Culture

A new study by researchers at Woods Hole Oceanographic Institution (WHOI) found that New England's historic lobster fishery may turn a higher profit by operating with less gear in the water and a shorter season. The findings could provide a path forward for the lobster fishing industry, which is under pressure to move away from traditional pot fishing that uses long vertical lines of rope known to entangle and kill endangered North Atlantic right whales and other protected species. The study was published this week in the journal Marine Policy.

"The story the data tells is optimistic," says lead author Hannah Myers, a graduate student at the University of Alaska Fairbanks and a guest student at WHOI. "We know that taking rope out of the water column is the best way to protect whales, and that can likely be done in a way that could benefit fishers as well."

American lobsters (Homarus americanus) found on the U.S. Atlantic coast bring in more revenue than any other fishery in the country, with a record high of more than $670 million in 2016. However, this doesn't necessarily mean the fishery is operating efficiently, researchers say.

In order to maintain healthy fish stocks, many fisheries have a limited season, catch quotas and/or gear restrictions. These measures often reduce associated fishing costs, such as for bait and fuel, while also ensuring that the available fish are bigger and more abundant. Although the U.S. lobster fishery has some restrictions, the trap limit is very high and for the most part fishers can operate year-round.

By evaluating three different scenarios to understand the connection between lobster fishing effort and catch, the researchers found that tightening restrictions could make the industry more profitable in the long run.

In Massachusetts, where a three-month fishing closure was implemented in 2015 in Cape Cod Bay and surrounding areas where North Atlantic right whales come to feed each winter and spring, fishers caught significantly more lobster since the closure was implemented--particularly in the areas most affected by it.

Further north, Canadian fishers in the Gulf of Maine operate with far fewer traps and a six-month season, and catch about the same amount of lobster as their American counterparts with 7.5 times less fishing effort. In Maine, a 10 percent drop in the number of lobster traps fished in recent years has not prevented fishers from bringing in record landings.

Fishing gear entanglements are the most serious threat to the survival of endangered North Atlantic right whales, only about 400 of which are alive today. During peak lobster season, right whales must navigate through more than 900,000 endlines--ropes that connect surface buoys to traps on the seafloor--in waters off the northeastern U.S. coastline, which is an important area for their feeding and migratory habitat.

"Entanglements often cause chronic injury, stress, and even starvation if the animal doesn't immediately drown," says Michael Moore, a coauthor of the paper and director of WHOI's Marine Mammal Center. "If the public could see the trauma these entangled animals endure, they would be extremely concerned."

Understanding the economic implications that right whale protection measures may have is important to the lobster fishing industry and the many communities along New England's coast that it supports, the researchers say. This study shows that reducing the amount of gear in the water or shortening the season does not necessarily mean fishers will catch less, and is in fact likely to benefit the industry in the long-term. This is especially important, given the economic devastation of the COVID-19 crisis.

Overall, their findings were consistent across the board: fishing with less gear and a shorter season corresponded with higher landings and higher profits.

A promising molecular pair has offered hope that could lead to the development of a new treatment to slow down Parkinson's disease, a study by Nanyang Technological University, Singapore (NTU Singapore) and Harvard University has found.

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 7 to 10 million people worldwide. Patients with the illness have reduced levels of dopamine in the brain, causing them to have difficulty controlling motor movements, with symptoms such as tremor and rigidity of muscles in hands, arms, and legs. They can also develop some non-motor symptoms, like sleep disturbance, depression, and loss of smell.

Through laboratory investigations and in vivo experiments, the team led by Professor Yoon Ho Sup from the NTU School of Biological Sciences and Professor Kwang-Soo Kim from McLean Hospital and Harvard Medical School in the United States found that the 'molecular pair', Prostaglandin E1 (PGE1) - a type of hormone - and Prostaglandin A1 (PGA1), can be the key to boosting dopamine levels and slowing Parkinson's disease.

PGE1 and PGA1 do so by binding to Nurr1, a class of proteins crucial to the development and maintenance of dopamine in the brain.

Their binding causes Nurr1 to be activated, resulting in a marked increase in dopamine production while preventing dopamine-producing brain cells from dying. After activating Nurr1, the mice with Parkinson's disease showed significant improvements in their motor functions.

Although much research still needs to be done, these findings could provide a new avenue for the creation of Nurr1-activating drugs to combat Parkinson's disease - an illness with no cure currently. While there are already treatment methods like dopamine-raising medication or deep brain stimulation using electric currents, these treatments have side-effects and can only address the patient's symptoms, not slow down, or halt the disease.

Prof Yoon said, "Considering the essential function of Nurr1, we have been searching for its activating molecules in the body. Finally, we have successfully identified that PGE1/PGA1 is the molecular pair that acts specifically on Nurr1 and can lead to neuroprotective effects on the brain."

"Given that all candidate Parkinson's drugs have failed to show neuroprotective abilities in clinical trials, our findings may offer an opportunity to design mechanism-based disease-modifying therapeutics to treat Parkinson's disease with little side effect."

The findings were published in the peer-reviewed journal Nature Chemical Biology in May 2020, and were made by researchers from Singapore, the United States, and South Korea.

Prostaglandins (PGE1/PGA1) - the key to combating Parkinson's disease

One of a number of hormone-like substances in the body, Prostaglandins are responsible for a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation.

Their regulatory roles in activating the dopamine function of Nurr1 have not been studied until now.

To identify and characterise how PGE1/PGA1 activates Nurr1, the team of researchers used nuclear magnetic resonance and X-ray crystallography to decipher the structures of the molecules involved, successfully unveiling details of how PGA1 binding leads to the activation of Nurr1 for the first time.

These findings from experiments on cells were then supported by in vivo experiments with experimentally induced Parkinson's disease, which showed significant improvements in their motor functions when PGE1 and PGA1 were administered.

Prof Kim said, "By uncovering the molecular interactions, we gain insights into the biological function and regulation of Nurr1 in health and disease such as Parkinson's disease. Our findings in this study are adding to what we know about how dopamine neurons function and point towards the development of novel therapeutics of Parkinson's disease."

Highlighting the significance of the findings, co-author Professor Lim Kah Leong, Vice Dean (Research) of NTU Lee Kong Chian School of Medicine said, "PGA1 is not a new kid on the block, but a molecule known to exhibit anti-inflammation and anti-tumour properties. Prostaglandins like PGE1 are available for clinical use, for example in obstetrics cases. This means that the compound can potentially be re-positioned to treat Parkinson's patients, which can accelerate the time needed to take an experimental drug to the clinic."

The scientists are now looking to design a synthetic form of PGE1/PGA1 and to validate it as a potential new drug that can target Nurr1, thereby halting or reversing the onset of Parkinson's disease.

More than 50 percent of all eventual cerebral palsy (CP) cases spend time in the Neonatal Intensive Care Unit, making early CP evaluation a crucial element of any hospital's high-risk follow-up program. The earlier children are diagnosed, the better their chances of early access to evidence-based interventions targeted specifically for CP. Unfortunately, U.S. hospitals average an age of about 2 years at diagnosis, compared to the target of 12 months of age or younger.

Now, five hospital systems in the United States have become the first in the world to successfully implement, in clinical practice, international CP diagnosis guidelines that were released in 2017. Their efforts, which resulted in an average decrease of 10 months in time-to-diagnosis, demonstrate the practicality and effectiveness of the guidelines for improving age at diagnosis -- a key requirement for early interventions, which can improve CP-related developmental outcomes substantially.

The endeavor was proposed and funded by the Cerebral Palsy Foundation. The lead institution -- Nationwide Children's Hospital, which had participated in the development of the international guidelines and was the first hospital to implement the guidelines clinically -- trained and collaborated with experts at four other institutions eager to reduce age at CP diagnosis (UCLA Mattel Children's Hospital, Los Angeles; the University of Texas Health Science Center at Houston; University of Utah Health, Salt Lake City; and Kennedy Krieger Institute, Baltimore).

"Working as a network made this effort much more impactful," says Nathalie Maitre, MD, PhD, director of the NICU Follow-Up Program at Nationwide Children's and principle investigator on the network project. "Everyone has been transparent, communicative and respectful, allowing us all to learn from each other and see how others navigate guideline implementation with their unique cultures and resources."

Each member institution's high-risk infant follow-up program started by analyzing their strengths, weakness, opportunities and threats, as well as their suppliers, inputs, process, outputs and customers, to identify key elements for change. Throughout the effort, they participated in continual process improvement assessments and monthly network-wide discussions.

After 9 months of guideline implementation work, the group achieved an average diagnosis age of 9.5 months -- a 10-month improvement over baseline.

"In a research network, you tell people what to do, how to do it and why they're doing it," says Dr. Maitre, lead author on the network's recent Pediatrics publication. "In implementation science, you just give people some of the tools for how to succeed and then stand back. They have to believe in the 'why,' and they have to decide what exactly to do to make it work for them. This team rose to the challenge in exceptional ways."

The guidelines involve neonatologists, developmental pediatricians, therapists and other developmental specialists, but they also rely heavily on neurologists, who Dr. Maitre says, were instrumental in successfully implementing and evaluating the assessments and neuroimaging for early diagnosis. All institutions required significant training to implement the guideline-based neuroimaging and neurologic screenings, which were combined with motor function assessments, biomarkers and clinical history to determine a diagnosis.

The network has grown since its initial implementation period. Now Dr. Maitre and Rachel Byrne, executive director of the Cerebral Palsy Foundation, are developing systematic engagement and education efforts for primary care providers and hospitals in underserved communities. Dr. Maitre is also actively involved in delivering a telehealth version of the guideline implementation program to help families stay connected to care during COVID-19.

Dr. Maitre believes that network-based propagation and widespread implementation of the guidelines is the first step toward globalized clinical detection of CP during infancy -- with the follow-up goal that ever-improving early intervention efforts will then become the new standard of CP care.

Providers who are interested in implementing the guidelines in their own programs can attend training and workshops at Nationwide Children's annual conference on the subject: "Implementation of Early Detection and Intervention for Cerebral Palsy."

An article in CMAJ (Canadian Medical Association Journal) analyzes the strengths and limitations of digital contact tracing for people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to help governments decide if and how they might adopt this technology.

"Although the benefits of digital contact tracing may be appealing, in considering whether to adopt these technologies, public health agencies and governments must also consider their technological limitations and the inherent trade-offs between privacy and effectiveness," writes Dr. Robert Kleinman, Stanford University School of Medicine, with his coauthor.

Integrating app-based contract tracing with traditional contact tracing techniques may help leverage benefits and mitigate the limitations of each approach.

Apps must be field tested in real-world situations to understand their ability to identify exposures. To identify significant numbers of contacts, apps need to be adopted by a large proportion of the population. Governments considering digital contact tracing, such as the government of Alberta, should incorporate privacy protection, establish thresholds for exposure identification, encourage widespread adoption of the technology and ensure communication among public health agencies across provincial, state and national borders.

The authors caution that access to widespread, accurate testing for SARS-CoV2, the virus that causes coronavirus disease 2019 (COVID-19), is key to the success of digital contact tracing.

In a perspective piece published today in the journal Science, UC San Diego experts describe in detail the growing evidence that SARS-CoV-2, the novel coronavirus that causes COVID-19, can be spread by asymptomatic people via aerosols -- a reality that deeply underscores the ongoing importance of regular widespread testing, wearing masks and physical distancing to reduce the spread of the virus.

HIGHLIGHTS

Asymptomatic people spread virus in aerosols. Mounting evidence suggests that SARS-CoV-2 is silently spread in aerosols exhaled by contagious infected persons displaying no symptoms. A recent study estimated that a single minute of loud speaking might generate between 1,000-100,000 virion-containing aerosols or virus particles suspended in the air. Due to their small size, aerosols can remain airborne for hours and travel long distances. Small, virus-containing aerosols can also penetrate more deeply into the lungs, bypassing the immune system, which can lead to more severe cases of COVID-19.

Traditional measures target droplets, not buoyant aerosols. Traditional respiratory disease controls based on physical spacing are designed to reduce transmission from large droplets produced in the sneezes and coughs of infected individuals. However, a large fraction of the spread of COVID-19 appears to be occurring through airborne transmission of smaller aerosols produced by infected but asymptomatic individuals during breathing and speaking. Droplets settle to surfaces within six feet and spread via contact. Contrarily, infectious aerosols can accumulate in indoor, uncirculating air for hours, where they can be more easily inhaled deeply into the lungs.

Infectious aerosols can travel further than six feet. Given how little is known about the airborne behavior of infectious aerosols, it's difficult to define a safe distance for physical distancing. However, a six-foot perimeter indoors without a mask is likely not enough if an asymptomatic person is actively shedding the virus, researchers say. A good comparison is exhaled smoke: The distance from a smoker at which you can smell smoke indicates the distance at which you might also inhale infectious aerosols. Many factors affect aerosol spread indoors and outdoors, such as air flow and ventilation, number of people in the space, time of exposure , sunlight, temperature and humidity.

Masks are essential. Properly fitted masks provide a critical physical barrier, reducing the number of infectious viruses in the exhaled breath of asymptomatic individuals. Countries that have been most effective in limiting the spread of COVID-19 have implemented universal masking. For example, Taiwan (population 24 million), where masking orders were universal and quickly enacted, did not implement a lockdown during the pandemic; yet it maintained a low incidence of approximately 441 cases and 7 deaths. By contrast, New York State (population 20 million) has had more than 353,000 COVID-19 cases and 24,000 deaths.

Loss of smell (anosmia) and changes in taste (dysgeusia) were strongly associated with SARS-CoV-2, according to a Canadian study published in CMAJ (Canadian Medical Association Journal).

"We found that anosmia and dysgeusia were the most distinctive symptoms associated with SARS-CoV-2 infection and that these symptoms could be severe, as shown by the complete loss of perception of odours such as coffee and garbage," writes Dr. Alex Carignan, Medical Microbiologist and Infectious Diseases consultant at CIUSSS de l'Estrie - CHUS, Université de Sherbrooke and Centre de recherche du CHUS, Sherbrooke, Quebec, with coauthors.

Among 2883 adults tested for SARS-CoV-2, the virus that causes COVID-19, in the Eastern Townships in Quebec between March 10 and March 23, 2020, researchers identified 134 positive cases. Almost two-thirds (63%) of these people reported either loss of smell, changes in taste or both symptoms, compared with 8% in the control group who did not have SARS-CoV-2.

"These symptoms should be considered as common and distinctive features of SARS-CoV-2 infection and should serve as an indication for testing and possible retesting of people whose first test result is negative," the authors write.

The findings add to research from California, Italy and Germany that reported altered smell and taste in a majority of people who tested positive for SARS-CoV-2.

ITHACA, N.Y. - A recent survey found that online shoppers return 70% of the clothing they order, more than any other category of purchase. This has an indirect but real impact on the environment.

Online shoppers tend to order multiple sizes and colors, with the intent of sending back the items that don't fit or aren't the right color, a practice known as "bracket shopping." An augmented reality (AR) tool allowing shoppers to see an image of themselves in the garment, however, made them more likely to want to buy it, according to new research by a team including Fatma Baytar, assistant professor of fiber science and apparel design and director of the Body Scan Research Group.

While not as effective as physically trying it on, the researchers found that AR boosted participants' attitudes toward the garment, potentially improving the experience and efficiency of online shopping.

"Bracket purchases increase shelving and shipping costs," Baytar said. "We're hoping these technologies can reduce those costs, while also decreasing the carbon footprint associated with return shipping."

The study, "Evaluating Garments in Augmented Reality When Shopping Online," was published April 6 in the Journal of Fashion Marketing and Management.

Current virtual try-on technologies offer two methods of improving online shopping. One involves creating an avatar by inputting key body measurements and then trying clothes on the avatar. The other method is AR - using a computer, phone or tablet screen as a mirror reflecting a shopper and background while overlaying the chosen garments on the shopper' image.

Baytar and collaborators from Iowa State University and Virginia Polytechnic Institute focused on the latter technology, asking participants to virtually try on a dress, select a size to "order" and then physically try on the dress in that size. Participants evaluated the AR dress for size, fit and performance, then did the same following the physical try-on.

Results for the AR technology were mixed. According to Baytar, study participants were able to find the right size with AR try-on, but had trouble evaluating the fit - particularly at the bust, waist and hips. One explanation, Baytar said, was that although the image of the dress was taken when the dress was on a dress form, rather than hanging flat, it was still a 2D image. Adding to the difficulty evaluating fit: The dress form's hourglass shape did not match the body shape of all participants.

Evaluating product performance - style, fabric, color, coordination with other items, touch and feel, weight, fit, comfort and appearance on the body - was significantly different when experienced in AR versus real life. Color was the only performance factor that showed no difference across the two try-on experiences.

But even with the limitations, participants responded well to the virtual dress.

"Attitudes to the AR garment and the real garment were really high, which means the participants liked it and their purchase intentions were relatively high, though they were higher for the real garment," Baytar said. "This is still a promising technology, because AR can provide good visual information that improves consumer attitudes and purchase intentions. We think a company could use this technology to create a buzz when introducing a new style."

Baytar and her colleagues also wanted to know how telepresence - consumers' sense of being present in a virtual environment - would impact their attitudes toward the AR garment and purchase intentions. As expected, the study showed that higher telepresence corresponded to more positive attitudes toward the AR garment.

The study was completed in 2016 but has new significance, Baytar said, with brick and mortar stores being closed during the COVID-19 crisis.

"The technology we used was limited, and even four years later the technology still needs to be improved," Baytar said. "We can expect that as these technologies evolve, people will trust online shopping more, they will trust that they will get the right size that fits them and will look like it did on the screen."

May 27, 2020 - Previous studies have reported improved quality of life and mental health in transgender women undergoing facial feminization surgery (FFS) surgery to provide a more feminine facial appearance. But there is still limited evidence on these and other benefits of facial gender confirmation surgery.

A new study from two leading centers documents improved outcomes after FFS, including subjective and objective evidence of a more feminine appearance, leading to improved quality of life. "Facial feminization achieved improved quality of life, feminized cephalometries, feminine gender appearance, good overall aesthetics, and high satisfaction that were present at one month and stable at greater than six months," write lead authors Shane Douglas Morrison, MD, MS, of University of Washington, Seattle; Thomas Satterwhite, MD, Align Surgical Associates, San Francisco, CA; and Fermín Capitán-Cañadas, PhD, of the FACIALTEAM Surgical Group at HC Marbella International Hospital, Spain.

The researchers analyzed the outcomes of 66 consecutive patients undergoing FFS at their two centers. The patients' average age was 39 years; two-thirds had begun their gender-affirmation process within the previous five years. The study appears in the June issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).

As is typical for FFS, the patients underwent a range of different procedures designed to provide a more feminine facial appearance: an average of 4.2 procedures per patient. The most common procedures focused on reducing and reshaping the underlying bone of the forehead, jaw, and chin - identified by patients as "most masculine" features of their faces.

Before-and-after evaluations showed improvement in several key outcomes. On a 100-point facial feminization score (with 100 denoting complete satisfaction), median score increased from 47.2 before FFS to 80.6 at six months after surgery. The facial feminization score has previously been shown to be correlated with a standard quality-of-life assessment (Short Form-36 scale).

The study also included cephalometry - a set of computerized measurements to assess whether the facial structure had more typically feminine or masculine characteristics. Although the differences in these objective measurements were small, "their synergistic effects to overall alteration of the face are substantial," the researchers write.

On subjective observer ratings in a subgroup of patients, average score on a range from one (most feminine) to five (most masculine) was 1.83 in transgender women after FFS, compared to 1.25 in a group of cisgender women. On a ten-point general aesthetic outcome scale, average scores were 6.09 for the FFS patients and 7.63 for cisgender women. "Our cohort of FFS patients had feminine gender appearance and good overall aesthetic outcomes," the researchers write. "However, their gender appearance and general aesthetic outcomes were still not equal to those of cisgender women controls."

Facial feminization surgery is one of the fastest-growing areas in plastic surgery and is increasingly recognized as a medically necessary treatment for gender dysphoria. The new report is one of the first prospective studies of FFS, using standard assessments performed before and after surgery.

Click here to read "Prospective Quality-of-Life Outcomes after Facial Feminization Surgery: An International Multicenter Study."
DOI: 10.1097/PRS.0000000000006837

Oak Brook, IL - The June issue of SLAS Discovery features a special collection of research reviews and perspectives curated by the journal's Editorial Board.

In this issue, Guest Editor Veli-Pekka Jaakola, Ph.D., (Confo Therapeutics, Belgium) highlights a series of articles focused on new screening tools and assays that find new chemical matter for medically relevant membrane protein targets. In addition, an overview of a new and emerging protein-lipid reconstitution methodology utilizing styrene maleic acid (SMA) polymers is featured.

Articles in the special collection include:

Screening Technologies for Inward Rectifier Potassium Channels: Discovery of New Blockers and Activators

Correlation of Optical and Automated Patch Clamp Electrophysiology for Identification of Nav1.7 Inhibitors

Application of High-Throughput Automated Patch-Clamp Electrophysiology to Study Voltage-Gated Ion Channel Function in Primary Cortical Cultures

Image-Based Marker-Free Screening of GABAA Agonists, Antagonists, and Modulators

Applied Biophysical Methods in Fragment-Based Drug Discovery

Keeping It Clean: The Cell Culture Quality Control Experience at the National Center for Advancing Translational Sciences

A Novel Inhibition Modality for Phosphodiesterase 2A

Development of a Cell-Based Immunodetection Assay for Simultaneous Screening of Antiviral Compounds Inhibiting Zika and Dengue Virus Replication

The Impact of Variable Selection Coverage on Detection of Ligands from a DNA-Encoded Library Screen

Exploring the Lower Limit of Individual DNA-Encoded Library Molecules in Selection

Scientists at Sanford Burnham Prebys Medical Discovery Institute have mapped for the first time the vast network of proteins that interact with proinsulin, the protein the body normally processes into insulin. The study, published in Diabetes, also revealed one protein--called PRDX4--that may be essential for proinsulin folding and insulin production. The research suggests that boosting PRDX4 levels may be a novel therapeutic approach to improving the health of people with diabetes.

"Type 2 diabetes is a progressive condition, and over time the insulin-producing beta cells in the pancreas 'burn out' and die. Our recent work suggests that proinsulin misfolding plays a role in beta cell failure and the development of type 2 diabetes," says Pamela Itkin-Ansari, Ph.D., adjunct associate professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys and senior and co-corresponding author of the study. "Our hope is that by fixing proinsulin misfolding, potentially by targeting PRDX4, we may be able to protect or even restore the health of beta cells and achieve a functional cure."

Proteins are the workhorses of the cell, and their function depends on their shape. When proteins are misfolded or damaged, their shape becomes flawed and they can't perform their regular duties. Faulty proteins need to be fixed or eliminated before they accumulate, clump or become toxic, and cause diseases. Incorrect protein folding is linked to many degenerative diseases, including Alzheimer's, Parkinson's and diabetes.

Mapping proinsulin's "social network"

In the study, the scientists obtained pancreatic islets, which contain the insulin-producing beta cells, from six healthy people--including men and women of Caucasian, Hispanic and African-American ethnicities. Using a special molecular technique, the researchers isolated all the proteins that the proinsulin physically interacts with, or "touches," as it travels within a beta cell and is processed into insulin.

This work uncovered more than 400 proteins that interact with proinsulin and identified one, called PRDX4, that plays a key role in proper proinsulin folding. Further work confirmed that PRDX4 is inactivated in islets from people with type 2 diabetes--indicating that the protein holds potential as a therapeutic target.

"Protein folding is a remarkably complex process," says Randal Kaufman, Ph.D., director and professor in the Degenerative Diseases Program at Sanford Burnham Prebys and co-corresponding author of the study. "This study unravels some of that complexity and helps explain the link between type 2 diabetes, proinsulin folding and insulin production."

The scientists are already repeating this study in islets from people with type 2 diabetes to understand how proinsulin folding changes or fails during disease. Once these findings are in hand, they will have an even deeper understanding of interventions that may fix or prevent the misfolding.

More than 422 million people worldwide have diabetes, according to the World Health Organization, and these numbers are rising due to increased obesity. Type 2 diabetes accounts for 90% of diabetes cases and occurs when the body doesn't properly use insulin--the protein that removes sugar from the blood. Most current medications help tissues absorb more sugar or increase insulin secretion. No treatments exist that promote proper proinsulin folding to keep beta cells functioning.

"I lost my father to diabetes, so I know firsthand how dangerous this condition can be and what an effective treatment means to patients and their families," says Itkin-Ansari. "This study is a first step toward a future when we might be able to help more people manage type 2 diabetes and live a long, healthy life."

Maintaining abstinence from alcohol can be exceptionally challenging. A main goal of addiction research has been to find out exactly why it's tough to give up the drink. In Frontiers in Behavioral Neuroscience, a team of researchers investigating how alcohol withdrawal leads to changes in the brain have now identified a possible new target for the treatment of depression related to alcohol withdrawal - a key predictor of relapse.

Somatostatin neurons are inhibitory 'brake' type neurons that are capable of silencing other neurons. They have recently emerged as a strong candidate for treatments of psychiatric disorders. Lead author of the study, Nigel Dao, of Pennsylvania State University in the USA, stated that "little work has focused on somatostatin neurons role in addiction and we were excited to explore this uncharted territory and bring forth discoveries of new therapeutic options."

The researchers randomly assigned mice to alcohol drinking or non-alcohol drinking groups. After 6 weeks, all mice then underwent forced abstinence where they had access to water only. The mice were then tested for anxiety and depression like behaviors using the elevated plus maze, open field test, sucrose preference test and the forced swim test. The brains were then analyzed using fluorescence immunochistochemistry and electrophysiology.

The results showed that withdrawal from alcohol resulted in emotional disturbances that mimic some of the symptoms of depression seen in people, including a lack of interest in rewarding things, as well as a heightened response to stressful events.

When studying the brains of the mice, the researchers found that alcohol withdrawal produced divergent effects on the physiology of somatostatin neurons in the prefrontal cortex and ventral bed nucleus of the stria terminalis. Both brain regions are well known for their role in emotional processing and addiction.

Dao states that "the effects of alcohol withdrawal appeared more pronounced in females, underscoring the complex relationship between addiction and emotional disorders seen in men and women."

The study is limited as it was conducted in mice; it therefore remains to be determined if these results can be replicated in human patients. Furthermore, the results of the study only revealed what alcohol withdrawal combined with stress exposure could do to the physiology of somatostatin neurons. Senior author of the study, Dr. Nicole Crowley of Pennsylvania State University in the USA, stated that "there is much more to do uncover how it brings about these changes on a synaptic and molecular level," adding that she "wants to understand how to activate or silence these neurons as a potential treatment."

The results of this research shed light on the possibility that targeting the somatostatin neurons in the brain, might be a viable candidate for treating depression particularly related to alcohol withdrawal.

Crowley adds that "if we can help people cope with the negative emotions that they feel during alcohol withdrawal, both short term and long term, we can help them maintain their abstinence."

Young people, men and people in "individualistic" societies report higher levels of loneliness, according to a large-scale global study.

The study - based on responses from more than 46,000 participants around the world - is the first published research to come from the BBC Loneliness Experiment.

The ages of participants ranged from 16-99, and the results show a steady decrease in loneliness as people age.

Based on the findings, a young man living in an individualistic society - such as the UK or the US - is more likely to report feeling lonely than an older woman in a collectivist society - such as China or Brazil.

The study was carried out by Exeter, Manchester and Brunel universities.

"Contrary to what people may expect, loneliness is not a predicament unique to older people," said Professor Manuela Barreto, of the University of Exeter.

"In fact, younger people report greater feelings of loneliness.

"Since loneliness stems from the sense that one's social connections are not as good as desired, this might be due to the different expectations younger and older people hold.

"The age pattern we discovered seems to hold across many countries and cultures."

Professor Pamela Qualter, from the University of Manchester, said: "With regard to gender, the existing evidence is mixed.

"There is an awareness that admitting to feeling 'lonely' can be especially stigmatising for men.

"However, when this word is not used in the measures, men sometimes report more loneliness than women. This is indeed what we found."

Using survey responses from 237 countries, islands and territories, the researchers were able to carry out an unprecedented analysis of cultural differences.

"This is particularly important because evidence for cultural differences in loneliness is very mixed and culture can affect actual and desired social interactions in opposite directions," said Professor Barreto.

"In addition, it can be argued that admitting to feeling lonely is also more stigmatising in individualistic societies, where people are expected to be self-reliant and autonomous.

"Again, our use of a measure that did not directly refer to loneliness allowed us to show that people living in more individualistic societies report more loneliness than people living in more collectivist societies."

In light of the COVID-19 pandemic, Professor Barreto said particular attention should be paid to how social changes might be affecting young people.

"Though it is true that younger people are better able to use technology to access social relationships, it is also known than when this is done as a replacement - rather than an extension - of those relationships, it does not mitigate loneliness," she said.

Rheumatologists at the University of Alberta are flagging similarities between the deaths of some COVID-19 patients and those with rheumatic illnesses, and are testing proven rheumatic treatments to see whether they help against the pandemic virus.

A substantial proportion of COVID-19 patients admitted to intensive care die of pneumonia due to a cytokine storm, where the body attacks itself rather than fighting off the illness, said Jan Willem Cohen Tervaert, director of rheumatology in the Department of Medicine.

In a new paper published in Autoimmunity Reviews, Cohen Tervaert and his colleagues note that such storms, whether in patients with COVID-19 or rheumatic diseases, are caused by dysfunctional "natural killer" (NK) immune cells.

They say that SARS-CoV-2, the virus that causes COVID-19, might attack NK cells directly by binding to angiotensin converting enzyme 2 (ACE-2), a receptor on the cells that COVID-19 researchers believe attracts and opens the door to the virus.

"This virus is so smart, it kills the cells that are supposed to kill it," Cohen Tervaert said.

Worldwide clinical trials are being carried out to test treatments typically used to treat cytokine storm in patients with juvenile arthritis and other rheumatic diseases.

These include intravenous immunoglobulin, a blood transfusion product prepared from the serum of thousands of healthy or previously infected patients, and rheumatic drugs such as tocilizumab and anakinra. Some researchers in China are even attempting to transplant healthy NK cells.

Cohen Tervaert said the U of A team is collaborating with researchers at the University of Calgary to further study the role of NK cells in COVID-19 patients. There are more COVID-19 patients in southern Alberta than in the Edmonton area.

In a healthy person, natural killer cells are responsible for both turning on and turning off the immune response when a body is attacked by disease, including viruses and even cancer. Unlike other immune cells (T and B cells), natural killer cells don't need to be trained or primed to fight infection.

"They are not thinkers," Cohen Tervaert said. "They immediately do their work without being exposed previously to a virus. As soon as a virus affects the cell and the cell wall changes, NK cells can attack that cell."

After the NK cells kill the virus-infected cells, the T and B immune cells come along and produce cytokines, making the immune reaction stronger and stronger.

"But at a certain time the immune reaction has to end," he said. "Natural killer cells play an important role in finishing that huge attack.

"If they don't work, the cytokine storm goes on and on, and the patient will die."

For those who have not been infected with the virus, Cohen Tervaert recommends regular mild to moderate exercise to boost their NK cells. His own daily routine includes step climbing, walking and weightlifting.

"If you sit the whole day in your room because you have to be isolated, your NK cell activity goes down," he said. "That's the big warning about the isolation of elderly people who are not allowed to go outside of their rooms. Over time they are more and more at risk to die from COVID-19."

A Northwestern University research team has developed a new method to conduct spectroscopic nanoscopy, an approach that could help researchers understand more complicated biomolecular interactions and characterize cells and diseases at the single-molecule level.

The new system, called asymmetrically dispersed spectroscopic single-molecule localization microscopy (SDsSMLM), builds upon existing sSMLM techniques developed at the McCormick School of Engineering to provide more precise spectroscopic single-molecule analysis to study how cells behind certain cancers, or diseases like diabetic retinopathy, function in their localized environments.

While current spectroscopic single-molecule localization microscopy techniques achieve super-resolution imaging and single-molecule spectroscopy simultaneously, current sSMLM designs suffer from reduced imaging resolution and spectral precision. This is caused by the system dividing a finite number of emitted photons -- atomic particles that transmit electromagnetic light -- between two separate channels for spatial and spectral imaging.

"We should not be satisfied to only know where a particular molecule is or where many molecules are without differentiating their properties," said Hao Zhang, professor of biomedical engineering, who led the research. "Our approach enables us to fully use all photons from each emission for both spatial imaging and spectral analyses. As a result, we significantly improved the spatial imaging resolution and spectral precision compared to existing sSMLM techniques."

A paper describing the work, titled "Symmetrically Dispersed Spectroscopic Single-molecule Localization Microscopy," was published May 25 in the journal Light: Science and Applications. Cheng Sun, professor of mechanical engineering, was a coauthor on the paper.

Unlike existing sSMLM approaches, which often use a 1:3 ratio to split photos between the spatial and spectral channels, SDsSMLM commits all available photos to create two mirrored spectral images. This approach extracts spectral information at the highest possible resolution. In addition, because the images are symmetrical, researchers can still identify spatial information by identifying the mid-point between the two spectral images.

When compared to an existing sSMLM using the same number of photos, the researchers found that SDsSMLM improved the spatial precision by 42 percent and spectral precision by 10 percent.

"We realized that the spatial information is totally overlooked in the spectral image in existing sSMLM techniques," Zhang said. "This approach allows us to apply all of the available photons for spectral analysis to push the resolution limit while also acquiring spatial imaging."

When used together with spectroscopic single-molecule imaging techniques, SDsSMLM can be adapted for 3D cellular imaging, an essential tool in cell biology and materials science that allows researchers to track how cells interact in their environments.

"This technique holds true for all molecules, regardless of their emission spectra and minute spectral variations, even among the same species of molecules," Zhang said. "With improved spatial resolution and spectral precision, sSMLM will find broader applications in multi-molecule imaging in cells and three-dimensional tracking for individual nanoparticles in biological and chemistry investigations."

In addition to the system's advanced imaging capabilities, SDsSMLM's compact nature allows for easy integration and reliable operation with conventional fluorescence microscope systems. Combined with an open source plug-in the researchers developed called RainbowSTORM, Zhang hopes other members of the biological research community will incorporate this advanced technique within their own work.

"Our design is standalone and can be installed in a majority of microscope systems," Zhang said. "We hope other researchers take advantage of what we've created."

New guidelines for scientists and regulators show how deliberate infection of volunteers for vaccine trials can be done ethically

Peer-reviewed paper by University of Warwick researcher argues that we do not need to lower our ethical standards if appropriate safeguards are in place

Researcher also argues that deliberate infection should be considered to speed up vaccine development

Allowing consenting volunteers to be deliberately infected with COVID-19 for the purposes of developing a vaccine could be done ethically and potentially speed up its development, a University of Warwick researcher has argued in new research.

Dr Adair Richards at the University of Warwick has developed a set of ethical guidelines to guide researchers on an ethical approach to deliberately infecting volunteers who have been given a vaccine candidate with COVID-19.

He argues that this may significantly speed up the process of vaccine development and potentially save many lives. The work has been externally double-blind peer-reviewed and is published today (28 May) in the Journal of Medical Ethics.

Dr Adair Richards is an Honorary Associate Professor in the University of Warwick’s Department of Chemistry and carries out research ethics training for postgraduate researchers in science and medicine. He said: "Currently there are several vaccine candidates that are undergoing human safety testing, but to find out whether they work we need to discover what happens when a vaccinated person is exposed to COVID-19. With new infections dropping in the countries where research is taking place, it may be a long time before many of the volunteers in these experiments naturally come into contact with the disease.

"Deliberately infecting volunteers with a disease as dangerous as COVID-19 has previously been considered to be unethical by the research community. However I believe that the current global situation is so different to those previously faced, that it is ethical in this case.

"In other areas of life it is not unusual for society to allow individuals to do things that put them at personal risk, such as to be a fire fighter or a health professional treating COVID-19 patients. Speeding up vaccine development even by a few weeks or months could result in saving many lives."

The research analyses each of the common arguments against these types of experiments: the risk of harm to volunteers; the risk of no useable vaccine; the validity of a volunteer's informed consent; the reputational risk to research; and that this could be a slippery slope to increasingly unethical research.

Dr Richards demonstrates that these arguments can be overcome and in fact we do not need to lower our ethical standards to permit these types of experiment, and that it is possible to put sufficient ethical safeguards in place.

The article provides guidance for regulators and researchers and poses three key questions for those planning vaccine development studies:

Has reasonable care been taken to maximise the potential benefits of the proposed study and minimise the risks of harm to participants?

Is the informed consent process sufficiently robust?

What do we need to do now to amend our processes to speed up the consideration and approval processes for proposed COVID-19 vaccine candidate phase II and phase III trials?

Dr Richards adds: "My research shows that it is incorrect to rule out human challenge experiments as unethical in relation to COVID-19 vaccine development. I argue that you can apply the same standards of ethics, but that they lead us now to a different conclusion because the facts are different.

"Very large numbers of people globally are affected both directly and indirectly from COVID-19, and the saving of a few weeks or months of time in vaccine development can be expected to result in saving a large number of lives. There are also good ways to minimise the risk of harm to volunteers, and it is ethical, and I argue, admirable to allow a volunteer to choose to take a personal health risk to help serve a greater benefit to humanity."