Culture

A standardised test that can now be used in the seven main languages in India will support the diagnosis of dementia and mild cognitive impairment.

Researchers have adapted the Addenbrooke's Cognitive Examination (ACE-III), a well-known screening instrument for dementia detection/diagnosis, to be used in Hindi, Telugu, Kannada, Malayalam, Urdu, Tamil and Indian English.

The work was carried out by the University of East Anglia (UEA) in the UK and in India at the National Institute of Mental Health and Neurosciences (NIMHANS) and Manipal Hospitals, Bengaluru; Nizam's Institute of Medical Sciences, Hyderabad; Shree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum; All India Institute of Medical Sciences, Delhi; and Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry.

The study, 'Dementia diagnosis in seven languages: the Addenbrooke's Cognitive Examination-III in India', is published in the Archives of Clinical Neuropsychology.

Prof Suvarna Alladi, professor of neurology at NIMHANS in Bengaluru, was the lead researcher.

Prof Alladi said: "With the rising burden of dementia globally, there is a need to harmonise dementia research across diverse populations.

"The ACE-III is a well-established cognitive screening tool to diagnose dementia, but there have been few efforts to standardise the use of it across cohorts speaking different languages. We aimed to standardise and validate ACE-III across seven Indian languages, and to assess the diagnostic accuracy of the test to detect dementia and mild cognitive impairment."

The researchers said a major proportion - 58 per cent - of people with dementia reside in low- and middle-income countries, and by 2050 that will increase to 68 per cent. Therefore, standardising diagnostic tools for dementia is important to accurately determine prevalence rates and to establish risk and protective factors for dementia.

A total of 1203 study participants from Hyderabad, Delhi, Trivandrum, Bangalore and Puducherry were examined by an experienced neurologist, who also interviewed a reliable family caregiver for each participant and reviewed their demographic and cognitive histories and medical records to determine their eligibility for the study. The study included controls and participants who were diagnosed with dementia or mild cognitive impairment, but those with moderate or severe dementia were excluded.

In accordance with the original version of ACE-III, the Indian versions look at five different cognitive functions: attention; memory; fluency; language; and visuospatial functions.

Culturally appropriate modifications were formulated based on the clinical and research expertise of the authors, and each of the five domains of the test were evaluated for cultural relevance, translatability, comparable difficulty and adaptability. For example, in the memory section, participants were asked about Indian politicians and movie actors.

A common administration and scoring guide was developed and psychologists were trained to ensure standardised test assessment in seven Indian languages.

Prof Eneida Mioshi, professor of dementia care research at UEA's School of Health Sciences, said: "Accounting for cultural differences and linguistic characteristics of different populations is crucial for the development of a common instrument to diagnose dementia.

"The development of a common diagnostic tool will facilitate harmonisation of dementia research across diverse populations, and catalyse the development of preventative and treatment strategies for larger cohorts of dementia from diverse demographic and geographic backgrounds."

ACE-III had previously been adapted and validated into one of the Indian languages - Gujarati. Additionally, the ACE-III tool has been validated in languages including Arabic, English, French, German, Greek, Hebrew, Italian, Japanese, Korean, Mandarin, Portuguese, Spanish and others.

Prof Mioshi said: "The adapted versions of ACE-III show great diagnostic accuracy in identifying dementia and mild cognitive impairment in a linguistically diverse context. Not only the ACE-III is a quick and inexpensive method of screening for dementia, it will also allow for harmonisation in future cross-national research studies, propelling Indian dementia research forward."

Prof Alladi said: "This adapted version of ACE-III can be used to uniformly diagnose cognitive impairment in people speaking different languages from both rural and urban populations located across India."

WEST LAFAYETTE, Ind. -- Similarly to how a picked lock gives away that someone has broken into a building, the stiffening of a structure surrounding cells in the human body can indicate that cancer is invading other tissue.

Monitoring changes to this structure, called the extracellular matrix, would give researchers another way to study the progression of disease. But detecting changes to the extracellular matrix is hard to do without damaging it.

Purdue University engineers have built a device that would allow disease specialists to load an extracellular matrix sample onto a platform and detect its stiffness through sound waves. The device is described in a study published in the journal Lab on a Chip and demonstrated in a YouTube video at https://youtu.be/hPvY0Sj0vxY.

"It's the same concept as checking for damage in an airplane wing. There's a sound wave propagating through the material and a receiver on the other side. The way that the wave propagates can indicate if there's any damage or defect without affecting the material itself," said Rahim Rahimi, a Purdue assistant professor of materials engineering, whose lab develops innovative materials and biomedical devices to address health care challenges.

Each tissue and organ has its own unique extracellular matrix, sort of like how buildings on a street vary in structure depending on their purpose. The extracellular matrix also comes with "landlines," or structural and chemical cues, that support communication between individual cells housed in the matrix.

Researchers have tried stretching, compressing or applying chemicals to samples of the extracellular matrix to measure this environment. But these methods also are prone to damaging the extracellular matrix.

Rahimi's team developed a nondestructive way to study how the extracellular matrix responds to disease, toxic substances or therapeutic drugs. The initial work for this study was performed in collaboration with the lab of Sophie Lelièvre, a professor of cancer pharmacology at Purdue, to identify how risk factors affect the extracellular matrix and increase the risk of developing breast cancer.

The device is a "lab-on-a-chip" connected to a transmitter and receiver. After pouring the extracellular matrix and the cells it contains onto the platform, the transmitter generates an ultrasonic wave that propagates through the material and then triggers the receiver. The output is an electrical signal indicating the stiffness of the extracellular matrix.

The researchers first demonstrated the device as a proof-of-concept with cancer cells contained in hydrogel, which is a material with a consistency similar to an extracellular matrix. The team now is studying the device's effectiveness on collagen extracellular matrices.

The device could easily be scaled up to run many samples at once, Rahimi said, such as in an array. This would allow researchers to look at several different aspects of a disease simultaneously.

Researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), working with an international network of scientists, have identified an inflammatory regulatory circuit in the eye controlled by a subtype of endothelial cells, the cells that line the interior of blood vessels. The discovery was made by analyzing gene expression in 8000 cells of the choroid--the vascular layer at the rear of the eye between the retina and the sclera. The results, published today in the Journal of Experimental Medicine, open new perspectives on the study and treatment of retinal vascular diseases and inflammatory disorders that affect the choroid.

In the retina, photoreceptors capture the light energy entering the eye and convert it into electrical pulses that give rise to visual perception, explained Ignacio Benedicto, CNIC researcher and study coordinator. "The activitiy and survival of photoreceptors depends on the choroid. The blood vessels that irrigate the choroid are essential for correct retina function because they provide oxygen and nutrients to the photoreceptors and remove waste products."

Enrique Rodríguez-Boulan, investigator at Weill Cornell Medicine and study codirector, said: "Failure of choroid function is associated with the development of ocular diseases such as age-related macular degeneration (called AMD), which causes blindness and affects 8.7% of the world population and 25% of people older than 80 years". In Spain alone, there are an estimated 700,000 people with AMD, and this blindness-linked disease is set to become increasingly common in the future due to progressive population aging.

Unfortunately, the most frequent form of AMD is incurable, and little is known about what causes the disease. This is in part due to the limited state of knowledge about the cell components of the choroid and the mechanisms of molecular communication between them.

The study published in the Journal of Experimental Medicine provides valuable information about how the endothelial cells in the choroid may regulate the development of inflammatory and vascular diseases in the retina.

Three subtypes of endothelial cells

The authors analyzed the choroid of adult mice using the 'single cell RNAseq' technique, which allows analysis of gene expression simultaneously in thousands of individual cells.

This analysis revealed that the choroid contains at least three types of endothelial cells. "One subtype is located specifically in the vessels closest to the retina and expresses the gene Indian Hedgehog at levels 300 times higher than are observed in endothelial cells from other organs," said Benedicto.

Indian Hedgehog encodes a protein called IHH, which is secreted to the cell exterior. The research team therefore wanted to identify the cells that respond to this endothelial signal. First author Guillermo Lehmann, currently an investigator at Regeneron Pharmaceuticals, explained: "Thanks to the use of transgenic mice, we were able to show that IHH acts on a population of pluripotent perivascular cells whose existence in the choroid was undocumented until now. In response to IHH, these cells regulate the numbers of a type of immune cells called mast cells in the choroid."

The team also found that when they eliminated the expression of IHH in the endothelium, choroidal macrophages reduced the expression of the anti-inflammatory marker CD206. Retinal damage in these mice provoked an exacerbated inflammatory response and a more pronounced vision loss than seen in similarly treated control animals.

The results open new perspectives on the study and treatment of retinal vascular diseases and inflammatory conditions affecting the choroid.

The marine heatwave of 2016 was one of longest and hottest thermal anomalies recorded on the Great Barrier Reef in Australia, influencing multiple species of marine ectotherms, including coral reef fishes.

Dr Celia Schunter from School of Biological Sciences and the Swire Institute of Marine Science (SWIMS), The University of Hong Kong (HKU) and a team of international scientists conducted a study attempting to understand the molecular response of five species to the 2016 heatwave conditions that killed a third of the Great Barrier Reef corals. This is the world-first study tracking how wild fish populations respond to a severe marine heatwave. The results of the study were published in the journal Science Advances.

Marine heatwaves (MHWs) are elevated extreme temperatures in the oceans for an extended period of time, similar to an atmospheric heatwave. These elevated temperatures can have a significant impact on marine life, possibly pushing the thermal limits of many organisms. With the frequency and intensity of heatwaves predicted to increase in the future, this could have greater impacts on the performance of ectotherms, when compared to slight thermal increments over years or decades.

"To understand the challenges fish face under such conditions we used a molecular approach to evaluate how acute warming events directly affect reef fish communities in nature," said Dr Celia Schunter. "We chose to work with five different species which are commonly found on the reef to be able to understand differences in reactions among fish species with different life histories to get a broader overview of the reaction and impact."

"Our study shows that reef fishes are directly affected by heatwaves, but their responses vary greatly among species," said co-author Associate Professor Jodie Rummer from the ARC Centre of Excellence for Coral Reef Studies at James Cook University (Coral CoE at JCU). Dr Rummer was part of the international team that studied changes in the expression of thousands of different genes in five species of coral reef fish, collected at different points before, during and after the 2016 heatwave.

"Changes in gene expression can tell us how an animal responds physiologically to an environmental shock, such as a heatwave," said Dr Celia Schunter from HKU School of Biological Sciences and SWIMS, one of the lead authors in the study. "We measured RNA levels in livers in the fish. This can control when proteins are made and in what amount, and these proteins dictate how the cells of the body function. We saw many genes change expression levels across the timepoints of a heatwave revealing important functions such as cellular stress response and changes in metabolic functions."

Through these genetic analyses, the team identified species-specific physiological responses to the heightened temperatures. "Fast water warming causes an increase of the metabolic demands in fishes, which are similar to what happens to an athlete doing intense exercises. When water temperature increases, fishes have a higher demand for energy and oxygen, which leaves a signal that is measurable with genetic techniques. This higher energy demand at warming can affect their reproduction, swimming and development, and that is why it is important to understand the response to warming." said Dr Moisés A Bernal, co-author of the study from Auburn University.

Interestingly, "these patterns of gene expression also changed with the duration of the heatwave," said Dr Rummer. "This suggests that the physiological mechanisms the fish use to cope with the warmer waters changed as the heatwave progressed. The results suggest fish populations are influenced by both the intensity of a heatwave and how long it lasts." This signals potential long-term consequences for the health of fish populations as extreme heat events increase in frequency, duration and magnitude under human-induced climate change.

At a species level, Dr Rummer says the responses varied in intensity. Some fish struggled less than others. "The spiny damselfish responded strongly to the warmer conditions, with changes in the expression of thousands of genes, suggesting it is particularly sensitive to heatwaves. Other species appear to be more tolerant, with fewer changes in gene expression." said Dr Rummer . Two of the five studies species studied can also be found in waters around Hong Kong and Southern China as well as many more closely related fish species providing also some context for possible effects for waters around Hong Kong.

The study provides a possible approach for predicting which fish species are most at risk under repeated heatwave conditions, said another co-author Professor Timothy Ravasi, from the Marine Climate Change Unit at the Okinawa Institute of Science and Technology Graduate University (OIST). "This has ramifications for policy makers and for the fishing industry, because not all species will be equally affected. We need to screen a large number of species to predict which will be sensitive and which will be more tolerant to warming waters and heatwaves."

"Over time, the fish may adapt to rising temperatures, or even migrate to cooler waters," Professor Ravasi said. "But these heatwaves are happening now, and it's necessary to understand and consider the immediate consequences."

In 2015 the South China Sea experienced a heatwave of a similar magnitude than the heatwave on the Great Barrier Reef studied here. The coastal waters of Hong Kong and the South China Sea are predicted to experience more frequent and intense marine heatwave events as seen on the global scale. It is now clear that these extreme events can have far-reaching effects on marine fishes, but also economic implications on aquaculture and fishing industries Dr Celia Schunter urges the need for more research into the impacts of such events in the marine waters of Hong Kong to avert the potential collapse in the marine ecosystem and the industries relying on it.

Sugars like polysaccharides are found everywhere in nature and are believed to be essential for life to arise. In humans, they cover the surface of all cells and the family of polysaccharides called GAGs (glycosaminoglycans) are particularly abundant and difficult to analyse.

GAGs of the heparan sulfate type play key roles in regulating many biological functions, including inflammation, neurodegeneration and tumor metastasis. In fact, a special type of heparan sulfate called heparin is currently one the most used drugs in the clinic where it is used to prevent coagulation. Researchers are therefore intensively trying to map the detailed structures of heparan sulfates and link them to their biological functions.

So far, only a few structures have been successfully identified, but that may be about to change. In a new study in Nature Communications from the Danish National Research Foundation Centre for Glycomics at the Department of Cellular and Molecular Medicine, University of Copenhagen, Rebecca and her team has invented a new method that will boost the mapping of these structures.

"Determining the structures is a key question in the research about sugars. If we know the structure, we can determine what the cues are for specific biological functions and consider potential ways to exploit this in the development of therapeutics. This is hugely important and clinically relevant, as shown by the widely used anti-coagulant heparins, and the potential application of new heparin-based drugs for multiple diseases in the future," says Dr Rebecca Louise Miller, corresponding author of the new study and Assistant Professor at the Copenhagen Center for Glycomics.

A new technology and new EU funding

The researchers' new method is called "Shotgun ion mobility mass spectrometry sequencing" or SIMMS2. The technique relies on advanced mass spectrometry to break the sugar structures into smaller fragments, separate them, and fingerprint them compared to known standards. Virtual reassembly of the sugar pieces into a picture of the original sugar like a big jigsaw puzzle - only infinitely more complicated - can for the first time determine larger sequences of polysaccharides that are big enough to capture the cues that direct functions like anti-coagulation.

"The instrumentation behind this new method was invented by the company Waters Ltd in 2006 and is available to many pharmaceutical companies and researchers. This means that the method could be easily implemented and widely used for drug discovery by many research groups in a short period of time," says Professor Jeremy Turnbull, University of Liverpool and Copenhagen Center for Glycomics, a co-author on the study.

The GAG team at Copenhagen Center of Glycomics recently reported the first cell-based method (GAGOme) to produce all variants of GAGs for discovery of functions and development of therapeutics (Chen et al, Nature Methods 2018), and this will be combined with the new method for sequencing of GAG structures. The hope is to follow up on many promising therapeutic effects of heparins in cancer and neurogenerative diseases and pioneer new use of GAGs in medicine.

To continue the development of the SIMMS method and pioneer new use of GAGs in medicine, Miller and Turnbull were recently awarded an EU grant worth €3.8m to a consortium that also includes researchers from Freie Universität Berlin, University of Utrecht, University of Liverpool and Karolinska Institutet in Stockholm. They will also apply the method to understand heparan sulfate structural cues that regulate stem cells to generate specialized neurons for treatment of Parkinson's disease.

Nitrogen is essential for all living things. Synthetic fertilizer, which contains rich reactive nitrogen, has sustained food production and thereby the global population, but the nitrogen it emits is also a burden to the environment--air pollution, soil acidification, water eutrophication, to name just some of the consequences.

Although numerous field studies have been conducted to understand the implications of atmospheric nitrogen deposition in the environment, conventional manipulative experiments have mostly been employed, by adding nitrogen solution directly onto grassland or forest floors (soil).

In an article recently published in Atmospheric and Oceanic Science Letters, Dr Yuepeng Pan, from the Institute of Atmospheric Physics, Chinese Academy of Sciences, and his coauthors, challenge the traditional approach in evaluating the impacts of nitrogen deposition.

"There are three ways for nitrogen to be deposited: rainfall, aerosol and gas; and spraying nitrogen solution onto soil assumes that atmospheric deposition occurs mainly as rainfall (wet deposition)," says Dr Pan. "However, dry deposition of gaseous and particulate reactive nitrogen species, especially ammonia, is also an important deposition process."

Dr Pan also points out that there have only been a limited number of field studies that have investigated the bidirectional exchange of ammonia between the atmosphere and plants, not to mention the impacts of ammonia on natural ecosystems.

"Ammonia plays a vital role in nitrogen deposition and haze pollution. To make things worse, atmospheric ammonia concentrations have increased worldwide in recent decades," suggests Dr Pan. "The next generation of field experiments simulating nitrogen deposition should further consider ammonia."

WESTMINSTER, Colorado - MARCH 20, 2020 - Many millions of homeowners use feeders to attract birds. But a two-year study featured in the journal Invasive Plant Science and Management suggests there may be one unintended consequence to this popular hobby. Bird feed mixtures may be helping to spread troublesome weeds that threaten agricultural crops.

When researchers examined the contents of 98 commercially available bird feed mixes, they uncovered several significant findings:

The mixes contained seeds from 29 weed species.

96 percent of the mixes contained seeds for pigweed species weeds, which can represent a significant threat to agriculture.

One in 10 contained Palmer amaranth or waterhemp seeds that demonstrated resistance to glyphosate in a greenhouse screening.

Seeds from kochia, common ragweed, foxtail species and wild buckwheat were also found in many of the mixes.

The researchers also explored which harvested bird feed ingredients contributed most to weed seed contamination. They found that proso millet grain was closely linked to the presence of pigweed species weeds, while safflower and sunflower contributed most to the presence of kochia and common ragweed, respectively.

"While it is difficult to estimate the precise role commercial bird feed plays, there is a distinct possibility it may be an overlooked pathway for spreading troublesome weed species into new regions," says Eric Oseland of the University of Missouri.

To mitigate the risks, researchers recommend careful weed management in crop fields designated for bird feed, as well as the use of sieving during packaging to reduce weed seed contamination. They also point to the proven effectiveness of regulatory measures adopted in Europe to limit weed seed content in bird feed.

Bats are famous for their sonar-based navigation. They use their extremely sensitive hearing for orientation, emitting ultrasound noises and receiving an image of their surroundings based on the echo. Seba's short-tailed bat (Carollia perspicillata), for example, finds the fruits that are its preferred food using this echolocation system. At the same time, bats also use their voices in a somewhat deeper frequency range to communicate with other members of their species. Seba's short-tailed bats employ a vocal range for this purpose that is otherwise only found among songbirds and humans. Like humans, they produce sound through the larynx.

Together with his team, neuroscientist Julio C. Hechavarria from the Institute for Cell Biology and Neuroscience at Goethe University investigated brain activity preceding vocalisation in Seba's short-tailed bats. The scientists were able to identify a group of nerve cells that create a circuitry from the frontal lobe to the corpus striatum in the interior of the brain. When this neural circuit fires off rhythmic signals, the bat emits a vocalisation about half a second later. The type of rhythm seemed to determine whether the bats were about to utter echolocation or communication vocalisations.

Since it is nearly impossible to make a prediction within half a second, the Frankfurt researchers trained a computer to test their hypothesis: The computer analysed the recorded sounds and the neural rhythm separately and attempted to make prognoses using the various rhythms. The result: in its predictions of echolocation versus communication vocalisations, the computer was correct about 80 percent of the time. Predictions were particularly accurate when considering signals from the frontal lobe, an area that in humans has been linked to action planning, among other functions.

The Frankfurt scientists argue that the rhythms they observed in the bat brain are similar to neural rhythms often recorded from the human scalp, and concluded that brain rhythms could be linked to sound production in mammals in general.

Julio Hechavarria: "For over 50 years, bats have served as an animal model for studying how the brain processes auditory stimuli and how human language develops. For the first time, we were able to show how distant brain regions in bats communicate with each other during vocalization. At the same time, we know that the corresponding brain networks are impaired in individuals who, for example, stutter as a result of Parkinson's disease or emit involuntary noises due to Tourette syndrome. We therefore hope that by continuing to study vocal behaviour in bats, we can contribute to a better understanding of these human diseases."

About one in five Danes are affected by depression at some point in their lives. The severe depressions may be treated with the so-called 'tricyclic antidepressants', an antidepressant drug that is more effective than the drugs used for mild and moderate depressions.

But unfortunately, the tricyclic antidepressants also have a downside: significantly more and more serious side effects. So serious that many people stop taking the drug and thus receive no treatment for their depression.

Now, researchers from the Faculty of Health and Medical Sciences at the University of Copenhagen, in collaboration with Lundbeck A/S and the National Institutes of Health in Baltimore, have discovered a substance that may solve that problem.

'We have discovered a substance, Lu AF60097, that works in a different way from the ones presently in use. If the new substance works, it may help the existing drugs get rid of the serious side effects', says Professor at the Department of Neuroscience at the Faculty of Health and Medical Sciences, Claus Juul Løland.

Therapeutic effect without side effects

Serotonin is a so-called neurotransmitter, a chemical substance found in the brain. In a person with severe depression, the level of serotonin is very low. Antidepressant drugs make adjustments to get a higher level of active serotonin.

'The antidepressants we use today work by going in and binding to the same site as serotonin on the serotonin transporter (SERT). The antidepressants block the return transport of serotonin and thereby also the removal of the active serotonin. But such blockage requires a relatively large dose of the antidepressant substance. And with the tricyclic antidepressants, that causes some serious side effects', says Claus Juul Løland.

The side effects can be anything from life-threatening heart problems to severely dry mouth, visual disorders, development of mania, weight problems and digestive challenges.

The substance discovered by the researchers binds to another site on SERT: the 'allosteric site'. When a substance binds to the allosteric site rather than the same site as serotonin, it is possible to regulate the function of the serotonin transporter instead of completely blocking it.

'In this case, we have shown that when we bind this substance to the allosteric site while giving the tricyclic antidepressant, we can amplify the binding of the antidepressant substance. Therefore, we can use a much smaller concentration of the antidepressant substance. It might cause fewer side effects, but have the same therapeutic effect', says Claus Juul Løland.

From concept to drug

The researchers have, over a long period of time and in several rounds, screened a number of substances from Lundbeck's drug library to find a substance that had a sufficiently strong link to the allosteric site to make it possible to study the pharmacological effect. With Lu AF60097, they finally succeeded.

But there is still a long way to go before the substance can be used as an actual drug. The researchers have shown that a substance that binds to the allosteric site can have this pronounced, pharmacological effect in cells and in rats. From here, it is up to the pharmaceutical companies to develop substances that may have the same effect in humans.

'We have taken the first step. But perhaps also the biggest. We have shown that the concept works. If it also works in practice, hopefully in the future it can be used to treat people with severe depression'.

The American Dust Bowl of the 1930s - captured by the novels of John Steinbeck - was an environmental and socio-economic disaster that worsened the Great Depression.

The Dust Bowl was an extreme event. But due to climate change, massive crop failures are more likely to happen again in the future. New research in Frontiers in Sustainable Food Systems aimed to answer what these impacts may look like.

The Dust Bowl was centered on the Great Plains of the USA, where decades of unsustainable deep plowing had displaced native, moisture-retaining grasses. An atypical La Niña then brought intense droughts, high temperatures, and strong winds which blew away the topsoil in the form of large-scale dust storms.

Apart from its direct impact on people (around 7,000 deaths and two million homeless), the Dust Bowl had a catastrophic effect on crops where wheat and maize production in the USA plummeted by 36% and 48% during the 1930s.

Currently, the Intergovernmental Panel on Climate Change predicts that in another three to four decades that most of the USA will have further warmed by 1.5-2 °C. This compounds issues that already exist today, where global food security is under pressure from the increased frequency of extreme weather events.

"We wanted to forecast how a multi-year production decline in a major exporting country, similar to that which occurred during the Dust Bowl, would affect modern food supplies globally via international trade," says first author Dr Alison Heslin, a postdoctoral researcher at the Center for Climate Systems Research of Columbia University and NASA's Goddard Institute for Space Studies.

"In today's system of global food trade, disruptions are not bound by borders. Shocks to production are expected to affect trade partners who depend on imports for their domestic food supply."

To assess the possible impacts of a second dust bowl, the authors first developed two alternative computer simulations of the worldwide trade in wheat. They then delivered a shock to these model systems in the form of a four-year-long Dust Bowl-like anomaly, restricted to the USA.

Under one simulation, countries first use their reserves and then divide the absorbed shock between imports and exports, propagating it in one direction by increasing imports and in another by decreasing exports.

Under the more complicated second model, the USA first reduces only its exports, propagating the shock to all receiving trade partners, after which all countries with a shortage respond by increasing their imports.

Their results predict a severity similar to that of the original event, estimated from historical data. The results show that the USA would fully exhaust 94% of its reserves over the first four years of a Dust Bowl-liked agricultural shock.

They also show that without exception, all countries to which the USA exports wheat would decrease their reserves, even though they didn't themselves suffer crop failure.

"We focused on a subset of the possible impacts, specifically changes in trade, drawing down strategic reserves and decreases in consumption," says co-author Dr Jessica Gephart, Assistant Professor at the Department of Environmental Science of the American University in Washington DC.

"We found that global wheat trade contracts and shifts toward other wheat exporters, and that wheat reserves around the world decline, in many cases to zero. This suggests that the impacts would not only raise prices for US consumers but would also raise prices far beyond the US borders," says Gephart.

Key impacts of another four-year dust bowl could include an initial 31% loss of global wheat stocks, and by the end of the four years, between 36-52 countries could have used up over 75% of their starting reserves. The 10 countries with the highest initial reserves (China, USA, India, Iran, Canada, Russia, Morocco, Australia, Egypt, Algeria) would see their reserves decline by 15-22 % relative to the starting points.

However, a silver lining is that due to the high initial starting point of global reserves, most supply shocks, even in countries without reserves, could be addressed through trade flow adjustments without reducing consumption.

"Our results remind us that mitigating climate risks requires accounting for not only the direct effects of climate change, like local extreme weather events, but also the climate impacts which travel through our interconnected system of global trade."

"In the context of food security, we show that accessing food reserves can, for a time, buffer populations from trade-induced supply shortages but as reserves deplete, people are at risk of food shortages," says Heslin.

Growth ability at acidic conditions is important to bacteria. Enteric bacteria such as Escherichia coli and Salmonella can colonize and cause disease in the host's intestinal tract, but they have to combat acidic environments during the whole process of invading the host.

The stomach, with pH value as low as 1.5-2.5, is recognized as a natural antibiotic barrier. After entering into the small intestine, E. coli will encounter a less acidic environment (with pH value of 4-6), reproduce rapidly, and cause disease to the host ultimately.

Recently, a research team led by Prof. XIAN Mo and Prof. ZHAO Guang from the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS) discovered a novel bacterial acid tolerance system, which confers the growth capability to E. coli at pH of 4.2.

Up to now, five acid resistance systems have been reported. These acid resistance systems can enable E. coli to survive in gastric acid for hours, but they play no role in rapid multiplication of E. coli under moderate acidic conditions.

CpxA, the newly discovered system, can sense acidification directly through protonation of histidine residues. It will also activate its cognate regulator protein CpxRx to stimulate the expression of fabA and fabB genes for biosynthesis of unsaturated fatty acids, increasing unsaturated fatty acid contents in membrane lipid.

Changes in membrane lipid composition lower the fluidity and proton permeability of cell membrane, increasing the intracellular pH homeostasis.

Experiment results showed that E. coli mutant deficient in this system cannot grow in mouse intestine. Besides E. coli, this acid tolerance system also exists in pathogenic bacteria including Salmonella, Shigella, Vibrio cholerae, Yersinia pestis and Pseudomonas aeruginosa, which may be a new target for the development of antimicrobials.

The related findings were published in Nature Communications on Mar. 20.

Triglycerides, those fats that seem to be the bane of any diet, remain a mystery for many researchers. Plenty of them are in Big Macs, deep pan pizza and the like, but some are a necessity to fuel the body for daily activities.

Researchers Mark Castleberry, a doctoral student, and professor Sean Davidson, both in the UC College of Medicine, have found a way to produce in the laboratory a human protein produced in the liver known as Apolipoprotein A5 (APOA 5). It plays an important role in metabolizing and clearing excess levels of triglycerides from the bloodstream.

Their findings are available in the American Society for Biochemistry and Molecular Biology's Journal of Lipid Research online. Castleberry, who is studying in the UC Department of Molecular Genetics, Biochemistry and Microbiology, is the paper's first author.

"We are really interested in understanding triglycerides because hypertriglyceridemia -- too much fat in your blood -- is a big factor leading to cardiovascular disease, diabetes, obesity and other health concerns," explains Davidson, who holds appointments in UC's departments of Pathology and Laboratory Medicine and Molecular Genetics, Biochemistry and Microbiology. "When you have a lot of fat that is hanging around in your circulation it's important to clear as much of it out as soon as possible."

"APOA5 is highly involved in how fast triglycerides get taken out of your circulation," says Davidson, who has a doctorate in biochemistry. "The more APOA5 you have the faster the triglyceride is removed. Everybody agrees it is an important protein but scientists don't know much about its structure or how it does what it does. If we could figure out how it works we could come up with a drug that uses the same mechanism or trigger it to work better."

The work demonstrates UC's commitment to research as described in its strategic direction called Next Lives Here.

Castleberry says researchers inserted a human gene coded by DNA into bacteria genetically engineered to produce human proteins. Once those proteins were produced they were removed from the host and purified for use in studies at the lab bench and in mouse models.

"We can quickly make a much greater amount of this protein using bacterial production than if we tried to isolate it from blood in humans," explains Castleberry. "The mice in this study were basically fed a large bowl of fat and triglycerides."

"We could analyze their blood after we fed them and observe the level of fat change as they digested the meal," said Castleberry. "We were able to give our protein to the mice that had that fatty meal and rapidly clear the triglycerides that would have accumulated in their blood."

Chemists at Texas A&M University are taking a p[h]age from bacteria's playbook in order to beat viruses at their own game and develop new drugs to fight cancer and a host of other human diseases in the process.

For decades, scientists have relied on phage display -- a technique used to identify novel peptide ligands, or peptides that bind to other proteins or molecules -- as a versatile tool in a variety of applications ranging from drug discovery to materials science. A team led by Texas A&M chemist and 2018 Texas A&M Presidential Impact Fellow Dr. Wenshe R. Liu has learned a new trick from an old master, bacteria, successfully harnessing its ability to make short peptides containing noncanonical amino acids (ncAAs) that equip them with special properties, such as enzyme degradation resistance and targeted protein binding capabilities.

Using a clever strategy to "trick" the system so that only viruses containing peptides with ncAAs are capable of reproducing, the Liu research group has found a way to stack the phage display library construction deck, effectively expanding the genetic code of bacteriophages and paving the way for new peptide-based therapeutics. Their findings were published Friday (March 13) in the journal Nature Communications.

"Utilizing unnatural amino acids, we greatly expand the utility of phage display for identifying new peptide therapeutics," Liu said.

Phage display is one of several tools that scientist rely on to find new peptides with potential use as drugs to treat diseases, explains 2018 Texas A&M chemistry Ph.D. graduate Dr. Jeffery M. Tharp, a postdoctoral associate at Yale University and lead author on the team's paper, the third thus far representing his thesis work at Texas A&M. In addition, it is one of the first from the Texas A&M Drug Discovery Laboratory, founded by Liu and fellow Texas A&M chemists in 2018.

"Phage display uses viruses, or phages, to 'fish out' specific peptides from a pool of millions of different peptide variants; however, it is very difficult to use this technique to find peptides containing ncAAs," Tharp added. "In our paper, we developed a new method of phage display that allows for easy retrieval of potential peptide drugs containing diverse ncAAs. In addition, we used our new technique to identify novel peptides containing ncAAs that are very strong inhibitors of sirtuin 2 -- an enzyme that is involved in regulating human lifespan and is a promising drug target for the treatment of human cancers."

The Liu group collaborated with the Laboratory for Molecular Simulation (LMS), including Texas A&M chemistry Ph.D. candidate and LMS interim manager Andreas Ehnbom and Texas A&M High Performance Research Computing Associate Director Dr. Lisa M. Pérez, who performed the molecular dynamics simulations that enabled the team to understand the selectivity involved for specific peptides.

"The beauty of this work, at least in my mind, is that it crosses multiple disciplines of chemistry -- synthetic chemistry, chemical biology and computations," Ehnbom said.

Tharp notes that the founders of phage display were awarded the 2018 Nobel Prize in Chemistry in recognition of the technique's versatility, relative ease of use and effectiveness across myriad disciplines. In combination with the resulting new molecules, he predicts the Liu group's new method will be similarly useful for all applications of phage display.

"This technique allows ncAAs with unique structures to be incorporated into the phage peptides, which can help identify more potent peptide drugs," Tharp added. "In addition, we can include reactive ncAAs into the phage peptides, which can potentially be used to make better materials and drug delivery systems."

Tharp says the team will continue to use their new phage display technique to search for other peptides containing ncAAs that inhibit enzymes related to human disease while continuing to develop other methods that expand its utility.

Merging synthetic biology and materials science, researchers genetically coaxed specific populations of neurons to manufacture electronic-tissue "composites" within the cellular architecture of a living animal, a new proof-of-concept report reveals. The approach may enable the creation of diverse, complex and functional synthetic structures and materials within living systems. Similar to optogenetics, which uses pulses of laser light to modulate the behavior of genetically modified neurons, the emerging field of bioelectronic medicine seeks to use electrical stimulation to produce cellular or organ-specific effects. Many cells and tissues respond to electrical fields - particularly neurons - and electrical stimulation has been shown to affect a variety of cellular activities. Clinical applications range from soothing post-amputation pain to tissue regeneration. However, while approaches to modify the electrical properties of a cell and its response to electrical stimulation exist, they often affect large, diverse cell populations or off-target tissue elements, producing undesirable side effects. To date, no approach has been able to integrate electroactive polymers with cell-type specificity, thus enabling a more targeted use of electrical fields and stimulation - a capability that could significantly improve the therapeutic potential of bioelectronic medicine. Leveraging the complex and powerful biosynthetic machinery of living cells, Jia Liu and colleagues present a proof-of-concept of genetically targeted-chemical assembly. Liu et al. engineered an enzyme, which, when expressed, instructed gene-targeted neurons to synthesize and assemble electroactive polymers onto their plasma membrane, effectively changing the electrical properties of specific populations of cells. The targeted approach allowed for in vivo bioelectronic manipulation of neuron properties as well as of specific behaviors in freely moving C. elegans worms, without compromising the natural function of the cells. "Future work will seek to demonstrate long-term integration of these elements for intriguing scientific and translational application via modulating portions of neural activity," write Kevin Otto and Christine Schmidt in a related Perspective.

Common assumption has long held that Ritalin, Adderall and similar drugs work by helping people focus.

Yet a new study from a team led in part by Brown University researchers shows that these medications -- usually prescribed to individuals diagnosed with attention deficit hyperactivity disorder, but often used by otherwise healthy people as a "study aid" -- actually work by directing the brain to fix its attention on the benefits, rather than the costs, of completing difficult tasks.

The study, published on Thursday, March 19 in the journal Science, marks the first time that scientists have examined precisely how stimulants such as Ritalin alter cognitive function. Their research could open opportunities for further studies to help medical professionals better understand how to identify and treat ADHD, depression, anxiety and other mental disorders.

"People tend to think, 'Ritalin and Adderall help me focus,'" said Michael Frank, the study's co-senior author and a professor of cognitive, linguistic and psychological sciences at Brown. "And they do, in some sense. But what this study shows is that they do so by increasing your cognitive motivation: Your perceived benefits of performing a demanding task are elevated, while the perceived costs are reduced. This effect is separate from any changes in actual ability."

According to Frank, stimulants such as Ritalin increase the amount of dopamine released in the striatum, a key region in the brain related to motivation, action and cognition. Previous research has shown that dopamine, a "chemical messenger" that ferries information between neurons, can greatly influence cognitive and physical behavior. Several past studies have found, for example, that both rodents and humans are more motivated to perform physically demanding tasks with higher dopamine.

What has remained unknown, though, is whether dopamine can have similar motivational effects on cognition -- and that's what a new collaborative project between Frank, Brown postdoctoral researcher Andrew Westbrook and Dutch neuropsychiatry scholar Roshan Cools set out to understand.

"We've known for a long time that when you give people these types of stimulants, you get enhanced performance," said Westbrook, the study's lead author. "But is that due to an increased ability, or is it due to increased motivation? We didn't know which of these two factors were contributing and to what degree."

Frank's team had previously developed mathematical models suggesting that dopamine alters the degree to which the striatum emphasizes the benefits, rather than the costs, of completing physical and mental actions. Drawing upon these models, Westbrook worked with Frank and Cools to develop an experiment that examined how stimulants that elevated dopamine levels affected people's mental cost-benefit analyses.

The researchers worked with 50 healthy women and men ages 18 to 43 in a lab at Radboud University in the Netherlands. First, they measured the natural dopamine levels in each subject's striatum using brain imaging technology. Then, they asked the subjects whether they would take part in a series of cognitively demanding tests, some easier and others more difficult, in exchange for certain amounts of money. Subjects who agreed to take the hardest tests stood to make the most money.

Each of the subjects completed the experiment three times -- once after taking a placebo; once after taking methylphenidate, the generic version of Ritalin; and once after taking sulpiride, an antipsychotic that elevates dopamine levels when taken in low doses and is often used to treat symptoms of schizophrenia and major depressive disorder at much higher doses. The researchers used a double-blind experiment design, where neither they nor the subjects knew which pill was being given to each subject.

The results largely matched Westbrook's computer-modeled predictions. Those with lower dopamine levels made decisions that indicated they were more focused on avoiding difficult cognitive work -- in other words, they were more sensitive to the potential costs of completing the task. Those with higher dopamine levels, on the other hand, made decisions that showed they were more sensitive to differences in the amount of money they could earn by choosing the harder test -- in other words, they focused more on the potential benefits. Westbrook said the latter held true whether the subjects' dopamine levels were naturally higher or whether they had been artificially elevated by medications.

Westbrook said the results support the idea that, medication or no medication, dopamine typically acts as a motivation regulator for human brains.

"The thoughts that pop into our head, and the amount of time we spend thinking about them, are regulated by this underlying cost-benefit decision-making system," Westbrook said. "Our brains have been honed to orient us toward the tasks that will have the greatest payoff and the least cost over time."

All of us have slightly different base levels of dopamine, said Frank, who is affiliated with the Carney Institute for Brain Science at Brown. Those who have lower levels tend to be more risk-averse, because they spend more time focusing on the potential costs of completing a difficult task. Those with higher levels tend to be more impulsive and active, because they focus more on the benefits.

No single dopamine level is inherently better than another, Frank said -- an active, high-dopamine person may take fulfilling, happiness-boosting risks but may also be more prone to injury; a risk-averse, low-dopamine person may avoid injuries and disappointments but may also miss out on adventures. And dopamine levels don't necessarily stay the same from one day to the next: They may decrease in response to danger or lack of sleep, and they may increase when people feel safe and supported.

In other words, Westbrook said, most people can trust natural dopamine levels to guide them toward the right decisions. Of course, previous experiments have made it clear that many people with particularly low dopamine levels -- including those who are diagnosed with depression or ADHD -- can benefit from dopamine-boosting stimulant medications. But he said those medications are never certain to improve the lives of those who are healthy and who choose to use them recreationally. Doing so could, in fact, lead some to make poorer decisions.

"When you raise dopamine in someone who already has a high dopamine level, every decision seems like it has benefit, which could distract from the real beneficial tasks," Westbrook said. "People might behave in ways that aren't consistent with their goals, like taking part in impulsive gambling or risky sex behaviors."

Westbrook and Frank hope their study helps future researchers and medical professionals better understand cognitive mechanisms, allowing them to identify connections between dopamine levels and disorders such as anxiety, depression, ADHD and schizophrenia.

"We want to know, what are the drivers of what changes cognitive ability and function?" Frank said. "Our research is focused on carving nature at its joints, so to speak -- disentangling neural and cognitive functions to understand people's different thought processes and evaluate what's best for their needs, whether it's therapy or medication."