Culture

Imagine going to a surgeon to have a diseased or injured organ switched out for a fully functional, laboratory-grown replacement. This remains science fiction and not reality because researchers today struggle to organize cells into the complex 3D arrangements that our bodies can master on their own.

There are two major hurdles to overcome on the road to laboratory-grown organs and tissues. The first is to use a biologically compatible 3D scaffold in which cells can grow. The second is to decorate that scaffold with biochemical messages in the correct configuration to trigger the formation of the desired organ or tissue.

In a major step toward transforming this hope into reality, researchers at the University of Washington have developed a technique to modify naturally occurring biological polymers with protein-based biochemical messages that affect cell behavior. Their approach, published the week of Jan. 18 in the Proceedings of the National Academy of Sciences, uses a near-infrared laser to trigger chemical adhesion of protein messages to a scaffold made from biological polymers such as collagen, a connective tissue found throughout our bodies.

Mammalian cells responded as expected to the adhered protein signals within the 3D scaffold, according to senior author Cole DeForest, a UW associate professor of chemical engineering and of bioengineering. The proteins on these biological scaffolds triggered changes to messaging pathways within the cells that affect cell growth, signaling and other behaviors.

These methods could form the basis of biologically based scaffolds that might one day make functional laboratory-grown tissues a reality, said DeForest, who is also a faculty member with the UW Molecular Engineering and Sciences Institute and the UW Institute for Stem Cell and Regenerative Medicine.

"This approach provides us with the opportunities we've been waiting for to exert greater control over cell function and fate in naturally derived biomaterials -- not just in three-dimensional space but also over time," said DeForest. "Moreover, it makes use of exceptionally precise photochemistries that can be controlled in 4D while uniquely preserving protein function and bioactivity."

DeForest's colleagues on this project are lead author Ivan Batalov, a former UW postdoctoral researcher in chemical engineering and bioengineering, and co-author Kelly Stevens, a UW assistant professor of bioengineering and of laboratory medicine and pathology.

Their method is a first for the field, spatially controlling cell function inside naturally occurring biological materials as opposed to those that are synthetically derived. Several research groups, including DeForest's, have developed light-based methods to modify synthetic scaffolds with protein signals. But natural biological polymers can be a more attractive scaffold for tissue engineering because they innately possess biochemical characteristics that cells rely on for structure, communication and other purposes.

"A natural biomaterial like collagen inherently includes many of the same signaling cues as those found in native tissue," said DeForest. "In many cases, these types of materials keep cells 'happier' by providing them with similar signals to those they would encounter in the body."

They worked with two types of biological polymers: collagen and fibrin, a protein involved in blood clotting. They assembled each into fluid-filled scaffolds known as hydrogels.

The signals that the team added to the hydrogels are proteins, one of the main messengers for cells. Proteins come in many forms, all with their own unique chemical properties. As a result, the researchers designed their system to employ a universal mechanism to attach proteins to a hydrogel -- the binding between two chemical groups, an alkoxyamine and an aldehyde. Prior to hydrogel assembly, they decorated the collagen or fibrin precursors with alkoxyamine groups, all physically blocked with a "cage" to prevent the alkoxyamines from reacting prematurely. The cage can be removed with ultraviolet light or a near-infrared laser.

Using methods previously developed in DeForest's laboratory, the researchers also installed aldehyde groups to one end of the proteins they wanted to attach to the hydrogels. They then combined the aldehyde-bearing proteins with the alkoxyamine-coated hydrogels, and used a brief pulse of light to remove the cage covering the alkoxyamine. The exposed alkoxyamine readily reacted with the aldehyde group on the proteins, tethering them within the hydrogel. The team used masks with patterns cut into them, as well as changes to the laser scan geometries, to create intricate patterns of protein arrangements in the hydrogel -- including an old UW logo, Seattle's Space Needle, a monster and the 3D layout of the human heart.

The tethered proteins were fully functional, delivering desired signals to cells. Rat liver cells -- when loaded onto collagen hydrogels bearing a protein called EGF, which promotes cell growth -- showed signs of DNA replication and cell division. In a separate experiment, the researchers decorated a fibrin hydrogel with patterns of a protein called Delta-1, which activates a specific pathway in cells called Notch signaling. When they introduced human bone cancer cells into the hydrogel, cells in the Delta-1-patterned regions activated Notch signaling, while cells in areas without Delta-1 did not.

These experiments with multiple biological scaffolds and protein signals indicate that their approach could work for almost any type of protein signal and biomaterial system, DeForest said.

"Now we can start to create hydrogel scaffolds with many different signals, utilizing our understanding of cell signaling in response to specific protein combinations to modulate critical biological function in time and space," he added.

With more-complex signals loaded on to hydrogels, scientists could then try to control stem cell differentiation, a key step in turning science fiction into science fact.

This release has been removed upon request of the submitting institution. Please contact Stacy Anderson, Stacy.Anderson@mountsinai.org for more information.

A research team from the Institut national de la recherche scientifique (INRS) has developed a process for the electrolytic treatment of wastewater that degrades microplastics at the source. The results of this research have been published in the Environmental Pollution journal.

Wastewater can carry high concentrations of microplastics into the environment. These small particles of less than 5 mm can come from our clothes, usually as microfibers. Professor Patrick Drogui, who led the study, points out there are currently no established degradation methods to handle this contaminant during wastewater treatment. Some techniques already exist, but they often involve physical separation as a means of filtering pollutants. These technologies do not degrade them, which requires additional work to manage the separated particles.

Therefore, the research team decided to degrade the particles by electrolytic oxidation, a process not requiring the addition of chemicals. "Using electrodes, we generate hydroxyl radicals (* OH) to attack microplastics. This process is environmentally friendly because it breaks them down into CO2 and water molecules, which are non-toxic to the ecosystem," explains the researcher. The electrodes used in this process are more expensive than iron or steel electrodes, which degrade over time, but can be reused for several years.

An effective treatment

Professor Drogui envisions the use of this technology at the exit of commercial laundries, a potential source of microplastics release into the environment. "When this commercial laundry water arrives at the wastewater treatment plant, it is mixed with large quantities of water, the pollutants are diluted and therefore more difficult to degrade. Conversely, by acting at the source, i.e., at the laundry, the concentration of microplastics is higher (per litre of water), thus more accessible for electrolytic degradation," explains the specialist in electrotechnology and water treatment.

Laboratory tests conducted on water artificially contaminated with polystyrene showed a degradation efficiency of 89%. The team plans to move on to experiments on real water. "Real water contains other materials that can affect the degradation process, such as carbonates and phosphates, which can trap radicals and reduce the performance of the oxidation process," says Professor Drogui, scientific director of the Laboratory of Environmental Electrotechnologies and Oxidative Processes (LEEPO).

If the technology demonstrates its effectiveness on real commercial laundry water, the research group intends to conduct a study to determine the cost of treatment and the adaptation of the technology to treat larger quantities of wastewater. Within a few years, the technology could be implemented in laundry facilities.

A student infected with COVID-19 returning home from university for Christmas would, on average, have infected just less than one other household member with the virus, according to a new model devised by mathematicians at Cardiff University and published in Health Systems.

Professor Paul Harper and colleagues defined an equation to predict the number of secondary household infections using variables for prevalence of the virus, the probability of secondary transmission, the number of household occupants and the total number of students returning home.

The model predicts that each infected student allowed to return home would produce, on average, 0.94 secondary infections.

"With the potential movement of over 1 million UK students for the Christmas vacation, even a modest 1% infection level (meaning 10 in 1,000 students are infected, perhaps many of them without symptoms at the time of travel) would equate to 9,400 new secondary household cases across the country," says Professor Harper.

As the study does not consider transmission to the students' wider home communities or include the journey home - which may give rise to a larger number of cases, particularly if public transport is taken - the numbers are a lower bound on the likely impact of transmissions and new cases.

However, although the indicative levels of secondary infections are potentially very large, multiple strategies can be adopted to help reduce the number of students taking Covid-19 home, the authors say. These include strongly advising students not to mix in the days leading up to departure, implementing staggered departure times and facilitating mass testing of students before they head home.

The authors have provided computer code and an online app (http://bit.ly/Secondary_infections_app) to allow anyone to rerun and adapt the simulations. "The code and app are quick to run with a focus on accessibility so that a user can rapidly change the input probabilities to suit their data, thereby generating their own results based on localised parameters," the authors say.

Their results have been presented to the Welsh Government and have informed policy in relation to the two-week firebreak in Wales in October/November and for the forthcoming vacation. The data has also been communicated across the governments of England, Scotland and Northern Ireland.

Variation in consumption of market-acquired foods outside of the traditional diet -- but not in total calories burned daily -- is reliably related to indigenous Amazonian children's body fat, according to a Baylor University study that offers insight into the global obesity epidemic.

"The importance of a poor diet versus low energy expenditure on the development of childhood obesity remains unclear," said Samuel Urlacher, Ph.D., assistant professor of anthropology at Baylor University, CIFAR Azrieli Global Scholar and lead author of the study. "Using gold-standard measures of energy expenditure, we show that relatively lean, rural forager-horticulturalist children in the Amazon spend approximately the same total number of calories each day as their much fatter peri-urban counterparts and, notably, even the same number of calories each day as children living in the industrialized United States.

"Variation in things like habitual physical activity and immune activity have no detectable impact on children's daily energy expenditure in our sample," he said.

The study -- "Childhood Daily Energy Expenditure Does Not Decrease with Market Integration and Is Not Related to Adiposity in Amazonia" -- is published in The Journal of Nutrition, the American Society for Nutrition's flagship journal, and was funded by the National Science Foundation.

"That initial result alone is exciting in confirming our prior finding of relative stability in children's daily energy expenditure across different lifestyles and environments," Urlacher said. "But our study goes further. It shows that Amazonian children who eat more high-calorie market foods -- but not those who spend fewer calories every day -- consistently have more body fat.

"Together, these findings support the view that change in diet is likely the dominant factor driving the global rise in childhood obesity, particularly in the context of rapid urbanization and market integration in low- and middle-income countries," he said.

The global rate of overweight/obesity among school-age children and adolescents has risen from 4% in 1975 to 18% as of 2016, according to the NCD Risk Factor Collaboration. That reflects a major global health crisis. Children who are overweight/obese often remain so into adulthood. They have shorter life expectancy and a greater lifetime risk of developing noncommunicable diseases, including Type 2 diabetes and heart disease.

"While the most rapid rise in childhood overweight and obesity is now in rural areas and in low- and middle-income countries, few previous studies have actually measured, rather than simply estimated, children's energy expenditure in these settings to identify the cause of energy imbalance," Urlacher said.

To investigate school-age children's diets and energy expenditure during early market integration and transition to overweight/obesity, Urlacher and co-researchers* collected data among 43 rural and 34 peri-urban Shuar children in Amazonian Ecuador. The Shuar are a large indigenous population of around 50,000. Children in the rural study sample live in a geographically isolated region and rely predominantly on a subsistence-based lifestyle based on hunting, fishing, foraging and small-scale horticulture. In contrast, children in the peri-urban study sample live in a regional market center with access to roads, a hospital, stores, restaurants and other market amenities.

To measure variation in market integration among households, researchers collected information on things such as income and access to running water. They also measured children's physical activity using wearable devices and immune activity by measuring biomarkers in minimally invasive finger-prick blood samples. Most importantly, the researchers measured children's daily energy expenditure using the "doubly labeled water" stable isotope-tracking method and children's resting energy expenditure using respirometry - both participant-friendly, gold-standard techniques.

The study found that:

Peri-urban children average 65% more body fat than rural children, with more than a third of peri-urban children classified as overweight compared to zero rural children.

Peri-urban children eat more than four times as many market-acquired items as rural children.

Peri-urban and rural children have similar levels of physical activity.

Peri-urban children spend 108 calories per day less than rural children while at rest. This is related in part to 16-47% lower levels of immune activity.

Measures of market integration, immune activity and physical activity have no detectable impact on children's overall energy expenditure, with peri-urban and rural children spending roughly the same number of calories.

Variation in consumption of market foods, but not in daily energy expenditure, is related to children's body fat.

The study is the first to measure children's energy expenditure across market integration in a single population simultaneously with measures of diet, physical activity and immune activity. The finding of no effect of market integration on measured daily energy expenditure is consistent with previous reports among adults and infants, Urlacher said. It also supports an evolutionary model of childhood energy constraint and allocation trade-offs described in detail by the researchers in their 2019 paper published in the journal Science Advances.

By measuring multiple aspects of the energy balance equation simultaneously, the researchers believe that their findings provide persuasive evidence for a likely primary role of changing dietary intake, rather than reduced daily energy expenditure, in driving the rise in childhood obesity in many populations.

"Our findings are in line with a growing body of research pointing toward poor diet being the most important factor underlying the development of childhood obesity," Urlacher said. "Exercise is absolutely still a critical part of this equation and is essential for living a healthy life, but diet increasingly appears to be most directly related to children's adiposity and long-term energy balance."

The researchers plan to advance this work by collecting longitudinal data to assess individual children's lifetime development of obesity and cardiometabolic diseases. They also plan to collect more detailed dietary data and analyze a wider range of lifestyle and biological factors to identify causal pathways. Central to these efforts is determining how to best apply findings to improve children's health in low- and middle-income countries.

"Childhood obesity is a complex problem that must be addressed on many different levels, ranging from the biological to the environmental, economic, social and political," Urlacher said.

"At the end of the day, everyone working on this problem wants the same thing: to improve children's lifelong health and well-being. We hope that this work can ultimately contribute to that effort, particularly for the Shuar whose generosity and partnership made this research possible."

Tokyo, Japan - Researchers from Tokyo Metropolitan University have discovered that fruit flies with genetic modifications to enhance glucose uptake have significantly longer lifespans. Looking at the brain cells of aging flies, they found that better glucose uptake compensates for age-related deterioration in motor functions, and led to longer life. The effect was more pronounced when coupled with dietary restrictions. This suggests healthier eating plus improved glucose uptake in the brain might lead to enhanced lifespans.

The brain is a particularly power-hungry part of our bodies, consuming 20% of the oxygen we take in and 25% of the glucose. That's why it's so important that it can stay powered, using the glucose to produce adenosine triphosphate (ATP), the "energy courier" of the body. This chemical process, known as glycolysis, happens in both the intracellular fluid and a part of cells known as the mitochondria. But as we get older, our brain cells become less adept at making ATP, something that broadly correlates with less glucose availability. That might suggest that more food for more glucose might actually be a good thing. On the other hand, it is known that a healthier diet actually leads to longer life. Unravelling the mystery surrounding these two contradictory pieces of knowledge might lead to a better understanding of healthier, longer lifespans.

A team led by Associate Professor Kanae Ando studied this problem using Drosophila fruit flies. Firstly, they confirmed that brain cells in older flies tended to have lower levels of ATP, and lower uptake of glucose. They specifically tied this down to lower amounts of the enzymes needed for glycolysis. To counteract this effect, they genetically modified flies to produce more of a glucose-transporting protein called hGut3. Amazingly, this increase in glucose uptake was all that was required to significantly improve the amount of ATP in cells. More specifically, they found that more hGut3 led to less decrease in the production of the enzymes, counteracting the decline with age. Though this did not lead to an improvement in age-related damage to mitochondria, they also suffered less deterioration in locomotor functions.

But that's not all. In a further twist, the team put the flies with enhanced glucose uptake under dietary restrictions, to see how the effects interact. Now, the flies had even longer lifespans. Curiously, the increased glucose uptake did not actually improve the levels of glucose in brain cells. The results point to the importance of not just how much glucose there is, but how efficiently it is used once taken into cells to make the energy the brain needs.

Though the anti-aging benefits of a restricted diet have been shown in many species, the team were able to combine this with improved glucose uptake to leverage the benefits of both for even longer lifespans in a model organism. Further study may provide vital clues to how we might keep our brains healthier for longer.

The spread of COVID-19 in Brazil overwhelmed the health systems in all the country's regions, particularly in areas where they were already fragile, according to a collaborative effort involving the Barcelona Institute for Global Health (ISGlobal), an institution supported by the "la Caixa" Foundation, the University of Sao Paulo, the Catholic University of Rio de Janeiro, the D'Or Institute of Research and Education and the Oswaldo Cruz Foundation. The findings, published in The Lancet Respiratory Medicine, reveal that a large percentage of COVID-19 patients that were hospitalised in Brazil required intensive care and respiratory support, and many did not survive.

The COVID-19 pandemic has put an enormous strain on healthcare systems across the world by increasing the demand for healthcare professionals and the need for beds in intensive care units and respiratory support such as ventilators. However, the mortality rate among confirmed cases has greatly varied between countries and this is in great part due to differences in the capacity and preparedness of their health systems.

"To date, there is very limited data on the mortality of patients hospitalised with COVID-19 or on how the health systems have coped with the pandemic in low- and middle-income countries" explains Otavio Ranzani, ISGlobal researcher and first author of the study. Brazil, for example, is an upper middle-income country with a unified health system for its 210 million inhabitants. However, the country's unique health system has been undermined by recent economic and political crises and there is great heterogeneity across different regions of the country.

Ranzani and his colleagues used data from a nationwide surveillance system to evaluate the characteristics of the first 250,000 patients admitted to hospital with COVID-19 in Brazil, whether they required intensive care or respiratory support, and how many of them died. They also analysed the impact of COVID-19 on healthcare resources and in-hospital mortality across the country's five big regions.

The analysis shows that almost half (47%) of the 254,288 patients admitted to hospital with COVID-19 were under 60 years-old. The in-hospital mortality rate was high (38%) and rose to 60% among those admitted to the intensive care unit (ICU) and to 80% for those who were mechanically ventilated. Although COVID-19 overwhelmed the health system in all five regions, hospital admissions and mortality were considerably higher in the North and Northeast regions at the beginning of the pandemic (for example, 31% of patients aged under 60 died in hospitals in the Northeast versus 15% in the South).

"These regional differences in mortality reflect differences in access to better health care that already existed before the pandemic", explains Fernando Bozza, study coordinator and researcher at the National Institute of Infectious Disease. "This means that COVID-19 not only disproportionately affects the most vulnerable patients but also the most fragile health systems", he adds. "Brazil's health system is one of the largest across the globe to provide care to everyone free of charge and has a solid tradition in the surveillance of infectious diseases. However, COVID-19 overwhelmed the system's capacity", says Ranzani.

The authors conclude that the high mortality observed in hospitals underlines the need for improving the structure and the organisation of the health system, particularly in low- and middle-income countries. This implies increasing available resources - from equipment and consumables, to ICU beds and trained healthcare staff.

One of the most vexing aspects of the COVID-19 pandemic is doctors' inability to predict which newly hospitalized patients will go on to develop severe disease, including complications that require the insertion of a breathing tube, kidney dialysis or other intensive care. Knowledge of a patient's age and underlying medical conditions can help predict such outcomes, but there are still surprises when younger, seemingly healthier patients suffer severe complications that can lead to death.

Now, scientists at Washington University School of Medicine in St. Louis have shown that a relatively simple and rapid blood test can predict -- within a day of a hospital admission -- which patients with COVID-19 are at highest risk of severe complications or death.

The study, published Jan. 14 in JCI Insight, involved nearly 100 patients newly admitted to the hospital with COVID-19.

The blood test measures levels of mitochondrial DNA, a unique type of DNA molecule that normally resides inside the energy factories of cells. Mitochondrial DNA spilling out of cells and into the bloodstream is a sign that a particular type of violent cell death is taking place in the body.

"Doctors need better tools to evaluate the status of COVID-19 patients as early as possible because many of the treatments -- such as monoclonal antibodies -- are in short supply, and we know that some patients will get better without intensive treatments," said co-senior author Andrew E. Gelman, PhD, the Jacqueline G. and William E. Maritz Endowed Chair in Immunology and Oncology in the Department of Surgery.

"There's so much we still don't understand about this disease," he added. "In particular, we need to understand why some patients, irrespective of their ages or underlying health in some cases, go into this hyperinflammatory death spiral. Our study suggests that tissue damage may be one cause of this spiral, since the mitochondrial DNA that is released is itself an inflammatory molecule."

The researchers said the test could serve as a way to predict disease severity as well as a tool to better design clinical trials, identifying patients who might, for example, benefit from specific investigational treatments. They also said they would like to evaluate whether the test could serve as a way to monitor the effectiveness of new therapies. Presumably, effective treatments would lower mitochondrial DNA levels.

"We will need larger trials to verify what we found in this study, but if we could determine in the first 24 hours of admission whether a patient is likely to need dialysis or intubation or medication to keep their blood pressure from dropping too low, that would change how we triage the patient, and it might change how we manage them much earlier in the disease course," said co-senior author Hrishikesh S. Kulkarni, MD, an assistant professor of medicine.

The researchers, including co-first authors Davide Scozzi, MD, PhD, a staff scientist, and Marlene Cano, PhD, a postdoctoral research scholar, evaluated 97 patients with COVID-19 at Barnes-Jewish Hospital, measuring their mitochondrial DNA levels on the first day of their hospital stays. They found that mitochondrial DNA levels were much higher in patients who eventually were admitted to the ICU, intubated or died. The researchers found this association held independently of a patient's age, sex and underlying health conditions.

On average, mitochondrial DNA levels were about tenfold higher in patients with COVID-19 who developed severe lung dysfunction or eventually died. Those with elevated levels were almost six times more likely to be intubated, three times more likely to be admitted to the ICU and almost twice as likely to die compared with those with lower levels.

Further, the test predicted outcomes as well as or better than existing markers of inflammation currently measured in patients hospitalized with COVID-19. Most other markers of inflammation measured in patients with COVID-19, including those still under investigation, are general markers of systemic inflammation, rather than inflammation specific to cell death, according to the researchers.

"Viruses can cause a type of tissue damage called necrosis that is a violent, inflammatory response to the infection," Gelman said. "The cell breaks open, releasing the contents, including mitochondrial DNA, which itself drives inflammation. In COVID-19 patients, there has been anecdotal evidence of this type of cell and tissue damage in the lung, heart and kidney. We think it's possible that measures of mitochondrial DNA in the blood may be an early sign of this type of cell death in vital organs."

The researchers also emphasized that the test is quick and straightforward to perform in most hospital settings because it uses the same machinery that processes the standard PCR test for COVID-19. The method they developed allows mitochondrial DNA levels to be quantified directly in the blood. Without requiring intermediate steps to extract the DNA from the blood, the technique returned results in less than an hour.

Before they can apply for approval from the Food and Drug Administration (FDA), the scientists will need to verify that the test is accurate in a larger multi-center trial. They have plans to expand the research to more sites.

The study utilized samples obtained from the School of Medicine's COVID-19 biorepository, which was developed by co-authors Jane O'Halloran, MD, PhD, an assistant professor of medicine; Charles Goss, PhD, an instructor in biostatistics; and Phillip Mudd, MD, PhD, an assistant professor of emergency medicine.

Nearly 38 million people around the world are living with HIV, which, with access to treatment, has become a lifelong chronic condition. Understanding how infection changes the brain, especially in the context of aging, is increasingly important for improving both treatment and quality of life.

In January, researchers at the Mark and Mary Stevens Neuroimaging and Informatics Institute (USC Stevens INI), part of the Keck School of Medicine of USC, and other international NeuroHIV researchers, published one of the largest-ever neuroimaging studies of HIV. The researchers pooled magnetic resonance imaging (MRI) data from 1,203 HIV-positive individuals across Africa, Asia, Australia, Europe and North America. Their findings were published in JAMA Network Open, an open-access journal from the American Medical Association.

"Brain injury caused by HIV can lead to cognitive challenges, even in those receiving treatment," says Talia Nir, PhD, a postdoctoral scholar at the USC Stevens INI's Laboratory of Brain eScience (LoBeS) and first author of the study. "Establishing a common pattern of effects on the brain across different populations is a key step toward addressing those issues. The strength of this large dataset is that it is more representative of an era where treatment for HIV infection is widely available."

The researchers looked at the link between blood plasma, which is routinely collected to monitor immune function and treatment response, and the volume of various structures in the brain. Lower white blood cell counts generally indicate that the immune system is being suppressed. Here, they found, for example, that participants with lower white blood cell counts also had less brain volume in the hippocampus and thalamus, parts of the brain's limbic system involved in regulating memory, emotion and behavior.

These findings are important because they were largely derived from brain scans of individuals undergoing antiretroviral therapy--and they indicate that people receiving such treatment may exhibit a different brain injury signature compared to untreated individuals, which earlier studies tended to focus on. They highlight deficits in brain areas that are also vulnerable to age-related neurodegenerative diseases.

Accelerated atrophy of the hippocampus, the region that showed the most consistent effects in the study, is a hallmark of neurodegenerative diseases such as Alzheimer's disease. Common age and HIV-related pathological processes, such as inflammation and blood brain barrier impairment, may accelerate age-related neurodegenerative processes.

"There are many factors that contribute to brain tissue loss and subsequent cognitive impairments as we age, and a person's immune function is no exception," says Neda Jahanshad, PhD, associate professor of neurology at the INI and one of the senior authors of the study. "Through these large-scale efforts, we're beginning to understand the link between immune function and brain alterations in individuals living, and aging, with HIV."

The analysis was a product of the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium's HIV Working Group, established by Jahanshad and colleagues in 2013 to pool harmonized data across neuroimaging studies. The ENIGMA network at large, led by the institute's associate director, Paul M. Thompson, PhD, unites neuroimaging researchers in 45 countries to study psychiatric disorders, neurodegenerative diseases and other aspects of brain function. In addition to housing ENIGMA, the USC Stevens INI is a powerhouse of neuroimaging and related science, known for large cohort analyses of imaging, genetics, behavioral, clinical and other data. Investigators from 13 existing HIV studies in the United States, France, Serbia, Australia, Thailand and South Africa collaborated on the JAMA Network Open paper.

Next, the team will analyze imaging data over time, including diffusion imaging data, another type of MRI data that maps the brain's white matter pathways, to further understand how clinical markers of HIV infection affect the brain and the rate of neurodegeneration. As part of that ongoing work, they are inviting researchers around the world to join the ENIGMA-HIV Working Group.

"With a greater collaborative effort, we hope to be able to assess how genetic, environmental, lifestyle and treatment-related factors may further impact neurological outcomes," Nir says.

Having genitals of a certain shape and size gives male flies a major reproductive advantage, new research shows.

University of Exeter scientists examined the reproductive success of male Drosophila simulans flies both alone with a female and in various states of competition with other males.

Certain genital shapes were consistently better in terms of number of offspring sired.

However - surprisingly, given how fast genital form evolves - the selection documented was rather weak.

"Male genitals generally, and in Drosophila specifically, evolve very quickly, so we were really surprised to find this weak selection," said Professor David Hosken, of the University of Exeter.

"Selection is the major mechanism of evolution and hence where we see rapid evolution, we might reasonably expect to see relatively strong selection.

"While genitals evolve rapidly across the animal kingdom, so much so that genital form is often the only way to tell species apart, paradoxically selection on them does not appear especially strong.

"At present, it is not entirely clear how we can reconcile fast evolution with weak selection."

The study examined the effect of male genital form on reproduction after mating both with and without rival males present.

In trials when rival males were present, the impact of mating both before and after a rival was measured.

Future research will investigate possible ways to resolve the apparent paradox of fast evolution and weak selection, including potential for a permissive genetic architecture to efficiently translate any selection into rapid evolution.

Guangzhou, January 15, 2021: New journal BIO Integration (BIOI) publishes its fourth issue, volume 1, issue 4. BIOI is a peer-reviewed, open access, international journal, which is dedicated to spreading multidisciplinary views driving the advancement of modern medicine. Aimed at bridging the gap between the laboratory, clinic, and biotechnology industries, it will offer a cross-disciplinary platform devoted to communicating advances in the biomedical research field and offering insights into different areas of life science, in order to encourage cooperation and exchange among scientists, clinical researchers, and health care providers.

The issue contains an original article, three review articles, a mini review article and a commentary:

"Experimental Study on the Viscoelastic Flow Mixing in Microfluidics" by authors Meng Zhang, Wu Zhang, Zihuang Wang and Weiqian Chen. This original article discusses how the integration of microfluidic technology with blood flow research could provide a new approach to understanding related disease mechanisms and analysis of drug mixing and delivery in blood flow.

"A Review for Antimicrobial Peptides with Anticancer Properties: Re-purposing of Potential Anticancer Agents" by Cuiyu Zhong, Lei Zhang, Lin Yu, Jiandong Huang, Songyin Huang and Yandan Yao. This review article assesses several examples of antimicrobial peptides (ACPs) used in tumor therapy for their ability in penetrating or lysing tumor cell membrane, and discusses recent advances and challenges in the application of ACPs.

"Metabolic Syndrome "Interacts" With COVID-19" by Zeling Guo, Shanping Jiang, Zilun Li and Sifan Chen. In this review article, the authors focus on the close interaction between COVID-19 and metabolic syndrome, as well as the potential of repurposing metabolic-related drugs and the importance of treating metabolic diseases in COVID-19 patients.

"Coronavirus Pneumonia and Pulmonary Thromboembolism" by Mingkang Yao, Phei Er Saw and Shanping Jiang. In this review article, the authors summarize the harm that coronavirus pneumonia wreaks and highlight the clinical relationship between PTE and coronavirus infection. The potential mechanism and the prophylaxis and therapeutic measures are also discussed to call for more effort and research to investigate the strategies for PTE in COVID-19.

"Microbes in Oncology: Controllable Strategies for Bacteria Therapy" by Meng Du, Jinsui Yu, Yaozhang Yang, Fei Yan and Zhiyi Chen. In this mini review article, the authors introduce the unique advantages of bacteria in cancer treatment and highlight the issues associated with the application of bacterial therapy, focusing on the incorporation of various methodologies in the advancement of some controllable strategies in bacterial therapy.

"Understanding of the Entry Mechanism of Nanoparticles into Tumors Determines the Future Direction of Nanomedicine Development" by Phei Er Saw and Sangyong Jon. In this commentary, the authors discuss insights on the entry mechanism of nanoparticles into tumors.

Scientists at the Institute of Physics of the University of Tartu have found a way to develop optical quantum computers of a new type. Central to the discovery are rare earth ions that have certain characteristics and can act as quantum bits. These would give quantum computers ultrafast computation speed and better reliability compared to earlier solutions. The University of Tartu researchers Vladimir Hizhnyakov, Vadim Boltrushko, Helle Kaasik and Yurii Orlovskii published the results of their research in the scientific journal Optics Communications.

While in ordinary computers, the units of information are binary digits or bits, in quantum computers the units are quantum bits or qubits. In an ordinary computer, information is mostly carried by electricity in memory storage cells consisting of field-effect transistors, but in a quantum computer, depending on the type of computer, the information carriers are much smaller particles, for example ions, photons and electrons. The qubit information may be carried by a certain characteristic of this particle (for example, spin of electron or polarisation of photon), which may have two states. While the values of an ordinary bit are 0 or 1, also intermediate variants of these values are possible in the quantum bit. The intermediate state is called the superposition. This property gives quantum computers the ability to solve tasks, which ordinary computers are unable to perform within reasonable time.

Qubits of mixed-ion crystals

Researchers of the Institute of Physics of the University of Tartu showed that microcrystals, synthesised on the basis of mixed optical fluoride crystal matrices doped with erbium, praseodymium and some other ions of rare earth elements, can work as qubits that enable ultrafast optical quantum computing.

Professor Vladimir Hizhnyakov, member of the Estonian Academy of Sciences, says that when selecting the ions, their electronic states of very different properties are of utmost importance. "They must have at least two states in which the ion interaction is very weak. These states are suitable for basic quantum-logic operations on single quantum bits. In addition, a state or states are needed in which the ion interaction is strong - these states enable quantum-logic operations with two or more qubits. All these states must have a long (milli- or microsecond) lifetime and optical transitions must be allowed between these states," Hizhnyakov explained.

He says that so far, finding such electronic states of rare earth ions was not considered possible, and that is why scientists have not looked for such states suitable for qubits among them. "So far, mostly the spin states of atomic nuclei have been studied for the role of qubits. However, their frequency is a million times lower than the frequency of our quantum bits. This is why also quantum computers created on the basis of these qubits would be significantly slower than computers with our electronic states-based quantum bits," he explained.

Higher speed and fewer errors

An ultrafast working cycle would allow, according to Hizhnyakov, to overcome one the major obstacles in the creation of quantum computers. Qubits are namely very sensitive to their environment, which is why any environmental interference may lead to errors in quantum computation. "The coherence time of qubits, i.e. the duration of the pure quantum state, is very short. The faster the computation cycle, the less interference is caused by the surrounding environment in the work of qubits," Hizhnyakov explained.

It has been ascertained that the spectral hole-burning method, previously developed at the Institute of Physics of the University of Tartu can be used for selecting a set of qubits in a microcrystal acting as a computer instance. According to Hizhnyakov, this at present one of most powerful methods of optical spectroscopy, which allows to find those ions in a microcrystal that are the most suitable for use as computer qubits.

Although it is still a long way full of obstacles to an actually working quantum computer, researchers of the laser spectroscopy laboratory of the University of Tartu have started building a pilot prototype of quantum computer based on the new method. According to the researchers, they are on the threshold of presenting the work of the basic elements of the new type of quantum computer.

The completed research study is a part of the joint project "Spectroscopy of entangled states of clusters of rare-earth impurity ions for quantum computing", conducted by the Laboratory of Laser Spectroscopy and the Laboratory of Solid State Theory at the Institute of Physics of the University of Tartu.

Bone turnover markers (BTMs) in blood and urine are useful tools in monitoring osteoporosis treatment effects and may be useful for improving patient adherence.

In 2011, a Joint Committee on Bone Metabolism of the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) designated Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (β-CTX) in blood as reference bone turnover markers for bone formation and bone resorption, respectively, in osteoporosis. However, the effective clinical implementation of these recommendations requires the standardization/harmonization of commercial assays [1].

The newly published review 'Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and β-CTX in blood' describes the current status of assays for PINP and β-CTX in blood, as well as the plans for and ongoing progress towards the achievement of harmonization or standardization of commercial assays for these reference markers [2].

As well as a review of the structures of PINP and β-CTX molecules, the authors provide a succinct, referenced summary of current commercial assays, their descriptions, and performance characteristics. Key characteristics and performance specifications of the four commercially available assays for serum PINP and the three commercially available β-CTX assays are provided, as well as regression equations for the Roche and IDS iSYS automated assays for PINP and β-CTX.

Among their recommendations, the authors find:

The universal harmonization of PINP assays is a realistic goal which needs to be achieved and is a requirement for international multicentre trials to be conducted using any commercially available assays and for the development of clinical guidelines with uniform reference intervals and treatment targets.

The harmonization (if not the standardization) of commercially available assays should be possible by the use of common calibrators and the development of a reference method for PINP for subjects with a GFR > 60 mL/min/1.73 m2. Any new commercial assay developed in the future should be traceable to the new developed calibrators and reference method.

Corresponding author Professor Samuel Vasikaran, noted:

"In contrast to PINP, there is a significant bias between the two automated assays for β-CTX in blood, but the synthesis of a reference standard preparation and standardization of assays for β-CTX is possible and will be a goal of the IFCC/IOF Joint Committee on Bone Metabolism."

Professor Etienne Cavalier, Chair of the IFCC-IOF Committee of Bone Markers (C-BM), added:

"The IFCC-C-BM looks forward to working in collaboration with commercial reagent manufacturers to prepare commutable international reference materials and develop common measurement procedures for PINP and β-CTX in blood. Once harmonization or standardization, as appropriate, is achieved, regulatory authorization of these modified assays will be sought."

Professor Nicholas Harvey, Chair of the IOF Committee of Scientific Advisors, added:

"Together with IFCC, the International Osteoporosis Foundation looks forward to the important next steps which will lead to reliable reference ranges across assays and thus greater capacity for these measures to inform both clinical care and research. The project demonstrates the huge value of such international collaborations in setting the state of the art to improve bone health globally."

Over the last half-century, the probability of heat extreme events has changed by orders of magnitude in almost every region of the world, with occurrences that are now up to a hundred times more in respect to a century ago. Of all-natural disasters, extreme high temperature events are the main cause of weather-related mortality and they are also expected to be the main factor responsible for additional deaths due to climate change in the coming years.

In cities, the heat island effect creates higher temperatures than in vegetated areas. But conditions within urban areas are not equal in all their parts - either due to their physical form or to the specific needs or vulnerabilities of inhabitants - therefore not all districts of a city are equally vulnerable to heatwaves. Thus, identifying those areas which are particularly vulnerable to heat stress is particularly important to implement interventions at local level aimed at improving the capacity to cope with the impacts of heat waves on citizens' health.

The literature review "The heat-health nexus in the urban context: A systematic literature review exploring the socio-economic vulnerabilities and built environment characteristics", published on the Journal "Urban Climate" and conducted by the CMCC Foundation in collaboration with Ca' Foscari University of Venice, aimed at exploring which vulnerability factors determine the nexus between the heat and the health outcome in a urban context. The analysis selected forty articles from the vast literature on the subject, extracted from two well-known databases of peer-reviewed literature (Scopus e PubMed).

"It was central to our research to consider interdisciplinary areas that rarely coexist together in the same analysis" explains Marta Ellena, CMCC researcher and lead author of the study. "There are many studies in literature that investigate which characteristics can influence the vulnerability of individuals to heat stress, considering physical and mental health, demographics, social and economic status. In this analysis, we have added to these factors also the built environment characteristics, because the temperature-mortality relationship does not occur in a territorial vacuum. Rather, it is 'embedded' within the urban fabric, according to the context-specific way natural, physical and socio-economic processes interact."

Through the concept of "enhanced exposure", the study notes how different aspects of the physical environment can exacerbate (or mitigate) climate impacts within different places across cities.

"The population exposure is certainly linked to the physical exposure of the district to heat. The built-up areas within the cities collect solar energy during the day and release it during the night. Therefore, the urban contexts heat up and stay warm much more than the surrounding green areas, even during the night. This happens to a more or less severe extent based on their shape and design" says Margaretha Breil, urban planner and researcher at CMCC. "But we cannot consider only the physical exposure: alongside this phenomenon, known as "heat island", there are other conditions that can make a context more difficult to live in, and even more deadly".

As emerges from the study, social disadvantage can further intensify the exposure to the heat risk. Research cited in the paper found that mortality associated with heatwaves is higher where there are high levels of crime and low social cohesion. On the other hand, it was found to be less for communities characterized by extended family ties that allow for mutual care rather than forcing isolation.

"The quality of life in cities is not only determined by the shape of the urban space, but also by its accessibility. If there is access to a green area, citizens' quality of life improves. And this is true both during a pandemic, as we are all seeing in this period, and during a heatwave" explains Breil. "Nevertheless, if the green area is place of crime or heavy traffic, it is as if it did not exist: those who are afraid to go out or do not find pleasure in going out stay at home during a heatwave. And at home, the most vulnerable can even die".

As the authors highlight, understanding of these aspects and aggregate them into heat vulnerability indices could be crucial to identify and implement efficient social and physical infrastructure measures using ad hoc spatial planning considerations and urban governance decisions.

The NASA/ESA Hubble Space Telescope has observed the supernova remnant named 1E 0102.2-7219. Researchers are using Hubble's imagery of the remnant object to wind back the clock on the expanding remains of this exploded star in the hope of understanding the supernova event that caused it 1700 years ago.

The featured star that exploded long ago belongs to the Small Magellanic Cloud, a satellite galaxy of our Milky Way located roughly 200 000 light-years away. The doomed star left behind an expanding, gaseous corpse -- a supernova remnant -- known as 1E 0102.2-7219.

Because the gaseous knots in this supernova remnant are moving at different speeds and directions from the supernova explosion, those moving toward Earth are colored blue in this composition and the ones moving away are shown in red. This new Hubble image shows these ribbons of gas speeding away from the explosion site at an average speed of 3.2 million kilometers per hour. At that speed, you could travel to the Moon and back in 15 minutes.

Researchers have studied the Hubble archive looking for visible-light images of the supernova remnant and they have analysed the data to calculate a more accurate estimate of the age and centre of the supernova blast.

According to their new estimates [1], light from this blast arrived at Earth 1700 years ago, during the decline of the Roman Empire. This supernova would only have been visible to inhabitants of Earth's southern hemisphere. Unfortunately, there are no known records of this titanic event. Earlier studies proposed explosion dates of 2000 and 1000 years ago, but this new analysis is believed to be more robust.

To pinpoint when the explosion occurred, researchers studied the tadpole-shaped, oxygen-rich clumps of ejecta flung out by this supernova blast. Ionised oxygen is an excellent tracer because it glows brightest in visible light. By using Hubble's powerful resolution to identify the 22 fastest moving ejecta clumps, or knots, the researchers determined that these targets were the least likely to have been slowed down by passage through interstellar material. They then traced the knots' motion backward until the ejecta coalesced at one point, identifying the explosion site. Once that was known, they could calculate how long it took the speedy knots to travel from the explosion centre to their current location.

Hubble also measured the speed of a suspected neutron star -- the crushed core of the doomed star -- that was ejected from the blast. Based on the researchers' estimates, itmust be moving at more than 3 million kilometres per hour from the centre of the explosion to have arrived at its current position. The suspected neutron star was identified in observations with the European Southern Observatory's Very Large Telescope in Chile, in combination with data from NASA's Chandra X-ray Observatory.