Brain

Childhood malnutrition in India remains a major problem. A new study shows that the problem is concentrated in specific geographic areas, which could help policymakers working to address the issue.

Malnutrition is a huge problem in India, with one in five children underweight for their height and nearly two in five children suffering from stunting, which is caused by undernutrition. Although the country is working to address the issue, India lags behind other countries at similar levels of development.

One reason that the problem has proved so intractable may be that malnutrition is not evenly spread across the country or even across states, but rather persists in smaller geographic clusters with high rates of poverty and undernutrition, according to a new study led by IIASA researcher Erich Striessnig in collaboration with former IIASA colleague Jayanta Bora, who is now working at the Indian Institute of Dalit Studies (IIDS), New Delhi.

"Malnutrition is a humanitarian crisis in India. It poses a huge burden to the affected individuals, communities, as well as society as a whole," says Striessnig. "It also poses an obstacle to development. Children growing up under detrimental living conditions will perform poorly at school and are likely to be less productive later on when they enter the labor force, deteriorating the developmental outlook for the country as a whole."

The study, published in the journal Spatial Demography, was made possible by new data from the Indian National Family Health Survey, which for the first time included comparable information down to the district level.

"This created a chance to look at the distribution of childhood malnutrition across India at much finer spatial scales than previously available," says Striessnig.

To explore the data, the researchers used cluster analysis on a wide range of socioeconomic factors. Through this analysis, a pattern of marked spatial clustering among Indian districts emerged. Rather than being evenly spread across states or the nation as a whole, malnutrition is highly concentrated, with districts across most of southern India providing relatively better conditions for growth and improved nutritional status, as compared to districts in the central, particularly rural parts of India along the so called "tribal belt".

"It's not surprising that the bad living conditions of those around you also affect your own chances to improve your living conditions and those of your children. If everyone around you lives in a state of disempowerment, the government is unlikely to come and help you. The degree of segregation affects the vulnerability of the worst off," explains Bora.

The new study also finds that childhood malnutrition was correlated with lower levels of maternal education and access to mass media, as well as, unsurprisingly, household poverty and whether the mother was also underweight.

"What surprised us the most was the clear geographic demarcation of clusters. Without adding any information on climatic zones, which is one of the more important aspects to look into next, the model still identifies very regionally marked clusters," says Striessnig.

The study could help Indian decision makers to create more strategic investments to more effectively address the problem at the lower administrative level. "The representatives of political parties should pay more attention to this, so that it could help in enriching the sustainable development goals for India," says Bora.

Bora adds, "Policy interventions are often guided towards the state level. But states in India are gigantic and by looking at states, one might miss substantial sub-state heterogeneity in the living conditions of children growing up, particularly between urban and rural areas."

In the past few decades, it was discovered that the rate at which we age is strongly influenced by biochemical processes that, at least in animal models, can be controlled in the laboratory. Telomere shortening is one of these processes; another one is the ability of cells to detect nutrients mediated by the mTOR protein. Researchers have been able to prolong life in many species by modifying either one of them. But what if we manipulate both? A team from the Spanish National Cancer Research Centre (CNIO) now studied it for the first time, with unexpected results. Blocking nutrient sensing by treatment with rapamycin, an mTOR inhibitor, delays the ageing of healthy mice but, curiously, it worsens diseases and premature ageing that occur in mice with short telomeres. This finding has important implications for the treatment of diseases associated with short telomeres, but also for age-related diseases that are also associated with short telomeres. The study, done by the Telomeres and Telomerase Group headed by Maria Blasco at the CNIO, is published in Nature Communications with Iole Ferrara-Romeo as the first author.

Telomeres, at the end of chromosomes, preserve the genetic information of the cells. They shorten with age until they can no longer fulfil their function: the cells stop dividing and the tissues age since they are no longer able to regenerate.

On the other hand, the ability of cells to detect nutrients depends on a cascade of biochemical signals that activates the mTOR protein. This is a fundamental molecular pathway because it controls the growth of cells and the whole organism. It also plays a central role in ageing: if the mTOR pathway is blocked, ageing slows down. But this had only been demonstrated in young and healthy mice. What happens when mice have short telomeres, associated with ageing and certain diseases called telomere syndromes?

An mTOR inhibitor is rapamycin, a drug that prolongs life in yeasts, flies, worms and mice, and that significantly reduces the incidence of cancer in mice with normal telomeres.

The researchers wanted to test whether rapamycin could also extend the life of mice with short telomeres, but they found that the opposite happens: they age up to 50% faster. This basic finding allowed the authors to discover that mTOR is, in fact, important for the survival of mice with short telomeres, and therefore blocking it has a negative effect.

Implications for the treatment of the 'telomere syndromes'

But it also has clinical implications. Short telomeres are associated with or are the cause of the so-called telomere syndromes, diseases such as dyskeratosis congenita, aplastic anaemia, pulmonary and hepatic fibrosis, and other degenerative diseases for which few treatments exist. Blocking the mTOR pathway with rapamycin was considered a possible strategy against these diseases, but the results of the study suggest that it would not work and could even be harmful.

"In light of all the beneficial effects of inhibition of the mTOR pathway in extending longevity, here we set to address whether rapamycin treatment could also ameliorate the premature ageing phenotypes and the decreased lifespan of telomerase-deficient mice with short telomeres," the authors write. But, although "in control mice [with normal telomeres] rapamycin extended the lifespan, in mice with short telomeres it reduced it. We did not expect that. These results are of clinical interest for human diseases in which patients have critically short telomeres," explain Maria Blasco and Paula Martínez, authors of the paper.

More sensitive to nutrients

Another surprise for the researchers was the finding that in mice with short telomeres the mTOR pathway is hyper-activated, that is, their cells are more sensitive than usual to the presence of nutrients. The authors interpret that it is precisely the greater ability to detect nutrients that allows these mice to survive, an unexpected conclusion that could open new avenues for research in the treatment of telomere syndromes.

"This discovery indicates that hyper-activation of the mTOR pathway is necessary to compensate for problems arising from having short telomeres," Blasco explains.

In fact, it is known that mTOR is also hyper-activated in some organs of elderly mice, which may indicate that this is a phenomenon associated not only with abnormally accelerated ageing but also with natural physiological ageing.

By studying the sick hearts removed from four patients undergoing heart transplants, researchers have identified a protein and a signaling pathway that may contribute to sudden death in an inherited form of heart disease.

The patients were receiving new hearts to treat Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a rare genetic disease that causes abnormal heart rhythms (arrhythmias) and increases the risk of sudden cardiac death, particularly during exercise or emotional excitement. ARVC affects between 1 in 1,000 and 1 in 1,250 people and is a leading cause of sudden death among young athletes who have no prior symptoms or cardiovascular disease diagnosis.

"We have identified a new pathway in heart cells that explains how arrhythmias occur in patients with ARVC," says Long-Sheng Song, MD, professor of internal medicine at the University of Iowa Carver College of Medicine and one of the leaders of the study team that included researchers from the UI and the Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China. "We hope that new drugs targeting this pathway can now be developed, which might help us treat this devastating, progressive disease more effectively."

The team led by Song at the UI and Shihua Zhao, MD, at the Chinese Academy of Medical Sciences and Peking Union Medical College in China published their findings March 3 in the journal Circulation.

Current treatment of ARVC involves using medication or implantable cardioverter defibrillator devices to prevent the dangerous arrhythmias. However, because the molecular mechanisms that cause the arrhythmias are not well understood, there are no treatments that target the underlying problem.

By comparing cellular proteins in the hearts removed from the ARVC patients to proteins in healthy hearts, Song and his colleagues discovered a significant reduction in the levels of a protein called integrin β1D in ARVC heart muscle cells. This difference was not seen in other types of heart disease such as hypertrophic cardiomyopathy and ischemic heart disease.

To study the role of integrin β1D, the researchers created genetically modified mice that lacked the protein in their heart muscle cells. At rest, the mice appeared to have normal heart function, but under stress or exertion, mice lacking integrin β1D were more likely to develop arrhythmias.

Overall, the study found that loss of integrin β1D prevents the mouse heart muscle cells from properly controlling the calcium levels that are critical for maintaining normal heartbeat. Increased heart rate or stress made the faulty calcium control worse in the mouse hearts. The team found that integrin β1D helps control normal calcium signaling by stabilizing another important heart protein called RyR2. Gene mutations that disrupt the RYR2 protein cause many heart conditions that involve arrhythmias and lead to heart failure.

The findings implicate the loss of the integrin β1D protein as a possible cause of ventricular arrhythmias in ARVC patients.

The team was also able to connect the loss of the integrin protein to a set of genetic mutations that cause ARVC in people. These mutations affect a so-called desmosomal protein that helps to form tight end-to-end contacts between heart muscle cells. The new study suggests that ARVC-causing mutations in a desmosomal protein result in the activation of a signaling pathway, which in turn leads to the loss of the integrin beta 1D protein.

"Our findings suggest that preventing the loss of integrin β1D using existing or new drugs to inhibit this signaling pathway might provide a way to treat ARVC," Song says.

The next step for the research team will be to use their mouse model to identify compounds that target the signaling pathway and alter integrin β1D levels and calcium control and see if these compounds can also block or prevent the development of ARVC.

Distributional semantics obtains representations of the meaning of words by processing thousands of texts and extracting generalizations using computational algorithms. Despite the popularity of distributional semantics in such fields as computational linguistics and cognitive science, its impact on theoretical linguistics has so far been very limited.

Research by Gemma Boleda, head of the Computational Linguistics and Language Theory (COLT) research group and ICREA research professor with the Department of Translation and Language Sciences at UPF, published in the journal Annual Review of Linguistics, provides a critical review of the abundant studies available on distributional semantics, putting special emphasis on the results that are relevant for theoretical linguistics, specifically in three areas: semantic change, polysemy and composition, and the grammar-semantics interface.

The research by Gemma Boleda seeks to connect theoretical and computational approaches to advance in the collective knowledge about how language works. One of the methods she has extensively researched is distributional semantics, which allows obtaining representations of words automatically. These representations have been shown to reflect significant linguistic properties, such as how two words are similar: a person will tell you that "dog" and "puppy" are very similar, and yet "dog" and "democracy" are hardly similar at all; distributional semantics will say the same, thanks to the fact that it induces linguistic properties based on texts written by people. Therefore, distributional semantics provides radically empirical representations.

Distributional semantics allows analysing the use of words and the evolution of their meaning

Distributional semantics provides an attractive, complementary framework to other, more traditional methods, not only because it is radically empirical but also because it provides multidimensional representations: two words can be likened on one dimension of meaning ("pizza" and "pasta" are types of food), or on another ("pizza" and "wheel" are round). To represent all aspects of meaning, multidimensional representations are needed. Distributional semantics can capture the common uses of two words, as well as their differentiating factors.

One of the important applications of distributional semantics in theoretical linguistics is the detection of changes in meaning. If language data from different periods are processed, such as books in English from 1900, 1950 and 1990, distributional semantics can be used to automatically detect some words' change in meaning. For example, the word "gay" in English at the beginning of the last century meant "happy" and has been used increasingly to mean "homosexual".

Aspects of research into distributional semantics that contribute to language theory

From the analysis of the works studied, Boleda concludes that there is sufficient evidence for the solid results of distributional semantics to be imported directly to research in theoretical linguistics.

"There are at least four aspects of research in distributional semantics that can contribute to language theory. The first aspect is exploratory: distributional representations can be used to explore large-scale data, for example by examining the similarity of words. The second is as a tool to identify specific cases of linguistic phenomena. For example, words can be identified whose meanings have changed when comparing the representations obtained from texts from different periods. The third is as a test bench: evaluating different linguistic hypotheses in distributional terms. The fourth and most difficult is the discovery of new linguistic phenomena or relevant theoretical trends in the data", the author explains in her work.

High blood pressure, inflammation, and the sensation of pain may rely in part on tiny holes on the surface of cells, called pores. Living cells react to the environment, often by allowing water and other molecules to pass through the cell's surface membrane. Protein-based pores control this flow.

One set of pores, called pannexins, are like tiny "black holes" of biology; their existence has been confirmed by computational and functional evidence but until very recently, they were never actually seen. They help cells communicate with and react to their surroundings, but until scientists see what they look like, it is hard to know how. Now, a team of researchers from Cold Spring Harbor Laboratory (CSHL) and Cornell University have developed very high-resolution images of these elusive structures.

"We all knew these pores had to exist... but there's definitely been some mystique about pannexins," said postdoctoral researcher Kevin Michalski, who co-led the project. "Without images, it's been really difficult to figure out exactly what these pores are doing."

Michalski spent more than six years trying to get a clear image of pannexins.

"I had spent so long trying to set up experiments without really being able to see what I was working with. That's what makes this so exciting," Michalski explained. "For the first time, we can definitely see this detailed structure--it's all new information."

Michalski and Johanna Syrjanen, also in the Furukawa lab at CSHL collaborated with the Kawate lab at Cornell University, and published their findings in the journal eLife. They used a technique called cryo-electron microscopy (cryo-EM) to capture a half-million images of a pannexin pore, called "pannexin 1," from many different angles. They then merged the images to form a three-dimensional model. Pannexin 1 is made up of seven identical proteins in a donut-like ring around a central pore.

Watch a video of the pannexin 1 model: https://www.youtube.com/watch?v=uvYjnHa_LPA

Researchers have hypothesized that pannexin 1 is responsible for releasing the signals that trigger a failing cell's self-destruction. These signals prompt macrophages to destroy the ailing cell, clearing the way for new cells to thrive. Without the replacement of ailing cells with new cells, organisms age.

"But what's interesting is that even cells that don't go through the process of self-destruction can have pannexins," Michalski said. "That means that there has to be some other important mechanisms that this pore is performing."

"The way pannexin 1 is shaped on a cell is different from another kind of pore that my lab recently revealed," added Professor Hiro Furukawa, who oversaw the research. "It appears that there are more kinds of pores than scientists originally anticipated. How and when they open and close are important questions to be explored."

The flow of water, salts, and other molecules into a cell across a pore regulates the cell's size. Cells that misregulate their size or water flow could contribute to high blood pressure, pain, and inflammation. Pannexins are also thought to allow much larger molecules to pass through their pores. Understanding how molecules negotiate their way through a pannexin could lead to new classes of drugs.

LOS ALAMOS, N.M., March 2, 2020--A new machine-learning computer model accurately predicts damaging radiation storms caused by the Van Allen belts two days prior to the storm, the most advanced notice to date, according to a new paper in the journal Space Weather.

"Radiation storms from the Van Allen belts can damage or even knock out satellites orbiting in medium and high altitudes above the Earth, but predicting these storms has always been a challenge," said Yue Chen, a space scientist at Los Alamos National Laboratory and principal investigator on the project jointly funded by NASA and NOAA. "Given that the Van Allen Probes, which provided important data about space weather, recently de-orbited, we no longer have direct measurements about what's happening in the outer electron radiation belt. Our new model uses existing data sets to 'learn' patterns and predict future storms so satellite operators can take protective measures, including temporarily shutting down part of or even the whole satellite to avoid damage."

This predictive model for megaelectron?volt (MeV) electrons inside the Earth's outer Van Allen belt builds on a previous model that successfully predicted radiation storms one day in advance. This new model, called PreMevE 2.0, improves forecasts by incorporating upstream solar wind speeds. It predicts future events by training on existing data sets from NOAA and Los Alamos satellites to learn important patterns of electron behavior.

"With the expectation that similar patterns may reveal themselves in the future, our model is capable of making predictions by capturing some critical signatures as a precursor to those future events," explained Youzuo Lin, a computational scientist at Los Alamos who developed the machine-learning algorithms for the model.

"By testing the model with multiple machine-learning algorithms, this work confirms the predictability of MeV electrons, as well as the robustness of using low-Earth-orbit electron observations to drive predictions," added Chen. "In addition, the framework set up in this work allows us to easily include more input parameters to predict more energetic electrons in the next step."

The machine learning framework developed for PreMevE 2.0 can also be applied to many broad applications that use time-related measurements, such as capturing earthquake patterns among large volumes of seismic time-series data, enabling detection of small earthquakes out of the noisy environments.

Recent progress in theoretical mineral physics based on the ab initio quantum mechanical computation method has been dramatic in conjunction with the rapid advancement of computer technologies. It is now possible to predict stability, elasticity, and transport properties of complex minerals quantitatively with uncertainties that are comparable or even smaller than those attached in experimental data. These calculations under in situ high-pressure (P) and high-temperature (T) conditions are of particular interest, since they allow us to construct a priori mineralogical models of the deep Earth. In the present article, we briefly review our recent accomplishments in studying high-P phase relations, elasticity, thermal conductivity and rheological properties of major lower mantle silicate and oxide minerals including (Mg,Fe)SiO3 bridgmanite, its high-pressure form post-perovskite, CaSiO3 perovskite, (Mg,Fe)O ferroplericlase, and some hydrous phases (AlOOH, MgSiO4H2, FeOOH). Our analyses indicate that the pyrolitic composition can be used to describe the Earth's properties quite well in terms all of densities, and P and S wave velocity. Computations also suggest some new hydrous compounds which could persist down to the deepest mantle and that the post-perovskite phase boundary is the boundary not only of the mineralogy but also of the thermal conductivity.

Chemical changes in the oceans more than 800 million years ago almost destroyed the oxygen-rich atmosphere that paved the way for complex life on Earth, new research suggests.

Then, as now, the planet had an "oxidizing" atmosphere, driven by phytoplankton - the "plants" of the ocean - releasing oxygen during photosynthesis.

However, new research from an international team including the University of Exeter and spanning Toulouse, Leeds, London and Nanjing, suggests ocean changes in the early Neoproterozoic era (from one billion to 800 million years ago) may have locked away phosphorus - a vital nutrient for life - limiting phytoplankton growth and oxygen release.

The study suggests the amount of phosphorus available remained "just sufficient" to support the oxidising atmosphere - preventing a return to the "reducing" (oxygen-poor) atmosphere that existed over a billion years earlier.

"Ocean chemistry in this period changed to become 'ferruginous' (rich in iron)," said Dr Romain Guilbaud, of CNRS (Toulouse).

"We know ocean chemistry affects the cycle of phosphorus, but the impact on phosphorus availability at this time hadn't been investigated until now.

"By analysing ocean sediments, we found that iron minerals were very effective at removing phosphorus from the water."

Phytoplankton growth also boosts atmospheric oxygen because, having split carbon and oxygen and released the oxygen, plants die and their carbon is buried - so it cannot recombine with oxygen to form carbon dioxide.

Despite reductions in photosynthesis and this organic burial of carbon, both due to limited phosphorus, the study suggests oxygen in the atmosphere dropped no lower than 1% of current levels - "just enough" to maintain an oxidizing atmosphere.

"Our observations suggest significant potential variability in atmospheric oxygen concentrations across Earth's 'middle age'," said Professor Tim Lenton, Director of the Global Systems Institute at the University of Exeter.

He added: "One question about the emergence of complex life is why it didn't happen sooner.

"Lack of oxygen and lack of nutrients are two possible reasons, and our study suggests both of these may have been the case in the early Neoproterozoic era.

"In fact, if phosphorus levels in the water had dropped any lower, it could have tipped the world back into a 'reducing' atmosphere suitable for bacteria but not for complex life."

A return to a "reducing" atmosphere would have reversed the Great Oxidation Event, which occurred about 2.5 billion years ago, during which photosynthesis by cyanobacteria in the oceans introduced free oxygen to the atmosphere.

Horseradish flea beetles use plant defense compounds, so-called glucosinolates, from their host food plants for their own defense. Like their hosts, they have an enzyme which converts the glucosinolates into toxic mustard oils. A research team at the Max Planck Institute for Chemical Ecology in Jena, Germany, has now found that these glucosinolates are present in all life stages of the horseradish flea beetle; however, the enzyme required to convert these into toxic substances is not always active. Although larvae are able to successfully fend off attack from a predator, such as the harlequin ladybird, pupae are predated because they lack enzyme activity (Functional Ecology, February 2020, doi: 10.1111/1365-2435.13548).

As their name suggests, horseradish flea beetles feed on horseradish, but also on other plants that are equipped with a so-called "mustard oil bomb", such as rapeseed, mustard and other cruciferous plants. This defensive mechanism is based on two components: glucosinolates (or mustard oil glucosides) - plant defense compounds - and the enzyme myrosinase. When the plant tissue is damaged, the non-toxic glucosinolates come into contact with the myrosinase, which converts the glucosinolates into toxic mustard oils, so the "bomb is triggered". The horseradish flea beetle copies the plant defense system by taking up non-toxic glucosinolates from its food plants, and producing its own beetle myrosinase (see our press release on the closely related striped flea beetles "Beetles that taste like mustard", https://www.ice.mpg.de/ext/index.php?id=1105&L=0, May 8, 2014). A team of scientists led by Franziska Beran, head of the Research Group "Sequestration and Detoxification in Insects" at the Max Planck Institute for Chemical Ecology in Jena, Germany, now wanted to find out whether all developmental stages, from egg to beetle, can defend themselves with their mustard oil bomb and whether it represents an effective protection against predators. Their experiments revealed that glucosinolates can be found in all life stages of the horseradish flea beetle. However, the beetle myrosinase was not active in all of them. The researchers determined myrosinase activity by measuring the sugars, which are cleaved off the glucosinolates by the myrosinase enzyme. These sugars accumulate over time.

„Larvae showed a high level of enzyme activity, whereas the activity could hardly be detected in pupae. The ability to fend off predators by using plant defense substances therefore differs considerably between the different life stages", Theresa Sporer, the first author of the study, describes the results. To find our whether the differences in enzyme activity are really important for an efficient defense, the scientists offered the larvae and pupae of the horseradish flea beetle to a voracious predator, the larvae of the harlequin ladybird. "What we observed in this experiment was impressive", Johannes Körnig, a co-author of the study, reports. "When a lady beetle larva attacks a flea beetle larva, it feeds only very briefly, then moves away from their prey and frequently vomits. They rather starve to death than feed on larvae which are protected by a mustard oil bomb." In contrast, pupae had no chemical protection and were eaten by ladybird larvae. Likewise, a comparison of larvae which had either stored glucosinolates or not, depending on which plant they fed beforehand, showed that these plant chemical compounds are in fact crucial for defense: Larvae that had stored glucosinolates were able to fend off predators, whereas larvae without glucosinolates were killed.

For the researchers, it was still surprising that pupae were not chemically protected. After all, during this developmental stage they are immobile and cannot escape. Therefore, one would expect that a particularly good chemical defense would compensate for the immobility of pupae. However, it is still unclear which predators feed on pupae. The scientists hypothesize that nematodes and microbial pathogens could be important natural enemies.

Further studies are planned to find out whether the beetle's mustard oil bomb can also be successfully used against enemies in the natural habitat of the horseradish flea beetle. Moreover, they would like to investigate which substances are important for the pupae's defense against their natural enemies and whether pupae deploy other defense mechanisms. The results will also be of interest for gardeners, since horseradish flea beetles are suspected to be responsible for the drop of yield in horseradish cultivation.

In response to stressors, individuals exhibit different coping styles, each characterized by a set of behavioural, physiological, and psychological responses. The active behavioural style refers to efforts to blunt the impact of stressors and is related to resilience to stress, whereas the passive behavioural style refers to efforts to avoid confronting stressors and is associated with vulnerability to psychopathology. This is a well-known scientific question, shortly called the "fight or flight". However, the biological basis of the brain has not been fully understood.

Recently, the research team led by Prof. ZHOU Jianging from University of Science and Technology of China (USTC) of Chinese Academy of Science (CAS) found that prefrontal corticotropin-releasing factor (CRF) neurons are recruited during behavioural challenges, and manipulation of CRF neurons motivates the selection of behavioural styles under challenges. They also demonstrated that activation of CRF neurons promotes persistent stress-resistant behaviours. The study was published in Neuron.

By using calcium imaging in vivo and cell-specific targeted viral-mediated gain- or loss-of-function tools, such as pharmacogenetic designer receptors exclusively activated by designer drugs (DREADD) approaches, the researchers investigated how mPFC CRF neurons regulate behavioural style selection during various stress in CRF transgenic mice.

The results showed that genetic ablation or chemogenetic inhibition of dorsal mPFC (dmPFC) CRF neurons increased immobility under the tail-suspension and forced-swimming challenges and induced social avoidance behaviour, whereas activation had the opposite effect on the same measures.

Furthermore, they found that increasing CRF neuronal activity promoted durable resilience to repeated social defeat stress.

These results uncover a critical role of mPFC CRF interneurons in bidirectionally controlling motivated behavioural style selection under stress. This study may point to novel therapeutic targets such as neural circuit modulation for treatment of major depression and post-traumatic stress disorder.

Bremer Canyon Marine Park is already known as a biodiversity hotspot for marine species such as whales and dolphins, however, a recent expedition focused on the deep sea has now revealed rich and diverse ecosystems inhabiting the cold waters deep within the canyon. Led by researchers from the University of Western Australia (UWA), these discoveries were only made possible by the philanthropic Schmidt Ocean Institute's (SOI) deep-sea remotely operated vehicle, SuBastian, which is capable of sampling depths to 4,500 meters.

The team strategically collected deep-sea corals, associated fauna, seawater, and geological samples from the abyssal depths (~4,000 meters) to the continental shelf (~200 meters). "We have already made a number of remarkable discoveries from the Bremer Canyon" said Dr Julie Trotter, the Chief Scientist from UWA who led the expedition. "The vertical cliffs and ridges support a stunning array of deep-sea corals that often host a range of organisms and form numerous mini-ecosystems".

These new discoveries are being integrated into a comprehensive package of biological, geological, and bathymetric data. Such rare records of these deep-sea habitats are a new and very important contribution to the Marine Parks, which will help managers as well as the broader community to better understand and protect these previously unknown ecosystems.

The deeper waters in the three oceans that surround Australia, including the world's largest barrier reef and submarine canyons, are largely unexplored. The expedition explored the Bremer, Leeuwin and Perth canyons, all of which have extensive fossil coral deposits, with the Leeuwin especially notable for a massive pedestal-like coral graveyard.

"This has global implications given these waters originate from around Antarctica which feed all of the major oceans and regulate our climate system" said Professor Malcolm McCulloch from UWA.

Australia has only one oceanographic vessel available for scientific research and no supporting deep sea underwater robots, which makes this expedition so important and rare.

Facing the Southern Ocean, the Bremer Canyon provides important information on the recent and past histories of climate change and ocean conditions in this region, as well as global scale events. Because the Southern Ocean completely encircles Antarctica, it is the main driver of the global climate engine and regulates the supply of heat and nutrient-rich waters to the major oceans. "A particular species of solitary cup coral was found during the expedition. This is significant because we are working on the same coral in the Ross Sea on the Antarctic shelf, in much colder waters", said collaborator and co-Chief Scientist Dr Paolo Montagna from the Institute of Polar Sciences in Italy. "This is an important connection between disparate sites across the Southern Ocean, which helps us trace changes in water masses forming around Antarctica and dispersing northward into the Indian and other oceans".

You can view some of the amazing species discoveries in 4K here. Additional high resolution images and Broll can be found here. You can learn more at https://schmidtocean.org/cruise/coralandcanyonadventure/.

Tsukuba, Japan - Angioimmunoblastic T-cell Lymphoma (AITL) is an intractable form of non-Hodgkin lymphoma with a bleak prognosis. In a recent study, researchers from the University of Tsukuba, Japan, have demonstrated that T-cell Receptor (TCR) signaling activated by specific gene mutations led to development of AITL-like lymphoma in experimental mice. Further results from a linked clinical trial suggest that the multi-kinase inhibitor dasatinib, used to treat specific leukemias, shows potential as an effective drug for this disease for relapsed or refractory AITL.

Lymphomas form a group of related cancers that affect the lymphatic system. They are classified according to the type of white blood cells (lymphocytes) affected as B-cell lymphomas or T-cell lymphomas. AITL is a rare and often aggressive T-cell lymphoma with a five-year survival of below 30%. Patients with AITL present with high fever, skin rash, and symptoms suggestive of immune activation. Many patients have specific altered genes including the DNMT3A, TET2, IDH2, and RhoA genes, though the exact role these gene mutations play in the development of the disease is not fully understood.

Researchers at the University of Tsukuba first showed that TET2 loss paired with expression of the G17V RHoA mutant in mice led to development of AITL-like lymphoma. By targeting the TCR pathway, dasatinib successfully suppressed disease progression in AITL model mice and prolonged survival. "Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment," says Dr Mamiko Sakata-Yanagimoto, Associate Professor at the department of Hematology, Faculty of Medicine, and a senior author of the study.

The researchers followed this with a phase 1 clinical trial involving patients with relapsed/refractory AITL following prior chemotherapy and/or autologous stem cell transplantation. Dasatinib, administered as a single drug, achieved partial responses in all evaluable patients; moreover, there were no previously undocumented safety concerns.

"Recently, many new drugs have been introduced as promising therapeutics for Primary T-Cell Lymphomas including AITL," says Professor Shigeru Chiba, main author of the study. "However, currently there are no monotherapies that satisfactorily improve overall survival in relapsed or refractory cases. Our work suggests that targeting the TCR pathway should be considered in developing AITL treatment strategies."

Dasatinib, an oral drug long used to treat specific Philadelphia chromosome-positive leukemias, is on the WHO Model List of Essential Medicines. Given the encouraging outcomes of this study, further research is needed to firmly establish its place amongst therapeutics for AITL, especially regarding efficacy against specific mutations as well as clinical applicability and safety profile.

Scientists have discovered the earliest known example of an animal evolving to lose body parts it no longer needed.

Mystery has long surrounded the evolution of Facivermis, a worm-like creature that lived approximately 518 million years ago in the Cambrian period.

It had a long body and five pairs of spiny arms near its head, leading to suggestions it might be a "missing link" between legless cycloneuralian worms and a group of fossil animals called "lobopodians", which had paired limbs all along their bodies.

But the new study - by the University of Exeter, Yunnan University and the Natural History Museum - reveals Facivermis was itself a lobopodian that lived a tube-dwelling lifestyle anchored on the sea floor, and so evolved to lose its lower limbs.

"A key piece of evidence was a fossil in which the lower portion of a Facivermis was surrounded by a tube," said lead author Richard Howard.

"We don't know the nature of the tube itself, but it shows the lower portion of the worm was anchored inside by a swollen rear end.

"Living like this, its lower limbs would not have been useful, and over time the species ceased to have them.

"Most of its relatives had three to nine sets of lower legs for walking, but our findings suggest Facivermis remained in place and used its upper limbs to filter food from the water.

"This is the earliest known example of 'secondary loss' - seen today in cases such as the loss of legs in snakes."

The Cambrian period is seen as the dawn of animal life, and the researchers were fascinated to find a species evolving to be "more primitive" even at this early stage of evolution.

"We generally view organisms evolving from simple to more complex body plans, but occasionally we see the opposite occurring," said senior author Dr Xiaoya Ma.

"What excited us in this study is that even at this early stage of animal evolution, secondary-loss modifications - and in this case, reverting 'back' to lose some of its legs - had already occurred.

"We've known about this species for about 30 years, but it's only now that we've got a confident grasp of where it fits in the evolutionary tree.

"Studies like this help us understand the shape of the tree of life and figure out where the adaptations and body parts we now see have come from."

Co-author Greg Edgecombe, of the Natural History Museum, said: "For several years we and others have been finding lobopodians from the Cambrian period with pairs of appendages along the length of the body - long, grasping ones in the front, and shorter, clawed ones in the back.

"But Facivermis takes this to the extreme, by completely reducing the posterior batch."

The Chengjiang Biota in Yunnan Province, south-west China has been a source of well-preserved Facivermis fossils.

Using these fossils, the study placed Facivermis in the Cambrian lobopodian group, which gave rise to three modern animal groups (phyla): Arthropoda (including insects, shrimps and spiders), Tardigrada (water bears) and Onychophora (velvet worms).

Washington, DC, February 27, 2020 - A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that the long-term stability of treatment gains for children and adolescents diagnosed with obsessive-compulsive disorder (OCD), participating in a stepwise manualized treatment, is excellent.

"OCD is a persistent and highly disabling psychiatric disorder and affects 0.25 to 4 percent of children and adolescents. Untreated, pediatric OCD can become chronic and disrupts the child's normal development, contributing to poor quality of life and functional impairment," said first author Karin Melin, PhD and Head Nurse at the Department of Child and Adolescent Psychiatry, Sahlgrenska University Hospital,

Gothenburg, Sweden. "Early diagnosis and treatment are crucial for the prevention of possible lifelong impairment, and these findings suggest that most participants respond well to treatment for pediatric OCD, and the long-term outcome is correspondingly good."

Immediate improvements in child and adolescent OCD symptoms following treatment in the study that included a first step of manualized cognitive-behavioral therapy (CBT). If needed, extended treatment with CBT, or a switch to pharmacotherapy with sertraline, was sustained and further improved over a three-year period after treatment.

Additional long-term improvements were also found in psychosocial functioning and a reduction in depressive symptoms associated with treatment.

"Single treatment with manualized CBT, seems to be the most beneficial and safest treatment to offer children and adolescents who initially present with OCD," added Dr. Melin.

These findings are based on results from The Nordic Long-term OCD Treatment Study . The study population consisted of 269 participants in the age 7-to-17 years of age who were diagnosed with OCD. All participants received individualized CBT for 14 weeks; non-responders to initial CBT were randomized to continue CBT or pharmacotherapy with sertraline for 16 weeks. Three years after initial CBT, 90 percent of participants were rated as responders and 73 percent were in clinical remission.

Many of the membrane proteins in eukaryotic cells are decorated with complex sugar trees called glycans. In addition to being extremely diverse, these sugar trees serve as a way to identify the respective organism, a cell type or its stage of maturity. For instance, the various blood groups in humans feature different glycans.

Complex sugars that are attached to lipids form a special class of glycans. In biology, these are known as lipid-linked oligosaccharides, or LLOs. LLOs are made up of a fat molecule embedded in the cell membrane and a sugar structure that extends either into the lumen of cell organelles or extracellularly.

Researchers from ETH Zurich, the University of Bern and the University of Chicago have now elucidated the structure of one of the enzymes responsible for the formation of LLOs. Their study has just been published in the latest issue of the journal Nature.

Modular protein architecture

The enzyme in question, known as ALG6, belongs to a superfamily of enzymes that the researchers call glycosyltransferases of the category C. Embedded in cell membranes, these link simple sugar molecules with other sugars in order to build sugar trees. They also link sugar molecules with proteins. In this capacity, glycosyltransferases play several key biological roles in all kinds of organisms, ranging from bacteria and fungi to highly developed mammals.

This enzyme superfamily had been a long-standing mystery to biologists because its individual members share hardly any structural motifs. The only things they do have in common is that they are membrane proteins that transfer sugars from one molecule to another, and that the sugars used for this transfer are always attached to lipids.

Based on the structure of ALG6, the group led by ETH Professor Kaspar Locher has now discovered that the members of this enzyme family have a modular design. Their research indicates that ALG6 and its relatives are made up of two modules: one whose structure is preserved during development, and a second, structurally variable module.

"We believe it's this modular design that helped these enzymes to evolve in different directions and, in turn, adapt to a large variety of different substrates," says Joël Bloch, an ETH doctoral student and the lead author of the study.

The findings finally explain the mechanism behind the enzyme family. "Our study has far-reaching implications for cell biology and for the production of therapeutic substances based on glycobiology," Bloch explains. These insights will be especially valuable in antibody engineering, which is currently of great interest to the pharmaceutical industry. They will also benefit the production of customised glycans in general, which are important for therapeutic proteins such as antibodies.

A record in cryo-electron microscopy

The researchers also see their results as a breakthrough in determining the molecular structures of proteins using cryo-electron microscopy (cryo-EM). In 2017, the Swiss researcher Jacques Dubochet received the Nobel Prize in Chemistry for his contribution to this groundbreaking technology, which has since become the method of choice for the structural elucidation of large molecular complexes.

Determining the structures of small proteins at high resolution, especially those embedded in membranes, had not been possible using cryo-EM because measurements taken of particles below a certain mass do not permit precise structural calculations.

Working together with a research group from the University of Chicago, the ETH team have now found a solution to this problem. In collaboration with the Chicago-based researchers they produced a synthetic antibody that binds to ALG6. This antibody increased the mass of the ALG6 enzyme such that its structure could be determined in high resolution using cryo-EM.

"With our approach, we currently hold the world record for the highest structural resolution obtained for a membrane-bound complex of this size," Locher says with a hint of pride. He explains that these advances with cryo-EM will enable many other scientists to elucidate the structures of small membrane proteins: "Our approach paves the way for the scientific community to make rapid progress in the study of membrane proteins associated with a wide range of diseases."

A chemo-enzymatic toolbox

As if that were not enough, the ETH researchers, in collaboration with chemists from the University of Bern, have now developed methods for synthesising highly complex lipid-linked oligosaccharides in the lab - something that had not been possible with conventional synthesis methods in organic chemistry.

As a result, the researchers have now gained new insight into the essential cellular pathway of LLO biosynthesis, helping them explain how cells build complex glycans. "This marks a milestone in glycobiology that could form the basis for many glycobiologists' future research and for the production of glycoproteins," Locher says.