Culture

Researchers at the Institut national de la recherche scientifique (INRS), in collaboration with American scientists, have uncovered a new parvovirus strategy for reaching the cell nucleus which is their site of replication.

This new method of entry is a good example of host-driven evolution. Their results were published in the journal Proceedings of the National Academy of Sciences of the United States of America. The parvoviruses are extremely contagious and persistent in the environment. They are transmitted mainly through the feces of a contaminated animal. They can infect invertebrates, vertebrates, mammals and humans. To reach the nucleus of host cells, parvoviruses use mostly enzymatic reactions. They are first absorbed by the cell inside a vesicle, a membrane compartment. To escape, parvoviruses activate a viral enzyme domain called phospholipase A2 (PLA2), a key mechanism discovered in 2001 by the same INRS laboratory.

However, some types of parvoviruses, as well as other nonenveloped viruses, do not have this enzyme domain and must therefore escape from the vesicle by some other means. Using molecular biology and structural studies, INRS researchers have discovered that a new virus targeting the giant tiger shrimp uses a more mechanical response. This type of parvovirus contains an inner pentamer helix bundle held together by calcium ions. When the microorganism is in the vesicle, where the calcium concentration is decreased by the elimination of toxic substances, the bundle is released and opens-up the protein shell (capsid) enclosing its genetic material and the membrane, allowing viral DNA to escape into the nucleus for replication.

“It turns out the incorporation of a PLA2 enzymatic domain is only one strategy, even as far as the family of parvoviruses is concerned. Here, we show yet a new strategy that may not be limited to one parvovirus lineage, but to other economically very important parvoviruses, such as parvoviruses of domestic fowl and farmed mink,” says Judit Pénzes, a former postdoctoral fellow at INRS and first author of the paper published on August 18, 2020.

A Host-Driven Evolution

INRS Professor Emeritus Peter Tijssen, lead author of the publication, raises another interesting point: the host-driven convergent evolution of this method of entry into the cell. “Two parvoviruses with different DNA sequences, which both targeting shrimps, have adopted similar strategies for reaching the nucleus,” he says.

Using a microscope nearly two floors high, the FEI Titan Krios, Judit Pénzes was able to solve the complete structure of the virus on a near-atomic scale. “You could already feel the energy rumbling through the enormous machine upon entering the facility. I think that it’s probably the same to what scientists involved in space exploration must have felt when they saw a rocket ready to lift off for the first time,” says the postdoctoral student.

Eventually, the discovery of this mechanism could lead to a better understanding of how viruses enter cells and even to a cure. “If we know how the parvovirus manages to release its DNA into the nucleus of the host cell, we can try to find a molecule to block this action,” concludes Professor Tijssen. The collaboration with the Florida-based research team will allow them to deepen the knowledge on this subject and possibly find other methods of entry that are yet unknown.

Researchers have shaken up a once accepted timeline for cataclysmic events in the early solar system. About 4.5 Ga (giga-anum, or billion years ago), as a large disc of dust and ice collapsed around our newly formed star, planets and smaller celestial bodies were formed. What followed was a chaotic and violent period of collisions and impacts as the familiar eight planets carved out their orbits to resemble the balanced system we observe today. Geological and geochemical records indicate that after about 600-700 million years after formation - but still early in the solar system's existence - the Earth-Moon system experienced a period of frequent and cataclysmic impacts from asteroids and other bodies. This period is dubbed the late heavy bombardment (LHB) period.

It was once thought that this period had a relatively sudden onset, but a research team at Hiroshima University and The University of Tokyo in Japan have found evidence that this bombardment period may have started much earlier, and decreased in intensity over time.

The team published their findings on August 26 in Earth and Planetary Science Letters.

"According to Apollo's lunar rock studies from the 1970s, the Earth, Moon, and the entire inner solar system are thought to have suffered from numerous meteoritical impacts at around 3.9 Ga. This event is regarded as a key process during the early evolution of our planet, said Mizuho Koike, an author of the study and an assistant professor from The Graduate School of Advanced Science and Engineering at Hiroshima University. "However, the validity of the LHB idea is being questioned recently. To settle this debate, a solid database of the 'impact ages' is required."

The team started building this database using rocks found on Earth that originated from a large, ancient asteroid, called Vesta, to see if they could corroborate the timeframe of the LHB period. If the solar system indeed experienced the LHB period roughly 3.9 Ga, Vesta, like Moon, would likely hold similar evidence of such an event around the same time period. What the team found was a record of impacts 300 to 500 million years earlier than expected.

"We found that the rocks from Vesta recorded the multiple impacts that occurred between 4.4 to 4.15 Ga, clearly earlier than the predicted peak of LHB at ~3.9 Ga. In contrast, no impact evidence was identified at 3.9 Ga or later. These findings suggest that Vesta (and probably other asteroids as well) did not record the LHB. Instead, they experienced massive impacts at the earlier stage," said Koike.

It is still unclear what this means for the LHB period as a whole, but Koike and her colleagues plan to further investigate the chronology of the early solar system.

"Our study reveals that the previously expected impact model was not correct, at least on Vesta," Koike said. "Extrapolating this to the wider solar system, the concept of LHB may not be appropriate to the planets' evolutions, including to the Earth and Moon. To verify such an examination, we are planning to investigate the impact histories on other asteroids and planetary materials by applying our present analytical techniques."

By doing so, the team may be able to add to their database and, ideally, peer with more clarity into our solar systems distant past.

Wolves today live and hunt in packs, which helps them take down large prey. But when did this group behavior evolve? An international research team has reported specimens of an ancestral wolf, Canis chihliensis, from the Ice Age of north China (~1.3 million years ago), with debilitating injuries to the jaws and leg. The wolf survived these injuries long enough to heal, supporting the likelihood of food-sharing and family care in this early canine.

"Top predators are rare in the fossil record because of their position in the food pyramid. Devastating injuries that are healed are even rarer. Fossils preserving grotesque injuries from the distant past have long fascinated paleontologists, and they tell stories rarely told," noted Dr. Xiaoming Wang, curator of vertebrate paleontology at the Natural History Museum of Los Angeles County, who co-led the study.

Dr. Haowen Tong, professor at the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences in Beijing, led the excavations that discovered the fossils in the Nihewan Basin, a well-known Ice Age site in northern China.

Based on its skeleton, C. chihliensis was a large canine with strongly built jaws and teeth specialized for eating meat and cracking bone. Injuries in the skeleton provide additional evidence for how the animal used to move and behave. The study represents the first known record of dental infection in C. chihliensis, likely incurred while crushing bone to reach the marrow inside, which modern wolves do when hunting prey larger than themselves.

One C. chihliensis also badly fractured its shin (tibia), splintering it into three parts. The injury must have incapacitated the wolf, an active predator that hunted by chasing prey--yet it survived, as evidenced by healing of the bone. Survival suggests that, while recovering, it procured food in some way other than by hunting--likely with the support of a pack.

To help interpret the injuries, the study also examined specimens of another extinct large canine: the dire wolf, Canis dirus, which has abundant fossils at the world-famous Rancho La Brea asphalt seeps in Los Angeles, California. The dire wolf was geologically younger than C. chihliensis, having lived at Rancho La Brea approximately 55,000 to 11,000 years ago. Despite the age difference, the dire wolf--which previous studies had established to have been a pursuit predator of large prey, with a social structure likely similar to grey wolves today--sustained injuries to the teeth, jaws, and legs similar to C. chihliensis.

"It is incredible to see these dental infections and fractured tibia from this early Chinese wolf--and find similar injuries in our dire wolves at Rancho La Brea," said Dr. Mairin Balisi, National Science Foundation postdoctoral research fellow at the La Brea Tar Pits and Museum, and co-author of the study. "Museum collections are valuable for many reasons. In this case, they've enabled us to observe shared behavior across species, across continents, across time."

The cell membrane, the wall-like boundary between the cell interior and its outside environment, is primarily made up of two kinds of biomolecules: lipids and proteins. Different lipid species closely pack together to form a double layer, or "bilayer," the membrane's fundamental structure, while proteins are embedded within or attached to the bilayer.

Membrane proteins are responsible for various important cellular activities, and their dysfunction can lead to serious health issues. Studying membrane protein structures and how they behave will help scientists better understand their connection to diseases and aid in developing therapeutics.

A team of researchers led by Vanderbilt University has recently shed light on how membrane proteins could be influenced by the lipids around them. By developing a novel type of membrane model, the scientists were able to show that the shape and behavior of a protein can be altered by exposure to different lipid compositions.

The researchers confirmed the artificial membrane's structure using x-ray and neutron scattering at the Department of Energy's (DOE's) Brookhaven (BNL) and Oak Ridge National Laboratories (ORNL). Their findings were published in the Journal of the American Chemical Society.

"This work showed that a protein can change quite profoundly in different membrane lipid environments, and we think this opens up a whole new area of research," said Charles Sanders, professor of biochemistry at Vanderbilt University and corresponding author of the new study.

Lipid layouts and cell membrane models

Cell membranes are composed of a variety of lipid molecules. Recently, studies have shown that certain lipids in cell membranes can come together to form clusters, also known as rafts. Some scientists suggest that rafts may move throughout the membrane and co-exist with ungrouped molecules. "A lipid raft is like a clique at a party," said Sanders. "They may move around the party, but it's always the same people talking to each other."

His lab is exploring how rafts might impact membrane proteins and cellular activities associated with them. In the new work, Sanders and a team of researchers have created a synthetic membrane capable of incorporating abundant quantities of two lipid molecules thought to make up rafts in cell membranes: cholesterol and sphingomyelin. Their approach involved developing disc-shaped biological structures, known as bicelles, that can produce a simplified model of a cell membrane's lipid bilayer.

"Cholesterol and sphingomyelin are ubiquitous in cell membranes but have not been present together in previous versions of bicelles," said John Katsaras, a biophysicist and neutron scattering scientist at ORNL and study co-author. "This new class of bicelles has a lipid composition that we believe is more biologically relevant."

Complementary techniques give comprehensive analysis

After developing the bicelles, the researchers used small-angle neutron and x-ray scattering techniques to precisely determine the material's shape and structural organization.

"It's really hard to confirm the actual morphology of bicelles. Small-angle neutron and small-angle x-ray scattering are the only ways to get a good overall characterization of these particles," said James Hutchison, a Vanderbilt University researcher and study co-author.

The team used a joint-access program for small-angle neutron and x-ray scattering that allows researchers to more conveniently request beam time at the Bio-SANS instrument at ORNL's High Flux Isotope Reactor (HFIR) and the Bio-SAXS instrument (LiX) at BNL's National Synchrotron Light Source II (NSLS-II).

Neutrons can detect light elements like hydrogen, whereas x-rays are more sensitive to heavier elements, which means each scattering technique can reveal unique information about the same material. By using both methods, the researchers built a more accurate model of the membrane system.

"Neutron and x-ray scattering are very complementary to each other," said Shuo Qian, a neutron scattering scientist at ORNL and study co-author. "Together, those techniques were able to provide a full picture of the bicelle structure."

Complementary bicelle measurements were also performed using transmission cryo-electron microscopy at Vanderbilt University.

Uncovering new protein properties

To assess how the new model membrane could be used to understand lipid composition and membrane protein relationships, the scientists introduced their bicelles to a well-studied protein fragment, referred to as C99. This fragment makes up one region of a membrane protein called amyloid precursor protein, which experts believe is connected to Alzheimer's disease.

Using various characterization methods, the team pinpointed differences in the protein fragment's structure and dynamics when embedded in the new membrane model. Notably, they observed the C99 fragments self-associate with one another in regions that had not previously been reported in other model membranes. The researchers hypothesize these newly uncovered binding sites could play a role in regulating other protein interactions with this fragment.

The team aims to run additional experiments to confirm whether the new bicelle system possesses a lipid raft environment. Scientists have already identified lipid raft properties in artificial vesicles, a spherical hollow biological structure that is enveloped by a lipid bilayer, but not in other small particles, such as bicelles

"There is no known non-vesicle small particle that has lipid raft-like properties," said Hutchison. "It would be a slam dunk to prove it."

At the south pole of Jupiter lurks a striking sight--even for a gas giant planet covered in colorful bands that sports a red spot larger than the earth. Down near the south pole of the planet, mostly hidden from the prying eyes of humans, is a collection of swirling storms arranged in an unusually geometric pattern.

Since they were first spotted by NASA's Juno space probe in 2019, the storms have presented something of a mystery to scientists. The storms are analogous to hurricanes on Earth. However, on our planet, hurricanes do not gather themselves at the poles and twirl around each other in the shape of a pentagon or hexagon, as do Jupiter's curious storms.

Now, a research team working in the lab of Andy Ingersoll, Caltech professor of planetary science, has discovered why Jupiter's storms behave so strangely. They did so using math derived from a proof written by Lord Kelvin, a British mathematical physicist and engineer, nearly 150 years ago.

Ingersoll, who was a member of the Juno team, says Jupiter's storms are remarkably similar to the ones that lash the East Coast of the United States every summer and fall, just on a much larger scale.

"If you went below the cloud tops, you would probably find liquid water rain drops, hail, and snow," he says. "The winds would be hurricane-force winds. Hurricanes on Earth are a good analog of the individual vortices within these arrangements we see on Jupiter, but there is nothing so stunningly beautiful here."

As on Earth, Jupiter's storms tend to form closer to the equator and then drift toward the poles. However, Earth's hurricanes and typhoons dissipate before they venture too far from the equator. Jupiter's just keep going until they reach the poles.

"The difference is that on the earth hurricanes run out of warm water and they run into continents," Ingersoll says. Jupiter has no land, "so there's much less friction because there's nothing to rub against. There's just more gas under the clouds. Jupiter also has heat left over from its formation that is comparable to the heat it gets from the sun, so the temperature difference between its equator and its poles is not as great as it is on Earth."

However, Ingersoll says, this explanation still does not account for the behavior of the storms once they reach Jupiter's south pole, which is unusual even compared to other gas giants. Saturn, which is also a gas giant, has one enormous storm at each of its poles, rather than a geometrically arranged collection of storms.

The answer to the mystery of why Jupiter has these geometric formations and other planets do not, Ingersoll and his colleagues discovered, could be found in the past, specifically in work conducted in 1878 by Alfred Mayer, an American physicist and Lord Kelvin. Mayer had placed floating circular magnets in a pool of water and observed that they would spontaneously arrange themselves into geometric configurations, similar to those seen on Jupiter, with shapes that depended on the number of magnets. Kelvin used Mayer's observations to develop a mathematical model to explain the magnets' behavior.

"Back in the 19th century, people were thinking about how spinning pieces of fluid would arrange themselves into polygons," Ingersoll says. "Although there were lots of laboratory studies of these fluid polygons, no one had thought of applying that to a planetary surface."

To do so, the research team used a set of equations known as the shallow-water equations to build a computer model of what might be happening on Jupiter, and began to run simulations.

"We wanted to explore the combination of parameters that makes these cyclones stable," says Cheng Li (Phd '17), lead author and 51 Pegasi b postdoctoral fellow at UC Berkeley. "There are established theories that predict that cyclones tend to merge at the pole due to the rotation of the planet and so we found in the initial trial runs."

Eventually, however, the team found that a Jupiter-like stable geometric arrangement of storms would form if the storms were each surrounded by a ring of winds that turned in the opposite direction from the spinning storms, or a so-called anticyclonic ring. The presence of anticyclonic rings causes the storms to repel each other, rather than merge.

Ingersoll says the research could help scientists better understand how weather on Earth behaves.

"Other planets provide a much wider range of behaviors than what you see on Earth," he says, "so you study the weather on other planets in order to stress-test your theories."

Paradox-free time travel is theoretically possible, according to the mathematical modelling of a prodigious University of Queensland undergraduate student.

Fourth-year Bachelor of Advanced Science (Honours) student Germain Tobar has been investigating the possibility of time travel, under the supervision of UQ physicist Dr Fabio Costa.

"Classical dynamics says if you know the state of a system at a particular time, this can tell us the entire history of the system," Mr Tobar said.

"This has a wide range of applications, from allowing us to send rockets to other planets and modelling how fluids flow.

"For example, if I know the current position and velocity of an object falling under the force of gravity, I can calculate where it will be at any time.

"However, Einstein's theory of general relativity predicts the existence of time loops or time travel - where an event can be both in the past and future of itself - theoretically turning the study of dynamics on its head."

Mr Tobar said a unified theory that could reconcile both traditional dynamics and Einstein's Theory of Relativity was the holy grail of physics.

"But the current science says both theories cannot both be true," he said.

"As physicists, we want to understand the Universe's most basic, underlying laws and for years I've puzzled on how the science of dynamics can square with Einstein's predictions.

"I wondered: "is time travel mathematically possible?"

Mr Tobar and Dr Costa say they have found a way to "square the numbers" and Dr Costa said the calculations could have fascinating consequences for science.

"The maths checks out - and the results are the stuff of science fiction," Dr Costa said.

"Say you travelled in time, in an attempt to stop COVID-19's patient zero from being exposed to the virus.

"However if you stopped that individual from becoming infected - that would eliminate the motivation for you to go back and stop the pandemic in the first place.

"This is a paradox - an inconsistency that often leads people to think that time travel cannot occur in our universe.

"Some physicists say it is possible, but logically it's hard to accept because that would affect our freedom to make any arbitrary action.

"It would mean you can time travel, but you cannot do anything that would cause a paradox to occur."

However the researchers say their work shows that neither of these conditions have to be the case, and it is possible for events to adjust themselves to be logically consistent with any action that the time traveller makes.

"In the coronavirus patient zero example, you might try and stop patient zero from becoming infected, but in doing so you would catch the virus and become patient zero, or someone else would," Mr Tobar said.

"No matter what you did, the salient events would just recalibrate around you.

"This would mean that - no matter your actions - the pandemic would occur, giving your younger self the motivation to go back and stop it.

"Try as you might to create a paradox, the events will always adjust themselves, to avoid any inconsistency.

"The range of mathematical processes we discovered show that time travel with free will is logically possible in our universe without any paradox."

New research presented at this year's annual meeting of the European Association for the Study of Diabetes (EASD), held online this year, shows the importance of good cardiovascular health in preventing type 2 diabetes (T2D) among middle-aged individuals, regardless of any genetic predisposition they may have towards developing the disease. The study was conducted by Kan Wang, Dr. Fariba Ahmadizar, and colleagues at the Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, the Netherlands.

Data on the association between different CVH categories and lifetime risk of T2D are scarce. Besides, it remains unclear whether being genetically predisposed to T2D has a modifying effect on how CVH affects a person's odds of developing diabetes during their life.

The team used data from the prospective population-based Rotterdam Study to produce a CVH 'score' for each participant with 0 having the worst health status, and 12 having the best. Scores were calculated from measurements taken of body mass index, blood pressure, total cholesterol, smoking status, diet, and physical activity at the start of the study. Individuals were then placed into one of three categories according to their CVH score: poor (CVH score 0-5), intermediate (CVH score 6-7), and ideal (CVH score 8-12).

Genetic predisposition to T2D was quantified in the form of a Genetic Risk Score (GRS) derived from the 403 common genetic variants identified so far as being involved in determining susceptibility to T2D. The sample population was then divided into three equal-sized groups (tertiles) according to each participant's GRS, resulting in them being classed as low, medium, or high genetic risk. Incidence of T2D among the study population during the 17.8 years follow-up period was used by the researchers to estimate the remaining lifetime risk of developing T2D at 55, 65, and 75 years of age for each CVH category. Further analysis was undertaken to estimate lifetime T2D risk for each CVH category based on GRS status.

The sample population contained 5993 people free of T2D at baseline (average age 69.1 years, and 58% female). There were 2020 (33.7%) as ideal CVH, 2605 (43.5%) as intermediate CVH, and 1368 (22.8%) as poor CVH. A total of 869 participants went on to develop T2D in the 17.8 years follow-up period of the study.

The authors found that at age 55, the remaining lifetime risk of T2D was 22.6% for individuals classed as having ideal CVH, 28.3% for intermediate CVH, and 32.6% for poor CVH.

For individuals in each of the three GRS tertiles, the researchers then calculated the remaining lifetime risk of T2D at age 55 based on their CVH category. Those with the highest genetic risk had a likelihood of developing T2D of 23.5% if their CVH was ideal, 33.7% if they had intermediate CVH, and 38.7% when CVH was classed as poor.
The team found: "At age 55 years, more favourable CVH was associated with a lower lifetime risk for type 2 diabetes and was not counterbalanced by the genetic susceptibility for T2D."

They conclude: "Our results highlight the importance of favourable cardiovascular health in preventing T2D among middle-aged individuals regardless of their genetic predisposition."

The following papers will be presented at a Lancet journals' session at ECCVID 2020, organised by European Society of Clinical Microbiology and Infectious Diseases. The conference will take place online on Wednesday 23rd to Friday 25th September 2020, the society's first online conference focussing exclusively on COVID-19.

Contact details for corresponding authors are provided should you wish to arrange an interview the authors. Funding information is listed on the first page of each Article.

Timely preventive measures against COVID-19 such as providing hotel room accommodation for homeless people in the UK are estimated to have prevented hundreds of deaths in this vulnerable population, according to research presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, held online 23-25 September) and published in The Lancet Respiratory Medicine ahead of a special conference session featuring The Lancet journals.

On March 26, 2020, the UK Government instructed local authorities to provide accommodation for people sleeping rough during the pandemic. Dormitory-style night shelters were subsequently closed, and special accommodation referred to as COVID-PROTECT was established, focusing on people sleeping in these facilities and those sleeping rough. This system was in fact designed, very rapidly, by some of the co-authors of this study.

"COVID-PROTECT accommodation has mainly been in commercial hotels that have been left otherwise vacant during the pandemic. Most people who were living in homeless hostels before the pandemic have stayed in their existing location, with increased infection control," explain the authors, who include Dan Lewer of the University College London (UCL) Collaborative Centre for Inclusion Health, London, UK, and colleagues.

In this study - the first study to model SARS-CoV-2 transmission in a homeless population - the researchers used computer modelling capable of assessing multiple possible scenarios to come to their estimates. It explored the effect of the pandemic on 46565 individuals experiencing homelessness: some 35817 living in 1065 hostels for homeless people, 3616 sleeping in 143 night shelters, and 7132 sleeping outside.

They ran the model under scenarios looking at the effect of a 'second wave' and prevention measures that protect homeless people: specialist hotel accommodation, infection control in homeless settings, and reduced mixing with the general population.

The authors used data from charities that support homeless people and information provided by hostels to estimate that 4% of the homeless population had acquired SARS-CoV-2 by May 31, 2020, based on surveillance data from hostels and also further data provided by the St Mungo's homeless charity, UK. The model estimated that 24 deaths actually occurred among homeless people in the first wave in England. However, it also estimated that the preventative measures imposed might have avoided over 21,000 infections, 266 deaths, 1164 hospital admissions and 338 ICU admissions among the homeless population.

If preventative measures are continued as they were during the first wave, the authors project a relatively small number of additional cases between June 1, 2020, and Jan 31, 2021, with over 1,700 new infections, 31 deaths, 122 hospital admissions, and 35 ICU admissions with a second wave in the general population.

However, if preventative measures are lifted, outbreaks in homeless settings might lead to larger numbers of infections and deaths, even with low incidence in the general population. In a scenario with no second wave and relaxed measures in homeless settings in England (effectively a return to the system homeless people experienced pre-pandemic), the model projects more than 12,000 new infections, 184 deaths, 733 hospital admissions, and 213 ICU admissions between June 1, 2020, and Jan 31, 2021.

The researchers did not model what they called the true nightmare scenario - a second wave and less preventive measures, because further surges of COVID-19 (as are currently happening in the UK) will lead to more intensive preventive measures in the general population.

The authors say: "During the first wave of COVID-19 in England, our modelling suggests that people experiencing homelessness were protected by interventions in the general population, infection control in hostels, and closing of dormitory-style accommodation."

They add: "In England, homeless people living in hostels or in COVID-PROTECT have been offered testing when symptomatic, and occasionally mass screening exercises have been undertaken. We are not aware of any outbreaks in these settings to date. The results of our model suggest that closing of dormitory-style accommodation and increased infection control in single-room accommodation might have contributed to the absence of outbreaks."

They conclude*: "The two main implications for practice are that night shelters should not be re-opened while there is sustained transmission of SARS-CoV-2 in the community, and that heightened infection control measures in hostels should be continued even when incidence of COVID-19 is low in the general population. While there is uncertainty in the impact of COVID-19 on people experiencing homelessness, there is clear potential for outbreaks in hostels and night shelters. A large number of deaths can be avoided by maintaining the additional support that has so far been provided in England. Relaxing these measures would be risky."

Co-author Dr Alistair Story, also of the University College London (UCL) Collaborative Centre for Inclusion Health, London, UK, adds**: "COVID-19 cases are surging again. Our work demonstrates that safe single room accommodation for homeless people is life-saving and must be scaled and sustained to meet need. As the winter months approach, homeless people cannot face a choice between freezing to death or risking infection in crowded emergency night shelters. This is not an acceptable choice in a civilised society."

DALLAS (September 23, 2020) - Researchers at Center for BrainHealth®, part of The University of Texas at Dallas, recently examined how cells in the brains of people at risk for developing Alzheimer's disease make and use energy. Relationships between the brain's energy metabolism and the risk of Alzheimer's disease have been reported previously. But this is the first study to clearly distinguish different energy molecules in the brain using high-powered imaging called magnetic resonance spectroscopy (MRS) at 7-Tesla. The findings from this study could help the development of tests for the earlier detection and treatment of Alzheimer's disease.

The study was published in Frontiers in Aging Neuroscience (August 2020) by Center for BrainHealth researchers Sandra Bond Chapman, PhD, chief director; Namrata Das, MD, MPH, a research neuroscientist in Alzheimer's Disease and the study's lead author; Jeffrey Spence, PhD, director of biostatistics; Audette Rackley, head of special programs; and Jimin Ren, PhD, a researcher at UT-Southwestern Medical Center.

This imaging technique allows scientists to look at how the human brain makes and uses energy at the cellular level. Other techniques are invasive, which is why until now most research on the brain's energy metabolism has been conducted in deceased patients or in model organisms like mice.

"The biggest finding is that the peaks from the MRS scan could be separated to look at the brain's energy. It's almost like seeing a heartbeat for the first time," said Chapman.

The findings add a methodology for studying the early pathological biomarkers for Alzheimer's disease in patients with amnestic mild cognitive impairment, a condition that sometimes leads to the development of the disease. Participants with higher brain energy metabolisms in their parieto-occipital lobes had poorer memory and attention skills.

Energy use and production are the core of all cells' biological mechanism, especially in the brain due to its high energy requirements. The brain's extraordinary energy requirements may lead to the dangerous buildup of beta-amyloid and tau proteins seen in patients with Alzheimer's disease.

"We want to look at how the brain energy metabolism differs between healthy participants, participants with amnestic mild cognitive impairment, and those with Alzheimer's disease," said Dr. Das. "Later on, we want to understand if energy abnormalities upstream trigger or aggravate the amyloid, tau, and glucose metabolism abnormalities in the brain." The earlier that Alzheimer's disease is detected and treated, the better the patients' outcomes.

Two nationwide COVID-19 antibody seroprevalence studies from Brazil show that many cities along the Amazon were hit hardest at the beginning of the epidemic in May and June, along with poorer and Indigenous communities. The research is presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, held online 23-25 September) and published in The Lancet Global Health, as part of a special conference session featuring The Lancet journals.

"Brazil has become a global hotspot for the COVID-19 pandemic in terms of reported cases and deaths," explains lead author Professor Cesar Victora, Federal University of Pelotas, Pelotas, Brazil. "Existing seroprevalence studies in Brazil have focused on the more developed parts of the country, represented by the southern and southeastern regions. So it is vital that we have more accurate data on the national situation."

The researchers did two household surveys in the most populous cities in all 133 so called 'mesoregions' - regional hubs used by the Brazilian Institute of Geography and Statistics to report on demographic and socioeconomic data across Brazil, covering 26 states and the Federal District. The studies included more than 25000 participants in the period May 14-21 and over 32000 in June 4-7. At each location, the researchers randomly selected households and randomly selected one individual from all household members to test for COVID-19 antibodies.

Participants also answered short questionnaires on sociodemographic information (sex, age, education, ethnicity, household size, and household assets) and compliance with physical distancing measures.

For the 83 (62%) of cities with sample sizes of more than 200 participants in both surveys, the pooled seroprevalence increased by more than 50%, from 1·9% to 3·1%, from the first survey to the second survey. City-level prevalence ranged from 0% to 25·4% in both surveys. 11 (69%) of 16 cities with a prevalence above 2.0% in the first survey were located along a 2000 km stretch of the Amazon river in the northern region, including well-known cities such as Belem, Manaus and Macapa, which are all state capitals located along the Amazon.

In the second survey, the authors found 34 cities with prevalence above 2.0%, which included the same 11 Amazon cities plus 14 from the northeast region, where prevalence was increasing rapidly. Prevalence levels were lower in the south and centre-west, and intermediate in the southeast, where the highest level was found in Rio de Janeiro (7·5%).

In the second survey, prevalence was similar in men and women, but an increased prevalence was observed in participants aged 20-59 years compared to younger or older persons, and in those living in crowded conditions (4·4% for those living with households with six or more people). Prevalence generally increased the more individuals there were per household.

Prevalence among Indigenous people, at 6.4%, was more than four times higher than that found among White people (1.4%). The poorest 20% of the population had a seroprevalence of 3.7%, more than double the 1·7% found in the wealthiest 20%.

The authors say: "Our most remarkable finding was the cluster of high prevalence in 11 cities along the Amazon River, with levels that were among the highest ever reported in population-based studies. This finding of high prevalence in a tropical region contradicts common wisdom that continents such as Africa might be protected against COVID-19 because of high ambient temperature."

The authors believe the high rates of seroprevalence in Indigenous Brazilians are due to a cluster of factors, geographical region, household size (usually overcrowded living conditions), and poverty. Mortality rates for most medical conditions are higher in Indigenous Brazilians, and this population was largely left behind during Brazil's rapid economic and health advances that began in the 1990s.

Overall, the authors say: "Our results must be interpreted in terms of the controversial management of the pandemic by the national government. Testing was restricted to individuals with severe symptoms during the early stages of the pandemic and contact tracing was virtually non-existent. Two consecutive health ministers were either dismissed or resigned in less than 1 month because of their opposition to the president's stance regarding physical distancing and the use of hydroxychloroquine to treat COVID-19, and since May 15, the country has not had a health minister... The controversial handling of the epidemic by the federal government is likely to have contributed to the rapid spread of COVID-19 in the country's most susceptible populations."

While initially many state governors were supportive of social distancing measures and some form of lockdown, the country has now gradually reopened, despite the persisting high incidence of new cases and deaths.

The authors conclude: "The effect of relaxing these measures is still too early to assess, but further waves of serological surveys will allow monitoring of the progression of the pandemic and help assess the effectiveness of policy changes."

The authors have also carried out two additional seroprevalence surveys* since the two reported in this paper, with an average prevalence of 3.8% in the third study from June 21-24, followed by a sharp decline to 1.4% in the last survey round that was carried out from August 27-30, after an interval of 66 days. This surprised the researchers, since they were expecting cumulative seroprevalence to continue rising (seroprevalence measures the proportion of individuals who have had the infection at some point, not the proportion who are currently infected).

Professor Victora says*: "We don't know what this says about immunity. Even though circulating antibodies, especially those that are neutralising, can quickly decay, the immune system may retain a memory of the infection. In the case of new contact with the virus, B and T cells will then be rapidly activated to produce antibody and cellular protection. All we know so far, for sure, is that so called 'herd immunity' should not be solely assessed on the basis of circulating antibody levels. The full picture is much more complex."

New Rochelle, NY, September 23, 2020 - Forensic DNA analysis enables new and increasingly sophisticated technology for solving cold cases. Through advances in DNA sequencing and bioinformatics, this relatively new and urgent field is enabling a broad range of cold cases, including homicides and other violent crimes, to be solved. The first issue of Forensic Genomics has just been published. Click here to read the issue now.

"Advances in forensic genomics and genealogy have helped solve an unprecedented number of cold cases in the past few years. Forensic Genomics will document and facilitate continued innovation in the field and drive validation and adoption of this exciting new technology for forensics professionals," says Editor-in-Chief David Mittelman, PhD, Founder & Chief Executive Officer, Othram, Inc.

Incorporating robotics and automation into forensic workflows can help reduce casework backlogs in crime laboratories. An article by Kevin Miller PhD, Hamilton Company, and coauthors, describes the "Validation of a High-Throughput Automated Liquid Handling DNA Extraction System to Maximize Efficiency in Forensic Casework."

An article by William Thomas, moderator of Mind Over Murder Podcast, provides a first-hand view of what it is like to suffer the unsolved murder of a loved one. Important insights for the future of the field are put forth.

The News section highlights new forensic DNA methods that are helping to solve cold cases. It focuses on the emergence of DNA sequencing as a more accurate method for collecting genetic information from challenging forensic evidence and also covers database tools for turning the genetic information into meaningful results.

New research presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, online 23-25 September) confirms that men with COVID-19 have worse outcomes than women, possibly related to them experiencing higher levels of inflammation. The study is by Dr Frank Hanses, University Hospital Regensburg, Germany, and colleagues, and shows that men have a 62% increased risk of COVID-19 associated death compared with women, after adjustment for various factors. (see figure 2 of poster).

Increasing evidence suggests a gender difference in SARS-CoV-2 infections. In most cohorts, men are overrepresented and previously published data show a higher incidence of severe courses of COVID-19 in men. To collect clinical data from the pandemic, the international multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) registry was established.

The German Society of Infectious Diseases (DGI) sponsored this registry aiming to provide scientists and doctors with reliable clinical data to enable them to answer numerous urgent questions, such as when do COVID-19 patients develop severe symptoms? What is the best possible treatment? Which measures have been successful up to now? Under the new initiative, it is planned to make the collected data available to the scientific community for use in crowd-based analyses.

In this study, the authors present a first analysis of the LEOSS dataset on the impact of sex in COVID-19. They retrospectively assessed 3,129 adult patients with COVID-19, enrolled between March and July 2020. Baseline characteristics include socio-demographics and comorbidities according to the Charlson Comorbidity Index (number of pre-existing conditions) (CCI).

Clinical manifestation of COVID-19 was described in four phases: uncomplicated (asymptomatic/mild symptoms), complicated (need for oxygen supplementation), critical (need for critical care) and recovery. Symptoms, vital signs, inflammatory markers and therapeutic interventions were analysed over all phases as was clinical outcome.

The male:female ratio in this mostly hospital-based cohort was 1.48 with a male predominance in all age groups. Male predominance was even more pronounced in the age groups >65 years and >75 years. Mean CCI and most comorbidities did not differ significantly between men and women, while coronary artery disease (18% vs 10%) and smoking rates were higher in male patients (14.5 vs 10.5%) than female patients.

Progression to a critical phase (generally reflecting ICU admission) was seen more often in men than in women (30.6% vs 17.2%). Mean hospital length of stay was longer in male patients (15.4 vs 13.3 days).

Both crude mortality (19.2% vs 12.9%) and COVID-19 attributable mortality (17.1% vs 10.3%, figure 1, e-poster), were significantly higher in men. Being male proved to be an independent risk factor for a 62% increased risk of COVID-19 associated death in an analysis adjusted for various factors.

While most laboratory parameters were comparable between male and female patients with COVID-19, men had significantly higher inflammatory markers (IL-6, CRP, PCT, ferritin) across all phases of disease (figure 3, e-poster).

The authors conclude: "Men are more likely to progress to critical phases of COVID-19. Men have higher death rates as well as more frequent ICU admissions and longer hospital stays, that are all associated with higher inflammatory parameters during all phases of COVID-19. In our cohort, this effect was not explained by differences in comorbidities, age or BMI between male and female patients."

"We need further studies on what exactly makes men more vulnerable to COVID-19", concludes Dr Hanses. "We do not yet know which biological or possibly social factors lead to these marked differences."

A US study from the city of Detroit, presented at this week's ESCMID Conference on Coronavirus Disease (ECCMID, online 23-25 September) shows that the initial SARS-CoV-2 viral load in nasopharyngeal samples has been decreasing as the pandemic progressed. The authors also observed that the decline in viral load was associated with a decrease in death rate. The study is by Dr Said El Zein, Wayne State University/ Detroit Medical Center, Detroit, MI, USA, and colleagues.

The dynamics of the SARS-CoV-2 viral load (VL) on a population level remain poorly characterised. In this study, the authors present data describing the downward trend in the initial SARS-CoV-2 VL in nasopharyngeal swab samples of hospitalised patients in Detroit, Michigan during the period of April 4- June 5, 2020.

They conducted a retrospective study that included all hospitalised patients who had initial nasopharyngeal swab samples analysed at the Detroit Medical Center, that returned positive for SARS-CoV-2 by PCR testing between April 4 and June 5, 2020. To estimate the viral load, the authors used the so-called cycle threshold (Ct) value provided by the test for each sample - a higher Ct indicates a lower viral load. Based on their studies, the authors designated high, intermediate, and low VL samples to have a Ct value of 25 or under, 26-36, and 37 or over, respectively.

During the first week of the study (week of April 4, 2020), 49% of the initial VL samples were in the intermediate group, compared to 25.5% each in the low and high VL categories respectively. Thereafter, there was a progressive decline in the percentage of samples in the high and intermediate VL categories with a concomitant rise in the percentage of samples in the low VL category.

By week five of the study, 70% of the positive samples had an initial low VL. This trend in initial VL coincided with a decrease in the percent of deaths (see figure 1 in abstract). Almost half of the patients in the high VL group died (45%) compared to 32% and 14 % of the intermediate and low VL categories respectively (Figure 2).

The authors concldue: : "During the April-June 2020 period of the COVID-19 pandemic, the initial SARS-CoV-2 load steadily declined among hospitalised patients with a corresponding decrease in the percent of deaths over time.Though confounding variables have not been evaluated, this suggests an association between initial viral load and mortality."

Dr El Zein adds: "Exact reasons for a decrease in initial viral load over time are unclear. A downward trend in the initial VL may reflect a reduction in the severity of the pandemic and trends in the viral load values over time may represent a marker to assess the progress of the pandemic. Rapid implementation of social distancing measures, lockdown and widespread use of facemasks may have contributed to a decrease in the exposure to the virus."

New research presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, online 23-25 September) suggests that, as lockdown took effect and case numbers dropped, the amount of virus patients were exposed to (viral load) fell, and this could be linked to lower proportions of patients requiring intensive care and dying. The study is by Dr Chiara Piubelli, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy, and colleagues.

In March 2020, Italy was one of the countries most severely hit by the SARS-CoV-2 (COVID-19). Then, the burden of cases gradually decreased until the end of May. The aim of this work was the evaluation of a possible association between the severity of clinical manifestations and viral load over time, during the epidemiological transition from high to low transmission setting.

The authors analysed 373 cases of COVID-19 diagnosed at the emergency room of the IRCCS Sacro Cuore Don Calabria Hospital, and obtained the proportion of patients admitted to the intensive care unit. To estimate viral load, the estimated the so-called cycle theshold (Ct) for each sample - a higher cycle threshold indicates a lower viral load.

The proportion of patients requiring intensive care significantly reduced from 6.7% in March, to 1.1% in April, and to zero in May. For viral load, they observed a trend of Ct increasing from 24 to 34 (median values) (indicating decreasing viral load) between March and May, with a statistically significant difference between March and April.

The authors conclude: "We observed a reduction over time of the proportion of patients with COVID-19 requiring intensive care, along with decreasing median values of viral load. As the epidemiological context changed from high to low transmission setting, people were presumably exposed to a lower viral load, which has been previously associated with less severe clinical manifestations."