Brain

Proteins are the essential substrate of learning and memory. However, while memories can last a life-time, proteins are relatively short-lived molecules that need to be replenished every couple of days. This poses a huge logistic challenge on over 85 billion neurons in the brain: billions of proteins need to be continuously produced, shipped, addressed and installed at the right location in the cell. Scientists at the Max Planck Institute for Brain Research have now addressed a bottleneck in the protein trafficking system, dendritic branch points. They find that surface diffusion of proteins is more effective at providing proteins to distal dendritic sites than cytoplasmic diffusion.

"Dendritic arborization of neurons is one of the fascinating features that evolved to increase the complexity of the interactions between neurons. However, a more complex dendritic arbor also increases the difficulty of the logistical task to supply proteins to each part of the neuron," says Tatjana Tchumatchenko, Research Group Leader at the Max Planck Institute for Brain Research who led the study.

Neurons distribute thousands of different protein species, necessary for maintaining synaptic function and plasticity across their dendritic arbor. However, the majority of proteins are synthesized hundreds of microns away from distal synapses, in the soma (its cell body). How do proteins reach distal sites? "In this study, we focused on passive protein transport which corresponds to free diffusion. In contrast to active transport via molecular motors, diffusion is energetically cheap. However, there is a downside: passive transport is slow and non-directional," explains Fabio Sartori, graduate student in the Tchumatchenko group and the lead author of the new study.

Surface diffusion is more effective

What happens when proteins encounter dendritic branch points? Branch points are like cross roads for traffic, some of the proteins will turn right, others will turn left. Cross roads for cars can be traffic bottlenecks. Similarly, the more branch points proteins meet on their journey, the lower the total protein number downstream. As a result, a neuron needs to produce more proteins to maintain a minimal protein number at distal synapses. "We used experimental data provided by our collaborators and developed a new computational framework to compare two classes of proteins, based on their "transport medium": soluble proteins that diffuse in the cytoplasm and membrane proteins," says Sartori. "Interestingly, we find that surface diffusion is on average 35 percent more effective than cytoplasmic diffusion in providing proteins to downstream locations.

Each protein has a typical distance it can cover while diffusing, this is its diffusion length. The higher this value is, the more proteins will reach distal dendrites. If a dendritic branch has a large radius, then it can carry more proteins. The combination of two factors, the width (or "radii") of dendrites and how far proteins can move, determines the number of proteins a neuron needs to produce to supply all synapses. Sartori and colleagues found that by optimizing dendritic radii, a neuron can reduce the total protein count and thereby the protein synthesis cost by several orders of magnitude. „Our results suggest that neuronal dendritic morphologies play a key role in shaping neuronal function and reflect optimization strategies and constraints imposed by protein trafficking," concludes Tchumatchenko.

Scientists have revealed that plants have a 'sealing' mechanism supported by microbes in the root that are vital for the intake of nutrients for survival and growth.

Plant Scientists from the Future Food Beacon at the University of Nottingham have demonstrated that the mechanism controlling the root sealing in the model plant Arabidopsis thaliana influences the composition of the microbial communities inhabiting the root and reciprocally the microbes maintain the function of this mechanism. This coordination of plant-microbes plays an important part in controlling mineral nutrient content in the plant. The study has been published online by the journal Science.

Gabriel Castrillo of the Future Food Beacon and lead author on the research said: "In mammals the specialized diffusion barriers in the gut are known to coordinate with the resident microbiota to control nutrient flow. Although similar regulatory mechanisms of nutrient diffusion exist in plant roots, the contribution of the microbes to their function was unknown until now.

This study has, for the first time, shown the coordination between the root diffusion barriers and the microbes colonising the root. They combine to control mineral nutrient uptake in the plant, which is crucial for proper growth and reproduction. Understanding this could lead to the development of plants more adapted to extreme abiotic conditions, with an enhanced capacity for carbon sequestration from the atmosphere. Alternatively, plants with a high content of essential mineral nutrients and the capability to exclude toxic elements could be developed."

All living organisms have evolved structures to maintain a stable mineral nutrient state. In plant roots and animal guts these structures comprise specialized cell layers that function as gate-keepers to control the transfer of water and vital nutrients.

To perform this function, it is crucial that cells forming these layers are sealed together. These seals need to maintain integrity in the presence of local microbial communities. In animals, microbes inhabiting the gut are known to influence the intestinal sealing and, in some cases, this can cause diseases.

In roots, two main sealing mechanisms have been found: Casparian Strips, which seal cells together, and suberin deposits that influence transport across the cell plasma membrane. This research shows how these sealing mechanisms in multicellular organisms incorporate microbial function to regulate mineral nutrient balance.

Food security represents a pressing global issue. Crop production must double by 2050 to keep pace with global population growth. This target is even more challenging given the impact of climate change on water availability and the drive to reduce fertilizer inputs to make agriculture become more environmentally sustainable. In both cases, developing crops with improved water and nutrient uptake efficiency would provide a solution and this.
This discovery could lead to the development of new microbial approaches to control nutrient and water diffusion, presenting new opportunities to design more resilient crops, new feeding strategies and possible ways to harness carbon dioxide through carbon sequestration.

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More than half of lesbian, gay and bisexual individuals who misuse alcohol or tobacco also have a co-occurring psychiatric disorder, compared to one-third of heterosexuals, a new University of Michigan study finds.

"The degree of disparities in alcohol, tobacco and other psychiatric disorders by sexual identity was very surprising," said Rebecca Evans-Polce, assistant research scientist at the U-M School of Nursing and first author of the study. "The differences for women are more striking."

For example, 63% of bisexual women who misused tobacco also had a psychiatric issue--anxiety or mood disorder or PTSD--compared to 46% of heterosexual women with a tobacco use disorder. Among those who met criteria for a past-year tobacco use disorder, bisexual women were also more likely to have PTSD (31%) compared with heterosexual women (13%), she said.

Discrimination, stress and childhood trauma were associated with greater odds of psychiatric disorders among lesbian, gay or bisexual individuals, with greater social support inversely associated with tobacco use disorder and coexisting psychiatric disorders.

Studies have shown that lesbian, gay and bisexual individuals have greater risk for both substance use disorders and psychiatric disorders, and the prevalence varies by gender. The U-M study is one of the few that looks at whether they are at greater risk for substance use disorders and co-occurring psychiatric disorders, Evans-Polce said.

Bisexual women, compared to heterosexual women, had a particularly high prevalence of anxiety disorders, (32.5% vs. 16% heterosexual), mood disorders (35% vs. 15% heterosexual) and post-traumatic stress disorder (21% vs. 6% heterosexual).

One of the largest differences was that bisexual individuals (18%) overall were four times more likely to have PTSD than heterosexuals (4%). Bisexual men had a particularly high prevalence of past-year alcohol use disorder (31% vs. 17% heterosexual) and tobacco use disorder (41% vs. 23% heterosexual).

More research is needed to understand why studies repeatedly find such high risk for bisexual women. One reason could be that women experience more stress and trauma.

"In addition, combined social inequities and stress resulting from both sexism and heterosexism may contribute," Evans-Polce said. "Other factors identified in research by our (Center for the Study of Drugs, Alcohol, Smoking and Health) have shown that bisexual women also report much earlier onset of alcohol use and are more likely to experience adverse childhood experiences."

The findings underscore the importance of mental health screening for sexual minorities with alcohol or tobacco use disorders, she said. Evans-Polce and colleagues analyzed 35,796 responses from the National Epidemiologic Study on Alcohol and Related Conditions-III.

MIAMI--The United Nations recently released a new report projecting future coral reef bleaching globally. The lead author of the report, Ruben van Hooidonk, is a scientist with NOAA's Cooperative Institute of Marine and Atmospheric Studies based at the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science.
Results highlights from the report include:

Under the fossil-fuel aggressive SSP5-8.5, annual severe bleaching (ASB) is projected to occur within this century for 100% of the world's coral reefs. The average projected year of ASB is 2034, nine years earlier than was projected as a global average for RCP8.5 using CMIP5 models. This suggests the previous CMIP5 generation of projections of future bleaching conditions underestimated the near future threat of annual severe bleaching.

Projected exposure to annual severe bleaching conditions varies greatly among and within countries under SSP5-8.5. Coral reefs with relatively early and late exposure to annual bleaching conditions occur in all of the ocean basins; however, some countries have more temporary refugia than others. Six of the 20 countries with the greatest reef area have >25% temporary refugia (i.e., projected ASB after 2044), including: Indonesia (35%), western Australia (70%), The Bahamas (26%), Madagascar (30%), India (37%), and Malaysia (47%). Thirteen of the 20 countries with the greatest reef area have >25% of reef areas that are projected to experience annual bleaching conditions relatively early. Some of these countries include the Philippines, Solomon Islands, Fuji, Cuba, and Saudi Arabia.

The average year for the projected timing of ASB under SSP2-4.5 is 2045, 11 years later than the average year projected under SSP5-8.5. Successful mitigation in line with the Paris Agreement would do little to provide reefs with more time to adapt or acclimate prior to severe coral bleaching conditions occurring annually.

There are three major results from the projections that assume coral adaptation levels between 0.25 and 2C: 1) Each quarter degree of assumed adaptation adds ~7 years to the global average timing of projected annual severe bleaching; 2) The great majority of coral reefs (>80%) are expected to experience ASB this century even if 2C of adaptation is assumed; 3) There is great spatial variation in the benefits to reefs, in terms of later ASB timing, at each assumed adaption level. The extent to which corals will adapt to increasing sea temperatures is unknown, but some level of adaptation is expected. If we assume 1C of adaptation, the global average ASB timing is ~30 years later than if no adaptation is assumed.

van Hooidonk is based at NOAA's Atlantic Oceanographic and Meteorological Laboratory. To view the full report, visit the UN Environment Programme at https://www.unep.org/resources/global-assessments-sythesis-report-path-to-sustainable-future

How much information can you get from a speck of purple pigment, no bigger than the diameter of a hair, plucked from an Egyptian portrait that's nearly 2,000 years old? Plenty, according to a new study. Analysis of that speck can teach us about how the pigment was made, what it's made of--and maybe even a little about the people who made it. The study is published in the International Journal of Ceramic Engineering and Science.

"We're very interested in understanding the meaning and origin of the portraits, and finding ways to connect them and come up with a cultural understanding of why they were even painted in the first place," says materials scientist Darryl Butt, co-author of the study and dean of the College of Mines and Earth Sciences.

Faiyum mummies

The portrait that contained the purple pigment came from an Egyptian mummy, but it doesn't look the same as what you might initially think of as a mummy--not like the golden sarcophagus of Tutankhamen, nor like the sideways-facing paintings on murals and papyri. Not like Boris Karloff, either.

The portrait, called "Portrait of a Bearded Man," comes from the second century when Egypt was a Roman province, hence the portraits are more lifelike and less hieroglyphic-like than Egyptian art of previous eras. Most of these portraits come from a region called Faiyum, and around 1,100 are known to exist. They're painted on wood and were wrapped into the linens that held the mummified body. The portraits were meant to express the likeness of the person, but also their status--either actual or aspirational.

That idea of status is actually very important in this case because the man in the portrait we're focusing on is wearing purple marks called clavi on his toga. "Since the purple pigment occurred in the clavi--the purple mark on the toga that in Ancient Rome indicated senatorial or equestrian rank- it was thought that perhaps we were seeing an augmentation of the sitter's importance in the afterlife," says Glenn Gates of the Walters Art Museum in Baltimore, where the portrait resides.

The color purple, Butt says, is viewed as a symbol of death in some cultures and a symbol of life in others. It was associated with royalty in ancient times, and still is today. Paraphrasing the author Victoria Finlay, Butt says that purple, located at the end of the visible color spectrum, can suggest the end of the known and the beginning of the unknown.

"So the presence of purple on this particular portrait made us wonder what it was made of and what it meant," Butt says. "The color purple stimulates many questions."

Lake pigments

Through a microscope, Gates saw that the pigment looked like crushed gems, containing particles ten to a hundred times larger than typical paint particles. To answer the question of how it was made, Gates sent a particle of the pigment to Butt and his team for analysis. The particle was only 50 microns in diameter, about the same as a human hair, which made keeping track of it challenging.

"The particle was shipped to me from Baltimore, sandwiched between two glass slides," Butt says, "and because it had moved approximately a millimeter during transit, it took us two days to find it."  In order to move the particle to a specimen holder, the team used an eyelash with a tiny quantity of adhesive at its tip to make the transfer. "The process of analyzing something like this is a bit like doing surgery on a flea."

With that particle, as small as it was, the researchers could machine even smaller samples using a focused ion beam and analyze those samples for their elemental composition.

What did they find? To put the results in context, you'll need to know how dyes and pigments are made.

Pigments and dyes are not the same things. Dyes are the pure coloring agents, and pigments are the combination of dyes, minerals, binders and other components that make up what we might recognize as paint.

Initially, purple dyes came from a gland of a genus of sea snails called Murex. Butt and his colleagues hypothesize that the purple used in this mummy painting is something else--a synthetic purple.

The researchers also hypothesize that the synthetic purple could have originally been discovered by accident when red dye and blue indigo dye mixed together. The final color may also be due to the introduction of chromium into the mix.

From there, the mineralogy of the pigment sample suggests that the dye was mixed with clay or a silica material to form a pigment. According to Butt, an accomplished painter himself, pigments made in this way are called lake pigments (derived from the same root word as lacquer). Further, the pigment was mixed with a beeswax binder before finally being painted on linden wood.

The pigment showed evidence suggesting a crystal structure in the pigment. "Lake pigments were thought to be without crystallinity prior to this work," Gates says. "We now know crystalline domains exist in lake pigments, and these can function to 'trap' evidence of the environment during pigment creation."

Bottom of the barrel, er, vat

One other detail added a bit more depth to the story of how this portrait was made. The researchers found significant amounts of lead in the pigment as well and connected that finding with observations from a late 1800s British explorer who reported that the vats of dye in Egyptian dyers' workshops were made of lead.

"Over time, a story or hypothesis emerged," Butt says, "suggesting that the Egyptian dyers produced red dye in these lead vats." And when they were done dyeing at the end of the day, he says, there may have been a sludge that developed inside the vat that was a purplish color. "Or, they were very smart and they may have found a way to take their red dye, shift the color toward purple by adding a salt with transition metals and a mordant [a substance that fixes a dye] to intentionally synthesize a purple pigment.  We don't know."

Broader impacts

This isn't Butt's first time using scientific methods to learn about ancient artwork. He's been involved with previous similar investigations and has drawn on both his research and artistic backgrounds to develop a class called "The Science of Art" that included studies and discussions on topics that involved dating, understanding and reverse engineering a variety of historical artifacts ranging from pioneer newspapers to ancient art.

"Mixing science and art together is just fun," he says. "It's a great way to make learning science more accessible."

And the work has broader impacts as well. Relatively little is known about the mummy portraits, including whether the same artist painted multiple portraits. Analyzing pigments on an atomic level might provide the chemical fingerprint needed to link portraits to each other.

"Our results suggest one tool for documenting similarities regarding time and place of production of mummy portraits since most were grave-robbed and lack archaeological context," Gates says.

"So we might be able to connect families," Butt adds. "We might be able to connect artists to one another."

The genetic code of the SARS-CoV2 virus is exactly 29,902 characters long, strung through a long RNA molecule. It contains the information for the production of 27 proteins. This is not much compared to the possible 40,000 kinds of protein that a human cell can produce. Viruses, however, use the metabolic processes of their host cells to multiply. Crucial to this strategy is that viruses can precisely control the synthesis of their own proteins.

SARS-CoV2 uses the spatial folding of its RNA hereditary molecule as control element for the production of proteins: predominantly in areas that do not code for the viral proteins, RNA single strands adopt structures with RNA double strand sections and loops. However, until now the only models of these foldings have been based on computer analyses and indirect experimental evidence.

Now, an international team of scientists led by chemists and biochemists at Goethe University and TU Darmstadt have experimentally tested the models for the first time. Researchers from the Israeli Weizmann Institute of Science, the Swedish Karolinska Institute and the Catholic University of Valencia were also involved.

The researchers were able to characterise the structure of a total of 15 of these regulatory elements. To do so, they used nuclear magnetic resonance (NMR) spectroscopy in which the atoms of the RNA are exposed to a strong magnetic field, and thereby reveal something about their spatial arrangement. They compared the findings from this method with the findings from a chemical process (dimethyl sulphate footprint) which allows RNA single strand regions to be distinguished from RNA double strand regions.

The coordinator of the consortium, Professor Harald Schwalbe from the Center for Biomolecular Magnetic Resonance at Goethe University Frankfurt, explains: "Our findings have laid a broad foundation for future understanding of how exactly SARS-CoV2 controls the infection process. Scientifically, this was a huge, very labour-intensive effort which we were only able to accomplish because of the extraordinary commitment of the teams here in Frankfurt and Darmstadt together with our partners in the COVID-19-NMR consortium. But the work goes on: together with our partners, we are currently investigating which viral proteins and which proteins of the human host cells interact with the folded regulatory regions of the RNA, and whether this may result in therapeutic approaches."

Worldwide, over 40 working groups with 200 scientists are conducting research within the COVID-19-NMR consortium, including 45 doctoral and postdoctoral students in Frankfurt working in two shifts per day, seven days of the week since the end of March 2020.

Schwalbe is convinced that the potential for discovery goes beyond new therapeutic options for infections with SARS-CoV2: "The control regions of viral RNA whose structure we examined are, for example, almost identical for SARS-CoV and also very similar for other beta-coronaviruses. For this reason, we hope that we can contribute to being better prepared for future 'SARS-CoV3' viruses."

Washington, DC, November 19, 2020 - The COVID-19 pandemic has necessitated widespread social isolation, affecting all ages of global society. A new rapid review in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports on the available evidence about children and young people specifically, stating that loneliness is associated with mental health problems, including depression and anxiety-potentially affecting them years later.

The review, which synthesizes over 60 pre-existing, peer-reviewed studies on topics spanning isolation, loneliness and mental health for young people aged between 4 and 21 years of age, found extensive evidence of an association between loneliness and an increased risk of mental health problems for children and young people.

"As school closures continue, indoor play facilities remain closed and at best, young people can meet outdoors in small groups only, chances are that many are lonely (and continue to be so over time)," said lead author, Maria Loades, DClinPsy, Senior Lecturer in Clinical Psychology at the University of Bath, UK.

"This rapid review of what is known about loneliness and its impact on mental health in children and young people found that loneliness is associated with both depression and anxiety. This occurs when studies measured both loneliness and mental health at the same point in time; when loneliness was measured separately; and when depression and anxiety were measured subsequently, up to 9 years later," Dr. Loades added. "Of relevance to the COVID-19 context, we found some evidence that it is the duration of loneliness that is more strongly associated with later mental health problems."

From the selected studies there was evidence that children and young people who are lonely might be as much as three times more likely to develop depression in the future, and that the impact of loneliness on mental health outcomes like depressive symptoms could last for years. There was also evidence that the duration of loneliness may be more important, than the intensity of loneliness, in increasing the risk of future depression among young people.

For many young people, loneliness will decrease as they re-establish social contacts and connections as lockdown eases (e.g., as they return to school or college). For some a sense of loneliness may persist as they struggle to resume social life, particularly for those who were more vulnerable to being socially isolated before lockdown.

"It's key that children and young people are allowed to return to activities such as playing together, even if outdoors, as soon as possible, and that they are able to resume attending school, which gives them a structure for their day, and provides them with opportunities to see peers and to get support from adults outside of the nuclear family," said Dr. Loades. Furthermore, she added "children need more in their strategy for easing lockdown. Alongside this, the government could target children's wellbeing in public health messaging. And meanwhile, we should also continue to embrace technology as a way to keep in touch."

So whilst we do what we can to mitigate the effects of loneliness and re-establish social connections, we also need to prepare for an increase in mental health problems, in part due to loneliness, and also due to the other unintended consequences of lockdown, such as a lack of structure, physical inactivity and social and/separation anxiety that might be triggered when resuming social interactions outside of the home.

There are several levels at which we can prepare for the heightened demand:

Take a universal approach to promoting wellbeing through public messaging, and by schools doing activities to promote wellbeing in children and young people as they resume normal activities.
Seek to identify those who are struggling with loneliness as early as possible and do so by targeted interventions to help them overcome their struggles. This may be through the provision of extra support in schools, helping them overcome anxieties about returning to school, or giving them an extra hand with reconnecting socially with peers.

For those who continue to struggle over time, and can't get back to doing the things they normally do as a result of their struggles, we need to ensure that they are made aware that services are open, and can provide specialist help, and to make sure that they know how to access this help and are supported to do so.

Rochester Institute of Technology students discovered lost text on 15th-century manuscript leaves using an imaging system they developed as freshmen. By using ultraviolet-fluorescence imaging, the students revealed that a manuscript leaf held in RIT's Cary Graphic Arts Collection was actually a palimpsest, a manuscript on parchment with multiple layers of writing.

At the time the manuscript was written, making parchment was expensive, so leaves were regularly scraped or erased and re-used. While the erased text is invisible to the naked eye, the chemical signature of the initial writing can sometimes be detected using other areas of the light spectrum.

"Using our system, we borrowed several parchments from the Cary Collection here at RIT and when we put one of them under the UV light, it showed this amazing dark French cursive underneath," said Zoë LaLena, a second-year imaging science student from Fairport, N.Y., who worked on the project. "This was amazing because this document has been in the Cary Collection for about a decade now and no one noticed. And because it's also from the Ege Collection, in which there's 30 other known pages from this book, it's really fascinating that the 29 other pages we know the location of have the potential to also be palimpsests."

The imaging system was originally built by 19 students enrolled in the Chester F. Carlson Center for Imaging Science's Innovative Freshman Experience, a yearlong, project-based course that has the imaging science, motion picture science, and photographic sciences programs combine their talents to solve a problem.

When RIT switched to remote instruction in March due to the coronavirus outbreak, the students were unable to finish building it, but thanks to a donation from Jeffrey Harris '75 (photographic science and instrumentation) and Joyce Pratt, three students received funding to continue to work on the project over the summer. Those three students--LaLena; Lisa Enochs, a second-year student double majoring in motion picture science and imaging science from Mississauga, Ontario; and Malcom Zale, a second-year motion picture science student from Milford, Mass.--finished assembling the system in the fall when classes resumed and began analyzing documents from the Cary Collection.

Steven Galbraith, curator of the Cary Graphic Arts Collection, said he was excited they discovered the manuscript leaf was a palimpsest because similar leaves have been studied extensively by scholars across the country, but never tested with UV light or fully imaged.

Collector, educator, and historian Otto Ege made leaf collections out of medieval manuscripts that were damaged or incomplete and sold them or distributed them to libraries and special collections across North America, including to the Cary Collection. Galbraith said he's excited because it means that many other cultural and academic institutions with Ege Collection leaves now may have palimpsests in their collection to study.

"The students have supplied incredibly important information about at least two of our manuscript leaves here in the collection and in a sense have discovered two texts that we didn't know were in the collection," said Galbraith. "Now we have to figure out what those texts are and that's the power of spectral imaging in cultural institutions. To fully understand our own collections, we need to know the depth of our collections, and imaging science helps reveal all of that to us."

The students are interested to see if more manuscript leaves from Ege collections across the country are palimpsests. They imaged another Ege Collection leaf at the Buffalo and Erie County Public Library that turned out to be a palimpsest and are reaching out to other curators across the country. As they begin stitching the lost text back together, paleographers can examine the information they contain.

The students have been selected to share their results at the 2021 International Congress on Medieval Studies and also plan to present the project at next year's Imagine RIT: Creativity and Innovation Festival.

When it comes to children, it is becoming clear that COVID-19 impacts them more than was initially realized. Yet there is relatively little information about SARS-CoV-2, the virus that causes the disease, in pediatric populations. Scientists at Children's Hospital Los Angeles have just published the largest pediatric COVID-19 study to date, suggesting, for the first time, a possible link between specific viral mutations and severity of the disease.

COVID-19 is not a genetic disease, but genetics of the SARS-CoV-2 virus play an important role in its spread. Mutations--mistakes in the virus' genome as it replicates--can affect how the virus transmits, and may play a role in disease severity. Understanding these links is critical to battling this pandemic.

"SARS-CoV-2 is genetically unstable," says Xiaowu Gai, PhD, the Director of Bioinformatics at Children's Hospital Los Angeles. "We tend to refer to 'the virus,' but when we think about the viral genome it's not a static, single virus but really a collection of the genetic changes in all the viruses within an infected patient."

Most of the mutations the SARS-CoV-2 virus undergoes are insignificant or can even weaken it, according to Dr. Gai, however, some mutations could change the course of the pandemic. For example, a mutation called D614G in what is called the Spike protein of the virus may contribute to increased transmissibility from person to person. At the beginning of the pandemic, the D614G mutation represented a small percentage of SARS-CoV-2 samples, but it has since increased so much that this version of the virus has taken over.

Now, Dr. Gai says, nearly every sample they sequence has this mutation. "What we don't know is whether this mutation and other mutations affect how severe the disease ends up being in a patient," he says. "That's what we're trying to find out." And for good reason--if doctors could predict which patients are more likely to have severe disease, lifesaving treatments could be administered sooner.

But there are few genetic studies published, and when it comes to understanding how the virus affects children, the data are even thinner. "There is really a lack of pediatric genomic studies for SARS-CoV-2," says Jennifer Dien Bard, PhD, Director of the Clinical Microbiology and Virology Laboratory at Children's Hospital Los Angeles. "We're trying to change that."

Drs. Gai and Dien Bard have worked within a multidisciplinary team in the Department of Pathology and Laboratory Medicine to genetically sequence every single COVID-19-positive sample they receive, putting CHLA at the forefront of pediatric viral genomic studies. Their efforts have resulted in the largest collection of clinically correlated pediatric genomic data published to date for SARS-CoV-2. Beyond sequencing the samples, the scientists are investigating how subgroups of the virus (called clades) could affect children differently.

"This study is very unique," says Dr. Dien Bard, "because in addition to having this large pool of genomic data, we're really looking at what it all means: How can we trace this virus? How do the genomics correlate with clinical outcomes? These kinds of studies just aren't out there yet, so we're trying to fill that need."

One of the trends to emerge from the study is that a certain grouping of mutations, called clade 20C, were more commonly seen in patients with the most severe COVID-19 symptoms. This study is the first to examine these potential links.

"Larger studies will be required to confirm that one subgroup of SARS-CoV-2 leads to worse prognosis," says Dr. Gai, "but this study is a clear example highlighting the importance of examining the genetics of the virus. These are the puzzle pieces that will help us get ahead of this pandemic."

OAK BROOK, Ill. - Women who experience food or housing insecurity may be at risk for undiagnosed breast cancer due to lapses in follow-up appointments, according to research being presented at the annual meeting of the Radiological Society of North America (RSNA).

"Diagnosing breast cancer at an early stage is very important for survival," said Aaron Afran, a third-year medical student at Boston University School of Medicine (BUSM). "Concerning mammography findings lead to the need for additional imaging, such as diagnostic mammography and ultrasound, and there can be a lapse in time between imaging appointments."

Researchers retrospectively reviewed the medical records of two groups of women undergoing breast imaging at Boston Medical Center (BMC) from January 2015 to December 2018. The first group included 4,959 women who underwent screening mammography and, based on a BI-RADS score of 0, were recommended for diagnostic imaging. The second group included 3,028 women who underwent diagnostic breast imaging and were recommended for a breast biopsy based on a BI-RADS score of 4 or 5.

The women were included in the study cohort if they had also completed the BMC's THRIVE screening tool designed to help primary care clinicians understand and address patients' unmet social needs, or social determinants of health (SDH).

The THRIVE questionnaire addresses eight social variables including housing, employment, transportation to medical appointments, whether the patient has trouble with caretaking responsibilities, and if the patient can afford food, medicine and utilities.

"Our goal with this study was to understand how social determinants of health influence the time interval between breast imaging and follow-up appointments," Afran said.

Of the 4,959 patients in the first group who underwent mammography screening, 1,510 patients (30.7%) had SDH data and were included in a multivariate analysis (mean age 59.1 years, 56.2% black, 18.2% white, 25.6% other race/unknown; 16.5% were Hispanic).

Of the 3,028 patients in the second group who had suspicious diagnostic imaging results, 812 patients (26.9%) had complete SDH data and were included in a multivariate analysis (mean age 60.9 years, 57.5% black, 22% white, 20.5% other race/unknown; 13.6% were Hispanic).

Results of the statistical analysis demonstrated that having food or housing insecurity was associated with longer lapses between diagnostic imaging and breast biopsy compared to interval times for women without those unmet social needs.

The study results confirm that unmet social needs are clearly relevant to patient care, noted senior author Michael D. Fishman, M.D., assistant professor of radiology at BUSM and section chief of breast imaging at BMC.

"To best serve our patient population at a safety-net hospital, we must think creatively about the social factors that are preventing our patients from receiving the best care," Dr. Fishman said. "Our findings indicate longer lapses between diagnostic imaging and biopsy for patients with unmet social needs, which begs the question: are unmet social needs associated with some amount of breast cancer mortality that could have been prevented? We seek to investigate this in future work."

According to a 2020 report from the Center for Economic and Policy Research, nearly one in three renters and one in six homeowners in the U.S. experienced housing insecurity during the first half of the year. According to the most recent data from the U.S. Department of Agriculture, 11.1% of U.S. households reported food insecurity in 2018.

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19, and all are free to access. The following were published between October 26 and November 13:

Are Older Populations at a Disadvantage? County-Level Analysis of Confirmed COVID-19 Cases in Urban and Rural America: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Seung-won Emily Choi, PhD, and Tse-Chuan Yang, PhD

"It's Pure Panic": The Portrayal of Residential Care in American Newspapers During COVID-19: Research article in The Gerontologist by Laura D. Allen, BS, and Liat Ayalon, PhD

Clinical Characteristics and Risk Factors for Mortality in Very Old Patients Hospitalized with COVID-19 in Spain: Research article in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Jose-Manuel Ramos-Rincon, MD, PhD, Verónica Buonaiuto, MD, Michele Ricci, MD, Jesica Martín-Carmona, MD, Diana Paredes-Ruíz, MD, María Calderón-Moreno, MD, Manel Rubio-Rivas, MD, PhD, José-Luis Beato-Pérez, MD, Francisco Arnalich-Fernández, MD, PhD, Daniel Monge-Monge, MD, Juan-Antonio Vargas-Núñez, MD, PhD, Gonzalo Acebes-Repiso, MD, Manuel Mendez-Bailon, MD, Isabel Perales-Fraile, MD, Gema-María García-García, MD, Pablo Guisado-Vasco, MD, Alaaeldeen Abdelhady-Kishta, MD, Maria-de-los-Reyes Pascual-Pérez, MD, Cristina Rodríguez-Fernández-Viagas, MD, Adrián Montaño-Martínez, MD, Antonio López-Ruiz, MD, Maria-Jesus Gonzalez-Juarez, MD, Cristina Pérez-García, MD, José-Manuel Casas-Rojo, MD, Ricardo Gómez-Huelgas, MD, PhD, and the SEMI-COVID-19 Network

Continuous Burdens: Puerto Rican Older Adults and COVID-19: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Catherine García, PhD, Fernando I. Rivera, PhD, Marc A. Garcia, PhD, Giovani Burgos, PhD, and María P. Aranda, PhD

"Goodness and kindness": Long distance caregiving through volunteers during the COVID-19 lockdown in India: Research article in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Senjooti Roy, PhD, and Liat Ayalon, PhD

Prioritizing Healthcare and Employment Resources during COVID-19: Roles of Benevolent and Hostile Ageism: Brief report in The Gerontologist by MaryBeth Apriceno, MA, Ashley Lytle, PhD, Caitlin Monahan, MA, Jamie Macdonald, PhD, and Sheri R Levy, PhD

Social isolation and psychological distress during the COVID-19 pandemic: A cross-national analysis: Research article in The Gerontologist by Harris Hyun-soo Kim, PhD, and Jong Hyun Jung, PhD

Life-Space Mobility and Active Aging as Factors Underlying Quality of Life among Older People before and during COVID-19 Lock-down in Finland - a Longitudinal Study: Research article in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Taina Rantanen, PhD, Johanna Eronen, PhD, Markku Kauppinen, MSc, Katja Kokko, Ph.D, Sini Sanaslahti, MSc, Niina Kajan, MSc, and Erja Portegijs, PhD

Lessons in Resilience: Initial Coping among Older Adults during the COVID-19 Pandemic: Research article in The Gerontologist by Heather R. Fuller, PhD, and Andrea Huseth-Zosel, PhD

Divergent: age, frailty, and atypical presentations of COVID-19 in hospitalized patients: Research report in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Paula Cristina Eiras Poco, MD, Márlon Juliano Romero Aliberti, MD, PhD, Murilo Bacchini Dias, MD, Silvia de Fatima Takahashi, MD, Fabio Campos Leonel, MD, Marcelo Altona, MD, Amanda Lagreca Venys Azevedo, MD, Isabela Akie Shin-Ike, MD, Bianca Aparecida Garcia, MD, Leticia Harumi Sumita, MD, Lara Mune de Oliveira Lima, MD, Flavia Barreto Garcez, MD, and Thiago J Avelino Silva, MD, PhD

"A Toxic Trend"?: Generational Conflict and Connectivity in Twitter Discourse Surrounding the #BoomerRemover Hashtag: Research article in The Gerontologist by Daniel Sipocz, PhD, Jessica D. Freeman, PhD, and Jessica Elton, PhD

Daily Stress Processes in a Pandemic: The Effects of Affect, Worry, and Age: Research article in The Gerontologist by Niccole A Nelson, MA, and Cindy S. Bergeman, PhD

In high school textbooks, human chromosomes are pictured as wonky Xs like two hotdogs jammed together. But those images are far from accurate. "For 90 percent of the time," said Jun-Han Su, "chromosomes don't exist like that."

Last year, before Su graduated with his Ph.D., he and three current Ph.D. candidates in the Graduate School of Arts and Sciences--Pu Zheng, Seon Kinrot and Bogdan Bintu--captured high-resolution 3D images of human chromosomes, the complex houses for our DNA. Now, those images could provide enough evidence to change those Xs into more complex but far more accurate symbols to not only teach the next generation of scientists but help the current generation unravel mysteries about how chromosome structure influences function.

All living things, humans included, must create new cells to replace those too old and worn-out to function. To do that, cells divide and replicate their DNA, which is wrapped into labyrinthine libraries inside chromatin, the stuff inside chromosomes. Extended in a straight line, DNA in a single cell can reach six feet, all of which gets wrapped into tight, complex structures in a cell nucleus. Just one mistake copying or re-winding that genetic material could cause genes to mutate or malfunction.

Zooming in close enough to see chromatin structure is hard. But looking at both structure and function is harder still. Now, in a paper published in August in Cell, Zhuang and her team report a new method to image the structure and behavior of chromatin together, connecting the dots to determine how one influences the other to maintain proper function or cause disease.

"It's quite important to determine the 3D organization," said Zhuang, the David B. Arnold, Jr. Professor of Science, "to understand the molecular mechanisms underlying the organization and to also understand how this organization regulates genome function."

With their new high-resolution 3D imaging method, the team started to build a chromosomal map from both wide-lens images of all 46 chromosomes and close-ups of one section of one chromosome. To image something that's still too small to image, they captured connected dots ("genomic loci") along each DNA chain. By connecting a lot of dots, they could form a comprehensive picture of the chromatin structure.

But there was a snag. Previously, Zhuang said, the number of dots they could image and identify was limited by the number of colors they could image together: three. Three dots can't make a comprehensive picture.

So, Zhuang and her team came up with a sequential approach: Image three different loci, quench the signal, and then image another three in rapid succession. With that technique, each dot gets two identifying marks: color and image round.

"Now we actually have 60 loci simultaneously imaged and localized and, importantly, identified," said Zhuang.

Still, to cover the whole genome, they needed more--thousands--so they turned to a language that's already used to organize and store huge amounts of information: binary. By imprinting binary barcodes on different chromatin loci, they could image far more loci and decode their identities later. For example, a molecule imaged in round one but not round two gets a barcode starting with "10." With 20-bit barcodes, the team could differentiate 2,000 molecules in just 20 rounds of imaging. "In this combinatorial way, we can increase the number of molecules that are imaged and identified much more rapidly," said Zhuang.

With this technique, the team imaged about 2,000 chromatin loci per cell, a more than ten-fold increase from their previous work and enough to form a high-resolution image of what the structure of chromosomes looks like in its native habitat. But they didn't stop there: They also imaged transcription activity (when RNA replicates genetic material from DNA) and nuclear structures like nuclear speckles and nucleoli.

With their 3D Google Maps of the genome, they could start to analyze how the structure shifts over time and how those territorial movements help or hurt cell division and replication.

Researchers already know chromatin is broken into different areas and domains (like deserts versus cities). But what those terrains look like in different cell types and how they function is still unknown. With their high-resolution images, Zhuang and team determined that areas with lots of genes ("gene-rich") tend to flock to similar areas on any chromosome. But areas with few genes ("gene-poor") only come together if they share the same chromosome. One theory is that gene-rich areas, which are active sites for gene transcription, come together like a factory to enable more efficient production.

While more research is needed before confirming this theory, one thing is now certain: local chromatin environment impacts transcription activity. Structure does influence function. The team also discovered that no two chromosomes look the same, even in cells that are otherwise identical. To discover what each chromosome looks like in every cell in the human body will take far more work than one lab can take on alone.

"It's not going to be possible to build just on our work," Zhuang said. "We need to build on many, many labs' work in order to have a comprehensive understanding."

Experts trained a computer to tell which skin cancer patients may benefit from drugs that keep tumors from shutting down the immune system's attack on them, a new study finds.

Led by researchers from NYU Grossman School of Medicine and Perlmutter Cancer Center, the study showed that an artificial intelligence tool can predict which patients with a specific type of skin cancer would respond well to such "immunotherapies" in four out of five cases. Specifically, the study examined patients with metastatic melanoma, skin cancer that has the capacity to spread to other organs and kills 6,800 Americans each year.

The results are important, say the study investigators, because, while the drug class studied, immune checkpoint inhibitors, has been more effective for many patients than traditional chemotherapies, half of patients do not respond to them. Adding to the urgency of efforts to determine which patients will respond, researchers say the drugs may cause side effects in many of them and are also expensive."

"Our findings reveal that artificial intelligence is a quick and easy method of predicting how well a melanoma patient will respond to immunotherapy," says study first author Paul Johannet, MD, a postdoctoral fellow at NYU Langone Health and its Perlmutter Cancer Center.

Publishing Nov. 18 in the journal Clinical Cancer Research, the new study is the first to explore artificial intelligence, or machine learning, to predict a melanoma patient's response to immune checkpoint inhibitors, say the study investigators. The team designed their computer program to "learn" how to get better at a task but without being told exactly how. Such programs build mathematical models that enable decision-making based on data examples fed into them, with the program getting "smarter" as the amount of training data grows.

For the investigation, the researchers collected 302 images of tumor tissue samples from 121 men and women treated for metastatic melanoma with immune checkpoint inhibitors at NYU Langone hospitals. Then, they divided these slides into 1.2 million portions of pixels, the small bits of data that make up digital images. These were fed into the computer along with factors such as the severity of the disease, which kind of immunotherapy regimen was used, and whether a patient responded to the treatment.

The study investigators repeated this process with 40 slides from 30 similar patients at Vanderbilt University to determine whether the results held true from a separate hospital system that used different equipment and sampling techniques.

The researchers note that aside from the computer needed to run the program, all of the materials and information used in the Perlmutter technique are already a standard part of cancer management that most, if not all, clinics use.

"A key advantage of our artificial intelligence program over other approaches such as genetic or blood analysis is that it does not require any special equipment," says study co-author Aristotelis Tsirigos, PhD, director of applied bioinformatics laboratories and clinical informatics at the Molecular Pathology Lab at NYU Langone.

Further, they argue that the AI method is more streamlined than current predictive tools such as analyzing stool samples or genetic information, which promises to reduce treatment costs and speed up patient wait times.

"Even the smallest cancer center could potentially send the data off to a lab with this program for swift analysis," says study senior author Iman Osman, MD. Osman is the Rudolf L. Baer MD Professor of Dermatology at NYU Langone and its Perlmutter Cancer Center.

Osman, who also serves as director of the interdisciplinary melanoma program and associate dean for translational research support at NYU Langone, adds that the algorithm is not yet ready for clinical use until they can boost the accuracy rate from 80 percent to 90 percent and test the algorithm at more institutions. She says the research team next plans to collect more data to better train the computer. Even at its current accuracy, Osman notes, the AI tool can still be used as a screening method to determine which patients across populations would benefit from more in-depth tests before treatment.

Air pollution experts from the University of Surrey have found that green infrastructure (GI), such as trees, can help reduce temperatures in many of Europe's cities and towns.

An urban heat island is an urban area that is significantly warmer than its surrounding rural areas. The temperature difference is typically larger at night than during the day.

With the UK government pledging to build 300,000 new homes every year, it is feared that many of the country's towns and cities will experience an increase in temperature brought about by more vehicles and building activity.

In a paper published by Environmental Pollution, experts from Surrey's Global Centre for Clean Air Research (GCARE) modelled how a UK town would be affected if its urban landscape included different types of GI.

The study focused on simulating temperature increases in the town of Guildford, UK, under different GI cover (trees, grassland and green roofs). The team adopted widely-used computer modelling systems that found that 78 per cent of Guildford was covered by grassland and trees.

The research team set out to investigate five scenarios:

What is the status quo with the current GI?

What would happen if the town had no GI?

What would happen if you replaced the current GI with only trees?

What would happen if you replaced the current GI with only green roofs?

What would happen if you replaced the current GI with only grassland?

The GCARE team found that trees are the most effective form of GI and the results showed that Guildford would be 0.128oC cooler if trees replaced all forms of GI in the town.

The team also found that trees are the best solution for the reduction in temperature spikes because they can better shade surfaces and influence aerodynamic mixing of air in the atmosphere caused by enhanced turbulence.

Professor Prashant Kumar, Director of GCARE at the University of Surrey, said: "As policymakers and political leaders rightly look to solve the nation's housing crisis, it is vitally important that they consider how this influx of new urban infrastructure will impact our environment and our planet.

"I hope that our study will give decision-makers the information they need when they are deciding which green infrastructure to establish in our communities. Our results suggest that, given a choice, trees are the most effective at reducing the urban heat island effect that many of our towns face."

Children in a Melbourne family developed a COVID-19 immune response after chronic exposure to the SARS-CoV-2 virus from their parents, a new case report has found.

The research, led by the Murdoch Children's Research Institute (MCRI) and published in
Nature Communications, showed that despite close contact with symptomatic infected parents, including one child sharing the parents' bed, the children repeatedly tested negative for COVID-19 and displayed no or minor symptoms.

MCRI's Dr Shidan Tosif said compared to adults, children with COVID-19 usually have very mild or asymptomatic infection, but the underlying differences between children's and adults' immune responses to the virus remained unclear.

The study looked at the immune profile in a Melbourne family of two parents with symptomatic COVID-19 and their three primary school aged children. Before COVID-19 took hold in Australia, the parents attended an interstate wedding without their children. After returning, they developed a cough, congested nose, fever and headache, and all family members were immediately recruited for the research study.

Samples including blood, saliva, nose and throat swabs, stools and urine were collected from the family every 2-3 days.

The researchers found SARS-CoV-2 specific antibodies in saliva of all family members and in detailed serology testing compared to healthy controls.

MCRI's Dr Melanie Neeland, who led the laboratory-based aspect of the report, said the team performed a careful analysis of the various subsets of immune cells and antibody types, showing that the children mounted an immune response that potentially contained the virus.

"The youngest child, who showed no symptoms at all, had the strongest antibody response," she said. "Despite the active immune cell response in all children, levels of cytokines, molecular messengers in the blood that can trigger an inflammatory reaction, remained low. This was consistent with their mild or no symptoms."

Dr Tosif said that while all family members fully recovered without requiring medical care, the team unfortunately could still not be certain how long, if at all, they would be protected from reinfection.

MCRI Associate Professor Nigel Crawford said the study raised the possibility that despite chronic exposure, children's immune systems allowed them to effectively stop the virus from replicating inside their cells.

"Investigating immune responses to SARS-CoV-2 across all age groups is key to understanding disease susceptibility, severity differences, and vaccine candidates," he said.