It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Saturday, June 19, 2021
Separating natural and man-made pollutants in the air
What COVID-19's lockdown to prevent infection taught us
IMAGE: (A) DOMINANT LAND COVER TYPES IN THE STUDY DOMAIN (74°E, 27°N--80°E, 30°N) ARE URBAN AREAS, CROPLANDS AND DESERT SHRUBLANDS. (B) TIMELINE OF LOCKDOWN POLICIES, WHERE BAU REFERS TO BUSINESS-AS-USUAL CONDITIONS... view more
CREDIT: MISRA P. ET AL., 2021, SCIENTIFIC REPORTS, SPRINGER NATURE DOI.ORG/10.1038/S41598-021-87673-2
COVID-19 has changed the world in unimaginable ways. Some have even been positive, with new vaccines developed in record time. Even the extraordinary lockdowns, which have had severe effects on movement and commerce, have had beneficial effects on the environment and therefore, ironically, on health. Studies from all around the world, including China, Europe and India, have found major drops in the level of air pollution. However, to fully understand the impact of anthropogenic causes, it is important to separate them from natural events in the atmosphere like wind flow.
To demonstrate this point, a new study by researchers at the Research Institute for Humanity and Nature, Japan, uses satellite data and mathematical modeling to explain just how great the lockdown effect on nitrogen oxides has been in Delhi, India, one of the world's most polluted cities, and its surrounding area. This study was carried out under the activity named "Mission DELHIS (Detection of Emission Change of air pollutants: Human Impact Studies)" as a part of RIHN project, Aakash (meaning "Sky" in Hindi, originated from sanskrit) (https://www.chikyu.ac.jp/rihn_e/covid-19/topics.html#topics6).
"Nitrogen oxides are good chemical tracers for testing model hypothesis, because besides their health effects, they have a short lifetime. Therefore, it is unlikely wind will bring nitrogen oxides from far away." explains Professor Sachiko Hayashida, who led the study.
Nitrogen oxides naturally change due to dynamic and photochemical conditions in the atmosphere, and are emitted from the Earth's surface by both natural and anthropogenic activities. Therefore, Hayashida argues, looking simply at their concentration levels in the atmosphere provides only a crude impression of man-made contributions.
"COVID-19 pandemic has given us an opportunity of social experiment, when we can discriminate the anthropogenic effects on nitrogen oxides from the natural ones caused by atmospheric conditions and natural emissions, because only anthropogenic emissions decreased due to the lockdown. These confounders affect policy to control air quality" she says.
Strict lockdown was enforced in Delhi for two months in 2020, from the end of March to the end of May. This period coincides with the transition in atmospheric conditions, such as actinic flux, from low in spring to high in early summer, and also from stagnant winds to high ventilation across the entire northern India region.
The researchers analyzed seasonal and inter-annual changes using multi-year satellite data to predict what the levels would be had there been no lockdown. They estimated top-down emissions using a steady-state continuity equation. The study's findings clearly show that the natural conditions could not explain the dramatic drop in 2020 nitrogen oxide levels. Not even close.
"Our calculations suggested that 72% of nitrogen oxides emissions in urban centres are the resulted solely from traffic and factories," said Hayashida.
Interestingly, the levels recovered after the lockdown more quickly in rural levels than they did in urban ones, an effect attributed to agricultural activities, such as crop-residue burning, which resumed almost immediately. Unlike factories, the agricultural activities continued, albeit at a lesser pace, during the lockdown, which was less stringent on agriculture.
Hayashida says that her team's approach should have an impact on how we study harmful chemical species emitted to the atmosphere.
"Our findings show the importance of analyzing top-down emissions and not just atmospheric concentrations. We expect our approach to guide effective policy on air pollution," she said.
CAPTION
Mean top-down NOx emission in 2020 during (a) BAU (business-as-usual), and subsequent lockdown-phases (b)-(f).
CREDIT
Misra P. et al., 2021, Scientific Reports, Springer Nature doi.org/10.1038/s41598-021-87673-2
RA is an inflammatory autoimmune disease that causes pain, swelling and stiffness in the joints. It can also cause fatigue, and the underlying inflammation may affect other body systems. It is more common in women than in men. To date, active smoking has been the most reproducibly reported risk factor for a type of RA called anti-citrullinated protein antibody (ACPA) positive RA-particularly in people who carry the HLA-DRB1-shared epitope alleles.
Nguyen and colleagues set out to investigate the relationship between passive smoking and the risk of developing RA in a large prospective cohort of healthy French women.
The E3N-EPIC (Etude Epidémiologique au prèsdes femmes de la Mutuelle générale de l'Education Nationale) has collected data on healthy French women since 1990. RA cases have been identified with specific questionnaires and via the medication reimbursement database. Women were considered to have been exposed to passive smoking in childhood if they self-declared staying in a smoky room several hours a day during childhood, and to passive smoking as an adult if they self-declared being exposed for at least 1 hour a day.
79,806 women were included in the study. Among them, 698 cases of RA were identified. In the whole cohort, 10,810 (13.5%) were exposed to passive smoking as children, and 42,807 (53.6%) to passive smoking as adults.6,581 (8.25%) were exposed to both, and 47,036 (58.9%) were exposed to either.
In the whole population, passive smoking in childhood was positively associated with the risk of RA. When analysed by each person's own smoking status, passive smoking in childhood was associated with RA among women who had never smoked themselves, but not among those who had ever smoked themselves.
When the authors looked at passive smoking in adulthood, there was also a positive risk association in the whole population. But when analysed again by individual smoking status, the association with increased RA risk was only among never-smoking women, not those who had ever themselves been a smoker.
These results suggest that smoking by-products - whether actively or passively inhaled - could generate autoimmunity, at least towards antigens involved in RA pathogenesis.
In a poster examining another link between the lungs and inflammatory arthritis, Adami and colleagues looked at the association between concentration of air pollutants and biologic drug retention rates in people with chronic inflammatory arthritis (CIA) living in the Verona area of Italy.
This was a case-crossover study to compare the exposure to pollutants in the 30?day and 60-day periods preceding a drug switch or swap due to disease progression.
1,286 patients with CIA (888 with RA, 260 with psoriatic arthritis and 138 with ankylosing spondylitis) were included, and 13,636 daily air pollution records were retrieved. The authors found an exposure-dependent relationship between exposure to air pollutants and markers of inflammation in people with CIA. Exposures of greater than 50μg/m3 and greater than 40μg/m3 had a 150% and 65% higher risk of having C-reactive protein (CRP) levels above 5 mg/L, respectively.
If the pollution threshold was set at 30μg/m3(below the European Union health protection limit) there was still a 38% higher risk of having altered CRP (OR 1.383, 95% CI 1.206-1.588).
Air pollutants concentrations were higher before a switch or swap due to drug inefficacy. The authors concluded that environmental air pollution was a determinant of poor response to biologic treatment. Interventions to decrease fossil fuel combustion emissions might have beneficial effects on the persistence rate of biologic treatments in people with inflammatory arthritis.
HOUSTON - (June 18, 2021) - To boost employees' creativity, managers should consider offering a set of rewards for them to choose from, according to a new study by management experts at Rice University, Tulane University, the University of North Carolina at Greensboro and National Taiwan Normal University.
The study, co-authored by Jing Zhou, the Mary Gibbs Jones Professor of Management and Psychology at Rice's Jones Graduate School of Business, is the first to systematically examine the effects of reward choice in a field experiment, which was conducted in the context of an organizationwide suggestion program. An advance copy of the paper is published online in the Journal of Applied Psychology.
"Organizations spend a lot of resources and exert a great deal of effort in designing incentive schemes that reward the employees who exhibit creativity at work," Zhou said. "Our results showed that the effort may be a bit misplaced. Instead of discovering one reward type that is particularly effective at promoting creativity, what is more effective is to provide the employees with the opportunity to choose from several reward types, if they submit one or more ideas that are among the top 20% most creative ones."
Workers in the study were given a range of options: a financial reward for the individual employee or their team, a self-discretionary reward such as getting priority to select days off, or a donation the company made to a charity selected by the employee. Those choices had positive, significant effects on the number of creative ideas employees generated and the creativity level of those ideas, Zhou and her co-authors found.
The researchers arrived at their findings by conducting a quasi-experiment at a company in Taiwan over the course of several months. Then they conducted a second experimental study that included employees from 12 organizations in Taiwan to replicate the first study's results and compared the results with a control group.
The studies also found that rewards aimed at helping others, such as making a donation to a charity, might be especially powerful. But for less-creative employees, alternative rewards that benefit those in need might actually lower creativity and should be avoided, the authors said.
The researchers also found that the choice of rewards fostered creativity by raising the employees' belief in their ability to be creative. Alternative rewards also had a powerful impact on boosting the creativity of employees who earlier had scored high on an assessment of creative personality characteristics.
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Zhou co-authored the paper with Greg Oldham of Tulane, Aichia Chuang of the University of North Carolina at Greensboro and Ryan Shuwei Hsu of National Taiwan Normal University.
For a copy of the study, "Enhancing employee creativity: Effects of choice, rewards and personality," email jfalk@rice.edu.
For more information about and insights from Rice Business faculty research, visit the school's Rice Business Wisdom website, https://business.rice.edu/wisdom.
Follow Rice Business via Twitter @Rice_Biz.
Follow Rice News and Media Relations via Twitter @RiceUNews.
IMAGE: THE FLYPOL INSTRUMENT, WHICH WAS USED TO MEASURE BIOSIGNATURES FROM THE AIR, ABOARD THE HELICOPTER. view more
CREDIT: COURTESY OF LUCAS PATTY
Left hands and right hands are almost perfect mirror images of each other. But whatever way they are twisted and turned, they cannot be superimposed onto each other. This is why the left glove simply won't fit the right hand as well as it fits the left. In science, this property is referred to as chirality.
Just like hands are chiral, molecules can be chiral, too. In fact, most molecules in the cells of living organisms, such as DNA, are chiral. Unlike hands, however, that usually come in pairs of left and right, the molecules of life almost exclusively occur in either their "left-handed" or their "right-handed" version. They are homochiral, as researchers say. Why that is, is still not clear. But this molecular homochirality is a characteristic property of life, a so-called biosignature.
As part of the MERMOZ project (see info box), an international team led by the University of Bern and the National Centre of Competence in Research NCCR PlanetS, has now succeeded in detecting this signature from a distance of 2 kilometers and at a velocity of 70 kph. Jonas Kühn, MERMOZ project manager of the University of Bern and co-author of the study that has just been published in the journal Astronomy and Astrophysics, says: "The significant advance is that these measurements have been performed in a platform that was moving, vibrating and that we still detected these biosignatures in a matter of seconds."
An instrument that recognizes living matter
"When light is reflected by biological matter, a part of the light's electromagnetic waves will travel in either clockwise or counterclockwise spirals. This phenomenon is called circular polarization and is caused by the biological matter's homochirality. Similar spirals of light are not produced by abiotic non-living nature", says the first author of the study Lucas Patty, who is a MERMOZ postdoctoral researcher at the University of Bern and member of the NCCR PlanetS,
Measuring this circular polarization, however, is challenging. The signal is quite faint and typically makes up less than one percent of the light that is reflected. To measure it, the team developed a dedicated device called a spectropolarimeter. It consists of a camera equipped with special lenses and receivers capable of separating the circular polarization from the rest of the light.
Yet even with this elaborate device, the new results would have been impossible until recently. "Just 4 years ago, we could detect the signal only from a very close distance, around 20 cm, and needed to observe the same spot for several minutes to do so", as Lucas Patty recalls. But the upgrades to the instrument he and his colleagues made, allow a much faster and stable detection, and the strength of the signature in circular polarisation persists even with distance. This rendered the instrument fit for the first ever aerial circular polarization measurements.
Useful measurements on earth and in space
Using this upgraded instrument, dubbed FlyPol, they demonstrated that within mere seconds of measurements they could differentiate between grass fields, forests and urban areas from a fast moving helicopter. The measurements readily show living matter exhibiting the characteristic polarization signals, while roads, for example, do not show any significant circular polarization signals. With the current setup, they are even capable of detecting signals coming from algae in lakes.
After their successful tests, the scientists now look to go even further. "The next step we hope to take, is to perform similar detections from the International Space Station (ISS), looking down at the Earth. That will allow us to assess the detectability of planetary-scale biosignatures. This step will be decisive to enable the search for life in and beyond our Solar System using polarization", says MERMOZ principal investigator and co-author Brice-Olivier Demory, professor of astrophysics at the University of Bern and member of the NCCR PlanetS says.
The sensitive observation of these circular polarization signals is not only important for future life detection missions. Lucas Patty explains: "Because the signal directly relates to the molecular composition of life and thus its functioning, it can also offer valuable complementary information in Earth remote sensing." It can for instance provide information about deforestation or plant disease. It might even be possible to implement circular polarization in the monitoring of toxic algal blooms, of coral reefs and the effects of acidification thereon.
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Publication details:
C.H. Lucas Patty et. Al., Biosignatures of the Earth I. Airborne spectropolarimetric detection of photosynthetic life, Astronomy & Astrophysicshttps://doi.org/10.1051/0004-6361/202140845
SAINT-EX - Search and characterisation of exoplanets
The SAINT-EX research group (funded by the SNF Professorship of Prof. Brice-Olivier Demory) focuses on the:
-detection of temperate Earth-sized exoplanets (SAINT-EX observatory),
-remote sensing of life in planetary atmospheres/surfaces (MERMOZ),
-instrumentation for non-invasive, in-vivo cancer diagnosis and staging (BrainPol).
The MERMOZ (Monitoring planEtary suRfaces with Modern pOlarimetric characteriZation) project aims to investigate whether we can identify and characterize Earth's life from space, by building a benchmark library of surface feature signatures with remote full-Stokes spectro-polarimetry. In this framework, our planet is considered as a proxy for other solar system bodies and exoplanets.
MERMOZ is a project in partnership between the Universities of Bern, Leiden and Delft (NL).
The project's feasibility study is funded by the Centre for Space and Habitability (CSH) and the NCCR PlanetS.
In 2014, the Swiss National Science Foundation awarded the University of Bern the National Centre for Competence in Research (NCCR) PlanetS, which it manages together with the University of Geneva.
Since its involvement in the first moon landing in 1969, the University of Bern has been participating in space missions of the major space organizations, such as ESA, NASA, ROSCOSMOS and JAXA. It is currently co-leading the European Space Agency's (ESA) CHEOPS mission with the University of Geneva. In addition, Bernese researchers are among the world leaders when it comes to models and simulations of the formation and development of planets.
With the discovery of the first exoplanet, the University of Geneva positioned itself as one of the leading institutions in the field. This led, for example, to the construction and installation of the HARPS spectrograph on ESO's 3.6 m telescope at La Silla in 2003 under Geneva's leadership. This was followed by the ESPRESSO instrument on ESO's VLT telescope in Paranal. The "Science Operation Center" of the CHEOPS mission is also in Geneva.
ETH Zurich and the University of Zurich are also partner institutions in the NCCR PlanetS. Scientists from the fields of Astrophysics, Data Processing and Earth Sciences lead projects and make important contributions to NCCR PlanetS research. In addition, ETH is a world leader in instrumentation for various observatories and space missions.
The NCCR PlanetS is organized into the following research areas:
-Early stages of planet formation
-Architecture of planetary systems, their formation and evolution
-Atmospheres, surfaces and the interior of planets
Bernese space exploration: With the world's elite since the first moon landing
When the second man, "Buzz" Aldrin, stepped out of the lunar module on July 21, 1969, the first task he did was to set up the Bernese Solar Wind Composition experiment (SWC) also known as the "solar wind sail" by planting it in the ground of the moon, even before the American flag. This experiment, which was planned and the results analyzed by Prof. Dr. Johannes Geiss and his team from the Physics Institute of the University of Bern, was the first great highlight in the history of Bernese space exploration.
Ever since Bernese space exploration has been among the world's elite. The University of Bern has been participating in space missions of the major space organizations, such as ESA, NASA, ROSCOSMOS and JAXA. It is currently co-leading the European Space Agency's (ESA) CHEOPS mission with the University of Geneva. In addition, Bernese researchers are among the world leaders when it comes to models and simulations of the formation and development of planets.
The successful work of the Department of Space Research and Planetary Sciences (WP) from the Physics Institute of the University of Bern was consolidated by the foundation of a university competence center, the Center for Space and Habitability (CSH). The Swiss National Fund also awarded the University of Bern the National Center of Competence in Research (NCCR) PlanetS, which it manages together with the University of Geneva.
The end of Darwin's nightmare at Lake Victoria?
According to a study conducted by researchers from the University of Liège (Belgium), the lake is not only suffering from the introduction of the Nile perch into its waters
Lake Victoria, which came under the spotlight in 2004 by the documentary "Darwin's nightmare", is not only suffering from the introduction and commercialisation of the Nile perch. A study lead researchers from the University of Liège (Belgium) has highlighted other worrying phenomena, particularly climatic ones, which have an equally important impact on the quality of the lake's waters.
Located in East Africa, just south of the Equator, Lake Victoria is the source of the Nile and is the largest tropical lake in the world. With a surface area of 68,800 km² (twice the size of Belgium), it is considered to be one of the largest water and fishery resources in East Africa, supporting more than 47 million people in the three neighbor countries (Uganda, Tanzania and Kenya).
Lake Victoria is best known to the general public following the release of the 2004 documentary Darwin's Nightmare, which focuses on the environmental and social effects of the Nile perch fishing industry. Voracious predator that can grow up to two metres long and weigh 200kg, the Nile perch is the largest freshwater fish. Its introduction into Lake Victoria in the 1950s and its population explosion in the 1960s gradually wiped out the native fish species living in the lake, causing a major ecological disaster. Today, the Nile perch population remains ubiquitous but has declined slightly due to overfishing, allowing some species to partially recover.
What is less well known - and perhaps interacting with the presence of the Nile perch - but equally damaging to the ecosystem, is the general water quality of the lake. "This declined sharply between the 1960s and the 1990s due to eutrophication, which is caused by increased inputs of nutrients (nitrogen and phosphorus) into the water bodies (rivers and lakes) as a result of increased human activities in the catchment area (intensive agriculture with fertilisers or domestic wastewater) resulting from population growth and economic development, explains Alberto Borges, FNRS Research Director at the Laboratory of Chemical Oceanography from the University of Liege. »
This eutrophication leads to a significant development of micro-algae (phytoplankton). In particular, cyanobacteria, blue-green micro-algae, can be problematic for human health as some forms are toxic. Moreover, the excess phytoplankton biomass (the organic matter from these algae) cannot generally be transformed by the rest of the food web," continues the researcher. This excess remains unused and stagnant at the bottom of the lakes, creating a phenomenon of anoxia, the absence of oxygen in the bottom waters of the lakes. This leads to the degradation of the ecosystem. »
Since the 1990s, no large-scale study of the water quality of Lake Victoria had been undertaken. It was within the framework of the LAVIGAS project - funded by the FNRS and led by Alberto Borges - that a research team was able to study the biomass and composition of phytoplankton as well as the nutrient status of the lake during three scientific missions (2018 -2019). This study shows that the phytoplankton biomass has decreased by about seven times compared to the 1990s," says the researcher, "and that the species composition has also changed in a subtle way." What seems to be good news for the environment of Lake Victoria may only be so on the surface...
Paradoxically, the quantity of nutrients remained comparable to that of the 1990s. This paradox can be explained, however, because in addition to nutrients, phytoplankton (like all plants) also need light to grow. In lakes, the amount of light for phytoplankton obviously depends on the solar radiation at the surface of the lake, but also on the depth of the water on which the phytoplankton cells reside. This depth, known as the mixing layer, depends mainly on the intensity of the wind. If the wind is intense, the depth of the mixing layer is greater, and the phytoplankton cells spend less time near the surface where the light is more intense, and do not develop as well," explains Alberto Borges. Our work shows that current weather conditions are windier than in the 1990s, so the depth of the mixed layer is greater and phytoplankton growth less intense than in the 1990s." The weaker winds of the 1990s were related to the prevailing conditions of El Niño, a natural oscillation in global climate that originates from the large-scale atmospheric circulation over the Pacific Ocean and affects climate worldwide.
This rather complex story shows that the established climate regime in the Pacific Ocean (El Niño) affects the ecology of a lake in Africa, on the other side of the planet! More specifically, it shows that the growth of phytoplankton - and therefore the rest of the food chain - in large tropical lakes responds to eutrophication in a complex way and is strongly modulated by climate," says Alberto Borges. "This means that the current improvement in water quality in Lake Victoria may only be temporary, and that conditions could deteriorate again in the future if vertical mixing in the lake decreases due to reduced wind intensity (a new period of prevailing El Niño conditions) or due to continued climate warming.
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Study: Men doing more family caregiving could lower their risk of suicide
Men overinvest in economic-provider work, and underinvest in family care work
Colorado State University Professor of Psychology Silvia Sara Canetto has spent many years researching patterns and meanings of suicide by culture, trying to make sense of the variability in women's and men's suicide mortality around the world. Suicide rates are generally higher in men than in women, but not everywhere - which suggests cultural influences.
Canetto and colleagues have completed a new study that provides insight into what may contribute to men's suicide vulnerability. The study tests Canetto's theory that men's suicide mortality is related to men's private-life behaviors, specifically their low engagement in family care work - not just the adversities they may encounter in aspects of their public lives, such as employment.
Theories of male suicide
Many theories have been proposed to explain male suicide, Canetto said. Most link men's suicide mortality to the stresses and the demands of their employment and their economic-provider roles. These theories typically predict that male suicide rates would be higher when their employment and economic-provider roles are under threat.
Within this perspective, the typical suicide-prevention recommendation is to strengthen men's employment/economic provider role, for example, via programs that protect or support finding employment. Studies show, however, that economic adversities, including male unemployment, do not fully explain men's suicide vulnerability.
According to Canetto, men overinvest in economic-provider work, and underinvest in family care work--a pattern that leaves them vulnerable when economic-provider work is threatened or lost.
Men's family caregiving, unemployment, and suicide
The multinational and multidisciplinary study, published in Social Psychiatry and Psychiatric Epidemiology by Canetto, Ying-Yeh Chen, ZiYi Cai, Qingsong Chang, and Paul Yip, offers evidence of a suicide-protective role for men who engage in family caregiving. In their study, family caregiving was defined as, for example, providing personal care or education for a child, and/or providing care for a dependent adult.
The researchers examined suicide, male family caregiving, and unemployment in 20 countries, including the United States, Austria, Belgium, Canada and Japan. Suicide rates were found to be lower in countries where men reported more family care work.
In countries where men reported more such care work, higher unemployment rates were not associated with higher suicide rates in men. By contrast, in countries where men reported less family care work, higher unemployment rates were associated with elevated male suicide rates. Incidentally, unemployment benefits did not reduce male suicide rates.
Taken together, the findings of this ecological study suggest that men's family care work may protect them against suicide, particularly under difficult economic circumstances, Canetto said.
"Our study took a public health perspective. It examined population-level social and economic factors that may be driving population suicide patterns, across a range of countries," Canetto said. "Its findings point to new directions for suicide prevention."
"It appears that men benefit from doing family care work in terms of suicide protection. Doing family care work would be a way for men to diversify their sources of meaning and purpose, as well as their social capital and networks" stated Canetto. Men's greater involvement in family care work would also relieve women of their disproportionate caregiving load, and give children more resources.
The study's findings suggest incorporating support for engagement in family care work in programs aimed at reducing men's suicide mortality. "This means expanding beyond dominant frameworks of men's suicide prevention with their employment-support focus," Canetto explained. "It also means going beyond treating suicide as just a mental health problem to be solved with mental health 'treatments.'"
Finally, Canetto pointed out that the study's findings are consistent with other research findings. Collectively, they suggest that "having both family care work and family economic responsibilities is more conducive to well-being, health and longevity for men and women than a gendered division of family labor."
IMAGE: CLOSTRIDIOIDES DIFFICILE (C. DIFFICILE) IS CLASSIFIED AS AN URGENT ANTIBIOTIC RESISTANCE THREAT BY THE CDC. THE 3-D STRUCTURE SHOWS HOW A KEY C. DIFFICILE TOXIN, TCDB (GREY SURFACE MODEL), ENGAGES... view more
CREDIT: UCI SCHOOL OF MEDICINE
Irvine, CA - June 18, 2021 - A new study paves the way for the development of next generation therapeutics for the prevention and treatment of Clostridioides difficile infection (CDI), the most frequent cause of healthcare-acquired gastrointestinal infections and death in developed countries.
Published today in Nature Communications, the study reveals the first 3D structure of the Clostridioides difficile toxin B (TcdB) in complex with chondroitin sulfate proteoglycan 4 (CSPG4), a human receptor. The study was co-led by senior author Rongsheng Jin, PhD, a professor in the Department of Physiology & Biophysics at the University of California, Irvine, School of Medicine, and Min Dong, PhD, an associate professor at Harvard Medical School.
"TcdB is one of two homologous C. difficile exotoxins, which are major virulence factors responsible for the spread of C. difficile infections," explained Jin. "TcdB alone is capable of causing the full-spectrum of diseases associated with CDI in humans."
Previous studies had identified CSPG4 as a potential receptor for TcdB, however the pathophysiological relevance and molecular details were unknown. Results from this new study reveal a unique binding site involving TcdB and CSPG4, and also show that CSPG4-binding residues are highly conserved across most TcdB variants known to date.
CDI has become the most common cause of antibiotic-associated diarrhea and gastroenteritis-associated death in developed countries, accounting for approximately 223,900 infections, 12,800 deaths, and $1 billion in healthcare costs in the United States in 2017. It is classified as one of the top five "urgent threats" by CDC. There is also growing global concern surrounding the emergence of rapidly spreading hypervirulent C. difficile strains, reminiscent of the current COVID pandemic.
"What these new findings tell us is that a rationally designed CSPG4-mimicking decoy could neutralize major TcdB variants, providing a unique therapeutic avenue for combating some of the hypervirulent C. difficile strains," said Jin. In contrast, researchers also revealed that the therapeutic mechanism for bezlotoxumab, the only FDA approved anti-TcdB antibody, is sensitive to escaping mutations in some bacterial strains.
The current standard of care for CDI involves treatments using broad spectrum antibiotics, which often lead to frequent disease recurrence. While bezlotoxumab could reduce the recurrence rate of CDI in some patients, results from this and some earlier studies indicate it has weaker potency against some TcdB variants.
"We have designed a CSPG4-mimicking decoy based on the 3D structure we observed, which could neutralize major TcdB variants and is superior to bezlotoxumab on a major TcdB variant from a hypervirulent strain (TcdB2) in our studies. As a highly conserved cellular receptor of TcdB, a CSPG4 decoy molecule would be difficult for TcdB to escape, since any mutations that disrupt toxin binding to the decoy would also disrupt binding to its native receptors," said Jin.
The team of researchers has also developed a family of recombinant protein therapeutics based on these new findings, as well as on an earlier discovery on how TcdB recognizes another human receptor Frizzled (FZD).
"We are now examining the therapeutic features of these novel antitoxin molecules, and we believe they could provide broad-spectrum protection and neutralization against most known TcdB variants, thus improving existing antibody therapeutics for CDI," said Jin, whose team has filed a patent on these neutralizing molecules.
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This work was supported by part by the National Institutes of Health, Niedersächsisches Vorab, Deutsche Forschungsgemeinschaft, and the Burroughs Wellcome Fund.
About the UCI School of Medicine
Each year, the UCI School of Medicine educates more than 400 medical students, and nearly 150 doctoral and master's students. More than 700 residents and fellows are trained at UCI Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and master's degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/master's in public health, or an MD/master's degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.
"WE ARE STARDUST"
New research adds a wrinkle to our understanding of the origins of matter in the Milky Way
New information about how different cosmic rays arrive at Earth hints at unique sources or propagation methods for different elements
New findings published this week in Physical Review Letters suggest that carbon, oxygen, and hydrogen cosmic rays travel through the galaxy toward Earth in a similar way, but, surprisingly, that iron arrives at Earth differently. Learning more about how cosmic rays move through the galaxy helps address a fundamental, lingering question in astrophysics: How is matter generated and distributed across the universe?
"So what does this finding mean?" asks John Krizmanic, a senior scientist with UMBC's Center for Space Science and Technology (CSST). "These are indicators of something interesting happening. And what that something interesting is we're going to have to see."
Cosmic rays are atomic nuclei--atoms stripped of their electrons--that are constantly whizzing through space at nearly the speed of light. They enter Earth's atmosphere at extremely high energies. Information about these cosmic rays can give scientists clues about where they came from in the galaxy and what kind of event generated them.
An instrument on the International Space Station (ISS) called the Calorimetric Electron Telescope (CALET) has been collecting data about cosmic rays since 2015. The data include details such as how many and what kinds of atoms are arriving, and how much energy they're arriving with. The American, Italian, and Japanese teams that manage CALET, including UMBC's Krizmanic and postdoc Nick Cannady, collaborated on the new research.
Iron on the move
Cosmic rays arrive at Earth from elsewhere in the galaxy at a huge range of energies--anywhere from 1 billion volts to 100 billion billion volts. The CALET instrument is one of extremely few in space that is able to deliver fine detail about the cosmic rays it detects. A graph called a cosmic ray spectrum shows how many cosmic rays are arriving at the detector at each energy level. The spectra for carbon, oxygen, and hydrogen cosmic rays are very similar, but the key finding from the new paper is that the spectrum for iron is significantly different.
There are several possibilities to explain the differences between iron and the three lighter elements. The cosmic rays could accelerate and travel through the galaxy differently, although scientists generally believe they understand the latter, Krizmanic says.
"Something that needs to be emphasized is that the way the elements get from the sources to us is different, but it may be that the sources are different as well," adds Michael Cherry, physics professor emeritus at Louisiana State University (LSU) and a co-author on the new paper. Scientists generally believe that cosmic rays originate from exploding stars (supernovae), but neutron stars or very massive stars could be other potential sources.
Next-level precision
An instrument like CALET is important for answering questions about how cosmic rays accelerate and travel, and where they come from. Instruments on the ground or balloons flown high in Earth's atmosphere were the main source of cosmic ray data in the past. But by the time cosmic rays reach those instruments, they have already interacted with Earth's atmosphere and broken down into secondary particles. With Earth-based instruments, it is nearly impossible to identify precisely how many primary cosmic rays and which elements are arriving, plus their energies. But CALET, being on the ISS above the atmosphere, can measure the particles directly and distinguish individual elements precisely.
Iron is a particularly useful element to analyze, explains Cannady, a postdoc with CSST and a former Ph.D. student with Cherry at LSU. On their way to Earth, cosmic rays can break down into secondary particles, and it can be hard to distinguish between original particles ejected from a source (like a supernova) and secondary particles. That complicates deductions about where the particles originally came from.
"As things interact on their way to us, then you'll get essentially conversions from one element to another," Cannady says. "Iron is unique, in that being one of the heaviest things that can be synthesized in regular stellar evolution, we're pretty certain that it is pretty much all primary cosmic rays. It's the only pure primary cosmic ray, where with others you'll have some secondary components feeding into that as well."
"Made of stardust"
Measuring cosmic rays gives scientists a unique view into high-energy processes happening far, far away. The cosmic rays arriving at CALET represent "the stuff we're made of. We are made of stardust," Cherry says. "And energetic sources, things like supernovas, eject that material from their interiors, out into the galaxy, where it's distributed, forms new planets, solar systems, and... us."
"The study of cosmic rays is the study of how the universe generates and distributes matter, and how that affects the evolution of the galaxy," Krizmanic adds. "So really it's studying the astrophysics of this engine we call the Milky Way that's throwing all these elements around."
A global effort
The Japanese space agency launched CALET and today leads the mission in collaboration with the U.S. and Italian teams. In the U.S., the CALET team includes researchers from LSU; NASA Goddard Space Flight Center; UMBC; University of Maryland, College Park; University of Denver; and Washington University.The new paper is the fifth from this highly successful international collaboration published in PRL, one of the most prestigious physics journals.
CALET was optimized to detect cosmic ray electrons, because their spectrum can contain information about their sources. That's especially true for sources that are relatively close to Earth in galactic terms: within less than one-thirtieth the distance across the Milky Way. But CALET also detects the atomic nuclei of cosmic rays very precisely. Now those nuclei are offering important insights about the sources of cosmic rays and how they got to Earth.
"We didn't expect that the nuclei - the carbon, oxygen, protons, iron - would really start showing some of these detailed differences that are clearly pointing at things we don't know," Cherry says.
The latest finding creates more questions than it answers, emphasizing that there is still more to learn about how matter is generated and moves around the galaxy. "That's a fundamental question: How do you make matter?" Krizmanic says. But, he adds, "That's the whole point of why we went in this business, to try to understand more about how the universe works."
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Robot-assisted surgery: Putting the reality in virtual reality
Cardiac surgeons may be able to better plan operations and improve their surgical field view with the help of a robot. Controlled through a virtual reality parallel system as a digital twin, the robot can accurately image a patient through ultrasound without the hand cramping or radiation exposure that hinder human operators. The international research team published their method in IEEE/CAA Journal of Automatica Sinica.
"Intra-operative ultrasound is especially useful, as it can guide the surgery by providing real-time images of otherwise hidden devices and anatomy," said paper author Fei-Yue Wang, Director of the State Key Laboratory of Management and Control of Complex Systems, Institute of Automation, Chinese Academy of Sciences. "However, the need for highly specialized skills is always a barrier for reliable and repeatable acquisition."
Wang noted that the availability of onsite sonographers can be limited, and that many procedures requiring intra-operative ultrasound also often require X-ray imaging, which could expose the operator to harmful radiation. To mitigate these challenges, Wang and his team developed a platform for robotic intra-operative trans-esophageal echocardiography (TEE), an imaging technique widely used to diagnose heart disease and guide cardiac surgical procedures.
"Our result has indicated the use of robot with a simulation platform could potentially improve the general usability of intra-operative ultrasound and assist operators with less experience," Wang said.
The researchers employed parallel control and intelligence to pair an operator with the robot in a virtual environment that accurately represents the real environment. Equipped with a database of ultrasound images and a digital platform capable of reconstructing anatomy, the robot could navigate the target areas for the operator to better visualize and plan potential surgical corrections in computational experiments.
"Such a system can be used for view definition and optimization to assist pre-planning, as well as algorithm evaluations to facilitate control and navigation in real-time," Wang said.
Next, the researchers plan to further integrate the currently proposed parallel real/virtual system with specific clinical needs to assist the translational research of such imaging robots.
"The ultimate goal is to integrate the virtual system and the physical robot for in-vivo clinical tests, so as to propose a new diagnosis and treatment protocol using parallel intelligence in medical operations," Wang said.
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S. Y. Wang, J. Housden, T. X. Bai, H. B. Liu, J. Back, D. Singh, K. Rhode, Z.-G. Hou, and F.-Y. Wang, "Robotic intra-operative ultrasound: Virtual environments and parallel systems," IEEE/CAA J. Autom. Sinica, vol. 8, no. 5, pp. 1095-1106, May 2021. http://www.ieee-jas.net/en/article/doi/10.1109/JAS.2021.1003985
IEEE/CAA Journal of Automatica Sinica aims to publish high-quality, high-interest, far-reaching research achievements globally, and provide an international forum for the presentation of original ideas and recent results related to all aspects of automation.
The first Impact Factor of IEEE/CAA Journal of Automatica Sinica is 5.129, ranking among Top 17% (11/63, SCI Q1) in the category of Automation & Control Systems, according to the latest Journal Citation Reports released by Clarivate Analytics in 2020. In addition, its latest CiteScore is 11.2, and has entered Q1 in all three categories it belongs to (Information System, Control and Systems Engineering, Artificial Intelligence) since 2018.
While ADHD is clinically defined to have impairments in cognitive functioning, cannabis use by itself is also associated with cognitive impairments: "[T]he evidence to date does not clearly support either an addictive effect or an interaction - whether protective or harmful - with cannabis use," according to the study by Philip B. Cawkwell, MD, of Stanford University School of Medicine, and colleagues. They underscore the need for further research to clarify possible effects of cannabis on brain structure, function, and behavior in young people with ADHD.
'Urgent need' for definitive studies of cannabis risk in teens with ADHD
The trends toward legalization and increased accessibility and potency of cannabis pose special concerns in young people living with ADHD. About one-fourth of teens with substance use disorder also have ADHD, while youth with ADHD are six times more likely to have drug or alcohol abuse. Some people with ADHD may even feel that cannabis improves their symptoms, studies suggest. Both groups have similar difficulties on cognitive tests, suggesting that youth with ADHD might be particularly vulnerable to effects of cannabis on cognitive function.
Dr. Cawkwell and colleagues performed a systematic review of research on the combined effects of cannabis use and ADHD in adolescence. Out of hundreds of initial "hits," the search identified just 11 studies assessing any type of neurodevelopmental outcome in adolescents or young adults with ADHD who did use cannabis compared with those who did not use cannabis.
Seven studies assessed neuroimaging findings for young ADHD patients, showing some significant differences in brain structure in cannabis users. Findings included decreased thickness in areas involved with motor and sensory function (such as the right precentral and postcentral gyri) and increased thickness in areas involved in the brain's "reward" system (such as the left nucleus accumbens). Given the limitations of the studies, the authors stress that these findings must be considered with caution and that it was impossible to determine whether or not these findings reflect causal relationships.
Functional imaging studies also reported differences in cannabis users with ADHD. Findings included differences in performance on standardized tasks and reduced density of dopamine transporters, thereby affecting the availability of dopamine, which plays a key role in the reward system.
Four studies looked at the results of neuropsychological tests or questionnaires in young people with ADHD who did and did not use cannabis. Cannabis use was associated with impaired performance on tests of sustained attention. However, the studies found no significant interaction between ADHD and cannabis use.
"Surprisingly, as cannabis use demonstrates clear and consistent adverse effects on cognition as measured by neuropsychological task performance, no study identified a significant differential impact of cannabis use on these measures for individuals with ADHD compared to non-users," Dr. Cawkwell and colleagues write. "However, this lack of interaction may just be due to the limited number of studies to date, rather than a true lack of impact," caution the study authors.
The authors note that the key limitation to this research is both the number of studies and the overall number of participants are limited. Some studies suggested differences in the effects of cannabis use at earlier ages ? a critical gap for further research. Additional factors the authors suggest need further examination include the potency of cannabis (which has roughly tripled in the past two decades, according to prior research) and the frequency of use.
Future studies may provide more definitive answers - particularly the ongoing "ABCD" study, which will provide long-term data on more than 10,000 participants followed up from age 10 to 20. Dr. Cawkwell and coauthors conclude: "[T]his important study may begin to provide answers to some of the questions that this paper has shown to be unanswered - including understanding whether cannabis does truly alter neural circuitry in youth with ADHD, how this impacts task performance, and perhaps most critically, the longer-term functional outcomes for adolescents with ADHD who also use cannabis."
The Harvard Review of Psychiatry is the authoritative source for scholarly reviews and perspectives on a diverse range of important topics in psychiatry. Founded by the Harvard Medical School Department of Psychiatry, the journal is peer reviewed and not industry sponsored. It is the property of Harvard University and is affiliated with all of the Departments of Psychiatry at the Harvard teaching hospitals. Articles encompass major issues in contemporary psychiatry, including neuroscience, epidemiology, psychopharmacology, psychotherapy, history of psychiatry, and ethics.
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