Culture

Within both plant and animal cells, motor proteins act like the engines in a busy train system. They shuttle material in the cell from one location to another. And just as commuter trains travel a predictable route in a defined direction, their volume of transport is commensurate with need. At rush hour, more trains are in operation. At midnight, there's no point in running trains every 10 minutes.

In a growing plant cell, motor proteins called kinesins work as transporters that haul materials built in one part of the cell to the place where they are needed. Kinesins travel along tracks of polymers known as microtubules to get where they are going. Moving cargo costs the cell energy and resources, and this process is closely controlled to prevent waste.

Now biologists at Washington University in St. Louis have discovered the molecular brakeman that holds kinesins in check until their cargo is needed.

The importin IMB4 is a regulator that controls a kinesin specifically involved with building the plant cell wall. It works by physically binding to the kinesin, said Ram Dixit, associate professor of biology in Arts & Sciences. IMB4 holds the kinesin in an inactive state -- protecting it from degrading while it waits -- and prevents the kinesin from traveling along a microtubule until its cargo is needed. The new research is published in the journal Developmental Cell.

"The cell wall is like the plant's exoskeleton, and building it is one of the growing plant's most important functions. We have identified a key molecular regulator that closely controls cell wall deposition by physically binding to a kinesin," Dixit said. "We still don't know what signals cause IMB4 to release the brakes, but we now understand how it holds kinesins back until they are needed."

Ready movers

A rigid cell wall is an essential and energetically expensive investment for a plant. The cell wall confers strength and enables the cell to withstand the turgor pressure that is necessary for growth.

In Arabidopsis plants, cell wall deposition depends on a kinesin-4, called Fragile Fiber 1 or FRA1. FRA1 was identified more than a decade ago, but a 2015 study in Dixit's lab confirmed that its motility and abundance were correlated with cellular growth rates.

Postdoctoral fellow Anindya Ganguly, lead author of the paper, was intrigued by what the research team had seen. In rapidly growing cells of seedling stems, they saw lots of FRA1 kinesins moving along microtubules. But further down the stem, where the cells had ceased to elongate, the motor proteins were gone.

"Similar to rush hours, when plants are rapidly growing, you need to deliver a lot of cell wall material to keep up with growth," Ganguly said. "Efficient, high-volume transport depends on having a lot of motor proteins. The regulator we discovered keeps a surplus of these transporter proteins around during times of rapid growth."

Ganguly and co-authors discovered that the importin IMB4 binds directly to the motor domain of the FRA1 kinesin. Then, using a combination of mutant analysis, microscopy of FRA1 within living cells and protein biochemistry, the team showed that this interaction inhibits the movement of FRA1.

"This importin essentially jams the motor, the engine of the kinesin," Dixit said. "You inhibit mobility by virtue of prohibiting its association with its track."

"The site where we think it binds, based on some analysis we did here, includes amino acids that are very conserved in other kinesin families in both plants and animals," Dixit said. "So we think that there's a good chance that this mechanism might be generally applicable."

Twisted sister

With a handle on IMB4, researchers now have a better understanding of the mechanical workings of the engines of cell wall deposition. Another study published by the Dixit lab this month identifies a regulator involved in building the scaffold on which kinesins move.

In this study, the researchers examined a mutant Arabidopsis plant that exhibits a twisted growth pattern. Its leaves and stems swirl back in on themselves; its roots are tangled and skewed.

These so-called spiral mutants suffer from misaligned microtubules (the "tracks" that the kinesins walked along in the other study). In the mutant, severing proteins were thought to snip and shorten the microtubules at the points where they cross over each other.

But when Dixit and postdoctoral fellows Yuanwei Fan and Graham Burkart set out to parse intracellular activity in the spiral mutant, they uncovered a more interesting and nuanced mechanism. Importantly, they discovered that the plant-specific SPR2 protein regulates the minus-end dynamics of microtubules in the mutant.

Microtubules have a fast-growing and more dynamic end, identified as a "plus" end, and a slow-growing, less dynamic "minus" end. Microtubules grow and shrink from the plus side, while the minus side has generally been considered static in plants -- until now.

Remarkably, in the spiral2 mutant, the minus-ends are extremely dynamic and shorten at much higher rates compared to wild-type plants.

"Not only did we find that this protein localizes to the minus end, in plants, and regulates the minus-end dynamics, but we were able to recapitulate that behavior in vitro," Dixit said. "We can say that this protein and this protein alone is sufficient to localize to the minus ends, track the minus ends, and stabilize them."

Interestingly, the SPR2 plant protein shares some characteristics with mammalian proteins that stabilize the minus ends of microtubules in the tissues that line the surfaces of organs and in neurons.

This separate, microtubules work is funded by the National Institutes of Health, and is published online in advance of the March 19 issue of the journal Current Biology.

Keeping track of cell shapes and functions

Taken together, this new research on the regulators of motor proteins and microtubules helps explain the inner workings of plant cells that gives rise to their shape and enables them to alter their growth in response to developmental and environmental signals.

The work on IMB4 and the FRA1 kinesin is part of Dixit's effort with the Center for Engineering MechanoBiology (CEMB), a National Science Foundation-funded science and technology center jointly led by Washington University and the University of Pennsylvania. Within CEMB, Dixit leads a research cohort focused on determining how cells adapt to, and change, their mechanical environment.

"The center's focus is really to uncover, understand and ultimately be able to control the role of mechanical forces writ large on biological systems," Dixit said.

"One of the thing that's unique about the center is that it brings together both plant and animal systems. That hasn't been done before," Dixit said. "The idea is that we will be able to uncover some universal principles that are applicable to both kingdoms."

Ever notice how a cut inside the mouth heals much faster than a cut to the skin? Gum tissue repairs itself roughly twice as fast as skin and with reduced scar formation. One reason might be because of the characteristics of gingival mesenchymal stem cells, or GMSCs, which can give rise to a variety of cell types.

"This study represents the convergence of a few different paths we've been exploring," says Songtao Shi, chair and professor of Penn Dental Medicine's Department of Anatomy and Cell Biology and the senior author on the study. "First, we know as dentists that the healing process is different in the mouth; it's much faster than in the skin. Second, we discovered in 2009 that the gingiva contains mesenchymal stem cells and that they can do a lot of good therapeutically. And, third, we know that mesenchymal stem cells release a lot of proteins. So here we asked, How are the gingival mesenchymal stem cells releasing all of these materials, and are they accelerating wound healing in the mucosal tissues?"

The work appears in the journal Science Translational Medicine.

Xiaoxing Kou, a visiting scholar at Penn Dental Medicine, was the first author on the work. Shi and Kou collaborated with colleagues Chider Chen and Anh Le from Penn Dental Medicine as well as Yanheng Zhou from Peking University, Xingtian Xu from the University of Southern California, Los Angeles, Claudio Giraudo and Maria L. Sanmillan from the Children's Hospital of Philadelphia, and Tao Cai from the National Institute of Dental and Craniofacial Research.

From earlier work by Shi's group and others, it was clear that mesenchymal stem cells perform many of their functions by releasing signaling molecules in extracellular vesicles. So to understand what distinguishes mesenchymal stem cells in the gingiva from those in the skin, the Penn-led team began by comparing these extracellular vesicles between the two types. They found that the GMSCs contained more proteins overall, including the inflammation-dampening IL-1RA, which blocks a proinflammatory cytokine. IL-1RA also happens to be used as a therapy to treat rheumatoid arthrisits, an inflammatory condition.

Next the team zoomed in to look at what might be controlling the release of IL-1RA and other cytokines. They had a suspect in the protein Fas, which they had earlier connected to immune regulation. They found that in gingival MSCs had more Fas than skin MSCs, and that mice deficient in Fas had reduced IL-1RA as well as reduced secretion of IL-1RA.

Further molecular probing revealed that Fas formed a protein complex with Fap-1 and Cav-1 to trigger the release of small extracellular vesicles. To identify the connection with wound healing, they examined wound tissue and found that IL-1RA was increased in GMSCs around the margins of wounds. Mice lacking IL-1RA or in which the protein was inhibited took longer to heal gingival wounds.

In contrast, when the researchers isolated IL-1RA that had been secreted from GMSCs and injected it into wounds, it significantly accelerated wound healing.

"We found that mesenchymal stem cells, and especially gingival mesenchymal stem cells, release large amount of cytokines through an extracellular vesicle," says Kou.

These findings may have special significance for people with diabetes, a major complication of which is delayed wound healing. In the study, the researchers found that GMSCs in mice with diabetes were less able to secrete extracellular vesicles compared to GMSCs in healthy mice, and their GMSCs also had less IL-1RA secretion. Introducing extracellular vesicles secreted from the GMSCs of healthy mice reduced wound healing time in diabetic mice.

"Our paper is just part of the mechanism of how these stem cells affect wound healing," Kou says, "but I think we can build on this and use these cells or the extracellular vesicles to target a lot of different diseases, including the delayed wound healing seen in diabetic patients."
Moving forward, Shi, Kou and colleagues want to move their work into the clinic.

"We are targeting translational therapies," says Shi. "These cells are easy to harvest from the gingiva, and that makes them a beautiful cell for clinical use. We have a lot of work ahead of us, but I can see using these cells to reduce scar formation, improve wound healing, and even treat many inflammatory and autoimmune diseases."

The low priority given to children and young people's health threatens the UK's future prosperity, argues an expert writing in The BMJ today.

Professor Russell Viner at University College London's Institute of Child Health, says countries that invest in child health "reap impressive economic rewards, with each pound spent on children's health returning over £10 to society over a lifetime."

In contrast, poor health in childhood "leads to reduced workforce participation and productivity and lowers national wealth."

Professor Viner, who takes up the role of president of the Royal College of Paediatrics and Child Health this week, points out that the UK has a higher proportion of children and young people in its population than almost all other Western European countries that will provide us "a future demographic dividend of a larger working-age population if, and only if, we protect their health."

But he argues that "we are poorly positioned to reap these benefits, as our children's health outcomes are substantially worse than those in most other wealthy European countries."

He points out that Scotland and Wales have both recently announced new national strategies to improve children's health. Yet in England, health services for children and young people "struggle for priority and there is no sign yet of a national strategy."

For example, the NHS Five Year Forward View mentions children and young people briefly only in relation to prevention and mental health, while the 2016 General Practice Forward View mentions children only once, despite children making up a large proportion of primary care attendances.

And although patients aged 0-18 years made up 25% of A&E attendances in 2015-16, the 2013 Transforming Urgent and Emergency Care Services in England mentions this group briefly twice.

This lack of focus has begun to tell, writes Viner. Across the UK, large gaps in the paediatric workforce have lowered morale in children's services, recruitment into paediatric training positions in 2017 was the worst ever, and workforce deficiencies, low morale and lack of focus on children are cited as reasons for large numbers of services receiving poor ratings for safety and effectiveness.

He says the moral and economic reasons for action are clear, and he calls for "a new focus on health services for the children and young people who carry all our futures."

For each UK country this means a targeted health strategy, formulated in partnership with children and their families, and covering early life from from conception to adulthood. For England it also means a greater visibility within NHS England priorities in primary care and emergency care and in the new integrated care systems.

"The Royal College of Paediatrics & Child Health is keen to work with governments to achieve these aims. Business as usual for child health will not build a healthy and prosperous United Kingdom," he concludes.

The impacts of global warming are felt especially in mountainous regions, where the rise in temperatures is above average, affecting both glacierized landscapes and water resources. The repercussions of these changes are manifold and varied, from retreating glaciers to an increase in the frequency and intensity of snow avalanches. A team of researchers from the University of Geneva (UNIGE), Switzerland, has employed dendrochronology- the reconstruction of past disasters as recorded in growth series of trees- to disentangle the role of global warming in the triggering avalanches. The results of this study are published in the Proceedings of the National Academic of Science - PNAS.

Avalanches are a natural phenomenon and occur repeatedly in mountain areas; nonetheless, rising temperatures are altering their triggering. This can lead to disasters and serious consequences in mountain areas where they can severely affect the socio-economic development and the destruction of traffic infrastructure, and buildings. This is the case in the Indian state of Himachal Pradesh, where increasing residential numbers and tourism are exerting pressure on land use. Along the road to Leh, 500 km north of New Delhi, the Indian government has started to drill one of the largest tunnels of the Indian sub-continent. With the ongoing climate warming, the access road to the tunnel is becoming increasingly threatened by snow avalanches. This is why UNIGE researchers conducted their fieldwork at the spot from 2013 to 2015, in a valley located at between 3,000 and 4,000 m.

Trees: silent witnesses to the upsurge in the number of avalanches

The aim of the research group was to evaluate - and add to - the information currently available about avalanches with two goals: i. to identify the nature of the changes in avalanche activity currently taking place; and ii. to assess future needs for tackling these changes. In the absence of data comparable to the information collected in European surveys, for which records often exist for the past few centuries, the UNIGE researchers focused on trees: they examined stumps (when the tree had been removed) or cored trees that were still standing to reconstruct past snow avalanches at the study site. The scientists were able to date individual events by analysing the growth rings and wounds left on the trees by avalanches. The research included nearly 150 trees. &laquoSince we knew the position of each affected tree, we were able to reconstruct the dynamics, lateral extent and runout distance of every avalanche,» explains Juan Antonio Ballesteros-Cánovas, a senior lecturer at UNIGE's Institute for Environmental Sciences (ISE). &laquoThis technique meant we could go back to 1855 and record 38 avalanches over this period in the valley, the largest survey conducted to date in the Himalayas.»

The models used for testing the impact of climate change combine the risks of avalanche with local climate data. They were adjusted to include the likely effect on topographical features resulting from earlier avalanches. Since they destroy the plant cover, they are an aggravating risk factor. The results brooked no argument: from the second half of the twentieth century, there has been an increase in the number of avalanches, both in terms of frequency and intensity. The frequency has risen from one event per decade to almost one event every year.

The impact of temperature on the cryosphere

Avalanches are bigger, travel greater distances and are triggered earlier in the year. These changes can be attributed clearly to rising temperatures, which have reached 0.2 to 0.4 degrees annually in some parts of the Himalayas. And rising air temperature are also affecting the cryosphere: glaciers are receding and permafrost is melting, losing its role as a sediment stabiliser. In addition, the structure of the snowpack is changing: it is being transformed by increasingly warmer air temperatures and/or altered by rain-on-snow events. Snow is now also falling earlier in the season, and is being destabilised before spring, at a time when it is thicker, leading to an increase in the number and intensity of avalanches. Since the snow is wet, avalanches are descending slowly but over a greater distances than in the past.

The research was being carried out within the framework of the Indian Himalayas Climate Adaptation Program (IHCAP), a partnership led jointly by the Indian and Swiss authorities with strong scientific input from UNIGE.

HOUSTON, March 14, 2018 - Two University of Houston scientists are reporting that defects in a portion of the brain's hippocampus, called the dentate gyrus, is regulated by the nuclear receptor LXRβ (Liver X receptor Beta). The dentate gyrus, or DG, is responsible for emotion and memory and is known to be involved in autism spectrum disorders (ASD).

Margaret Warner, professor of biology and biochemistry, and Jan-Åke Gustafsson, professor of biology, biochemistry and founding director of the UH Center of Nuclear Receptors and Cell Signaling, describe the work in the Proceedings of the National Academy of Sciences.

For four decades they have worked together, making discovery after discovery about the role of nuclear receptors in brain functions, and they show no sign of slowing down.

Tracking down the culprit

Neurogenesis, or the regulation of growth of the dentate gyrus, occurs prenatally and postnatally.

"Our findings suggest early changes in DG neurogenesis ultimately provide an aberrant template upon which to build the circuitry that is involved in normal social function," said Warner.

Their studies propose that defects in the neurogenesis of the DG seem to be involved in the etiology of autism spectrum disorders and their associated behaviors. Specifically, defects in the nuclear receptor LXRβ has emerged as the possible culprit of defects in the DG.

Why this gray matter matters

In the world of physiology (how the organisms in our bodies communicate and keep us alive), nuclear receptors rule the day. They are a class of proteins within cells that control hormones and regulate metabolism. One of these proteins, LXRβ, may be the one that holds the key to the genesis of autism. Warner and Gustafsson established this the only way they could - by taking LXRβ out of the equation.

"Knocking out LXRβ led to autistic behavior and reduced cognitive flexibility," said Warner. "In this paper we share our findings that that deletion of the LXRβ causes hypoplasia or underdevelopment in the DG and autistic-like behaviors, including abnormal social interaction and repetitive behavior."

They went on to report: "The behavioral studies confirmed that ablation of LXRβ caused behavior disorders relevant to major ASD symptoms. Social interaction deficits, as key phenotypic traits of ASD, were evident..."

Gustafsson said the findings are the path forward in autism research.

"The Liver X receptor Beta is important in the dentate gyrus and in autism and more studies on the receptor are going to help us cure or treat autism," he said.

He should know. He's the scientist who discovered LXRβ in 1996.

"Until 1996 we did not know that this receptor even existed and it is so important in brain function," said Warner.

[Background]

Most medications, agricultural chemicals and functional materials, indispensable for maintaining and improving our lives, are composed of organic molecules. Organic synthesis using a catalyst is the method for the rapid and large scale supply of such organic molecules without imposing a heavy burden on the environment. In this research field, Prof. Noyori in 2001 and Profs. Suzuki and Negishi in 2010 were awarded the Nobel Prize in Chemistry; Prof. Noyori, for "chirally catalyzed hydrogenation reactions," and Profs. Suzuki and Negishi, for "palladium-catalyzed cross-couplings."

In recent years, catalysts consisting of only organic molecules but without metal elements, i.e. organocatalysts, have been regarded to be next-generation catalysts, and have received much attention. However, some organic chemistry reactions cannot take place with a single catalyst. Many investigations have therefore been carried out on using two or more catalysts in a synergistic manner for organic synthesis, creating a new category in this research field. In the human body, for example, several catalysts (enzymes) work in a synergistic manner for synthesizing complex organic molecules that exert important functions. Likewise, organic synthesis could potentially be carried out by two or more catalysts in one flask. Nonetheless, it has been thought to be a difficult task to realize such catalytic systems because catalysts themselves react with each other in many cases to abolish their catalytic ability.

[Results]

The research team of Kanazawa University successfully synthesized a ketone from an aldehyde and a benzyl, or from an aldehyde and an allylic carbonate, by the synergistic action of an organocatalyst and a palladium catalyst in one flask (Figure 1). Thorough examination of the reaction conditions revealed the importance of thiazolium N-heterocyclic carbene as the organocatalyst and palladium with augmented activity by bisphosphine, an organic phosphorus compound, as the metal catalyst (Figure 2). It should be mentioned that no catalytic reactions were found to take place in the absence of either of the two catalysts, indicating that two catalysts are indispensable for such a reaction to take place.

Synthetic conversion of an aldehyde into a ketone by conventional methods required a complicated process with multiple chemical reaction steps or a metal reagent that would impose a substantial burden on the environment. The newly developed protocol, on the other hand, enables the synthesis of a ketone of complex chemical structure from an aldehyde under simple and mild conditions (Figure 3). The key to success is that the aldehyde, which is known to act as an electrophile in chemical reactions, in fact worked here as a nucleophile. Thus, the novel protocol enables the rapid and simple synthetic conversion of an aldehyde into a ketone, which is an important basic structure found in a variety of medications and medication candidate chemicals.

[Future prospects]

It was thought to be difficult for a transition metal catalyst and an organocatalyst to function in a synergistic manner in one flask with their individual functional activities maintained. The present study represents a milestone in this field. Furthermore, a novel design guideline has now been established in the field of "organic synthesis using catalysts." It is expected that, by changing the combination of catalysts to be employed, a variety of synthetic reactions that have so far been difficult could be developed, which should pave the way for new technologies for synthesizing medications and medication candidates in a simple and easy manner but without waste.

A new lab-based study has shown that when airway cells damaged by cigarette smoke are exposed instead to glo vapour, the biological effects caused by smoke exposure are reversed.

glo is British American Tobacco's tobacco heating product (THP). It is designed to heat rather than burn tobacco, and the vapour produced has around 90-95% less of certain toxicants compared to cigarette smoke**.

Previous studies have shown that the biological impact of glo vapour on cells in the lab is much reduced compared to cigarette smoke. But the reversibility of the damage following switching to a product like glo has not been extensively studied.

'Products like glo are very new, so understanding the biological impact of vapour from glo and how that compares to cigarette smoke is a core component of our scientific research,' said Dr James Murphy, Head of Reduced Risk Substantiation at British American Tobacco.

In this study, human airway cells were exposed repeatedly to either cigarette smoke or vapour over a period of four weeks. For the first two weeks, the lung tissue was exposed to cigarette smoke for 15 minutes at a time, three times a week. The exposed tissue was then split into three groups: one group continued to be repeatedly exposed only to cigarette smoke for a further 2 weeks; a second group was exposed repeatedly to glo vapour and a third group was exposed only to air.

The results obtained were then compared to results obtained by exposing airway tissue only to air for the full 4-week period.

The results show that switching completely to glo after 2 weeks of repeated exposure to cigarette smoke reversed some of the biological impacts of the smoke. Significant reductions were observed in the amount of certain molecules produced in response to inflammation, for example, in comparison to that seen in lung tissue exposed to cigarette smoke for the full 4-week period.

These results add to evidence suggesting that glo may have the potential to be reduced risk compared to smoking conventional cigarettes.

'We have developed a suite of tests to assess our next generation products, because we know it is by taking the results of all these tests together that gives us a real feel for the bigger picture and the potential for glo to be reduced risk compared to a conventional cigarette,' says Murphy.

The results are presented today at the annual conference of the Society of Toxicology in San Antonio, Texas, US.

(Boston)--For the first time, researchers have produced a nearly complete three-dimensional structure for the yeast Nuclear Pore Complex (NPC). This discovery represents a major step toward identifying the atomic structure of the NPC, which soon may provide researchers with a better understanding of how the central transport channel functions.

The NPC is the largest channel in the cell and spans the double membrane of the nuclear envelope. This remarkable channel provides a gateway to transport macromolecules back and forth between the nucleus and the cytoplasm. Due to its large size and dynamic nature a full structural and functional understanding of the NPC had been impeded until now.

The structure of the NPC was determined using a novel Integrative Modeling approach in which information from a large number of different experiments was used to computationally determine a set of models that best fit all the input data. The sheer size and complexity of the channel required data contributed directly from nine laboratories. In total, researchers were able to accurately place 552 NPC proteins, known as nucleoporins, within this large channel which is shaped somewhat like a wagon wheel with eight major spokes that connect the core scaffold to a more flexible central channel region (the central transporter).

"This transport gateway provides a control point to regulate development and cell growth. Unraveling the architecture of this mammoth transport machine provides us with a great deal of insight into how this channel is constructed and suggests how it may function," explained corresponding author Christopher Akey, PhD, professor physiology and biophysics at Boston University School of Medicine.

According to the researchers, these findings may one day help explain changes in cancer cells.

In February 2016, faced with a drastic increase in the number of Zika infections and in order to establish a link between the virus and neurological complications, the World Health Organization (WHO) declared a "Public Health Emergency of International Concern (PHEIC)". In March 2016, with the aid of the REACting consortium, Inserm took charge of the establishment, sponsorship and scientific follow-up of a cohort of pregnant women exposed to Zika in the French territories in the Americas, monitored by the French Antilles-French Guiana Clinical Investigation Center (Inserm CIC 1424). The objective? To study the fetal and neonatal complications associated with Zika virus infection in an epidemic situation. This cohort was funded by the French Ministry of Health and Solidarity (Exceptional Support of Research and Innovation) and included in the European ZIKAlliance program.

Several thousand women who were pregnant during the Zika epidemic in the French territories in the Americas were enrolled in this cohort between March 2016 and August 2017. The article published in NEJM addresses those women from the cohort who presented with Zika virus infection confirmed by laboratory testing between March 2016 and November 2016. These women were then monitored every month until the end of their pregnancy. All complications and treatments received were recorded and if fetal abnormality was detected during an ultrasound, an additional examination by magnetic resonance imaging was performed.

The results obtained by the researchers show a 7 % rate of congenital neurological abnormalities observed in the fetuses and neonates of the cohort, which is a lot lower than that initially observed in Brazil, and close to what was observed in the US registry.

The study confirms an especially high risk in the event of infection occurring during the first trimester.

When broken down, the results show that the frequency of neurological complications is:

12.7% when the mother is infected during the 1st trimester

3.6% when the mother is infected during the 2nd trimester

5.3% when the mother is infected during the 3rd trimester

Likewise, the percentage of severe microcephaly (head circumference

3.7% when the mother is infected during the 1st trimester

0.8% when the mother is infected during the 2nd trimester

0 when the mother is infected during the 3rd trimester

"These are the initial findings of the analyses of this cohort, given that the babies are still very young. It will be essential to monitor all the children in order to identify any later complications," explains Bruno Hoen, physician researcher at Inserm and University Hospital of Guadeloupe and principal investigator of the study.

"Even if these complication rates are low in relation to other viral infections in pregnant women, they remain worrying given that the Zika virus can infect over 50 % of a given population in the epidemic phase", comments Arnaud Fontanet, who heads the Emerging Diseases Epidemiology Unit at Institut Pasteur, and who is co-investigator of the study.

REACTing (REsearch and ACTion targeting emerging infectious diseases)

Inserm and its Aviesan partners have created REACTing, a multidisciplinary consortium that brings together research groups and laboratories of excellence, in order to prepare for and coordinate research to combat the health crises linked to emerging infectious diseases. Since its creation, REACTing has also set up programs centered around the Chikungunya, Ebola and Zika epidemics.

Clinical research at Inserm

The Clinical Research Unit manages sponsor activities for the clinical trials of which Inserm is a sponsor and, together with the Directorate of Health Care Supply (DGOS), jointly supervises the Clinical Investigation Centers (CIC). In 2017, he was in charge of 238 studies, including 15 European and/or international projects.

Mongooses living in large groups develop "specialist" diets so they don't have to fight over food, new research shows.

Banded mongooses cooperate closely but are also prone to violence - both between groups and within them - and competition for food increases as a group grows.

To get round this, individual mongooses find a dietary "niche", according to researchers from the universities of Exeter and Roehampton.
Group living has advantages and disadvantages, and the findings suggest specialisation is one way to prevent groups being torn apart by fighting.

"Social animals can gain many benefits from group living, but they also suffer from competition over shared food resources," said Professor Michael Cant, of the Centre for Ecology and Conservation on the University of Exeter's Penryn Campus in Cornwall.

"Our research shows that banded mongooses respond to this competition by developing specialised foraging preferences.

"The study helps to explain why animals vary so much in their foraging behaviour, even when they live in the same place and have access to the same food."

The study examined wild banded mongooses in Uganda. Their diet includes millipedes, ants, termites and beetles, and sometimes vertebrates such as frogs, mice and reptiles.

The researchers tested opposing theories: that increased competition would lead to more varied diets, or that it would cause mongooses to find a dietary "niche".

They were able to compare individual mongoose diets by analysing the chemical composition of their whiskers, using the stable isotope facility at the Environment and Sustainability Institute, also at Exeter's Penryn Campus.

Rather than eating a wider range of foods, mongooses in large groups tended to become specialists in eating certain things - leaving other foodstuffs for different members of their groups.

"This is the first test of these competing ideas about the effect of social competition on diet in mammals," Dr Harry Marshall, Lecturer in Zoology at the Centre for Research in Ecology, Evolution and Behaviour at the University of Roehampton.

"This research confirms the hypothesis that mongooses adopt niche dietary preferences in response to competition from within their social groups.

"The findings suggest that group living may be one of the processes that promotes greater specialisation."

The findings are part of the Banded Mongoose Research Project, which has been running in Uganda for more than 20 years.

The paper, published in the journal Ecology Letters, is entitled: "Intragroup competition predicts individual foraging specialisation in a group-living mammal."

Researchers have fused living and non-living cells for the first time in a way that allows them to work together, paving the way for new applications.

The system, created by a team from Imperial College London, encapsulates biological cells within an artificial cell. Using this, researchers can harness the natural ability of biological cells to process chemicals while protecting them from the environment.

This system could lead to applications such as cellular 'batteries' powered by photosynthesis, synthesis of drugs inside the body, and biological sensors that can withstand harsh conditions.

Previous artificial cell design has involved taking parts of biological cell 'machinery' - such as enzymes that support chemical reactions - and putting them into artificial casings. The new study, published today in Scientific Reports, goes one step further and encapsulates entire cells in artificial casings.

The artificial cells also contain enzymes that work in concert with the biological cell to produce new chemicals. In the proof-of-concept experiment, the artificial cell systems produced a fluorescent chemical that allowed the researchers to confirm all was working as expected.

Lead researcher Professor Oscar Ces, from the Department of Chemistry at Imperial, said: "Biological cells can perform extremely complex functions, but can be difficult to control when trying to harness one aspect. Artificial cells can be programmed more easily but we cannot yet build in much complexity.

"Our new system bridges the gap between these two approaches by fusing whole biological cells with artificial ones, so that the machinery of both works in concert to produce what we need. This is a paradigm shift in thinking about the way we design artificial cells, which will help accelerate research on applications in healthcare and beyond."

To create the system, the team used microfluidics: directing liquids through small channels. Using water and oil, which do not mix, they were able to make droplets of a defined size that contained the biological cells and enzymes. They then applied an artificial coating to the droplets to provide protection, creating an artificial cell environment.

They tested these artificial cells in a solution high in copper, which is usually highly toxic to biological cells. The team were still able to detect fluorescent chemicals in the majority of the artificial cells, meaning the biological cells were still alive and functioning inside. This ability would be useful in the human body, where the artificial cell casing would protect the foreign biological cells from attack by the body's immune system.

First author of the study Dr Yuval Elani, an EPSRC Research Fellow also from the Department of Chemistry, said: "The system we designed is controllable and customisable. You can create different sizes of artificial cells in a reproducible manner, and there is the potential to add in all kinds of cell machinery, such as chloroplasts for performing photosynthesis or engineered microbes that act as sensors."

To improve the functionality of these artificial cell systems, the next step is to engineer the artificial coating to act more like a biological membrane, but with special functions.

For example, if the membrane could be designed to open and release the chemicals produced within only in response to certain signals, they could be used to deliver drugs to specific areas of the body. This would be useful for example in cancer treatment to release targeted drugs only at the site of a tumour, reducing side effects.

While a system like that may be a way off yet, the team say this is a promising leap in the right direction. The work is the first example of fusing living and non-living components to emerge from Imperial and King's College's new FABRICELL centre for artificial cell science.

Having a larger family is linked to a heightened tooth loss risk for mums, suggest the results of a large European study published online in the Journal of Epidemiology & Community Health.

The popular saying: 'gain a child, lose a tooth' suggests that fertility may be linked to tooth loss, but there are no hard data to back this up.

To try and plug this gap, the researchers drew on data from Wave 5 of the Survey of Health, Ageing, and Retirement in Europe (SHARE).

SHARE contains information on the health, educational attainment, and household income of more than 120,000 adults aged 50+ from 27 European countries plus Israel.

Wave 5 was conducted in 2013, and included questions on the full reproductive history and number of natural teeth of 34,843 survey respondents from Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Italy, Luxembourg, The Netherlands, Slovenia, Spain, Switzerland and Israel.

The average age of the respondents in Wave 5 was 67, and they reported an average of 10 missing teeth--normally adults have 28 plus 4 wisdom teeth in their mouth.

As might be expected, tooth loss increased with age, ranging from nearly 7 fewer teeth for women in their 50s-60s up to 19 fewer teeth for men aged 80 and above. Higher levels of educational attainment were also linked to lower risk of tooth loss among women.

The researchers looked at the potential impact of having twins or triplets rather than singletons, and the sex of the first two children, on the assumption that if the first two were of the same sex, the parents might be tempted to try for a third child.

They applied a particular type of statistical technique (instrumental variables regression), which exploits random natural variation in a variable that is only associated with the exposure and affects the outcome only through that exposure, so mimicking a randomised controlled trial.

A third child after two of the same sex was associated with significantly more missing teeth for women, but not men, if compared with parents whose first two children were different sexes.

This suggests that an additional child might be detrimental to the mother's, but the not the father's, mouth health, say the researchers.

They acknowledge that their analyses covered narrow groups with particular types of fertility patterns, and relatively small numbers in the groups of interest, so the results should be interpreted with caution and taken as evidence of cause only for this small group.

What's more, the precise contribution of parenting rather than pregnancy related factors needs to be unravelled further, they say.

But they conclude: "On the basis of our findings, enhanced promotion of oral hygiene, tooth friendly nutrition and regular (preventive) dental attendance - specifically targeted at expecting and parenting mothers - seem to be sensible strategies for clinicians and health policy."

Before the Wi-fi and the Internet, the telephone and the telegraph, the original instant messaging services of society were homing pigeons. After becoming the first domesticated birds, for an estimated 2,000 years, these reliable messengers have brought news from battlefronts and between heads of state.

Then, about 200 years ago, fanciers from Belgium created an international sporting sensation, breeding racing pigeons to have ever faster flights and longer homing skills. Nowadays, these birds can fly up to 1,000 kilometers from home at speeds up to 70 kilometers per hour, and the best of them fetch thousands of euros on the breeding market in a continual effort to one-up the competition.

Recently, scientists have been using state-of-the art genomic tools to also help home in on the special traits of racing pigeons.

A scientific team led by Malgorzata Anna Gazda and Miguel Carneiro, performed the first whole genome sequencing of 10 racing pigeons as well as data from 35 different breeds, and has now identified new clues in racing pigeons that may help enhance their performance. The study also including looking at gene expression differences (using RNA sequencing expression data) in the brains and muscle tissue of racing pigeons versus other breeds.

"Our genome-wide scan of selection sheds light on the genetic architecture and mode of selection underlying the faster flight, endurance, and accurate navigation of racing pigeons," said Malgorzata Anna Gazda. "It furthermore provides a catalog of candidate genes, with some compelling examples of genes likely to underlie racing performance phenotypes."

Their analyses demonstrated that racing pigeons are unique, and genetically differentiated from other pigeon breeds, and that there is adaptation in several regions of their genomes, and key differences in gene expression in brain and muscle tissues.

But as with other traits, there is no single gene responsible for the differences.

"Strikingly, among a dataset of 17,425,765 million variants, we did not find a single example of a variant with diagnostic alleles between racing and non-racing pigeons," said Miguel Carneiro. "It is unlikely that any single genetic change is sufficient to account for the superior flight and orientation abilities of racing pigeons. In addition, we recovered a considerable number of signatures of selection across the genome, indicating a polygenic basis for the adaptations to extreme performance in this breed. This pattern is perhaps expected considering the number of body systems that must interact for superior racing performance (cardiovascular, respiratory, musculoskeletal, and nervous systems)."

In particular, they have identified a number of candidate genes that were found to have variants in the racing pigeons, with (one, called is also differentially expressed in muscle, and both have functions can be related to athletic performance).

"Despite the paucity of fixed genetic variation between racing and non-racing pigeons, our genome-wide screen suggests that signatures of positive selection are common across the genome of racing pigeons," said Miguel Carneiro.

Their RNA-seq analysis revealed low to moderate changes in gene expression between racing and non-racing pigeons. The patterns from a total of 242 RNA transcripts were shown to be differentially expressed with brain showing fewer differences (29) when compared to muscle (213).

"The genes CASK, SIK1, and PTPRD are good candidates to be implicated in racing performance phenotypes," said Malgorzata Gazda. "CASK has been implicated in the development of neuromuscular junctions which play a critical role in the function of skeletal muscle. Differences in the morphology and physiology of such junctions have been associated with muscle performance. SIK1 has been shown to regulate muscle function and growth by controlling the expression of muscle specific genes SIK1 has also been shown to regulate hepatic lipogenesis, which plays an important role in energy homeostasis. Finally, PTPRD influences the magnitude of long-term potentiation of synapses in the hippocampus, a brain region that plays a role in spatial memory and is thought to be associated with bird navigation."

The authors conclude from that the greater athleticism and superior navigation of racing pigeons are complex, polygenic traits, and that adaptive changes in this breed were the result of selection on variation present in the breeds that formed the founding population.

Future follow-up studies, such as genome-wide association studies (GWAS) or selective breeding to map locations near candidate genes, will be performed to delve deeper into the complex physiological and adaptive changes of racing pigeon navigation, flight and faster speeds.

Astronomers have discovered that all galaxies rotate once every billion years, no matter how big they are.

The Earth spinning around on its axis once gives us the length of a day, and a complete orbit of the Earth around the Sun gives us a year.

"It's not Swiss watch precision," said Professor Gerhardt Meurer from the UWA node of the International Centre for Radio Astronomy Research (ICRAR).

"But regardless of whether a galaxy is very big or very small, if you could sit on the extreme edge of its disk as it spins, it would take you about a billion years to go all the way round."

Professor Meurer said that by using simple maths, you can show all galaxies of the same size have the same average interior density.

"Discovering such regularity in galaxies really helps us to better understand the mechanics that make them tick-you won't find a dense galaxy rotating quickly, while another with the same size but lower density is rotating more slowly," he said.

Professor Meurer and his team also found evidence of older stars existing out to the edge of galaxies.

"Based on existing models, we expected to find a thin population of young stars at the very edge of the galactic disks we studied," he said.

"But instead of finding just gas and newly formed stars at the edges of their disks, we also found a significant population of older stars along with the thin smattering of young stars and interstellar gas."

"This is an important result because knowing where a galaxy ends means we astronomers can limit our observations and not waste time, effort and computer processing power on studying data from beyond that point," said Professor Meurer.

"So because of this work, we now know that galaxies rotate once every billion years, with a sharp edge that's populated with a mixture of interstellar gas, with both old and young stars."

Professor Meurer said that the next generation of radio telescopes, like the soon-to-be-built Square Kilometre Array (SKA), will generate enormous amounts of data, and knowing where the edge of a galaxy lies will reduce the processing power needed to search through the data.

"When the SKA comes online in the next decade, we'll need as much help as we can get to characterise the billions of galaxies these telescopes will soon make available to us."

In a world first, Australian researchers have harnessed the power of diamonds in a breakthrough that could lead to radical improvements in the way human bodies accept biomedical implants.

Researchers from RMIT University have for the first time successfully coated 3D printed titanium implants with diamond.

The development is the first step toward 3D printed diamond implants for biomedical uses and orthopaedics -- surgical procedures involving the human musculoskeletal system.

While titanium offers a fast, accurate and reliable material for medical grade and patient-specific implants, our bodies can sometimes reject this material.

This is due to chemical compounds on titanium, which prevent tissue and bone from interacting effectively with biomedical implants. Synthetic diamond provides an inexpensive solution to this problem.

The breakthrough has been made by biomedical engineer Dr Kate Fox and her team at RMIT's School of Engineering.

"Currently the gold standard for medical implants is titanium but too often titanium implants don't interact with our bodies the way we need them to," Fox said.

"To work around this, we have used diamond on 3D scaffolds to create a surface coating that adheres better to cells commonly found in mammals.

"We are using detonation nanodiamonds to create the coating, which are cheaper than the titanium powder.

"This coating not only promotes better cellular attachment to the underlying diamond-titanium layer, but encouraged the proliferation of mammalian cells. The diamond enhances the integration between the living bone and the artificial implant, and reduces bacterial attachment over an extended period of time.

"Not only could our diamond coating lead to better biocompatibility for 3D-printed implants, but it could also improve their wear and resistance. It's an exceptional biomaterial."

The breakthrough was made possible with recent advances in the 3D printing of titanium scaffolds at RMIT's Advanced Manufacturing Precinct. The coating is created via a microwave plasma process at the Melbourne Centre for Nanofabrication. The titanium scaffolds and diamond are combined to create the biomaterial.

"It will be a number of years before a technology like this is rolled out, and there are many steps to take until we see it available to patients," Fox said. "But what we have done is taken the first crucial step in a long and potentially incredible journey."

PhD researcher Aaqil Rifai, who is working on the new technology with Fox, said diamond is so effective because carbon is a major component of the human body.

"Carbon has an incredible level of biocompatibility," Rifai said. "Our body readily accepts and thrives off diamond as a platform for complex material interfacing."

In addition to orthopaedics, diamond has also been used to coat cardiovascular stents - tubes that help keep the heart's arteries open - and on joints, as well as in bionics and prosthetics.

For now, the researchers are concentrating on how the technology can be used for orthopaedics.

"3D printing is a groundbreaking revolution in the modern era. With 3D printing we can design patient specific implants of medical grade. The technology is fast, accurate, reliable and saves labour time," Rifai said.

"The scalability of 3D printing is growing rapidly, so we can expect to see diamond coatings to become common in orthopaedics sometime in the near future."

The breakthrough has been reported in ACS Applied Materials and Interfaces and involved researchers from a range of disciplines at RMIT and other Australian universities.