Culture

Clinician-scientists at Nanyang Technological University, Singapore's (NTU Singapore) Lee Kong Chian School of Medicine (LKCMedicine) have demonstrated a way to improve the speed, handling time and cost of COVID-19 laboratory tests. The improved testing method yields results in 36 minutes - a quarter of the time required by existing gold-standard tests.

Their new approach could enable the wider adoption of COVID-19 testing for diagnosis in academic or research laboratories, and allow for screening and research especially in countries and regions with limited laboratory capabilities. The test, which can be done with portable equipment, could also be deployed in the community as a screening tool.

Currently, the most sensitive method for testing for COVID-19 is through a laboratory technique called polymerase chain reaction (PCR), in which a machine amplifies viral genetic material by copying it over and over again so any trace of the SARS-CoV-2 virus can be detected.

A big bottleneck in sample testing is RNA purification - separating RNA from other components in the patient sample - a laborious process that requires chemicals that are now in short supply worldwide. Its steps have to be performed by highly trained technical staff and can take a few hours. Currently, automated equipment for sample preparation costs hundreds of thousands of dollars, and requires specialised laboratory facilities.

The method developed by NTU LKCMedicine combines many of these steps and allows direct testing on the crude patient sample, cutting down the turnaround time from sample-to-result, and removing the need for RNA purification chemicals.

Details of the new approach were published in the scientific journal Genes in June.

Mr Wee Soon Keong, a PhD candidate at NTU LKCMedicine and the first author of the paper, said: "While polymerase chain reaction (PCR) is a venerable technology that has proven to be a workhorse for biological research, it has some drawbacks when used outside of the laboratory environment. The process is fiddly and time-consuming. Our rapid COVID-19 test involves a single-tube reaction that reduces hands-on time and biosafety risk for lab personnel, as well as the likelihood for carryover contamination during the processing of samples."

Aside from testing for COVID-19, the same method developed by the NTU LKCMedicine team can also be used to detect other viruses and bacteria, including the dengue virus, which is set to plague Singapore as the country braces itself for one of the worst dengue outbreaks amid the coronavirus pandemic.

Leader of the research team, Associate Professor Eric Yap, who also heads the Microbial Genomics Laboratory, said: "We previously demonstrated that this method works for dengue virus as well. When used directly on a crude blood sample with dengue virus, the test yielded results in 28 minutes. As Singapore battles the dual outbreak of dengue and COVID-19, both with similar early symptoms, our test could help in differentiating between the two infectious diseases."

Professor James Best, Dean of NTU LKCMedicine, said: "As Singapore continues with proactive testing to detect, isolate, and contain the possible spread of the coronavirus, rapid portable screening tools like the one developed by Assoc Prof Yap and his team could come in handy at testing sites in the community, allowing for infected patients to be identified quickly, and swift action to be taken to prevent transmission."

From benchtop to portable testing

Typically, in PCR tests, the genetic material on a swab sample collected from a patient has to be extracted to remove any substances in the sample that prevent the PCR test from working. An example of an inhibitor in respiratory samples is mucin (a main component of mucus).

The test designed by the NTU LKCMedicine team, which includes senior research fellow Dr Sivalingam Paramalingam Suppiah, uses the 'direct PCR' method, removing the need for RNA purification, a time-consuming and costly step. Instead, they added inhibitor-resistant enzymes and reagents targeting compounds that obstruct RNA amplification, such as mucin, a main component of mucus. These enzymes and reagents, which are commercially available, have high resistance to such compounds that otherwise inhibit PCR, rendering the test inaccurate.

The biochemical mix of crude sample and inhibitor-resistant enzymes and reagents is placed into a single tube, which is inserted into a laboratory thermocycler, a machine used to amplify genetic material in PCR. After 36 minutes, results reveal whether there is any trace of COVID-19 with confidence.

"By skipping the RNA extraction step with our direct-PCR method, we see cost savings on nucleic acid extraction kits, and avoid the problem of reagents in short supply when lab testing is ramped up and the demand increases globally," said Dr Sivalingam.

The team also tested this method on a portable thermocycler, which can be deployed in low-resource settings and endemic areas, pointing to the possibility of having this test done in community healthcare settings by frontline healthcare workers.

Assoc Prof Yap said: "We are now trying to deploy such direct-PCR methods, developed by ourselves and others, for routine diagnostics. We need to determine the actual utility and benefits in a real-world setting, and to understand if there are any trade-offs. When one bottleneck is removed, other challenges may emerge - like ensuring quality control, or reducing manual errors."

The team is now looking to use this method for COVID-19 testing at the NTU Clinical Diagnostic Laboratory at LKCMedicine that Assoc Prof Yap heads.

"Our goal is to develop ultrafast and automated tests that yield results in minutes, and that can be performed by healthcare workers in the clinic with similar accuracy and sensitivity as in specialised laboratories. This will allow us to take PCR testing out of conventional laboratories nearer to the point-of-care, and into the low-resource settings that need them the most," he said.

Therapy-loaded nanoparticles may be directed to the brain by functionalization with ligands targeting BBB-associated proteins. However, such targeting strategies have inherent brain-specificity limitations, as the target proteins are also significantly expressed in peripheral organs, thereby limiting the clinical application of such strategies. We have developed a counterintuitive targeting strategy which exploits the high impermeability of the BBB itself to selectively retain molecular labels (i.e. targets) on the surface of brain endothelium. Nanoparticles capable of binding the displayed targets are consequently directed specifically to the brain microvasculature with minimal targeting to peripheral organs. This two-step targeting strategy therefore paves the way to overcome the peripheral 'off-target' nanoparticle accumulation, increasing the clinical translation of nanoparticle-based therapies. The results have been published in the July 23 issue of Proceedings of the National Academy of Science (Impact Factor = 9.5804).

July 27, 2020 - Kawasaki / Japan: The Innovation Center of NanoMedicine (Director: Prof. Kazunori Kataoka, Location: Kawasaki-City, Abbreviation: iCONM) announced that a new strategy to specifically target to the brain was discovered in collaboration with the Department of Bioengineering, Graduate School of Engineering, University of Tokyo. The details are published in the Proceedings of the National Academy of Science (Impact factor = 9.350 in 2019) issued on July 23. (Note 1)

Treatment of neurological diseases is severely hindered by the poor delivery of therapies to the brain due to the presence of the blood-brain barrier (BBB), a highly impermeable cellular barrier composed primarily by the specialized endothelial cells lining the brain microvasculature. Nanotechnology-based strategies have achieved modest success in delivering therapeutics to the brain by loading them onto nanomachines (Note 2) decorated with ligands which bind to proteins associated with the BBB (Note 3). However, such targeting strategies have inherent brain-specificity limitations, as the target proteins are also significantly expressed in peripheral organs, leading to increased accumulation of nanomachines for instance in the lung and heart. Therefore, the clinical translation of current strategies is hampered by detrimental peripheral side-effects and reduced effective therapeutic doses reaching the brain. Hence, new strategies which exploit alternative features of the BBB need to be developed to overcome 'off-target' accumulation of nanomachines.

The group of Prof. Kataoka have developed a simple, yet counterintuitive strategy which turns the problem of therapy delivery to the brain, that is, the high impermeability of brain endothelial cells, into the solution to achieve specific brain targeting of nanomachines with minimal accumulation increase in peripheral organs.

The high impermeability of brain endothelial cells is in large part due to a markedly reduced level of endocytosis compared to peripheral endothelial cells. This feature may therefore be exploited to promote free, unconjugated molecular labels to be selectively retained on the surface of brain endothelial cells while being quickly removed (endocytosed) from the surface of endothelial cells of other organs in the body. In this way, nanomachines capable of efficiently recognizing the displayed molecular labels are specifically targeted to the brain with minimal targeting into other organs.

The feasibility of such an approach has been demonstrated by employing biotin-containing antibodies against the protein Platelet Endothelial Cell Adhesion Molecule (PECAM)-1, which is expressed in the vasculature of most organs. The authors demonstrated that if nanomachines decorated with the protein avidin (capable of very strongly binding to biotin) are injected into mice a short time-period after injection of biotin-PECAM-1 antibodies, the nanomachines accumulate preferentially in the lung, with accumulation also seen in the brain, heart and pancreas (note 4). However, if the time-interval between antibody and nanomachine injection is increased to allow removal of the antibody from the surface of peripheral endothelial cells, the ability of the nanomachines to accumulate in the lung, heart and pancreas steadily decreases, while accumulation in the brain remains constant. Hence, after an 8 hr time-interval, the nanomachines were only targeted to the brain, with no increase in accumulation seen in any peripheral organ.

This novel two-step targeting strategy therefore paves the way to overcome the limitation of peripheral "off-target" nanomachine accumulation, thereby increasing the clinical translation of nanomachine-based therapies.

Existing limited evidence suggests that wearing face coverings to protect against COVID-19 does not lead to a false sense of security and is unlikely to increase the risk of infection through wearers foregoing other behaviours such as good hand hygiene, say researchers from the University of Cambridge and King's College London.

Writing in BMJ Analysis, the researchers say that the concept of 'risk compensation' is itself the greater threat to public health as it may discourage policymakers from implementing potentially effective measures, such as wearing face coverings.

Wearing face coverings, particularly in shared indoor spaces, is now mandated or recommended in more than 160 countries to reduce transmission of SARS-CoV-2, the virus that causes COVID-19. Worn correctly, face coverings can reduce transmission of the virus as part of a set of protective measures, including maintaining physical distance from others and good hand hygiene.

While it is not clear how much of an effect face coverings have, scientists have urged policymakers to encourage the wearing of face coverings because the risks are minimal while the potential impact is important in the context of the COVID-19 pandemic.

However, early in the pandemic, the World Health Organization warned that wearing face coverings could "create a false sense of security that can lead to neglecting other essential measures such as hand hygiene practices". This type of behaviour is known as 'risk compensation'.

A team led by Professor Dame Theresa Marteau at the Behaviour and Health Research Unit, University of Cambridge, has examined the evidence for risk compensation to see whether concerns might be justified in the context of face coverings to reduce transmission of SARS-CoV-2.

The idea behind risk compensation is that people have a target level of risk they are comfortable with and they adjust their behaviour to maintain that level risk. At an individual level, risk compensation is commonplace: for example, people run for longer to offset an eagerly anticipated indulgent meal and a cyclist may wear a helmet to cycle at speed.

At a population level, evidence for risk compensation is less clear. A commonly-cited example is the mandated wearing of bike helmets purportedly leading to an increase in the number of bike injuries and fatalities. Another often-cited example is the introduction of HIV pre-exposure prophylaxis (PrEP) and HPV vaccination purportedly leading to an increase in unprotected sex.

Professor Marteau and colleagues say the results of the most recent systematic reviews - a technique that involves examining all available evidence on a topic - do not justify the concerns of risk compensation for either of these examples. In fact, for HPV vaccination, the opposite effect was found: those who were vaccinated were less likely to engage in unprotected sexual behaviour as measured by rates of sexually transmitted infection.

At least 22 systematic reviews have assessed the effect of wearing a mask on transmission of respiratory virus infections. These include six experimental studies, involving over 2,000 households in total - conducted in community settings that also measured hand hygiene. While none of the studies was designed to assess risk compensation or looked at social distancing, their results suggest that wearing masks does not reduce the frequency of hand washing or hand sanitising. In fact, in two studies, self-reported rates of hand washing were higher in the groups allocated to wearing masks.

The team also found three observational studies that showed people tended to move away from those wearing a mask, suggesting that face coverings do not adversely affect physical distancing at least by those surrounding the wearer. However, they say that as none of these studies have been peer-reviewed, they should be treated with caution.

"The concept of risk compensation, rather than risk compensation itself, seems the greater threat to public health through delaying potentially effective interventions that can help prevent the spread of disease," said Professor Marteau.

"Many public health bodies are coming to the conclusion that wearing a face covering might help reduce the spread of SARS-CoV-2, and the limited evidence available suggests their use doesn't have a negative effect on hand hygiene," added co-author Dr James Rubin from the Department of Psychological Medicine, King's College London.

In their article, the team argue that it is time to lay risk compensation theory to rest. Professor Barry Pless from McGill University, Montreal, Canada, once described it as "a dead horse that no longer needs to be beaten." The authors go further, saying "this dead horse now needs burying to try to prevent the continued threat it poses to public health, from by slowing the adoption of more effective interventions".

A five-year study of wind energy potential in Saudi Arabia has culminated in a comprehensive blueprint for progressing the Kingdom's national wind energy strategy. Exhaustive high-resolution modeling was combined with a unique set of wind and weather observations and analysis of land-use restrictions, cost and technologies to guide the optimal buildout of wind turbines.

The program was led by KAUST's Marc Genton in close collaboration with atmospheric simulation experts at the University of Notre Dame in the USA. "Through our novel methodology and ad-hoc computer simulations, we have accurately quantified wind energy resources in Saudi Arabia and have provided a detailed plan for a cost-effective implementation of the government's wind energy target of 16 gigawatts of installed capacity by 2030," says Genton. "Our work shows that Saudi Arabia is well positioned to become a role model for wind energy development in the Middle East and worldwide."

The reliable calculation of wind energy resources is a prerequisite for the development of a strong wind energy industry. Although wind energy potential has been rigorously quantified in many developed countries, this critical step remains a major obstacle for many emerging economies due to the lack of widespread wind monitoring data and well-developed high-resolution atmospheric models.

"We spent five years researching the right methodology and the most appropriate simulations and finding suitable ground data," says Genton. "We also engaged with collaborators at the University of Notre Dame, who had a lot of expertise in simulating atmospheric phenomena at regional scales with computer models. With their simulations and help in developing new methods, we are able to accurately characterize the weather occurring in the atmosphere at spatial scales of up to thousands of kilometers."

Genton points out that typically, the main challenge of such studies is how to validate the computer simulations against measured data. Fortunately, the researchers were able to make use of the highly detailed wind and atmospheric measurements recorded through the King Abdullah City for Atomic and Renewable Energy (KA-CARE) program.

"The KA-CARE dataset was a game changer in showing that our model simulations provide accurate results," says Genton. "Our findings can now be used by policymakers to efficiently plan for the development of wind energy infrastructure, and our generalizable methodology can be used by the scientific community to identify optimal locations and the most suitable technological options for wind energy harvesting in other contexts and other countries."

Philadelphia, July 24, 2020--Researchers at Children's Hospital of Philadelphia (CHOP) have developed a new computational algorithm that has, for the first time, identified a spectrum of mutations in the noncoding portion of the human genome across five major pediatric cancers. The study, which was published today in Science Advances, used the algorithm to analyze more than 500 pediatric cancer patients' mutations and gene expression profiles to develop a comprehensive list of potentially cancer-causing mutations.

"Noncoding mutations are very important because the noncoding portion of the genome typically regulates how genes are turned on and off, much like a control switch, which has implications for the uncontrolled growth that occurs in cancer," said Kai Tan, PhD, Professor of Pediatrics at CHOP and senior author of the study. "However, these regions are also challenging to study, and our knowledge about them not as developed as that of coding regions. Our computational model has identified a set of targets in pediatric cancers that we hope to study further and eventually move to clinical practice."

The researchers developed a computation tool called PANGEA (predictive analysis of noncoding genomic enhancer/promoter alterations) to analyze noncoding mutations and their impact on gene expression in more than 500 pediatric cancer patients who had five major types of pediatric cancer: B cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML), neuroblastoma, Wilms tumor, and osteosarcoma. PANGEA identified all types of mutations that are associated with gene expression changes, including single nucleotide variants, small indels, copy number variations, and structural variants.

Previous studies on noncoding mutations have focused on single nucleotide variants and small indels, which are insertions or deletions of bases in the genome that are relatively short in length. However, structural variants are regions of DNA much larger in size - 1 kilobase or larger - a quality that makes them more difficult to identify but also more likely to contribute to changes in gene regulation that lead to cancer.

Using PANGEA, the researchers found that structural variants are indeed the most frequent cause of potentially cancer-causing mutations and identified 1,137 structural variants that affect the expression of more than 2,000 genes across the five pediatric cancer types.

In analyzing the data, the researchers found that coding and noncoding mutations affect distinct sets of genes and pathways, which is likely due to the different genomic locations of these two types of genes. The researchers found that genes involved in metabolism - the rewiring of which is a hallmark of cancer - are more frequently affected by noncoding mutations. However, it is unclear to what degree noncoding mutations facilitate metabolism rewiring in the five cancer types the researchers studied.

"Our results highlight the need for comparative analysis of both coding and noncoding mutations, which might reveal novel cancer-related genes and pathways," said Tan. "Identifying putative mutations is a starting point that will facilitate experimental work to validates these predictions."

MEDFORD/SOMERVILLE, Mass. (July 24, 2020) --Biomedical engineers at the Tufts University School of Engineering have developed tiny lipid-based nanoparticles that incorporate neurotranmitters to help carry drugs, large molecules, and even gene editing proteins across the blood-brain barrier and into the brain in mice. The innovation, published today in Science Advances, could overcome many of the current limitations encountered in delivering therapeutics into the central nervous system, and opens up the possibility of using a wide range of therapeutics that would otherwise not have access to the brain.

"The power of our method is that it is extremely versatile and relatively non-disruptive," said Qiaobing Xu, associate professor of biomedical engineering at Tufts University and corresponding author of the study. "We can deliver a wide range of molecules by packaging them into the lipid-based nanonparticles without chemically modifying the drugs themselves. We can also achieve delivery across the blood-brain barrier without disrupting the integrity of the barrier."

Xu cautioned that more studies and clinical trials are needed to determine the efficacy and safety of the delivery method in humans.

The blood-brain barrier consists of a layer of endothelial cells that line the blood vessels in the brain and allows only a highly select set of molecules to pass from the bloodstream into the fluid surrounding the neurons and other cells of the brain.The ability to safely and efficiently deliver therapeutic molecular cargos across the barrier and into the brain has been a long-standing challenge in medicine.

The treatment of neurodegenerative disorders, brain tumors, brain infections and stroke has been limited by the difficulty in safely delivering small molecule drugs and macromolecules, such as peptides and proteins, into the brain. Current approaches, such as direct injection or disruption of the barrier to make it "leaky," are fraught with risks, including infection, tissue damage and neurotoxicity. The use of carriers, such as modified viruses and monoclonal antibodies to ferry cargo into the brain, has limitations, including production cost and safety. Other carriers, such as nanoparticles, nanocapsules and polymers, have shown promise but the modifications required to ensure delivery can be complicated.

The study authors made use of the fact that certain neurotransmitters have the chemical "passport" required to gain access throughout the brain. By attaching a lipid (fat-like) molecule to the neurotransmitter, the resulting NT-lipidoid can be doped into lipid nanoparticles (LNPs) - tiny bubbles of lipid that can encapsulate other molecules within, in particular therapeutic drugs. The LNPs can be injected intravenously, and carry the drugs to the blood-brain barrier, while the NT-lipidoid helps the LNPs to carry the drugs across the barrier. The LNPs can then fuse with neurons and other cells in the brain to deliver their therapeutic payload.

Using the LNPs with NT-lipidoid, the researchers successfully delivered into the brain of a mouse:

a small molecule antifungal drug, amphotericin B;

macromolecules including a Tau antisense oligonucleotide, which inhibits the production of tau protein connected to Alzheimer's disease; and

the gene editing protein GFP-Cre.

The researchers observed the effect of diminished tau protein, as well as direct evidence of the gene editing protein entering neurons. In fact, the latter was the first demonstration of genome editing within neurons delivered via intravenous injection, according to the researchers.

While more studies and clinical trials are needed, the delivery method could be a significant advance in convenience and a general application for central nervous system drug delivery. The Tufts researchers found that the addition of the NT-lipidoid to many varieties of LNPs can render them permeable to the blood-brain barrier. That means that LNPs can be optimized for lipid length and ratios to package drugs of different types, from small molecules to DNA to large enzyme complexes, and then provided the same blood-brain barrier permeability by addition of the NT-lipidoid.

"It's simple, effective, and potentially broadly applicable - we can modify the container for the drug, and by adding the NT-lipidoid, it's like attaching an address label for delivery into the brain," said Feihe Ma, post-doctoral scholar in the Xu lab at Tufts. "We envision that a wide range of neurological therapeutics could eventually be tried that were previously thought to be impractical due to limitations in delivery," said Liu Yang, graduate student in the Xu lab. Ma and Yang are co-first authors of the study.

What The Study Did: The use of medical leave among emergency medical service responders and firefighters in New York during the COVID-19 pandemic is compared with earlier periods.

Authors: David J. Prezant, M.D., of the Bureau of Health Services and the FDNY World Trade Center Health Program of the Fire Department of the City of New York, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.16094)

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

Most meteorites that have landed on Earth are fragments of planetesimals, the very earliest protoplanetary bodies in the solar system. Scientists have thought that these primordial bodies either completely melted early in their history or remained as piles of unmelted rubble.

But a family of meteorites has befuddled researchers since its discovery in the 1960s. The diverse fragments, found all over the world, seem to have broken off from the same primordial body, and yet the makeup of these meteorites indicates that their parent must have been a puzzling chimera that was both melted and unmelted.

Now researchers at MIT and elsewhere have determined that the parent body of these rare meteorites was indeed a multilayered, differentiated object that likely had a liquid metallic core. This core was substantial enough to generate a magnetic field that may have been as strong as Earth's magnetic field is today.

Their results, published in the journal Science Advances, suggest that the diversity of the earliest objects in the solar system may have been more complex than scientists had assumed.

"This is one example of a planetesimal that must have had melted and unmelted layers. It encourages searches for more evidence of composite planetary structures," says lead author Clara Maurel, a graduate student in MIT's Department of Earth, Atmospheric, and Planetary Sciences (EAPS). "Understanding the full spectrum of structures, from nonmelted to fully melted, is key to deciphering how planetesimals formed in the early solar system."

Maurel's co-authors include EAPS professor Benjamin Weiss, along with collaborators at Oxford University, Cambridge University, the University of Chicago, Lawrence Berkeley National Laboratory, and the Southwest Research Institute.

Oddball irons

The solar system formed around 4.5 billion years ago as a swirl of super-hot gas and dust. As this disk gradually cooled, bits of matter collided and merged to form progressively larger bodies, such as planetesimals.

The majority of meteorites that have fallen to Earth have compositions that suggest they came from such early planetesimals that were either of two types: melted, and unmelted. Both types of objects, scientists believe, would have formed relatively quickly, in less than a few million years, early in the solar system's evolution.

If a planetesimal formed in the first 1.5 million years of the solar system, short-lived radiogenic elements could have melted the body entirely due to the heat released by their decay. Unmelted planetesimals could have formed later, when their material had lower quantities of radiogenic elements, insufficient for melting.

There has been little evidence in the meteorite record of intermediate objects with both melted and unmelted compositions, except for a rare family of meteorites called IIE irons.

"These IIE irons are oddball meteorites," Weiss says. "They show both evidence of being from primordial objects that never melted, and also evidence for coming from a body that's completely or at least substantially melted. We haven't known where to put them, and that's what made us zero in on them."

Magnetic pockets

Scientists have previously found that both melted and unmelted IIE meteorites originated from the same ancient planetesimal, which likely had a solid crust overlying a liquid mantle, like Earth. Maurel and her colleagues wondered whether the planetesimal also may have harbored a metallic, melted core.

"Did this object melt enough that material sank to the center and formed a metallic core like that of the Earth?" Maurel says. "That was the missing piece to the story of these meteorites."

The team reasoned that if the planetesimal did host a metallic core, it could very well have generated a magnetic field, similar to the way Earth's churning liquid core produces a magnetic field. Such an ancient field could have caused minerals in the planetesimal to point in the direction of the field, like a needle in a compass. Certain minerals could have kept this alignment over billions of years.

Maurel and her colleagues wondered whether they might find such minerals in samples of IIE meteorites that had crashed to Earth. They obtained two meteorites, which they analyzed for a type of iron-nickel mineral known for its exceptional magnetism-recording properties.

The team analyzed the samples using the Lawrence Berkeley National Laboratory's
Advanced Light Source, which produces X-rays that interact with mineral grains at the nanometer scale, in a way that can reveal the minerals' magnetic direction.

Sure enough, the electrons within a number of grains were aligned in a similar direction -- evidence that the parent body generated a magnetic field, possibly up to several tens of microtesla, which is about the strength of Earth's magnetic field. After ruling out less plausible sources, the team concluded that the magnetic field was most likely produced by a liquid metallic core. To generate such a field, they estimate the core must have been at least several tens of kilometers wide.

Such complex planetesimals with mixed composition (both melted, in the form of a liquid core and mantle, and unmelted in the form of a solid crust), Maurel says, would likely have taken over several million years to form -- a formation period that is longer than what scientists had assumed until recently.

But where within the parent body did the meteorites come from? If the magnetic field was generated by the parent body's core, this would mean that the fragments that ultimately fell to Earth could not have come from the core itself. That's because a liquid core only generates a magnetic field while still churning and hot. Any minerals that would have recorded the ancient field must have done so outside the core, before the core itself completely cooled.

Working with collaborators at the University of Chicago, the team ran high-velocity simulations of various formation scenarios for these meteorites. They showed that it was possible for a body with a liquid core to collide with another object, and for that impact to dislodge material from the core. That material would then migrate to pockets close to the surface where the meteorites originated.

"As the body cools, the meteorites in these pockets will imprint this magnetic field in their minerals. At some point, the magnetic field will decay, but the imprint will remain," Maurel says. "Later on, this body is going to undergo a lot of other collisions until the ultimate collisions that will place these meteorites on Earth's trajectory."

Was such a complex planetesimal an outlier in the early solar system, or one of many such differentiated objects? The answer, Weiss says, may lie in the asteroid belt, a region populated with primordial remnants.

"Most bodies in the asteroid belt appear unmelted on their surface," Weiss says. "If we're eventually able to see inside asteroids, we might test this idea. Maybe some asteroids are melted inside, and bodies like this planetesimal are actually common."

People are very skilled with their hands, but take a very long time to learn various dexterous abilities. It takes babies generally around five months before they can purposely grip an object. Learning more complicated skills such as eating with fork and knife or tying one's shoelaces can take another five to six years. By that age, many other primate species already have offspring of their own. Why do we take so much longer than our closest relatives to learn fine motor skills?

Brain development in primates follows fixed patterns

Sandra Heldstab, an evolutionary biologist in the Department of Anthropology at the University of Zurich, and her colleagues Karin Isler, Caroline Schuppli and Carel van Schaik observed 36 different primate species over a period of more than seven years to try to answer this question. She studied 128 young animals in 13 European zoos from birth until the age at which they had reached adult-level dexterity. What surprised her was that all species learned their respective manual skills in exactly the same order. "Our results show that the neural development follows extremely rigid patterns - even in primate species that differ greatly in other respects," says Heldstab.

Large brain needed for dexterity

The researchers found, however, big differences in the specific fine motor skills of adults from different primate species. Large-brained species such as macaques, gorillas or chimpanzees can solve much more complex tasks using their hands than primates with small brains such as lemurs or marmosets. "It is no coincidence that we humans are so good at using our hands and using tools, our large brains made it possible. A big brain equals great dexterity," says Heldstab.

Humans develop fine motor skills later than primates

Dexterity comes at a cost, however: In species with large brains like humans, it takes a long time for infants to learn even the simplest hand and finger movements. "It's not just because we are learning more complex skills than lemurs or callitrichids, for example. It's mainly because we do not begin learning these skills until much later," says Heldstab. The researchers think that the reason for this may be that the larger brains of humans are less well developed at birth.

Essential to have enough time to learn

In addition, learning takes time and is inefficient, and it is the parents who pay for this until their offspring are independent. "Our study shows once again that in the course of evolution, only mammals that live a long time and have enough time to learn were able to develop a large brain and complex fine motor skills including the ability to use tools. This makes it clear why so few species could follow our path and why humans could become the most technologically accomplished organism on this planet," concludes Sandra Heldstab.

Patients with frailty, older age and urinary tract infections (UTIs) are at greatest risk of developing sepsis following infection consultations in primary care, research has found.

A research study published today in PLOS Medicine by researchers from King's College London, with funding from National Institute for Health Research (NIHR), aimed to estimate the probability of a patient developing sepsis following an infection consultation in primary care if they were or were not prescribed antibiotics.

Sepsis is a severe reaction to an infection that can lead to life threatening damage to organ systems. Without treatment, sepsis can lead to multiple organ failure and death. There are more than 200,000 hospital admissions for sepsis each year in England and up to 59,000 deaths.

Antibiotic therapy may reduce the risk of sepsis, however unnecessary antibiotic prescribing is a major concern in primary care which may be contributing to the development of antimicrobial resistance.

Researchers analysed all registered patients at 706 general practices in the UK, with 66.2million person years of follow-up from 2002 to 2017. The cohort included 35,244 first episodes of sepsis, of which 51% were female, with a median age of 71 years.

The study aimed to estimate the probability of a patient developing sepsis following an infection consultation in primary care, if antibiotics are or are not prescribed, and to estimate the number of antibiotic prescriptions required to prevent one episode of sepsis.

The risk of sepsis following an infection consultation in primary care increased with age, and the number of antibiotic prescriptions required to prevent one sepsis event decreased with age.

Frailty level was also associated with greater risk of sepsis. Patients at age 55 years with severe frailty have similar probability of sepsis as a non-frail 85-year-old.
At all ages, the probability of sepsis was greatest for urinary tract infection, followed by skin infection, and then by respiratory tract infection.

The authors concluded antibiotic prescriptions may be safely more reduced in groups with lower probability of sepsis.
Professor Martin Gulliford from King's College London said: "This research helps to identify groups of patients in which antibiotic prescribing may be more safely reduced. Risks of sepsis, and benefits of antibiotics, are more substantial among older adults, patients with more advanced frailty or following UTIs."

Jo Rycroft-Malone, NIHR Programme Director and Chair of the Health Services and Delivery Research (HS&DR) Programme said: "Reducing the use of antibiotics and tackling antimicrobial resistance remain research priorities for the NIHR. The results of this study are valuable for the practice of antibiotic prescribing looking forward as they indicate where practitioners may be able to safely reduce their use."

BATON ROUGE, Louisiana - A hormone that connects the body's metabolism and immune response system may explain why COVID-19 is so dangerous for people with obesity.

"The problem for people with obesity is that their leptin levels are always high, and that can affect the response to a COVID-19 infection," said Candida Rebello, PhD, RD, lead author of a new paper that traces the link between obesity and the virus.

The hormone leptin regulates appetite and metabolism. Leptin also regulates the cells that fight infection. Leptin is produced by fat cells, and to a lesser extent by tissues in the lungs. The more fat a person has, the more leptin circulates in their body.

Elevated leptin levels hamper the body's ability to fight off infections, in the lungs and elsewhere, Dr. Rebello said. High leptin levels promote a low-grade systemic inflammatory state.

"If you have obesity, there are a number of underlying health issues that make it more difficult for you to fight off a COVID-19 infection," said John Kirwan, PhD, Pennington Biomedical Executive Director and a co-author of the review. "Your entire body, including your lungs, may be inflamed. Your immune response is likely compromised, and your lung capacity reduced.

"Add in a virus that further weakens the body's ability to fight infection, that can limit the body's ability to control lung inflammation, and you have the recipe for disaster."

COVID-19 vaccine developers should take the immunocompromised state resulting from obesity into consideration, in much the same way they would advancing age.

The researchers say the role of leptin in COVID-19's development bears investigation along with the viral proteins that alter the immune systems of people with obesity. One potential avenue of treatment may be a drug that prevents inflammatory responses to the virus.

Another potential avenue of investigation includes examining how proinflammatory fat tissue in people with obesity might contribute to activating fewer infection-fighting cells and why those cells die more quickly.

COLUMBUS, Ohio - Research conducted at The Ohio State University Wexner Medical Center and The Ohio State University College of Medicine found that spinal cord injuries in mice cause an acquired bone marrow failure syndrome that may contribute to chronic immune dysfunction.

"We also found that it's possible to overcome certain aspects of spinal cord injury-induced bone marrow failure. This could have an immediate impact on people affected by spinal cord injury," said lead author Phillip Popovich, chair of the Ohio State Department of Neuroscience and executive director of Ohio State's Belford Center for Spinal Cord Injury and Center for Brain and Spinal Cord Repair.

Findings are published online in the journal Nature Communications.

Spinal cord injury (SCI) is known to cause immune system dysfunction, which increases the risk of infections. This, in turn, increases hospitalizations and premature death.

Immune cells are made in the bone marrow. Healthy bone marrow requires proper communication with the nervous system, notably the spinal cord.

"Our research shows that spinal cord injury causes stem cells in the bone marrow - those required to make new immune cells - to rapidly divide. But after cell division, these cells become trapped in the bone marrow. We discovered one possible explanation for this," said Randall S. Carpenter, first author and recently graduated PhD student from Ohio State's Neuroscience Graduate program.

Notably, in bone marrow of mice with spinal cord injuries, there's an increase in chemical signaling between stem progenitor cells and support cells in the bone marrow. This enhanced signaling locks the cells down so they can't move away from the "niches" in which they are born and develop.

This lockdown can be reversed by post-injury injections of the FDA-approved drug Plerixafor, a small molecule inhibitor of CXCR4, a chemokine receptor. Even though Plerixafor frees blood stem cells and mature immune cells from bone marrow, other techniques showed that the intrinsic long-term functional capacity of bone marrow stem/progenitor cells is still impaired for several months post-injury.

Bone marrow failure diseases develop when the bone marrow can't produce enough healthy mature white and red blood cells. Normal aging and various diseases including diabetes, cancers and chemotherapy also trap mature and immature cells in the bone marrow.

"In spinal cord injury patients, Plerixafor could be a potentially safe and effective way to mobilize cells from the bone marrow niche to help restore immune function. In fact, Plerixafor is already used in other clinical indications to help reverse immunodeficiency in patients; it just hasn't been used after spinal cord injury," Popovich said. "While this study was done in mice, these new data help explain observations that have been made in humans with spinal cord injuries," Popovich said. "More research is needed to understand why the bone marrow failure develops, and whether it's permanent."

Curtin University researchers have unexpectedly discovered a new way to make crystalline graphite, an essential material used in the making of lithium ion batteries.

Described in a research paper published today in Nature's Communications Materials, the new technique does not require the typical metal catalysts or special raw materials to turn carbon into crystalline graphite. Interestingly it was instead discovered by a research student in a lab, using an Atomic Absorption Spectrometer (AAS) - a piece of equipment, invented in Australia in the 1950s and developed to analyse the composition of liquids.

The Master-level student behind the discovery, Mr Jason Fogg, said that while the exact science behind why this new technique works is still to be confirmed, he believes it relates to the specific way the AAS heats the samples through short fast pulses.

"We used a special furnace that can heat the sample to 3000 degrees Celsius in seconds, something most furnaces cannot achieve," Mr Fogg said.

"To put the temperature into perspective, 3000 degrees Celsius is equal to about half the surface temperature of the Sun."

Dr Irene Suarez-Martinez, from Curtin's School of Electrical Engineering, Computing and Mathematical Sciences, said that while graphite is the most stable form of carbon, most carbon materials stubbornly refuse to turn into graphite, which is why she was absolutely shocked to learn about Mr Fogg's results.

"When he told me that he created perfect crystalline graphite from a known non-graphitising carbon material, I could not believe it, I was absolutely amazed at the results. It was only when we repeated the results three times that I was convinced," Dr Suarez-Martinez said.

The most astonishing result involved the polymer polyvinylidene chloride (PVDC), which Dr Suarez-Martinez described as a 'textbook example' of a very stubborn material.

As the world's demand for lithium ion batteries increases, scientists expect the commercial demand for crystalline graphite to also increase, and this research team is now determined to work out the precise details of why this special pulse heating method was so effective.

"Our hypothesis is that atmospheric oxygen soaks into the structure between pulses, and the rapid heating on the next pulses burns away the structures that would usually prevent graphite from forming," Dr Suarez-Martinez said.

"We're also interested to see if other complex carbons will also transform. Could this method be able to convert organic carbon material, such as food waste, into crystalline graphite?

"Right now we're only able to create very small amounts of crystalline graphite, so we are far from being able to reproduce this process on a commercial-level. But we plan to explore our method and hypotheses further."

Research has shown a global increase in the emergence of infectious diseases and epidemics, an accelerated loss of biodiversity and a marked increase in the breeding of domesticated animals. This subject was brought back to the fore by the COVID-19 outbreak and a new study in parasite ecology is providing some initial answers to the ongoing question of whether these events are connected. Its goal was to trace the global patterns of biodiversity and infectious diseases both spatially and temporally.

To achieve this, the researcher cross referenced various open databases* on human and animal health, livestock expansion and biodiversity loss. An initial analysis showed that the number of epidemics identified in humans in each country increased in correlation with local biodiversity loss (16,994 epidemics caused by 254 infectious diseases between 1960-2019). The emergence of epidemics is a worrying sign for the future of species conservation as it could well signal biodiversity's march towards extinction. The relation between the number of endangered species and the number of epidemics first increases, then peaks, before finally declining. However, the risk of an epidemic does not decrease with the disappearance of a species, but on the contrary, is further relayed by the growing number of head of cattle. Data from 2006-2019 confirms this second result placing it at the heart of a potential health risk. Livestock expansion worldwide directly affects wildlife as well as the incidence of epidemics in humans and in domesticated animals.

The study brings up the question of the place of farmed animals and their increase across the world, which varies according to factors such as human demographics and diet. In order to lower the health risk and protect biodiversity we need to take into account the cultural value of animals to reflect on the place of both wild and domesticated species. Future studies will examine the role played by livestock in pandemics by looking at, on the one hand, the cultivation of vegetable protein needed for feed, which contributes to reduce the space for wild animals, and on the other, on the role of livestock as an epidemiological bridge between wildlife and humans facilitating the transmission of pathogens.

If the eyes are the mirror of the soul, then thanks to the translucent corneas, we can look deep into that soul. And thanks to the work of scientists from the IPC PAS we can look into the depths of the cornea itself. And that without touching it! All thanks to the introduction of an innovative method of holographic optical tomography.

"Our idea was to spoil the coherent laser beam illuminating the cornea, so we could significantly extend the exposure time without endangering the delicate retina. At the same time, it allows us to maintain a high value of light power, which allows us to see even a very weak light backscattered from the cornea," explains professor Wojtkowski. Additionally, the volumetric nature of the collected data allowed for the optical "flattening" of the cornea curvature and obtaining exceptionally sharp images of all its layers across the entire section. This is not an easy task, because the transparency of the cornea, although it allows to look inside the eye, does not facilitate the examination of the cornea itself.

The old methods required contact of the measuring device with the eye, and thus anaesthesia of the eyeball was mandatory, and the measurement itself - long-lasting. However, even the newer ones, using the OCT (optical coherence tomography), have limitations due to not fast enough image collection, which, when examining an unanaesthetized eye, makes the obtained image blurry due to micro-movement of the eyeball.

The breakthrough came with super-fast cameras recording tens of thousands of frames per second, which made it possible to record images at lightning speed. The problem in standard OCT was the resolution and artifacts resulting from the fact that the cornea is curved and scanning it, the laser beam is arranged slightly differently in each part. This is where the scientists from the IPC PAS come in. Their method, known as holographic OCT tomography, allows them to capture the cornea in a fraction of a second and to record its entire depth in an extremely high, unprecedented resolution. The patient will not even have time to blink, and his cornea is already imaged, with the accuracy so high that even single cells can be viewed. And if she or he even blinks (well, let's say moves the eye), the computer will compensate for this movement, still giving a sharp image.

- Moreover our new device has no moving parts, and thanks to the phase modulation of the laser beam we can use more power without harming deeper tissues of the eye," explains professor Wojtkowski.

The method developed by scientists from the International Centre for Translational Eye Research at the IPC PAS has a chance to revolutionize the diagnosis of eye diseases, not only corneas, giving doctors a tool to examine patients quickly and painlessly. Thanks to the fact that it also makes visible what is invisible in an ordinary slit lamp and is equally non-invasive, patients will gain comfort and ophthalmologists will gain incomparably more information.