Culture

A new paper in Scientific Reports led by researchers at William & Mary's Virginia Institute of Marine Science challenges increased salinity and seawater temperatures as the established explanation for a decades-long increase in the prevalence and deadliness of a major oyster disease in the coastal waters of the mid-Atlantic.

Dr. Ryan Carnegie, the paper's lead author, says "We present an entirely new lens through which we can view our last 35 years of oyster history in the Chesapeake Bay region. We now know the great intensification of Dermo disease in the 1980s wasn't simply due to drought. It was more fundamentally due to the emergence of a new and highly virulent form of Perkinsus marinus, the parasite that causes Dermo."

In an unusual twist, the team's evidence suggests that transformation of this native parasite was in response to evolutionary pressures brought by the impacts of another, non-native oyster parasite known as MSX, first seen in Bay waters in 1959. Dermo's mid-80s rise in virulence, along with decades of overharvesting, habitat destruction, and the earlier devastation of MSX, brought the Bay's traditional oyster fishery to a historic low.

Carnegie says his team's findings can help better manage the Bay's modern oyster industry, which is now on the upswing due to disease-resistant aquaculture strains, reef restoration, and limits on the wild harvest. "The lesson," he says, "is that pathogens like P. marinus are highly dynamic, and our disease surveillance must be attentive to any changes that may occur. This includes the emergence of more virulent strains, or variants that may have different forms or life histories than we expect. Management should be continually tuned to any changes in disease dynamics."

The team's findings also give scientists and fishery managers a better understanding of the "rock-bottom" era for Bay oysters between the late 1980s and early 2000s. "The oysters reached this level of devastation not because they were unable to deal with Dermo after decades, if not centuries or millennia, of exposure," says Carnegie. "They hit rock bottom because they were challenged with a brand-new form of the parasite, and needed time to adapt. And now they are adapting, which is key to the oyster's recent recovery in the region."

Along with Carnegie, the paper's other authors are the late Susan Ford of Haskin Shellfish Research Laboratory at Rutgers University; Peter Kingsley-Smith of the South Carolina Department of Natural Resources; and Rita Crockett, Lydia Bienlien, Lúcia Safi, Laura Whitefleet-Smith, and Eugene Burreson of VIMS. Funding for the study comes from the VIMS Foundation A. Marshall Acuff, Sr., Memorial Endowment for Oyster Disease Research.

Evidence for a more virulent Dermo parasite

Dermo disease results when the eastern oyster Crassostrea virginica is infected by the protozoan parasite Perkinsus marinus. Infected oysters grow more slowly, exhibit poorer body condition, and reproduce less successfully than their healthy counterparts. Severe infections lead to oyster death and release of parasites into the surrounding water, potentially infecting other nearby oysters as they filter water for food. The disease does not affect people who eat the shellfish.

Native to the Gulf Coast, Dermo was first recorded in the Chesapeake Bay in 1949, though it had likely been there far longer. Prior to the 1980s, it typically occurred as a chronic disease that killed about 30% of oysters annually, mostly older animals that had been exposed to the parasite for several years. But, says Carnegie, "Around 1986, Dermo suddenly became an acute and profoundly destructive disease capable of killing more than 70% of host oysters within months of infection." The increased virulence of the Perkinsus parasite persists today.

Because the parasite's infectiousness is known to increase with higher salinity, scientists initially attributed the mid-1980s spike in Dermo's virulence to a multi-year drought that had struck the mid-Atlantic around that time, raising coastal salinities as freshwater input from rivers decreased. Increasing seawater temperatures also promote increased Dermo disease, and ocean warming has been blamed for the northward increase in Dermo's range since the 1980s. As time passed, however, Carnegie and other researchers began to realize that salinity and temperature alone did not fully explain the lasting increase in Dermo infections and associated oyster mortality along the East Coast.

"We began to ask why more protracted and intense droughts in earlier years, before the 1980s, hadn't produced a similar intensification of disease," says Carnegie, "and why subsequent wet periods didn't return the parasite to the low levels of infection characteristic of earlier years."

Motivated by these questions, Carnegie and colleagues compared samples from modern Bay oysters with samples taken in 1960 and stored at VIMS, using paper-thin tissue slices glued onto slides for viewing under a microscope. Finding striking and unexpected differences, they then took a comprehensive look at more than 8,000 tissue samples collected from oysters in Chesapeake Bay, South Carolina, and New Jersey between 1960 and 2018.

"Our analysis," says Carnegie, "clearly showed that a new parasite variant emerged between 1983 and 1990, concurrent with the historical mid-80s outbreaks of Dermo." Changes included a shift in the infection site--from deeper connective tissues to the lining of the digestive tract--changes in reproductive strategy, and a sharp decrease in cell size. In Chesapeake Bay, they found the most pronounced change between oysters sampled in 1985 and 1986, when the modern variant increased in frequency from 22% to 99% of observations.

"The picture that emerges," says Carnegie, "is the rise of a virulent new form of the Dermo parasite Perkinsus along the mid-Atlantic coast in the mid-80s, which dispersed from there and supplanted a form that previously had been widely distributed in Atlantic estuaries. While changes in pathogen virulence have been documented in other systems, the scope of changes we've seen, and their rapid spread across a wide area, is unusual."

"Our work underscores the importance of long-term environmental monitoring," he adds. "Without that, and the maintenance of associated natural history collections, this new perspective wouldn't have been possible."

Evolutionary pressures

The type of changes observed in the Dermo parasite suggest they represent a novel but predictable response to the devastating impacts of MSX, the disease caused by the non-native parasite Haplosporidium nelsoni, which was first reported in Bay waters in 1959. MSX killed more than 90% of Virginia's farmed oysters by 1961, and slashed the harvest of planted oysters from 3,347,170 bushels in 1959 to 361,792 bushels by 1983, an estimated loss of 1.8 billion animals. This decrease was likely compounded by simultaneous losses from wild populations.

A parasite that quickly kills its host effectively destroys its own home. Over evolutionary time scales, natural selection thus often leads to an equilibrium between a native parasite and its host, marked by the type of minor, long-term Perkinsus infections and low rates of Dermo mortality historically observed in Chesapeake Bay oysters.

But when a new parasite arrives on the scene, that evolutionary balance may shift. Carnegie and his team speculate that the devastating arrival of the non-native, MSX parasite in Bay waters drastically disrupted the long-established equilibrium between Dermo and Crassostrea, directly leading to the new, more virulent form of the disease.

"A huge reduction in oyster abundance--like that caused by the arrival of MSX--would severely impact a parasite such as P. marinus that depends entirely on a single host," says Carnegie. As evidence, he notes that Perkinsus declined sharply in abundance beginning in 1959; recent theoretical modeling underscores the possibility that an increase in parasite virulence could be a consequence of such reduction in host resources.

"The changes we saw in the Dermo parasite are likely adaptive with regard to the reduced oyster abundance and longevity it faced after rapid establishment of Haplosporidium nelsoni and MSX in 1959," says Carnegie. "Our findings, we hypothesize, illustrate a novel ecosystem response to a marine parasite invasion: an increase in virulence in a native parasite." An intriguing possibility is that the changes the researchers observed may represent a shortening of the Perkinsus life cycle, as it adapted to oysters with shorter life spans due to mortality from MSX.

Ben Mulhearn and colleagues estimated the incidence of GCA seen during the COVID-19 pandemic and compared it to data from 2019, before the pandemic hit. The two distinct peaks of COVID-19 reflected by UK hospital admissions of COVID-19-positive patients allowed the authors to investigate the relationship in time between COVID-19 and GCA incidence.

At the Royal National Hospital for Rheumatic Diseases in Bath, UK, there were 61 probable or definite GCA diagnoses made in 2020 compared to 28 in 2019- representing an excess of 33 cases in 2020, or an increase of 118%.Taking into account the fact that41% of the hospital's catchment population is over the age of 50, this equates to an annual incidence rate of 13.7 per 100,000 in 2019 and 29.8 per 100,000 in 2020. The previously estimated regional incidence rate for South West of the UK was 21.6 per 100,000.

The significantly increased incidence of GCA may be the result of widespread infection in the local population,withSARS-CoV-2 as a driving factor. Possible mechanisms include, but are not limited to, endothelial disruption by the virus, immune system priming towards T helper cell type 1 cellular immunity, and activation of the monocyte-macrophage system. More work is underway to assess the causal relationship between the two diseases, and it may be important to monitor the number of referrals for GCA as the pandemic continues.

MINNEAPOLIS/ST. PAUL (06/18/2021) -- Two recent studies led by researchers from the University of Minnesota Medical School add new evidence to the impact of how drug price increases affect U.S. patients and the overall cost of health care.

The first study, published today in the JAMA Network Open, provides new data on how dramatic increases in anti-infective drug prices altered the overall cost of outpatient health care and decreased patient access to appropriate drug treatment. The study protocol was reviewed by the U.S. Centers for Disease Control and Prevention and scanned more than 100 million de-identified patient records to find roughly 89,000 cases of interest between 2010 and 2018. The results showed that:

A standard-of-care (SOC) drug to treat hookworm increased from $32.77 to $1,660, which correlated with a decrease in patients receiving an appropriate drug from 43 percent to 28 percent.

A SOC drug to treat pinworm increased from $14.81 to $130, which correlated with a decrease in patients receiving an appropriate drug from 81 percent to 28 percent.

A SOC drug to treat Clostridioides difficile (a control with little price change) remained mostly stable, increasing from $53 to $68, which correlated with an increase in patients receiving an appropriate drug from 69 percent to 77 percent.

"Our study shows that dramatic drug price increases lead to much higher outpatient costs and decrease appropriate drug treatment due to access issues and health care professionals switching to a substandard drug," said co-first author of the study, William Stauffer, MD, MSPH, FASTMH, who is a professor of medicine at the U of M Medical School. "More studies need to be done to confirm these findings, but this should increase policymakers attention as they consider solutions to extreme drug pricing."

The second study looked at state legislative action on the issue so far. Published in the Journal of General Internal Medicine, the research team reviewed all U.S. state laws enacted since 2015 to address drug price increases, as well as state bills being considered in 2020, and found several shortcomings. The study has two recommendations:

Transparency laws were the most common type of legislative action, however, many of the transparency bills considered in 2020 don't require transparency until after the price increases occur -- some up to one year after. The study recommends requiring transparency before price increases occur, so that vulnerable patients have time to seek alternative treatment options.

Of those states that created affordability review bills, only 22 percent specify OPOE (off-patent, off-exclusivity) brand-name drugs, which are cheaper than patent-protected, brand-name drugs and more prone to price hikes -- as demonstrated by this team's 2020 study. The study recommends creating separate review thresholds for OPOE drugs to ensure they are not misclassified as brand-name drugs, which are allowed higher price increase thresholds.

"Prescription drug price increases inflate national health spending and are disproportionately felt by patients who are uninsured or have high deductibles," said Arman Shahriar, a U of M Medical School student and first author of the study. "Despite prescription drug price increases being a known problem for years, little has been done at the federal level, and states have not been unified in their approach. We want to make state lawmakers aware of the current landscape and future directions of this legislation."

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.

MINNEAPOLIS/ST. PAUL (06/18/2021) -- University of Minnesota Medical School researchers determined that the common blood pressure medication, losartan, is not effective in reducing hospitalization for mildly-ill COVID-19 outpatients.

In the multicenter, randomized, double-blinded clinical trial, non-hospitalized patients recently diagnosed with COVID-19 were given either losartan or a placebo and monitored for 15 days. The study's results, which were published in EClinicalMedicine, showed that although losartan does not reduce the likelihood of hospitalization, the medication does not appear to worsen symptoms of COVID-19 or have any significant or harmful side effects on patients with mild COVID-19.

"Based on our results, there is no benefit to starting losartan for newly diagnosed outpatients with COVID-19, but those who are already taking the medication for pre-existing health conditions should feel safe continuing it," said Michael Puskarich, MD, an associate professor in the Department of Emergency Medicine at the U of M Medical School and co-principal investigator of this study. He is also an emergency physician at Hennepin Healthcare.

Conflicting hypotheses since the start of the pandemic led this research team to investigate losartan as a potential treatment option. While some experts believed drugs like losartan may reduce inflammation and help those infected recover, others worried that the drug could worsen COVID-19 symptoms.

"Given SARS-CoV-2 binding with ACE2 there has been significant research interest into the utility of ACE and AT1R blocking agents to combat COVID-19. This study provides insight that for patients with mild COVID-19, who do not require hospital admission, that there is no benefit or harm from such agents," said co-principal investigator Christopher Tignanelli, MD, MS, an assistant professor in the Department of Surgery at the U of M Medical School and critical care surgeon with M Health Fairview.

The same team has been working on another trial for inpatients to evaluate if losartan prevents lung injury in hospitalized patients with COVID-19 pneumonia. They have completed enrollment and are currently analyzing the data.

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.

SAN ANTONIO (June 18, 2021) -- Researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and colleagues worldwide describe a new science-based intervention for hiccups in a research letter published June 18 in the journal JAMA Network Open.

In the publication, the scientists coined a new term for the intervention: the "forced inspiratory suction and swallow tool," or FISST. The team also reported the results of a survey of 249 users who were asked whether it is superior to hiccup home remedies such as breathing into a paper bag.

The need

"Hiccups are occasionally annoying for some people, but for others they significantly impact quality of life," said Ali Seifi, MD, associate professor of neurosurgery in UT Health San Antonio's Joe R. and Teresa Lozano Long School of Medicine. "This includes many patients with brain and stroke injury, and cancer patients. We had a couple of cancer patients in this study. Some chemotherapies cause hiccups."

Simple tool

FISST is a rigid drinking tube with an inlet valve that requires forceful suction to draw water from a cup into the mouth. The suction and swallow simultaneously stimulate two nerves, the phrenic and vagus nerves, to relieve hiccups.

Forceful suction induces the diaphragm, a sheaf of muscle that inflates the lungs during breathing, to contract. The suction and swallow also prompt the epiglottis, a flap that covers the windpipe during swallowing, to close. This ends the hiccup spasms.

User feedback

FISST stopped hiccups in nearly 92% of cases, users self-reported. In terms of satisfaction, 226 of 249 participants (90.8%) affirmatively answered questions about whether they found the tool easy to use.

On a different measure, subjective effectiveness, 183 of 203 participants (90.1%) indicated that FISST was effective when they used it. Fewer participants answered this question, possibly because it was last in the survey, Dr. Seifi said.

The tool, developed at UT Health San Antonio by Dr. Seifi with input from medical students, is being marketed by a Colorado company under a license agreement with the university and has been accepted by a major supermarket chain to be placed on shelves, Dr. Seifi said.

About the study

The research project began with 600 individuals who, because they stated they had hiccups, received FISST. Of this population, 290 persons responded to a survey about their experience with using the device, compared to other remedies they have used. Of them, 249 fully answered the survey and were included in the research analysis.

The scale was 1 to 5, with 5 meaning the respondents were very happy with FISST and 1 meaning that they preferred to use home remedies.

The respondents were primarily adults over 18 (70%) and were half female and half male. Nearly 80% of the respondents were white.

As far as frequency of hiccups, 69% reported having them at least once a month, and most cases (65%) were transient, less than two hours in duration.

Clinical trial is goal

Future directions include conducting a double-blind clinical trial in Europe and America that gives FISST to one group of trial enrollees and a non-functional, sham device to another group. The challenge is developing something that resembles FISST but doesn't work, Dr. Seifi said.

BIRMINGHAM, Ala. - Will a reduction in tau protein in brain neurons protect against Parkinson's disease and Lewy body dementias?

A new study, published in the journal eNeuro, suggests the answer is no. If this is borne out, that result differs from Alzheimer's disease, where reducing endogenous tau levels in brain neurons is protective for multiple models of the disease -- which further suggests that the role of tau in the pathogenesis of Lewy body dementias is distinct from Alzheimer's disease.

Both Parkinson's disease dementia and Lewy body dementia are characterized by intracellular aggregates of misfolded alpha-synuclein protein in brain neurons, and the two diseases together are the second most common cause of neurodegenerative dementia after Alzheimer's.

University of Alabama at Birmingham researchers, led by Laura Volpicelli-Daley, Ph.D., associate professor of neurology, used a Parkinson's disease model she developed 11 years ago. Volpicelli-Daley applies very low concentrations of altered alpha-synuclein, which has taken on a pathologic conformation, to either in vitro or in vivo neurons. The nerve cells take up some of the fibrils. Inside the cells, the altered alpha-synuclein acts as a seed to attract the soluble alpha-synuclein that is naturally present in neurons. This transforms soluble alpha-synuclein into pathological, insoluble aggregates that impair neuron function and lead to cell death. These modified alpha-synuclein inclusions share morphology with those found in the Parkinson's disease brains after death.

This disease model -- termed templated alpha-synuclein inclusion formation -- was used to compare neurons that produce the normal amount of tau protein, against mutant neurons that lack one or both genes for tau, and thus have less or no tau protein. If endogenous tau contributes to disease progression, the heterozygous or knockout tau mutants were expected to show protection. However, the UAB researchers found no difference from the wild-type control.

In their results, the researchers first showed that there was indeed an interaction between tau and alpha-synuclein in the cells -- both proteins localized in presynaptic terminals of primary culture neurons, and in the cortex of the mouse brain, which is consistent with previous findings from preparations of human brains, and with several in vitro studies showing that the two proteins interact with each other.

However, the reduction or complete absence of tau did not prevent fibril-induced alpha-synuclein inclusion formation in primary hippocampal neurons growing in vitro. In mice, reduction or absence of tau also did not prevent fibril-induced alpha-synuclein formation in the motor control or limbic areas of the brain, including the cortex, amygdala, hippocampus and the substantia nigra pars compacta, as measured six weeks or six months after fibril injections.

Finally, while the alpha-synuclein fibrils in the mouse model caused the death of half of the wild-type neurons that produce the neurotransmitter dopamine, the dopaminergic neurons in tau-heterozygous or tau-knockout mice showed the same amount of neuron death, which meant no protection. In addition, reducing tau did not have any major impact on behavioral phenotypes of mice with fibril-induced α-synuclein inclusions.

"Here, we have shown that reduction of endogenous tau did not influence formation of templated alpha-synuclein inclusion formation or the loss of dopamine neurons," Volpicelli-Daley said. "This suggests that therapeutics directed to tau for Parkinson's disease may be more complicated than tau reduction. This is unlike Alzheimer's disease, where tau reduction has been suggested as a possible therapy."

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.

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."

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.

June 18, 2021 - At least so far, the currently limited research base does not establish that cannabis has additional adverse effects on brain development or functioning in adolescents or young adults with attention-deficit/hyperactivity disorder (ADHD), concludes a review in the July/August issue of Harvard Review of Psychiatry. The journal is published in the Lippincott portfolio by Wolters Kluwer.

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."

Birds build nests to keep eggs and baby nestlings warm during cool weather, but also make adjustments in nest insulation in such a way the little ones can keep cool in very hot conditions. Mammals, such as rabbits or groundhogs, sleep or hibernate in underground burrows that provide stable, moderate temperatures and avoid above-ground conditions that often are far more extreme outside the burrow.

Michael Dillon, an associate professor in the University of Wyoming Department of Zoology and Physiology, was part of a research group that examined animals' ability to respond to climate change likely depends on how well they modify their habitats, such as nests and burrows.

So, how are these animals doing? Are they succeeding, struggling, or are their efforts a mixed bag in adapting their habitats to climate change?

"One of the key reasons that we wrote this paper is that we don't know the answer to this very important question!," Dillon says. "We hope the paper will encourage scientists to begin answering this question."

Dillon is a co-author of a paper, titled "Extended Phenotypes: Buffers or Amplifiers of Climate Change?," that was published June 16 in Trends in Ecology & Evolution. The journal publishes commissioned, peer-reviewed articles in all areas of ecology and evolutionary science.

The lead author of the paper is Arthur Woods, a professor of biological sciences at the University of Montana. Other contributors to the paper were from the University of Tours in Tours, France; and Stellenbosch University in Stellenbosch, South Africa.

The study investigated extended phenotypes, which are modifications that organisms -- birds, insects and mammals -- make to their habitats.

"An extended phenotype can range from simply a hole in the ground occupied by an animal to leaves rolled into cavities by insects, to nests of all shapes and sizes built by birds and mammals, to termite mounds and bee colonies," Dillon says.

Extended phenotypes are important because they filter climate into local sets of conditions immediately around the organism. This is what biologists call the microclimate.

Because extended phenotypes are constructed structures, they often are modified in response to local climate variation and, potentially, in response to climate change. This process is called plasticity of the extended phenotype.

"One example might be a bird nest that is well insulated to protect eggs or young birds from cold. As climates warm, if the bird does not adjust insulation in the nest, it may, in fact, cause the young to overheat," Dillon explains.

In another prime example, termites build mounds that capture wind and solar energy to drive airflow through the colony, which stabilizes temperature, relative humidity and oxygen levels experienced by the colony.

However, the idea of microclimates is broader than constructed habitats. Microclimates typically differ substantially from nearby climates, which means that the climate in an area may provide little information about what animals experience in their microhabitats.

As an analogy, although a weather station might tell the public that the temperature in Laramie is 90 degrees Fahrenheit, simply by moving from the south to the north side of a building, one can experience microclimates that are strikingly different and often not captured by the weather data, Dillon says.

The same is true of animals of many different sizes. For example, a moose can move from an open sagebrush landscape to a shaded river corridor to cool off; a snake can move from its underground hole to a sunny rock to warm up; and a tiny insect shuttling between the top and bottom of a leaf can experience temperature differences of more than 20 degrees Fahrenheit.

"So, animals use microclimates, both by simply moving but also by building structures, such as nests, burrows, mounds and mines," Dillon says.

Across the globe, rising levels of carbon dioxide in the Earth's atmosphere are causing temperatures to rise and precipitation patterns to shift. For biologists, a key problem is to understand current effects of climate change on species, and to predict future effects, including how species' ranges may shift and what the relative risks of extinction are for different animal species' groups.

The research team favors a renewed effort to understand how extended phenotypes mediate how organisms experience climate change.

"We need a much better understanding of the basic biophysical principles by which extended phenotypes alter local conditions," says Sylvain Pincebourde, an ecologist in the Insect Biology Research Institute at the University of Tours and one of the paper's co-authors.

Another key challenge is to understand how much plasticity there is in extended phenotypes, and how much and how rapidly they can evolve.

"At this point, we pretty much have no idea," Dillon says. "Can structures that buffer temperature variability keep up with the pace of climate change?"

Just as the skeleton and muscles move the human body and hold its shape, all the cells of the body are stabilised and moved by a cellular skeleton. Unlike our skeleton, this cellular skeleton is a very dynamic structure, constantly changing and renewing itself. It consists of different types of protein filaments, which include intermediate filaments and microtubules. Now, a research team from the University of Göttingen is the first to succeed in observing a direct interaction between microtubules and intermediate filaments outside the cell, and also in quantitatively measuring this interaction. The results of the study were published in Nature Communications.

Microtubules are dynamic filaments that constantly grow and shrink again and, in this way, are responsible for many important processes in cells. The research team observed that intermediate filaments stabilise microtubules: when intermediate filaments are added to microtubules, shrinkage is suppressed and thus the lifespan of the microtubules is extended. To investigate whether this is actually due to direct interactions between the two filaments, a single microtubule was positioned crossed with a single intermediate filament.

Dr Laura Schaedel, who shares first authorship of the publication with Charlotta Lorenz (PhD student at the Institute for X-ray Physics at the University of Göttingen), explains: "The intermediate filament was 'pulled' over the microtubule like a bow over a violin string." Lorenz adds, "This allows the two filaments to bind to each other. However, this bond is broken again shortly afterwards due to the pulling. The process of 'tearing apart' provides information about the strength of the bond." Professor Stefan Klumpp from the Institute for the Dynamics of Complex Systems at Göttingen University, who led the project together with Professor Sarah Köster from the Institute for X-ray Physics, says, "In addition, we used models and simulations to show that the direct interaction leads to stabilisation." The stabilisation of dynamic microtubules can be an important issue for biological cells, for example to regulate their local stability. "The interactions that we observed are important because they enable better understanding of cellular processes," says Köster.

These results are in turn relevant for understanding many other processes, such as those involved in diseased cells. The new method to take direct measurements of the actual interaction of two different biopolymers can also be applied to other protein filaments, as well as to non-biological fibres.

The body is well protected against invading pathogens by barriers such as the skin. But if you injure yourself and break your skin, pathogens can easily enter your body through the wound and cause severe infections. If this occurs, the innate immune system takes over the first rapid defense with an effective arsenal of cellular weapons infiltrating the wounded tissue in large numbers. As one of the first cell types on the spot, neutrophil granulocytes are recruited within few hours from the bloodstream to the infection site to eliminate potential microbial invaders.

Swarming against infections

"Neutrophils are very efficient in hunting and killing bacteria," says Tim Lämmermann. The group leader at the MPI of Immunobiology and Epigenetics in Freiburg studies this important cell type. Neutrophils are highly abundant cells that make up about 50-70% of white blood cells in the human body. It is estimated that 100 billion neutrophils are produced from stem cells in the bone marrow in an adult every day. "These cells patrol almost all corners of our body, and they are very efficient in sensing anything potentially harmful in our body. Once individual neutrophils detect damaged cells or invading microbes in the tissue, they start secreting attractive signals that act through cell-surface receptors on neighboring neutrophils to recruit more and more cells." By using this intercellular communication, neutrophils can act together as a cell collective and coordinate effectively their clearance for pathogens as a swarm.

A fine line between host protection and tissue destruction

However, this form of beneficial inflammation can also overshoot and lead to massive tissue damage. If the intensity or the duration of the response becomes dysregulated, the same mechanisms that serve to eliminate invading pathogens can also cause collateral damage to healthy tissues. For example, the substances that neutrophils release to kill invading pathogens also erode the meshwork of proteins and sugars, which provides structural support to tissues. "In this study, we started with the question what stops the swarming response to avoid uncontrolled neutrophil accumulation and prevent excessive inflammation, which can contribute to degenerative diseases such as cancer, diabetes, and autoimmune diseases," says Tim Lämmermann. In former studies, he and his team already discovered the molecular mechanisms initiating the collective-like swarming behavior. However, the processes that bring this response to an end have remained unknown.

Neutrophil swarming is still a relatively novel topic in the inflammation and infection research fields, and the underlying mechanisms are just beginning to be investigated. The newest study by the lab of Tim Lämmermann now reveals how neutrophils self-limit their swarming activity in bacteria-infected tissues and thus balance search versus destroy phases for efficient pathogen elimination.

By using specialized microscopy for the real-time visualization of immune cell dynamics in living mouse tissues, the researchers demonstrate that swarming neutrophils become insensitive to their own secreted signals that initiated the swarm in the first place. "We identified a molecular break in neutrophils that stops their movement, once they sense high concentrations of accumulating swarm attractants in large neutrophil clusters" says Tim Lämmermann. "This was surprising as the prevailing view suggested that external signals released from the tissue environment are critical for stopping neutrophil activity in the resolution phase of an inflammation," comments Wolfgang Kastenmüller, collaborating scientist of the Max Planck Research Group Systems Immunology at the University of Würzburg.

An internal start-stop system for optimal bacterial clearance

In light of the discovered start-stop system in neutrophils, the researchers re-evaluated current views on how neutrophils navigate in tissues to eliminate bacteria efficiently. In experiments with neutrophils lacking the stop mechanism, the team observed immune cells excessively swarming and scanning large areas of bacteria-infected tissue, which contrasted the behavior of cells with functioning start-stop system. However, this amplified swarming and scanning did not make these cells better pathogen-killers. "Strikingly, we made the opposite finding. It is not beneficial when neutrophils move around too fast and run around like crazy. Instead, it appears more advantageous for them to stop and enjoy together a nice meal of bacteria - this is more efficient to contain bacterial growth in tissues," explains Tim Lämmermann.

With these results, the team paves the way for a better understanding of neutrophil biology, which is essential for immune host defense against bacteria and could inform therapeutic approaches in the future. Moreover, the swarming behavior and underlying mechanisms could also inform other categories of collective behavior and self-organization in cells and insects.