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Researchers adapt cell phone camera for SARS-CoV-2 detection

Source: Cell Press
Date: 12/10/2020
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Researchers have developed an assay that can detect the presence of SARS-CoV-2 in a nasal swab using a device attached to an ordinary smartphone, they report December 4 in the journal Cell. Although more research is needed before such a test can be rolled out, the results are promising and ultimately may be applicable to screening more broadly for other viruses.

“Our study shows that we can do the detection part of this assay very quickly, making the measurement with mass-produced consumer electronics,” says Daniel Fletcher, a bioengineer at the University of California in Berkeley and co-senior author on the paper. “We don’t need fancy laboratory equipment.”

Fletcher and other co-senior author Melanie Ott, a virologist at Gladstone Institutes and the University of California, San Francisco, began collaborating with Nobel laureate Jennifer Doudna, also a co-author on the study, about two years ago on a rapid, at-home test for HIV. They were looking to address the need for frequent testing that has arisen because of current drug trials that require close monitoring of patients’ viral loads. When COVID-19 hit the scene in January, they quickly pivoted their research to develop a test that would detect the presence of a different virus — SARS-CoV-2.

The test makes use of CRISPR-Cas technology. Specifically, RNA in the sample can be detected with the Cas13 enzyme, eliminating the need for reverse transcription of the RNA into DNA and then amplification by PCR technology used in current standard tests. When Cas13 binds to the RNA from the virus, it cleaves any surrounding RNA sequences; the researchers added an RNA-based probe to the reaction that gets cleaved and produces fluorescence that can be detected with the camera. The assay provides results within 30 minutes of detection time.

In the current study, which was primarily designed to be a test of the amplification-free CRISPR-Cas technology and the detector, the nasal swabs were spiked with SARS-CoV-2 RNA. The investigators are currently working on a solution that would induce a single-step reaction in which the RNA is released from the virus without the need for purification. Because it doesn’t require amplification, the assay is able to quantify the amount of virus in the sample.

“It’s super exciting to have this quantitative aspect in the assay,” Ott says. “PCR is the gold standard, but you have to go through so many steps. There are huge opportunities here for pathogens and for biology in general to make RNA quantification more precise.”

The fluorescence detector consists of a laser to produce illumination and excite the fluorescence and an added lens to help collect light. The phone is placed on top of it. “One takeaway is that the phone camera is ten times better than the plate reader in the lab,” Ott says. “This is directly translatable to it being a better diagnosis reader.” Previous research in Fletcher’s lab has led to phone-based devices that visually detect parasites in blood and other samples, and the current assay demonstrates how phone cameras can also be useful for molecular detection.

Ultimately, Fletcher and Ott would like to have this type of test be part of a broader system that could be used at home to screen not only for SARS-CoV-2 but other viruses — like those that cause colds and flu. But more immediately, the researchers hope to develop a testing device using this technology that could be rolled out to pharmacies and drop-in clinics. They would like to get the cost of testing cartridges down to about $10. The final device would probably not actually use a phone but have a phone camera built into it.

Ott notes that what they’ve learned developing this SARS-CoV-2 test can also be applied to their work with HIV tests. “We will need to change the extraction methods because we’ll be dealing with blood instead of nasal swabs, but it’s really helpful that we’ve developed the fluorescent detection part,” she says. “This is the start of an era when we can give the individual more authority and autonomy” in terms of being able to test themselves.

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Defects in mitochondria may explain many health problems observed during space travel

Source: Cell Press
Date: 11/25/2020
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For space exploration to be successful, it’s vital to understand–and find ways to address–underlying causes of the health issues that have been observed in astronauts who have spent extended periods of time off world. These problems include loss of bone and muscle mass, immune dysfunction, and heart and liver problems. Using data collected from a number of different resources, a multidisciplinary team is reporting discovery of a common thread that drives this damage: mitochondrial dysfunction. The researchers used a systems approach to look at widespread alterations affecting biological function. The findings are reported November 25 in the journal Cell.

“We started by asking whether there is some kind of universal mechanism happening in the body in space that could explain what we’ve observed,” says senior author Afshin Beheshti (@AfshinBeheshti), a principal investigator and bioinformatician at KBR in the Space Biosciences Division of the National Aeronautics and Space Administration (NASA) at Ames Research Center in California’s Silicon Valley and a visiting researcher at the Broad Institute. “What we found over and over was that something is happening with the mitochondria regulation that throws everything out of whack.”

The investigators analyzed data obtained from NASA’s GeneLab platform, a comprehensive database that includes data from animal studies, the NASA Twin Study, and samples collected from 59 astronauts over decades of space travel. Many of the scientists who participated in this study are involved with GeneLab’s Analysis Working Groups, which draw from institutions all over the world. The platform contains a range of “omics” data related to changes in tissues and cells that occur due to the combined effects of space radiation and microgravity, including proteomic, metabolomic, transcriptomic, and epigenomic data. 

The researchers used an unbiased approach to look for correlations that could explain the widespread changes observed. “We compared all these different tissues from mice that were flown in space on two different missions, and we saw that mitochondrial dysfunction kept popping up,” Beheshti says. “We looked at problems in the liver and saw they were caused by pathways related to the mitochondria. Then we looked at problems in the eyes and saw the same pathways. This is when we became interested in taking a deeper look.”

He explains that mitochondrial suppression, as well as overcompensation that can sometimes occur because of that suppression, can lead to many systemic organ responses. They can also explain many of the common changes seen in the immune system.

Using their discoveries from mice as a starting point, the researchers then looked at whether the same mechanisms could be involved with humans in space. Examining data from the NASA Twins Study, in which identical twins Scott and Mark Kelly were followed over time, the former on the International Space Station and the latter on the ground, they saw many changes in mitochondrial activity. Some of these changes could explain alterations in the distribution of immune cells that occurred in Scott during his year in space. They also used physiological data and blood and urine samples that had been collected from dozens of other astronauts to confirm that mitochondria activity in different cell types had been altered. 

“I was completely surprised to see that mitochondria are so important, because they weren’t on our radar,” Beheshti says. “We were focusing on all the downstream components but hadn’t made this connection.” He adds that mitochondrial dysfunction can also help explain another common problem with extended space travel: disrupted circadian rhythms. Since the team first reported their findings within NASA, other NASA scientists have begun making connections between mitochondrial changes and common space-related cardiovascular problems as well.

The hope is that now that mitochondrial issues have been identified as a cause of so many health risks related to space travel, countermeasures could be developed to address them. “There are already many approved drugs for various mitochondrial disorders, which would make it easier to move them toward this application,” Beheshti notes. “The low-hanging fruit now would be to test some of these drugs with animal and cell models in space.”

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Case study details leukemia patient who shed infectious SARS-CoV-2 for at least 70 days

Source: Cell Press
Date: 11/5/2020
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The majority of people infected with SARS-CoV-2 appear to actively shed infectious virus for about 8 days, but there is a wide range of variability from person to person. Understanding how long people can remain actively infected is important, because it provides new details about a disease and a virus that are still not well understood and informs public health decisions. Researchers report November 4 in the journal Cell an unusual case of one woman with leukemia and a low antibody count who was infected with the coronavirus for at least 105 days, and infectious for at least 70, while remaining asymptomatic the entire time.

“At the time we started this study, we really didn’t know much about the duration of virus shedding,” says senior author Vincent Munster, a virologist at the National Institute of Allergy and Infectious Diseases. “As this virus continues to spread, more people with a range of immunosuppressing disorders will become infected, and it’s important to understand how SARS-CoV-2 behaves in these populations.”

Munster, an expert in emerging infectious diseases, began publishing research on SARS-CoV-2 in January. He was contacted in April by infectious disease specialist Francis Riedo, a study co-author, about a patient in Kirkland, Washington, who had been infected very early in the COVID-19 pandemic. Riedo’s patient had had numerous positive PCR tests for the virus over a period of weeks, and he wanted to know if she was still shedding virus.

The patient, a 71-year-old woman, was immunocompromised due to chronic lymphocytic leukemia and acquired hypogammaglobulinemia. She never showed any symptoms of COVID-19. She was found to be infected with the virus when she was screened after being admitted to the hospital for severe anemia and her doctors recognized that she had been a resident of a rehabilitation facility experiencing a large outbreak.

Munster’s lab at NIAID’s Rocky Mountain Laboratories in Hamilton, Montana, began studying samples that were regularly collected from the patient’s upper respiratory tract. They found that infectious virus continued to be present for at least 70 days after the first positive test, and the woman didn’t fully clear the virus until after day 105. “This was something that we expected might happen, but it had never been reported before,” Munster says.

The investigators believe the patient remained infectious for so long because her compromised immune system never allowed her to mount a response. Blood tests showed that her body was never able to make antibodies. At one point she was treated with convalescent plasma, but Munster doesn’t think the treatment had an effect because of its low concentration of antibodies. Despite her inability to mount an antibody response, she never went on to develop COVID-19.

The team performed deep sequencing on all the virus samples obtained from the patient to see how the virus might have changed over the course of the patient’s infection. Samples collected at various times displayed different dominant gene variants. However, the investigators don’t think that these mutations played a role in how long the virus persisted, because they saw no evidence of natural selection. Selection would have been implicated if one of the variants had appeared to provide the virus with a survival benefit and had become the dominant variant, but none of them did. They also tested whether or not the mutations affected the ability or speed of the virus to replicate and found no differences.

Munster says that as far as he knows, this is the longest case of anyone being actively infect-ed with SARS-CoV-2 while remaining asymptomatic. “We’ve seen similar cases with influenza and with Middle East respiratory syndrome, which is also caused by a coronavirus,” he notes. “We expect to see more reports like ours coming out in the future.”

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Researchers simulate privacy leaks in functional genomics studies

Source: Cell Press
Date: 11/12/2020
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The functional genomics field, which looks at the activities of the genome and levels of gene expression rather than particular gene mutations, generally relies on aggregating information from many samples for its statistical power. This means that broadly sharing raw data is vital; however, sharing these data currently is challenging because of the privacy concerns of individuals within those datasets, leading to these data being largely inaccessible behind firewalls.

In a study publishing November 12 in the journal Cell, a team of investigators demonstrates that it’s possible to de-identify those data to ensure patient privacy. They also demonstrate how these raw data could be linked back to specific individuals through their gene variants by something as simple as an abandoned coffee cup if these sanitation measures are not put in place.

“The purpose of this study is to come up with practical ways to broadly share the raw data without creating undue privacy concerns,” says senior author Mark Gerstein, a professor of bioinformatics at Yale University.

Functional genomics research is frequently tied to a specific disease. For example, an investigation into a particular psychiatric condition might look at the expression of certain genes in a type of neuron. And, by nature of having their genetic material included in such a study, an individual’s medical status with regard to that condition could inadvertently be revealed.

This can happen through what’s known as a quasi-identifier. The way a quasi-identifier works is that if someone has enough individual data points about you, even if those data on their own are not sensitive or unique, they can be combined to create an identifier that is unique to you. In a non-genetic setting, this means if someone has your zip code, birthday, the model of car you drive, and other similar data that might not be considered private or sensitive on their own, they might eventually be able to combine them and create a unique profile that would link you to other data that you wouldn’t want public — data like financial records that were collected when you applied for a car loan. The same thing could happen if someone were able to obtain some of your genetic variants and link those variants to the presence of your genetic material in a study on a particular disease. This could in turn reveal a diagnosis, such as HIV status or an inherited cancer predisposition, that you would prefer to keep private.

In their study, the researchers constructed a “linkage attack” scenario to demonstrate how someone could make these kinds of connections from functional genomics studies’ data by using DNA obtained from a discarded coffee cup. After adding samples from two consenting participants to a functional genomics database, the researchers gathered used coffee cups from the same individuals. They sequenced genetic material left on the cups and were able to successfully match that material to the samples in the database and infer sensitive health information about the participants. The researchers were also able to use DNA information “stolen” from a genotyping database to match the identities of 421 people with phenotypic information found in a test functional-genomics dataset that the researchers constructed for 436 people.

However, the researchers also identified steps that can be taken to thwart these kinds of linkage attacks and safeguard participants’ health information when functional genomics datasets are shared. “Functional genomics is special because variants are usually not needed for data processing,” says first author Gamze Gürsoy, a postdoctoral researcher at the Gerstein lab. “Because of this, we can sanitize the variants to prevent data being linked back to the private information connected to the phenotypes included in these studies, while still retaining the utility of the data.”

To achieve this balance between privacy and data usefulness, the researchers propose a file-format manipulation that will allow raw functional genomics data to be shared while largely reducing sensitive information leakage by generalizing information about phenotypic variants. The file format is based on a widely used standard file-format system, is compatible with a range of software and pipelines, and when tested, showed little loss of utility. The researchers have also developed a framework with which other researchers can tune the level of privacy and utility balance they want to achieve with the file format based on the policies and consents of the donors.

“As more data are released for these kinds of functional genomics studies, concerns about security and privacy shouldn’t be lost,” Gerstein says. “At the dawn of the Internet, people didn’t realize how important their online activities would become. Now that type of digital privacy has become so important to us. If we move into an era where getting your genome sequenced becomes routine, we don’t want these worries about health privacy to become dominating.”

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STEM CELLS RESTORE OVARIAN FUNCTION AND FERTILITY TO MICE TREATED WITH CHEMOTHERAPY

Source: Brigham and Women's Hospital
Date: 8/15/2023
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Researchers at Brigham and Women’s Hospital have demonstrated that mice with ovarian failure caused by chemotherapy can restore their fertility using induced pluripotent stem cells (iPSCs). Not only were the mice able to make functional eggs from the iPSCs, but those eggs developed into pups that could reproduce.

Although more research is needed before this approach can be evaluated in humans, this marks a big step toward reaching that goal. The study was published in July 2023 in Lancet Biomedicine.

“This research shows a novel, cell-based approach to treating infertility,” says senior author Raymond Manohar Anchan, MD, PhD, director of the Stem Cell Biology and Regenerative Medicine Research Laboratory at the Brigham. “It builds on earlier work from our lab that demonstrated that iPSCs can be used to generate ovarian and oocyte cell types.”

Using Stem Cells to Restore Ovarian Function

In the study, mice were treated with chemotherapy known to be toxic to the gonads.

The iPSCs used in the research were derived from somatic ovarian granulosa cells. The cells were cultured in a three-dimensional environment that mimics the structure of the ovary, using human ovarian follicular fluid that otherwise would have been discarded by an in vitro fertilization clinic. The stem cells were engineered to carry a label with green fluorescent protein so their lineage could be traced after placing them in the mice.

“Because we labeled the stem cells, this gives us a high level of confidence that the developed eggs came from the stem cells that we introduced,” Dr. Anchan says. “These eggs clearly carry the label. Furthermore, we used short tandem repeat lineage training to confirm the stem-cell lineage of the resultant pups and litters.”

Nine of the mice that received iPSC transplants were crossbred with wild-type mice and were able to bear pups. Those pups were also bred to confirm their viability and fertility.

‘Epigenetic Memory’ Helps Stem Cells Form Ovarian Tissues

Dr. Anchan says another important finding from this work is that, in addition to being able to differentiate into egg cells, the stem cells can also make the reproductive hormones estrogen and progesterone. Additionally, the stem cells not only restored fertility to the ovary where they were placed but also boosted activity in the other ovary.

“We know this is the case because we get eggs in both ovaries, not just the one we injected,” Dr. Anchan says. “The stem cells are secreting something that helps the other ovary to recover some of its function. We confirmed this because not all the eggs contain the protein label.”

The researchers use the term “epigenetic memory” to describe the ability of cells taken from an organ to differentiate into the various cell types from that organ. Once placed into the ovaries of the mice, some of the cells were able to make follicles—the cavity where the eggs develop. “It’s intriguing because a single type of stem cell has the ability to do many different things,” Dr. Anchan adds.

Translating Ovarian Research to Human Cells

Ongoing experiments in Dr. Anchan’s lab are taking the next step toward translating these findings into approaches that would benefit human patients with ovarian failure. A common cause of this issue in women still of reproductive age is the chemotherapy regimen used to treat breast cancer. These drugs are known to deplete the follicles in the ovaries.

Dr. Anchan and his colleagues are already conducting research in cell cultures of human ovarian cells. They have shown that the iPSCs derived from discarded amniocytes can produce estradiol and progesterone when the same protocol is used. “Of course, we will need to come up with different ways to test the normal genetics of any eggs that may form before we begin to think about human trials,” he notes.

One thing that is still unknown is whether this approach would be effective only in patients who have lost ovarian function due to chemotherapy treatments or whether it would also work in those whose ovaries stop working prematurely due to a genetic condition. This is something the team plans to study, both in human cells and in animal models.

The authors also note that if this approach proves effective, it could provide the opportunity to develop a type of “autologous” hormone replacement therapy using patients’ own ovarian cells.

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Feeding C-section newborns their mother’s poop may help build healthy microbiota: study

Source: Cell Press
Date: 10/1/2020
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Infants delivered by cesarean section have an increased risk of developing asthma and allergies as babies and toddlers, probably because they don’t get exposed to the microbiota in the mother’s vagina and perineum during birth, negatively impacting how their immune systems develop. While a few studies have looked at whether swabbing a newborn’s skin with vaginal fluid immediately after birth reduces this risk, a paper published October 1 in the journal Cell offers a more drastic way to expose newborns to their mother’s microbiota: by diluting a small amount of their mother’s feces in breast milk and feeding it to them just after birth. The researchers report that the proof-of-concept procedure appears to be safe and at three months resulted in the newborns having a microbial makeup that looks more similar to babies born vaginally than to those born by C-section.

“From a clinical point of view, this transfer of microbial material is happening during a vaginal delivery,” says co-senior author Sture Andersson, of the Pediatric Research Center at the University of Helsinki and Helsinki University Hospital in Finland. “This is a gift the mother gives to her baby.”

At birth, the immune system is undeveloped, but once a baby begins living in the outside world, their immune system matures in response to microbial exposure. Although every person’s microbiota is individualized, the overall patterns of which bacteria types colonize the gut are different in babies born vaginally and those born by C-section. These variations appear to make a difference in how the immune system learns to respond to outside stimuli, including potential allergens.

The mothers who took part in the study were recruited with leaflets placed in doctors’ waiting rooms. About 30 women contacted the researchers to learn more, and 17 agreed to participate. Ten of them were found to have contraindications, such as a recent course of antibiotics or a potentially dangerous microbe, and ultimately seven mothers who were scheduled to have C-sections were enrolled.

The babies were given the fecal microbiota transplants (FMTs) shortly after birth. The mothers’ fecal samples were collected three weeks beforehand. The babies stayed in the hospital for two days after the transplant to make sure there were no complications. The babies’ own fecal microbiota was tested at birth (the meconium) and again at two days, one week, two weeks, three weeks, and three months. The babies also had blood work done two days after birth.

The investigators found that by three months of age, the microbiotas of the babies who received the FMTs were similar to those of babies born vaginally. They were different from those of babies born by C-section, as well as from their mothers’ microbiotas. As a baseline for these comparisons, the researchers used data collected previously at the same hospital, as well as global datasets.

“This was not designed as a safety study, but we found it to be effective and supporting the concept of vertical transfer from mother to baby,” says co-senior author Willem de Vos, of the Human Microbiome Research Program at the University of Helsinki and the Laboratory of Microbiology at Wageningen University in the Netherlands. “However, it’s very important to tell people that this is not something they should try on their own. The samples have to be tested for safety and suitability.”

Andersson notes that despite how unpalatable this research may seem to most people, the mothers who agreed to participate in the study were very motivated. One woman who was having twins was told the FMT could be giving to one baby, with the other one used as a sort of control. She declined, stating that she didn’t want one of her babies to have an unfair advantage by receiving the transplant.

In future work, the researchers plan to study the development of the immune systems in C-section babies who receive FMTs and compare it to those who don’t. Unlike the current study, which was observational, the future studies will have a control group and will be blinded to the mothers.

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Survey finds American support for human-animal chimera research

Source: Cell Press
Date: 10/1/2020
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In September 2015, the US National Institutes of Health placed a funding moratorium on research that involves introducing human pluripotent stem cells into animal embryos — a practice that experts say is vital for advancing the field of regenerative medicine. To assess attitudes on human-animal chimeric embryo research, investigators conducted a survey among 430 Americans. The results of the survey, which found that 82% of people are supportive of at least some parts of this research, appear October 1 in the journal Stem Cell Reports.

“The take-home point is that the overall support for this kind of research across the American public is strong,” says co-author Francis Shen, a professor of law at the University of Minnesota and executive director of the Harvard Massachusetts General Hospital Center for Law, Brain, and Behavior. “I think this speaks to the public’s interest in the transformative potential of regenerative medicine for addressing disease in a variety of organs.”

“Public attitudes were more supportive than I thought would have been possible in the current political climate,” says first author Andrew Crane, a researcher in the Department of Neurosurgery at the University of Minnesota.

Crane and senior author Walter Low, a professor in the Department of Neurosurgery and Stem Cell Institute at the University of Minnesota, conduct research on stem cell applications for neurological disorders like Parkinson’s disease. One project focuses on generating human neural stem cells within pig brains. After learning that colleagues in Japan had done a survey on public attitudes about this type of research, they decided to conduct a similar study in the United States. Low and Crane began a collaboration with the Japan group and with Shen, who specializes in ethics at the intersection of law and neuroscience.

The study included two waves of data collection: 227 participants were surveyed in July 2018 and 203 additional participants were surveyed in June 2020. The participants were recruited through an Amazon service called Mechanical Turk and were paid $1 for completing the survey. The questions in the survey were similar to those included in the Japanese study.

The participants knew “next to nothing “about this research going into the survey, Shen explains. “We used images, and we clarified how this research might be done, breaking it down into steps.”

The survey questions were designed to assess opinions on the progressive steps of human-animal chimeric embryo research, by asking participants which aspects of research they were willing to accept based on their personal feelings. For example, it included scenarios about first injecting human stem cells into a pig embryo, then transplanting that embryo into a pig uterus to produce a pig with a human organ, and finally transplanting that organ into a human patient. It also broke down research by organ, with support for some tissue types being higher than others: 61% for heart, 64% for blood, 73% for liver, and 62% for skin, versus 44% for sperm/eggs and 51% for brain.

“With regard to putting human brain cells into animal brains, we’ve heard concerns about the animals having some sort of human consciousness, but that’s quite far off from where the science is right now and from anything that we’ve tried to advocate for in our research,” Crane says. “We understand this is a concern that should not be taken lightly, but it shouldn’t prohibit us from moving the research forward.”

The survey was also designed to assess cultural differences, and the researchers were surprised to find that support was relatively high even among religious and cultural conservatives. The largest factor influencing opposition to the research was concern about animal rights.

“As investigators in the US, we’ve hit a roadblock with a lot of this research with regard to funding,” Crane says. He adds that a lack of funding could lead to the research moving to countries with fewer ethical safeguards in place.

“The three biggest concerns about this research are animal welfare, human dignity, and the possibility of neurological humanization,” Shen concludes. “We would love to do focus groups to look deeper at some of these questions.”

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First look at how hallucinogens bind structurally to serotonin receptors

Source: Cell Press
Date: 9/17/2020
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Although hallucinogenic drugs have been studied for decades, little is known about the underlying mechanisms in the brain by which they induce their hallucinogenic–and (for disorders like depression and anxiety) potential therapeutic–effects. A paper publishing September 17 in the journal Cell reveals the first X-ray crystallography structure of LSD bound to its target in the brain, the serotonin receptor. The paper also includes the first cryo-electron microscopy (cryo-EM) structure of a prototypical hallucinogen coupled with the entire serotonin receptor complex.

“Millions of people have taken these drugs recreationally, and now they’re emerging as therapeutic agents,” says senior author Bryan Roth, a professor in the Department of Pharmacology at the University of North Carolina School of Medicine. “Gaining this first glimpse of how they act at the molecular level is really, really important, and it’s key to understanding how they work.”

Scientists believe that activation of the 5-HT2A serotonin receptor (HTR2A) in the brain is essential to the effects of hallucinogenic drugs. “These receptors are expressed at very high levels in the human cerebral cortex,” Roth says. “When they’re activated, they cause neurons to fire in an asynchronous and disorganized fashion, putting noise into the system. We think that’s one of the reasons they cause a psychedelic experience. However, it’s not at all clear how they exert their therapeutic actions.”

In this study, Roth collaborated with Georgios Skiniotis, a structural biologist at the Stanford University School of Medicine. “A combination of several different advances allowed us to do this research,” Skiniotis says. “One of these is better, more homogeneous preparations of the receptor proteins. Another is the evolution of cryo-EM technologies, which allows us to obtain high-resolution structures of complexes without having to crystalize them.”

In the paper, the investigators revealed the first X-ray crystallography structure of LSD bound to HTR2A. In addition, cryo-EM was used to uncover images of a prototypical hallucinogen, called 25-CN-NBOH, bound together with the entire receptor complex, including the effector protein Gαq. In the brain, this complex modulates the release of neurotransmitters and influences many biological and neurological processes.

Roth, a psychiatrist and biochemist, leads the Psychoactive Drug Screening Program, funded by the National Institute of Mental Health. This gives him access to hallucinogenic drugs for research purposes. Normally, these compounds are difficult to study in the lab because they’re regulated by the Drug Enforcement Agency as Schedule 1 drugs.

“One of the main goals of my work is to understand how hallucinogens exert their actions on the brain,” Roth says. “If we can understand how they work at the molecular level, this will ultimately give us clues into human consciousness, perception, and awareness.”

Going forward, the investigators plan to apply their findings to structure-based drug discovery for new therapeutics. One of the goals is to discover potential candidates that may be able offer therapeutic benefit without the psychedelic effects.

“The more we understand about how these drugs engage and activate the receptors, the better we’ll understand their signaling properties,” Skiniotis says. “This work doesn’t give us the whole picture yet, but it’s an important piece of the puzzle.”

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Operation Outbreak simulation teaches students how pandemics spread

Source: Cell Press
Date: 9/3/2020
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In 2015, a team of specialists in modeling disease outbreaks got together with educators to create Operation Outbreak, an educational platform and simulation intended to teach high school and college students the fundamentals of responses to pandemics. The program, which is open source and freely available, was designed to simulate outbreaks with different variables (such as R0 and mode of transmission) and to generate data in the context of real human behavior. It includes a Bluetooth-based app that carries out contact tracing by recording transmission events between phones. The details are highlighted in a Commentary published August 31 in the journal Cell.

Operation Outbreak came about after Todd Brown, then a middle school teacher in Florida, contacted Pardis Sabeti (@PardisSabeti), a computational biologist at the Broad Institute of Harvard and MIT, after reading a profile of her in a magazine. He and his students were studying the ongoing Ebola outbreak in West Africa, and he was developing a simulation of how the virus spread using stickers.

As they continued to work together, Sabeti and her team, including Andrés Colubri (@codeanticode), at the time a computational scientist in her lab, began studying mumps outbreaks across Boston college campuses. The idea to create an educational app that “spread” viruses through Bluetooth was soon born. And as recently as December 2019, they were running simulations modeling the outbreak of a virus with a very similar modus operandi to SARS-CoV-2.

“We decided to use a SARS-like virus since it had been high on many pandemic researchers’ lists as a concern,” says Colubri, who is now at the University of Massachusetts Medical School. “To make the simulation more challenging, we included an element of asymptomatic spread. This was a natural concern that would elevate a pandemic’s potential even further.”

This summer, as the COVID-19 pandemic continued to spread, Operation Outbreak was rolled out to 2,000 students in Chicago who were participating as “social distancing ambassadors” as part of the One Summer Chicago program. Participants used the app to track and trace behaviors and learn how “infections” spread in different parts of the city.

“The platform and curriculum are very flexible from an academic and also an experiential learning standpoint,” Brown says. “We tried to gamify the education, so that players’ behaviors and decisions affect not only them, but the entire group they’re playing with.”

The simulation includes elements that have become a familiar part of our daily lives, like limitations in testing abilities and shortages of personal protective equipment (PPE). The program also offers the ability to simulate additional elements that could arise in the current pandemic or in future ones, such as other circulating viruses that can complicate diagnosis.

“We are in one of the most unique situations in the history of the world, by virtue of being able to engage students,” says Brown, who is now community outreach director at Sarasota Military Academy. “Kids are more primed to learn when something directly affects them and their families. This is a chance for future generations to become aware of how infections spread and to recognize warning signs.”

“I hope we can convey that we don’t have to wait for the next pandemic to learn how to respond to them,” Sabeti says. “Ultimately, we can exquisitely model every aspect of viruses and how they spread, even in the ways that we react through vaccines, protective gear, and diagnostics.”

The team has put together a scalable curriculum, including a textbook and series of educational videos, that can be integrated at schools around the country. The materials, which have been funded by philanthropy, are open source and are available for free.

This work is supported by the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute. Additional funding grants include L’Oreal USA Women in Science Changing the Face of STEM, Toshiba America Foundation, Florida Association of International Baccalaureate World Schools, and Voya Financial.

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Fear of stricter regulations spurs gun sales after mass shootings, new analysis suggests

Source: Cell Press
Date: 8/11/2020
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It’s commonly known that gun sales go up after a mass shooting, but two competing hypotheses have been put forth to explain why that’s the case: is it because people fear more violence and want to protect themselves, or is it because mass shootings trigger discussions about tighter gun regulations, which sends people out to stock up? In a new study appearing August 11 in the journal Patterns, investigators used data science to study this phenomenon. By working with spatio-temporal data from all the states in the US, they determined that the increase in firearm purchases after mass shootings is driven by a concern about regulations rather than a perceived need for protection.

“It’s been well documented that mass shootings are linked to increases in firearm purchases, but the motivation behind this connection has been understudied,” says first author Maurizio Porfiri, Institute Professor at the New York University Tandon School of Engineering, who is currently on research sabbatical at the Technical University of Cartagena in Spain. “Previous research on this topic has been done mostly from the perspective of social science. We instead used a data-science approach.”

Porfiri and his colleagues employed a statistical method called transfer entropy analysis, which is used to study large, complex systems like financial markets and climate-change models. With this approach, two variables are defined, and then computational techniques are used to determine if the future of one of them can be predicted by the past of the other. “This is a step above studying correlation,” Porfiri explains. “It’s actually looking at causation. Unique to this study is the analysis of spatio-temporal data, by examining the behavior of all the US states”

The data that were put into consideration came from several sources: FBI background checks, which enabled the approximation of monthly gun sales by state; a Washington Post database on mass shootings; and news coverage about mass shooting from five major newspapers around the country. The news stories were put in two categories: those that mentioned gun regulations and those that didn’t. In all, the study used data related to 87 mass shootings that occurred in the United States between 1999 and 2017.

The researchers also rated individual states by how restrictive their gun laws are. “We expected to find that gun sales increased in states that have more permissive gun laws, but it was less expected in states with restrictive laws. We saw it in both,” Porfiri says. “Also, when we looked at particular geographic areas, we didn’t find any evidence that gun sales increased when mass shootings happened nearby.”

He adds that one limitation of the data is that news coverage may not fully capture public sentiment at a given time. In addition, although the study was successful in determining causal links among states, more work is needed to study the nature of these relationships, especially when one has laws that are much more restrictive than another

Porfiri usually uses computational systems to study topics related to engineering, including ionic polymer metal composites and underwater robots. His reason for studying mass shootings is personal: he received his Ph.D. in 2006 from Virginia Tech, which, the following year, was the site where—at that time—the deadliest mass shooting in the country took place. One member of his Ph.D. committee was killed in the shooting, and he knew many others who were deeply affected.

For him, this project is part of a larger effort to study gun violence. “Mass shootings are a small part of death from guns,” Porfiri says. “Suicide and homicide are much more common. But mass shootings are an important catalyst for a larger discussion. I plan to look at the wider role of guns in the future.”