Culture

March 17, 2021-- A new study published online in the Annals of the American Thoracic Society reveals how socioeconomic factors partially explain the increased odds that Black and Hispanic Americans have of testing positive for SARS-CoV-2, the virus that causes COVID-19.

In "Association of Race and Ethnicity With COVID-19 Test Positivity and Hospitalization Is Mediated by Socioeconomic Factors," Hayley B. Gershengorn, MD, associate professor, Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine and co-authors looked at the medical records of 15,473 patients tested and 295 hospitalized with COVID-19 between March 1, 2020 and July 23, 2020 at University of Miami hospitals and clinics. This research was conducted as a retrospective cohort study--one that follows two groups of former patients.

Dr.Gershengorn and colleagues found that the socioeconomic factors of population density at the patient's recorded address, median income, and household size were significantly related to race/ethnicity and explained some of the relation of race/ethnicity with both test positivity and hospitalization. They found no association between race or ethnicity with death rates or other outcomes for hospitalized patients.

"The associations between race/ethnicity and test positivity or hospitalization were not as strong once we adjusted for these socioeconomic factors," she said.

Of patients who were tested for SARS-CoV-2, 29.0 percent were non-Hispanic white, 48.1 percent were Hispanic white, 15.0 percent were non-Hispanic Black, 1.7 percent were Hispanic Black, and 1.6 percent were "other." Among those tested, 1,256 patients (8.1 percent) tested positive and, of the hospitalized patients, 47 (15.9 percent) died. After adjustment for demographics, race/ethnicity was associated with test positivity and hospitalization.

The researchers conducted a mediation analysis to see if household income, population density and household size explained the association of race and ethnicity with COVID-19 outcomes. Mediation analysis is a statistical technique to help explain underlying reasons for an association of an exposure (in this case, race/ethnicity) and an outcome (in this case, test positivity).

"Numerous studies have demonstrated an association of race and/or ethnicity with outcomes (e.g., case positivity, hospitalization, and, sometimes, mortality) in COVID-19," saidDr.Gershengorn. "Specifically, we have seen that, on the whole, non-white and/or Hispanic people tend to fare worse than non-Hispanic white individuals. Appropriately, much has been written about how these associations with worse outcomes almost assuredly have little to do with differences in biology or intrinsic susceptibility to infection across races and ethnicities. Rather, these associations reflect external factors to which minority individuals are more often subject. One of these proposed factors is socioeconomic circumstance; this hypothesis has face validity, but had not been demonstrated in COVID-19. We set out to prove that socioeconomic disparities mediate the association of race and/or ethnicity with worse outcomes in COVID-19."

Of the three socioeconomic factors the researchers examined, they found that median income mediated the largest proportion of COVID-19 positive tests--27 percent. Population density mediated 17 percent and household size mediated 20 percent.

"We found that all three socioeconomic factors were associated with higher odds of test positivity, regardless of race or ethnicity," she stated. "For example, after accounting for other differences, individuals of all races and ethnicities living in the highest population density neighborhoods had 2.5-fold higher odds of test positivity than those living in areas with the lowest population density." Death following hospitalization for COVID-19 was no more common for Black or Hispanic patients than for non-Hispanic white patients.

The researchers believe it would be useful for similar studies to be done in other regions of the U.S.--and parts of the world--with different ethnic/racial makeups and socioeconomic pressures, in order to show the consistency of their findings in other settings and to better understand which (if any) socioeconomic factors impact the association of race and ethnicity with COVID-19 outcomes.

The research team finds it likely that the associations they found between the specific social determinants of health they evaluated and disease risk would be generalizable to other infections with droplet and airborne transmission. Improvements in the social situations of all patients living in more crowded, less well-off communities may pay dividends for their health when the next pandemic, or the next season of influenza, hits.

Dr. Gershengorn adds, "We need to recognize that however much we measure and adjust for potential mediators--socioeconomic factors, access to health care, access to education--we still have structural racism in this country that likely drives many health-related outcomes for minority people. Quantifying the impact of structural racism is important, but more important is working to abolish it."

Researchers at University of Illinois Urbana-Champaign developed software to improve the accuracy of 3D-printed parts, seeking to reduce costs and waste for companies using additive manufacturing to mass produce parts in factories.

"Additive manufacturing is incredibly exciting and offers tremendous benefits, but consistency and accuracy on mass-produced 3D-printed parts can be an issue. As with any production technology, parts built should be as close to identical as possible, whether it is 10 parts or 10 million," said Professor Bill King, Andersen Chair in the Department of Mechanical Science and Engineering and leader of the project.

The team's software allows for the rapid and automatic measurement of additively manufactured parts - a processes that is typically time consuming and costly. It also allows for increased accuracy.

"Factories that rely on 3D printing are being built rapidly all over the world. Our software helps ensure production is consistent, accurate, and cost-effective," King said.

The software tracks how the accuracy of an additively manufactured part depends on which printer made the part and where the part was located in the printer. This process works by measuring parts using optical scanning technology and analysis of the scan data. This analysis allows a user to determine which parts are accurate and identifies which printers, and settings, produce the most accurate parts.

Researchers at University of Illinois Urbana-Champaign developed software to improve the accuracy of 3D-printed parts, seeking to reduce costs and waste for companies using additive manufacturing to mass produce parts in factories.

"Additive manufacturing is incredibly exciting and offers tremendous benefits, but consistency and accuracy on mass-produced 3D-printed parts can be an issue. As with any production technology, parts built should be as close to identical as possible, whether it is 10 parts or 10 million," said Professor Bill King, Andersen Chair in the Department of Mechanical Science and Engineering and leader of the project.

The team's software allows for the rapid and automatic measurement of additively manufactured parts - a processes that is typically time consuming and costly. It also allows for increased accuracy.

"Factories that rely on 3D printing are being built rapidly all over the world. Our software helps ensure production is consistent, accurate, and cost-effective," King said.

The software tracks how the accuracy of an additively manufactured part depends on which printer made the part and where the part was located in the printer. This process works by measuring parts using optical scanning technology and analysis of the scan data. This analysis allows a user to determine which parts are accurate and identifies which printers, and settings, produce the most accurate parts.

OSAKA, Japan. Quantum computers have seen a lot attention recently as they are expected to solve certain problems that are outside the capabilities of normal computers. Primary to these problems is determining the electronic states of atoms and molecules so they can be used more effectively in a variety of industries - from lithium-ion battery designs to in silico technologies in drug development. A common way scientists have approached this problem is by calculating the total energies of the individual states of a molecule or atom and then determine the difference in energy between these states. In nature, many molecules grow in size and complexity, and the cost to calculate this constant flux is beyond the capability of any traditional computer or currently establish quantum algorithms. Therefore, theoretical predictions of the total energies have only been possible if molecules are not sizable and isolated from their natural environment.

"For quantum computers to be a reality, its algorithms must be robust enough to accurately predict the electronic states of atoms and molecules, as they exist in nature, " state Kenji Sugisaki and Takeji Takui from the Graduate School of Science, Osaka City University.

In December 2020, Sugisaki and Takui, together with their colleagues, led a team of researchers to develop a quantum algorithm they call Bayesian eXchange coupling parameter calculator with Broken-symmetry wave functions (BxB), that predicts the electronic states of atoms and molecules by directly calculating the energy differences. They noted that energy differences in atoms and molecules remain constant, regardless to how complex and large they get despite their total energies grow as the system size. "With BxB, we avoided the common practice of calculating the total energies and targeted the energy differences directly, keeping computing costs within polynomial time", they state. "Since then, our goal has been to improve the efficiency of our BxB software so it can predict the electronic sates of atoms and molecules with chemical precision."

Using the computing costs of a well-known algorithm called Quantum Phase Estimation (QPE) as a benchmark, "we calculated the vertical ionization energies of small molecules such as CO, O2, CN, F2, H2O, NH3 within 0.1 electron volts (eV) of precision," states the team, using half the number of qubits, bringing the calculation cost on par with QPE.

Their findings will be published online in the March edition of The Journal of Physical Chemistry Letters.

Ionization energy is one of the most fundamental physical properties of atoms and molecules and an important indicator for understanding the strength and properties of chemical bonds and reactions. In short, accurately predicting the ionization energy allows us to use chemicals beyond the current norm. In the past, it was necessary to calculate the energies of the neutral and ionized states, but with the BxB quantum algorithm, the ionization energy can be obtained in a single calculation without inspecting the individual total energies of the neutral and ionized states. "From numerical simulations of the quantum logic circuit in BxB, we found that the computational cost for reading out the ionization energy is constant regardless of the atomic number or the size of the molecule," the team states, "and that the ionization energy can be obtained with a high accuracy of 0.1 eV after modifying the length of the quantum logic circuit to be less than one tenth of QPE." (See image for modification details)

With the development of quantum computer hardware, Sugisaki and Takui, along with their team, are expecting the BxB quantum algorithm to perform high-precision energy calculations for large molecules that cannot be treated in real time with conventional computers.

This is a landmark study in so far as being the first to raise the alarm that, despite early successes with Covid-19 vaccines, further research is warranted on a next generation of Covid-19 vaccines.

The results from this study, however, only indicate that the AstraZeneca vaccine does not have at least 60% efficacy against mild-moderate Covid-19 due to the B.1.351 (N501Y.V2) variant.

Based on a broader body of evidence, the World Health Organization recommends that this vaccine still be deployed in countries where the B.1.351 variant circulates, as it likely still protects against severe infection, hospitalisation, and death caused by Covid-19.

Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics (VIDA) Research Unit at the University of the Witwatersrand, Johannesburg, led the trial in South Africa:

"Despite the disappointing finding that the AstraZeneca vaccine did not protect against mild Covid infection because of the B.1.351 variant first identified in South Africa, peer review and publication of our research validates the findings and makes a compelling case for the development of a second-generation vaccines worldwide," says Madhi.

First-generation vaccines refer to those designed to respond to the original SARS-CoV-2 virus. Second-generation vaccines refer to technology and design innovations that can provide protections against the constantly evolving variants that cause Covid-19 disease.

A rapid response to variant reality

The findings of this study were previously publicised as a preprint on Sunday, 7 February 2021, and concluded that the ChAdOx1 nCoV-19 vaccine provided minimal protection against mild to moderate Covid-19 infection from the B.1.351 coronavirus variant first identified in South Africa in mid-November 2020.

Prior to the evolution of the B.1.351 and P.1 variants, the South African National Department of Health (NDOH) had ordered and taken delivery of approximately one million doses of the Oxford AstraZeneca vaccine on 1 February 2021, after a published pooled analysis of this vaccine in December 2020 showed an overall vaccine efficacy of 66.7% in the UK and Brazil.

"We were in a state of euphoria about the high efficacy of several Covid-19 vaccines against the original virus, but then the AstraZeneca study threw us a curve-ball," says Madhi. "In this study now published in NEJM, we found that two doses of ChAdOx1 nCoV19 had no efficacy against non-hospitalized mild to moderate Covid-19, mainly due to the B.1.351 variant."

What the SA study published in NEJM reveals

The randomised, multi-centre, double-blinded trial enrolled 2026 participants between 24 June and 9 November 2020.

The trial was a phase 1b/11 trial that aimed to evaluate the safety, immunogenicity, and efficacy of the AstraZeneca vaccine ChAdOx1 nCoV19 in preventing symptomatic Covid-19. Immunogenicity refers to the ability of a foreign substance, such as an antigen, to provoke an immune response. Vaccine efficacy refers to the percentage reduction of a disease in a clinical trial.

"A trial enrolling just 2026 participants is considered small, while phase 3 trials enroll tens of thousands of participants," says Madhi. "Yet the startling data that our small trial generated was irrefutable, and the implications profound."

Profile of a South African AstraZenca Covid-19 vaccine trial participant

The majority of participants enrolled were relatively young (under 65-years-old), generally healthy, and HIV-negative. The median [middle] age of participants was 30 years old. More than half (56.5%) of the trial participants identified as male, 70.5% were Black Africans, 12.8% were white, and 14.9% identified as 'mixed' race.

"These demographics are important because they reflect characteristics of the overall population in South Africa. Conducting clinical trials in diverse settings like these is critical to understanding how vaccines work in local contexts," says Madhi.

Testing a hypothesis

The primary ojective of this trial was to establish this vaccine's efficacy against all-severity Covid-19, irrespective of variants.

A secondary objective was to evaluate the vaccine's efficacy against the B.1.351 variant specifically.

"When this trial began in June 2020, we were testing a vaccine against SARS-COV-2," says Madhi. "By January 2021, SARS-CoV-2 had spawned variants, including the B.1.351 first discovered in South Africa. As a secondary objective, we tested a hypothesis: would this vaccine prove at least 60% efficacious in preventing mild to moderate Covid-19 disease? It did not."

The results showed that a two-dose regimen of ChAdOx1-nCov19 did not show protection against mild to moderate Covid-19 due to the B.1.351 variant.

Crucially, Madhi notes that, "This vaccine may still help protect high-risk individuals with co-morbidities from contracting severe Covid-19 disease, having to be hospitalised, mechanically ventilated, or dying. The AstraZeneca vaccine remains essential in the arsenal against this virus, particularly in Africa, which has already received 14 million doses of this vaccine as the Covid-19 immunization programme starts in multiple countries."

How the WHO took note

On 15 February 2021, the WHO recommended that the AstraZeneca vaccine still be rolled out, even in countries where the B.1.351 variant or other similar variants of concern are circulating.

A WHO news release says that the vaccine was reviewed on 8 February by the WHO Strategic Advisory Group of Experts on Immunization (SAGE), which makes recommendations for vaccines' use in populations (i.e. recommended age groups, intervals between shots, advice for specific groups such as pregnant and lactating women). The SAGE recommended the vaccine for all age groups 18 years and above.

"While the AstraZeneca vaccine - like many other first-generation Covid-19 vaccines - is unlikely to interrupt transmission of SARS-CoV-2 or protect against mild infection from variants like B.1.351, these first-generation vaccines could still provide the only sustainable option to prevent flooding our hospitals with severe Covid-19 cases, and to mitigate Covid-19 deaths once the third wave hits," says Madhi.

Second-generation vaccine innovation

The development of an Oxford AstraZeneca and other Covid-19 vaccines targeting the B.1351 variant is currently underway.

The South African study increased awareness worldwide of the necessity of developing vaccines that target variants specifically - and even reimagining vaccines entirely.

Innovations in vaccine technologies, platforms and designs suggest exciting advances in this field.

"The finding of our [Oxford AstraZeneca Covid-19 vaccine] study are truly a turning point in Covid vaccine development - and a rude awakening," says Madhi. "This one small South African study has alerted the world to the fact that second generation Covid-19 vaccines will be required to provide protection against inevitable and persistent SARS-COV-2 variants. If we had not conducted this trial in South Africa, the world would be none the wiser."

According to a new study published in the Journal of the Royal Society of Medicine, the carbon footprint of personal protective equipment (PPE) provided to health and social care staff in England during the first six months of the COVID-19 pandemic was equivalent to flying from London to New York 244 times every day. The good news is that adopting a range of strategies including increased UK manufacture, reusing and recycling could reduce the environmental impact of PPE dramatically while maintaining the safety of staff and patients.

The study, by Brighton and Sussex Medical School and Brighton and Sussex University Hospitals NHS Trust, found that the 3 billion items of PPE used from February to July last year generated 591 tonnes of carbon dioxide a day, or 27,000 times the average individual's carbon footprint. The 1.8 billion gloves used had the biggest environmental impact, followed by aprons, face shields and masks.

The study also suggested ways in which PPE use in the future could lessen environmental impact. This includes reusing gowns and face shields where possible, recycling PPE waste, and manufacture of PPE in the UK. But the biggest impact could be through reducing the volumes of PPE used, for example using hand-washing instead of wearing gloves.

Chantelle Rizan, a doctor in the NHS and a research fellow at the Royal College of Surgeons of England, led the study. She said: "COVID-19 has impacted many aspects of life. Ours is the first study to look at the environmental harm of using PPE on such scale, and the results are concerning. However, a combination of strategies could have reduced the carbon footprint by 75%. We are not advocating actions that could increase risk of infection, however, guidelines around use of PPE aren't always consistent or up to date with the latest science. It may be perfectly safe to wash hands rather than use gloves in many situations, and that is something that needs further exploration."

Professor Neil Mortensen, President of the Royal College of Surgeons of England, said: "It's clear the virus will be with us for some time yet, so the need for PPE to keep staff and patients safe is still paramount. But the findings of this new study are sobering, and we must also consider how to reduce the environmental impact of PPE, including making greater use of reusable items or how PPE and other plastic healthcare waste can be recycled - something the College's Sustainability in Surgery working group is looking at."

Researchers at Lund University in Sweden have designed a new bioink which allows small human-sized airways to be 3D-bioprinted with the help of patient cells for the first time. The 3D-printed constructs are biocompatible and support new blood vessel growth into the transplanted material. This is an important first step towards 3D-printing organs. The new study has been published in Advanced Materials.

Chronic lung diseases are the third leading cause of death worldwide with an EU cost of more than €380 billion annually. For many chronic diseases there is no cure and the only end-stage option for patients is lung transplantation. However, there are not enough donor lungs to meet clinical demand.

Therefore, researchers are looking at ways to increase the amount of lungs available for transplantation. One approach is fabricating lungs in the lab by combining cells with a bioengineered scaffold.

"We started small by fabricating small tubes, because this is a feature found in both airways and in the vasculature of the lung. By using our new bioink with stem cells isolated from patient airways, we were able to bioprint small airways which had multiple layers of cells and remained open over time", explains Darcy Wagner, Associate Professor and senior author of the study.

The researchers first designed a new bioink (a printable material with cells) for 3D-bioprinting human tissue. The bioink was made by combining two materials: a material derived from seaweed, alginate, and extracellular matrix derived from lung tissue.

This new bioink supports the bioprinted material over several stages of its development towards tissue. They then used the bioink to 3D-bioprint small human airways containing two types of cells found in human airways. However, this bioink can be adapted for any tissue or organ type.

"These next generation bioinks also support the maturation of the airway stem cells into multiple cell types found in adult human airways, which means that less cell types need to be printed, simplifying the nozzle numbers needed to print tissue made of multiple cell types", says Darcy Wagner.

Wagner notes that the resolution needs to be improved to 3D-bioprint more distal lung tissue and the air sacks, known as alveoli, that are vital for gas exchange.

"We hope that further technological improvements of available 3D printers and further bioink advances will allow for bioprinting at a higher resolution in order to engineer larger tissues which could be used for transplantation in the future. We still have a long way to go", she says.

The team used a mouse model closely resembling the immunosuppression used in patients undergoing organ transplantation. When transplanted, they found that 3D-printed constructs made from the new bioink were well-tolerated and supported new blood vessels.

"The development of this new bioink is a significant step forward, but it is important to further validate the functionality of the small airways over time and to explore the feasibility of this approach in large animal models", concludes Martina De Santis, the first author of the study.

The use of artificial light at night around the world has increased enormously in recent years, causing adverse effects on the survival and reproduction of nocturnal organisms. Artificial light at night interferes with vital ecological processes such as the nighttime pollination of plants by nocturnal insects, which could have consequences for agricultural crop yields and reproduction of wild plants.

Scientists from the University of Zurich and Agroscope have now demonstrated for the first time that artificial light at night also adversely affects insects' pollination behavior during the daytime. In an experiment, they used commercial streetlamps to illuminate natural plant-pollinator communities during the nighttime on six natural meadows. Six other natural meadows were left dark. The research team concentrated its analysis on 21 naturally occurring plant species and the insect orders Diptera, Hymenoptera and Coleoptera.

Differing interactions depending on plant species
"Our findings indicate that artificial light during the nighttime alters the number of plant-pollinator interactions during the daytime, depending on the plant species," says Eva Knop from UZH's University Research Priority Program Global Change and Biodiversity and Agroscope. For example, three plant species received significantly fewer, and one other species slightly fewer, pollinator visits during the daytime. A different plant species, in contrast, received many more pollinator visits, and one other a little more, under LED illumination.

Interestingly, nocturnal pollinator activity also varied in the presence of artificial light. For example, woodland geraniums (Geranium sylvaticum) in illuminated and dark meadows received the same number of pollinator visits, but not by the same insects: whereas dipterous insects reduced their visits to plants that were illuminated during the night, beetles (Coleoptera) tended to increase their visits. Two other plant species exhibited similar trends.

Indirect ecological effects of light pollution
The indirect ecological impact of light pollution has been ignored thus far. "Since insects play a vital role in pollinating crops and wild plants and are already endangered by habitat destruction and climate change regardless of artificial light, it is important to study and clarify these indirect mechanisms," Knop says.

On the basis of their findings, Knop and her colleagues call for "the ecological impact of light pollution to be researched more thoroughly and for actions to be devised to avert adverse effects on the environment." They say they see ways to do this even though artificial light is an integral feature of populated areas. Public lighting, for instance, could be carefully designed in combination with new technologies to reduce it to a minimum.

Not least because of the COVID-19 pandemic, conspiracy theories are more topical than ever. They are reported and discussed in almost all media and communication channels. But what influence do they have on our behavior? Scientists led by behavioral economist Loukas Balafoutas investigated this question in a recently published study. The result: We don't need to believe in conspiracy theories for them to have an impact on us. Merely being confronted with them suffices.

Previous studies have shown that beliefs in conspiracy theories have an influence on the behavior of their adherents. For example, they lead to lower voter turnout or a lower willingness to get vaccinated. For years now, conspiracy theories have been experiencing a real boom - it is almost impossible to ignore them. This has prompted a research team led by Loukas Balafoutas to conduct a laboratory experiment to investigate whether conspiracy theories also have an impact on us when we do not believe in them and are only briefly confronted with them. "Our study shows that subjects who were exposed to a conspiracy theory for just three minutes acted differently in a subsequent behavioral experiment than subjects from the control group," reports Loukas Balafoutas, Professor of Experimental Economics at the Department of Finance at the University of Innsbruck. The researchers were recently able to publish these results in the journal "Economic and Political Studies".

Conspiracy theories change behavior

In the so-called EconLab of the University of Innsbruck, the researchers conducted their experiment before the COVID-19 pandemic. Half of the 144 participants in the study were shown a 3-minute video depicting the 1969 moon landing as a fake. The control group, on the other hand, watched an equally long video about the space shuttle program. Subsequently, the test persons participated in the so-called "money request game". The players were divided into pairs and asked to make a simultaneous integer bid between 5 and 14 euros. Whoever made the smaller bid received the amount of that bid plus 10 euros; whoever made the larger bid received only the amount of the bid. In the event of a tie, both participants received exactly their bid. In this game, the best response to a bid larger than 5 euros from the other participant is to bid exactly one euro less. If the other participant bids 5 euros, the best response is to bid 14 euros. "In this experiment, we found that subjects who had previously watched the conspiracy theory video bid smaller amounts. This shows that these test persons act more strategically. On the one hand, this can possibly lead to a higher profit in the game, but at the same time this approach also carries the risk of incurring a loss," explains Balafoutas. "So our aim here is not to evaluate this behavior as better or worse, but simply to show that people who were exposed to a conspiracy theory shortly beforehand display different behavior than the control group in a subsequent situation that is completely different in terms of content. From this we conclude that the conspiracy theory has an influence on how someone perceives the world and other people," Balafoutas continues.

Trust remains

In another experiment, the so-called "trust game," the researchers tested the extent to which exposure to a conspiracy theory leads to an impairment of trust toward others. In this game, players were divided into pairs. In each pair, both players received 5 euros. One of the players (A) could decide to invest part or all of the amount. The invested amount was tripled and given to the other player (B), who could then transfer part of the money back to player A - but did not have to. Larger amounts invested by A in this game correspond to a higher level of trust. "It is quite a positive message that we did not find any negative influence of the conspiracy theory here. Trust in the other person was statistically the same in both groups. That's important, because in our society we need a certain level of trust for it to function at all," Balafoutas says.

That the scientists studied conspiracy theories in the lab is no coincidence. "As researchers, we don't want to contribute to spreading conspiracy theories into society. Therefore, caution is always required in such studies. They must be carried out in an ethically justifiable manner and must also be approved in advance. It is particularly important to debrief the test subjects after such an experiment," explains Loukas Balafoutas.

One of the most vital functions performed by the cells in our body is DNA repair, a task so crucial to our well-being that failing to execute it can lead to consequences as dreadful as cancer. The process of DNA repair involves a complex interplay between several gene pathways and proteins. One such pathway is the "Fanconi anemia (FA) pathway," whose genes participate in DNA repair. FANCM, a component of this pathway, is tasked with the elimination of harmful DNA "inter-strand cross-links," and interacts with another component called MHF in order to function. The importance of the FANCM-MHF complex is well-documented: its loss can result in chromosomal instabilities that can lead to diseases such as FA itself and cancer. However, little is known about its structure and the basis of its stability.

Against this backdrop, Associate Professor Tatsuya Nishino and his colleague Dr. Sho Ito from Tokyo University of Science decided to explore the crystalline structure of this intriguing complex using X-ray diffraction techniques. "DNA damage and chromosome segregation are mechanisms necessary for the maintenance and inheritance of genes possessed by all organisms. MHF (also known as CENP-SX) is an enigmatic complex that plays a role in DNA repair and chromosome segregation. We wanted to find out how it performs these two different functions in the hope that it might give us insights into novel phenomena," explains Prof. Nishino. Their findings are published in Acta Crystallographica Section F: Structural Biology Communications.

The scientists prepared a recombinant version of the FANCM-MHF complex, consisting of FANCM from chickens and MHF1 and MHF2. They were able to purify three different types of protein crystals--tetrahedral, needle-shaped, and rod-shaped--from similar crystallization conditions. Surprisingly, upon determining the structure with X-ray crystallography, they found that two of the crystal forms (tetrahedral and needle-shaped) contained only the MHF complex without FANCM.

Intrigued by this discovery, the scientists used biochemical techniques to examine what caused the FANCM-MHF complex to disassemble. They attributed it to the presence of a compound called 2-methyl-2, 4-pentanediol (MPD), an organic solvent commonly used in crystallography, and exposure to an oxidizing environment.

But, how exactly does the dissociation happen? The scientists believe that this may have been caused partly by certain non-conserved amino acids in the chicken FANCM which causes the complex to aggregate with other FANCM-MHF complexes and disassemble. Additionally, they surmise that the small, flexible structure of MPD may have also allowed it to bind to and facilitate the release of FANCM, dismantling the complex.

The findings are extraordinary and can be used to improve the stability of the FANCM-MHF complex for future studies on its structure and function. Dr. Ito believes we have much to expect in the future from this complex. "A good understanding of this complex can help us treat cancer and genetic diseases, create artificial chromosomes, and even develop new biotechnological tools," he speculates.

Thanks to Prof. Nishino and Dr. Ito's efforts, we are already one step closer to that goal!

Hepatitis B virus (HBV) infections are among the major global health problems. Particularly problematic is the high number of chronic courses of the disease, causing the deaths of more than 800.000 people globally every year. So far, there is no therapy to cure the condition. "With the discovery of a new hepatitis B virus in donkeys and zebras capable of causing prolonged infections, we now have the opportunity for a better understanding of the chronic course of the disease and thus also for mitigation or prevention of severe clinical consequences," explains Prof. Dr. Jan Felix Drexler, DZIF researcher at the Charité - University Medicine Berlin. In the German Center for Infection Research (DZIF), he identifies and characterizes emerging viruses that could be dangerous for humans.

"Five years ago we were able to show for the first time that donkeys harbor viruses that are genetically related to the human hepatitis C virus," explains Andrea Rasche, lead author of the study and DZIF scientist at the Charité - University Medicine Berlin. Since HBV and the hepatitis C virus (HCV) often occur together in humans, the researchers have also searched for HBV worldwide in donkeys. In addition to field work, extensive molecular, serological, histopathological and evolutionary biology methods were used. "We have studied nearly 3000 samples from equids, i.e. from donkeys, zebras and horses in five continents, and we found that donkeys are global carriers of the new hepatitis B virus," explains Drexler.

The origins of the new HBV could be linked to the domestication of donkeys in Africa a few thousand years ago. Donkeys are naturally infected with HBV as well as with HCV. Zebras are also infected with HBV; horses are also likely to be receptive, but in initial studies, the scientists could not confirm any naturally infected horses. In naturally infected donkeys, the course of the infection is similar to chronic hepatitis B in humans.

"The new hepatitis B virus appears to use an unknown receptor for entry into the host cell," explains Felix Lehmann, second lead author of the study and DZIF scientist at Giessen University (JLU) where he studied the molecular biology of virus binding and entry in cell culture. The emergence of human HBV and the development of its receptor use remain unclear and are jointly investigated by the researchers from Berlin and Giessen.

"Since the virus is unable to infect human liver cells, human infection with this virus can be ruled out with a high degree of probability," emphasises Prof. Dr. Dieter Glebe, Head of the National Reference Centre for Hepatitis B and D viruses at JLU and DZIF scientist in the "hepatitis" research unit. The scientists are convinced that with the virus in donkeys and zebras, they can develop a better understanding of the pathogenesis of chronic hepatitis B and of HBV/HCV co-infection to lay a foundation for new therapies.

A new study uncovers which cell types can be infected by SARS-CoV-2 due to their viral entry factors. The study also suggests that increased gene expression of these viral entry factors in some individuals partially explains the differences of COVID-19 severity reported in relation to age, gender and smoking status. The study evolved from the Human Cell Atlas Lung Biological Network with main contributions from Helmholtz Zentrum München, the Broad Institute of MIT and Harvard, the Wellcome Sanger Institute and University Medical Center Groningen.

COVID-19 does not affect everyone in the same way. While the coronavirus SARS-CoV-2 primarily manifests in the lung, it can infect other organs, too. Clinical observations throughout the pandemic also suggest that some population groups - such as elderly people, men and smokers - tend to be more severely affected by the disease. So far, the molecular reasons for this have not been described.

Previous studies had shown that in order to infect human cells, SARS-CoV-2 needs the cell to contain specific genetic viral entry factors - namely an ACE2 receptor and a protease (TMPRSS2 or CTSL). Knowing which cell types express both ACE2 and a protease would therefore give us information about which cells can potentially be infected with SARS-CoV-2.

The Human Cell Atlas (HCA) consortium is aiming to map every cell type in the human body, transforming our understanding of biology and disease. Within this, researchers from the HCA Lung Biological Network joined forces to contribute and analyse gene expression data from individual cells. Together, they analysed more than 100 datasets of single-cell gene expression of healthy people, to see which cell types express both ACE2 and a protease.

The analysis showed that specific cell types in the epithelium of the lung and airways, but also in the liver, the colon, and the eye are rich in genetic viral entry factors (=high expression of ACE2 receptor and a protease) - and therefore contain the necessary molecules to allow SARS-CoV-2 infection.

Moreover, the researchers found that the expression of genes underlying the viral entry factors is increased in the cells of elderly people and slightly in men compared to women. In addition, cells from smokers (in particular airway cells) express more SARS-CoV-2 entry factors than from non-smokers. These findings match differences in disease severity that have been reported for COVID-19 patients in those population groups and thus offer a molecular explanation for this difference (next to other factors which were not investigated in this study such as a weaker immune system).

Big data for biomedical research

"Fighting the pandemic, we cannot rely on conclusions that are limited to a few observations only. Instead, we must rely on robust analysis of big data. For example, to assess whether the ACE2 receptor required for virus entry is more abundant in cells of the elderly population, we need a strong representation of many diverse individuals in our dataset. Using data from the Human Cell Atlas, we could model how genetic viral entry factors in cells are expressed across the population," says Malte Lücken, computational biologist at Helmholtz Zentrum München and co-first author of the study.

"A key aspect of this large-scale study was the age range of samples we were able to analyse. This study included data from human developmental stages, samples from children and young adults, as well as samples from elderly people. This gave us unique power to assess changes occurring over the human lifetime. The sheer scale of the data allowed us to see molecular differences with age, sex and smoking status," said Kerstin Meyer, an author on the paper from the Wellcome Sanger Institute.

"This study was the epitome of a whole field coming together. Within the Human Cell Atlas consortium everyone who generated data on the healthy human lung contributed their data, both published and unpublished, to enable our analysis. When we then reached out beyond the consortium, more labs also contributed data to the effort. Only through these contributions was our analysis made possible," adds Fabian Theis, Director of the Institute of Computational Biology at Helmholtz Zentrum München.

Strengths and limitations

The study investigated which cells are most likely to be infected by SARS-CoV-2. The results partially explain how disease severity might differ between population groups because of the molecular profile of cells. This provides a target for further intervention research. Moving forward, the findings may also help to better understand the spread of the corona virus across the body. The connection between viral entry factor expression and increased ease of infection or disease severity has been shown in mice and in the lab, but requires further validation in humans.

The health of women aged 65 and over appears to be related, in addition to their own socioeconomic characteristics, with that of their partners, as a result of traditional gender norms. This is one of the main conclusions of research led by Jordi Gumà, a researcher at the UPF Department of Political and Social Sciences, conducted in conjunction with Jeroen Spijker, a Ramon y Cajal I3 researcher at the Centre for Demographic Studies of the Autonomous University of Barcelona (CED-UAB), focusing on the case of Spain.

The study, published in Gaceta Sanitaria, analyses the health differences among the Spanish population aged between 65 and 81 years living in couples.

According to Jordi Gumà, a member of the UPF Sociodemography Research Group (DEMOSOC), this situation is aggravated by several causes: "The fact that they often act as caregivers for their spouse (husband), has a double impact on women's health as a result of gender inequality: because they are economically dependent on their partners; and for having to assume a greater daily burden as caregivers", he explains.

The study, recently published in its final printed version in the journal Gaceta Sanitaria, analyses the health differences among the Spanish population aged between 65 and 81 years living in couples, considering the socioeconomic characteristics of the two members individually and combined. It is a pioneering approach with respect to the research carried out to date, which has so far focused on individual analysis.

The general aim of the study was to determine whether in addition to the individual's level of education, a standard indicator in this type of research, the characteristics of their partner (level of education and health status) and of the household in general (economic capacity and spousal age gap) affect the health of people aged 65 or over living with a partner.

The health status of the other member of the couple, a decisive factor

The study shows that living with a partner who is not in good health is associated with almost double the likelihood of being in the same situation, and that women's health is significantly better if their level of education is higher than their partner's, and this result is less significant in the case of men.

"According to our results, living with an older husband whose health is delicate penalizes women's health".

"The health status of the other member of the couple is the variable displaying the greatest effect on the health of the Spanish population aged 65 and over living under this model of cohabitation, although women's health seems to be more sensitive to the educational level of their partner and the general economic situation of the household", the authors assert.

In this sense, the research finds a clear gender component: "According to our results, living with an older husband whose health is delicate penalizes women's health. Conversely, the additional workload is lower for husbands when their wife's health is poor because men tend to share this burden with other, mainly female family members, particularly daughters or daughters-in-law", they point out.

Moreover, the study demonstrates the existence of an assortative mating effect, as two individuals with similar behaviour are more likely to match up, irrespective of socioeconomic status. This selective mating (partner resemblance) at younger ages, can have a cumulative effect on health over the years as a result of behavioural factors such as smoking, diet, alcohol consumption, etc.

The peculiar case of Spain, with very traditional gender roles

The study focused on analysing the case of Spain, based on a sample of nearly 1,800 people taken from the European Union Statistics on Income and Living Conditions (EU-SILC) survey (2015 wave) on the elderly (65 to 81 years) living with a partner. Based on separate logistic regression models for men and women, the authors obtained the estimate of the likelihood of not having good self-perceived health.

In Spain, the educational expansion and the massive insertion of women into the labour market started later than in other Western European countries.

They assure that they chose Spain as a case study because until now, research on joint (partner and own) education profiles and health status have focused on the United States or northern, western and central European countries, but no country from southern Europe had yet been analysed.

In addition, according to the authors, Spain is an especially interesting case because the educational expansion and the massive insertion of women into the labour market started later than in other Western European countries. Accordingly, "the productive and reproductive roles in Spain are still very much gendered for the older cohorts studied here, whereby the female socioeconomic status is almost totally determined by their partner's status", they state.

Research that may help steer healthcare policies

In the authors' opinion, one relevant contribution by their study to public policy is that "not only typical vulnerable groups like single-person, single-parent or low-income households should be targeted, but also retired low-educated partnered individuals, even if their partner is more highly educated". Moreover, "the results of the study are particularly relevant for health professionals who are in daily contact with patients as health inequalities are larger at the household level than at the individual level", they conclude.

An international team of scientists from the University of Turku, Finland and PennState University, USA have solved a long-standing mystery of how living organisms distinguish RNA and DNA building blocks during gene expression paving the way for the design of new antiviral drugs. The new insights were published in the journal Nature Communications.

All cellular organisms use two types of nucleic acids, RNA and DNA to store, propagate and utilize their genetic information. The synthesis of DNA is carried out by enzymes called DNA polymerases and is needed to accurately transfer the genetic information from generation to generation. Synthesis of RNA is carried out by enzymes called RNA polymerases and is needed to utilize the genetic information to ultimately produce proteins that in turn fulfil most structural and catalytic functions in all modern-day living organisms.

The ancient problem faced by RNA and DNA polymerases is that the DNA and RNA building blocks are very hard to distinguish. Those building blocks are identical except for a small part of the molecule, called the 2'OH group that is present in the RNA building blocks but is absent from the DNA building blocks.

DNA polymerases avoid using the RNA building blocks by featuring a cavity called the active site that is just big enough to bind the DNA building blocks but is too small to accommodate the slightly bigger RNA building blocks. As a result, only DNA building blocks bind to the active site cavity and get attached to the growing DNA polymer.

- RNA polymerases cannot use the same strategy because the smaller DNA building blocks will always fit into the same active site cavity as the RNA building blocks, explains Senior Researcher Georgi Belogurov.

RNA Polymerase Active Site Cavity Deforms the DNA Building Blocks

To understand how RNA polymerases avoid using DNA building blocks, a research team from the University of Turku headed by Belogurov performed complex biochemical measurements using RNA polymerases that were altered by carefully engineered mutations. At the same time, the research team at Penn State University, USA, led by Professor Katsuhiko Murakami obtained a detailed three-dimensional structure of RNA polymerase with the DNA building block.

By the combined analysis of the biochemical and structural data Doctoral Candidate Janne Mäkinen, the first author of the study, and his colleagues discovered that RNA polymerase evolved the active site cavity that deforms the DNA building blocks so that they are no longer suitable for incorporation into the RNA chain.

- The deformed DNA building blocks then dissociate from the RNA polymerase instead of being attached to the growing RNA polymer, says Mäkinen.

Human and Viral RNA Polymerases Select RNA Building Blocks Differently - Finding Enables Development of More Effective Antiviral Drugs

The study was financially supported by the Academy of Finland, Sigrid Juselius Foundation (Finland), and the National Institute of Health (USA) and has long-reaching implications for translational research.

- RNA viruses such as SARS-Cov-2 that is the causative agent of COVID-19 disease also synthesise RNA as a part of their infectious cycle. Viruses use their own RNA polymerases that are very different from RNA polymerases of the human cell but also need to select the RNA building blocks and reject the DNA building blocks, says Georgi Belogurov.

By careful comparison of the newly discovered selectivity mechanism with the findings of other research teams, Mäkinen and colleagues concluded that viral and human RNA polymerases use different mechanisms to reject the DNA building blocks. They suggest it may be possible to design a synthetic molecule similar to a DNA building block that would selectively bind and inhibit viral RNA polymerase but will be rejected by the human RNA polymerases and therefore will not interfere with the synthesis of RNAs needed by the human cell.

- This paves the way for the designing of potent and selective antiviral drugs targeting viral RNA polymerases, says Belogurov.

A single-celled alga undergoes genome surgery to remove non-essential parts. This can lead to a most efficient cellular factory for producing sustainable biofuels from sunlight and carbon dioxide.

Researchers from the Qingdao Institute of BioEnergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS) have stripped hundred-kilobase genome from a type of oil-producing microalgae, knocking out genes non-essential for it to function. By doing so, they have created a "genome scalpel" that can trim microalgal genomes rapidly and creatively.

The 'minimal genome' microalgae produced is potentially useful as a model organism for further study of the molecular and biological function of every gene, or as a 'chassis' strain for synthetic biologists to augment for customized production of biomolecules such as biofuels or bioplastics.

The study was published in The Plant Journal on March 14, 2021.

Creation of a 'minimal genome' -- a genome stripped of all duplicated or apparently non-functional 'junk genes' -- can be very useful for investigating fundamental questions about genetic function and for designing cell factories that produce valuable compounds.

Such minimal genomes have been created for simple organisms, but rarely for eukaryotic organisms, including algae or plants. In higher eukaryotes, "junk" regions can take up to 70 percent of the genome. Deleting what only appears to be "junk genes" in fact can have harmful effects on the organism or even kill it.

For the first time, researchers from QIBEBT have produced a genome with targeted deletions, of hundred kilobases in size each, for a type of algae called Nannochloropsis oceanica.

N. oceanica are microalgae (single-celled algae) that have tremendous potential for production of biofuels, biomaterials and other platform chemicals in a renewable and sustainable manner while reducing greenhouse gas emissions. However, realizing the potential of these microalgae requires extensive genetic engineering of the organism to maximize yields and minimize production costs.

The QIBEBT team first identified the non-essential chromosomal regions -- ones whose genes were rarely expressed, or activated. They identified ten such 'low-expression regions', or LERs. They then used CRISPR-Cas9 gene-editing technique to snip out two of the largest LERs -- over 200 kilobases in size.

"Despite the all snipping, the microalgae still showed essentially normal growth, lipid content, fatty acid saturation levels and photosynthesis," said study first-author WANG Qintao, of the Single-Cell Center (SCC) in the QIBEBT. "In some cases, there was even a slightly higher growth rate and biomass productivity than the organism in the wild."

"We interestingly found normal telomeres in the telomere-deletion mutants of Chromosome 30," said the corresponding author XU Jian, of the SCC in QIBEBT. "This phenomenon implies the losing of distal part of chromosome may induce telomere regeneration."

Already, the substantially snipped genome should serve as a closer-to-minimal genome in Nannochloropsis, which can serve as the chassis strain for customized production of biomolecules using further metabolic engineering atop this chassis.

Now that they have proven they can strip down the genome of such a complex eukaryote, the researchers now want to see if they can snip out still further LERs and other non-lethal regions, to craft a fully minimal Nannochloropsis that makes biofuels from CO2 with the highest efficiency.