Culture

A unique group of dogs helped the Inuit conquer the tough terrain of the North American Arctic, major new analysis of the remains of hundreds of animals shows.

The study shows that the Inuit brought specialised dogs with them when they migrated from Alaska and Siberia instead of adopting local dogs they would have come across during their migration. They instead maintained their own dogs, suggesting they were keen to enhance or keep the special features they had. By analysing the shape of elements from 391 dogs, the study shows that the Inuit had larger dogs with a proportionally narrower cranium to these earlier dogs. The Inuit dogs are the direct ancestors of modern Arctic sledge dogs, although their appearance has continued to change over time.

Experts had thought the Inuit used dogs to pull sledges, and this is the first study which shows they introduced a new dog population to the region to do this. These dogs then spread across the North American Arctic alongside Inuit migrants.

Dr Carly Ameen, an archaeologist from the University of Exeter who led the study, said: "Dogs have lived in North America for as long as humans, but we show here that the Inuit brought new dogs to the region which were genetically distinct and physically different from earlier dogs.

"Thousands of years ago there was not the huge number of dog breeds as we know them today. Through analysing the DNA and morphology of the remains of hundreds of dogs we've found that the dogs used by the Inuit had distinctive skull and teeth shapes, and would have likely looked different in life to dogs already in the Arctic."

Experts also examined the DNA from 921 dogs and wolves who lived during the last 4,500 years. This analysis of the DNA, and the locations and time periods in which they were found, shows dogs from Inuit sites occupied from around 2,000 years ago were genetically different from the dogs already in the region.

Study co-lead author Tatiana Feuerborn, from the Globe Institute in Denmark and the Centre for Palaeogenetics in Sweden, said: "Archaeological evidence has shown us that before the Inuit arrived in North America dog sledging was a rarity. Our analysis of the DNA suggests dogs brought by the Inuit were distinct from the earlier dogs of the North American Arctic to fill specialist role in helping communities thrive in this hostile environment by aiding with transportation and hunting. The genetic legacy of these Inuit dogs can still be seen today in Arctic sledge dogs."

The Inuit were specialised sea mammal hunters, and were more mobile than other groups living in the Arctic, migrating huge distances across the region over 1,000 years ago, with the help of dog sledges and water craft. Today, sledge dogs whose origins can be traced back to the Inuit period continue to be an important part of Arctic communities.

1.7 million. That's how many people are infected with the human immunodeficiency virus (HIV) each year worldwide. 1.7 million people who are condemned to lifelong antiretroviral therapy (ART) or risk developing fatal AIDS . Out of the 37.9 million people living with HIV (PLWH), 22.3 million have access to ART, allowing them to have an almost normal lifespan. Unfortunately, however, the medications only go so far: they don't reach the cells where the virus lies dormant for years. Moreover, potential long-term adverse effects of these medications remain unknown.

Still, HIV research has been making steady strides to help the large number of PLWH. HIV laboratories around the globe are trying to unlock the "secrets" of the virus and find its weak spots in order to prevent or cure the infection. At the Montreal Clinical Research Institute (IRCM), scientists Éric A. Cohen and Tram NQ Pham have recently identified a way to thwart HIV infection at its very early stages. Their discovery is the subject of an article in the scientific journal Cell Reports.

The window of vulnerability: a few crucial first days

"Contrary to popular belief, HIV is not so easily transmitted," says Éric Cohen, director of the Human Retrovirology Research Unit at the IRCM and a virology professor in the Department of Microbiology, Infectious Diseases and Immunology at Université de Montréal. "We are studying the window of vulnerability of the virus, meaning the moments in the infection process when it could be weakened or attacked. We focused on the very early stages following viral invasion."

Once transmitted, HIV does not immediately spread through the body. It initially has to multiply locally, mainly in the genital tissues. It is only after this initial, local expansion that the virus spreads. This localized expansion offers a very brief window of vulnerability before the virus efficiently establishes a systemic infection.

The immune response is like an armed struggle: an enemy infiltrates and the body defends itself. Viruses are the intruders, and white blood cells are soldiers trying to hold down the fort. The white blood cells are equipped with their own "infantry units": lymphocytes, phagocytes, granulocytes and others. The phagocyte group has an even more specialized unit known as 'plasmacytoid dendritic cells' (PDCs). These small, round-shaped cells patrol the body, specializing in both pathogen detection and antiviral response orchestration. In other words, they are the whistleblowers, the ones through which the entire defence process is set into motion. When they detect a threat, they change shape and develop protuberances called dendrites. "Most importantly, they start producing large amounts of interferon, a protein that triggers a state of infection resistance in other cells," Cohen explained.

As its name implies, HIV preferentially targets the immune system: it attacks and weakens the body's own defences, and the infected person becomes susceptible to the slightest infection. As soon as it arrives, HIV gets PDCs out of the way and prevents them from sounding the alarm. "The virus doesn't seem to kill them directly, but it makes them disappear in a way that is still not understood," said Pham, the senior research associate in the Human Retrovirology Research Unit. "The loss of PDCs from both the infection site and throughout the body helps establish the infection."

A humanized mouse model to fight HIV infection

"Given what HIV does to PDCs, we wondered what would happen if we boosted PDC levels and their function both prior to and during infection," said Cohen. To test this, the scientists used a special protein known as Flt3 receptor ligand to stimulate the production of PDCs from the bone marrow of humanized mice. These rodents are engineered to have a human immune system in place of the mouse's own machinery. Consequently, in an infected humanized mouse, HIV behaves as it otherwise would in a human host.

Administration of this special protein maintained high levels of PDCs in these mice and produced some striking results: 1) the initial number of infected mice was reduced; 2) the time it took for the virus to be detectable in the blood was lengthened; and 3) the amount of virus in the blood, also known as viremia, was significantly reduced. "We observed up to a 100-fold decrease in viremia," Pham noted. "In other words, the initial infection is suppressed by maintaining a high level of PDCs."

The Implications for designing a vaccine

This seminal work also showed that the injection of the Flt3 receptor ligand not only increased PDC abundance, but also boosted their ability to detect the virus and produce interferon following its detection.

Of course, HIV infection normally goes unnoticed and by the time the viremia is detectable, it is a little too late. In this context, the discovery by Cohen and Pham is highly important in terms of prevention and a potential cure. "These new findings will be crucial in the design of an HIV vaccine, which is basically aimed at teaching the immune system to defend itself by introducing it to a weakened form of the virus," said Cohen. "We can now focus on PDCs in order to control the seeding and expansion of the virus at the early stage of infection."

A school- and family-based intervention, called the CHIRPY DRAGON program, may be an effective intervention for preventing obesity in children in urban China, according to a study published November 26 in the open-access journal PLOS Medicine by Bai Li of the University of Bristol, Peymane Adab of the University of Birmingham , and Wei Jia Liu of the Guangzhou Centre of Disease Control and Prevention, and colleagues.

In low- and middle-income countries where childhood obesity is increasing rapidly, there is a lack of rigorous development and evaluation of prevention interventions. Previous childhood obesity prevention trials conducted in China have not provided robust, high-quality evidence of effective interventions. Without effective prevention programs, China is estimated to have 50 million overweight/obese children by 2030. In the new study, the researchers developed CHIRPY DRAGON (CHInese pRimary school children PhYsical activity and DietaRy behAviour chanGes InterventiON), with the goal of preventing obesity in urban, primary school-aged children in China. Participants in the randomized controlled trial included 1,461 six-year-old children from 40 primary schools in Guangzhou, China.

One group of schools received a package of activities designed to increase healthy eating and physical activity (i.e., the CHIRPY DRAGON program) over 12 months and the other group of schools continued with their usual activities. Children, particularly girls and those who were overweight or obese at baseline, in the group of schools receiving the program had a lower body-mass index at the end of the 12-month period, compared with children in the schools not receiving the program. In the intervention group, significant beneficial effects were also observed for the consumption of fruits and vegetables, sugar-sweetened beverages and unhealthy snacks, in addition to sedentary behavior and physical activity. The program was also good value for money (£1,760 per quality-adjusted life-years). It is not yet determined whether this intervention program can be successfully transferred to other contexts, but it may be effective in other locations that share similar characteristics to urban China.

A new actor in the immune system of plants has been identified. KAUST scientists have identified the protein MAP4K4 is needed to mount proper defenses against environmental pathogens.

The discovery helps explain the tight control of immune signaling in plants and reveals targets in a molecular pathway that could be manipulated by crop breeders. "Our findings are directly applicable to make plants more resistant to pathogens," says study author, Heribert Hirt, Professor of Plant Science at KAUST's Desert Agriculture Initiative.

MAP4K4 (short for mitogen-activated protein kinase kinase kinase kinase 4) is a well-established player in human immunity and inflammation, but its role in plant disease resistance was unknown. Hirt and his collaborators stumbled on it during a large screen for proteins involved in signal transduction in the weedy thale cress Arabidopsis. By studying mutant plants that lack a working copy of MAP4K4, Hirt's team then drilled down into the core functions of this protein.

First, they showed that MAP4K4 was essential for proper immune responses to flg22, a peptide derived from a bacterial protein found within the filamentous flagellum of disease-causing microbes. Working with colleagues in France, the KAUST researchers--led by Hirt and postdoctoral fellow, Yunhe Jiang--then detailed how.

They demonstrated that MAP4K4 directly adds chemical tags (in the form of phosphate groups) at several sites of another protein, BIK1. This helps stabilize BIK1 and promotes the production of highly toxic molecules that play a central role in pathogen resistance, explains Jiang. The researchers also showed that MAP4K4 tags a repressor of BIK1 with phosphate decorations. This chemical adornment disables the negative regulator to further promote BIK1 activation.

So far, Hirt and his lab group in the Biological and Environmental Science and Engineering Division of KAUST have only described this function of MAP4K4 in Arabidopsis immunity. They reported the findings on 2 September 2019 in Reports.

"The next step is to test our findings also in crops by generating knock-out mutants," Hirt says. "This is quite feasible now by using CRISPR-Cas9 gene-editing technology that is established in tomato, rice and other species of agricultural importance."

The researchers also plan to examine the roles of other regulatory proteins within the MAP4K family, of which at least 10 exist in plants. Intriguingly, Jiang showed that one family member, MAP4K3, seems to act synergistically with MAP4K4 to control BIK1 stabilization and pathogen-induced immune responses.

Closely related MAP4K proteins may thus share overlapping functions but also have distinct features that collectively contribute to the fidelity of immune signaling in plants. A better knowledge of these signaling mechanisms could help agribusinesses keep plant pathogens at bay.

In every weather situation, plants need to be robust and flexible at the same time. These structural properties come from its cell wall: It's responsible to keep the plant in shape, to compensate its osmotic pressure and to protect it against pathogens e.g. bacteria, viruses or fungal attacks. The cell walls of plants are largely built from polymers and - the polysaccharide - cellulose. As a linking agent, polysaccharides have the important task to connect long-chain polymers and to build a molecular network of tiny strands, called fibrils. Those contribute to the tensile strenght of the plant.
One of the sugar building blocks is the branched-chain monosaccharid Apiose, derived from the latin word „Apium", a plant genus, to which celeriac and parsley are part of.

„Apiose is preoccupying the Plant Biochemical Research for more than a hundred years, since its function in plants has not yet been fully understood. Besides, the mechanism, which is responsible for the production of Apiose in nature, was still not known", tells Bernd Nidetzky, CSO of the Austrian Centre of Industrial Biotechnology (acib) and Director of the Institute of Biotechnology and Bioprocestechnology at the Technical University of Graz, Austria.

One enzyme, four steps

acib and TU Graz together with the Universities Pavia (Italy) and Barcelona (Spain) discovered, how Apiose is produced by a single enzyme called UAXS(UDP-apiose/UDP-xylose Synthase). For the first time, the scientists were able to decode the entire mechanism of this enzyme. These groundbreaking discoveries were published in the prestigious journal Nature Catalysis. „Isolated from the cress Arabidopsis thaliana, the catalyst possesses special properties: Whereas most biosynthetic processes for the manufacturing of complex molecules need several reaction steps, the UAXS-enzyme selectively catalyzes four reaction steps", Nidetzky reveals. By doing so, the enzyme is able to break down organic carbon compounds as well as to establish new molecular compounds. This results in the change from an six ring sugar molecule (Hexose) to a structural converted five ring sugar (Pentose). By creating new organic carbon compounds, the enzyme is responsible for giving plants their strenght properties.

The elucidation of the encymatic mechanism of Adipose was able due to the interdisciplinary collaboration from the research areas enyzmology and biocatalysis, structural biology and molecular modelling.

New insights in the capabilities and uses of enzymes

The unusual and highly complex reaction sequence of Apiose biosynthesis enables the enymologists new, fascination insights into the molecular evolution of higher plants and gives information about how certain enzymes are able to coordinate multi step processes, leading to a final product. Nidetzky: „By understanding the biogenesis of the carbohydrate Apiose in plants grants us the basis for future industrial applications, for instance the production of valuable sugar molecules for possible products e.g. fine chemicals or novel biopharmaceuticals."

When listening to a song or watching a dance, humans tend to follow the rhythm of the music. This is because one fundamental aspect of music is its rhythm, the way we synchronize with the temporal regularities of a melody or a dance. A recent study explores how our brain fuses with musical rhythm and the extent to which humans share this ability with other animals.

Alexandre Celma-Miralles and Juan Manuel Toro, an ICREA research professor with the Department of Information and Communication Technologies (DTIC), and members of the Comparative Cognition and Language (LCC) research group at the Center for Brain and Cognition (CBC) at UPF, explain this peculiarity in an article published this November in the journal Brain and Cognition.

"This study explores the relationship between the rhythmic structure of music and the spatial dimension of sound. We study how the brain interacts with sounds that are spatially separate to build up a metrical structure", explain Celma-Miralles and Toro, the authors of the study.

So, they compared the neural responses of professional musicians with those of untrained listeners while both groups listened to a waltz. In one of the study experiments, the participants had to pay attention to sounds defined by their spatial position (the sounds were separated in space). In another experiment the participants had to pay attention to a visual distraction. Data for the study were obtained from the frequencies of EEG recordings of each subject.

Rhythm and beat are enhanced by experience

The researchers found that regardless of the participant's musical training, the brains of all listeners synchronized with the rhythm. The results also showed that musicians' neuronal responses were much stronger and more resistant to distractions than those of non-musicians. That is, the study revealed that training facilitates rhythmic synchronization.

As the researchers state, "the most relevant point of this study is that it demonstrates that our brains are prepared to follow rhythm, regardless of whether we listen to a song or watch a dance". This reinforces the idea that the neuronal processing of rhythm and beat is facilitated by previous experience with rhythmic events during long periods of formal musical training.

Researchers from the national psychiatric project iPSYCH have found that autism and ADHD share changes in the same genes. The new knowledge relates directly to the biological causes of the two child psychiatric disorders.

In Denmark, approximately one per cent of schoolchildren have autism and two to three per cent are diagnosed with ADHD. Autism and ADHD are different developmental disorders, but they can have certain common symptoms. For example, children with autism can demonstrate violent or aggressive behaviour, be impulsive, and have problems in school and with social relations - and these same symptoms can be shared by children with ADHD.

Researchers from iPSYCH, Denmark's largest research project in the field of psychiatry, have now discovered that the similarities between the two diagnoses can be linked to changes in the same genes. The new study is the largest study to date of rare mutations in the genome of people with ADHD and autism.

"The very fact that mutations are found to the same extent and in the same genes in children with autism and in children with ADHD, points towards the same biological mechanisms being involved," says Anders Børglum, who is professor at Aarhus University, principal investigator at iPSYCH and one of the leading researchers behind the study. The study was carried out in collaboration with the Broad Institute and Harvard.

First time a gene is linked to ADHD and autism

The results have just been published in the international journal Nature Neuroscience.

"This is the first time that the genome has been mapped so comprehensively for both ADHD and autism, and the discovery that children with ADHD have the same amount of deleterious gene mutations in their DNA as children with autism is both striking and quite surprising," says Anders Børglum.

The findings point directly towards which biological causal mechanisms are shared by ADHD and autism.

"In the study, the gene that is most frequently affected by mutations in people with ADHD or autism is the so-called MAP1A gene. The gene is involved in the formation of the physical structure of nerve cells - their inner 'skeleton', so to speak - and is important for the development of the brain," explains Anders Børglum.

This is the first time that this gene has been linked to the development of ADHD and autism, and the mutations found by the researchers give a significantly increased risk of developing autism and/or ADHD.

"We discovered an increased burden of mutations that destroy or severely affect the MAP1A gene in those with ADHD and autism, while very few of the control subjects had such changes in the gene," explains Anders Børglum.

This means that the risk of ADHD and autism increases by more than 15 times for people who carry such a mutation. The researchers have analysed the genes of approximately 8,000 people with autism and/or ADHD, and 5,000 people without either of the two disorders, all from Denmark. The study also incorporated additional data from approx. 45,000 international control subjects who did not have any psychiatric disorders.

"The study shows that many more genes for ADHD and autism can be identified directly by studying more people in a similar way with extensive DNA sequencing, thereby providing a more complete picture of the biological causal mechanisms and possible approaches to medical treatment," explains the researcher.

As part of the project, Anders Børglum and his colleagues have had access to samples from the Danish National Biobank at the Statens Serum Institut and to data from the Danish Psychiatric Central Research Register. People born in Denmark between 1981 and 2005 were matched with diagnoses of autism, ADHD and mental retardation.

Over 40% of online petitions started by residents of central Russia get results. In the Far East, this is the case with only 2% of online petitions, while in the regions of the North Caucasus it is even less. Russian experts, Nadezhda Radina https://www.hse.ru/en/org/persons/62303992 (HSE University) and Daria Krupnaya, studied the willingness of authorities and businesses to respond to citizens' digital activism based on data from the Change.org platform.

Results Versus Inaction
Traditionally, a petition is a collective appeal, usually to authorities or organizations. An electronic petition is an appeal published online, and they are conducted mostly on specialized sites. The most well-known ones in Russia are:

Roi.ru (Russian Public Initiative)
Change.org
OnlinePetition
democrator.ru

Change.org is active in 196 countries and 14 languages. Officials have the right to ignore petitions posted on the site (petition results on the site are not legally binding, insofar as the platform does not collect enough information about the signers). However, a large public response puts pressure on officials and businesses to take action.

'Nearly every hour, a petition on Change.org achieves victory,' the site says. Of the 22,452 Russian-language petitions created on the site from 2012 to 2017 that the researchers analyzed, 4% (918) received the status of 'fulfilled' (as indicated by the petition's creator after the collection of signatures).

Topics and Issues
The issues of petitions provide insight into the concerns of a given region. About half (44%) of the 22.4 thousand filed petitions in Russia concern social issues, and the second largest portion (18%) concern political issues.

Breakdown of Russian petition issues by category (%):
Society - 44%
Politics - 18%
Culture - 11%
Animals - 9%
Environment-- 6%
Education - 4%
Sports - 3,8%
Medicine - 3%
Economy - 0,7%
Religion - 0,5%
The North-West Federal District is primarily distinguished by its concern for social issues - 51% of petitions started in this region fell into this category. Russia's most politically active residents can be found in central Russia: 43.8% of petitions from the Central Federal District concern the resignation of officials, changing decisions, amending laws, fighting corruption, and so on. Political issues also dominate petitions created in Siberian (34%) and North Caucasian (23%) districts.

Emulating the Centre
'With the exception of the strong political bent of petitions started in the Central Federal District, there were no significant differences found between regions of Russia in terms of the kinds of demands being made -- people are concerned about similar problems everywhere,' the study authors note.

With a share of 42%, the Central Federal District had the highest number of petitions that were successful in Russia, while the Far Eastern and the North Caucasian districts had the lowest -- 2% and 1%, respectively.

Federal District Ratings
by percent share of successful petitions in Russia (%)
1. Central - 42%
2. North-West - 14%
3. Privolzhsky - 13%
4. Southern - 12%
5. Siberian - 9%
6. Ural - 7%
7. Far Eastern - 2%
8. North Caucasus - 1%
Petitions concerning society, culture, politics, and animal welfare enjoy the highest success rates. The Central Federal District's success rate can be explained by the population's civic activity in urban areas, the greater responsiveness of the petition addressees, more advanced infrastructure (for example, the quality and accessibility of the Internet), and users' involvement with technology that facilitates active participation.

Examples of successful petitions from the site Change.org
(number of signatures)
'Social Insurance Fund, stop the torture: give me my wheelchair. It's the law.' (209,701)
'Help!!! The authorities have lifted the ban on shooting the Baikal seals!!!' (374,326)
'Provide cancer patients with life-saving medicine! We have the right to life!' (428,105)
'Stop discrimination on the basis of appearance and age at PJSC Aeroflot' (50 223)
'We demand compensation for the victims of the St. Petersburg metro terrorist attack on 03.04.2017' (157 649)
'Novgorod officials must provide housing to WWII veterans, as required by law.' (191 740)
Regional Values
The response of government bodies and businesses to petitions from non-state platforms provides an indication of the quality of a given region's management. Successful petitions point to a willingness to enter into dialogue with civil society, and the issues of the petitions provide insight into the values of a given region.

By grouping the successful petitions by issue category, the researchers divided the federal districts into three clusters:

So long as they contribute to the animal rights protections, governmental bodies and businesses are safe to ignore other demands of the population. In the Far Eastern Federal District, 95% of successful petitions were in defense of animal rights.
Governmental bodies and businesses respond only to crucial problems. The Ural, North Caucasian and Siberian federal districts rank highest in social issue victories. According Ronald Inglehart's system of value classification, rational survival values are predominantly shared here, with a certain tendency toward post-materialistic values.
In response to population demands, governmental bodies and businesses are partly willing to address a wide range of current issues. In the Central, Volga, South and North-West federal districts -- mostly urban areas with city populations of a million people or more -- there is a predominance of post-materialist values (rational values of self-expression). In these regions, petitions on social issues (48.3%), political issues (17%), as well as on cultural issues (12.7%), education (11.3%) and sports (4.5%) were successful.

Probing the functional segments, or 'motifs', of proteins has helped scientists identify the minimal ingredients needed for them to form biological patterns.

Writing in the journal eLife, the researchers describe how they dissected the biological phenomenon of protein pattern formation into its main functional modules, and then rebuilt the process from the ground up in a completely new way.

Proteins self-organise to form patterns in living cells, which are essential for key functions such as cell division, communication and movement. A striking example is the MinDE system of the bacterium Escherichia coli (E. coli). This system produces oscillations of two protein types, MinD and MinE, between two poles of the rod-shaped bacteria, positioning the machinery for cell division to midcell. It can be reconstituted in the laboratory, allowing scientists to control and manipulate the functional elements needed for pattern formation via protein mutations.

"Because of its simplicity, the MinDE system has been invaluable in understanding the mechanisms of protein-based pattern formation," says Philipp Glock, a PhD student at the Max Planck Institute of Biochemistry in Munich, Germany, and co-lead author alongside Fridtjof Brauns and Jacob Halatek, both from the Ludwig Maximilians University of Munich. "A key question that remains is whether this structural and functional complexity can be reduced further to reveal a set of minimal ingredients for pattern formation."

To answer this, Glock and his colleagues created a minimalistic version of MinE, which plays an antagonistic role in the two-protein MinDE system, by dissecting the protein in a set of core functional motifs, guided by theoretical modelling. One motif, the short helical sequence of amino acids which MinE uses to interact with MinD, is not enough to produce patterns on its own. But adding other functional motifs of MinE one at a time enabled the scientists to fully design new minimal pattern-forming protein mutants.

The team found that at least one other functional motif is required to form patterns. This can either be a motif for membrane binding or a dimerizing motif, which binds to other molecules of the same kind. Neither of these motifs needs to be from native MinE, but can be replaced and potentially simplified further.

Mathematical modelling then allowed the authors to explain why these features are required and how they enable patterns to form. Moreover, they predicted how these patterns adapt to the cell shape in E. coli. The team says that testing these predictions is an exciting goal for future experiments.

"Our work provides a starting point for a modular and tunable experimental platform to design protein-based pattern formation from the bottom-up," says Petra Schwille, PhD, Director of the Department of Cellular and Molecular Biophysics at the Max Planck Institute of Biochemistry, and co-senior author alongside theoretical physicist Erwin Frey, from the Ludwig Maximilians University of Munich. She adds that while the patterns created by the new system are less regular than those formed by the native MinDE system, they are still sufficient for reproducing and studying basic biological processes.

The model can now be used to study which functional features, regardless of a particular protein system, need to be combined to allow for self-organisation and pattern formation in biology. "Our modular approach may also provide the necessary data for computer modelling of pattern formation in other types of bacteria, as well as more complex organisms," Schwille concludes.

The health of cells is maintained, in part, by two types of movement of their nucleoli, a team of scientists has found. This dual motion within surrounding fluid, it reports, adds to our understanding of what contributes to healthy cellular function and points to how its disruption could affect human health.

"Nucleolar malfunction can lead to disease, including cancer," explains Alexandra Zidovska, an assistant professor in New York University's Department of Physics and the senior author of the study, which appears in the journal eLife. "Thus, understanding the processes responsible for the maintenance of nucleolar shape and motion might help in the creation of new diagnostics and therapies for certain human afflictions."

Recent discoveries have shown that some cellular compartments don't have membranes, which were previously seen as necessary to hold a cell together. Researchers have since sought to understand the forces that maintain the integrity of these building blocks of life absent these membranes.

What has been observed is the nature of this behavior. Specifically, these compartments act as liquid droplets made of a material that does not mix with the fluid around them--similar to oil and water. This process, known as liquid-liquid phase separation, has now been established as one of the key cellular organizing principles.

In their study, the researchers focused on the best known example of such cellular liquid droplet: the nucleolus, which resides inside the cell nucleus and is vital to cell's protein synthesis.

"While the liquid-like nature of the nucleolus has been studied before, its relationship with the surrounding liquid is not known," explains Zidovska, who co-authored the study with Christina Caragine, an NYU doctoral student, and Shannon Haley, an undergraduate in NYU's College of Arts and Science at the time of the work and now a doctoral student at the University of California at Berkeley. "This relationship is particularly intriguing considering the surrounding liquid--the nucleoplasm--contains the entire human genome."

Yet, unclear is how the two fluids interact with each other.

To better understand this dynamic, the scientists examined the motion and fusion of human nucleoli in live human cells, while monitoring their shape, size, and smoothness of their surface. The method for studying the fusion of the nucleolar droplets was created by the team in 2018 and reported in the journal Physical Review Letters.

Their latest study showed two types of nucleolar pair movements or "dances": an unexpected correlated motion prior to their fusion and separate independent motion. Moreover, they found that the smoothness of the nucleolar interface is susceptible to both changes in gene expression and the packing state of the genome, which surrounds the nucleoli.

"Nucleolus, the biggest droplet found inside the cell nucleus, serves a very important role in human aging, stress response, and general protein synthesis while existing in this special state," observes Zidovska. "Because nucleoli are surrounded by fluid that contains our genome, their movement stirs genes around them. Consequently, because the genome in the surrounding fluid and nucleoli exist in a sensitive balance, a change in one can influence the other. Disrupting this state can potentially lead to disease."

In a study published today, scientists report that the long-term success of clownfish depends more on living in a good neighbourhood than it does on good genes.

The natural home of the clownfish is the anemone, but not all anemones are equal. Study co-author Professor Geoff Jones, from the ARC Centre of Excellence for Coral Reef Studies at James Cook University (Coral CoE at JCU), says the reproductive success of the clownfish depends almost entirely on having a high-quality anemone home.

"For a clownfish, it's not 'who' you are, but 'where' you are that matters for your future reproductive success," Prof Jones said.

"In terms of their genes, clownfish are as good as they can be at finding a suitable habitat. The rest comes down to luck--of being in the right place at the right time."

"The success of big families that extend over many generations is linked to high-quality habitats, not their shared genes."

The quantitative genetic study comprises ten years of research on the coral reefs of Papua New Guinea. Family trees were established for the entire clownfish population at an island in Kimbe Bay, a well-known biodiversity hot spot. The team of scientists identified each fish individually and sampled its DNA to establish who was related to whom over five successive generations.

After constructing Kimbe Island's clownfish family tree, the researchers were able to assess the ability of the population to persist and the genetic potential to adapt to increasingly rapid environmental change. Unfortunately, the potential is almost nil.

"There are no particular genetic variants that contribute more offspring to the next generation. The quality of the host anemone contributes most to the ability of the clownfish to renew its population," Prof Jones said.

The scientists say that if high-quality anemones remain healthy, this will ensure the clownfish population can persist.

However, anemones, and coral reefs in general, are under direct threat from the impacts of climate change.

In increasingly warming waters, corals are more susceptible to bleaching. The process is the same for anemones -- their symbiotic algae leave when under stress. If they stay away long enough then the anemone starves to death, killing the fish's home at the same time.

The study is the first of its kind to evaluate the genetic capacity of a natural marine population to adapt to environmental change. This was otherwise largely the domain of evolutionary studies of species on land.

It is not surprising that intergenerational relationships in a marine population had yet to be sampled, according to co-author Dr Benoit Pujol, an evolutionary biologist from France's National Centre of Scientific Research (CNRS).

"Working out who is related to whom in the marine environment is extremely challenging," Dr Pujol said.

"Long-term genetic datasets for individuals within a marine population are incredibly rare. Until now, we just haven't had the data required to answer this question."

"But now that we have it, we find that Nemo is at the mercy of a habitat that is degrading more and more every year," added co-author Dr Serge Planes, a Director of Research at France's National Centre of Scientific Research (CNRS).

"To expect a clownfish to genetically adapt at a pace which would allow it to persist is unreasonable," he said.

"Their future depends on our ability to maintain the quality of their habitat," the authors conclude.

Miharu Nakanishi, Chief Researcher of Tokyo Metropolitan Institute of Medical Science, and her colleagues finds that psychological well-being at 52 years were prospectively associated with cognitive function at 69 years. The authors used data in women from the British 1946 birth cohort in the Medical Research Council's National Survey of Health and Development. There was a significant association between greater personal growth and lower self-acceptance at 52 years, and better cognition at 69 years.

November 26, 2019 - Tokyo, Japan -People around the world are living longer, and dementia has consequently become recognized as a public health priority in many countries. The Lancet Commission paper in 2017 collated a large body of medical research evidence that aims to address the dementia epidemic and following challenge for health and social care. It is estimated that as much as 35% of dementia cases could be prevented by targeting nine modifiable risk factors. However, relatively little is known about psychological well-being in this context.

Tokyo, Japan - Miharu Nakanishi, Chief Researcher of Tokyo Metropolitan Institute of Medical Science, and her colleagues finds that psychological well-being at 52 years were prospectively associated with cognitive function at 69 years. The authors used data in women from the British 1946 birth cohort in the Medical Research Council's National Survey of Health and Development.

Recent studies suggest that specific domains of psychological well-being, including negative affect, positive affect, and purpose in life, are related to cognitive function in older adults. Using the cohort data, the authors finds that there was a significant association between greater personal growth and lower self-acceptance at 52 years, and better cognition at 69 years. This association is adequately robust to control for childhood cognitive ability, physical activity, and other variables among nine modifiable risk factors.

The present study would add new implications to the risk reduction messages by more attention to the health promotion of middle-aged women who face midlife crises.

"Global environmental change should be considered a disability rights issue", first author Dr Aleksandra Kosanic and her colleagues Dr Mialy Razanajatovo (also University of Konstanz), Dr Jan Petzold (Center for Earth System Research and Sustainability (CEN), University of Hamburg) and Dr Amy Dunham (Rice University, USA) argue in their recently published Letter in Science, which has since been picked up on by Forbes and Scientific American. The researchers believe that climate change and the resulting loss of ecosystem services will affect the world's disabled populations disproportionately by exacerbating inequalities and increasing marginalization. Not only may disabled communities experience limited access to knowledge, resources and services, which may prevent them from effectively responding to climate change, they write. Disabled populations may also prove more vulnerable to extreme climate events, as research on Hurricane Katrina has revealed, to the loss of ecosystem services or to infectious diseases.

A government scheme to support the mental health of people affected by terrorist attacks needs to provide a better system of immediate psychological help, according to research led by the Care Policy and Evaluation Centre at the London School of Economics and Political Science (LSE).

The study, funded through the NIHR Policy Innovation and Evaluation Research Unit, explored the effectiveness of the Department of Health and Social Care's 'Screen and Treat Programme', which was set up to identify and refer people to mental health services following terrorist attacks in Tunisia, Paris and Brussels in 2015 and 2016.

Dr Eva Cyhlarova, who carried out the research, said that: "Terrorist attacks have wide-reaching consequences. Mental health needs are common for those affected. We wanted to see how effective the Screen and Treat programme was in identifying and referring people to mental health services and to understand how the agencies involved worked together. Our evaluation showed that the programme worked well in many ways, but it was available too late."

Most of the 77 people who responded to the study questionnaire said that the attacks had a major impact on their lives, according to the findings, published in the Journal of Health Services Research & Policy.

Many people reported anxiety, depression, difficulty going out or travelling, sleep problems, panic attacks, flashbacks and hyper-vigilance. A third had reduced their working hours and a similar proportion had taken sick leave.

Of those interviewed, two-thirds sought help from their GP before being contacted by the Screen and Treat programme (which was available only about a year after the first of the terrorist attacks). Almost all thought that their GP had not been helpful in dealing with post-traumatic stress disorder (PTSD) or referring to appropriate care. Interviewees reported that they used help offered by organisations external to National Health Service (NHS), with mixed experiences.

The study found that the Screen and Treat programme was valuable but identified several areas for improvement which could inform agencies' future planning responses. One recommendation is that there is a system to provide immediate psychological help after a terrorist attack. Although people who accessed support through the programme were generally satisfied with their treatment, most people thought it should have been available sooner.

Dr Cyhlarova also interviewed people from a range of agencies who organised and delivered the programme to understand how organisations work together as part of the response.

Professionals who worked in the planning and set-up of the programme understood the delays, with one respondent saying: 'We were slow off the mark in terms of contacting people...people said they could have done with that six months earlier.' All professionals who were interviewed as part of the study felt that the delay in setting up the programme limited its effectiveness. Waiting times for treatment also varied from no delay to a few months. One person who received treatment said: 'There was a delay in getting to the right person. I could have been somewhere else by now.'

The study found that the main reasons for slow responses were funding and data-sharing issues. Several professionals felt the service should be built into the NHS and involve local services (including GPs) rather than being managed from central government.

Professor Martin Knapp, who led the research, commented: "In future, evaluations should be embedded in the response to major incidents, with the aim of reaching the entire population of potentially affected individuals. Better understanding of people's responses to this type of trauma over time in wider contexts (for example group contexts) would help identify other factors important for resilience and recovery to be incorporated in future responses."

Researchers believe that autism is caused by mutations that occur sporadically in the egg or sperm or during pregnancy. Activity-dependent neuroprotective protein (ADNP) is a dominant gene whose de novo (during pregnancy) mutations are known to cause autism-related intellectual disabilities. A new Tel Aviv University study has found that ADNP mutations continue to occur in old age and accumulate in the brains of Alzheimer's disease patients.

The study was led by Prof. Illana Gozes and conducted by her PhD students Yanina Ivashko-Pachima and Adva Hadar, in collaboration with Iris Grigg, Oxana Kapitansky and Gidon Karmon. Hadar was co-supervised by co-author Prof. David Gurwitz of TAU's Sackler Faculty of Medicine. Collaborating laboratories included those of Vlasta Korenková (BIOCEV, Czech Republic), Michael Gershovits (Weizmann Institute of Science), C. Laura Sayas (Universidad de La Laguna, Tenerife, Spain), R. Frank Kooy (University of Antwerp, Belgium) and Johannes Attems (Newcastle University, UK). It was published on October 30 in Molecular Psychiatry.

Prof. Gozes is the first incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, head of the Elton Laboratory for Molecular Neuroendocrinology at TAU's Department of Human and Molecular Genetics, Sackler Faculty of Medicine and a member of TAU's Adams Super Center for Brain Studies and the Sagol School of Neuroscience.

"We discovered thousands of mutations in aging human brains, especially in the individual Alzheimer's brains," explains Prof. Gozes. "We were surprised to find a significant overlap in Alzheimer's genes undergoing mutations with genes that impact autism, intellectual disability and mechanisms associated with the cell skeleton/transport system health. Importantly, the cell skeleton/transport system includes the protein Tau, one of the major proteins affected in Alzheimer's disease, which form the toxic neurofibrillary tangles."

The protein ADNP was first discovered in Prof. Gozes's laboratory at TAU 20 years ago. Postmortem studies have indicated that it undergoes mutations in the aging Alzheimer's brain.

"Brain changes associated with Alzheimer's disease may begin 20 or more years before any symptoms appear," adds Prof. Gozes. "As neuronal damage increases, the brain can no longer compensate for the changes, and individuals show cognitive decline. Currently, the diagnosis of Alzheimer's occurs when the brain damage of individual patients is already widespread, so that current drugs can at most offer symptomatic relief. But they provide no cure."

In their new study, Prof. Gozes and her group propose a paradigm-shifting concept in the understanding of Alzheimer's disease. According to the research, accumulating mosaic somatic mutations -- uninherited genetic alterations passed on during cell division -- promote brain pathology. This could provide an avenue toward developing new diagnostic measures and therapies.

Through a complete sequencing of protein encoding DNA (a technique called RNA-sequencing) and further bioinformatics analysis, the team identified thousands of mutations in the aging Alzheimer's brain. Further sophisticated cell cultures and live cell imaging technologies allowed for the identification of protective molecules that could serve as potential drug candidates.

"We found in cell cultures that the ADNP-derived snippet, the drug candidate NAP, inhibited mutated-ADNP toxicity and enhanced the healthy function of Tau, a key brain protein involved in Alzheimer's disease and other brain diseases," says Prof. Gozes. "We hope that new diagnostics and treatment modes will be developed based on our discoveries."

The study was partially supported by the Israel Science Foundation, AMN Foundation, ERA-NET Neuron, Alicia Koplowitz Foundation, Spanish Friends of Tel Aviv University, Anne and Alex Cohen, Canadian Friends of Tel Aviv University, and Drs. Ronith and Armand Stemmer, French Friends of Tel Aviv University. Additional support included UK, Czech, Spanish and EU grants to the international collaborators.

The use of ADNP and related mutations for Alzheimer's diagnosis and for ADNP-related peptide/peptide mimetics AD/ASD treatment is under patent protection (I. Gozes, A. Hadar, Y. Ivashko-Pachima). Prof. Gozes also serves as the chief scientific officer of Coronis Neurosciences, a company developing NAP (CP201) for the treatment of ADNP syndrome, the autism spectrum disorder.