaces in the mice. They gave mice either of two experimental compounds known to interfere with PGE2-EP2 binding in the animals. They also incubated cultured mouse and human macrophages with these substances. Doing so caused old myeloid cells to metabolize glucose just as young myeloid cells do, reversing the old cells' inflammatory character.

More striking, the compounds reversed mice's age-related cognitive decline. Older mice who received them performed as well on tests of recall and spatial navigation as young adult mice.

One of the two compounds the Stanford scientists used was effective even though it doesn't penetrate the blood-brain barrier. This suggests, Andreasson said, that even resetting myeloid cells outside the brain can achieve profound effects on what goes on inside the brain.

Neither compound is approved for human use, she noted, and it's possible they have toxic side effects, although none were observed in the mice. They provide a road map for drug makers to develop a compound that can be given to people.

Chemotherapy and radiation treatments are known to cause harsh side effects that patients can see or feel throughout their bodies. Yet there are additional, unseen and often undiscussed consequences of these important therapies: the impacts on their future pregnancies and hopes for healthy children.

Extensive evidence shows that chemotherapy and radiation treatments are genotoxic, meaning they can mutate the DNA and damage chromosomes in patients' cancerous and noncancerous cells alike. When this occurs in a germline cell - which are egg cells in women and sperm in men - it can lead to serious fetal and birth defects in a resulting pregnancy. For the few chemotherapies that have been studied, the risk of mutated sperm diminishes over time, as the treatment agents leave the body and men produce new sperm that were never exposed to the genotoxic agents. But for most chemotherapeutic drugs, there is still no information on their impact on DNA mutations and chromosomal damage to human sperm.

Exacerbating the problem, there are currently no efficient and affordable tests that can be used to track men's germ cell health by identifying when the sperm are carrying treatment-related chromosomal mutations such as aneuploidy (abnormal number of chromosomes) or chromosome breaks, rearrangements, or deletions. But evidence from a new study led by Andrew Wyrobek at the Lawrence Livermore National Laboratory, and now at the Lawrence Berkeley National Laboratory (Berkeley Lab), suggests that this may soon change.

In a paper published in the journal PLOS ONE, an international team reported success adapting an established cellular DNA analysis technique called fluorescence in situ hybridization (FISH) to probe sperm DNA for a wide variety of chromosomal defects simultaneously. This version of the FISH technique, known as the AM8 sperm FISH protocol, is the result of decades of work done by the research team of lead author Andrew Wyrobek. A medical biophysicist at Berkeley Lab, Wyrobek studies the effects of ionizing radiation and human-made chemicals on breast cancer, brain function, and male reproductive health.

"This work is the first demonstration that our sperm assay can simultaneously measure aneuploidy and other chromosomal aberrations in sperm from men who have undergone genotoxic treatments," said Wyrobek. "When sperm with these chromosomal abnormalities fertilize an egg, the resulting fetus and live-born child may have severe health issues. For example, fetuses with trisomy 18 - an extra copy of chromosome 18 or a fetus with an unbalanced chromosomal rearrangement - typically die in utero or within a year of birth."

And, most importantly, according to Wyrobek, the assay can detect balanced chromosomal abnormalities, which are rearrangement with no loss or gain of genetic material. Balanced rearrangements are compatible with live birth and heritable to future pregnancies, and affected children are likely to experience reduced fertility when they want to have children of their own.

The team - which included scientists from Lawrence Livermore National Laboratory, Stanford University, MD Anderson Cancer Center, and the National Autonomous University of Mexico - evaluated the AM8 FISH approach on sperm from nine Hodgkin lymphoma patients, who provided samples before, during, and after a multi-drug treatment regimen and radiation therapy.

Results from the FISH protocol tests indicated that sperm produced during the Hodgkin lymphoma treatment had 10 times more chromosomal defects compared with sperm produced prior to treatment. But by month six post-treatment, the patients' sperm had returned to pre-treatment quality.

"We are excited by these results because they are a first step toward applying this method to any human situation - such as aging, illness, drugs, or exposure to environmental toxicants - to determine genetic risks to male germ cells and to examine the persistence of chromosomally damaged sperm," said Wyrobek. "We believe this approach has a wide range of applications in healthcare and family planning, as it can be used to identify environmental exposures that increase the risk for producing chromosomally abnormal sperm that can affect the health of future pregnancies and children for generations to come."

However, according to Wryobek, the sperm FISH method is still in an early research phase and it will require additional validation and commercial development before it becomes available in doctor's offices.

A new study in Frontiers in Psychiatry has for the first time, demonstrated differences in the prevalence of post-traumatic stress symptoms (PTSS) in different groups of rescue workers and emergency personnel, including firefighters, police officers and psychiatric nurses. The researchers showed that the varying experiences and circumstances these workers encounter, such as handling aggressive people, working with families or dealing with deaths and suicide, are tied to varying levels of PTSS and suicidal thoughts, with emergency department staff and psychiatric nurses showing the highest levels of PTSS and suicidal thoughts out of the emergency professions studied. The findings highlight the urgent need for bespoke training and counselling services across the rescue and emergency industries, which would help staff to cope with the trauma they experience, improving their quality of life and mental wellbeing in such high-risk professions. The study was led by Dr Leila Soravia and Dr Thomas Müller at the University of Bern's Hospital of Psychiatry in Switzerland.

Rescue workers and emergency personnel often encounter traumatic events as part of their roles and are therefore at a higher risk of developing PTSD and suicidal thought patterns than the general public. Dr Soravia explains:

"Though rescue workers across different professions will often be engaged at the same event or emergency, they have very different roles and responsibilities on the scene: this can mean the stress experienced by different workers is very subjective - whether that's from dealing with deaths, working with families of victims, or being exposed to violence. The mental wellbeing training that is offered to staff to teach them how to cope with this stress and trauma also often varies across these different professions. We therefore speculated that the prominence of PTSS and other related factors would vary across different rescue workers, which has not been studied so far."

The researchers distributed an anonymous online survey to rescue workers across Bern, Switzerland, which included police officers, firefighters, ambulance personnel, emergency department staff and psychiatric nurses. All the participants were asked questions about traumatic events they had experienced before and during the course of their job, any PTSS or suicidal thoughts they experienced, and were also asked to rate how well they thought they coped with stress and PTSS.

The study found significant differences in the prevalence of PTSS between different professions, and notably, emergency department staff and psychiatric nurses featured the highest prevalence of PTSS. For individuals who demonstrated PTSS, dysfunctional coping strategies, such as alcohol abuse or avoidance of a situation or emotion related to their stress was one of the most robust predictors of their symptoms.

"The findings highlight how even the same emergency situations can affect the mental health of rescue workers differently. We urgently need profession-specific training that can improve emergency workers' abilities to cope with the stresses of their job to reduce their PTSS and enhance their quality of life in such high-risk professions," highlights Dr Soravia.

"Long term studies would help us understand the predictors of PTSS in emergency personnel - a more profound understanding of these symptoms could then be a valuable basis for mental wellbeing training and support in the future."

Shelled pteropods, microscopic free-swimming sea snails, are widely regarded as indicators for ocean acidification because research has shown that their fragile shells are vulnerable to increasing ocean acidity. 

A new study, published in the journal Scientific Reports, shows that pteropods sampled off the coasts of Washington and Oregon made thinner shells than those in offshore waters. Along the coast, upwelling from deeper water layers brings cold, carbon dioxide-rich waters of relatively low pH to the surface. The research, by a team of Dutch and American scientists, found that the shells of pteropods collected in this upwelling region were 37 percent thinner than ones collected offshore.

Sometimes called sea butterflies because of how they appear to flap their "wings" as they swim through the water column, fat-rich pteropods are an important food source for organisms ranging from other plankton to juvenile salmon to whales. They make shells by fixing calcium carbonate in ocean water to form an exoskeleton. 

 "It appears that pteropods make thinner shells where upwelling brings water that is colder and lower in pH to the surface, " said lead author Lisette Mekkes of Naturalis Biodiversity Centers and the University of Amsterdam in the Netherlands. Mekkes added that while some shells also showed signs of dissolution, the change in shell thickness was particularly pronounced, demonstrating that acidified water interfered with pteropods' ability to build their shells. 

The scientists examined shells of pteropods collected during the 2016 NOAA Ocean Acidification Program research cruise in the northern California Current Ecosystem onboard the NOAA Ship Ronald H. Brown. Shell thicknesses of 80 of the tiny creatures - no larger than the head of a pin - were analyzed using 3D scans provided by micron-scale computer tomography, a high-resolution X-ray technique. The scientists also examined the shells with a scanning electron microscope to assess if thinner shells were a result of dissolution. They also used DNA analysis to make sure the examined specimens belonged to a single population.  

 "Pteropod shells protect against predation and infection, but making thinner shells could also be an adaptive or acclimation strategy," said  Katja Peijnenburg,  group leader at Naturalis Biodiversity Center. "However, an important question is  how long can pteropods continue making thinner shells in rapidly acidifying waters?"

The California Current Ecosystem along the West Coast is especially vulnerable to ocean acidification because it not only absorbs carbon dioxide from the atmosphere, but is also bathed by seasonal upwelling of carbon-dioxide rich waters from the deep ocean. In recent years these waters have grown increasingly corrosive as a result of the increasing amounts of atmospheric carbon dioxide absorbed into the ocean. 

"Our research shows that within two to three months, pteropods transported by currents from the open-ocean to more corrosive nearshore waters have difficulty building their shells," said Nina Bednarsek, a research scientist from the Southern California Coastal Water Research Project in Costa Mesa, California, a coauthor of the study. 

Over the last two-and-a-half centuries, scientists say, the global ocean has absorbed approximately 620 billion tons of carbon dioxide from emissions released into the atmosphere by burning fossil fuels, changes in land-use, and cement production, resulting in a process called ocean acidification.

"The new research provides the foundation for understanding how pteropods and other microscopic organisms are actively affected by progressing ocean acidification and how these changes can impact the global carbon cycle and ecological communities," said Richard Feely, NOAA Pacific Marine Environmental Laboratory and chief scientist for the cruise.

Social distancing and working from home help prevent transmission of the novel coronavirus but can be conducive to unhealthy behavior such as bingeing on fast food or spending more time in a chair or on a couch staring at a screen, and generally moving about less during the day. Scientists believe the reduction in physical activity experienced during the first few months of the pandemic could lead to an annual increase of more than 11.1 million in new cases of type 2 diabetes and result in more than 1.7 million deaths.

The estimates are presented by researchers at São Paulo State University (UNESP), Brazil, in a review article published in Frontiers in Endocrinology. The authors stress that there is an "urgent need" to recommend physical activity during the pandemic.

"Recent studies have shown that people with diabetes face a higher risk of developing the severe form of COVID-19, and of dying if the condition is not properly controlled. Others have shown that social distancing and confinement have considerably reduced levels of physical activity, increased sedentary behavior and lowered the quality of people's nutrition. Our article serves as a warning about the harmful consequences of these trends," said Emmanuel Gomes Ciolac, a professor at UNESP's Department of Physical Education in Bauru, and principal investigator for the study.

The first author of the article is Isabela Roque Marçal, who is studying for a master's degree at UNESP. She was previously a research intern at the University of Leuven, Belgium, with a scholarship from FAPESP.

Among other data sources, the review covers the findings of an international online survey conducted by a group of 35 research institutions on several continents. According to the results, which are preliminary in that they refer to the first 1,000 volunteers to complete the questionnaire, the level of physical activity decreased 35% in the initial months of confinement, and this was accompanied by a 28.6% increase in sedentary behavior, such as sitting or lying for long periods, and unhealthy eating. Previous studies had already shown that a lack of physical activity helped cause some 33 million cases of type 2 diabetes in 2019 and 5.3 million deaths in 2018.

Based on data for the period before the pandemic, the researchers estimated that the current prevalence of physical inactivity (not getting the minimum amount of exercise recommended by health authorities) was 57.3% among over-forties generally and 57.7% among people at risk for diabetes, so that a lack of exercise can be considered responsible for 9.6% of diabetes cases (11.1 million) and 12.5% of all-cause deaths worldwide (1.7 million) if this prevalence persists for a long time.

Exercising at home

"It's important to be aware of the difference between insufficient levels of physical activity and sedentary behavior," Ciolac said. "An insufficiently active person is an individual who doesn't get the minimum amount of exercise recommended by the World Health Organization." The WHO recommends at least 150 minutes of moderate aerobic exercise or 75 minutes of vigorous aerobic exercise per week for adults aged 18-64.

Sedentary behavior, he continued, is associated with the time spent sitting, reclining or lying down. Research shows that watching television or working at a computer for long hours can be bad for the health of even physically active people. Those who are required to use a computer all day for their work should get up every 30 minutes or so to stretch their legs and get whatever light exercise is possible.

Confinement should not prevent people from performing more intense physical activity. The WHO's recommendations, for example, include taking online exercise classes, many of which are free of charge, playing with children, doing household chores such as cleaning and gardening, going up and down stairs, even walking on the spot.

The UNESP group also recommend exercises using body weight to improve muscle tone, such as situps, pushups, squatting, and standing up from a chair, as well as aerobic exercises that can safely be performed near the home, such as walking, jogging and cycling. Meals should be as healthy as possible, with plenty of vegetables and fruit, avoiding processed foods.

Computer simulations hold tremendous promise to accelerate the molecular engineering of green energy technologies, such as new systems for electrical energy storage and solar energy usage, as well as carbon dioxide capture from the environment. However, the predictive power of these simulations depends on having a means to confirm that they do indeed describe the real world.

Such confirmation is no simple task. Many assumptions enter the setup of these simulations. As a result, the simulations must be carefully checked by using an appropriate “validation protocol” involving experimental measurements.

“We focused on a solid/liquid interface because interfaces are ubiquitous in materials, and those between oxides and water are key in many energy applications.” — Giulia Galli, theorist with a joint appointment at Argonne and the University of Chicago

To address this challenge, a team of scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, the University of Chicago and the University of California, Davis, developed a groundbreaking validation protocol for simulations of the atomic structure of the interface between a solid (a metal oxide) and liquid water. The team was led by Giulia Galli, a theorist with a joint appointment at Argonne and the University of Chicago, and Paul Fenter, an Argonne experimentalist.

“We focused on a solid/liquid interface because interfaces are ubiquitous in materials, and those between oxides and water are key in many energy applications,” said Galli.

“To date, most validation protocols have been designed for bulk materials, ignoring interfaces,” added Fenter. “We felt that the atomic-scale structure of surfaces and interfaces in realistic environments would present a particularly sensitive, and therefore challenging, validation approach.”

The validation procedure they designed uses high-resolution X-ray reflectivity (XR) measurements as the experimental pillar of the protocol. The team compared XR measurements for an aluminum oxide/water interface, conducted at beamline 33-ID-D at Argonne’s Advanced Photon Source (APS), with results obtained by running high-performance computer simulations at the Argonne Leadership Computing Facility (ALCF). Both the APS and ALCF are DOE Office of Science User Facilities.

“These measurements detect the reflection of very high energy X-ray beams from an oxide/water interface,” said Zhan Zhang, a physicist in Argonne’s X-ray Science division. At the beam energies generated at the APS, the X-ray wavelengths are similar to interatomic distances. This allows the researchers to directly probe the molecular-scale structure of the interface.

“This makes XR an ideal probe to obtain experimental results directly comparable to simulations,” added Katherine Harmon, a graduate student at Northwestern University, an Argonne visiting student and the first author of the paper. The team ran the simulations at the ALCF using the Qbox code, which is designed to study finite temperature properties of materials and molecules using simulations based on quantum mechanics.

“We were able to test several approximations of the theory,” said Francois Gygi from the University of California, Davis, part of the team and lead developer of the Qbox code. The team compared measured XR intensities with those calculated from several simulated structures. They also investigated how X-rays scattered from the electrons in different parts of the sample would interfere to produce the experimentally observed signal.

The endeavor of the team turned out to be more challenging than anticipated. “Admittedly, it was a bit of a trial and error at the beginning when we were trying to understand the right geometry to adopt and the right theory that would give us accurate results,” said Maria Chan, a co-author of the study and scientist at Argonne’s Center for Nanoscale Materials, a DOE Office of Science User Facility. “However, our back and forth between theory and experiment paid off, and we were able to set up a robust validation protocol that can now be deployed for other interfaces as well.”

“The validation protocol helped quantify the strengths and weaknesses of the simulations, providing a pathway toward building more accurate models of solid/liquid interfaces in the future,” said Kendra Letchworth-Weaver. An assistant professor at James Madison University, she developed software to predict XR signals from simulations during a postdoctoral fellowship at Argonne.

The simulations also shed new insight on the XR measurements themselves. In particular, they showed that the data are sensitive not only to the atomic positions, but also to the electron distribution surrounding each atom in subtle and complex ways. These insights will prove beneficial to future experiments on oxide/liquid interfaces.

The interdisciplinary team is part of the Midwest Integrated Center for Computational Materials, headquartered at Argonne, a computational materials science center supported by DOE. The work is presented in an article titled “Validating first-principles molecular dynamics calculations of oxide/water interfaces with X-ray reflectivity data,” which appeared in the November 2020 issue of Physical Review Materials. This project received support from the DOE Office of Basic Energy Sciences, a Laboratory Directed Research and Development Award, and the Department of Defense. ALCF computing time was awarded through DOE’s ASCR Leadership Computing Challenge.

The United States incarcerates more residents than any other country, however there is limited research that examines how people view such punishment, and whether views about punishment change with development. Previous research on this topic raises two very different possibilities: 1) children are typically more optimistic than adults, making them more likely to report that people's moral character improves following punishment, and 2) children are more likely than adults to report that others' characteristics - including moral traits - are unchangeable, making them less likely than adults to report that punishment affects moral growth. Researchers probed these contrasting possibilities further in two studies exploring children's and adults' views about the impact of punishment on perceived moral character.

This work was conducted by researchers at Columbia University. It appears in Child Development, a journal of the Society for Research in Child Development.

"Children in our study reported that punishment - regardless of how severe - caused positive moral change among 'mean' individuals," said James P. Dunlea, a doctoral student in the Department of Psychology at Columbia University. "Unlike children, adults expected that 'nice' individuals' positive qualities worsened following punishment."

The samples collected in each of the studies was relatively diverse in terms of children's and adults' race/ethnicity. While "White or European American" was the category most often identified in each of the studies, the samples also included "Black or African-American," "Asian or Asian-American," "Native-American or Pacific Islander," and "multi-racial" adults and children.

The first study included 94 children between the ages of six and eight years old and 94 adults between 18 and 52 years old. Children and adults in the current work were given descriptions about morally good ("nice") and morally bad ("mean") individuals who were punished for breaking the law (went to prison) or control characters who went on a business trip. Children in the punishment condition saw a series of PowerPoint animations depicting the punished individual entering and then being driven away from his home by a police car. Children in the control condition were shown animations depicting the individual entering and then being carried away from his home by an airplane. Adults in each condition read descriptions of the scenarios. Participants in both age groups were asked to rate the moral character of the individual using a five-point scale; they did so at the beginning of the incarceration/trip and after the incarceration/trip. Findings from the first study showed that children, but not adults, reported that "mean" individuals became "nicer" after one especially severe form of punishment (incarceration). Moreover, adults, unlike children, reported that "nice" individuals became less "nice" following incarceration. Experimenters interviewed children in-person; adults completed the study online.

The second study focused on 77 children (no adults) between six and eight years old. Experimenters showed children pairs of individuals on a laptop and then were asked questions about them. One individual in each pair was described as receiving a relatively severe punishment (going to jail after committing a transgression) whereas the other individual was described as receiving a relatively less severe punishment (going to time-out after committing a transgression). Experimenters specified that each individual in the pair committed the same transgression.

Experimenters asked children to rate the moral character of the punished individuals before punishment and after punishment. Children also rated the perceived severity of each punishment. Despite acknowledging that incarceration is a more severe type of punishment than time-out, children reported that "mean" individuals became "nicer" regardless of punishment type; a difference in the perceived magnitude of change did not emerge across punishment types.

"These findings suggest that with age, people in the United States become increasingly pessimistic about the impact of punishment on moral character," said Larisa Heiphetz, co-author, and assistant professor in the Department of Psychology at Columbia University. "Our work suggests that these adults may believe that redemption is not for everyone or at the very least, that a specific form of severe punishment (incarceration) is not the way for it to be achieved."

The authors acknowledge that their current research did not focus on why children and adults reported different views of the impact of severe punishment on moral character. They suggest that future research should consider why adults view punishment severity as an obstruction to moral improvement.

Mitochondria are vital for the human body as cellular powerhouses: They possess more than 1,000 different proteins, required for many central metabolic pathways. Disfunction of these lead to severe diseases, especially of the nervous system and the heart. In order to transport proteins and metabolites, mitochondria contain a special group of so-called beta-barrel membrane proteins, which form transport pores in the outer mitochondrial membrane. So far, scientists have not been able to explain the operating mode of the sorting and assembly machinery (SAM) for the biogenesis of these beta-barrel proteins. A team led by Prof. Dr. Toshiya Endo from Kyoto University/Japan, Prof. Dr. Nils Wiedemann and Prof. Dr. Nikolaus Pfanner from the University of Freiburg and Prof. Dr. Thomas Becker from the University of Bonn has now solved the structure and function of the SAM complex. The researchers have published their results in the journal Nature.

The SAM complex consists typically of two beta-barrel subunits named Sam50, which are capped on their outside by the two additional subunits Sam35 and Sam37. The researchers found that while the SAM complex forms a new beta-barrel protein, it contains only one Sam50. The second beta-barrel subunit functions as a flexible placeholder: it temporarily leaves the SAM complex, freeing the space for the new beta-barrel protein to form. This dynamic mechanism suggests how a new beta-barrel protein can mature to full size in the SAM complex and only be released as a completely folded protein. "This enabled us to identify a new principle for the formation of membrane proteins that perform vital functions in our cells," explains Wiedemann.