Culture

Less than a nanometer thick, stronger and more versatile than steel

image: Structure of borophane sheet. Red, hydrogen; teal, boron.

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(Image by Qiucheng Li and Chaitanya Kolluru.)

Scientists create stable nanosheets containing boron and hydrogen atoms with potential applications in nanoelectronics and quantum information technology.

What’s thinner than thin? One answer is two-dimensional materials — exotic materials of science with length and width but only one or two atoms in thickness. They offer the possibility of unprecedented boosts in device performance for electronic devices, solar cells, batteries and medical equipment.

In collaboration with Northwestern University and the University of Florida, scientists from the U.S. Department of Energy’s (DOE) Argonne National Laboratory report in Science magazine a breakthrough involving a 2D material called borophane, a sheet of boron and hydrogen a mere two atoms in thickness.

“We have tackled a significant challenge in determining the atomic structures from scanning tunneling microscopy images and computational modeling at the atomic scale with the help of computer vision.” — Argonne’s Maria Chan, nanoscientist at the Center for Nanoscale Materials.

One of the most exciting developments in materials science in recent decades has been a 2D sheet of carbon (graphene), which is one atom thick and 200 times stronger than steel. A similarly promising and newer material is an atom-thick sheet of boron, called borophene — with an “e.” A multi-institutional team, including researchers in Argonne’s Center for Nanoscale Materials (a DOE Office of Science User Facility), first synthesized borophene in 2015.

While graphene is simply one atomic layer out of the many same layers in the common material graphite, borophene has no equivalent parent structure and is very difficult to prepare. What’s more, the rapid reaction of borophene with air means it is very unstable and changes form readily.

“Borophene by itself has all kinds of problems,” said Mark Hersam, Professor of Materials Science and Engineering at Northwestern University. “But when we mix borophene with hydrogen, the product suddenly becomes much more stable and attractive for use in the burgeoning fields of nanoelectronics and quantum information technology.”

The research team grew borophene on a silver substrate then exposed it to hydrogen to form the borophane. They then unraveled the complex structure of borophane by combining a scanning tunneling microscope with a computer-vision based algorithm that compares theoretical simulations of structures with experimental measurements. Computer vision is a branch of artificial intelligence that trains high performance computers to interpret and understand the visual world.

Even though the borophane material is only two atoms thick, its structure is quite complex because of the many possible arrangements for the boron and hydrogen atoms. “We have tackled a significant challenge in determining the atomic structures from scanning tunneling microscopy images and computational modeling at the atomic scale with the help of computer vision,” said Argonne’s Maria Chan, nanoscientist at the Center for Nanoscale Materials. Given the success in unraveling this complex structure, the team’s automated analytical technique should be applicable in identifying other complex nanostructures in the future.

“What is really encouraging from our results is that we found a borophane nanosheet on a silver substrate to be quite stable, unlike borophene,” said Pierre Darancet, nanoscientist at Argonne’s Center for Nanoscale Materials. “This means it should be easily integrated with other materials in the construction of new devices for optoelectronics, devices combining light with electronics.” Such light-controlling and light-emitting devices could be incorporated into telecommunications, medical equipment and more.

“These findings are an important step in realizing borophane’s incredible potential as a two-dimensional material for nanoelectronics,” Chan said.

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DOE/Argonne National Laboratory

Report: Disparities limiting access to healthcare services in PA's underserved communities

A new report by AARP Pennsylvania and Drexel University's College of Nursing and Health Professions highlights how geographic, racial/ethnic and economic factors are combining to restrict access to health care services for many Pennsylvanians, creating disparities that have become more pronounced during the COVID-19 pandemic.

"Disrupting Disparities in Pennsylvania: Retooling for Geographic, Racial and Ethnic Growth" shows that health inequities are most acute among those living in rural and low resourced areas of the state, and among underrepresented populations (particularly Black/African American and Latino), who lack access to health care, experience digital divide and face persistent local healthcare workforce shortages. The study draws on interviews with key stakeholders statewide, a comprehensive literature review and analyses of databases on the health of Pennsylvanians.

"The pandemic is effectively exacerbating inequities for those living in poorer rural and urban areas by limiting their ability to schedule, and get to, COVID-19 vaccine appointments," said Laura N. Gitlin, PhD, dean of Drexel University's College of Nursing and Health Professions. "For years, social conditions that have led to poor health have also combined with limited resources and unequal access to quality care to create significant disparities in underserved areas of Pennsylvania. These disparities persist and have been exacerbated by COVID-19."

"The COVID-19 public health crisis has wreaked havoc on older Pennsylvanians, bringing to the forefront the deep disparities that exist in access to health care and internet connectivity," said AARP Pennsylvania State Director Bill Johnston-Walsh. "Now, more than ever, there is an urgent need to bring about systemic and structural change to promote and assure equitable solutions for older adults across the Commonwealth."

Pennsylvania demographic trends point toward a significant expansion of the number of older adults living in poverty with poor access to health care. Currently, about 40% of Pennsylvanians are 50 and older, with nearly 19% over the age of 65. Those older adults currently live predominately in rural areas and are white with low household income. However, by 2040, the Commonwealth will experience exponential growth in the aging population led by the southeastern part of the state, which is the most populous, racially and ethnically diverse region.

"Our research shows that gaps in access to health care and internet will only continue to grow as Pennsylvania's population becomes older and with the increase in number of low-income adults living in the southeastern part of the state," said Rose Ann DiMaria-Ghalili, PhD, associate dean for Interprofessional Research and Development at Drexel University's College of Nursing and Health Professions.

Geography plays a key role in access to health services and COVID-19 vaccines in other ways. The report finds that each of Pennsylvania's 67 counties has at least one "pharmacy desert," such with few to no pharmacies available. With local pharmacies serving as a key component of Pennsylvania's COVID-19 vaccine distribution plan -- especially in rural areas of the state -- pharmacy deserts directly impact access to vaccines for those at high risk.

The report shows health care costs are also a leading contributor to health inequities. For example, 6% of adults aged 45-64 do not currently have health insurance and 11% report not seeing a doctor because of cost, with the largest percentages coming from counties representing both rural and urban areas of the Commonwealth.

An increased role for telehealth services could represent a significant step toward improving access to quality health care statewide. Unfortunately, the report documents, a digital divide is furthering inequities for those without access to broadband internet and telehealth care. Few Pennsylvania counties are able to support 100% of their population connecting to the internet. In addition, 8% of households in eight counties report no internet access at all.

"Critically, older Pennsylvanians are disproportionately impacted by the digital divide, whether due to lack of access to broadband, internet or smart devices, or due to digital literacy," said Gitlin from Drexel. "The digital divide hampers their ability to access telehealth services and schedule COVID-19 vaccine appointments online."

"During the pandemic many senior centers, adult day services, libraries and other community settings remain closed. This means that older adults, who do not have access to the internet in their homes, remain disconnected," said AARP's Johnston-Walsh. "Without access to the internet, or the know-how to navigate the decentralized system of scheduling a vaccine appointment, older Pennsylvanians are at a disadvantage to protecting themselves from the pandemic."

The report finds additional barriers to accessing health care for many residents, including a significant workforce shortage. An estimated 14% of Pennsylvanians live in a medically underserved area and 22% live in an area that is both medically underserved and designated as having a health professions shortage. Residents of these areas primarily live in rural areas, or are of minority status, poorly educated, live in poverty and have limited access to transportation.

"Not only do we need more health professionals and direct care workers, we need to prepare the health care workforce to be culturally competent and capable of addressing age-related health care issues including preventing and managing chronic conditions and their impact on everyday activities of living and aging in place at home," said Drexel's Gitlin.

"Solutions to help disrupt health disparities impacting the 50-plus population in Pennsylvania are urgently needed," said Angela Foreshaw-Rouse, operations and outreach manager for AARP Pennsylvania. "The time is now to assure that all individuals are able to live long and healthy lives regardless of where they live or their racial/ethnic background."

Highlights of Disrupting Disparities in Pennsylvania: Retooling for Geographic, Racial and Ethnic Growth include:

COVID-19:

Each of the 67 counties in PA have at least one pharmacy desert (which was defined at census tract level). Pharmacy deserts will lead to vaccination deserts with vaccine rollout, causing greater disparities in those areas.

Community-based organizations that provide services for older adults report challenges in delivering virtual services during the pandemic, reporting technology as a barrier.

During the pandemic many senior centers, libraries and other community settings remain closed and older adults who do not have access to the internet in their homes via computer or smartphone remain disconnected.

In addition to access-related challenges, distrust of the health care system, especially among Black Pennsylvanians, and safety concerns may contribute to COVID-19 vaccination hesitancy.

Geographic Challenges:

About 23% of older adults living in rural communities have cognitive difficulties or difficulties with independent living and lack access to community-based services, such as adult day services, personal care homes and low-income housing, supports that are commonplace in urban areas.

An estimated 14% of Pennsylvanians live in a medically underserved area and 22% live an area that is both medically underserved and designated a health professions shortage area. Residents of these areas primarily live in rural areas, or are of minority status, poorly educated, live in poverty and have limited access to transportation.

Rural communities currently have roughly half the physicians per capita as non-rural areas. There are also less hospital beds compared to urban areas and several rural counties have no hospitals.

Access to Health Care:

In PA, 6% of adults 45-64 years of age report not having health insurance and 11% report not seeing a doctor because of cost. The areas with the highest percentage of adults 45-64 years of age without health care coverage include Pike, Monroe, Susquehanna and Wayne Counties at 13% with Philadelphia at 10%.

The cost barrier is a critical issue: 18% of those 45-64 living in Lackawanna, Luzerne and Wyoming and Erie County, and 15% of those living in Philadelphia County reported not able to see a doctor in the past year because of cost.

Lacking broadband is an impediment to delivering telehealth services in rural areas.

Health and Digital Literacy:

Some 7% of Pennsylvanians 50+ report difficulty in understanding information from a health care professional, and older adults report a slightly higher rate of not being able to understand written information.

Individuals 65+ are less likely to use electronic devices to look for health information, communication with their physician, look up test results and track health charges.

Digital Divide:

Only in Bucks, Chester, Delaware and Montgomery Counties can over 95% of the population use or connect to the internet in their household.

12% of counties (Cameron, Clearfield, Forest, McKeon, Philadelphia, Sullivan, Union and Warren) have 8% of households with no internet access.

Smartphones can lessen the internet access divide by enabling individuals to access the internet on their phone.

During the pandemic, many senior centers, libraries and other community settings remain closed and older adults, who do not have access to the internet in their homes via computer or smartphone, remain disconnected.

Lack of broadband internet is an impediment to delivering telehealth services in rural areas.

Workforce Shortage and Competencies:

Pennsylvania faces a significant workforce shortage in health care professionals including direct care workers, dentists, nurse practitioners, physical therapists, physicians, physician assistants, pharmacists, psychiatrists, registered dietitians, registered nurses, occupational therapists and social workers.

An estimated 14% of Pennsylvanians live in a medically underserved area and 22% live an area that is both medically underserved and designated a health professions shortage area.

Residents of these areas primarily live in rural areas, or are of minority status, poorly educated, live in poverty and have limited access to transportation.

The workforce is unprepared to address complex and co-morbid conditions and lack training in the specialty of geriatrics.

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Drexel University

Women had 'alarmingly high rates' of mental health problems during start of the pandemic

A study at the University of Chicago Medicine found U.S. women experienced increased incidence of health-related socioeconomic risks (HRSRs), such as food insecurity and interpersonal violence, early in the COVID-19 pandemic. This was associated with "alarmingly high rates" of mental health problems, including depression and anxiety. The research was published April 5 in the Journal of Women's Health.

Other studies have found evidence for higher rates of anxiety and depression and related issues, such as alcohol overuse, connected to the pandemic -- but this study is the first to link early pandemic-related changes in HRSRs to mental health effects in women.

"Most national surveys tend to report aggregated findings rather than stratifying by gender," said Stacy Lindau, MD, Professor of Obstetrics and Gynecology and Medicine-Geriatrics at UChicago Medicine. "Those early studies gave us snapshots of the health and behaviors of the whole population, but gave us limited insight on women. Yet, women constitute the majority of the essential workforce, including healthcare workers, and we wanted to make sure that women's experiences were being documented."

The researchers conducted a survey of 3,200 U.S. women over the age of 18 between April 10 and 24, 2020. More than 40% of participants reported experiencing at least one HRSR during the prior year, which included issues such as food insecurity, housing instability, difficulties with their utilities, transportation challenges and interpersonal violence; 22% reported experiencing two or more HRSRs during the year before the pandemic.

But by the first spring of the pandemic, nearly half of all women -- including 29% of those who did not experience pre-pandemic HRSRs -- reported new (incident) or worsening HRSRs. The greatest challenge was an increase in food insecurity. Nearly 80% of those without pre-pandemic HRSRs who reported a new HRSR became food insecure. Almost a quarter experienced interpersonal violence.

"It's incredible and concerning that nearly half of women -- including more than a quarter of those who had no health-related socioeconomic risks -- had experienced incident or worsening conditions," said Lindau. "It's even more striking that more than a quarter of the women who had none of these risks in January or February 2020 now had at least one by April. That points to the likelihood that a large portion of women were already near the edge of vulnerability. When the world shut down, transportation became more difficult, food access became harder, and very soon after the crisis began, many women found themselves struggling to meet basic needs."

Those who experienced socioeconomic risks prior to the pandemic also experienced the greatest increase in insecurity. Three-quarters of women with pre-pandemic HRSRs experienced new or worsening risks during the early pandemic; 38% experienced two or more, with more than half experiencing increased food insecurity.

Significantly, the survey also found that 29% of women reported symptoms of depression and anxiety -- nearly twice the estimated pre-pandemic rates. One in six women screened positive for symptoms of post-traumatic stress, a rate similar to that seen after other significant disasters, such as the SARS and Ebola epidemics. Those who experienced at least one new or worsening HRSR were at significantly higher risk of experiencing anxiety and post-traumatic stress.

"Given very high rates of these problems, we're really concerned about the current capacity of our mental health system," said co-author Marie Tobin, MD, Professor of Psychiatry at UChicago Medicine. "Women are principally responsible for parenting, family caregiving and other essential work -- they are key to managing and recovering from this pandemic, and now are afflicted by very significant socioeconomic risk levels that appear to be drivers of anxiety, depression and traumatic stress. We should be especially concerned that socioeconomically vulnerable women are at high risk for developing pandemic-related psychiatric morbidity."

These results, the investigators say, should help spur healthcare providers and policy makers to address the underlying and modifiable health-related socioeconomic risk factors in order to prevent these negative outcomes.

"We can't change a person's gender, but we can act to ensure that all people have the basic nutrition and shelter they need to survive," said Lindau. "We can intervene on transportation barriers, we can pass policies to delay or offset rent or utilities payments. These are modifiable factors that can be addressed by leveraging the humanitarian resources of our communities and implementing policies that ensure everyone can live independently with their basic needs met. Ensuring equitable access to the basics would be a powerful buffer against mental illness in general and could help mitigate costly and painful mental health crisis among women and everyone who depends on us in the context of this and other public health emergencies."

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University of Chicago Medical Center

New method expands the world of small RNAs

image: Discovering more 'RNA code' by PANDORA-seq (right optic) compared to traditional RNA-seq (left optic).

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Qi Chen lab, UC Riverside.

RIVERSIDE, Calif. -- A team led by a biomedical scientist at the University of California, Riverside, has developed a new RNA-sequencing method-- "Panoramic RNA Display by Overcoming RNA Modification Aborted Sequencing," or PANDORA-seq -- that can help discover numerous modified small RNAs that were previously undetectable.

RNA plays a central role in decoding the genetic information in DNA to sustain an organism's life. It is generally known as the intermediate molecule used to synthesize proteins from DNA. Cells are full of RNA molecules in complex and diverse forms, two main types being ribosomal RNA, or rRNA; and transfer RNA, or tRNA; which are involved in the synthesis of proteins.

Small RNAs play essential roles in health and diseases, including cancer, diabetes, neurological diseases, and infertility. Examples of small RNAs are microRNA; piwi-interacting RNA, or piRNA; and tRNA-derived small RNA, or tsRNA. Small RNAs can get modified by chemical groups and thus acquire new functions.

The development of high-throughput RNA sequencing technologies -- useful for examining the quantity and sequences of RNA in a biological sample -- has uncovered an expanding repertoire of small RNA populations that fine-tune gene expression and protect genomes.

"PANDORA-seq can be widely used to profile small RNA landscapes in various physiological and disease conditions to facilitate the discovery of key regulatory small RNAs involved in these conditions," said Qi Chen, an assistant professor of biomedical sciences in the UCR School of Medicine, who led the study published today in Nature Cell Biology. "Modified small RNAs wear an 'invisibility cloak' that prevents them from being detected by traditional RNA-sequencing methods. How many such modified RNAs are there? What is the origin of their sequences? And what exactly is their biological function? These are questions PANDORA-seq may be able to answer."

PANDORA-seq employs a stepwise enzymatic treatment to remove key RNA modifications, which then takes off the invisibility cloak used by the modified small RNAs.

"PANDORA-seq has opened Pandora's box of small RNAs," said Tong Zhou, a bioinformatician at the University of Nevada, Reno School of Medicine and a co-corresponding author of the study. "We can now dance with these once invisible partners in the RNA ballroom."

According to Chen, PANDORA-seq uncovers a surprising small-RNA landscape that is dominated by tsRNAs and rRNA-derived small RNAs, or rsRNAs, rather than microRNAs, which were previously believed to dominate many mammalian tissues and cells.

"With PANDORA-seq, we found unprecedented microRNA/tsRNA/rsRNA dynamics when somatic cells are reprogrammed to induced pluripotent stem cells, which are generated by adult cells and have properties similar to those of embryonic stem cells, making them capable of differentiating into all cell types of the body," said Sihem Cheloufi, an assistant professor of biochemistry at UCR and a co-corresponding author of the paper. "Some tsRNAs and rsRNAs can impact protein synthesis and even affect lineage differentiation in embryonic stem cells."

Chen explained the current best-studied classes of small RNAs in mammals are microRNAs, which are abundant in mammalian somatic cells and control the kind and amount of proteins the cells make; and piRNAs, which are mainly expressed in the testis and modulate germ cell development.

"Currently, these small RNAs can be comprehensively profiled by high-throughput methods such as RNA sequencing," he said. "However, the widely used small RNA sequencing protocols have intrinsic limitations, which prevent certain modified small noncoding RNAs from being detected during RNA sequencing. PANDORA-seq overcomes these limitations."

Junchao Shi, a doctoral student working in Chen's lab and the research paper's first author is enthusiastic about the use of PANDORA-seq.

"The new method could revolutionize the view of small RNA landscapes," he said. "Frankly, all previous studies using traditional RNA-sequencing may now need to be revisited."

Cheloufi said the team now wants to understand how tsRNA/rsRNA are generated, how they function in stem cells, and how they orchestrate cell fate decisions during development.

"Answers to these questions are timely to develop diagnostic tools, identify therapeutic targets, and advance regenerative medicine," she said.

While developing PANDORA-seq, Chen was reminded of the parable of the blind men and the elephant, which teaches truth is only revealed when various parts come together.

"We sometimes forget the big picture, being focused on just a small part of it," he said. "Perhaps the only way to arrive at total truth -- the big picture -- is to push against our boundary of knowledge and confirm the revealed truth with newly devised technology."

"It is fascinating to observe down the lenses of a microscope in the lab the profound cell fate change during cellular reprogramming and differentiation," said Reuben Franklin, a doctoral student in Cheloufi's lab and a coauthor on the study. "But PANDORA-seq allows us to eavesdrop on the molecular players during these processes."

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University of California - Riverside

Reopen and regenerate: Exosome-coated stent heals vascular injury, repairs damaged tissue

Researchers from North Carolina State University have developed an exosome-coated stent with a "smart-release" trigger that could both prevent reopened blood vessels from narrowing and deliver regenerative stem cell-derived therapy to blood-starved, or ischemic, tissue.

Angioplasty - a procedure that opens blocked arteries - often involves placing a metal stent to reinforce arterial walls and prevent them from collapsing once the blockage is removed. However, the stent's placement usually causes some injury to the blood vessel wall, which stimulates smooth muscle cells to proliferate and migrate to the site in an attempt to repair the injury. The result is restenosis: a re-narrowing of the blood vessel previously opened by angioplasty.

"The inflammatory response that stents cause can decrease their benefit," says Ke Cheng, corresponding author of the research. "Ideally, if we could stop smooth muscle cells from over-reacting and proliferating, but recruit endothelial cells to cover the stent, it would mitigate the inflammatory response and prevent restenosis." Cheng is the Randall B. Terry Jr. Distinguished Professor in Regenerative Medicine at NC State and a professor in the NC State/UNC-Chapel Hill Joint Department of Biomedical Engineering.

There are drug-eluting stents currently in use coated with drugs that discourage cell proliferation, but these anti-proliferative drugs also delay stent coverage by endothelial cells - which are the cells healthcare providers want to coat the stent.

To solve this problem, Cheng and his team developed a stent coating composed of exosomes derived from mesenchymal stem cells. Exosomes are tiny nano-sized sacs secreted by most cell types. The idea behind the coating was two-fold: first, since the exosomes are composed of materials not much different from cell membranes they 'camouflage' the stent to trick smooth muscle cells and the body's immune system. Second, the exosomes promote coverage of the stent by endothelial cells and, in the case of injury, travel downstream to the site to promote tissue repair.

To prevent premature depletion of the therapy, the stent releases exosomes when it encounters reactive oxygen species (ROS) - which are more prevalent during an inflammatory response.

"Think of it as a smart release function for the exosomes," Cheng says. "Ischemic reperfusion injuries, which occur when blood flow is diminished and then reestablished, create a lot of ROS. Let's say the heart is damaged by ischemia. The enhanced ROS will trigger the release of the exosomes on the stent, and regenerative therapy will travel through the blood vessel to the site of the injury."

The research team performed in vitro testing to ensure biocompatibility and test the release mechanism. They found that in the presence of ROS, the exosomes released up to 60% of their secretions within 48 hours post-injury.

In a rat model of ischemic injury, the researchers compared their exosome-eluting stent (EES) to both a bare metal stent (BMS) and a drug-eluting stent (DES). They found that in comparison to the BMS, their stent performed better in both decreasing stenosis and promoting endothelial coverage. While the DES performed similarly to the EES in preventing restenosis, the EES was less injurious to the vessel wall and had better endothelial coverage overall. In addition, the exosomes released from EES promoted muscle regeneration in rats with hind limb ischemia. The researchers plan to test the stent in a large animal model with an eye toward eventual clinical trials.

"This bioactive stent promotes vascular healing and ischemic repair, and a patient wouldn't need additional procedures for regenerative therapy after the stent is in place," Cheng says. "The stent is the perfect carrier for exosomes, and the exosomes make the stent safer and more potent in tissue repair."

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North Carolina State University

For 80% of Americans with resolved drug problem, significant personal achievements

BOSTON - Addiction is associated with social exclusion, loss of access to resources, and general disengagement from civic life. Now, a study recently published in the journal Psychology of Addictive Behaviors and led by David Eddie, PhD, of the Massachusetts General Hospital's Recovery Research Institute has found that the majority of Americans who have resolved an alcohol or other drug problem report achievements related to self-improvement, family engagement, and civic and economic participation since resolving their addiction. Additionally, it appears these achievements accumulate with time in addiction recovery.

Incorporating data from the Recovery Research Institute's landmark 2017 National Recovery Study, which indicated for the first time that 23.3 million Americans consider themselves to have resolved a significant alcohol or other drug problem, this study is the first to report the national prevalence of personal, civic, and economic achievements among people in addiction recovery.

"Individuals in addiction recovery face numerous challenges, yet in spite of this, findings from this study show that most individuals are able to rebuild important aspects of their lives," says Eddie. "And perhaps more importantly, we saw that these achievements were associated with greater happiness, well-being and quality of life."

These study results challenge commonly held beliefs about the nature of substance use disorders as constantly recurring disorders with little room for improvement. "The fact of the matter is that addiction is a good-prognosis disorder with significant improvement over time in recovery," says co-author John Kelly, PhD, director of the Recovery Research Institute. "With more years in recovery, individuals achieved an increasing number of achievements, which are then supportive of ongoing remission and recovery."

The study authors also note that there are certain individual factors associated with accrual of achievements, including (but not limited to) race, education level, age of initiation of regular substance use, and co-occurring psychiatric disorders. However, Eddie cautions that this shouldn't be taken to mean there are some who can't accomplish significant personal achievements after resolving an addiction: "Recovery is achievable for everyone, and the majority of Americans who resolve their substance use problem go on to accrue numerous life achievements. At the same time, there are many individuals who face greater barriers and hardships as they attempt to rebuild their lives, and as a society we should be addressing the barriers that hamper their rebuilding efforts."

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Massachusetts General Hospital

Surprising disconnect between physical characteristics and genetic ancestry in certain

A new study by Stanford University biologists finds an explanation for the idea that physical characteristics such as skin pigmentation are "only skin deep." Using genetic modeling, the team has found that when two populations with distinct traits combine over generations, traits of individuals within the resulting "admixed" population come to reveal very little about individuals' ancestry. Their findings were published March 27 in a special edition of the American Journal of Physical Anthropology on race and racism.

"When two founding groups first come together, a visible physical trait that differed between those founders initially carries information about the genetic ancestry of admixed individuals," says Jaehee Kim, a postdoctoral research fellow in biology at Stanford and first author of the study. "But this study shows that after enough time has passed, that's no longer true, and you can no longer identify a person's genetic ancestry based only on such traits."

A diminishing correlation

Working with Stanford biology professor Noah Rosenberg and others, Kim built a mathematical model to better understand genetic admixture - the process by which two populations that have long been separated come together and create a third admixed population with ancestral roots in both sources. They specifically studied how the relationship between physical traits and genetic admixture level changes over time.

The researchers considered several scenarios. In one, individuals within the admixed population mated randomly. In others, they were more likely to seek out partners with similar genetic admixture levels or who had similar levels of a trait, in a process known as assortative mating.

The study found that over time, traits that might have initially been indicative of an individual's genetic ancestry ultimately no longer carried that information. While this decoupling of ancestry and traits occurred more slowly if mating was assortative rather than random, decoupling still happened in all scenarios.

"In the model, if assortative mating depends on a genetically inherited trait, a correlation between the trait and genetic ancestry would last longer than if mating had occurred randomly, but the correlation would still disassociate eventually," said Rosenberg, senior author of the paper, who holds the Stanford Professorship in Population Genetics and Society in the School of Humanities and Sciences.

The team's research was inspired in part by a study conducted by a different team in Brazil, a country with much genetic admixture in its history. After sampling individuals and studying their genomes, the biologists from the 2003 study hypothesized that decoupling occurred between physical traits and genetic admixture and claimed that over time traits such as skin pigmentation revealed little about the fraction of a person's ancestors originating from European, African or Native American origins. The Stanford team found that their model largely supported this hypothesis.

Only skin deep

To understand the decoupling, the researchers say, consider a trait such as skin pigmentation that is due in part to variations among a series of genes. If a person happens to receive most of their genetic ancestry from one population but the key genetic variants that determine their skin pigmentation from another, their skin pigmentation may appear to be a "mismatch" to their genetic ancestry. The reshuffling of genetic variants that occurs in every generation increases the probability of such mismatches.

The researchers recognize that there are limitations to their modeling approach. The model didn't consider environmental conditions that also play a role in trait development. A person's height, for example, has some genetic basis, but also depends on factors like nutrition. The model also focused only on scenarios in which the initial admixture happened all at once, and didn't explore the role of new members of the source populations entering the admixed population over time. In the future, Rosenberg plans to add some of these features into the initial model.

According to Kim, the new findings have important implications for understanding the social meaning of physical traits.

"When societies attach social meaning to a trait like skin pigmentation, the model suggests that after admixture has been ongoing for enough time, that trait is not going to be telling us much about genetic ancestry - or about other traits that are based in genetics," she said.

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Stanford University

Virtual "urgent care" may lead to higher rates of downstream follow-up care

Even before the pandemic made telehealth a hot topic, people with minor urgent health needs had started to turn to companies that offer on-demand video chats with physicians that they don't normally see.

Insurers and employers even started buying access to this direct-to-consumer form of virtual care, hoping it might reduce in-person care, including emergency department visits.

But a new University of Michigan study casts some doubt on whether that will actually happen.

Published in the April issue of Health Affairs, the study finds that patients who had an on-demand virtual care visit for an upper respiratory infection in the three years before the pandemic began were slightly more likely to receive additional follow-up care than similar patients who had their first visit in person.

The study compared data from more than 28,700 virtual visits with data from more than 57,400 in-person visits for acute respiratory infections in 2016 through 2019. Those visits, and any follow-up care, were all covered by a large insurer. All the virtual visits were done through a direct-to-consumer telehealth company that the insurer had partnered with.

The authors say it's important to note that the vast majority of the patients did not require any further care for their infections, which included ear infections, bronchitis, laryngitis, sore throat and pneumonia.

But 10.3% of the patients first seen through a direct-to-consumer telehealth visit ended up having an in-person visit in the next week, compared with 5.9% of those who had their first visit in person. This includes second telemedicine visits or visits to clinics, urgent care centers and emergency rooms.

Less than 1% of all the patients in the study visited an emergency department after their initial visit, and the percentage was only slightly lower among people whose first visit was through a direct-to-consumer virtual provider compared with those who started with an in-person visit.

Kathleen Li, M.D., M.S., is the first author of the paper and an alumna of the IHPI Scholars program at the U-M Institute for Healthcare Policy and Innovation, and conducted the study as part of the institute's telehealth research effort.

She notes that direct-to-consumer telehealth providers usually don't have access to patients' electronic health records, so they may not know the patient's full medical history or underlying conditions.

As an emergency physician at Michigan Medicine, Li notes that often patients will come to the ED after trying to reach their primary care physician and not being able to get an appointment quickly.

Li was a co-author on a recent National Poll on Healthy Aging report from IHPI that found that 1 in 8 older adults had gone to the ED after not being able to get a timely appointment with their regular provider.

"If an appointment with a patient's regular provider isn't available right away, or the patient isn't able to get to the clinic in person during standard business hours, on-demand virtual care does offer convenience," she says. "But things have changed so much with the pandemic, and more primary care providers are now offering telehealth visits with themselves or members of their teams. It remains to be seen how primary care-based telehealth models will affect downstream use and cost of care."

Senior author Chad Ellimoottil, M.D., M.Sc., who directs IHPI's Telehealth Research Incubator, says that while the insurance claims data in the study were available to the IHPI team, that may not be the case for most direct-to-consumer telehealth, especially if the patient pays directly rather than using insurance.

"As more companies enter the marketplace of direct-to-consumer telehealth, it's going to be important to understand the outcomes for patients, and the broader implications for the health care system," says Ellimoottil, a urologist and telehealth researcher. "Data transparency is essential. We need to be able to directly compare outcomes of patients seen by direct-to-consumer telehealth companies with in-person care and with telemedicine provided by the patient's own primary care provider."

For employers that offer a direct-to-consumer telehealth option through their benefits package, Li says, the bottom line comes down to balancing how much the instant access may result in an increase in visits or additional follow-up care, against the benefit of less time spent away from work and a potential reduction in inappropriate emergency department visits.

"We need to optimize both the use of telehealth and of in-person emergency care," she says.

Credit: 
Michigan Medicine - University of Michigan

Nearly half of those convicted of sharing explicit images of partners online show remorse

In a new study, researchers found nearly half of those who share explicit images of others without permission feel remorse after the fact and 24% try to deflect blame onto victims. Amy Hasinoff, a researcher at the University of Colorado Denver, joined Danish researcher Sidsel K. Harder, to take a deeper dive into the issue of sexual abuse and image sharing.

Hasinoff and Harder looked at how people who shared explicit images online spoke to police officers about the harmful acts they committed. While looking over cases where the image-sharer was caught and convicted, researchers found nearly half, 44%, of those cases involved the guilty party acknowledging sexual abuse, acknowledging shame, and telling redemption stories about making better choices in the future.

Deflecting Shame

In almost a quarter of all cases, people who committed image-based abuse assign the primary blame to the victim, consistent with the neutralization technique of denial of the victim. Denial of the victim is when the offender claims that the victim deserved what happened to them. The offender may justify the wrongdoing by saying that the victim was a bad person or deserved the abuse in some way.

"Sometimes, people choose to share sexual images of others without their permission," said Hasinoff. "They do this specifically to cause harm, and sometimes they do it out of negligence and carelessness or because they think it doesn't matter or they feel entitled."

Narrating Redemption

While many of those convicted of non-consensual image sharing shift the blame to someone else, 44% show some sort of remorse and acknowledge that they committed harmful actions. These people all plead "guilty" and express that they were ashamed of what they have done as a result of their anger with the victims, their need for respect from male peers, or their carelessness.

"What is particularly striking about this study is that a group of people who've done something really abusive are able to manage their shame by transforming their negative emotions into redemption stories about their better future selves," said Hasinoff. "At the same time, telling a redemption story, apologizing, or expressing shame does not guarantee a victim's or a community's forgiveness."

A redemption story is when a person who's done something bad talks about how they plan to never repeat that in the future and can include trying to make amends too. In this case, making amends could include apologizing, paying for services to remove images from the internet, or other ways of making things right with the person they harmed.

Hasinoff points out there are limitations to any study on shame and remorse since you never know if it is sincere. At the same time, emotions are social, especially shame, meaning that we can only ever feel it in relation to other people, and so it always depends on context. Even when we feel shame on our own, in our own minds, without others present, shame is typically still about what we think others think about us.

Why is this significant?

According to researchers, rather than stigmatizing people who have shared images non-consensually, future interventions might focus on helping them accept the guilt for their actions, and future research might investigate how to create the best conditions for someone who has shared images without consent to acknowledge the harmfulness of what they have done.

"Instead of seeing everyone who shares a sexual image without permission as an irredeemable 'bad person' and just punishing them, it might be better for the victim if the person who committed this kind of harm could get some guidance and help to understand the effects of what they did and to try to find meaningful ways to repair that harm," said Hasinoff. "This is a society-wide problem that is rooted in gender norms - like the way some men feel entitled to treat women as sexual objects - so part of the solution has to be helping people understand why and how to unlearn those ideas."

Credit: 
University of Colorado Denver

Doping by athletes could become tougher to hide with new detection method

WASHINGTON, April 5, 2021 -- As the world awaits the upcoming Olympic games, a new method for detecting doping compounds in urine samples could level the playing field for those trying to keep athletics clean. Today, scientists report an approach using ion mobility-mass spectrometry to help regulatory agencies detect existing dopants and future "designer" compounds.

The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2021 is being held online April 5-30. Live sessions will be hosted April 5-16, and on-demand and networking content will continue through April 30. The meeting features nearly 9,000 presentations on a wide range of science topics.

Each year, the World Anti-Doping Agency (WADA) publishes a list of substances, including steroids, that athletes are prohibited from using. However, it can be difficult to distinguish an athlete's natural or "endogenous" steroids from synthetic "exogenous" ones administered to boost performance.

And regulatory bodies face another challenge: "As quickly as we develop methods to look for performance-enhancing drugs, clandestine labs develop new substances that give athletes a competitive advantage," says Christopher Chouinard, Ph.D., the project's principal investigator. Those designer drugs evade detection if testing labs don't know to look for their specific chemical structures.

Chouinard's team at Florida Institute of Technology is trying to outsmart cheaters with an assay that can differentiate endogenous and exogenous steroids and can also anticipate the structure of new compounds that might show up in athletes' urine samples.

Currently, testing labs analyze samples using tandem mass spectrometry (MS) and gas or liquid chromatography. These approaches break up molecules in the sample and separate the fragments, yielding spectra that can reveal the identity of the original, intact compounds. But it can be tough to differentiate molecules with minor structural differences -- including isomers -- that distinguish endogenous steroids from exogenous ones, such as the synthetic anabolic steroids athletes take to build muscle.

To accentuate those differences, Chouinard pairs MS with ion mobility (IM) spectrometry, a separation technique he learned as a graduate student with Richard Yost, Ph.D., at the University of Florida. Yost's team and others found that the differences between isomers could be made even more apparent if the molecules in a sample were modified prior to IM-mass spec analysis by reacting them with other compounds. After Chouinard set up his own lab in 2018, he applied this technique by reacting steroid samples with ozone or acetone in the presence of ultraviolet light -- reactions already well-established among researchers who study lipid isomers, but new in the anti-doping arena.

Last year, Chouinard's team reported they had successfully used these reactions with IM-MS to improve isomer separation, identification and quantification for a few steroids in sample solutions. Now, the researchers report they have tested this technique in urine against nearly half the prohibited steroids on WADA's list and have shown it can successfully characterize and identify these compounds. They also showed the method can characterize and identify banned glucocorticoids, such as cortisone, that improve athletic performance by suppressing inflammation from injuries. Detection limits are below one nanogram per ml.

In addition to tracking down known dopants, the team wants to be able to find newly created illicit steroids not yet known to WADA. With Florida Institute of Technology collaborators including Roberto Peverati, Ph.D., they are developing computational modeling and machine learning techniques to try to predict the structure, spectra and other characteristics of these molecules. "If we can develop methods to identify any theoretical steroids in the future, we could dramatically reduce doping because we would be able to detect these new species immediately, without the lag time that's been associated with anti-doping testing over the last 40 years," Chouinard says.

Though the assays themselves are quick, simple and inexpensive, IM instruments are costly, with a price ranging up to roughly a million dollars, Chouinard notes. However, he adds, with the support of anti-doping funding organizations like the Partnership for Clean Competition (PCC), more labs might be willing to foot that bill, so long as the method offers a significant advantage in detection and deterrence.

Credit: 
American Chemical Society

See further: Scientists achieve single-photon imaging over 200km

image: (a) Visible-band photograph of the mountains taken by a standard astronomical camera equipped with a telescope. The elevation is approximately 4500 m. (b) Schematic diagram of the experimental setup. (c) Photograph of the setup hardware, including the optical system (top and bottom left) and the electronic control system (bottom right). (d) View of the temporary laboratory where lidar was implemented at an altitude of 1770 m.

Image: 
LI Zhengping et al.

A research team led by Professor PAN Jianwei and Professor XU Feihu from University of Science and Technology of China achieved single-photon 3D imaging over 200 km using high-efficiency optical devices and a new noise-suppression technique, which is commented by the reviewer as an almost "heroic" attempt at single photon lidar imaging at very long distances.

Lidar imaging technology has enabled high precision 3D imaging of target scene in recent year. Single photon imaging lidar is an ideal technology for remote optical imaging with single-photon level sensitivity and picosecond resolution, yet its imaging range is strictly limited by the quadratically decreasing count of photons that echo back.

Researchers first optimized transceiver optics. The lidar system setup adopted a coaxial scanning design for the transmit and receive optical paths, which can align the transmitting and receiving spots more precisely and achieve higher-resolution imaging in comparison with tradition method.

To differentiate weak echo signal from strong background noise, the team developed a single-photon avalanche diode detector (SPAD) with a 19.3% detection efficiency and a low dark count rate (0.1kHz). Further, researchers coated telescope to achieve high transmission at 1550 nm. All these improvements achieved higher collection efficiency than before.

Researchers also adopted an efficient temporal filtering technique for noise suppression. The technique can reduce the total number of noise photon counts to be about 0.4 KHz, which is at least 50 times smaller than previous works.

Experiment results showed that the system can achieve accurate 3D imaging at up to 201.5 km with single-photon sensitivity.

This work could provide enhanced methods for low-power, single-photon lidar for high-resolution active imaging and sensing over long ranges and open up a new road for the application of long-range target recognition and earth observation.

Credit: 
University of Science and Technology of China

Scientists scour genes of 53,000+ people to better battle dangerous diseases

image: Stephen S. Rich, PhD, a genetics researcher at the University of Virginia School of Medicine, helped lead the massive effort to better understand heart, lung, blood and sleep disorders.

Image: 
UVA Health

A new analysis of the entire genetic makeup of more than 53,000 people offers a bonanza of valuable insights into heart, lung, blood and sleep disorders, paving the way for new and better ways to treat and prevent some of the most common causes of disability and death.

The analysis from the Trans-Omics for Precision Medicine (TOPMed) program examines the complete genomes of 53,831 people of diverse backgrounds on different continents. Most are from minority groups, which have been historically underrepresented in genetic studies. The increased representation should translate into better understanding of how heart, lung, blood and sleep disorders affect minorities and should help reduce longstanding health disparities.

"The Human Genome Project has generated a lot of promises and opportunities for applying genomics to precision medicine, and the TOPMed program is a major step in this direction," said Stephen S. Rich, PhD, a genetics researcher at the University of Virginia School of Medicine who helped lead the project. "An important feature of TOPMed is not only publishing the genomic data on 53,000 people with massive amounts of data related to heart, lung, blood and sleep disorders but also the great diversity of the participants who donated their blood and data."

Historic Genome Analysis

The groundbreaking work identified 400 million genetic variants, of which more than 78% had never been described. Nearly 97% were extremely rare, occurring in less than 1% of people. This sheds light on both how genes mutate and on human evolution itself, the researchers say.

Of the groups studied, people of African descent had the greatest genetic variability, the researchers found. The resulting data is the best ever produced on people of African ancestry, the scientists report in the prestigious journal Nature.

The work also offers important new insights into certain gene variants that can reduce people's ability to benefit from prescription drugs. This can vary by race and ethnic group.

"TOPMed is an important and historic effort to include under-represented minority participants in genetic studies," said Rich, who served on the project's Executive Committee and chaired the Steering Committee. "The work of TOPMed should translate not only into better scientific knowledge but increase diversity at all levels - scientists, trainees, participants - in work to extend personalized medicine for everyone."

Rich was joined in the effort by UVA's Ani Manichaikul, PhD; Joe Mychaleckyj, DPhil; and Aakrosh Ratan, PhD. All four are part of both the Center for Public Health Genomics and UVA's Department of Public Health Sciences.

Credit: 
University of Virginia Health System

Humans were apex predators for two million years

image: Human Brain

Image: 
Dr. Miki Ben Dor

Researchers at Tel Aviv University were able to reconstruct the nutrition of stone age humans. In a paper published in the Yearbook of the American Physical Anthropology Association, Dr. Miki Ben-Dor and Prof. Ran Barkai of the Jacob M. Alkov Department of Archaeology at Tel Aviv University, together with Raphael Sirtoli of Portugal, show that humans were an apex predator for about two million years. Only the extinction of larger animals (megafauna) in various parts of the world, and the decline of animal food sources toward the end of the stone age, led humans to gradually increase the vegetable element in their nutrition, until finally they had no choice but to domesticate both plants and animals - and became farmers.

"So far, attempts to reconstruct the diet of stone-age humans were mostly based on comparisons to 20th century hunter-gatherer societies," explains Dr. Ben-Dor. "This comparison is futile, however, because two million years ago hunter-gatherer societies could hunt and consume elephants and other large animals - while today's hunter gatherers do not have access to such bounty. The entire ecosystem has changed, and conditions cannot be compared. We decided to use other methods to reconstruct the diet of stone-age humans: to examine the memory preserved in our own bodies, our metabolism, genetics and physical build. Human behavior changes rapidly, but evolution is slow. The body remembers."

In a process unprecedented in its extent, Dr. Ben-Dor and his colleagues collected about 25 lines of evidence from about 400 scientific papers from different scientific disciplines, dealing with the focal question: Were stone-age humans specialized carnivores or were they generalist omnivores? Most evidence was found in research on current biology, namely genetics, metabolism, physiology and morphology.

"One prominent example is the acidity of the human stomach," says Dr. Ben-Dor. "The acidity in our stomach is high when compared to omnivores and even to other predators. Producing and maintaining strong acidity require large amounts of energy, and its existence is evidence for consuming animal products. Strong acidity provides protection from harmful bacteria found in meat, and prehistoric humans, hunting large animals whose meat sufficed for days or even weeks, often consumed old meat containing large quantities of bacteria, and thus needed to maintain a high level of acidity. Another indication of being predators is the structure of the fat cells in our bodies. In the bodies of omnivores, fat is stored in a relatively small number of large fat cells, while in predators, including humans, it's the other way around: we have a much larger number of smaller fat cells. Significant evidence for the evolution of humans as predators has also been found in our genome. For example, geneticists have concluded that "areas of the human genome were closed off to enable a fat-rich diet, while in chimpanzees, areas of the genome were opened to enable a sugar-rich diet."

Evidence from human biology was supplemented by archaeological evidence. For instance, research on stable isotopes in the bones of prehistoric humans, as well as hunting practices unique to humans, show that humans specialized in hunting large and medium-sized animals with high fat content. Comparing humans to large social predators of today, all of whom hunt large animals and obtain more than 70% of their energy from animal sources, reinforced the conclusion that humans specialized in hunting large animals and were in fact hypercarnivores.

"Hunting large animals is not an afternoon hobby," says Dr. Ben-Dor. "It requires a great deal of knowledge, and lions and hyenas attain these abilities after long years of learning. Clearly, the remains of large animals found in countless archaeological sites are the result of humans' high expertise as hunters of large animals. Many researchers who study the extinction of the large animals agree that hunting by humans played a major role in this extinction - and there is no better proof of humans' specialization in hunting large animals. Most probably, like in current-day predators, hunting itself was a focal human activity throughout most of human evolution. Other archaeological evidence - like the fact that specialized tools for obtaining and processing vegetable foods only appeared in the later stages of human evolution - also supports the centrality of large animals in the human diet, throughout most of human history."

The multidisciplinary reconstruction conducted by TAU researchers for almost a decade proposes a complete change of paradigm in the understanding of human evolution. Contrary to the widespread hypothesis that humans owe their evolution and survival to their dietary flexibility, which allowed them to combine the hunting of animals with vegetable foods, the picture emerging here is of humans evolving mostly as predators of large animals.

"Archaeological evidence does not overlook the fact that stone-age humans also consumed plants," adds Dr. Ben-Dor. "But according to the findings of this study plants only became a major component of the human diet toward the end of the era."

Evidence of genetic changes and the appearance of unique stone tools for processing plants led the researchers to conclude that, starting about 85,000 years ago in Africa, and about 40,000 years ago in Europe and Asia, a gradual rise occurred in the consumption of plant foods as well as dietary diversity - in accordance with varying ecological conditions. This rise was accompanied by an increase in the local uniqueness of the stone tool culture, which is similar to the diversity of material cultures in 20th-century hunter-gatherer societies. In contrast, during the two million years when, according to the researchers, humans were apex predators, long periods of similarity and continuity were observed in stone tools, regardless of local ecological conditions.

"Our study addresses a very great current controversy - both scientific and non-scientific," says Prof. Barkai. "For many people today, the Paleolithic diet is a critical issue, not only with regard to the past, but also concerning the present and future. It is hard to convince a devout vegetarian that his/her ancestors were not vegetarians, and people tend to confuse personal beliefs with scientific reality. Our study is both multidisciplinary and interdisciplinary. We propose a picture that is unprecedented in its inclusiveness and breadth, which clearly shows that humans were initially apex predators, who specialized in hunting large animals. As Darwin discovered, the adaptation of species to obtaining and digesting their food is the main source of evolutionary changes, and thus the claim that humans were apex predators throughout most of their development may provide a broad basis for fundamental insights on the biological and cultural evolution of humans."

Credit: 
Tel-Aviv University

Deep dive into key COVID-19 protein is a step toward new drugs, vaccines

image: The nucleocapsid phosphoprotein (blue) of SARS-CoV-2 (N) (grey) plays critical roles in multiple processes of the SARS-CoV-2 infection cycle, including replication and transcription, and packaging and protecting the genomic RNA (gRNA) (red). The N protein exists as a dimer in solution and interacts with gRNA predominantly through its structured N-terminal domain. N binds RNA multivalently and as more N proteins become available, stabilizing interactions between RNA and proteins occur, resulting in an organized nucleocapsid. Fluorescence imaging of 1-1000 RNA with a Cy3 fluorescent tag demonstrates that RNA-Cy3 with the addition of FL-N, becomes organized and condensed (red puncta background).

Image: 
OSU College of Science

CORVALLIS, Ore. - Researchers in the Oregon State University College of Science have taken a key step toward new drugs and vaccines for combating COVID-19 with a deep dive into one protein's interactions with SARS-CoV-2 genetic material.

The virus' nucleocapsid protein, or N protein, is a prime target for disease-fighting interventions because of the critical jobs it performs for the novel coronavirus' infection cycle and because it mutates at a comparatively slow pace. Drugs and vaccines built around the work of the N protein carry the potential to be highly effective and for longer periods of time - i.e., less susceptible to resistance.

Among the SARS-CoV-2 proteins, the N protein is the viral RNA's biggest partner. The RNA holds the genetic instructions the virus uses to get living cells, such as human cells, to make more of itself, and the N protein binds to the RNA and protects it.

Published in Biophysical Journal, the findings are an important jump-off point for additional studies of the N protein and its interactions with RNA as part of a thorough look at the mechanisms of SARS-CoV-2 infection, transmission and control.

Elisar Barbar, professor of biochemistry and biophysics at Oregon State, and Ph.D. candidate Heather Masson-Forsythe led the study with help from undergraduate students Joaquin Rodriguez and Seth Pinckney. The researchers used a range of biophysical techniques that measure changes in the size and shape of the N protein when bound to a fragment of genomic RNA - 1,000 nucleotides of the 30,000-nucleotide genome.

"The genome is rather large for a virus and requires many copies of the N protein to stick to the RNA to give the virus the spherical shape that is necessary for the virus to make more copies of itself," Barbar said. "Our study helps us quantify how many copies of N are needed and how close they are to each other when they stick to the RNA. "

Biophysical studies of N with large segments of RNA by nuclear magnetic resonance are rare, Barbar said, because of the difficulty of preparing the partially disordered N protein and long RNA segments, both prone to aggregation and degradation, but these kinds of studies are a specialty of the Barbar lab. Other researchers' studies generally have been limited to much smaller pieces of RNA and smaller pieces of the N protein.

Rather than just looking at the RNA-binding regions of the N protein on their own, the 1,000-nucleotide view allowed scientists to learn that the protein binds much more strongly when it's a full-length dimer - two copies attached to one another - and to identify regions of the protein that are essential for RNA binding.

"The full protein has structured parts but is actually really flexible, so we know that this flexibility is important for RNA binding," Masson-Forsythe said. "We also know that as N proteins start to bind to the longer RNA, the result is a diverse collection of bound protein/RNA complexes as opposed to one way of binding."

Drugs that thwart the N protein's flexibility would thus be one potential avenue for pharmaceutical researchers, she said. Another possibility would be drugs that disrupt any of those protein/RNA complexes that prove to be of special significance.

Credit: 
Oregon State University

New IT system may help film scriptwriters achieve box-office success

image: Pablo García-Sánchez, a researcher at the UGR's Department of Computer Architecture and Technology and lead author of this study

Image: 
University Of Granada

Could the next Hollywood blockbuster be written by a computer? Scientists from the University of Granada (UGR) and the University of Cádiz (UCA) have designed the world's first computer system based on artificial intelligence techniques that can help film scriptwriters create storylines with the best chance of box-office success.

The researchers focused their analysis on the "tropes" of existing films--that is, the commonplace, predictable, and even necessary clichés that repeatedly feature in film plots, based on rhetorical figures. These storytelling devices and conventions enable directors to readily convey scenarios that viewers find easy to recognise.

As tropes are ideas that are employed repeatedly throughout different films or series, it is often said that virtually all storylines have already appeared in the television series "The Simpsons". This reflection provided the inspiration for the title of the article about this new study, which has just been published in the prestigious journal PLOS ONE: "The Simpsons did it: Exploring the film trope space and its large scale structure". Its authors are Pablo García-Sánchez and Juan Julián Melero, from the UGR's Department of Computer Architecture and Technology, and Antonio Vélez and Manuel Jesús Cobo from the Department of Computer Engineering at the University of Cádiz.

Examples of tropes

García-Sánchez, the lead author of the original study, explains: "Some examples of tropes would be the inevitable villain that the heroes must take on in Marvel films; the detective who hands over his badge and gun; the protagonist's arrival in hell (used in dramas and thrillers such as "Cell 211" or "Below Zero"); the hero's journey (which dates back thousands of years, such as in Homer's Odyssey, but also features in films such as "Star Wars", "The Lord of the Rings", and "Harry Potter"); or the well-kept secret that is suddenly revealed, disrupting the entire plot of a psychological thriller."

The researchers devised a methodology to understand how tropes operate, to visually represent how they relate to one another and to different genres, and, above all, to infer which combinations might be the most successful in creative terms. In other words, using artificial intelligence, their study sought to predict which narrative devices or plot twists may or may not work well with audiences.

To achieve this objective, the researchers consulted an online database called TVTropes, which includes more than 25,000 tropes associated with 10,766 films. This platform is continually updated by fans, making it ideal the ideal source of data for the researchers to analyse. Using the free TropeScraper software, developed at the UGR, they scraped or extracted a list of tropes used in the films and then conducted a mapping exercise based on the user rating and popularity (number of votes) for each film, according to the IMDb website.

The network analysis of these tropes (in what the UGR and UCA researchers have dubbed the "troposphere") was conducted using programmed algorithms to reveal the relationship between the films that share similar tropes and thus build a picture of the existing communities of tropes and communities of films. Using this method, they were able to measure the popularity of the tropes and determine whether they were transversal (general or basic) across all films or highly specific/specialised, and whether they were on the rise (emerging tropes) or, on the contrary, on the decline.

Assisting the creative process

"This research can help film scriptwriters and directors during the creative process. While our system is not yet equipped to write automatically (although that's our next step), it does provide the resources with which to determine what combination of ideas (tropes) may work best," notes García-Sánchez.

The inspiration for the study came when the researchers began to question the over-simplicity of the "same old" characters used repeatedly in video games that quickly become boring. García-Sánchez continues: "We began to wonder how we could model the characters in such a way that they would provide a more interesting experience."

Thanks to the interrelationship between tropes, the films in which they appear, and the ratings given by users to each of these tropes, "depending on the combination and design of the actions based the tropes, we can now broadly ascertain the level of interest each kind of storyline is likely to generate," explains García-Sánchez.

"For example, some tropes are thematic, so what if we mix tropes that, on the face of it, are very different? What if we were to mix those from science fiction with those that typically appear in musicals in the same film, would that work?" This is just one of the inquiries being conducted by the researchers, who also plan to analyse in more depth which areas of the troposphere receive more attention and are currently enjoying growing success or, conversely, are causing interest to decline.

Using this same procedure, it would also be interesting to study the evolution of tropes in a given genre, country, or decade, and to better understand audience consumption and the viewing public's interaction with audio-visual productions.

Credit: 
University of Granada