Culture

An experimental vaccine is effective at preventing pneumonia in mice infected with the COVID-19 virus, according to a study from Washington University School of Medicine in St. Louis. The vaccine, which is made from a mild virus genetically modified to carry a key gene from the COVID-19 virus, is described in the journal Cell Host and Microbe.

"Unlike many of the other vaccines under development, this vaccine is made from a virus that is capable of spreading in a limited fashion inside the human body, which means it is likely to generate a strong immune response," said co-senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and a professor of molecular microbiology, and of pathology and immunology. "Since the virus is capable of replicating, it can be grown to high levels in the lab, so it's easy to scale up and should be more cost-effective than some of the other vaccine candidates. So while what we have shown is just the proof of concept, I think it's very promising. Our vaccine candidate is now being tested in additional animal models with the goal of getting it into clinical trials as soon as possible."

Diamond and colleagues - including co-senior author Sean Whelan, PhD, the Marvin A. Brennecke Distinguished Professor and head of the Department of Molecular Microbiology; and co-first authors Brett Case, PhD, a postdoctoral researcher in Diamond's laboratory, and Paul W. Rothlauf, a graduate student in Whelan's laboratory - created the experimental vaccine by genetically modifying vesicular stomatitis virus (VSV), a virus of livestock that causes only a mild, short-lived illness in people. They swapped out one gene from VSV for the gene for spike from SARS-CoV-2, the virus that causes COVID-19. The hybrid virus is called VSV-SARS-CoV-2.

Spike protein is thought to be one of the keys to immunity against COVID-19. The COVID-19 virus uses spike to latch onto and infect human cells, and the human body defends itself by generating protective antibodies targeting spike. By adding the gene for spike to a fairly harmless virus, the researchers created a hybrid virus that, when given to people, ideally would elicit antibodies against spike that protect against later infection with the COVID-19 virus.

The same strategy was used to design the Ebola vaccine that was approved by the U.S. Food and Drug Administration in 2019. That vaccine - which is made from VSV genetically modified with a gene from Ebola virus - has been safely administered to thousands of people in Africa, Europe and North America, and helped end the 2018 to 2020 Ebola outbreak in the Democratic Republic of the Congo.

As part of this study, the researchers injected mice with VSV-SARS-CoV-2 or a lab strain of VSV for comparison. A subgroup was boosted with a second dose of the experimental vaccine four weeks after the initial injections. Three weeks after each injection, the researchers drew blood from the mice to test for antibodies capable of preventing SARS-CoV-2 from infecting cells. They found high levels of such neutralizing antibodies after one dose, and the levels increased 90-fold after a second dose.

Then, the researchers challenged the mice five weeks after their last dose by spraying the COVID-19 virus into their noses. The vaccine completely protected against pneumonia. At four days post infection, there was no infectious virus detectable in the lungs of mice that had been given either one or two doses of the vaccine. In contrast, mice that had received the placebo had high levels of virus in their lungs. In addition, the lungs of vaccinated mice showed fewer signs of inflammation and damage than those of mice that had received the placebo.

The experimental vaccine is still in the early stages of development.

Mice do not naturally become infected with the COVID-19 virus, so to assess whether the vaccine elicited a protective immune response in them, the researchers used genetically modified mice or, in unmodified mice, employed a complicated technique to induce susceptibility to infection. The researchers are in the process of repeating the experiments in other animal models that are naturally susceptible to the COVID-19 virus. If the vaccine also protects those animals from COVID-19, the next step would be to scale up production under what the Food and Drug Administration refers to as "good manufacturing practice (GMP) conditions" and launch a clinical trial in people.

While the data are promising, this vaccine is still months behind in the race to develop a pandemic-ending vaccine. Six vaccines are in the final stage of testing in people, and Anthony Fauci, MD, director of the U.S. National Institute of Allergy and Infectious Diseases, has said he expects a vaccine to be ready for mass distribution early next year.

"It's really going to depend on how successful the first vaccines that come out for COVID are," Whelan said. "If they don't produce a robust, durable immune response or there are safety issues, there might be the opportunity for a second-generation vaccine that could induce sterilizing immunity and interrupt the cycle of transmission."

Sweden's policy of allowing the controlled spread of Covid-19 viral infection among the population has so far failed to deliver the country's previously stated goal of herd immunity. Commenting on recent antibody testing clinical and research findings, authors of a paper published by the Journal of the Royal Society of Medicine, write that Sweden's higher rates of viral infection, hospitalisation and mortality compared with neighbouring countries may have serious implications for Scandinavia and beyond.

Rather than imposing a hard lockdown in March as most European and Scandinavian countries did, Sweden's strategy in dealing with the pandemic has been to rely on people's individual responsibility to curtail the spread of the disease. This follows the Swedish sociocultural concept of 'folkvett'; the common sense of the people as a collective.

The health authorities predicted that 40% of the Stockholm population would have had the disease and acquired antibodies by May 2020. However, the actual prevalence figure was around 15%. While clinical and research findings suggest that severely infected Covid-19 patients do acquire antibodies in the immediate and early recovery phase of their illness, antibodies are much less commonly found in only mildly ill or asymptomatic patients. This means they are very likely not to be immune, and so cannot act as a bulwark against further spread of infection amongst the community.

Lead author Professor David Goldsmith said: "It is clear that not only are the rates of viral infection, hospitalisation and mortality (per million population) much higher than those seen in neighbouring Scandinavian countries, but also that the time-course of the epidemic in Sweden is different, with continued persistence of higher infection and mortality well beyond the few critical weeks period seen in Denmark, Finland and Norway." He added that in these countries, rapid lock-down measures brought in from early March seem to have been initially more successful in curtailing the infection surge and thus the malign consequences of Covid-19 on the country as a whole.

Prof Goldsmith said: "We in the UK would do well to remember we nearly trod the same path as Sweden, as herd immunity was often discussed here in early March. Right now, despite strict (but tardy) lock-down in the UK, and the more measured Swedish response, both countries have seen high seven-day averaged Covid-19 death rates compared to other Scandinavian and European countries."

The authors do say, however, that only once the pandemic and impact of measures taken are fully understood, after one or two years at least, can we begin fairly then to judge what was done correctly.

A new study by Palaeontologists at the University of Southampton suggests four bones recently found on the Isle of Wight belong to new species of theropod dinosaur, the group that includes Tyrannosaurus rex and modern-day birds.

The dinosaur lived in the Cretaceous period 115 million years ago and is estimated to have been up to four metres long.

The bones were discovered on the foreshore at Shanklin last year and are from the neck, back and tail of the new dinosaur, which has been named Vectaerovenator inopinatus.

The name refers to the large air spaces in some of the bones, one of the traits that helped the scientists identify its theropod origins. These air sacs, also seen in modern birds, were extensions of the lung, and it is likely they helped fuel an efficient breathing system while also making the skeleton lighter.

The fossils were found over a period of weeks in 2019 in three separate discoveries, two by individuals and one by a family group, who all handed in their finds to the nearby Dinosaur Isle Museum at Sandown.

The scientific study has confirmed the fossils are very likely to be from the same individual dinosaur, with the exact location and timing of the finds adding to this belief.

Robin Ward, a regular fossil hunter from Stratford-upon-Avon, was with his family visiting the Isle of Wight when they made their discovery. He said: "The joy of finding the bones we discovered was absolutely fantastic. I thought they were special and so took them along when we visited Dinosaur Isle Museum. They immediately knew these were something rare and asked if we could donate them to the museum to be fully researched."

James Lockyer, from Spalding, Lincolnshire was also visiting the Island when he found another of the bones. Also a regular fossil hunter, he said: "It looked different from marine reptile vertebrae I have come across in the past. I was searching a spot at Shanklin and had been told and read that I wouldn't find much there. However, I always make sure I search the areas others do not, and on this occasion it paid off."

Paul Farrell, from Ryde, Isle of Wight, added: "I was walking along the beach, kicking stones and came across what looked like a bone from a dinosaur. I was really shocked to find out it could be a new species."

After studying the four vertebrae, paleontologists from the University of Southampton confirmed that the bones are likely to belong to a genus of dinosaur previously unknown to science. Their findings will be published in the journal Papers in Palaeontology, in a paper co-authored by those who discovered the fossils.

Chris Barker, a PhD student at the university who led the study, said: "We were struck by just how hollow this animal was - it's riddled with air spaces. Parts of its skeleton must have been rather delicate.

"The record of theropod dinosaurs from the 'mid' Cretaceous period in Europe isn't that great, so it's been really exciting to be able to increase our understanding of the diversity of dinosaur species from this time.

"You don't usually find dinosaurs in the deposits at Shanklin as they were laid down in a marine habitat. You're much more likely to find fossil oysters or drift wood, so this is a rare find indeed."

It is likely that the Vectaerovenator lived in an area just north of where its remains were found, with the carcass having washed out into the shallow sea nearby.

Chris Barker added: "Although we have enough material to be able to determine the general type of dinosaur, we'd ideally like to find more to refine our analysis. We are very grateful for the donation of these fossils to science and for the important role that citizen science can play in palaeontology."

The Isle of Wight is renowned as one of the top locations for dinosaur remains in Europe, and the new Vectaerovenator fossils will now go on display at the Dinosaur Isle Museum at Sandown, which houses an internationally important collection.

Museum curator, Dr Martin Munt, said: "This remarkable discovery of connected fossils by three different individuals and groups will add to the extensive collection we have and it's great we can now confirm their significance and put them on display for the public to marvel at.

"We continue to undertake public field trips from the museum and would encourage anyone who finds unusual fossils to bring them in so we can take a closer look. However, fossil hunters should remember to stick to the foreshore, and avoid going near the cliffs which are among the most unstable on the Island."

Isle of Wight Council Cabinet member for environment and heritage, Councillor John Hobart, said: "This is yet another terrific fossil find on the Island which sheds light on our prehistoric past - all the more so that it is an entirely new species. It will add to the many amazing items on display at the museum."

New research from two London hospital maternity units published in Anaesthesia (a journal of the Association of Anaesthetists) shows that 1 in 6 maternity workers tested positive for COVID-19 antibodies, showing they have had a previous infection. Of those testing positive, 1 in 3 were completely asymptomatic.

Worryingly, more than half (58%) of those who tested positive never met the UK Government's criteria for self-isolation, and thus did not self-isolate and continued to work as normal in their hospital. The study is by Dr Sohail (Sam) Bampoe and Dr Peter Odor, both Consultant Obstetric Anaesthetists at University College London Hospitals NHS Foundation Trust, and Honorary Associate Professors at University College London, London, UK.

COVID-19, the respiratory disease caused by the SARS-CoV-2 virus, is thought to cause a milder illness in pregnancy with a greater proportion of asymptomatic carriers. This has important implications for the risk of patient-to-staff, staff-to-staff and staff-to patient transmission among health professionals working in maternity wards.

The aim of this study was to investigate the prevalence of previously undiagnosed SARS-CoV-2 infection in health professionals from two hospital-level maternity units, University College London Hospital and St George's Hospital in London, UK, and to determine associations between health care workers' characteristics, reported symptoms and evidence of prior SARS-CoV-2 infection using antibody testing.

The study included 200 anaesthetists (40), midwives (108) and obstetricians (52) with no previously confirmed diagnosis of COVID-19, who were tested for prior COVID-19 infection using laboratory antibody tests. Comprehensive symptom and medical histories were also collected.

A total of 29/200 (14.5%) tested positive (seropositive). The highest positivity rate was found in midwives (17/108, 15.7%) followed by obstetricians (7/52, 13.5%) and anaesthetists (5/40, 12.5%). Of those who tested positive for COVID-19 antibodies, 10/29 (35.5%) were completely asymptomatic. Fever or cough were only present in 6/29 (20.7%) and 10/29 (34.5%) respectively. Anosmia (loss of sense of taste and smell) was the most common symptom occurring in 15/29 (51.7%) of seropositive participants. More than half (58.6%) of those who tested positive had not met the national criteria for self-isolation at any point, and therefore did not self-isolate and continued to provide patient care in the hospital setting.

The authors discuss that the positivity rate was more than twice as prevalent in UK obstetric health care workers as in the general population in the UK and three times as prevalent as in the general population in the USA. However, the prevalence of seroconversion of health care workers in these London hospitals was similar to estimates of seroconversion in the general population in Greater London at 14.5%, based on sampling from blood donors. They say: "Although these results would suggest that obstetric health care workers are at a similar risk of exposure to COVID-19 as the general population, the prevalence of seroconversion among this staff group appears to be lower than reported in other frontline health care worker groups."

The authors also discuss the possibility that greater proportion of asymptomatic infection in pregnancy and generally milder symptom profile in pregnant patients may explain why obstetric health care workers appear to have a lower risk of occupational viral transmission, as SARS-CoV-2 pregnant patients may be less infective than respiratory or acute emergency patients.

They also discuss that the risk posed by infectious staff members to colleagues, pregnant women, and their offspring remains unknown. At the beginning of the current SARS-CoV 2 pandemic, the UK government advised all those with a persistent cough or fever above 37.8C to self-isolate. The data in this new study revealed that only 41.4% of health care workers who tested positive for COVID-19 antibodies met those criteria and self-isolated at any point. This means that 58.6% continued to work -- and commute -- despite active SARS-CoV-2 infection. The data showed that in this population, neither cough nor fever predicted seropositivity and the only symptom predictive of a positive test was loss of taste and smell. The UK government have since added this symptom to those that mandate self-isolation. The authors say: "Our study strongly supports this updated advice, even though it would still fail to isolate approximately 6 out of 10 infected staff."

Some limitations to the study are discussed by the authors. Based on data from other similar viruses, the duration of antibody volumes sufficient to be detected is likely to be for at least six months. However, the exact duration of antibodies showing COVID-19 infection remains unknown and recent studies have shown that mild cases might end up testing negative. As such it is possible that some individuals who were infected earlier in the year, as well as some mild cases, did not have a strong enough antibody response at the date of testing to test positive. The testing methodology used in this study may therefore underestimate the true seroconversion prevalence.

The authors conclude: "Until we have robust evidence as to the risk posed by asymptomatic infected individuals to others, and as to the risk of COVID-19 to babies, particularly during pregnancy, our study suggests that extreme caution is advisable in maternity settings, particularly the consistent use of effective personal protective equipment (PPE) and other known effective measures including social distancing of staff and the regular washing of hands. We also recommend that all obstetric healthcare institutions should consider regular serology testing for staff, as well as the immediate isolation of any staff who lose their sense of taste and smell, even in the absence of cough or fever. Regular testing and consistent use of PPE are likely to be the cornerstones of pandemic control."

Mitochondria are the powerhouse of cells which continuously convert energy from food into the chemical energy currency called ATP. This essential process depends on large protein complexes within the inner membrane of mitochondria acting similar to batteries. A new study, led by Dr. Ruchika Anand and Prof. Andreas Reichert, Heinrich-Heine-University Duesseldorf, Institute of Biochemistry and Molecular Biology I, now found that two lipid-binding proteins located inside of mitochondria control the overall stability of these batteries. This was further shown to be linked to a unique mitochondrial lipid and its synthesis: cardiolipin. Increased build-up of a sugar-modified form of MIC26 was earlier found in blood plasma of the patients suffering from diabetic cardiomyopathy. This study provides the first link between mitochondrial structure, lipids and assembly of large respiratory protein units of mitochondria and their importance in diabetes and heart diseases.

Fat- or lipid-binding proteins called apolipoproteins are well known to bind to lipids (e.g. phospholipids and cholesterol) and to mediate formation of lipoproteins (e.g. HDL or LDL). The main function of lipoproteins is to help to transport lipids in the blood. They take part in uptake, clearance and distribution of all lipids in an organism. Several classes of these proteins are found with different functions. Surprisingly, two apolipoproteins (Apolipoprotein O (APOO/MIC26) and Apolipoprotein O-like (APOOL/MIC27) were earlier found at a location distinct from the blood, namely in mitochondria and associated with a large protein assembly called the MICOS complex. Apolipoprotein O (MIC26) occurs in two forms, a sugar-bound and a non-sugar bound form. While the non-sugar bound form is present inside the mitochondria, the sugar-bound form is found in the blood plasma. Increased quantity of the sugar-bound form in blood plasma was interestingly associated with diabetes and diabetic cardiomyopathy. A mutation in APOO/MIC26 is associated to mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features.

The research groups of Dr. Ruchika Anand and Prof. Dr. Andreas Reichert from the Institute of Biochemistry and Molecular Biology I of the Medical faculty at the HHU in collaboration with scientists Dr. Ilka Wittig from the Goethe University Frankfurt am Main, Germany, and Dr. Thomas Eichmann from the University of Graz, Austria determined the function of these apolipoproteins. They found that the cooperation of the two apolipoproteins of mitochondria (APOO/MIC26 and APOOL/MIC27) are required for the global stability of major mitochondrial protein complexes involved in energy conversion by oxidative phosphorylation. These mitochondrial complexes are arranged in large assemblies so that they can work properly and efficiently to convert the energy from the food into the chemical energy in the form of ATP. The internal structure of mitochondria is arranged and sculptured to accommodate these batteries in the folds of the inner membrane called cristae. APOO/MIC26 and APOOL/MIC27 cooperate to form proper mitochondrial structure including tubular structures located at the entry point of cristae termed crista junctions. The study revealed that both proteins are required together to maintain the correct levels of the mitochondrial specific lipid cardiolipin. The aforementioned scientists found that simultaneous deletion of APOO/MIC26 and APOOL/MIC27 in a cell cause major disturbances in cellular respiration together with occurrence of abnormal mitochondrial structure. This study exemplifies the importance of mitochondrial membrane structures and large protein assemblies in diseases such as diabetic cardiomyopathy and mitochondrial myopathy. This could help to gain further insights for future therapies. The work was published after peer review in Life Science Alliance on August 11th, 2020.

A group of researchers from four countries, including Brazil, have worked out exactly how a pollen tube, the plant cell that emerges from a grain of pollen, grows up to a thousand-fold to reach an ovule deep inside the flower. The key to this growth is an inflow and outflow of protons that creates electrical activity at the cell membrane and makes the cell grow. The results of the study will help scientists understand an array of related phenomena, such as seed production, the growth of fungi, and even how neurons develop.

The study was supported by FAPESP. The findings are described in a paper authored by researchers affiliated with institutions in Brazil, Denmark, Portugal and the United States and published in Nature Communications.

“A grain of pollen consists of a single cell. When it comes into contact with the female sex organ on the surface of a flower, it grows at a very high speed, forming what we call a pollen tube, until it reaches the base of the flower’s ovary and discharges the sperm cells. How this happens was very poorly understood until now” according to Maria Teresa Portes, who conducted the research during a postdoctoral fellowship at the University of Maryland in the US.

Scientists have long been intrigued by the exceptionally fast pace of pollen tube growth, which is the fastest type of cell growth observed among all living organisms. Its elongation originates at the tip of the tube and is termed tip growth. The species used in the study was Arabidopsis thaliana (thale cress), a small flowering plant native to Eurasia and Africa. It belongs to the mustard family (Brassicaceae) and is widely chosen as a model organism because of its usefulness for genetic experiments. Its pollen tube grows as much as 3 mm per day.

The researchers produced mutant varieties of the plant in the laboratory in which some genes were modified. They discovered that inactivating three AHA genes inhibited pollen tube growth. AHA refers to the autoinhibited H+-ATPase gene family.

In the mutant plants, only the eggs closest to the surface were fertilized. As a result, the plants produced only 5% of the normal number of seeds.

In a series of experiments, the researchers found that the proteins expressed from these genes acted as proton pumps, injecting protons from the environment to make the pollen tube cell more acidic and promote faster growth.

Proton pumps regulate the electrochemical gradient that energizes the nutrient uptake system and acid growth mechanism of plant cells.

“We wanted to understand how the cell organizes this growth process. Proton distribution in the ion gradient was found to be non-uniform, with protons bunching at the tip of the tube, and there are also gradients of molecules such as calcium and actin,” said Daniel Santa Cruz Damineli, another coauthor of the study who is currently a postdoctoral fellow in the University of São Paulo’s Medical School (FM-USP) in Brazil with a scholarship from FAPESP.

From seeds to neurons

Among several potential developments arising from the study’s findings is a deeper understanding of how seeds are produced, so that they can, in theory, be used to create improved varieties of food crops such as legumes and cereals.

“We don’t know everything about how the pollen tube is guided and how a plant’s male and female organs communicate,” Portes said. “This is a major research interest and could culminate in seed production. Plant growth necessarily involves this mechanism, which we’re just starting to understand more deeply.”

This knowledge should also help scientists understand tip-growth in other cells or organisms, such as that of fungal hyphae, neurons and cancer cells.

“Biologically speaking, how tip growth is orchestrated is poorly understood. Now we can study it further,” Damineli said.

Researchers from Skoltech, Lomonosov Moscow State University, and the Kharkevich Institute for Information Transmission Problems have studied the genomes of some 200 strains of bacteria to determine which proteins in the ribosome, part of the key cell machinery, can be safely lost and why. The paper was published in the journal Molecular Biology and Evolution.

The ribosome is a universal cellular machine, present in all eukaryotes and prokaryotes, that builds proteins in a process called translation. The two major components of the ribosome, the so-called small and large ribosomal subunits, consist of ribosomal RNA (rRNA) molecules and ribosomal proteins.

The composition of these fundamental 'protein factories' is fairly consistent across cells, but there is evidence that some bacteria function without a complete set of ribosomal proteins, so researchers have been looking to determine which of the proteins are truly essential for a working ribosome.

Skoltech professor and vice president for biomedical research Mikhail Gelfand and his colleagues analyzed ribosomal protein composition in 214 relatively small bacterial genomes. They identified a set of frequently lost proteins and showed that only nine ribosomal proteins were completely conserved, while each of the remaining 48 was lost in at least one strain from the dataset.

"Tiny genomes are characteristic of endosymbionts, bacteria that live within other bacteria or eukaryotic cells. In this non-changing environment and under weak selection they tend to lose non-essential (even if necessary for free-living bacteria) genes -- similar to multicellular parasites that often miss entire organs. The ribosome has been assumed to be the most conserved organelle with a standard set of proteins; but if you have only 121 genes -- the present bacterial record for simplicity -- you cannot encode all fifty-something ribosomal proteins, so some of them have to be lost. We have demonstrated that the patterns of this loss are not random," Professor Gelfand says.

Apparently, ribosomal proteins of the small subunit were more likely to be retained than the large subunit proteins, and most frequently lost proteins were located on the ribosome surface, where they formed fewer contacts with other ribosome components. They were also incorporated in the ribosome late in evolution, so it seems that bacteria tend to practice the 'last in, first out' approach when it comes to dropping ribosomal proteins.

The researchers also found that the three bacteria with the shortest genomes in the group lost the largest number of proteins; there was a correlation between genome size and a number of retained ribosomal proteins. Yet since ribosomal proteins are in the cell's essential toolkit, they are generally among the last to leave a 'downsizing' bacterial genome.

A career in professional football may yield an array of health benefits that extend beyond playing years: NFL players engage in vigorous training, tend to be more educated than other men in the U.S. and have higher median incomes than most fellow Americans--all factors associated with better overall health.

But new research from Harvard Medical School and the Harvard T.H. Chan School of Public Health suggests that even these advantages may not be enough to neutralize persistent gaps in health outcomes among Black, white and players of other racial backgrounds.

The analysis, based on self-reports among former NFL players, found that Black players were significantly more likely than white players to experience diminished quality of life due to impaired physical function, pain, cognitive troubles, depression and anxiety. In four of five health outcomes, the gaps were greatest between Black and white former players.

The findings, published on August 4 in Annals of Epidemiology, are based on a survey of 3,794 former NFL players, ages 24 to 89, conducted as part of the ongoing Football Players Health Study at Harvard University, a research initiative that encompasses a constellation of studies designed to evaluate various aspects of players' health across the lifespan.

The researchers categorized former players into three groups based on self-identified race: Black (1,423), white (2,215) and Hawaiian and other races (109)--a group that included American Indian/Alaskan Native, Native Hawaiian/Pacific Islander and Asian, among others.

Next, the researchers compared self-reported symptoms in five categories: physical functioning, pain, cognitive function, depression and anxiety.

The analysis showed that Black former NFL players were 50 percent more likely than white former players to have pain that interfered with daily activities, as well as depression and anxiety. Black former players were 36 percent more likely to have cognitive symptoms--including memory deficits and attention problems--that impacted their quality of life. Black former players were also nearly 90 percent more likely to report impaired physical functioning, compared with their white peers.

The study found that other nonwhite players, including Native Hawaiians, had a higher risk for all categories of adverse health outcomes, except impaired physical functioning.

"Our analysis points to persistent and dramatic gaps in health outcomes among former NFL players that are particularly pronounced among Black athletes and also present among other Hawaiians, Native Americans and Asian players," said study lead author Andrea Roberts, senior research scientist at the Harvard T.H. Chan School of Public Health.

"Our findings underscore the urgent need to develop public health interventions and policies that address underlying systemic factors that give rise to such disparities both among former athletes and in the general population," Roberts added.

To examine the role of other factors that may affect health outcomes, the researchers also looked at number of seasons played in the NFL, position played, concussion symptoms, surgeries, body-mass index, use of performance-enhancing drugs, lifestyle habits including drinking and smoking, as well as pain medication use. The differences persisted even when the researchers accounted for the possible influence of these factors.

Next, the researchers examined whether differences in health varied by a player's age, as a surrogate marker for diversity and equity in the era that they played in. Although younger nonwhite players were in the NFL during a period marked by greater diversity and greater equity, their risk for adverse health outcomes remained the same as that of older players.

The researchers suggested that factors such as discrimination prior to, during, or following a player's time in the NFL could account for the disparities. Systemic and structural racism has been linked with worse mental and physical health and higher mortality. Additionally, past research indicates that nonwhites are more likely to receive lower quality health care than whites.

"We tend to think that elite athletes may be shielded from health inequities, but our findings counter that notion and reveal important differences in quality of life among former athletes," said study senior author Marc Weisskopf, professor of environmental epidemiology and physiology at the Harvard Chan School. "These gaps echo well-documented health disparities in the general population and demand both short-term interventions and long-term solutions."

"As we begin to unpack the complexities around these health disparities between white and nonwhite players, we can begin to see the confluence of challenges that extend beyond the socioeconomic benefits of playing in the NFL," said study co-author Herman Taylor, a co-investigator of the Football Players Health Study and director of the Cardiovascular Research Institute at the Morehouse School of Medicine. "Meaningful solutions to systemic inequities that fuel health disparities will not emerge overnight. In the meantime, we urge players to consult their physicians about the health concerns we've outlined in this study that might impact their quality of life."

A new study published today demonstrates that a technology developed at the University of Central Florida could serve as a more reliable clinically-based model of amyotrophic lateral sclerosis (ALS) and a better screening tool for novel therapies than currently use preclinical models.

The Human-on-a-Chip®technology was developed by UCF Professor James J. Hickman in his Hybrid Systems Lab at UCF. It has been licensed to Hesperos, Inc., a company founded by Hickman and Michael L. Shuler, Ph.D.

"This study supports the ability of our Human-on-a-Chip system to more accurately and rapidly assess new treatments for ALS, and potentially speed up the overall drug development process," says Hickman, co-author of the paper, titled "A Human-Based Functional NMJ System for Personalized ALS Modeling and Drug Testing," published in the journal Advanced Therapeutics . "This is also the first data to demonstrate the efficacy of the Deanna protocol for the treatment of ALS, utilizing a clinically relevant assay system."

ALS is a progressive disease that damages nerves and over time causes the loss of muscle control and eventual death. Between 12,000-15,000 people in the nation are diagnosed with ALS with about 5,000 new cases every year, according to the Centers for Disease Control and Prevention. Also known as Lou Gerhig's disease, there is no cure.

In the new journal article, researchers from UCF and Cornell University describe a functional neuromuscular junction (NMJ) disease model comprising motoneurons derived from induced pluripotent stem cells (iPSCs) of ALS patients and wild type primary human muscle fibers housed in a compartmentalized chambered system. Most importantly, the functional system was able to reproduce assays used in the clinic to assess ALS deficits where a patient is given a task to do with increased speed to detect spasticity or loss of muscle strength. This was reproduced by stimulating the motoneurons at increasing frequency and monitoring the muscle to record "skips" as well as accelerated fatigue.

The iPSCs were derived from three separate ALS lines, two expressing SOD1 mutations and one expressing the FUS mutation. Compared to healthy controls, each of the three cell lines of ALS motoneurons exhibited mutant-specific pathological phenotypes at varying degrees of severity, including increased axonal varicosities, reduced axon branching and elongation, and increased excitability.

When ALS motoneurons were incubated in the dual chamber system with muscle tissue, functional NMJs were formed without cell death from axons transported through tiny tunnels to the muscle chamber. However, there were significant impairments in NMJ formation, electrical activity transmission, and muscle contraction with increasing stimulation frequency. These data suggest that the system is a valid model that recapitulates the morphological and functional deficits in ALS.

"To our knowledge, this is the first study to demonstrate that while different ALS mutations display various phenotypes, all have the common point-of-origin deficit at the NMJ for each mutation, which is useful for not only the familial form of the disease but potentially sporadic as well" said Hickman.

The Deanna protocol is a regimen of holistic, supplements that contains five components targeting various cellular mechanisms known to be pathologically altered in ALS and this over-the-counter ALS treatment is commercially available. While this strategy has been anecdotally reported to successfully treat ALS, there was previously no scientific evidence in a human functional model that support its therapeutic use.

In the study, upon treatment with the Deanna protocol the NMJ functional deficits were reversed. Specifically, treatment led to significant improvements in NMJ formation, electrical activity transmission and muscle contractions, even at higher frequencies of stimulation.

"Hesperos is looking forward to exploring how this interconnected multi-organ platform could be used to reveal additional patient-specific phenotypes in ALS and for high-content screening of drug candidates," said Michael L. Shuler, Ph.D., Chief Executive Officer of Hesperos.

STONY BROOK, NY, August 11, 2020 - Human networking involves every field and includes small groups of people to large, coordinated systems working together toward a goal, be it traffic management in an urban area, economic systems or epidemic control. A new study published in Nature Communications suggests by using a model of violin synchronization in a network of violin players, there are ways to drown out distractions and miscommunications that could be used as a model for human networks in society.

Titled "The Synchronization of Complex Human Networks," the study was conceived by Elad Shniderman, a graduate student in the Department of Music in the College of Arts and Sciences at Stony Brook University, and scientist Moti Fridman, PhD, at the Institute of Nanotechnology and Advanced Materials at Bar-llan University. He co-authored the paper with Daniel Weymouth, PhD, Associate Professor of Composition and Theory in the Department of Music and scientists at Bar-llan and the Weizmann Institute of Science in Israel. The collaboration was initiated at the Fetter Museum of Nanoscience and Art.

The research team devised an experiment involving 16 violinists with electric violins connected to a computer system. Each of the violinists had sound-canceling headphones, hearing only the sound received from the computer. All violinists played a simple repeating musical phrase and tried to synchronize with other violinists according to what they heard in their headphones.

According to Shniderman, Weymouth and their fellow authors: "Research on network links or coupling has focused predominantly on all-to-do coupling, whereas current social networks and human interactions are often based on complex coupling configurations.

This study of synchronization between violin players in complex networks with full control over network connectivity, coupling strength and delay, revealed that players can tune their playing period and delete connections by ignoring frustrating signals to find a stable solution. These controlled and new degrees of freedom enable new strategies and yield better solutions potentially applicable for other human networking models."

"Society in its complexity is recognizing how human networks affect a broad range of crucial issues, including economic inequality, stock market crashes, political polarization and the spread of disease," says Weymouth. "We believe there are a lot of important, real-world applications to the results of this experiment and ongoing work."

CAMBRIDGE, MA - New research from Harvard's Growth Lab finds a direct link between a country's incoming business travel and the growth of new and existing industries. The findings, published in the journal Nature Human Behaviour, support a Growth Lab hypothesis that moving knowhow, the tacit knowledge accumulated and transferred from brain to brain through a long process of imitation, repetition, and feedback, is critical to economic growth, and business travel plays a key part in that process. The research also raises new concerns about the economic implications of the international travel restrictions imposed to combat COVID-19.

Researchers Michele Coscia and Frank Neffke, working with Growth Lab Director Ricardo Hausmann, used anonymous transaction insights provided by Mastercard to map the flow of global business travel. This research is part of a collaboration between the Mastercard Center for Inclusive Growth and the Growth Lab at the Center for International Development at Harvard Kennedy School to understand the flow and accumulation of business 'knowhow,' a key driver for inclusive economic growth. Through this network, they created a Knowhow Index which ranks countries on incoming and outgoing knowhow. Germany, Canada, the US, UK, and Korea are the top sources of knowhow flows, while Austria, Ireland, Switzerland, Denmark, and Belgium received the most knowhow.

"We've been puzzled by the fact that business travel has been growing faster than world GDP, despite the widespread adoption of alternatives like Skype, FaceTime, email, etc.," said Hausmann, Rafik Hariri Professor of the Practice of International Political Economy at Harvard Kennedy School. "We posited that maybe there is a difference between moving information and moving brains. We obviously never imagined a complete shutdown of business travel, but the paper allows us to delve into the consequences."

The team created an interactive visualization that shows the effects of the disappearance of business travelers originating from a specific country. For example, if German businesspeople stopped traveling, the research estimates that Austria, South Africa, Switzerland, Nigeria, Czechia, and Turkey would be most affected, and global GDP would decrease by 4.8%.

"According to our study, the world is benefiting enormously by mobilizing the knowhow in brains through business travel. A permanent shutdown of this channel would probably imply a double-digit loss in global GDP," said Hausmann.

The research also suggests that business travel represents another development divide. "Obstacles to business travel, such as cumbersome visa regimes and long connections, constrain access to knowhow and limit growth opportunities, especially in developing countries," said Frank Neffke, research director at the Growth Lab.

An international team of scientists, including a researcher from Sechenov University, reviewed scientific articles on proteins (and genes encoding them) that help cancer cells enter the brain. An understanding of the processes that facilitate the formation of metastases in the brain will allow scientists to create new methods for cancer diagnosis and treatment. Details of the study can be found in the journal Trends in Cancer.

Brain tissues are very sensitive to changes in the levels of many substances and to the penetration of microorganisms and immune cells, but they need a large amount of nutrients and oxygen. Satisfying the needs of the brain requires a dense network of thin blood vessels, covered with a special shell that lets in essential substances and blocks all other compounds and cells. This shell, consisting of adjacent endothelial cells tightly connected to each other by special proteins, forms the blood-brain barrier (BBB), which prevents the free exchange of substances between blood vessels and brain tissues.

BBB works very well (letting in less than 2% of the molecules), but it is still not perfect: cancer cells sometimes manage to slip through it and trigger the development of metastases; since many drugs cannot get into the brain, this significantly complicates cancer treatment and worsens the prognosis for patients with metastases. The authors of the article decided to find out which genes give cancer cells such a 'superpower'.

'Metastasis formation is controlled by proteins and genes encoding these proteins. The purpose of this work was to systematise experimentally or clinically proven findings about the proteins and microRNAs that allow migration of tumour cells to the brain. It turned out that their production is typical for a number of metastases, while most of the cell molecules described in literature are unique for a particular type of tumour. Thus, the possibility of regulating genes that stimulate the migration of tumour cells to the brain may be a challenge faced by doctors in reducing the formation of intracerebral metastases in the future,' said Ilya Ulasov, one of the authors, a leading researcher at the Institute of Regenerative Medicine, Sechenov University.

Tumour cells are known to enter the brain both through dense contacts between the cells of the tunicae (layers of the blood vessels) and through these cells themselves. In the first case, cancer cells use enzymes and/or microRNAs to disrupt the structure of the dense contacts and increase the permeability of the BBB.

One of these enzymes is cathepsin C: it destroys the proteins of the dense contacts, and its inhibitors (substances that slow down its action) can suppress the growth of metastases in breast cancer. Two other enzymes - seprase and urokinase-type plasminogen activator - have shown similar effects in melanoma, and some metalloproteinases may be possible targets for anti-cancer therapy. Another protein, placental growth factor, triggers a chain of reactions to facilitate the development of metastases in lung, gastric or colorectal cancer.

MicroRNAs enable communication between cancer cells and their environment, including BBB cells and proteins. For example, miR-105 affects ZO-1 protein, contributing to the formation of metastases in breast cancer, while miR-143-3p can enhance BBB permeability in lung cancer.

The second way - penetration of cancer cells through BBB cells - is possible due to proteins of the cell wall, integrins, and certain groups of enzymes. In several types of cancer, metastasis cells showed an increased content of integrins avβ3 and avβ8. It is possible that they are involved in the formation of metastases in the brain and can serve as a biomarker of the disease. Another integrin, VLA-4, is produced in the metastases of most melanoma patients and promotes the binding of cancer cells and BBB cells, which opens the way to the brain.

In total, the authors reviewed 44 proteins, described the mechanism of their influence on the formation of metastases and listed the genes encoding them. The study will help scientists work out new ways to prevent and treat cancer, stroke and Alzheimer's disease, which also affect BBB integrity.

Researchers at Michigan Tech, TÜV SÜD UK National Engineering Laboratory and University of Edinburgh call for increased research on virus surface stability and interaction in "Surface Chemistry Can Unlock Drivers of Surface Stability of SARS-CoV-2 in Variety of Environmental Conditions" in the Cell Press journal Chem. They highlight the need to understand the different environmental conditions that affect the surface chemistry of viruses like SARS-CoV-2, the virus that causes the disease COVID-19.

Creating an Unfriendly Surface for Viruses

We're told to wash our hands with soap for 20 seconds to kill viruses. Why? Because the soap interacts with the surface chemistry of a virus, particularly the lipid, or fatty, casing around it, and essentially makes the virus explode.

Handwashing is a clear example of why understanding how viruses interact with surface environments is important. Increased research will better equip us to diminish how long viruses survive on surfaces or in the air, an important way to stop the spread.

"If the surface is not friendly, it's easier for the virus to fall apart. Where the virus has more friendly interactions with the surface, it's more likely to stay infectious," said Caryn Heldt, professor of chemical engineering and director of the Health Research Institute at Michigan Technological University.

"Viruses have unique ways of interacting with surfaces. The surface chemistry of the virus will change how the virus interacts with water," Heldt said. "If water such as humidity, which is common in your breath and in the air, gets between the virus and a surface, it can really change the way the virus interacts with that surface. The virus surface and the environment: you can't separate them out."

More Than One Way to Skin a Cat... Or a Virus

Part of the reason the scientific community's understanding of the SARS-CoV-2 virus continues to evolve is because there are only a few techniques available to measure the small amounts of virus particles required to infect a person as compared to other types of biomolecules, such as proteins.

"We need to understand how viruses interact with surfaces with and without water present, but the traditional ways we think of studying surface chemistry cannot detect these low levels of virus," Heldt said.

Heldt and coauthors said their article provides a broad overview of different ways researchers could learn more about these surface interactions on a chemical level.

Unlike the viruses that cause influenza, SARS-CoV-2 is mainly transmitted through aerosols, or particles that travel through and stay suspended in the air when people talk, sing, cough or sneeze.

The flu is transmitted by large droplets you breathe out, which fall to and stay infectious on surfaces. Heldt said surfaces have not been ruled out as a mode of transmission, but that the most common form of transition seems to be aerosol inhalation. "It's about how close you are to someone and for how long," she said.

Temperature and humidity in particular seem to have greater effects on the SARS-CoV-2 virus' virility.

"For the first time, we highlight potential mechanisms of the novel SARS-CoV-2 surface stability in various environmental conditions including temperature and relative humidity," said Aliakbar Hassanpouryouzband, a postdoctoral research associate at the University of Edinburgh.

While viruses are typically more stable when it's colder, which explains why flu season hits during the winter, that doesn't seem to be the case for the virus that causes COVID-19. However, researchers can infer from what heat does to molecules -- it increases their energy, causing them to move and vibrate more quickly -- that increased vibrations of virus molecules causes them to explode and no longer be infectious.

When it comes to humidity, viruses need to bind some water to their surfaces. But dehydrating a virus molecule isn't a cut-and-dried solution -- it can actually make some molecules more stable.

Along with further research into the effects of humidity, temperature and other environmental conditions, there's a need to explore the effects of pH balance and protein casings on the virus. The work to better understand the surface chemistry of SARS-CoV-2 will help scientists around the world design vaccines for this pandemic and those of the future.

"We hope that this article will assist experimental scientists worldwide in their investigations for unravelling the molecular drivers implicated in this new coronavirus transmission from the surfaces as well as in vaccine development and antiviral drug design," said Edris Joonaki, fluid properties expert at TÜV SÜD UK National Engineering Laboratory.

WASHINGTON, August 11, 2020 -- As we use resources, such as coal, oil, natural gas, copper, silicon and aluminum, to power massive computer farms and process digital information, our technological progress is redistributing Earth's matter from physical atoms to digital information -- the fifth state of matter, alongside liquid, solid, gas and plasma.

Eventually, we will reach a point of full saturation, a period in our evolution in which digital bits will outnumber atoms on Earth, a world "mostly computer simulated and dominated by digital bits and computer code," according to an article published in AIP Advances, by AIP Publishing.

It is just a matter of time.

"We are literally changing the planet bit by bit, and it is an invisible crisis," author Melvin Vopson said.

Vopson examines the factors driving this digital evolution. He said the impending limit on the number of bits, the energy to produce them, and the distribution of physical and digital mass will overwhelm the planet soon.

For example, using current data storage densities, the number of bits produced per year and the size of a bit compared to the size of an atom, at a rate of 50% annual growth, the number of bits would equal the number of atoms on Earth in approximately 150 years.

It would be approximately 130 years until the power needed to sustain digital information creation would equal all the power currently produced on planet Earth, and by 2245, half of Earth's mass would be converted to digital information mass.

"The growth of digital information seems truly unstoppable," Vopson said. "According to IBM and other big data research sources, 90% of the world's data today has been created in the last 10 years alone. In some ways, the current COVID-19 pandemic has accelerated this process as more digital content is used and produced than ever before."

Vopson draws on the mass-energy equivalence in Einstein's theory of general relativity; the work of Rolf Landauer, who applied the laws of thermodynamics to information; and the work of Claude Shannon, the inventor of the digital bit.

In 2019, Vopson formulated a principle that postulates that information moves between states of mass and energy just like other matter.

"The mass-energy-information equivalence principle builds on these concepts and opens up a huge range of new physics, especially in cosmology," he said. "When one brings information content into existing physical theories, it is almost like an extra dimension to everything in physics."

It's commonly known that gun sales go up after a mass shooting, but two competing hypotheses have been put forth to explain why that's the case: is it because people fear more violence and want to protect themselves, or is it because mass shootings trigger discussions about tighter gun regulations, which sends people out to stock up? In a new study appearing August 11 in the journal Patterns, investigators used data science to study this phenomenon. By working with spatio-temporal data from all the states in the US, they determined that the increase in firearm purchases after mass shootings is driven by a concern about regulations rather than a perceived need for protection.

"It's been well documented that mass shootings are linked to increases in firearm purchases, but the motivation behind this connection has been understudied," says first author Maurizio Porfiri, Institute Professor at the New York University Tandon School of Engineering, who is currently on research sabbatical at the Technical University of Cartagena in Spain. "Previous research on this topic has been done mostly from the perspective of social science. We instead used a data-science approach."

Porfiri and his colleagues employed a statistical method called transfer entropy analysis, which is used to study large, complex systems like financial markets and climate-change models. With this approach, two variables are defined, and then computational techniques are used to determine if the future of one of them can be predicted by the past of the other. "This is a step above studying correlation," Porfiri explains. "It's actually looking at causation. Unique to this study is the analysis of spatio-temporal data, by examining the behavior of all the US states"

The data that were put into consideration came from several sources: FBI background checks, which enabled the approximation of monthly gun sales by state; a Washington Post database on mass shootings; and news coverage about mass shooting from five major newspapers around the country. The news stories were put in two categories: those that mentioned gun regulations and those that didn't. In all, the study used data related to 87 mass shootings that occurred in the United States between 1999 and 2017.

The researchers also rated individual states by how restrictive their gun laws are. "We expected to find that gun sales increased in states that have more permissive gun laws, but it was less expected in states with restrictive laws. We saw it in both," Porfiri says. "Also, when we looked at particular geographic areas, we didn't find any evidence that gun sales increased when mass shootings happened nearby."

He adds that one limitation of the data is that news coverage may not fully capture public sentiment at a given time. In addition, although the study was successful in determining causal links among states, more work is needed to study the nature of these relationships, especially when one has laws that are much more restrictive than another

Porfiri usually uses computational systems to study topics related to engineering, including ionic polymer metal composites and underwater robots. His reason for studying mass shootings is personal: he received his PhD in 2006 from Virginia Tech, which, the following year, was the site where--at that time--the deadliest mass shooting in the country took place. One member of his PhD committee was killed in the shooting, and he knew many others who were deeply affected.

For him, this project is part of a larger effort to study gun violence. "Mass shootings are a small part of death from guns," Porfiri says. "Suicide and homicide are much more common. But mass shootings are an important catalyst for a larger discussion. I plan to look at the wider role of guns in the future."