Culture

What The Study Did: How commonly reported gastrointestinal symptoms were in patients with COVID-19 and viral RNA shedding was detected in these patients' stool are examined in this systematic review and meta-analysis.

Authors: Sravanthi Parasa, M.D., of Swedish Medical Center in Seattle, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.11335)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

A new study released today in Scientific Reports announced the surprising discovery of abundant, well-preserved 110-120-million-year-old footprints, belonging to a large bipedal ancestor of modern-day crocodiles from the Lower Cretaceous Jinju Formation of South Korea. The team of palaeontologist trackers that made the discovery includes researchers from Korea, Australia, and University of Colorado Denver professor, Martin Lockley.

While palaeontologists knew that some crocodiles from the "age of dinosaurs" were more adapted to life on land than their modern relatives, these were small animals about one meter long with footprints showing they walked on all fours.

"It shocked us to learn that the trackways represent bipedal animals 3-4 meters long," said team leader Professor Kyung Soo Kim, Chinju National University of Education.

The team named the 18-24 cm-long tracks Batrachopus grandis emphasizing the large size in comparison with much older and smaller 2-3 long cm tracks of the Batrachopus type, commonly found in the Jurassic of North America.

"Nobody expected such large bipedal crocs," said Martin Lockley, a University of Colorado professor who has been studying fossil footprints in Korea for 30 years. "The Jinju Formation is so rich in tracks; you can read the entire ecology."

The discovery of well-preserved tracks is important to palaeontologist trackers because they show details of skin impressions as clear as if made yesterday. Tracks also read the pattern of pads, showing foot bone structure and the tell-tale narrowness of trackways which show a bipedal gait, different from the sprawling posture of modern crocodiles. There has even been evidence from parallel trackways that show they may have travelled in social groups, just like their dinosaur cousins.

Among with the remains of some of the oldest terrestrially adapted crocodiles, are large Triassic species, more than 200 million years old, that some palaeontologists think may have been bipedal, based on anatomy.

"The Korean trackways prove this hypothesis, at least for the Cretaceous Period," said co-author of the study, Anthony Romilio. "It also proves this adaptation was effective for millions of years, even with big fierce dinosaurs running around."

The new study has also solved a tracking mystery dating back to 2012, when some poorly preserved tracks of a bipedal animal were first found in another South Korean rock unit, described as "enigmatic." There was debate over whether the giant pterosaurs were bipeds, quadrupeds or possibly even pterosaurian or human.

We move our eyes several times per second. These fast eye movements, called saccades, create large image shifts on the retina - making our visual system work hard to maintain a stable perceptual world. Remapping the retinal image compensates for this; however, errors in actual eye movements cause image shifts, even with remapping.

To do this, our eyes reduce sensitivity to the displacement of visual stimuli during saccades using a process called Saccadic Suppression of Displacement (SSD). However, SSD remains a mystery to researchers. A research team at Tohoku University's Research Institute of Electrical Communication, led by Professor Satoshi Shiori, investigated the mechanisms underlying SSD.

In their psychophysical experiment (Figure 2), an observer first stared at a fixation point for a random duration between 500 and 1300ms. After the fixation point disappeared, the observer had to shift their eyes to a target disc at the other side of the monitor. The target disc moved its location slightly during the observer's saccadic eye movement (about 500 ms), and the observer was asked to judge the direction of target disc displacement (either left or right). Researchers varied the target disc contrasts, before and after saccadic movements separately, to manipulate the retinal input strength. Furthermore, they analyzed the observer's accuracy to detect displacement at each contrast level.

Interestingly, the results show two distinct contrast effects which informed us about the involvement of two visual pathways. Higher contrast in pre-saccadic stimuli enhanced observers' sensitivity to detect visual motion, which is the typical contrast effect on vision. However, an opposite contrast effect was discovered for post-saccadic visual stimuli: higher contrast led to lower detection sensitivity. The research group explains the results successfully with a model which includes two major pathways of early vision: parvo-pathway and magno-pathway. In this model, the signals in the magno-pathway are responsible for detecting displacements while the signals in the parvo-pathway suppress erroneous motion information across saccades. SSD occurs when parvo-pathway signals suppress magno-pathway signals immediately after a saccade.

The understanding the mysterious phenomenon, visual stability across saccades, would help future AI/robots to perceive the world as we do.

Leesburg, VA, June 11, 2020--An open-access article published in the American Journal of Roentgenology (AJR) by radiologists in Singapore recommends a number of applied updates to the workflow of diagnostic ultrasound (US) to prevent nosocomial transmission of coronavirus disease (COVID-19) to frontline US service providers, who could inadvertently become vectors for onward transmission.

According to first author Apoorva Gogna and colleagues at Singapore General Hospital, "inpatient US services are segregated into the tertiary hospital and a colocated community hospital," adding that rooms with negative pressure ventilation are dedicated for isolation case scans. With all inpatient scans vetted for clinical urgency and COVID-19 status, patients not suspected of having COVID-19 arrive at a specified US imaging center via predefined route.

Suspected and confirmed COVID-19 cases, as well as intensive care patients or those in reverse isolation due to an immunocompromised state, receive portable bedside US by a sonographer and an attending radiologist. "This is in contrast to our regular inpatient portable US workflow in which a trained sonographer performs the scan alone and uploads the images (usually for several patients consecutively), and the images are then sent to a dedicated radiologist for reporting," explained Gogna et al. Acknowledging that throughput is diminished when an on-duty radiologist and a sonographer work in tandem, Gogna maintains that this sacrifice ensures neither repeat scans nor additional images will be necessary.

Before entering the patient's room, US equipment (e.g., battery, probe, gel) is inspected to prevent failure during the examination, then covered with disposable plastic; in the room, the two imaging staff are designated nonpatient contact and direct patient contact.

To help balance speed and clinical relevance, abbreviated scan protocols are acceptable, although Gogna points out that scanning time may not be significantly shortened. Sick patients may not be able to fully cooperate with the examination, and greater attention must be paid to safeguard against breaks in staff protection.

Meanwhile, outpatient US services at Singapore General Hospital are physically segregated into two locations (general US and subspecialty US), and every outpatient request is vetted and prioritized according to clinical urgency. To prevent cross contamination, inpatients are not allowed to move to the outpatient scan area. Gogna advises simple steps, such as rearranging the seating in outpatient waiting areas, to help US departments reinforce social distancing guidelines.

As of June 2020, all patients and visitors to Singapore General Hospital are required to wear face masks, and present policy restricts each patient to one accompanying person.

US staff--mostly segregated by location or by time--can be assigned to standby teams to cover any personnel shortage. As Gogna et al. note, "segregating manpower into redundant functional teams allows continued provision of essential services in the unfortunate event of intrahospital transmission that could require coworkers to be quarantined." Because staff segregation "does significantly affect department workload," the authors of this AJR article suggest reducing elective case listing.

Aquatic internet that sends data through light beams could enable divers to instantly transmit footage from under the sea to the surface.

The internet is an indispensable communication tool, connecting tens of billions of devices worldwide, and yet we struggle to connect to the web from under water. "People from both academia and industry want to monitor and explore underwater environments in detail," explains the first author, Basem Shihada. Wireless internet under the sea would enable divers to talk without hand signals and send live data to the surface.

Underwater communication is possible with radio, acoustic and visible light signals. However, radio can only carry data over short distances, while acoustic signals support long distances, but with a very limited data rate. Visible light can travel far and carry lots of data, but the narrow light beams require a clear line of sight between the transmitters and receivers.

Now, Shihada's team has built an underwater wireless system, Aqua-Fi, that supports internet services, such as sending multimedia messages using either LEDs or lasers. LEDs provide a low-energy option for short-distance communication, while lasers can carry data further, but need more power.

The Aqua-Fi prototype used green LEDs or a 520-nanometer laser to send data from a small, simple computer to a light detector connected to another computer. The first computer converts photos and videos into a series of 1s and 0s, which are translated into light beams turning on and off at very high speeds. The light detector senses this variation and turns it back into 1s and 0s, which the receiving computer converts back into the original footage.

The researchers tested the system by simultaneously uploading and downloading multimedia between two computers set a few meters apart in static water. They recorded a maximum data transfer speed of 2.11 megabytes per second and an average delay of 1.00 millisecond for a round trip. "This is the first time anyone has used the internet underwater completely wirelessly," says Shihada.

In the real world, Aqua-Fi would use radio waves to send data from a diver's smartphone to a "gateway" device attached to their gear. Then, much like a booster that extends the WiFi range of a household internet router, this gateway sends the data via a light beam to a computer at the surface that is connected to the internet via satellite.

Aqua-Fi will not be available until the researchers overcome several obstacles. "We hope to improve the link quality and the transmission range with faster electronic components," explains Shihada. The light beam must also remain perfectly aligned with the receiver in moving waters, and the team is considering a spherical receiver that can capture light from all angles.

"We have created a relatively cheap and flexible way to connect underwater environments to the global internet," says Shihada. "We hope that one day, Aqua-Fi will be as widely used underwater as WiFi is above water."

Highlights:

In 2018 scientists from Gladyshev lab specializing in aging research started a collaboration with Insilico Medicine resulting in a widely-publicized proof of concept microbiomic aging clock ;

The clock has been validated on multiple independent data sets;

The clock was shown to be biologically-relevant and used to demonstrate that diabetic patients look older than their chronological age;

The study was published in iScience and is expected to be used in new data analysis tools for COVID-19 and longevity research;

June 11th, 2020 - Recent advances in deep learning have allowed AI algorithms to outperform humans in image, text, and voice recognition. One particular use for AI in biology is deep aging clocks. Deep aging clocks are trained on large samples to predict human biological age using different data types, such as: pictures, videos, voice, blood biochemistry, gene and protein expression, and MRI. In a study recently published in iScience, Harvard and Insilico Medicine scientists used thousands of whole genome sequencing samples from gut bacteria to develop and validate a new deep microbiomic aging clock. This new tool indicates that the age of the host is a significant contributor to the gut community dynamics.

Over the last decade human gut microbiome studies have produced multiple surprising results. The bacteria in our gut are now known to be major contributors to the immune function, brain development and activity, central metabolism, obesity pathogenesis and many other processes. The growing realization of the role microbiota plays in human health makes it essential to understand what factors shape gut communities and how to manipulate them.

Such factors include the mode of birth, diet, physical activity and age. The effect age elicits on microflora dynamics is much better understood for the early stages of life. During the first year of life all people are much more similar in terms of diet and behaviour, compared to adults. Consequently, their gut flora goes through clearly defined stages. But upon transitioning to adulthood, multiple confounders such as diet, tobacco and alcohol consumption, and level of physical activity make individual microfloras extremely diverse. The NIH Human Microbiome Project has shown that there is no core community in adult guts, although the various combinations of microbial species tend to have similar functions and metabolic capabilities.

Multiple studies have identified some age-related trends in gut microflora. However, the findings usually have unclear general applicability due to localized sampling. In a joint project between Insilico Medicine and the laboratory of Vadim Gladyshev at Brigham and Women's Hospital and Harvard Medical School, the data from 13 public studies on human gut microbiome were aggregated to explore the possibility of developing an aging clock based on the microflora relative abundance profiles.

The initial attempt to predict chronological age based on gut community species composition was published in BioRxiv in December 2018. Since then the team further improved their approach and recently published their results in the iScience journal. More than 1100 species-level microflora compositions were used to train a Deep Neural Network in a cross-validated manner. The resulting ensemble predicts hosts' age in an independent data set collection with a mean error of 5.9-6.8 years.

The published intestinal age predictor proves that there are microflora succession patterns associated with age progression in the adult. The described workflow can be used to recreate similar models with data from other platforms and explore the effect of specific bacterial taxa on the course of human aging in a more controlled setting. The authors also suggest the ways to identify the microbes with potential to accelerate or slow down aging.

"We are happy to collaborate with the Gladyshev lab on this new microbiomic aging clock, which is the first of its kind. The development of this clock was a long and tedious journey as we originally thought that it would be impossible to build and after the demonstration of the first proof of concept, it took two years to refine and validate. We hope that the demonstrated approach will be used for COVID-19 research and later for longevity research for tracking the effects of different interventions and foods on the predicted intestinal age", said Alex Zhavoronkov, PhD, CEO of Insilico Medicine.

The reported aging clock can be accessed at aging.AI. Insilico Medicine aims to continue developing microbiomic tools and is planning to release COVIDOMIC -- a tool for exploring variables with an effect on the COVID-19 infection outcome, including those derived from patients' respiratory microbiome.

Improving the prediction of survival indicators in patients with breast cancer using tools from artificial intelligence and probabilistic modelling is the aim of ModGraProDep, an innovative system presented in a study led by Ramon Clèries, lecturer at the Department of Clinical Sciences of the Faculty of Medicine and Health Sciences of the University of Barcelona and member of the Oncology Master Plan/ICO-IDIBELL. The study has been published in the journal Artificial Intelligence in Medicine.

The new technology has been carried out by a team of experts on epidemiology, oncology and data management of the Oncology Master Plan - IDIBELL, the University of Barcelona, the Technical University of Catalonia, the Catalan Institute of Oncology (ICO), the Girona Biomedical Research Institute (IDIBGI), the University of Girona, the University of Alicante, the Epidemiology and Public Health Networking Biomedical Research Centre (CIBERESP), Carlos III Health Institute, the University Hospital Sant Joan de Reus, the Medical Oncology Service of ICO Girona, the Cancer Registry of Girona and Tarragona and the entity MC Mutual.

Mathematic modelling: new frontiers in the fight against cancer

One of the applications of numeric modelling for clinical indicators on oncology is the creation of predictive models to help oncologists and doctors to classify and value future scenarios of evolution in the patients with cancer. In this context, the prediction of survival in patients -with specific variables and ages- is a decisive element to consider treatments and identify subgroups among the patients. However, this information is sometimes estimated through numeric modelling since there is not enough sample population to calculate these indicators specifically.

The application of the new ModGraProDep Technology (Modelinng Graphical Probabilistic Dependencies) has led to two studies coordinated by the lecturer Mireia Vilardell, from the Section of Statistics at the Department of Genetics, Microbiology and Statistics of the Faculty of Biology of the UB, and the researcher Maria Buxó, from IDIBGI.

In the first case, ModGraProDep enables users to identify the structure of the database and to create a "synthetic" population of patients with the demographical features of the original cohort. With this new approach, they can identify potential patterns of patients and calculate indicators (for instance, the survival of a patient depending on the values of his or her variables). In a second study, ModGraProDep reveals itself as a new technology which can allocate values in a probabilistic manner in variables for which there was no information gathered yet.

The scientific team has designed a web application of great clinic interest in the field of oncology that enables having a prediction of indicators on survival and risk of cancer mortality -and other causes- of each patient for a maximum period of twenty years.

Newly discovered creatures can often be as impressive and exciting as the ones from the Japanese movies and shows. Many of those fictional characters, including inhabitants of the famous Pokémon universe, might have their analogues among the real animals native to Japan. Maybe, a new species of the dogfish shark published in the open-access journal Zoosystematics and Evolution is also "a real Pokémon" to be?

A new deep-water dogfish shark: Squalus shiraii, was discovered in the tropical waters of Southern Japan by an international team of scientists, led by Dr. Sarah Viana from South African Institute for Aquatic Biodiversity.

The new shark has the body length of 59-77 cm and some unique characteristics such as tall first dorsal fin and caudal fin with broad white margins. Currently, the species is known exclusively as a Japanese endemic, occurring in the tropical shallow waters of Southern Japan in the North-western Pacific.

Spurdogs represent commercially important for the world fish trade taxa. They are caught for a range of purposes: consumption of meat, fins and liver oil. Despite their high occurrence, the accurate identification data of species is scarce, population threats and trends remain unknown.

Japan currently represents one of the world's leading shark fish trade countries, though, during the last decades the amount of shark catches is decreasing and over 78 elasmobranch species traded in Japanese shark fin markets are now evaluated as threatened.

The new species Squalus shiraii previously used to be massively misidentified with shortspine spurdog, due to the resembling shape of body, fins and snout length. However, there are some differences, defining the specificity of the new species.

"Squalus shiraii has body brown in colour, postventral and preventral caudal margins whitish, dorsal and ventral caudal tips broadly white and black upper caudal blotch evident in adults. S. mitsukurii has body conspicuously black to dark grey and caudal fins black throughout with post-ventral caudal margin fairly whitish and black upper caudal blotch not evident in adults", shares lead author Dr. Viana.

Scientists propose the name for the newly described species as Shirai's spurdog in honor to Dr. Shigeru Shirai, the former Japanese expert of the group.

Japan -- Every second of every day, countless biochemical reactions take place in our bodies' cells. The organization of this complex system is the result of billions of years of evolution, fine-tuning our functions since the first primordial organisms.

One such vital reaction is 'methylation', where a methyl group -- a carbon atom linked to three hydrogen atoms -- attaches itself to a target molecule. Methylation is involved in the regulation of everything from DNA to proteins, and it is so vital that it can be found in all living organisms.

In a recent paper published in Communications Biology, a team of researchers lead by Jean-Michel Fustin and Hitoshi Okamura from Kyoto University's Graduate School of Pharmaceutical Sciences has uncovered an intimate connection between methylation and the body's circadian rhythms: a link that exists even in organisms that don't traditionally 'sleep', such as bacteria.

"Disfunction in methylation can cause any number of pathologies, from atherosclerosis to cancer," explains Fustin. "Previously we discovered that inhibiting methylation in mice and human cells disrupted their body clocks."

Methylation and the circadian rhythm, he adds, are ancient mechanisms retained in many organisms from bacteria to humans. "So, we hypothesized that the link between the two was also ancient."

The team began by collecting cells and tissue samples from different organisms and measuring their biological rhythms. On average, all organisms run on periods of 24 hours.

The next step was to find out what happens when methylation is disrupted, and as anticipated, significant alterations in the circadian clock were detected in all cell types, including in plants and algae. However, cyanobacteria -- photosynthetic bacteria -- seemed relatively resistant.

"The methylation pathway in bacteria is slightly different from other organisms. But when an alternative compound inhibiting a different part of methylation was used, the circadian clock was indeed strongly affected there as well," Fustin continues.

Applying their findings, the team then took a gene that is key in controlling bacterial methylation and introduced it into mouse and human cells. Exceptionally, the bacterial gene was able to protect the cells from the first methylation inhibition compound, with no alterations observed in circadian rhythms.

"Not only did we find the evolutionarily conserved link between two ancient biological pathways -- methyl metabolism and biological clocks -- but we also opened the door to a possible new treatment for methylation deficiencies," concludes Okamura.

"All organisms are more alike than you might think, and knowledge about how we evolved will allow us to better understand ourselves and the natural world."

When an embryo develops, a wide variety of proteins and enzymes trigger a series of biochemical reactions. The development of the lymphatic vasculature is crucially dependent on one specific protein - the growth factor VEGF-C. In order to become biologically active and to initiate downstream signalling events, the protein must first undergo processing steps. Thus far it was unclear, however, how and where the necessary factors come together that are required for VEGF-C activation, and which cell types provide these individual factors during development.

Using the zebrafish model, an international team of researchers has now gained new insights into how and at which spots the individual protagonists of the VEGF-C signalling pathway need to interact with each other in the embryo, in order to allow proper lymphatic vasculature development. The researchers identified special cells in the connective tissue that, at defined spots in the embryo, produce the important protein VEGF-C itself, as well as two -protein-processing enzymes which can activate the VEGF-C protein. In the case of one of these proteins, it was previously completely unknown that it had this function.

"The cells we have identified, the fibroblasts, represent what appear to be 'hot spots' for the occurrence of the activated protein," says Dr. Andreas van Impel from the University of Münster, who led the study. The results provide not only fundamental new insights into how the lymphatic system develops, but also, conversely, has relevance for human diseases. If the signalling pathway is miss-regulated in humans, genetically caused forms of lymphoedema will develop. Also, cancer cells can employ the lymphatic vessels to metastasize." If it turns out that a comparable fibroblast population is present in humans as well, our findings could impact future approaches to treat a variety of lymphatic related diseases," says Andreas van Impel. The study has been published in the journal "Nature Communications".

Background and method:

Worldwide, there are around a thousand groups of researchers working with zebrafish. These fish are suitable to investigate how an organism develops - including the bones, blood vessels and the lymphatic system. As fish embryos develop outside the womb and are transparent for a few days, the researchers can precisely monitor changes in development and identify connections with humans.

In their current study, the researchers investigated the protein VEGF-C, which is important for lymphatic vessel growth. In order for it to become biologically active, it has to be processed which means parts of the protein need to be cleaved off. VEGF-C can only bind and activate its receptor once two so-called pro-domains have been removed. The enzymes which process the protein are called proteases. In their study, the researchers examined the role of the secreted proteases ADAMTS3 and ADAMTS14 during the activation of VEGF-C.

Using state-of-the-art confocal microscopy, the researchers showed that embryos lacking both proteases as a result of genetic mutations fail to form lymphatic vessels - which led the researchers to conclude that the processing of VEGF-C can be carried out not only (as previously assumed) by ADAMTS3, but also by the related protease ADAMTS14.

This was something that the researchers found not only for the zebrafish proteins, but also in experiments with human cell culture lines. "Our observations indicate that this ability of the ADAMTS14 protein is conserved through evolution," says lead author Guangxia Wang, who is writing her PhD thesis at the CiM-IMPRS Graduate School at Münster University. The School is part of the "Cell Dynamics and Imaging" research focus.

In cell transplant experiments, the researchers were able to show that certain neuronal structures, as well as fibroblasts, represent the cellular sources for both proteases and, in addition, for the VEGF-C protein. "Activating the VEGF-C protein in these positions in the embryo was sufficient to trigger normal development of lymphatic vessels, which again emphazises the importance of this cell population for the regulation of lymphangiogenesis," says Andreas van Impel.

The researchers plan to undertake further investigations to find out how relevant the activity of ADAMTS14 is for the development and maintenance of the lymphatic system in mammals. "As mutations in the ADAMTS3 protease lead to diseases in humans, it seems reasonable to assume that ADAMTS14 is also a candidate gene for human syndromes," says group leader Prof. Stefan Schulte-Merker. Furthermore, the researchers would like to assess whether a comparable fibroblast population is also present in mice and humans which also synthesizes all - or at least some - of the proteins that play a central role in processing and consequently in controlling the activity of the VEGF-C signalling pathway.

An article published in the advanced online edition of the journal Computer Communications shows that the use of machine learning can improve the operation and performance of the Wi-Fi networks of the future, those of the 5G/6G ecosystem. The research was conducted by Marc Carrascosa and Boris Bellalta, researchers with the Wireless Networking Research Group at the UPF Department of Information and Communication Technologies (DTIC).

The authors focus their study on how to improve the association of Wi-Fi network users consisting of multiple access points, in order to be able to serve a large number of users. This type of Wi-Fi network is present in business and academic environments or in public spaces in cities (streets, parks, libraries, etc.).

"In this study, we look at how stations (PCs, tablets, mobile phones, etc.) may themselves decide dynamically which of the different access points available in their coverage area is offering the best service for their needs using Reinforcement Learning techniques", Carrascosa and Bellalta explain.

Each station takes decisions dynamically

In their proposal, each station is independent and takes decisions dynamically based on the quality of service offered by the Wi-Fi network over time, i.e., the station autonomously learns how the Wi-Fi network is behaving, identifying the impact of its own actions (choosing one or another access point) on the benefits received.

"For this learning, as a basis we use an algorithm called ε-greedy, which alternates between choosing access points at random to obtain information (exploring), and choosing the best access points used based on this accumulated information (exploiting)", the authors suggest. "Thus, the more information, the better decisions we take, considering, however, that there is a compromise between the time a station can devote to learning and the time it disposes of to use what it has learned successfully", they add.

A new algorithm that shortens station learning time

To solve the limitations of the ε-greedy algorithm, such as could be the high learning time, in their paper the authors propose a new algorithm that they call ε-sticky, which includes the concept of emotional attachment. It works so that once the station has found an access point that provides the service requested, even if it ceases to do so later, it does not immediately discard it to look for another new one again in the hope that in the future it might give the same good service.

With this new proposal, service disruptions to users and network instability are reduced, which also benefits stations that have not yet found an access point that offers the required service. "Despite not being the goal of our work, the extrapolation to humans' social behaviour is quite direct, as is the interpretation in this field of the results we present", Carrascosa and Bellalta comment.

"In the article, we study the impact of this change and how it allows us to get better results for the problem of Wi-Fi association. The ultimate goal is to show the effectiveness of machine learning techniques to solve problems in Wi-Fi networks that are not easily solved by preconfigured mechanisms. With our results, we also show that not all stations need to make use of these techniques, since if only a few stations implement the new algorithm, the entire network benefits", the authors uphold.

'DNA makes RNA makes protein' is a fundamental principle in molecular biology. The process of gene expression, namely creating RNA from a specific DNA sequence, is tightly regulated in different ways. The DNA itself carries a reversible chemical modification - called methylation - that can influence gene expression.

Scientists at EMBL Rome, in collaboration with Tim Bestor at Columbia University in New York and John Edwards at Washington University in St. Louis, Missouri, now show for the first time how DNA methylation instructs cells to repress parts of their genome by inducing the assembly of a silencing complex. Their work was published in Proceedings of the National Academy of Sciences (PNAS).

DNA methylation is the only epigenetic modification known to be inherited when cells divide, meaning once a specific DNA sequence is methylated it remains in that state throughout the lifespan of an organism. Methylation acts like a mark on the DNA that inactivates some genes in a manner that is dependent on the parental origin. DNA methylation also acts as a cellular defense mechanism against parasitic pieces of DNA that can move within the genome and threaten its integrity. The modification instructs cells to repress these so-called transposons.

Despite four decades of research, the precise mechanism by which DNA methylation represses gene expression has remained unknown. The scientists in Mathieu Boulard's group found that the protein TRIM28, which is a known silencing factor that had not been previously linked to DNA methylation, is required for the repression of methylated genes. However, TRIM28 does not directly interact with DNA, which meant that other proteins must be involved in the process.

Using a combination of genetic and biochemical analyses they showed that in the presence of DNA methylation, TRIM28 binds to the enzyme OGT, which modifies other proteins by adding sugar groups (a process known as glycosylation). They also show that methylation-directed glycosylation of specific DNA binding proteins prevents methylated genes from being expressed.

"Our study reveals that protein glycosylation plays a central role in DNA methylation, thereby unveiling the mechanism behind the most studied epigenetic modification," explains Matthieu Boulard, Group Leader at EMBL Rome.

The first evidence that glycosylation plays a major function in gene regulation came from another study at EMBL, which showed that glycosylation represses developmental genes in certain cells during the development of the fruit fly Drosophila. However, gene repression in this case does not involve DNA methylation.

Boulard says: "We show that DNA methylation in mammals induces gene silencing by activating a process that induces glycosylation of regulatory factors. These findings address one of the core questions in the field of epigenetics, which is the nature of the mechanism that represses methylated promoters."

Plastic products are durable. On one hand this is a great advantage, but on the other hand, if the plastic enters the environment, this advantage turns into a problem. According to current knowledge, natural degradation, as with organic matter, does not take place. It can only be estimated, how long plastic debris actually remains in the environment. Corresponding long-term experiments are lacking.

This applies particularly to the deep sea that is only poorly explored itself. Plastic objects that are found by chance with the help of deep-sea robots or other underwater vehicles are difficult to date. However, during an expedition with the German research vessel SONNE in 2015, researchers from the GEOMAR Helmholtz Centre for Ocean Research Kiel, the Max Planck Institute for Marine Microbiology in Bremen and the Kiel University were able to recover several pieces of waste from the seabed of the Eastern Pacific Ocean in a depth of more than 4000 metre. Conducting a little detective work allowed to constrain the age of deposition quite accurately. For the first time, this offered the opportunity to conduct a long-term study on plastic degradation in the deep sea. The study was published today in the international journal Scientific Reports.

In reality, in 2015 the team was out in the Pacific about 440 nautical miles (815 km) off the coast of Peru to investigate another long-term experiment in the so-called DISCOL area. There, German scientists had ploughed a piece of seafloor in 1989 in order to understand the environmental impacts arising from potential future mining of manganese nodules. They visited this site again in 1992, 1996 and in 2015 to study the recovery of the deep-sea ecosystem.

In 2015, the remotely operated deep-sea robot ROV KIEL 6000 observed almost incidentally some waste and recovered it from the seafloor. Among it was a plastic bag containing a Coke can, which was part of a special edition produced for the Davis Cup 1988. "The aluminum can itself would have corroded in the deep sea, if it was not wrapped tightly inside a plastic garbage bag that preserved it. This also indicates that the garbage bag must be of the same age", says Dr. Matthias Haeckel from GEOMAR, project manager on board back then and now co-author of the study.

A second recovered item was a curd box from a German manufacturer. The printed address shows a five-digit postal code. These were not introduced in Germany until 1990. However, the manufacturer was bought by a rival company in 1999, and the brand name disappeared.

"Since the DISCOL area is far away from important shipping routes, the plastic bag and the curd box could be attributed to the DISCOL expeditions in 1989 and 1992 or 1996," says Dr Haeckel. After all, this offered the extremely rare opportunity to examine in detail datable plastic objects from the deep sea. "It turned out that neither the bag nor the curd box showed signs of fragmentation or even degradation", says biochemist Dr. Stefan Krause from GEOMAR, lead author of the study. He led the onshore analyses in the home laboratories.

A scientifically most interesting finding was that the microbial community on the plastic surfaces differed from the one identified in the surrounding seafloor sediments. "All of the species can be found in the deep-sea sediment, but apparently, larger accumulations of plastics could locally cause a shift in the ratio of the predominant species," says Dr. Krause.

Overall, the study provides the first scientifically sound indication of the fate of plastic debris in the deep sea. "This study builds also an important basis for our new project HOTMIC, where we aim to trace the plastic waste entering the ocean from the continents to the large oceanic eddies and further to their final sink, the abyssal seafloor", says Dr Haeckel.

At the same time, the findings provide a good argument for him to pay even closer attention to compliance with regulations regarding waste on board. "Fortunately, the mentality has changed considerably since the 1990s. Today, both, the crews of the ships and the research teams on board take great care to ensure that no waste is disposed overboard," says Dr Haeckel.

Camelina sativa oil and fatty fish are rich in polyunsaturated omega-3 fatty acids, but their health benefits seem to differ. A new study from the University of Eastern Finland shows that Camelina sativa oil reduces the formation of fatty acid derivatives that may be harmful to cardiovascular health. Camelina sativa oil also seems to protect against oxidative stress. Fatty fish, on the other hand, increases the circulatory concentration of fatty acid derivatives that alleviate inflammation.

The study, conducted in collaboration between the University of Eastern Finland and Karolinska Institutet in Sweden, examined the associations of fatty and low-fat fish, and Camelina sativa oil, with lipid metabolism and low-grade inflammation. The study lasted for 12 weeks and it involved 79 men and women between 43 and 72 years of age and with impaired fasting glucose. The study participants were divided into four groups. One group replaced fats in their daily diet with Camelina sativa oil and reduced their intake of fish to one serving a week. Two of the groups ate fish four times a week: two servings of fatty fish, such as salmon or vendace, and two servings of low-fat fish, such as saithe or pike. The fourth group was a control group.

A high intake of omega-3 fatty acids from Camelina sativa oil and fatty fish reduced the circulatory proportions of arachidonic acid, which is a long-chain omega-6 fatty acid. Those using Camelina sativa oil also had lower concentrations of mediators derived from arachidonic acid, which may be harmful to cardiovascular health. Moreover, the intake of fatty fish increased the circulatory concentration of fatty acid derivatives that alleviate inflammation.

"Camelina sativa oil and fatty fish had a major effect on lipid metabolism. Our study shows that dietary fats can be used to target metabolic pathways that are linked to cardiovascular diseases and type 2 diabetes," Early Stage Researcher Topi Meuronen, the lead author of the article, from the University of Eastern Finland says.

In addition to its other beneficial effects, Camelina sativa oil was also observed to reduce the circulatory concentration of markers that are indicative of oxidative stress. Low-fat fish, however, did not have an effect on the metabolic pathways studied.

In addition to measuring traditional fatty acid concentrations from blood, the researchers were also interested in changes that occur in fatty acid metabolites, which serve as mediators. An examination of fatty acid metabolism on this level makes it possible to study the effects of dietary polyunsaturated fatty acid in more detail than before. These new results are promising and they support earlier findings on the health benefits of fatty fish. However, further research into fatty acid derived mediators, and especially into the effects of Camelina sativa oil's metabolites, is needed.

Patients with bipolar disorder who have multiple family members with severe mental disorders, are more difficult to treat and require more medicine. But if they receive an intensive course of treatment, the effect of this is just as good as for patients who do not have a family history of severe mental disorders.

Bipolar disorder is a serious mental disorder which affects >1 procent of the population during their lifetimes. Now, a new study from Aarhus University and Aarhus University Hospital Psychiatry - in collaboration with a number of American hospitals led by Massachusetts General Hospital in Boston - follows in the wake of previous studies in showing that patients with bipolar disorder have many family members who also suffer from severe mental disorders.

Treatment should be intensified

However, the new element in the study is that the course of the disorder is more complicated for patients who have e.g. a parent or sibling with a severe mental disorder. They had more depressive and manic episodes and more suicide attempts during their lifetime, while at the same time requiring a more intensive course of treatment with more medicine.

"The positive finding is that this extra effort in relation to treatment resulted in patients who both had and didn't have close relatives with severe mental disorders responding equally well to the treatment," explains one of the researchers behind the study, Medical Doctor and PhD Ole Köhler-Forsberg from Aarhus University and Aarhus University Hospital - Psychiatry.

The findings have just been published in the scientific journal Journal of Affective Disorders.

At the start of the study, patients with bipolar disorder self-reported the number of first-degree relatives with severe mental disorders. Of the participants, 85 per cent had at least one, and twenty per cent had five or more. Among the most frequent disorders were depression, alcohol abuse and bipolar disorder.

"We also found that a higher number of family relatives with severe mental disorders was linked to a lower level of education, lower income and earlier debut of the disorder. This suggests that mental disorders in the family also affect the lives of the patients in a very broad and general sense which goes beyond the disorder itself," says Ole Köhler-Forsberg.

The results are based on two large American randomised controlled trials with a total of 757 participants. The study is the first of its kind to include such a large group of patients and also to follow these patients over 24 weeks while they were treated with one of four different treatments.

"Future studies could take a closer look at how mental disorders in the family affect the patient, but also at the entire family and the lives of relatives, and whether efforts to help e.g. the children of people with mental disorders should begin earlier," says the researcher.