Culture

In Swahili, red-billed oxpeckers are called Askari wa kifaru, or "the rhino's guard." Now, a paper appearing April 9 in the journal Current Biology suggests that this indigenous name rings true: red-billed oxpeckers may act as a first line of defense against poachers by behaving like sentinels, sounding an alarm to potential danger. By tracking wild black rhinos, researchers found that those carrying oxpeckers were far better at sensing and avoiding humans than those without the hitchhiking bird.

While conservation efforts have rebounded the critically endangered black rhino's numbers, poaching remains a major threat. "Although black rhinos have large, rapier-like horns and a thick hide, they are as blind as a bat. If the conditions are right, a hunter could walk within five meters of one, as long as they are downwind," says Roan Plotz (@RoanPlotz), a lecturer and behavioral ecologist at Victoria University, Australia., who co-authored the paper with ecological scientist Wayne Linklater (@PolitEcol) of California State University - Sacramento. Oxpeckers, which are known to feed on the ticks and lesions found on the rhino's body, may make up for the rhino's poor eyesight by calling out if they detect an approaching human.

To study the role that oxpeckers might play, Plotz and his team recorded the number of oxpeckers on two groups of the rhinos they encountered. Rhinos tagged with radio transmitters--which allowed researchers to track them while evading detection from oxpeckers--carried the bird on their backs more than half the time. The untagged black rhinos they found, on the other hand, carried no oxpeckers most of the time--suggesting that other untagged rhinos that carried the birds might have avoided encountering the researchers altogether. "Using the differences we observed between oxpeckers on the tagged versus untagged rhinos, we estimated that between 40% and 50% of all possible black rhino encounters were thwarted by the presence of oxpeckers," says Plotz.

Even when the researchers were able to locate the tagged rhinos, the oxpeckers' alarm calls still appeared to play a role in predator defense. The field team ran a "human approach" experiment, where one researcher would walk towards the rhino from crosswind while a colleague recorded the rhino's behavior. The field team recorded the number of oxpecker carried, the rhinos' behavior upon approach, and the distance of the researcher when either the rhinos became vigilant or, if undetected, it became unsafe to get any closer.

"Our experiment found that rhinos without oxpeckers detected a human approaching only 23% of the time. Due to the bird's alarm call, those with oxpeckers detected the approaching human in 100% of our trials and at an average distance of 61 meters--nearly four times further than when rhinos were alone. In fact, the more oxpeckers the rhino carried, the greater the distance at which a human was detected," he says. He adds that these improved detection and distance estimates may even be conservative, because they don't take into account the untagged rhinos carrying oxpeckers that the team could not detect.

When a rhino perceived the oxpecker alarm call, it nearly always re-oriented itself to face downwind--their sensory blind spot. "Rhinos cannot smell predators from downwind, making it their most vulnerable position. This is particularly true from humans, who primarily hunt game from that direction," says Plotz.

Taken together, these results suggest that oxpeckers are effective companions that enable black rhinos to evade encounters with people and facilitate effective anti-predator strategies once found. Some scientists even hypothesize that oxpeckers evolved this adaptive behaviour as a way to protect their source of food: the rhinos.

"Rhinos have been hunted by humans for tens of thousands of years, but the species was driven to the brink of extinction over the last 150 years. One hypothesis is that oxpeckers have evolved this cooperative relationship with rhinos relatively recently to protect their food source from human overkill," says Plotz.

Despite this closely tied relationship, oxpecker populations have significantly declined, even becoming locally extinct in some areas. As a result, most wild black rhino populations now live without oxpeckers in their environment. But based on the findings in this study, reintroducing the bird back into rhino populations may bolster conservation efforts. "While we do not know that reintroducing the birds would significantly reduce hunting impacts, we do know oxpeckers would help rhinos evade detection, which on its own is a great benefit," says Plotz.

Plotz says that these findings, inspired by a Swahili name, also highlight the importance of local knowledge. "We too often dismiss the importance of indigenous people and their observations. While western science has been incredibly useful, there are many insights we can learn from indigenous communities."

Quantum computers that are exponentially faster than any of our current classical computers and are capable of code-breaking applications could be available in 12 to 15 years, posing major risks to the security of current communications systems, according to a new RAND Corporation report.

The security risks posed by this new category of computers can be managed if the U.S. government acts quickly, and a centrally coordinated, whole-of-nation approach is the best way to manage those challenges, according to RAND researchers.

"If adequate implementation of new security measures has not taken place by the time capable quantum computers are developed, it may become impossible to ensure secure authentication and communication privacy without major, disruptive changes," said Michael Vermeer, lead author of the report and a physical scientist at nonprofit, nonpartisan RAND. "The United States has the means and very likely enough time to avert a quantum disaster and build a safer future, but only if it begins preparations now."

Standard protocols for postquantum cryptography that can maintain the current level of computing security are expected to be drafted and released within the next five years.

However, the nationwide or global transition necessary to implement the standard protocols and mitigate the vulnerability from quantum computing is expected to take decades - far longer than the time that experts estimated would be available for the task, the report finds.

The report says that the sooner an interoperable standard for postquantum cryptography can be widely implemented, the more the eventual risk will be diminished.

Building cyber-resilience and cryptographic agility into the digital infrastructure also will offer an opportunity to adopt structural improvements in the use of cryptography in communication and information systems that could improve the nation's ability to respond to both current and future cyber threats.

If the United States acts in time with appropriate policies, risk reduction measures, a whole-of-government approach and a collective sense of urgency, it has an opportunity to build a future communications infrastructure that is as safe or safer than the status quo, according to RAND researchers.

The nation could reap the enormous benefits expected from quantum computing while enhancing privacy and security.

"The advent of quantum computers presents retroactive risk because information being securely communicated today without postquantum cryptography may be captured and held by others now in order to be decrypted and revealed later once quantum computers are created. This presents a vulnerability that urgently needs to be addressed," said Evan Peet, a co-author of the report and an economist at RAND.

Funding for the project was provided by RAND supporters and income from operations.

The report, "Securing Communications in the Quantum Computing Age: Managing the Risks to Encryption," is available at http://www.rand.org.

This report is part of a broader effort, to envision critical security challenges in the world of 2040, considering the effects of political, technological, social, and demographic trends that will shape those security challenges in the coming decades. The research was conducted within the RAND Center for Global Risk and Security.

Researchers at the University of California San Diego and the University of Cambridge have 3D printed coral-inspired structures that are capable of growing dense populations of microscopic algae. The work, published Apr. 9 in Nature Communications, could lead to the development of compact, more efficient bioreactors for producing algae-based biofuels. It could also help researchers develop new techniques to repair and restore coral reefs.

In tests, the printed coral structures grew a commercial strain of microalgae, Marinichlorella kaistiae, up to 100 times more densely than natural corals.

"Corals are one of the most efficient organisms at using, capturing and converting light to generate energy. And they do so in extreme environments, where light is highly fluctuating and there's limited space to grow. Our goal here was to use corals as inspiration to develop more productive techniques for growing microalgae as a form of sustainable energy," said first author Daniel Wangpraseurt, a marine scientist at the University of Cambridge.

To build the coral structures, Wangpraseurt teamed up with UC San Diego nanoengineering professor Shaochen Chen, whose lab specializes in a rapid, 3D bioprinting technology capable of reproducing detailed structures that mimic the complex designs and functions of living tissues. Chen's method can print structures with micrometer-scale resolution in just minutes.

This is critical for replicating structures with live cells, Chen said.

"Most of these cells will die if we were to use traditional extrusion-based or inkjet 3D printing processes because these methods take hours. It would be like keeping a fish out of the water; the cells that we work with won't survive if kept too long out of their culture media. Our process is high throughput and offers really fast printing speeds, so it's compatible with human cells, animal cells, and even algae cells in this case," he said.

The 3D printed corals are built to capture and scatter light more efficiently than natural corals. They consist of cup-shaped, artificial skeletons that support coral-like tissue. The skeleton is made up of a biocompatible polymer gel, called PEGDA, embedded with cellulose nanocrystals. The coral tissue consists of a gelatin-based polymer hydrogel, called GelMA, mixed with living algae cells and cellulose nanocrystals.

On the surface are tiny cylindrical structures that act as coral tentacles, which increase the surface area for absorbing light. Nanocrystals embedded in the skeleton and coral tissue, along with the corals' cup shape, also improve light absorption and enable more light to be focused onto algae cells so that they photosynthesize more efficiently.

In future studies, Chen and Wangpraseurt will build on this work to better understand the symbiosis between algae and corals. Their ultimate goal is to apply their findings to help coral reef restoration projects.

The discovery of the oldest known direct evidence of fibre technology -- using natural fibres to create yarn -- is reported in Scientific Reports this week. The finding furthers our understanding of the cognitive abilities of Neanderthals during the Middle Palaeolithic period (30,000-300,000 years ago).

Bruce Hardy and colleagues discovered a six-millimetre-long cord fragment consisting of three bundles of fibres twisted together and adhering to a 60-millimetre-long, thin stone tool. The authors speculate that the cord was wrapped around the tool as a handle or was part of a net or bag containing the tool. They date the cord fragment, which they discovered in Abri du Maras, France, to between 41,000-52,000 years ago. Using spectroscopy and microscopy, they identified that the cord likely consists of fibres taken from the inner bark of a non-flowering tree such as a conifer.

The authors suggest that production of the cord would have required extensive knowledge of the growth and seasonality of the trees used. They also speculate that Neanderthals may have needed an understanding of mathematical concepts and basic numeracy skills to create bundles of fibres (yarn), the three-ply cord and rope from multiple cords.

Prior to this discovery the oldest discovered fibre fragments in the Ohalo II site in Israel dated back to around 19,000 years ago. The findings of the new study suggest that fibre technology is much older, and that the cognitive abilities of Neanderthals may have been more similar to those of modern humans than previously thought.

Contrary to popular belief, Neanderthals were no less technologically advanced than Homo sapiens. An international team, including researchers from the CNRS, have discovered the first evidence of cord making, dating back more than 40,000 years (1), on a flint fragment from the prehistoric site of Abri du Maras in the south of France (2). Microscopic analysis showed that these remains had been intertwined, proof of their modification by humans. Photographs revealed three bundles of twisted fibres, plied together to create one cord. In addition, spectroscopic analysis revealed that these strands were made of cellulose, probably from coniferous trees. This discovery highlights unexpected cognitive abilities on the part of Neanderthals, who not only had a good understanding of the mathematics involved in winding the fibres, but also a thorough knowledge of tree growth. These results, published on 9 April 2020 in Scientific Reports, represent the oldest known proof of textile and cord technology to date.

The following laboratories contributed to this work: Histoire naturelle de l'Homme préhistorique (CNRS/Muséum national d'Histoire naturelle/Université de Perpignan Via Domitia), De la molécule aux nano-objets : réactivité, interactions et spectroscopies (CNRS/Sorbonne Université), along with the Centre de recherche et de restauration des musées de France (ministère de la Culture).

The excavations at the Abri du Maras have in particular benefited from funding from the French Ministry of Culture and the Auvergne-Rhône-Alpes Regional Archaeology Service.

An international team of scientists led by the University of the Witwatersrand in South Africa, has been able to reconstruct, in the smallest details, the skulls of some of the world's oldest known dinosaur embryos in 3D, using powerful and non-destructive synchrotron techniques at the ESRF, the European Synchrotron in France. They found that the skulls develop in the same order as those of today's crocodiles, chickens, turtles and lizards. The findings are published today in Scientific Reports.

University of the Witwatersrand scientists publish 3D reconstructions of the ~2cm-long skulls of some of the world's oldest dinosaur embryos in an article in Scientific Reports. The embryos, found in 1976 in Golden Gate Highlands National Park (Free State Province, South Africa) belong to South Africa's iconic dinosaur Massospondylus carinatus, a 5-meter long herbivore that nested in the Free State region 200 million years ago.

The scientific usefulness of the embryos was previously limited by their extremely fragile nature and tiny size. In 2015, scientists Kimi Chapelle and Jonah Choiniere, from the University of Witwatersrand, brought them to the European Synchrotron (ESRF) in Grenoble, France for scanning. At the ESRF, an 844 metre-ring of electrons travelling at the speed of light emits high-powered X-ray beams that can be used to non-destructively scan matter, including fossils. The embryos were scanned at an unprecedented level of detail - at the resolution of an individual bone cell. With these data in hand, and after nearly 3 years of data processing at Wits' laboratory, the team was able to reconstruct a 3D model of the baby dinosaur skull. "No lab CT scanner in the world can generate these kinds of data," said Vincent Fernandez, one of the co-authors and scientist at the Natural History Museum in London (UK). "Only with a huge facility like the ESRF can we unlock the hidden potential of our most exciting fossils. This research is a great example of a global collaboration between Europe and the South African National Research Foundation", he adds.

Up until now, it was believed that the embryos in those eggs had died just before hatching. However, during the study, lead author Chapelle noticed similarities with the developing embryos of living dinosaur relatives (crocodiles, chickens, turtles, and lizards). By comparing which bones of the skull were present at different stages of their embryonic development, Chapelle and co-authors can now show that the Massospondylus embryos were actually much younger than previously thought and were only at 60% through their incubation period.

The team also found that each embryo had two types of teeth preserved in its developing jaws. One set was made up of very simple triangular teeth that would have been resorbed or shed before hatching, just like geckos and crocodiles today. The second set were very similar to those of adults, and would be the ones that the embryos hatched with. "I was really surprised to find that these embryos not only had teeth, but had two types of teeth. The teeth are so tiny; they range from 0.4 to 0.7mm wide. That's smaller than the tip of a toothpick!", explains Chapelle.

The conclusion of this research is that dinosaurs developed in the egg just like their reptilian relatives, whose embryonic developmental pattern hasn't changed in 200 million years. "It's incredible that in more than 250 million years of reptile evolution, the way the skull develops in the egg remains more or less the same. Goes to show - you don't mess with a good thing!", concludes Jonah Choiniere, professor at the University of Witwatersrand and also co-author of the study.

The team hopes to apply their method to other dinosaur embryos to estimate their level of development. They will be looking at the rest of the skeleton of the Massospondylus embryos to see if it also shares similarities in development with today's dinosaur relatives. The arms and legs of the Massospondylus embryos have already been used to show that hatchlings likely walked on two legs (see doi: 10.1111/pala.12451).

Main findings:

1) High powered X-rays were used to reconstruct the skulls of some of the world's oldest known dinosaur embryos.

2) The skull could be seen in 3D at an unprecedented level of detail.

3) Dinosaur embryo skulls appear to develop in the same order as those of today's crocodiles, chickens, turtles and lizards.

4) These dinosaur embryos appear to have been fossilised at approximately 60% through their incubation period. This is much earlier than previously thought.

5) The dinosaur embryos have two types of teeth that range in size from 0.4 to 0.7mm wide. One of these sets would have been shed or resorbed before hatching.

Philadelphia, April 9, 2020 - Approximately five percent of women experience two or more miscarriages, a condition known as recurrent pregnancy loss (RPL). Although genetic testing is important for evaluating RPL, current tests have revealed shortcomings in clinical practice. A report in The Journal of Molecular Diagnostics, published by Elsevier, describes a new high-resolution melting analysis-based test (HRM) that is accurate, rapid, cheap, and easy to perform. When used prior to other tests, it improved cost-effectiveness by 30 percent, an important consideration in areas with limited healthcare resources.

"We speculated that the cost of genetic tests such as chromosomal microarray (CMA) or next-generation sequencing (NGS) will remain high enough to hinder their acceptance as affordable detection methods for RPL evaluation in underdeveloped regions," explained lead investigator Prof. Qiwei Guo, United Diagnostic and Research Center for Clinical Genetics, Women and Children's Hospital, School of Medicine and School of Public Health at Xiamen University, Xiamen, China. "Inspired by the success of prenatal screening and diagnosis for Down syndrome, we hypothesized that a well-accepted screening method like HRM combined with a diagnostic method (CMA or NGS) would advance the clinical practice of genetic testing for products of conception (POCs)."

The use of genetic tests for POCs has been limited in underdeveloped regions with large populations due to low test capacity and high cost. Prof. Guo and his co-investigators observed that although most patients with RPL wanted genetic testing, less than 5 percent had the testing performed, primarily because the cost (about US $440) was prohibitive.

HRM is recognized as one of the best screening methods for detecting point mutations and aneuploidy (the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46) for other medical conditions.

Investigators examined 765 miscarriage tissue samples that had undergone karyotyping, the conventional gold standard genetic test for RPL evaluation. Karyotyping shows the number, size, and appearance of the chromosomes, but the process can be labor intensive, time consuming, and susceptible to human error.

Of those 765 samples, approximately 60 percent showed the presence of numerical chromosomal abnormalities (NCAs). Almost two thirds of those with NCAs had the type of abnormalities that could be detected with HRM testing. Samples analyzed with HRM showed a high technical sensitivity (96.1 percent) and specificity (96.3 percent) as well as a high positive predictive value (95.9 percent) for the screening of chromosomal abnormalities.

Results determined that the costs of diagnosing an explained RPL using karyotyping or the HRM test alone were similar. Performing HRM screening before CMA/NGS testing, however, improved cost-effectiveness by approximately 30 percent. The data also suggested that the test was even more cost effective in women 35 years or older because of increased screening sensitivity.

"We suggest that the HRM test could be used as an initial screening tool followed by other diagnostic methods to improve the cost-effectiveness of RPL evaluation or as an alternative genetic test when other methods are unavailable or unaffordable," stated Prof. Guo. He added that another advantage of HRM testing is its high capacity, which is especially important in underdeveloped countries with large populations.

"We believe that identifying the causes of miscarriages not only assists clinicians in genetic counseling and therapeutic management, but also reduces the emotional distress and psychological burden on affected couples," noted Prof. Guo.

Liquid meltwater can sometimes flow deep below the Greenland Ice Sheet in winter, not just in the summer, according to CIRES-led work published in the AGU journal Geophysical Research Letters today. That finding means that scientists seeking to understand sea-level rise and the future of the Greenland Ice Sheet need to collect data during the dark Arctic winter with scant hours of daylight and temperatures that dip below -40 degrees.

"This observation raises questions for the Greenland research community, and motivates the need for future work on wintertime hydrology in Greenland," said lead author Lincoln Pitcher, a Visiting Fellow at CIRES, part of the University of Colorado Boulder. Pitcher began this work while he was a graduate student at the University of California Los Angeles, and his co-authors are from seven different states and Denmark.

When evidence suggested that some of Greenland's glaciers were storing meltwater through the winter, Pitcher set out for southwest Greenland to see if any of this meltwater was also leaving the ice sheet during winter. In February 2015, he and his colleague Colin Gleason of the University of Massachusetts at Amherst dragged a ground-penetrating radar across frozen rivers downstream of the edge of the ice sheet and drilled boreholes to see if any water was leaving the ice sheet and flowing beneath river ice. They surveyed rivers draining five Greenland Ice Sheet outlet glaciers and discovered meltwater flowing at just one site, the Isortoq River. In summertime, the Isotoq drains meltwater from the terminus of the Isunguata Sermia outlet glacier. In winter, the river appears frozen, but Pitcher and Gleason found slowly flowing liquid water there.

It was "a trickle, not a torrent," Pitcher said, and the water was flowing below half a meter of ice while temperatures were well below zero. Pitcher and Gleason collected water samples and geochemical analysis indicated that it had come from under the ice sheet itself.

The team concluded that it is possible the bed of the Greenland Ice Sheet can stay wet and drain small amounts of water year-round. This finding is important for understanding how meltwater from the ice surface moves through the ice sheet, is retained, refreezes and/or ultimately drains into rivers and/or the global ocean.

It is often assumed that Greenland's drainage system lies dormant during winter. Pitcher's team's findings highlight a growing need for year-round Arctic hydrologic investigations, not just in summer.

Dark matter, which cannot be physically observed with ordinary instruments, is thought to account for well over half the matter in the Universe, but its properties are still mysterious. One commonly held theory states that it exists as 'clumps' of extremely light particles. When the earth passes through such a clump, the fundamental properties of matter are altered in ways that can be detected if instruments are sensitive enough. Physicists Rees McNally and Tanya Zelevinsky from Columbia University, New York, USA, have now published a paper in EPJ D proposing two new methods of looking for such perturbations and, thus, dark matter. This paper is part of a special issue of the journal on quantum technologies for gravitational physics.

Until now, searches for dark matter clumps have relied on the fact that tiny changes in the values of fundamental constants will alter the 'tick rate' of atomic clocks, some of which may be precise enough to pick up this difference. McNally and Zelevinsky's work adds methods that involve measuring a small extra 'push' or acceleration on normal matter caused by the clump, using, firstly, gravity sensors and, secondly, gravitational wave detectors. Gravity sensors are already spread around the world in the IGETS network, which is used for geological research; and scientists at the LIGO observatories in the United States are already looking for gravitational waves. Thus, McNally and Zelevinsky can mine the data from these ongoing experiments for evidence of dark matter.

McNally explains that this work was inspired by two things: the benefits of re-purposing existing experiments, and science fiction. "I enjoy novels like A Fire Upon the Deep [by Vernor Vinge] and The Three-Body Problem [by Liu Cixin] that explore what might happen if fundamental constants change, and it's fun to explore such things in the real world." As for practical applications of this work, however, he advised taking things one step at a time. "First we need to find out what Dark Matter is, then maybe we can find out how to use it."

Jean and Peter Medawar wrote in 1977 that a virus is "simply a piece of bad news wrapped up in proteins." The "bad news" in the SARS-CoV-2 case is the genome made of a very long ribonucleic acid (RNA) molecule. Grappling with COVID-19 pandemic, the world seems to be lost with no sense of direction in uncovering what this coronavirus (SARS-Cov-2) is composed of. Being an RNA virus, SARS-Cov-2 enters host cells and replicates its genomic RNA and produces many smaller RNAs (called "subgenomic RNAs"). These subgenomic RNAs are used for the synthesis of various proteins (spikes, envelopes, etc.) that are required for the beginning of SARS-Cov-2 lineage. Thus, the smaller RNAs make good targets for messing up new coronavirus's conquering of our immune system. Though recent studies reported the sequence of the RNA genome, they only predicted where their genes might be, without concretely pinpointing what kind of genes are present and where exactly in the genome.

Led by Professors KIM V. Narry and CHANG Hyeshik, the research team of the Center for RNA Research within the Institute for Basic Science (IBS), South Korea, succeeded in dissecting the architecture of SARS-CoV-2 RNA genome, in collaboration with Korea National Institute of Health (KNIH) within Korea Centers for Disease Control & Prevention (KCDC). The researchers experimentally confirmed the predicted subgenomic RNAs that are in turn translated into viral proteins. Furthermore, they analyzed the sequence information of each RNA and revealed where genes are exactly located on a genomic RNA. "Not only to detailing the gene structure of SARS-CoV-2, we also discovered numerous new RNAs. Our work provides a high-resolution map of SARS-CoV-2. This map will help understand how the virus replicates and how it escapes the human defense system," explains Professor KIM V. Narry, one of the corresponding authors of the study.

It was previously predicted that 10 subgenomic RNAs make up the viral particle structure. However, the research team confirmed that 9 subgenomic RNAs actually exist, invalidating the remaining one subgenomic RNA. Researchers also found that there are dozens of unknown subgenomic RNAs, owing to RNA fusion and deletion events. "Though it requires further investigation, these molecular events may lead to the relatively rapid evolution of coronavirus. It is unclear yet what these novel RNAs do, but a possibility is that they may assist the virus to avoid the attack from the host," says Prof. Kim.

They believe if they figure out the unknown characteristics of RNA, the findings may offer a new clue for combatting the new coronavirus. Newly discovered features will also help to understand the life cycle of the virus and develop new strategies for antiviral therapy.

Behind the success of the study is the research team's pairing of two complementary sequencing techniques; DNA nanoball sequencing and nanopore direct RNA sequencing. The nanopore direct RNA sequencing allows to directly analyze the entire long viral RNA without fragmentation. Conventional RNA sequencing methods usually require a step-by-step process of cutting and converting RNA to DNA before reading RNA. Meanwhile, the DNA nanoball sequencing can read only short fragments, but has the advantage of analyzing a large number of sequences with high accuracy. These two techniques turned out to be highly complementary to each other to analyze the viral RNAs.

"Now we have secured a high resolution gene map of the new coronavirus that guides us where to find each bit of genes on all of the total SARS-CoV-2 RNAs (transcriptome) and all modifications RNAs (epitranscriptome). It is time to explore the functions of the newly discovered genes and the mechanism underlying viral gene fusion. We also have to work on the RNA modifications to see if they play a role in virus replication and immune response. We believe that our study will contribute to the development of diagnostics and therapeutics to combat the virus more effectively," notes Professor KIM V. Narry.

A pioneering study has shed new light on how a group of novel organelle-based disorders affect cells.

The study led by Professor Michael Schrader from the University of Exeter, and featuring an international, multi-disciplinary team of scientists, has explored on peroxisome alterations and their contribution to the disease.

Organelles are the functional units of a cell. They perform specialised functions, and defects in their enzymes performing those functions can result in metabolic disorders.

However, organelles are not just cellular factories in a production line, but are also highly dynamic. They are able to move around in the cell to interact and cooperate with other organelles and multiply by increasing in size and then dividing to adapt their number and functions to cellular needs.

Recently, scientists have identified a new group of disorders, characterised by defects in the membrane dynamics and division of organelles rather than by loss of metabolic functions.

Those disorders are caused by mutations in genes encoding for the organelle division machinery, such as Mitochondrial fission factor (MFF) - a key component of the division machinery of two organelles, mitochondria and peroxisomes.

MFF functions as an adaptor protein to recruit a mechanochemical enzyme, Dynamin-related protein 1 (DRP1), to mitochondria and peroxisomes. This enzyme can constrict and divide membranes and is essential for membrane fission and organelle multiplication.

Defects in either MFF or DRP1 block the division of mitochondria and peroxisomes and result in highly elongated organelles unable to divide. Patients with MFF deficiency present with developmental and neurological abnormalities.

The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown.

An international, multi-disciplinary team of scientists, led by Professor Michael Schrader from the University of Exeter, has now shed light on peroxisome alterations and their contribution to the disease.

Peroxisomes fulfil important protective functions in the cell and are vital for health; they contribute to cellular lipid metabolism and redox balance, which links them to the control of energy regulation, cellular ageing and age-related disorders. They also cooperate with mitochondria in the combat of viruses and anti-viral defence. Loss of peroxisome function leads to severe developmental and neurological defects such as those seen in MFF-deficiency.

"In this study, we show that MFF-deficiency impacts on the maturation of peroxisomes. Loss of MFF function results in an altered distribution of peroxisomal proteins and causes the accumulation of extremely long pre-peroxisomal membrane structures inside the cell, which have reduced import-competency for peroxisomal enzymes," said Professor Michael Schrader.

"We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH.

"Previous studies have shown that the peroxisomes in MFF-deficiency are largely functional, leading to the general assumption that defects in peroxisomal dynamics and division results only in elongated peroxisomes, which are otherwise unaltered. We have now revealed in MFF-deficient cells that this is not the case.

"Interestingly, we observed that the highly elongated peroxisomes in MFF-deficient cells are not fully static; their dynamics can be modulated, for example through the induction of organelle degradation.

"These experiments have provided us with new insights into the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity.

"In peroxisomal disorders, we often see altered numbers, different shapes or even different distributions of peroxisomes in patient cells. We also developed a mathematical modelling approach to help understand this.

"Understanding why this happens and how to modulate peroxisome numbers or distribution can provide new possibilities to improve cell performance in those patients."

"This might also be relevant to age-related conditions like dementia, deafness and blindness, as peroxisomal dynamics are known to have important protective functions within sensory cells."

The international research team combined human cell biology (Professor Michael Schrader), clinical diagnostics (Dr Sacha Ferdinandusse, Amsterdam University Medical Centre, NL; Professor Peter Freisinger, Department of Pediatrics, Reutlingen, GER), redox biology (Professor Marc Fransen, University of Leuven, BE), neurobiology (Dr Markus Islinger, University of Heidelberg, GER) and mathematic modelling (Dr David Richards, Centre for Biomedical Modelling and Analysis, LSI, Exeter, UK) to shed further light into the physical processes disturbed in MFF-deficient cells.

People with severe peroxisomal disorders, also known as Zellweger Spectrum Disorders, often die as children or young adults, and the team cooperates with a charity called Zellweger UK to raise awareness and to support families and sufferers.

Kanazawa, Japan - Hand-foot-and-mouth disease (HFMD) is an acute viral infection that usually affects infants and children below five years. In a study published in Scientific Reports in January 2020, an international research team including Kanazawa University, the Vietnam National Hospital of Pediatrics, Tokyo Metropolitan Institute of Medical Science, Nagasaki University and Hanoi Medical University, has demonstrated the emergence of a new enterovirus (EV) A71-C4 lineage during the 2015-2016 outbreak of HFMD in northern Vietnam. Further, through clinical studies and an experimental mouse model, they have shown that EV-A71 C4 subgenotype may be more virulent than the B5 subgenotype.

HFMD is a common contagious childhood illness caused by enteroviruses of the family picornaviridae, the most frequently reported being EV-A71, coxsackievirus A16 (CV-A16), and CV-A6. It typically runs a mild self-limiting course; however, in rare cases it may cause inflammation of the meninges and the hindbrain, resulting in paralysis, cardiopulmonary complications, or even death. While most cases resolve within a few weeks, EV-A71 infections may be more severe, with serious complications.

To determine the epidemiological characteristics and identify the various enterovirus strains responsible for HFMD in northern Vietnam, the research team collected and analyzed throat and rectal swabs from 488 affected children in Hanoi.

Son T. Chu, lead author of the study, explains: "CV-A6 was the most common strain, followed by EV-A71. Of these EV-A71, 92.1% were the B5 subgenotype and 7.9% were the C4 subgenotype. Whole-genome sequencing showed that seven of the eight C4a strains formed a new lineage, including two possible recombinants between EV-A71-C4 and CV-A8 strains."

The researchers evaluated the proportion of inpatients as a clinical measure of virulence. Hospitalized children with EV-A71 significantly outnumbered those with CV-A6. Further analysis among the EV-A71 infected children showed that the proportion of inpatients among C4-infected was significantly higher than that among B5-infected, implying greater virulence of C4 than B5.

"As the number of C4-infected patients was small, we applied another technique to compare virulence," says Kyousuke Kobayashi, neurovirologist and lead author. "We inoculated transgenic mice susceptible to EV-A71 infection with viral isolates and monitored them for limb weakness, acute flaccid paralysis, body weight and death. We found increased paralysis and significantly higher mortality among mice infected with C4 strains than those infected with B5 strains."

HFMD is an emerging public health problem with periodic large outbreaks in pediatric populations in East and Southeast Asia. Currently, there is no approved antiviral drug against EV-A71 and the best strategy to mitigate its impact is to develop appropriate vaccines. Though inactivated vaccines exist, more suitable candidate strains may be identified from among the newly emerged EV-A71-C4 strains for developing live attenuated vaccines.

It's time to encourage people to wear face masks as a precautionary measure on the grounds that we have little to lose and potentially something to gain, say experts in The BMJ today.

Professor Trisha Greenhalgh at the University of Oxford and colleagues say despite limited evidence, masks "could have a substantial impact on transmission with a relatively small impact on social and economic life."

The question of whether masks will reduce transmission of covid-19 in the general public is contested.

Although clinical trial evidence on the widespread use of facemasks as a protective measure against covid-19 is lacking, at the time of writing increasing numbers of agencies and governments, including the US Centers for Diseases Control and Prevention, are now advocating that the general population wears masks, but others, such as the World Health Organization and Public Health England are not.

Some researchers argue that people are unlikely to wear masks properly or consistently, and may ignore wider infection control measures like handwashing. Others say the public should not wear them since healthcare workers need them more.

But Greenhalgh and colleagues challenge these arguments and suggest that in the context of covid-19, many people could be taught to use masks properly and may well do this consistently without abandoning other important anti-contagion measures.

What's more, they say if political will is there, mask shortages can be quickly overcome by repurposing manufacturing capacity - something that is already happening informally.

They conclude that it is time to act without waiting for randomised controlled trial evidence.

"Masks are simple, cheap, and potentially effective," they write. "We believe that, worn both in the home (particularly by the person showing symptoms) and also outside the home in situations where meeting others is likely (for example, shopping, public transport), they could have a substantial impact on transmission with a relatively small impact on social and economic life."

In a linked editorial, Babak Javid at Tsinghua University in Beijing and colleagues agree that the public should wear face masks because the benefits are plausible and harms unlikely. And they say cloth masks are likely to be better than wearing no mask at all.

As we prepare to enter a "new normal," wearing a mask in public may become the face of our unified action in the fight against this common threat and reinforce the importance of social distancing measures, they conclude.

In an opinion piece, researchers recommend that health care workers should not be caring for covid-19 patients without proper respiratory protection, and that cloth masks are not a suitable alternative for health care workers.

Journal of Public Policy & Marketing has dedicated the second issue of its 2020 volume to better understanding and defining the uniquely related concepts of consumer power and consumer access. The guest editors and articles authors show how both concepts are in a constant state of change. They are influenced by technology, wealth, industry organization, and public policy.

Questions of access and power are particularly relevant in the context of today's United States with consumers simultaneously isolated and connected in ways never before imagined. Many of the articles in this issue offer prophetic insights though they were written well before and accepted only in the very early stages of the COVID-19 world health crisis.

"Denial Without Determination: The Impact of Systemic Market Access Denial on Consumer Power and Market Engagement"

Consumers may have access to a product or service, but that does not mean the consumer has the power to make ownership and usage a reality. Even when intervention levels the playing field, it still may take multiple purchase cycles before some consumers may attempt to take advantage of the new opportunities.

https://doi.org/10.1177/0743915619885393

"Access Granted? An Examination of Financial Capability, Trait Hope, Perceived Access, and Food Insecurity in Distressed Census Tracts"

Interestingly increasing a belief in hope is an effective way to improve the perception of access to adequate food sources among residents of food deserts. The authors suggest communication strategies that encourage this trait and improve the effectiveness of food and nutrition assistance programs.

https://doi.org/10.1177/0743915619889341

"The Effect of Consumers' Perceived Power and Risk in Digital Information Privacy: The Example of Cookie Notices"

Despite recent regulation (i.e., the GDPR), the design of cookie notices varies strongly in practice, with many websites providing cookie notices with low visibility and no or very limited choice. These most common designs are likely to increase consumers' risk perception, which reduces their purchase intent; website providers might, in contrast, benefit from offering consumers more choice over their private data.

https://doi.org/10.1177/0743915620902143

"Service Captivity: No Choice, No Voice, No Power"

This examination of "service captivity" offers insights into how consumers may feel trapped in a scenario where they can't exit a service relationship. The authors offer examples of how these consumers may gain access to new service providers.

https://doi.org/10.1177/0743915619899082

"Sound and Fury: Digital Vigilantism as a Form of Consumer Voice"

Via a pool of over 70,000 tweets associated with the 2017 Charlottesville Unite the Right rally, the authors categorize tweets into five categories and offer a perspective on how digital vigilantism was represented.

https://doi.org/10.1177/0743915620902403

"Sense of Power: Policy Insights for Encouraging Consumers' Healthy Food Choice"

Incorporating simple messages such as, "you are powerful" or "we all feel powerful sometimes" is enough to increase a consumer's sense of power and subsequently nudge them to make healthier food choices, particularly for consumers lower in socioeconomic status.

https://doi.org/10.1177/0743915620902148

"Children and Online Privacy Protection: Empowerment from Cognitive Defense Strategies"

Children and teens were already spending a growing amount of time online, but in the last several weeks, this seems to have increased even more. The authors investigate methods for improving safety beliefs and decisions to share personal videos on YouTube suggesting a combination of education and parental intervention empowers children and teens to protect their personal information online.

https://doi.org/10.1177/0743915619883638

"When Does the Social Service Ecosystem Meet Consumption Needs? A Power-Justice-Access Model of Holistic Well-Being from Recipients' Perspectives"

Research suggestions that respect is another dimension of consumer access and power. They show the fallacy of scorning low-income individuals' access to "luxuries," such as Starbucks coffee, and the importance of going beyond simple access and power and include the level of perceived justice (e.g., respect).

https://doi.org/10.1177/0743915620903318

"Consumer-Level Perceived Access to Health Services and Its Effects on Vulnerability and Health Outcomes"

Policymakers, health care organizations, and insurance providers can use perceived access to healthcare measure to better identify communities or populations that lack access, design programs and systems that reduce perceptions of health vulnerability in target populations, and ultimately improve consumers' health outcomes.

https://doi.org/10.1177/0743915620903299

Scientists report that the combined effects of rare, damaging mutations present at birth have a negative impact on healthspan and longevity, according to a study published this week in eLife.

The findings suggest one additional inherited damaging mutation could carve off six months of life, and combinations of these rare mutations determine how soon someone will develop diseases such as cancer, heart disease and dementia.

Most of the genetic variants linked to lifespan that researchers currently know about have been found in people who live long, such as centenarians who live to 100 or older. The variants responsible for survival of the rest of the population remain poorly understood.

Now, researchers have proposed that the remaining variance that contributes to lifespan could be attributed to the combination of very rare but highly damaging mutations that are present in every person's genome. "The role of ultra-rare damaging mutations that decrease lifespan and healthspan has been largely overlooked," says co-senior author Vadim Gladyshev, Professor at Brigham and Women's Hospital and Harvard Medical School, Boston, US. "They are different in different people, but in combination, they exhibit an unexpectedly large effect on lifespan."

"Until recently, only common gene variants could be probed in genetic studies due to a small number of participants," explains co-first author Anastasia Shindyapina, a postdoctoral researcher at Brigham and Women's Hospital, Harvard Medical School. "However, large datasets that sequenced tens of thousands of people now allow us to assess the effects of DNA variation that appear in less than one out of 10,000 subjects."

Ultra-rare protein-truncating variants (PTVs) are known to be some of the most damaging genetic variants. These tend to have a larger impact than more common genetic variants, and can dramatically change the amount and function of important proteins in the body. Increased frequency of PTVs has been linked to complex diseases such as schizophrenia, epilepsy and autism. In this study, Shindyapina, along with co-first author Aleksandr Zenin, researcher at Gero, Singapore, and their colleagues set out to learn how the number of PTVs a person is born with influences their lifespan. They also wanted to see whether accumulating additional PTVs throughout life can affect overall health and length of survival.

The team analysed genomic data from more than 40,000 people registered in the UK Biobank who on average were in their mid-fifties. They compared the individual 'burden' of PTVs (the total number of PTVs per each person's genome) with their lifespan and their 'healthspan': the time taken to develop complex diseases including cancer, heart disease, chronic obstructive pulmonary disease, stroke and dementia.

The team found that people who had a high burden of ultra-rare PTVs had a shorter healthspan and lifespan. Each additional ultra-rare PTV in a person's genome accounted for a reduction in lifespan of six months and a reduction in healthspan of two months.

In addition to the genetic variants we are born with, we accumulate more as we age. The research predicted that the natural accumulation of PTVs increases proportionally with age but their effects are likely to be minor compared with the effects of PTVs we are born with. "This implies that the genetic variation we accumulate throughout life only accounts for a small fraction of the increased risk of disease and death that we all face as we grow older, if our theoretical calculations are correct," explains author Andrei Tarkhov, researcher at Gero and PhD student at Skolkovo Institute of Science and Technology, Moscow, Russia.

"Our finding that accumulated mutations during a lifetime do not accelerate disease or death contradicts previous hypotheses," adds co-senior author Peter Fedichev, Principal Investigator at Gero. "Together our results illustrate the surprising role of rare mutations previously inaccessible for genetic studies in the aging process. They also demonstrate the power of whole exome and genome sequencing to uncover the genetic architecture of complex diseases in the interest of developing future therapeutics."