Culture

Osaka, Japan - On the outside, animals often appear bilaterally symmetrical with mirror-image left and right features. However, this balance is not always reflected internally, as several organs such as the lungs and intestines are left-right (LR) asymmetrical. Researchers at Osaka University, using an innovative technique for imaging movement of cell nuclei in living tissue, have determined the patterns of nuclear alignment responsible for LR-asymmetrical shaping of internal organs in the developing embryo.

Embryogenesis involves complex genetic and molecular processes that transform a single-celled zygote into a complete, living individual with multiple functional axes, including the LR axis. A long-standing conundrum of Developmental Biology is the breaking of LR symmetry in the developing embryo to initiate lateralization (dominance of one side over the other) of organs and other structures of the body along the LR axis. Mechanisms that induce LR asymmetry are well known in vertebrates; however, the biomechanics in invertebrates remain uncertain.

The research team focused on the development of the intestine, in particular the anterior midgut (AMG) of the Drosophila (fruit fly) as an appropriate model to study LR-asymmetric development in invertebrates. "Proper organ development often requires nuclei to move to a specific position within the cell," first author Dongsun Shin explains. "Our previous studies had revealed the molecular signaling pathways as well as the proteins responsible for the biomechanical control of asymmetric development, but the dynamics had not yet been determined."

To meet the challenge of dynamically tracking nuclei in living tissue, the researchers innovated a new method to investigate nuclear migration. Using a confocal laser scanning microscope, they obtained three-dimensional (3D) time lapse videos of immunostained Drosophila midgut at the appropriate embryonal stage. Then, applying mathematical modeling and computational imaging techniques they generated 3D-surface animated models of nuclear migration in the visceral muscles.

Through 3-D time-lapse movies, the researchers identified the initial LR-symmetrical distribution of AMG muscle nuclei along the antero-posterior (front-to-back) axis—termed 'proper nuclear positioning.' Further, they vividly imaged 'collective nuclear behavior' in which crowded nuclei actively rearranged their relative positions with LR symmetry. This symmetric initial 'proper nuclear positioning' and 'collective nuclear behavior' are responsible for subsequent LR-asymmetric development of the AMG. In contrast, experiments in genetically modified Drosophila embryos demonstrated that when the nuclei aligned with LR-asymmetry, the subsequent LR-asymmetric development of the AMG was lost. It is known that nuclei are the toughest intracellular organelles. Thus, based on these results, the researchers speculated that nuclei may act like structural pillars if they are collectively aligned, which support the structure of the gut and influence LR-asymmetrical changes in shape during its development.

Senior author Kenji Matsuno explains the potential of their findings: "This new method of tracking moving nuclei in vital tissue has helped clarify the role of nuclear alignment in asymmetrical shaping of internal organs during normal development. In addition, our findings are expected to be applied to controlling the shape of regenerative organs. This knowledge could potentially shape future research into organ regeneration which may have applications such as growing artificial organs to model disease mechanisms."

Echoing through history by reviving fungal specimens originally preserved and described a flabbergasting quarter of a millenium ago by the "Father of Modern Taxonomy" Carl Linnaeus, this study highlights the untapped potential of museum collections in modern research programmes. The results have just been published in the renowned Cell Press journal iScience.

The "desert coprinus" fungus Podaxis has fascinated scientists and explorers for centuries, still the genus has been subjected to relatively little research. These large mushrooms thrive in hostile and mostly species-free environments and while they occur seasonally and unpredictably in deserts and on termite mounds, researchers are faced with a problem common to many biologists: Where do we find it? The researchers from the Department of Biology turned to an unconventional sampling location: Museum collections. By requesting fungal spores from various collections, including the Linnaean Society of London and the Natural History Museum of Denmark, they were able to collect more than 200 specimens from every continent aside from Antarctica. The specimens varied in age from 2 to 250 years old.

Specimen from the South African National Collection of Fungi in Pretoria. Photo: Benjamin Schantz-Conlon

Given the finding that fungal spores can grow after 2-5 years in a museum, the limit for their revival was tested. Eventually the researchers succeeded in germinating and growing two Podaxis specimens collected in the 1770s and classified by Linnaeus in Uppsala. These results reveal an extraordinary capacity for Podaxis spores to remain viable through extended periods of drought and suggests that they can remain dormant in the environment for centuries before germinating once conditions allow.

- "It was really incredible to have these fungi growing in our lab, which we knew had been handled by a scientist as important as Linnaeus, who founded the system of naming species. It allowed us to perform experiments and produce genomes of a quality that would have been impossible with dried specimens," explains postdoc and first author Benjamin Schantz-Conlon of the Department of Biology, University of Copenhagen. Benjamin Schantz-Conlon continues: "It was very interesting to examine the adaptations allowing Podaxis to survive under extreme conditions, hereunder also in herbarium collections where the samples traditionally has been treated with mercury as a pesticide".

The researchers used the specimens to ask whether free-living Podaxis species growing in deserts were genomically and physiologically different from species growing on termite mounds. The results indicated that the association with termites gave rise to smaller genome sizes and a reduced tolerance to stressful conditions.

- "These findings suggest that Podaxis living in association with termites are experiencing a relaxed selection pressure and a potential protection from competition and exposure to stressors in the environment", says corresponding author Michael Poulsen, professor at the Department of Biology.

Podaxis growing on a termite mound. Photo: Z. Wilhelm de Beer
Previous research has shown there is an overlap between tolerance to extreme conditions such as deserts and pathogenicity. By comparing the transition from a free-living state in a desert to a symbiotic state within a termite mound, the researchers hoped to learn more about the evolution of fungi that shift to associate with hosts, including pathogens.

- "While Podaxis living in an obligate association with termites exhibited relaxed selection, we also found some Podaxis which could survive both on termite mounds and free-living in deserts. In this case, we saw little genomic or physiological difference between them and the fully free-living Podaxis, suggesting the adaptations for life in the desert may facilitate the initial colonization of termite mounds; something which is also seen in opportunistic pathogens."

An immense resource of knowledge is stored in museum collections and we should work to ensure that these specimens can be used to answer important questions in science in the future.

Hypertension is a widespread comorbidity of patients with obesity that greatly increases the risk of mortality and disability. In recent years, researchers have found that a high-calorie diet increases the density of blood vessels (hypervascularization) in the hypothalamus - an important "eating control" area in our brain. Researchers hypothesized that elevated hormone levels of leptin are associated with a higher risk of developing hypertension. However, the exact mechanisms that contribute to the condensed growth of blood vessels in the hypothalamus were unknown.

New research conducted by Cristina García-Cáceres' research group at Helmholtz Zentrum München has now revealed that obese mice do not increase the amount of blood vessels in the hypothalamus when they lack the hormone leptin. Leptin is produced by adipose tissue, is involved in the control of hunger and satiety, and plays an important role in the regulation of fat metabolism in humans and mammals.

Once the researchers increased the hormone leptin in these mice, certain brain cells, the astrocytes, boosted the production of a specific growth factor. This growth factor, in turn, promoted vessel growth. The result was an increased number of vessels in the hypothalamus (and no other brain region). The scientists thus demonstrated that leptin is mainly responsible for the increased concentration of vessels in the hypothalamus and that this process is mediated via astrocytes.

"We provide a paradigm shift in our understanding of how the hypothalamus controls blood pressure in obesity," explains first author Tim Gruber. "While previous research has focused primarily on neurons, our research highlights the new role of astrocytes, historically assumed less relevant than neurons, in controlling blood pressure".

Looking into the future, according to study leader Cristina García-Cáceres, one important question remains: How exactly do astrocytes communicate with neurons? "We have started to answer this question using in vivo real-time imaging of astrocyte-neuron circuit function in the hypothalamus," the researcher says.

Solar activities, such as CME(Coronal Mass Ejection), cause geomagnetic storm that is a temporary disturbance of the Earth's magnetosphere. Geomagnetic storms can affect GPS positioning, radio communication, and power transmission system. Solar explosions also emit radiation, which can affect satellite failures, radiation exposure to aircraft crew, and space activity. Therefore, it is important to understand space weather phenomena and their impact on the Earth.

Space weather research by continuous observation of cosmic rays on the ground is mainly conducted using observation data from neutron monitors and multi-directional muon detectors. Since the phenomenon of space weather is on a short-term, days-long scale, it is effective to investigate changes in the flow of cosmic rays for several hours, which requires a total sky monitor of cosmic rays. In the muon detector, the global muon detector network (GMDN) has been observing space weather phenomena since 2006, and in the neutron monitor, the Spaceship Earth project constitutes a similar observation network and the role of the all-sky monitor. Until now, observations by neutron monitors and muon detectors have been performed independently, and progress has been made in space weather research.

In February 2018, Professor Chihiro Kato of Shinshu University took the lead in acquiring simultaneous observations of the neutron monitor and muon detector at Syowa Station in the Antarctic in order to acquire bridging data of observations by the neutron monitor and muon detector. In the polar regions, unlike low latitude regions on the earth, it is possible to observe cosmic rays coming from the same direction with a neutron monitor and a muon detector due to the weaker deflection by the geomagnetism. This is the reason why Syowa Station was selected as the observation point.

Syowa muon detector and neutron monitor observed small fluctuation in CR count like a Forbush decrease on 2018.8. The research group including researchers from Shinshu University and the National Polar Research Institute found curious cosmic-ray density variation on this event by analyzing GMDN data.

On the CME event, a huge amount of coronal material released with a bundle of the solar magnetic field, called Magnetic Flux Rope (MFR), into the interplanetary space. MFR moves through interplanetary space as expanding. CR density is low inside of it because it is originally coronal material. When the Earth enters the MFR, CR counts on the ground decreases. This is called Forbush Decrease.

Normally, when MFR arrives on Earth, CR density observed at the ground level decreases rapidly, and then turns to increase recovering to the original level while the Earth is in the MFR. On this event, however, the CR exceeds the original level before the Earth exits the MFR.

This event attracts interest from researchers because 1) The solar activity is currently near the minimum and the scale of the event itself is small, 2) It causes a disproportionately large geomagnetic storm, and 3) There is high-speed solar wind catching up the MFR expected to interact with it.

By analysis of the GMDN and solar plasma data, it is concluded that the high-speed solar wind causes the unusual enhancement of the CR density by compressing the rear part of the MFR locally.

Cosmic ray observation data is closely related not only to space weather research but also to atmospheric phenomena such as sudden stratospheric temperature rise and is expected to be used in a wide range of fields in the future. The cosmic ray observation data at Syowa Station, including the phenomenon in August 2018, which was the subject of this research, is published on the website and updated daily:
http://polaris.nipr.ac.jp/~cosmicrays/

Alkaline zinc-iron flow battery (AZIFB) is well suitable for stationary energy storage applications due to its advantages of high open-cell voltage, low cost, and environmental friendliness. However, it surfers from zinc dendrite/accumulation and relatively low operation current density.

Recently, a research group led by Prof. LI Xianfeng from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Science (CAS) developed layered double hydroxide (LDH) membrane with high hydroxide conductivity and ion selectivity for alkaline-zinc iron flow battery.

The study was published in Nature Communications on June 7.

In order to enhance the operating current density of AZIFB, the researchers added LDHs nano materials into the AZIFB and designed a LDHs-based composite membrane with high performance. High selectivity and superb hydroxide ion conductivity were achieved through the combination of the well-defined interlayer gallery with a strong hydrogen bond network along 2D surfaces.

They identified that surface -OH groups of LDHs layer could assist the conduction of OH- by promoting proton transfer away from one water molecule to the original OH-.

Because of the high ionic conductivity, the LDHs-based membrane enabled the AZIFB to operate at 200 mA cm-2, along with an energy efficiency of 82.36%.

"This study offers a new insight to design and manufacture high-performance membranes for AZIFB," said Prof. LI.

Light--and all waves--can bend around the corners of obstacles found along its path. Because of this phenomenon, called diffraction, it is impossible to focus light onto a spot that is smaller than half its wavelength. In other words, the highest resolution one can theoretically achieve using an optical microscope is approximately 250 nm, a barrier called the diffraction limit. Unfortunately, this resolution is not enough for observing fine cellular structures, such as those found in neurons.

Over more than a century, microscopists were hamstrung by this classic barrier until the invention of super-resolution fluorescence microscopy. One particularly powerful approach was developed in the late 1990s and coined stimulated-emission depletion (STED) microscopy. This technique requires the target sample to contain fluorophores, which are compounds that absorb light at one wavelength and then re-emit it at a longer one. In the simplest version of STED microscopy, fluorophores are excited in a circular spot by irradiation with a diffraction-limited focused laser. Then, a donut-shaped portion around the spot is irradiated with less-energetic light--the depletion beam--which switches off the fluorescence by the process of stimulated emission. Thus, the net effect is that only the fluorophores in the center of the donut re-emit photons, and because that area can be made arbitrarily small, this allows for super-resolution microscopy.

Although STED microscopy was a true breakthrough for observing the morphology of live neurons at higher resolution, there is still room for improvement. In a recent study published in Neurophotonics, a team of scientists led by Dr. U. Valentin Nägerl from Université de Bordeaux developed a simple yet effective calibration method that allows for more precise STED imaging at higher tissue depths. Their approach is based on analyzing and correcting for one of the main sources of systematic error in STED microscopy for biological samples: spherical aberration of the depletion beam.

When imaging a tissue sample at depths higher than 40 μm, the depletion beam suffers various types of defocusing and degradation (aberration) and loses its carefully crafted shape, which is essential to the STED method. Spherical aberration is the biggest offender and was the one the researchers targeted. Their strategy was to first prepare a brain tissue phantom sample, a gel-based proxy with a refractive index similar to that of the actual brain. This phantom sample contained homogenously dispersed fluorophores and gold nanoparticles, which allowed the team to clearly visualize and quantify how the shape of the depletion beam got distorted as it penetrated deeper. Then, they calculated the necessary pre-adjustments that should be made to the depletion beam according to tissue depth so that its final shape more closely matches the ideal one. The adjustments were made using adaptive optics, which is a technology originally developed by astronomers to improve telescopic images that suffer from aberrations caused by the earth's atmosphere.

Once the shape of the depletion beam had been calibrated according to the phantom tests, the scientists proceeded to image live neural tissue. They compared the results of regular STED microscopy, corrected STED microscopy, and two-photon microscopy--a technique that is specifically adjusted for deep tissue imaging. The results were quite convincing: corrected STED images captured the fine details of deeper neural dendrites much better than standard STED images. "Using our calibration strategy, we could measure neuronal structures as small as 80 nm at a depth of 90 μm inside biological tissue and obtain a 60 percent signal increase after correction for spherical aberration," says Nägerl.

Ji Yi, professor of biomedical engineering at Johns Hopkins University remarks, "Super-resolution microscopy has been primarily applied for thin specimens, such as single layer cells, where light scattering is negligible. The team led by Valentin Nägerl implemented adaptive optics in a two-photon stimulated emission depletion microscopy (2P-STED), and achieved 80nm resolution of imaging neuron dendritic spines through 90 micron brain tissue. This is noteworthy because super-resolution is hard to maintain in thicker tissue--particularly given the highly scattering quality of brain tissue." Yi explains that the advance will facilitate study of neural activities and interactions.

Considering this novel calibration process is robust, straightforward to implement, and relatively inexpensive, it could be easily incorporated into standard laboratory practices to obtain better results with STED microscopes, so long as the prepared phantom sample matches the optical properties of the biological specimen. In this regard, Nägerl states: "Our approach is not limited to brain samples; it could be adapted to other tissues with known and relatively homogeneous refractive indices, as well as other types of preparations, even potentially in the intact, live mouse brain."

Stem cell biologist Hugo Vankelecom (KU Leuven) and his colleagues have discovered that the pituitary gland in mice ages as the result of an age-related form of chronic inflammation. It may be possible to slow down this process or even partially repair it. The researchers have published their findings in PNAS.

The pituitary gland is a small, globular gland located underneath the brain that plays a major role in the hormonal system, explains Professor Hugo Vankelecom from the Department of Development and Regeneration at KU Leuven. "My research group discovered that the pituitary gland ages as a result of a form of chronic inflammation that affects tissue and even the organism as a whole. This natural process usually goes unnoticed and is referred to as 'inflammaging' -- a contraction of inflammation and ageing. Inflammaging has previously been linked to the ageing of other organs." Due to the central role played by the pituitary, its ageing may contribute to the reduction of hormonal processes and hormone levels in our body - as is the case with menopause, for instance.

The study also provides significant insight into the stem cells in the ageing pituitary gland. In 2012, Vankelecom and his colleagues showed that a prompt reaction of these stem cells to injury in the gland leads to repair of the tissue, even in adult animals. "As a result of this new study, we now know that stem cells in the pituitary do not lose this regenerative capacity when the organism ages. In fact, the stem cells are only unable to do their job because, over time, the pituitary becomes an 'inflammatory environment' as a result of the chronic inflammation. But as soon as the stem cells are taken out of this environment, they show the same properties as stem cells from a young pituitary."

Chance of recovery?

This insight opens up a number of potential therapeutic avenues: would it be possible to reactivate the pituitary? This wouldn't just involve slowing down hormonal ageing processes, but also repairing the damage caused by a tumour in the pituitary, for example. "No fewer than one in every 1,000 people is faced with this kind of tumour -- which causes damage to the surrounding tissue -- at some point. The quality of life of many of these patients would be drastically improved if we could repair this damage. We may be able to do so by activating the stem cells already present -- for which our present study also provides new indications -- or even by transplanting cells. That said, these new treatment options are not quite around the corner just yet, as the step from fundamental research to an actual therapy can take years to complete. For the time being, our study sets out a potential direction for further research."

The study also suggests another interesting avenue: the use of anti-inflammatory drugs to slow down pituitary ageing or rejuvenate an ageing pituitary. "Several studies have shown that anti-inflammatory drugs may have a positive impact on some ageing organs. No research has yet been performed on this effect in relation to the pituitary."

From mice to humans

Vankelecom and his colleagues studied the pituitary of mice, so further research is required to demonstrate whether their findings also apply to humans. Vankelecom comments: "Mice have a much greater regeneration capacity than humans. They can repair damaged teeth, for instance, while humans have lost this ability over the course of their evolution. Regardless, there are plenty of signs suggesting that pituitary processes in mice and humans are similar, and we have recent evidence to hand that gene expression in the pituitaries of humans and mice is very similar. As such, it is highly likely that the insights we gained will equally apply to humans."

The inclusion of biological uncertainty and the latest case data can significantly improve the prediction accuracy of standard epidemiological models of virus transmission, new research led by KAUST and the Kuwait College of Science and Technology (KCST) has shown.

Modern mathematical epidemic models have been tested like never before during the COVID-19 pandemic. These models use mathematics to describe the various biological and transmission processes involved in an epidemic. However, when such factors are highly uncertain, such as during the emergence of a new virus like COVID-19, the predictions can be unreliable.

"The susceptible-exposed-infected-recovered model, SEIR, is a standard mathematical approach for forecasting the spread of an epidemic in a population," says Rabih Ghostine, formerly of KAUST and now at KCST. "This model is based on several assumptions, such as homogeneous mixing of the population and the omission of migration, births or deaths from causes other than the epidemic. The parameters in the traditional SEIR model also do not allow for quantification of uncertainty, being single values reflecting the modeler's best guess."

"We wanted to develop a robust mathematical model that takes into account such uncertainties and incorporates epidemic data in order to enhance forecasting accuracy," explained Ghostine.

Ghostine, along with KAUST's Ibrahim Hoteit and fellow researchers, developed an extended SEIR model compromising seven compartments: susceptible, exposed, infectious, quarantined, recovered, deaths and vaccinated. They then added uncertainty definitions and a data assimilation process to drive progressive improvement of the model.

"Our data assimilation approach exploits new incoming observations to calibrate the model with recent information in order to continuously provide improved predictions, and also to estimate uncertainties," says Ghostine. "This is a popular framework in the atmospheric and ocean research communities and is at the basis of all operational weather and ocean modeling."

The model uses an "ensemble" approach, in which a set of predictions is generated across different parameter uncertainties. This ensemble is then integrated forward in time to forecast the future state. A correction step is performed to update the forecast with the latest data. Validation using real data for Saudi Arabia showed the model to provide reliable forecasts for up to 14 days in advance.

"Mathematical models can play an important role in understanding and predicting COVID-19 transmission as well as provide crucial information to policymakers to implement appropriate measures and efficient strategies to control the pandemic spread and mitigate its impact," says Hoteit. "Our method, which we developed to simulate the COVID-19 spread in Saudi Arabia, can also be applied to forecast the spread of any pandemic in a population."

Pesticides safeguard agricultural yields by controlling harmful insects, fungi, and weeds. However, they also enter neighbouring streams and damage the aquatic communities, which are crucial for maintaining biodiversity, are part of the food web and support the self-purification of water. In a nationwide monitoring programme, a consortium of scientists led by the Helmholtz Centre for Environmental Research (UFZ) has shown that the governmental thresholds for pesticides are generally too high and that even these excessively high levels are still exceeded in over 80% of water bodies. As they published in the scientific journal Water Research the loss of biodiversity can only be halted if the environmental risk assessment of pesticides is radically revised.

For two years, the researchers studied pesticide contamination at more than 100 monitoring sites on streams flowing through predominantly agricultural lowland regions in 12 federal states in Germany. They found significant exceedances of the RAC value - the concentration of an active ingredient specified in the official approval procedure for a pesticide, which should not be exceeded in the water body in order to prevent negative effects on aquatic organisms. In most of the small streams investigated, the RAC values were exceeded (81%). In 18% of the streams, such exceedances were detected for more than 10 pesticides. "We have detected a significantly higher pesticide load in small water bodies than we originally expected", says Prof. Matthias Liess, ecotoxicologist at the UFZ and coordinator of the small water monitoring project. For example, in three water bodies, the insecticide thiacloprid exceeded the RAC value by more than 100-fold. In 27 streams the insecticides clothianidin, methiocarb, and fipronil as well as herbicides such as terbuthylazine, nicosulfuron, and lenacil exceeded the RAC value 10- to 100-fold.

Because of the extensive data set, the researchers were able to reveal that pesticides affect aquatic invertebrate communities at much lower concentrations than previously assumed by the pesticide risk assessment. The concentrations depend on which species are to be conserved. For example, sensitive insect species such as caddisflies and dragonflies require much lower (1.000-fold) threshold values than snails and worms. "For sensitive insect species, the pesticide concentration in the small lowland streams is the most relevant factor that determines their survival. In contrast, other environmental problems such as watercourse expansion, oxygen deficiency, and excessive nutrient content are less important. For the first time this study allows a ranking of environmental problems", says Liess.

For the current approval of pesticides, the high sensitivity of species in the ecosystem context is grossly underestimated. Until now, the ecological risk of pesticides in the field has been predicted based on laboratory studies, artificial ecosystems, and simulation models. However, according to Liess, the results from the laboratory do not reflect reality. "In addition to pesticides, many other stressors act on organisms in the ecosystem. These make them much more sensitive to pesticides. Natural stressors such as predation pressure or competition between species are not sufficiently taken into account in the risk assessment. But these obvious problems often go unnoticed because the degree of pesticide contamination and the effect of this have not been validated in the field - neither in Germany nor in other countries", he says.

In the course of the project, the scientists also found that the type of sampling has a drastic influence on the concentrations of pesticides measured. In addition to the scoop sample specified as standard by the EU Water Framework Directive, they also took an "event sample". Here, an automatically controlled sampler takes water samples from the water body after a rain event. "The event sample provides much more realistic results because the pesticides enter the water bodies as a result of the increased surface run-off from the field, especially during rain", says Liess. Compared to the scoop samples, the event-related samples show a 10-fold higher pesticide load. "In order to realistically depict the water pollution, samples must therefore be taken after rainfall events. That's why we need an official regular environmental monitoring to be able to assess the amount and the effects of pesticides," says Matthias Liess. He and his colleagues also demand that new scientific findings be incorporated into the approval process for new pesticides more quickly. "We are still using pesticides that were approved many years ago based on an outdated risk assessment. This must therefore change as soon as possible. Only in this way can we preserve the biodiversity in our waters and with it the services that these biotic communities provide for our ecosystems."

DUBLIN, June 15, 2021 - Scientists have identified how and why some Covid-19 patients can develop life-threatening clots, which could lead to targeted therapies that prevent this from happening.

The work, led by researchers from RCSI University of Medicine and Health Sciences, is published in the Journal of Thrombosis and Haemostasis.

Previous research has established that blood clotting is a significant cause of death in patients with Covid-19. To understand why that clotting happens, the researchers analysed blood samples that were taken from patients with Covid-19 in the Beaumont Hospital Intensive Care Unit in Dublin.

They found that the balance between a molecule that causes clotting, called von Willebrand Factor (VWF), and its regulator, called ADAMTS13, is severely disrupted in patients with severe Covid-19.

When compared to control groups, the blood of Covid-19 patients had higher levels of the pro-clotting VWF molecules and lower levels of the anti-clotting ADAMTS13. Furthermore, the researchers identified other changes in proteins that caused the reduction of ADAMTS13.

"Our research helps provide insights into the mechanisms that cause severe blood clots in patients with Covid-19, which is critical to developing more effective treatments," said Dr Jamie O'Sullivan, the study's corresponding author and research lecturer within the Irish Centre for Vascular Biology at RCSI.

"While more research is needed to determine whether targets aimed at correcting the levels of ADAMTS13 and VWF may be a successful therapeutic intervention, it is important that we continue to develop therapies for patients with Covid-19. Covid-19 vaccines will continue to be unavailable to many people throughout the world, and it is important that we provide effective treatments to them and to those with breakthrough infections."

The University of Ottawa has been awarded four new Canada Research Chairs (CRC) that will strengthen its expertise in artificial intelligence, health and law. The University is also proud to announce the renewal of two CRCs that will conduct leading-edge research in quantum communications and photonics.

"The Canada Research Chairs Program provides invaluable support to our researchers as they forge their paths of discovery at a world-class level," said Sylvain Charbonneau, vice-president, research. "The results of this most recent competition will undeniably help the University succeed in pursuing our goals of excellence, relevance and research impact."

The three new Tier 1 Canada Research Chairs are:

Khaled El Emam (Faculty of Medicine and CHEO Research Institute) -- Canada Research Chair in Medical Artificial Intelligence

Khaled El Emam's research will focus on developing a methodology for the synthesis of complex health data. This means applying artificial intelligence techniques to model personal clinical and biological information stored in databases. These models can be used to generate virtual patients that mimic the characteristics of real patients. This solves data-sharing problems and enables adding simulated patients to accelerate clinical studies.

Rita Horvath (Faculty of Medicine and CHEO Research Institute) -- Canada Research Chair in Mitochondrial Disease Pathogenesis to Therapy

Mitochondrial diseases are genetic disorders that are difficult to diagnose and cause a range of devastating physical, developmental and intellectual disabilities. Rita Horvath's research aims to understand the molecular mechanisms of mitochondrial disease, to provide accurate diagnosis and develop targeted therapies.

Carole Yauk (Faculty of Science) -- Canada Research Chair in Genomics and the Environment

Carole Yauk's research addresses an urgent need to modernize the toxicological risk assessment of environmental chemicals. She will develop and deploy genomics approaches that measure how toxic chemicals can alter the function of genes or damage genetic material. Her laboratory will work with regulatory and industry partners to determine the best use of this information, to predict toxicological risks to humans and wildlife.

The new Tier 2 Canada Research Chair is:

Emmanuelle Bernheim (Faculty of Law, Common Law Section) -- Canada Research Chair in Mental Health and Access to Justice

Emmanuelle Bernheim's research looks at improving access to the justice system for diverse groups, particularly those living with mental health issues, while focussing on community, political and research circles.

The two renewed Tier 2 Canada Research Chairs are:

Ksenia Dolgaleva (Faculty of Engineering) -- Canada Research Chair in Integrated Photonics

Photonic integration uses light for applications traditionally performed by electronics. Combining a laser source, waveguides that direct light and other optical components on a small semiconductor chip, photonics has a number of uses in areas such as medicine, information and communication technologies, and sensing. Ksenia Dolgaleva's research aims to increase the functionality of existing optical chips by developing integrated optical devices that can manipulate light in new ways. These devices will be able to change the colour of incident light and manipulate light with light. This is essential to all-optical processing of information channels without needing to convert them to an electrical current.

Ebrahim Karimi (Faculty of Science) -- Canada Research Chair in Structured Quantum Waves

Ebrahim Karimi's research program uses structured quantum waves to enhance capabilities and open new horizons in quantum communication protocols, simulators and sensing. Robust yet compact devices will be designed to efficiently structure electron and optical beams, increasing the security and capacity of information transmission -- the key to establishing the first quantum network across Ottawa -- as well as measuring and analyzing materials properties quickly on a small scale.

A review of more than 9,000 U.S. patients with severe COVID-19 infection showed less than 1% contracted the illness again, with an average reinfection time of 3.5 months after an initial positive test. Those are the findings from a study conducted by researchers from the University of Missouri School of Medicine and MU Health Care.

The researchers teamed up with the MU Institute for Data Science and Informatics and the Tiger Institute for Health Innovation to review data from 62 U.S. health care facilities. They found 63 of the 9,119 patients (0.7%) with severe COVID-19 infection contracted the virus a second time, with a mean reinfection period of 116 days. Of the 63 who were reinfected, two (3.2%) died. Patients categorized as non-white were at greater risk of reinfection than white patients.

"Our analysis also found asthma and nicotine dependence were associated with reinfection," said lead researcher Adnan I. Qureshi, MD, a professor of clinical neurology at the MU School of Medicine. "However, there was a significantly lower rate of pneumonia, heart failure and acute kidney injury observed with reinfection compared with primary infection."

Qureshi defined reinfection by two positive tests separated by an interval greater than 90 days after the initial infection resolved, as confirmed by two or more consecutive negative tests. He analyzed data from patients who received serial tests between December 2019 and November 2020.

"This is one of the largest studies of its kind in the U.S., and the important message here is that COVID-19 reinfection after an initial case is possible, and the duration of immunity that an initial infection provides is not completely clear," Qureshi said.

In addition to Qureshi, the study authors include fellow MU School of Medicine collaborators Iryna Lobanova, MD, research specialist in the Department of Neurology; S. Hasan Naqvi, MD, associate professor of clinical medicine; William Baskett, graduate student; Wei Huang, graduate student; and Chi-Ren Shyu, PhD, Director, MU Institute for Data Science and professor of Informatics, Electrical Engineering and Computer Science.

June 15, 2021 - Canadian researchers have discovered that a bee thought to be one of the rarest in the world, as the only representative of its genus, is no more than an unusual specimen of a widespread species.

Scientists with the Canadian Museum of Nature (CMN) and York University have reclassified the mystery bee, collected somewhere in Nevada in the 1870s, as Brachymelecta californica. They note that it's an aberrant individual of a species, the California digger-cuckoo bee, that is part of a group that includes five other species. All are cleptoparasitic bees, with females that lay eggs in the nests of digger bees. Brachymelecta californica itself is known to be widespread from western Canada to southern Mexico.

The paper setting the record straight is published today in the European Journal of Taxonomy. "The unusual specimen has puzzled bee researchers for decades, and deceived some of the world's great experts on bee taxonomy" says Dr. Thomas Onuferko, research associate with the CMN and the study's lead author. "They can now stop searching for more examples of this 'rare' bee."

The bee was first described in 1879 by American entomologist Ezra Townsend Cresson from the Nevada specimen. It was later placed in its own genus, and renamed Brachymelecta mucida in 1939, a name that has only ever been associated with this lone specimen.

It stood apart from other related bees because its abdomen's dorsal surface is unusually covered in pale hairs, these being partly dark in other specimens of what are now understood to be the same species. Another unusual feature is that the fore wings of the specimen each have two submarginal cells (the normal number for the bees in this group is three). These two features had confused everyone, until now.

In 2019, Onuferko was able to examine the rare specimen during a visit to the collections at Philadelphia's Academy of Natural Sciences of Drexel University. There, he discovered a series of other specimens with the same vague locality labels, but these bees were identified as Xeromelecta californica, a species that was also described by Cresson in the year before the description of the mystery species.

In some of the specimens, the pattern of veins in the wings is the same as in the mystery specimen. "At that point, I made the connection that these specimens might all be the same species," says Onuferko.

This connection was further boosted by the discovery in Dr. Laurence Packer's collection at York University of a bee that also had conspicuously pale hairs on its entire abdomen. DNA barcoding confirmed the specimen to be Xeromelecta californica. Hairs that are normally dark in this species were completely light. Onuferko and Packer, who also collaborated on the study, concluded that the hairs likely lacked pigmentation due to a form of partial albinism.

The finding surprised Packer because some of the best bee biologists had studied the specimen, but he adds, "Rummaging around in old collections is actually an important thing to do. There is a lot to discover within museum collections, and in this case the rummaging revealed that a rare bee is not so rare after all."

The discovery has prompted an unusual name change, which is based on rules of the organization that governs the naming of animal species--the International Commission of Zoological Nomenclature. Due to the chronology of dates in which the bees' various genus and species names were published, Brachymelecta californica takes precedence as the accepted name, and the five related species classified as Xeromelecta are now also part of the genus Brachymelecta. This genus, previously known from a single specimen, is now known from most of the bee collections in North America.

"The reclassification of this bee shows why it's important to describe new taxa from multiple examples and why entomologists collect specimens in series," explains Onuferko. It is impossible to know the range of variation within a species with a single specimen, and describing new species from a lone sample risks mistaking an aberrant specimen for a new species.

New species still occasionally get described from single specimens; however, in such cases the new species should be thoroughly justified (using both molecular and morphological evidence, if possible), to avoid taxonomic problems down the line.

The study's authors explain that many researchers have written about the mystery bee under its earlier classification as Brachymelecta mucida, meaning that intellectual resources were dedicated to a specimen that did not merit them. "Bee collectors were effectively in search of an elusive 'white whale; or more appropriately, a 'whitish bee', a species that evidently only existed in the minds of taxonomists," says Onuferko.

A recent UCLA clinical trial has shown encouraging results in helping daily smokers who are also heavy drinkers quit smoking and cut down their alcohol intake.

The study of 165 people tested two prescription drugs -- varenicline, for smoking addiction, and naltrexone, which is used to treat alcoholism. Studies have shown that varenicline, marketed under the brand name Chantix, may also be effective in reducing alcohol consumption.

Participants, who ranged in age from 21 to 65, smoked at least five cigarettes a day, with male participants generally consuming more than 14 drinks a week and women more than seven per week.

Over the 12-week study period, each participant received 2 milligrams of varenicline twice a day. Roughly half the group -- 83 participants -- also received a 50-milligram dose of naltrexone daily, while the other 82 received placebo pills. They were all told to quit smoking and drink less.

When researchers followed up 26 weeks after the study's conclusion, they found that nearly 36% -- 59 participants -- had quit smoking.

"The overall smoking quit rate in the trial is impressive," said lead author Lara Ray, a professor of psychology and of psychiatry and biobehavioral sciences who holds UCLA's Shirley M. Hatos Chair in Clinical Neuropharmacology. She noted that previous studies have suggested varenicline has a success rate at six months of about 25% to 30%.

"We exceeded the overall expectation for this medication," she said. "This is especially important in a diverse group of people." Ray said that while some previous studies have shown lower-than-average smoking cessation rates among Black participants, that was not the case in the current trial, in which more than half of participants were Black.

Surprisingly, the researchers said, those who had received varenicline plus a placebo had a significantly higher smoking quit rate (45%, or 37 of 82 participants) than those who were given varenicline and naltrexone (27%, or 22 of 83 participants).

"The quit rate for varenicline alone in this sample is highly encouraging, as this is the first large-scale trial of varenicline efficacy focused solely on heavy-drinking smokers," Ray said.

While participants who received varenicline plus naltrexone had a lower smoking quit rate, they had slightly better success than the placebo group at curbing their drinking. At the start of the study, participants averaged nearly seven drinks per drinking day; those on the varenicline-naltrexone combination reduced their consumption to three drinks per drinking day over the 12-week study period, while those receiving the varenicline-placebo combination cut down to four drinks -- both impressive decreases, Ray said.

"I am excited about both the smoking cessation rates and the drinking reductions," said Ray, who is also a member of UCLA's Brain Research Institute. "These findings suggests that desirable outcomes for smoking cessation and drinking reduction are achievable."

The study, which found no difference in quit and reduction rates between men and women, was published online in the American Journal of Psychiatry June 3 and is scheduled for publication in the journal's September print issue.

Approximately 20% to 25% of smokers are also heavy drinkers. Smoking and heavy drinking are major public health concerns that reduce people's life span and quality of life, and both have also been linked to worse health outcomes for COVID-19.

As with all addictions, quitting smoking and reducing drinking are difficult and complex processes. This study confirms that medications can play a role, Ray said, but she noted that it can be challenging for patients to take more than one prescribed medication.

"Varenicline alone is doing a great job, and this trial indicates that there is not much room for naltrexone to make a difference," Ray said. "But even medications like varenicline have their limitations. Medication is only part of the solution. There remains much research to be done on addictions and how to treat them."

Ray says that those who wish to quit smoking and reduce drinking may consider talking to their doctor about the possibility of using varenicline, and she recommends that they try to quit smoking and reduce their drinking at the same time.

"There is evidence that varenicline can help them with both," Ray said. "Varenicline appears quite effective at reducing drinking and helping people to quit smoking. Given that varenicline has been found to reduce drinking in trials for alcohol use disorder, it is possible that its effects on both drinking and smoking present an optimal alternative for this group of heavy-drinking smokers."

ReJoyce Green, a UCLA doctoral student in clinical psychology who works with Ray, and Karen Miotto, a UCLA clinical professor of psychiatry and the medical director of the clinical trial, are among the study's 14 authors.

The clinical trial and Ray's research are funded by the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, both part of the National Institutes of Health.

The study was conducted between July 2015 and December 2019 at an outpatient research facility at UCLA.

A new model that applies artificial intelligence to carbohydrates improves the understanding of the infection process and could help predict which viruses are likely to spread from animals to humans. This is reported in a recent study led by researchers at the University of Gothenburg.

Carbohydrates participate in nearly all biological processes - yet they are still not well understood. Referred to as glycans, these carbohydrates are crucial to making our body work the way it is supposed to. However, with a frightening frequency, they are also involved when our body does not work as intended. Nearly all viruses use glycans as their first contact with our cells in the process of infection, including our current menace SARS-CoV-2, causing the COVID-19 pandemic.

A research group led by Daniel Bojar, assistant professor at the University of Gothenburg, has now developed an artificial intelligence-based model to analyze glycans with an unprecedented level of accuracy. The model improves the understanding of the infection process by making it possible to predict new virus-glycan interactions, for example between glycans and influenza viruses or rotaviruses: a common cause for viral infections in infants.

As a result, the model can also lead to a better understanding of zoonotic diseases, where viruses spread from animals to humans.

"With the emergence of SARS-CoV-2, we have seen the potentially devastating consequences of viruses jumping from animals to humans. Our model can now be used to predict which viruses are particularly close to "jumping over". We can analyze this by seeing how many mutations would be necessary for the viruses to recognize human glycans, which increases the risk of human infection. Also, the model helps us predict which parts of the human body are likely targeted by a potentially zoonotic virus, such as the respiratory system or the gastrointestinal tract", says Daniel Bojar, who is the main author of the study.

In addition, the research group hopes to leverage the improved understanding of the infection process to prevent viral infection. The aim is to use the model to develop glycan-based antivirals, medicines that suppress the ability of viruses to replicate.

"Predicting virus-glycan interactions means we can now search for glycans that bind viruses better than our own glycans do, and use these "decoy" glycans as antivirals to prevent viral infection. However, further advances in glycan manufacturing are necessary, as potential antiviral glycans might include diverse sequences that are currently difficult to produce", Daniel Bojar says.

He hopes the model will constitute a step towards including glycans in approaches to prevent and combat future pandemics, as they are currently neglected in favor of molecules that are simpler to analyze, such as DNA.

"The work of many groups in recent years has really revolutionized glycobiology and I think we are finally at the cusp of using these complex biomolecules for medical purposes. Exciting times are ahead," says Daniel Bojar.