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Mutations in white blood cells can contribute to abnormal immune profile after hematopoietic stem cell transplantation.

Graft-versus-host disease (GvHD) is a potentially life-threatening medical condition that is common after allogeneic hematopoietic stem cell transplantation, the only curative treatment for various types of leukemias. In GvHD, white blood cells from transplant donor recognize recipient cells as non-self and attack recipient tissues. Understanding how these donor white blood cells remain active against recipient cells can pave the way for novel treatment strategies in GvHD.

A research project led by Professor Satu Mustjoki at the University of Helsinki investigated the role of T cell mutations in GvHD. Somatic or so-called acquired mutations during lifetime are common in cancer cells, but little is known about their existence and significance in other cells, such as cells in the body's defense system.

Published in the journal Nature Communications, the study first identified an index chronic GvHD patient with an activating somatic mutation in a gene called mTOR, which regulates cell growth and cell survival.

The authors then screened an international cohort of 135 GvHD patients and 54 healthy blood donors. By using next generation sequencing, the scientists found that 2.2% of chronic GvHD patients, but none of the healthy blood donors, harbored a mutation in mTOR.

"What makes our finding particularly significant is that the mutation now found was recurrent, meaning that the same mutation was found in several patients with chronic GvHD," says professor Satu Mustjoki.

"Our previous studies in rheumatoid arthritis had shown that acquired mutations could be found in T cells, but in these studies, the mutations had been isolated and the same mutations had not been found in more than one patient."

Individualized treatments for patients

Using single-cell RNA sequencing and T cell receptor sequencing on samples collected from the index patient, researchers found that the mTOR mutated CD4+ T cell clone expanded during the course of GvHD despite immunosuppressive treatment, suggesting the mutation contributed to the disease pathogenesis.

In addition, it was found that the mutation was located in so-called cytotoxic T cells and these cells were able to damage the body's own cells. Researchers also investigated the mTOR mutation in more detail by introducing it into a human cell line. The activating mTOR mutation promoted cell proliferation and cell survival.

The researchers performed a high-throughput drug screen with 527 drugs to identify potential targeted therapies. The index patients' CD4+ T cells were sensitive to a specific class of drugs called HSP90 inhibitors, suggesting that these drugs could be used to treat GvHD in the future.

"Our study helps to understand the mechanisms of activation of the immune system in GvHD. Although several different drug combinations have been tried in the treatment of GvHD, using our results, it is possible to find individualized treatments for patients", says doctoral candidate Daehong Kim from the University of Helsinki.

Further studies using larger cohorts of GvHD are warranted to understand whether clonal mutations in T cells modify GvHD severity, drug responses and clinical outcome.

A new data analysis funded by the National Institutes of Health finds patients who visited the emergency department for an opioid overdose are 100 times more likely to die by drug overdose in the year after being discharged and 18 times more likely to die by suicide relative to the general population. Additionally, in the year after emergency department discharge, patients who visited for a sedative/hypnotic overdose had overdose death rates 24 times higher, and suicide rates 9 times higher, than the general population. The findings, published in the American Journal of Preventive Medicine, highlight the need for interventions that reduce suicide and overdose risk that can be implemented when patients come to the emergency department.

"We knew that nonfatal opioid and sedative/hypnotic drug overdoses were a major cause of disease. What these new findings show is that overdose patients also face an exceptionally high risk of subsequent death--not just from an unintentional overdose, but also from suicide, non-suicide accidents, and natural causes," said Sidra Goldman-Mellor, Ph.D., lead study author and assistant professor of public health at the University of California, Merced.

Drug-related mortality is an ongoing public health problem. Deaths by drug overdose increased 225% between 1999 and 2015, with prescription drugs and heroin overdose accounting for the majority of these deaths. Although previous studies have detailed trends in emergency department visits related to opioid and sedative/hypnotic drug overdose, less is known about the risk of death in the year following emergency care for a drug overdose.

"We have tracked and reported patient survival for health concerns such as cancers and heart surgery for decades," said paper co-author Michael Schoenbaum, Ph.D., a senior advisor for mental health services, epidemiology, and economics at the National Institute of Mental Health (NIMH), part of the NIH. "We improve what we measure and should be doing the same type of tracking for people with overdose or suicide risk to inform our prevention and treatment programs."

To learn more about the risks for death that follow a nonfatal opioid overdose, a research team led by Dr. Goldman-Mellor examined discharge data for all visits to emergency departments in California between 2009 and 2011. These data were matched with death records from the California Department of Public Health, which provided information about the date and cause of death for all individuals who died between 2009-2012.

The researchers focused on patients who visited the emergency department for an opioid overdose (e.g., heroin, methadone) or for a sedative/hypnotic drug overdose (e.g., barbiturate, benzodiazepine) at least once during the 2009-2011 study period.

The data showed that for those who had visited for sedative/hypnotic drug overdose, the death rate in the following year was 18,080 per 100,000; for those who had visited for an opioid overdose, the death rate in the following year was 10,620 per 100,00 patients. The death rates for these groups were significantly higher than the death rate observed in a demographically matched group of Californians (3,236 per 100,000 people).

Eighty-eight percent of the unintentional deaths among patients who had visited for opioid overdose were caused by an unintentional overdose (1,863 per 100,000)--a rate 100 times higher than that of the general population. The suicide rate for this group (319 per 100,000 patients), which included some deaths by intentional drug overdose, was 18 times higher than that of the general population.

Sixty percent of unintentional deaths among patients who had visited for sedative/hypnotic overdose were caused by an unintentional drug overdose (342 per 100,00 patients)--a rate 24 times higher than that of the general population. Among those who had previously experienced a sedative/hypnotic drug overdose, the rate of death by suicide (174 per 100,000 patients) was almost 9 times higher than the general population.

"There are already promising emergency department-based interventions that could reduce overdose and other mortality risks, such as suicide, among these patients, but such interventions need to be much more widely implemented," said Dr. Goldman-Mellor. "Moreover, those interventions should target not just patients overdosing on opioids, but also those overdosing on sedative/hypnotic drugs, since their mortality risks were also very high."

Dr. Goldman-Mellor indicated that although this study provides important information about the outcomes of individuals presenting to emergency departments after an overdose, the findings should be replicated in other parts of the U.S. using more recent data, as patterns of opioid and sedative/hypnotic use (and related mortality) have changed substantially over time.

A world-first study led by Monash University has demonstrated significant benefits to a premature baby's heart and brain function when held by the parent in skin-to-skin contact.

Parent-infant skin-to-skin care (SSC) or kangaroo care, started in the late 1970s in Columbia when incubators to keep babies warm were not available. It is now widely recognised as a beneficial component of holistic care provided for pre-term infants.

Incorporating 40 pre-term babies born at around 30 weeks (normal is 40 weeks) and with an average weight of 1.3kg (normal is 3kg) the study, led by Professor Arvind Sehgal, Neonatologist & Head of Neonatal Cardiovascular Research at Monash Children's Hospital and Professor of Paediatrics at Monash Health, found that one hour a day of kangaroo care significantly improved blood flow to the brain and cardiac function, in comparison to measurements done while in the incubator.

This study, published in the Journal of Paediatrics, provides scientific evidence and rationale as to why the infant's heart rhythm and neurodevelopment is better with regular kangaroo care. Improving blood supply is important as it carries oxygen and nutrients to the brain and other organs, and guides neurodevelopment.

"The findings of our study are significant as this is a low cost intervention, easily applicable to infants in neonatal units across the world, and helps the most vulnerable of the populations we care for," Professor Sehgal said.

While SSC is a common practice worldwide, barriers still remain. These include concerns that infants might get cold or small premature babies are unstable and might not tolerate this handling, leading to compromised heart function or unstable blood pressure. However in this study, infants maintained their temperature (in fact, slightly higher than baseline), when measured one hour after SSC.

Previously noted benefits of kangaroo care include reduced stress and crying, increased parent-infant bonding. It is beneficial to parents (mothers) as well as it reduces stress, and increases breast milk supply.

"SSC is perhaps the normal physiological state, while the stress response of being separated from parents is the status of the pre-term infants the vast majority of the time," Professor Sehgal said.

"We hope this study encourages neonatal units around the world to promote kangaroo care, as well as reassure places where this is already being practised, that the effort and commitment from staff and parents is worthwhile."

CINCINNATI - After 20 years of trying, modern medicine remains unable to lower the roughly 40 percent mortality rate for the severe childhood immune disease called HLH (hemophagocytic lymphohistiocytosis), which damages vital organs and tissues.

Now, researchers report in the New England Journal of Medicine treating patients with a new drug that saved kid's lives with less toxicity and fewer side effects. Although the 34-patient study wasn't large enough to show whether the drug, emapalumab, can dent HLH's high mortality rate, doctors say their data are promising.

"This is a very important advance. For the first time we have a truly targeted way to treat HLH and a drug with very low toxicity," explains Michael Jordan, MD, co-principal investigator and physician-scientist in the Divisions of Immunobiology and Bone Marrow Transplantation and Immune Deficiency at Cincinnati Children's Hospital Medical Center.

"Because this is the first drug ever approved for HLH by the FDA, this report underscores that we should consider emapalumab administered with dexamethasone to be the standard of care for the 'second line' treatment of HLH, which occurs after more traditional approaches haven't been effective," he said.

The drug, which blocks the function of a pro-inflammatory immune system cytokine called interferon-gamma, is also being tested as the first-line agent for patients who haven't received previous treatment. This stems in part from a growing body of research showing that excessive interferon-gamma is increasingly being detected as pathogenic in HLH cases, study authors note.

The study's international research team was co-led by Jordan at Cincinnati Children's and co-principal investigator Franco Locatelli, MD, in the Department of Pediatrics, University of Rome in Italy.

Hiding Behind a Maze of Symptoms

A rare disorder, HLH overstimulates the immune system and causes hyperinflammation. Instead of defending against infection, HLH prompts the immune system to damage vital organs and tissues.

The challenge of unraveling how the disease works is complicated by the fact that for years the disease hid behind a maze of contradictory symptoms. Too often this led to misdiagnosis, ineffective treatments and the loss of young children who typically have the disease.

Jordan, who has been researching HLH since his clinical fellow days 20 year ago, is part of a small international army of physicians, scientists, patient families and a pharmaceutical company (Sobi, formerly NovImmune.) All joined forces to wage an unyielding years-long scientific war against a disease that ravages its young victims.

Getting Results

Led in part by the HLH Center of Excellence at Cincinnati Children's, the work is leading to new ideas for treatment and improved diagnostic capabilities. This better understanding of HLH includes more reliable testing assays to quickly and accurately diagnose it.

Researchers point out in their current study that the objective of HLH treatment is to suppress inflammation and allow patients to receive bone marrow transplant (BMT), the only curative therapy for the disease. Although a variety of immune-chemotherapeutic treatments have been tested, they have resulted in limited degrees of effectiveness.

The NEJM study was an open-label, single-group, Phase 2/3 study involving patients 18 years old and younger who had either untreated HLH or who had received previous treatment for the disease. At the study's cutoff point (July 20, 2017) a total of 34 patients (27 previously treated patients, 7 previously untreated) had received emapalumab, with 26 patients completing the study.

Sixty-three percent of previously treated patients and 65 percent of the patients without previous treatment responded to emapalumab therapy. Seventy percent of previously treated patients who received emapalumab proceeded to BMT, as did 65 percent of the patients who hadn't received previous therapy.

At the last observation, 74 percent of the previously treated patients and 71 percent of the patients who had not received previous treatment were still alive, according to researchers.

Treefrogs become easy targets for predators and parasites when they send mating calls, but they're finding a way to fool their enemies with a little help from a wingman.

Researchers at Purdue University have discovered that male treefrogs reduce their attractiveness to predators and parasites by overlapping their mating calls with their neighbors. By overlapping their calls at nearly perfect synchrony with neighboring treefrogs, an auditory illusion takes effect and those enemies are more attracted to the leading call, leaving the other frogs to find mates without risking their life. The work was recently published in American Naturalist.

"The male frogs are essentially manipulating the eavesdroppers through creating this auditory illusion," said doctoral student Henry Legett, who led the research with Ximena Bernal, associate professor of biological sciences at Purdue University. "Humans experience this illusion too, it's called the 'Precedence Effect.' When we hear two short sounds in quick succession, we think the sound is only coming from the location of the first sound."

Research at the Bernal lab focuses on the relationship between predation and communication - or what they simply refer to as eavesdropping.

"The illusion created by the male treefrogs calling in synchrony has no effect on female frogs, which was a surprising observation," Bernal says.

"These male frogs have figured out a way to trick these enemies. We thought the females might be more attracted to the leading caller, but it didn't really affect attraction at all. It's a win-win for the frogs because it helps reduce attacks from those enemies who were hoping to prey on the male frogs and females are not tricked by the illusion."

The study included experiments using playbacks of recorded calls from speakers and sound traps both in laboratory and field settings at the Smithsonian Tropical Research Institute in Panama, where Bernal is a research associate and frequently visits to work with students. Researchers discovered that after the initial male treefrog sends a mating call, other frogs follow suit within milliseconds.

"It's so fast, it's almost like a reflex," Legett said. "There's no way their brains have time to process that information. They hear their neighbor and they react immediately."

Bernal and Legett said the research has cultivated even more questions about how frogs communicate.

"You have to wonder why a male frog would call first, given that if increases his chances of being eaten," Legett said. "It's a very strategic game they're playing. The frog that calls first might not get lucky that time, but maybe he knows he'll get his chance the next time he hears one of his friends make the first call. These are the questions we'll keep asking as we move forward."

A new computational method for assigning the donor in single cell RNA sequencing experiments provides an accurate way to unravel data from a mixture of people. The Souporcell method, created by Wellcome Sanger Institute researchers and their collaborators could help study how genetic variants in different people affect which genes are expressed during infection or response to drugs.

Published this week in Nature Methods, the software could increase efficiency of single-cell experiments, assisting research into transplants, personalised medicine and malaria.

Single-cell RNA sequencing (RNAseq) can reveal exactly which genes are switched on in each individual cell, revealing cell types and what they do. Pooling multiple people's cells into a single cell RNAseq experiment helps to identify how different genomes affect this gene expression. However it is essential to be able to separate the resulting data by individual, which can be very difficult.

The authors tested Souporcell* against three other computational methods using placental cells, pluripotent stem cell lines** and malaria parasites.

Haynes Heaton, the first author from the Wellcome Sanger Institute, said: "Our method, called Souporcell, is able to separate mixtures of individuals' cells in scRNAseq experiments without knowing each individual's full genome sequence beforehand, unlike previous methods. One of the key features of the method is that it estimates the amount of background RNA from dead cells, which is often referred to as the soup. This then allows the removal of that source of noise, and hence the name Souporcell."

Being able to combine the cells into a single experiment increases the accuracy, enabling more information to be found, and also reduces the cost of these experiments.

Dr Martin Hemberg, a senior author from the Wellcome Sanger Institute, said: "The exact genetic sequence of each person can affect their response to infections, or to drug treatments. The new method enables single cell expression data from multiple people to be analysed, to show links between genotype and phenotype, in diseases and in the presence of drugs. This will have implications for personalised medicine."

In addition, some samples inherently have a mix of cells with different genomes, including samples from transplant patients who have their original cells and cells from the donor, or populations of parasites, such as malaria, from an infected individual.

Dr Mara Lawniczak, a senior author from the Wellcome Sanger Institute, said: "This method is helping us understand malaria. People get infected with multiple strains of malaria at once, but we don't know how these strains are competing with each other to reproduce. To even ask the question we have to be able to split out cells of different malaria strains, and Souporcell is enabling this."

Cancer is deadly, but available cancer treatment methods are quite limited. The use of therapeutic gas molecules such as H2, NO, CO and H2S for cancer treatment is promising owing to their unique properties for selectively killing cancer cells and protecting normal cells from damage from other traditional therapies. However, these gases and most of their prodrugs lack the abilities of active intratumoral accumulation and controlled gas release, causing limited therapeutic efficacy and potential side effects. The development of precision and intelligent gas delivery nanomedicines can maximize the profits of gas therapy by enhancing the bio-availability and bio-safety of therapeutic gases.

More and more gas-releasing nanomedicines are being developed by virtue of multifunctional nanoplatforms, making it ever-increasingly expectable to make breakthrough in cancer treatment. Even so, there are still many gaps between gas therapy and nanomedicines, needing to be filled.

In a new overview published in the Beijing-based National Science Review, scientists at Shenzhen University, China propose a series of engineering strategies of advanced gas-releasing nanomedicines for augmented cancer therapy from four aspects, 1) stimuli-responsive strategies for controlled gas release, 2) catalytic strategies for controlled gas release, 3) tumor-targeted gas delivery strategies, 4) multi-model combination strategies based on gas therapy.

"This review systematically dissects the roles of carrier and gas prodrug within nanomedicine for stimuli-responsive gas release, catalytic gas generation routes, tumor-targeted gas delivery approaches and gas therapy-based combination methods, and also provides an insight into their engineering principles and working mechanisms, and correspondingly proposed a series of superior engineering strategies of nanomedicines for gas therapy of cancer to guide the future research." Dr. Yingshuai Wang said "We believe this review could provide inspiration for constructing advanced gas-releasing nanomedicines."

Moreover, they have also pointed out current issues and gaps in knowledge, and have envisaged current trends and future prospects of advanced nanomedicines for gas therapy of cancer in this review.

"There are many gaps intriguing me, such as high tissue penetration stimuli-responsive gas release, the local, endless and prodrug-free generation of gases by catalysis, and the super ability of assisting other almost all therapies." Prof. Qianjun He adds "It is noticeable, in the recent fight of novel coronavirus pneumonia, hydrogen therapy is playing an vitally important role in assisting large numbers of patients to improve oxygen inhalation, relieve hypoxia, and scavenge inflammation. I hope our hydrogen-producing medicines would make bigger contribution to human being in the near future."

Climate and marine scientists are observing pervasive warming of the ocean and the land surfaces across the globe. Since the middle of the 19th century, the average global temperature recorded on the land surface has risen by around one degree centigrade, and by 0.6 degrees across the ocean surface. Global warming has been most pronounced in the alpine regions and the Arctic.

Over the period 1982 to 2011, however, a cooling trend was recorded in surface waters in some parts of the Southern Ocean around the Antarctic continent, specifically in the area south of 55 degrees latitude. This cooling was strongest in the Pacific sector of the Southern Ocean, where the ocean surface cooled by around 0.1°C per decade, and the weakest in the Indian and parts of the Atlantic sectors.

Climate and marine scientists have so far been unable to provide satisfactory explanations as to why parts of the Southern Ocean have bucked the trend of global warming. Now a group of scientists led by ETH Professor Nicolas Gruber has solved the puzzle with the help of simulations with a high-resolution ocean model.

Simulations highlight the influence of sea ice

In a paper just published in the journal AGU Advances, the scientists use a series of simulations to show that sea-ice changes are the most probable cause for the cooling of the surface waters in the Southern Ocean. Only when Alex Haumann, lead author and Professor Gruber's former doctoral student, and the team incorporated the observed changes in sea ice into the model were they able to correctly replicate the observed pattern of the temperature changes. When they omitted this effect and only took into account the other potential factors - such as a more vigorous ocean circulation or increased freshwater fluxes from the melting of the Antarctic glaciers - the pattern was not accurately simulated.

Their considering of the role of sea ice in causing the surface cooling was based on the observation that over the same period as the cooling took place, i.e., from 1982 to 2011, the sea-ice extent steadily increased in the Southern Ocean around Antarctica, while in the Arctic it shrunk significantly over the same period.

A few years ago, Haumann and Gruber and various colleagues already discovered the reason for this expansion of sea ice in the Southern Ocean. They noticed that stronger southerly winds over this period propelled more of the sea ice that is being formed along the coast out into the open sea, enhancing the melting there. The resulting stronger conveyor belt enhanced the transport of freshwater from near the continent out into the open ocean. This is because when sea ice is being formed from seawater, the salt is left behind, whereas when the sea ice melts in the summer well away from the coast, the freshwater is released into the surface, reducing the salinity of the seawater there.

This reduction in surface salinity strengthened the vertical stratification of the seawater: the fresher, and in this part of the ocean lighter water stays in the upper 100 m, while the denser saltier water remains below. In general, the saltier and colder the water, the greater its density and the greater its depth in the ocean.

Smaller heat exchange between the water layers

The stronger stratification reduced the exchange of heat between the deeper layers and the surface water, causing the heat to remain trapped at depth. In addition, the air above the Southern Ocean during winter is generally colder than the temperature of the seawater. Combined with the reduction of the vertical exchange of heat in the ocean, this ultimately created the observed situation where the surface water cooled and the subsurface warmed.

The strong role of salinity in controlling the vertical stratification is a peculiarity of the Southern Ocean, since there is actually very little difference in temperature between the ocean's surface water and the subsurface: only a few tenths of a degree. The strong salinity driven stratification also explains why the surface cooling did not induce deep mixing.

No material to feed global warming sceptics

 "The cooling of the Southern Ocean over three decades is really unusual, bearing in mind that otherwise all other parts of the planet, especially the land surface, have warmed up," says Nicolas Gruber.

Cooling in just one area of the ocean should not be interpreted as a reduction of the long-term warming of the global climate system as a whole. It is merely a redistribution of heat in the Southern Ocean from the surface to the deeper layers of the ocean. "We assume the strong winds pushing the sea ice in the Southern Ocean northward are potentially a side-effect of climate change," Gruber stresses. "Climate change is clearly man-made and cannot be disputed simply because one area of the ocean shows signs of cooling."

In addition, the current study went only up to 2011. "We have observed a trend reversal since 2015. The sea ice around the Antarctic is now starting to recede at a rapid rate," says the ETH Professor. "And this is very much in line with the overall trend of continuing global warming."

In mice, rats, and nonhuman primates, a newly developed SARS-CoV-2 virus vaccine candidate induced antibodies that neutralized several different SARS-CoV-2 strains. Critically, it did so without leading to a phenomenon known as antibody-dependent enhancement (ADE), which previous reports have raised as a concern. Based on the authors' observations, they propose that their vaccine candidate, "PiCoVacc," is safe in macaques and should be explored in clinical trials in humans. Rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Purified inactivated viruses - safe and effective for the prevention of diseases caused by viruses like influenza virus and poliovirus - have been traditionally used for vaccine development. Here, to develop preclinical models for such a SARS-CoV-2 vaccine, Qiang Gao and colleagues isolated an array of virus strains from 11 hospitalized patients from China, Italy, Switzerland, the UK and Spain. One strain was selected and developed into a purified, inactivated vaccine candidate, PiCoVacc. When tested in mice, PiCoVacc could elicit about ten-fold more antibodies against the virus spike protein than were found in serum from the recovered COVID-19 patients, the authors report. In mice and rats vaccinated with PiCoVacc and infected with the ten remaining virus strains three weeks later, PiCoVacc neutralized all strains, the authors say. They next vaccinated macaques at doses of either 1.5 micrograms or 6 micrograms three times over the course of two weeks. When later infected with SARS-CoV-2 strains, the animals who received the 6-microgram dose showed complete protection, and without observable ADE. The possibility that ADE could manifest after antibody titers wane could not be ruled out in this work, the authors note. "Collectively," they say, "these results suggest a path forward for clinical development of SARS-CoV-2 vaccines for use in humans." Clinical trials with PiCoVacc are expected to begin later this year.

Soils in deserts are very different from those found anywhere else. Extreme temperatures, little water and limited plant matter make an unusual environment. With little dead plant material to decompose and create a rich layer of organic matter, desert soils are unique.

Judith Turk, an assistant professor at the University of Nebraska-Lincoln, studies the top layer of desert soils, called the vesicular horizon. This surface layer of the soil is common in deserts and contains pores of different shapes, called vesicles and vughs.

"These horizons are important because of their role in many processes," Turk says. "Vesicular horizons determine how much water soaks into the soil and how much runs off. Since they occur in deserts, they control the distribution of the most limiting resource, which is water."

Vesicular pores are spherical, look a bit like bubbles, and are not connected to each other. Vughs are similar but more irregular in shape, almost like a clump of bubbles that have not fully separated from each other.

Turk wanted to learn how these horizons form across different desert soils. In their most recent experiment, they chose small plots of the soils and took samples. They then crushed the soil so the formation of pores would have to start from scratch. They checked the porosity of the soils over the course of a year to compare.

"First, we found that infiltration rates were lowered as a result of disturbance," Turk explains. "This would normally not be surprising, since disturbance compacts the soil, reducing porosity, and breaking up the pore networks that water flows through.

"However, the pores in V horizons are different," she says. "Most of the pores are not connected with each other and therefore contribute little to permeability of the soil. So, we weren't sure how disturbance would affect these horizons."

She adds that what did surprise them was how a soil's texture determined how well its porosity in this soil layer came back. They assumed that a soil with more silt would be better for vesicle formation but found vesicles formed more rapidly in relatively sandy soils.

"The capacity for vesicular pores to reform within a year after the V horizon is disturbed is something that is interesting," Turk says. "The post-disturbance V horizons being thinner with smaller pores tells us that what we observed in the undisturbed soils takes time to form."

It is important to study these soils because semi-arid lands cover about one third of the planet's land area. Soils with V horizons are often disturbed because populations of cities in arid environments are growing. There is construction of solar and wind farms, and these areas are popular for military exercises.

It's vital to take the researchers' findings into account when planning to disturb the soil. This allows people to understand how the soil might behave after the disturbance.

Turk plans to continue this research in the future. She would like to see an experiment done over a longer time scale to watch the newly formed layers blend into the undisturbed surrounding soil.

"Many people are surprised to learn that there are interesting soils in the desert," she says. "When I moved to California for graduate school, I fell in love with the desert lands of the western US. In the desert you can see the land surface and it's easy to imagine the processes that have built the soil landscapes that we see today."

New York, NY--May 6, 2019--Ammonia is a key component of fertilizer and vital in supporting plant growth and ultimately providing food for populations around the world. It is also a major pollutant that, after it is used in the food chain, enters municipal wastewater treatment plants where it is often not adequately removed. It is then released into the environment where it pollutes aquatic settings and damages ecosystems, triggering destructive algal blooms, dead zones, and fish kills.

Ammonia capture is now a critical challenge for the 21st century, especially as city populations are expected to increase dramatically, with a projected urban growth of 2.5 billion people by 2050. At the same time, providing improved sanitation to the 2.3 billion people who are currently unserved globally will entail the installation of new toilets, wastewater facilities, and sanitation infrastructure, putting even more stress on the environment.

To date, most ammonia capture is done through an extremely energy-intensive technique, the Haber-Bosch process, which is used by industry across the globe to produce fertilizer and accounts for 1-2% of the world's annual energy consumption. A Columbia Engineering team, led by Ngai Yin Yip, assistant professor of earth and environmental engineering, reports today that they have recovered ammonia through a new method that uses a very low level of energy, approximately a fifth of the energy used by the Haber-Bosch process. In addition, because the technique recycles ammonia in a closed loop, the ammonia can be recaptured for reuse in fertilizer, household cleaners, and other industrial products. The findings are published today by ACS Sustainable Chemistry & Engineering.

The management of nitrogen, an essential nutrient for life, has been recognized by the National Academy of Engineering as one of the Grand Challenges of the 21st century. Yip's group, which focuses on advancing sustainable production of both energy and water, wanted to invent a better, more ecological way to produce nitrogen, of which ammonia is a bioavailable form.

"It was clear that we needed a paradigm shift to transition to a circular economy model, where nitrogen is recovered and recycled, instead of the current unsustainable linear approach of costly production, utilization, and then discarding pollutants to the environment," Yip says.

Yip's team has expertise in membrane distillation, a technique that drives the permeation of volatile species, in this case, ammonia, from a feed stream to a collector stream, while the non-volatile species remain in the feed stream. The volatile species are driven across the membrane by a difference in vapor pressure, which is dependent on temperature and concentration. The researchers developed a technique, which they call "isothermal membrane distillation with acidic collector," or IMD-AC, that uses low-temperature heat, and applied it to selectively separate and capture ammonia from the ammonia-rich waste stream of urine (simulated for this project).

"Because our process is driven by moderate temperatures as low as 20-60 degrees Celsius, the energy can be supplied by cheap or even free waste heat from, for instance, cooling tower water, bath water, or solar thermal collectors," Yip says.

Next steps for the team include exploring ways to recover phosphorus, another key ingredient of fertilizer, sustainably and cheaply from urine.

"Now that we've demonstrated the sustainable recovery of nitrogen from urine," Yip adds, "we think that the growing population and sanitation trends present ideal opportunities for the introduction of decentralized urine diversion facilities for nutrient recovery, without costly retrofits or overhauls of the existing system, shifting wastewater management to a more sustainable and efficient paradigm."

Analysis of historical temperature data led by University of Warwick shows warm spells in winter occurring more often and for longer periods

Uses over a hundred years of data from the Central England Temperature (CET) record

Has implications for ecology, sustainability and agriculture

Warm winter spells have increased in frequency and duration two- to three times over since 1878, according to scientists led by the University of Warwick.

In a new analysis of historical daily temperature data published in the Journal of Applied Meteorology and Climatology, scientists from the Department of Physics at the University of Warwick, the British Antarctic Survey, and at the London School of Economics and Political Science examined data from the Central England Temperature (CET) record, the longest available instrumental record of temperature in the world. They focused on warm spells during the winter months, defined as sustained periods of time above a fixed temperature threshold.

The conclusions do not rely on identifying and counting winter warm spells directly but instead use observations of daily temperatures to show how the likelihood of different temperatures has changed. By applying a method called crossing theory to these probabilities, the scientists have provided information on the changing relationship between frequency, duration and intensity of these warm spells.

The researchers focused on the maximum daily temperatures in December, January and February in observations from 1878. Week-long warm intervals that return on average every 5 years now consistently exceed 13 degrees C. In the 1850s, a winter warm spell lasting more than 5 days with a daily maximum temperature above 12-13°C would typically take at least 5 years to reoccur. Nowadays they occur more often, typically every 4 years or less.

Climate variability is expected to increase as the global climate warms, and the increase of extended warm spells during winter can have an important impact on agriculture and the sustainability of ecosystems. However, ecosystems are not uniformly sensitive to changes at different temperatures. They are instead vulnerable to changes around critical temperature thresholds and these thresholds may be far from the distribution mean.

Lead author Professor Sandra Chapman of the University of Warwick Department of Physics said: "Our results show that it is possible to focus on warm spells above specific temperature thresholds that are critical for individual species and ecosystem functioning. It thus can be of direct value in supporting our understanding and assessment of climate change impacts.

Professor Stainforth from the Grantham Research Institute at the London School of Economics and Political Science said: "Sustained periods of warm weather can have a significant impact on agriculture and ecosystems even when they don't involve record-breaking extremes. The changing frequency and characteristics of such events may have substantial impacts and this new work demonstrates a novel and flexible method for deducing how they are changing. It provides a valuable new approach for studying the less obvious consequences of climate change."

Professor Eugene Murphy, Science Leader of the Ecosystems Team at British Antarctic Survey said: "Unusually extended periods of warm weather in winter can disrupt biological processes causing changes in the development of populations of plants and animals during the following spring. These changes can affect the biological balance that sustains ecosystems and the diverse biological communities they support, potentially reducing their resilience and capacity to cope with future change."

Bethesda, MD (May 6, 2020) -- In a new special issue of Clinical Gastroenterology and Hepatology, the clinical practice journal of the American Gastroenterological Association (AGA), leading international experts provide a comprehensive update on the treatment of inflammatory bowel diseases (IBD) for the practicing clinician.

The articles published in the special issue, "Management of Inflammatory Bowel Diseases: Clinical Perspectives" https://www.cghjournal.org/article/S1542-3565(20)30166-X/fulltext analyze and interpret key breakthroughs in IBD treatment, examine the increasingly complex and algorithmic treatments presented to reduce IBD-related morbidity, and focus on the importance of treating beyond symptom relief to achieve objective targets.

View the full issue line-up below. To receive any of the full studies or to speak with the authors, email media@gastro.org.

Introduction to the issue

* Management of Inflammatory Bowel Diseases: Clinical Perspectives https://www.cghjournal.org/article/S1542-3565(20)30166-X/fulltext; by Siddharth Singh, Laurent Peyrin-Biroulet, Ashwin Ananthakrishnan

Review articles

* Changing Global Epidemiology of Inflammatory Bowel Diseases: Sustaining Health Care Delivery into the 21st Century https://www.cghjournal.org/article/S1542-3565(20)30107-5/fulltext; Ashwin N. Ananthakrishnan, Gilaad G. Kaplan, Siew C. Ng

* Identifying Patients With Inflammatory Bowel Diseases at High vs. Low Risk of Complications https://www.cghjournal.org/article/S1542-3565(19)31322-9/fulltext; Corey A. Siegel, Charles N. Bernstein

* Positioning Therapies in the Management of Crohn's Disease https://www.cghjournal.org/article/S1542-3565(19)31237-6/fulltext; Nghia H. Nguyen, Siddharth Singh, William J. Sandborn

* Positioning of Therapies in Ulcerative Colitis https://www.cghjournal.org/article/S1542-3565(20)30096-3/fulltext; Silvio Danese, Gionata Fiorino, Laurent Peyrin-Biroulet

* How, When, and for Whom Should We Perform Therapeutic Drug Monitoring? https://www.cghjournal.org/article/S1542-3565(19)31092-4/fulltext; Severine Vermeire, Erwin Dreesen, Konstantinos Papamichael, Marla C. Dubinsky

* How Do We Treat Inflammatory Bowel Diseases to Aim For Endoscopic Remission? https://www.cghjournal.org/article/S1542-3565(19)31500-9/fulltext; Parambir S. Dulai, Vipul Jairath

* Use of Cross-Sectional Imaging for Tight Monitoring of Inflammatory Bowel Diseases https://www.cghjournal.org/article/S1542-3565(19)31392-8/fulltext; Mariangela Allocca, Silvio Danese, Valérie Laurent, Laurent Peyrin-Biroulet

* Predicting, Preventing and Managing Treatment-Related Complications in Patients with Inflammatory Bowel Diseases https://www.cghjournal.org/article/S1542-3565(20)30173-7/fulltext; Laurent Beaugerie, Jean-François Rahier, Julien Kirchgesner

* A Users Guide to De-escalating Immunomodulator and Biologic Therapy in Inflammatory Bowel Disease https://www.cghjournal.org/article/S1542-3565(19)31499-5/fulltext; Robert P. Hirten, Peter L. Lakatos, Jonas Halfvarson, Jean Frederic Colombel

* Inpatient Management of Inflammatory Bowel Disease Related Complications https://www.cghjournal.org/article/S1542-3565(20)30034-3/fulltext; Manreet Kaur, Robin L. Dalal, Seth Shaffer, David A. Schwartz, David T. Rubin

* Perioperative and Postoperative Management of Patients with Crohn's Disease and Ulcerative Colitis https://www.cghjournal.org/article/S1542-3565(19)31091-2/fulltext; Edward L. Barnes, Amy L. Lightner, Miguel Regueiro

* Management of Inflammatory Bowel Diseases in Special Populations: Obese, Old or Obstetric https://www.cghjournal.org/article/S1542-3565(19)31263-7/fulltext; Siddharth Singh, Sherman Picardo, Cynthia H. Seow

* Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases https://www.cghjournal.org/article/S1542-3565(20)30185-3/fulltext; Arie Levine, Jonathan M. Rhodes, James O. Lindsay, Maria T. Abreu, Michael A. Kamm, Peter R. Gibson, Christoph Gasche, Mark S. Silverberg, Uma Mahadevan, Rotem Sigall Boneh, Eyton Wine, Oriana M. Damas, Graeme Syme, Gina L. Trakman, Chu Kion Yao, Stefanie Stockhamer, Muhammad B. Hammami, Luis C. Garces, Gerhard Rogler, Ioannis E. Koutroubakis, Ashwin N. Ananthakrishnan, Liam McKeever, James D. Lewis

* Management of Patients With Immune Checkpoint Inhibitor-Induced Enterocolitis: a Systematic Review https://www.cghjournal.org/article/S1542-3565(20)30112-9/fulltext; Michael Collins, Emilie Soularue, Lysiane Marthey, Franck Carbonnel

The special issue also includes a compilation of AGA patient education resources on IBD https://www.cghjournal.org/article/S1542-3565(20)30167-1/fulltext. AGA's GI Patient Center https://www.gastro.org/practice-guidance/gi-patient-center also provides patient-education pages on Crohn's disease and ulcerative colitis written by AGA experts and presented in an easy-to-understand format for all patients.

About the AGA Institute

The American Gastroenterological Association (AGA) is the trusted voice of the GI community. Founded in 1897, AGA has grown to include more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. https://www.gastro.org/.

About Clinical Gastroenterology and Hepatology

The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org.

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Contact: Courtney Reed
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Researchers from the Faculty of Medicine of the University of Barcelona and the CELLEX Biomedical Research Centre from IDIBAPS, in collaboration with scientists from the University of Sydney, University of London and the Research Institute Sant Joan de Déu, have identified in a study with mice a protein which is fundamental to guarantee the restoration and regeneration of the liver after a transplant or hepatic surgery.

The study, led by the lecturers from the Department of Biomedicine Carles Rentero and Carles Enrich, showed the liver regeneration after a resection -operation which removes a part of the organ- could not happen in mice without the protein Annexin A6 (AnxA6). These results, published in the journal Hepatology, could have an impact in the future therapeutic strategy to treat liver damage.

The authors noted that the study is "highly relevant" for the growing number of patients with liver diseases worldwide. For these diseases, the only cure is a liver transplant, generally partial, and then they need the organ to be completely and healthfully restored.

One of the most abundant proteins in the liver

The liver of mammals has the ability to restore after a resection, traumatism or intoxication, as well as in certain physiological situations, such as pregnancy or lactation. This feature of the liver is the base of the success in living donor transplants.

In the study, researchers studied the function of AnxA6 in mice, one of the most abundant proteins in the liver. "This is the first study to identify the function of this protein in the liver in vivo, since its function is quite unknown in physiological processes and disease processes", says Carles Enrich.

The results show how the regeneration of this organ after liver resection did not happen in mice without the mentioned protein, which led to the death of the animals. This was related to an irreversible fall of the levels of glucose in the blood, a fundamental element in the hepatic functioning. "To restore a healthy liver after a hepatic resection, the remains of the organ have to take critical functions, such as keeping blood glucose levels between meals. For this regeneration to take place, the muscles have to decompose proteins in order to provide its basic constituents, aminoacids, so that the cells in the liver can take and use these molecules to create glucose", notes Carles Rentero.

In this sense, researchers saw that mice without AnzA6 did not have basic molecules to start creating glucose. "The study shows that SNAT4 transporters, proteins in the cell membrane that take aminoacids, do not appear in the surface of the liver cells in this mice, which makes it impossible to catch fundamental aminoacids such as blood alanine, and therefore production of glucose", notes Carles Enrich.

"Surprisingly -continues the researcher- the reinsertion of AnxA6 in the liver using genic therapy or putting glucose in the beverage for mice after the surgery restored the survival of these animals".

Potential influence in the research against hepatic damage

According to the researchers, these results shed light on the possibilities regarding whether AnzA6 or blood glucose can play a role when regenerating the liver and lighten liver failure, since it could change medical action protocols during a process of liver failure. However, this is very speculative, and it is only a possibility which should be studied", says Carles Rentero.

A new University of Wisconsin Oshkosh analysis of raptor teeth published in the peer-reviewed journal Palaeogeography, Palaeoclimatology, Palaeoecology shows that Velociraptors and their kin likely did not hunt in big, coordinated packs like dogs.

The raptors (Deinonychus antirrhopus) with their sickle-shaped talons were made famous in the 1993 blockbuster movie Jurassic Park, which portrayed them as highly intelligent, apex predators that worked in groups to hunt large prey.

"Raptorial dinosaurs often are shown as hunting in packs similar to wolves," said Joseph Frederickson, a vertebrate paleontologist and director of the Weis Earth Science Museum on the UWO Fox Cities campus. "The evidence for this behavior, however, is not altogether convincing. Since we can't watch these dinosaurs hunt in person, we must use indirect methods to determine their behavior in life."

Frederickson led the study in partnership with two colleagues at the University of Oklahoma and Sam Noble Museum, Michael Engel and Richard Cifell.

Though widely accepted, evidence for the pack-hunting dinosaur proposed by the late famed Yale University paleontologist John Ostrom is relatively weak, Frederickson said.

"The problem with this idea is that living dinosaurs (birds) and their relatives (crocodilians) do not usually hunt in groups and rarely ever hunt prey larger than themselves," he explained.

"Further, behavior like pack hunting does not fossilize so we can't directly test whether the animals actually worked together to hunt prey."

Recently, scientists have proposed a different model for behavior in raptors that is thought to be more like Komodo dragons or crocodiles, in which individuals may attack the same animal but cooperation is limited.

"We proposed in this study that there is a correlation between pack hunting and the diet of animals as they grow," Frederickson said.

In Komodo dragons, babies are at risk of being eaten by adults, so they take refuge in trees, where they find a wealth of food unavailable to their larger ground-dwelling parents. Animals that hunt in packs do not generally show this dietary diversity.

"If we can look at the diet of young raptors versus old raptors, we can come up with a hypothesis for whether they hunted in groups," Frederickson said.

To do this, the scientists considered the chemistry of teeth from the raptor Deinonychus, which lived in North America during the Cretaceous Period about 115 to 108 million years ago.

"Stable isotopes of carbon and oxygen were used to get an idea of diet and water sources for these animals. We also looked at a crocodilian and an herbivorous dinosaur from the same geologic formation," he said.

The scientists found that the Cretaceous crocodilians, like modern species, show a difference in diet between the smallest and largest teeth, indicating a distinct transition in diet as they grew.

"This is what we would expect for an animal where the parents do not provide food for their young," Frederickson said. "We also see the same pattern in the raptors, where the smallest teeth and the large teeth do not have the same average carbon isotope values, indicating they were eating different foods. This means the young were not being fed by the adults, which is why we believe Jurassic Park was wrong about raptor behavior."

Frederickson added that the method used in this study to analyze carbon in teeth could be applied to see whether other extinct creatures may have hunted in packs.