Culture

Over half of cannabis users with Parkinson's disease report clinical benefits

Amsterdam, NL, January 26, 2021 - With medicinal cannabis now legalized in many parts of the world, there is growing interest in its use to alleviate symptoms of many illnesses including Parkinson's disease (PD). According to results of a survey of PD patients in Germany in the Journal of Parkinson's Disease, over 8% of patients with PD reported using cannabis products and more than half of those users (54%) reported a beneficial clinical effect.

Cannabis products containing THC (tetrahydrocannabinol, the main psychoactive compound of cannabis) can be prescribed in Germany when previous therapies are unsuccessful or not tolerated, and where cannabis can be expected with not a very unlikely chance to relieve disabling symptoms. CBD (pure cannabidiol, derived directly from the hemp plant, a cousin of the marijuana plant) is available without a prescription from pharmacies and on the internet.

"Medical cannabis was legally approved in Germany in 2017 when approval was given for therapy-resistant symptoms in severely affected patients independent of diagnosis and without clinical evidence-based data," explained lead investigator Prof. Dr. med. Carsten Buhmann, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. "PD patients fulfilling these criteria are entitled to be prescribed medical cannabis, but there are few data about which type of cannabinoid and which route of administration might be promising for which PD patient and which symptoms. We also lack information about the extent to which the PD community is informed about medicinal cannabis and whether they have tried cannabis and, if so, with what result."

Investigators aimed to assess patient perceptions of medicinal cannabis as well as evaluate the experiences of patients already using cannabis products. They performed a nationwide, cross-sectional, questionnaire-based survey among members of the German Parkinson Association (Deutsche Parkinson Vereinigung e.V.), which is the largest consortium of PD patients in German-speaking countries with nearly 21,000 members. Questionnaires were sent out in April 2019 with the association's membership journal and were also distributed in the investigators' clinic.

Over 1,300 questionnaires were analyzed; results showed that interest in the PD community in medical cannabis was high, but knowledge about different types of products was limited. Fifty-one percent of respondents were aware of the legality of medicinal cannabis, and 28% were aware of the various routes of administration (inhaling versus oral administration), but only 9% were aware of the difference between THC and CBD.

More than 8% of patients were already using cannabinoids and more than half of these users (54%) reported that it had a beneficial clinical effect. The overall tolerability was good. Over 40% of users reported that it helped manage pain and muscle cramps, and more than 20% of users reported a reduction of stiffness (akinesia), freezing, tremor, depression, anxiety, and restless legs. Patients reported that inhaled cannabis products containing THC were more efficient in treating stiffness than oral products containing CBD but were slightly less well tolerated.

Patients using cannabis tended to be younger, living in large cities, and more aware of the legal and clinical aspects of medicinal cannabis. Sixty-five percent of non-users were interested in using medicinal cannabis, but lack of knowledge and fear of side effects were reported as main reasons for not trying it.

"Our data confirm that PD patients have a high interest in treatment with medicinal cannabis but lacked knowledge about how to take it and especially the differences between the two main cannabinoids, THC and CBD," noted Prof. Dr. med. Buhmann. "Physicians should consider these aspects when advising their patients about treatment with medicinal cannabis. The data reported here may help physicians decide which patients could benefit, which symptoms could be addressed, and which type of cannabinoid and route of administration might be suitable."

"Cannabis intake might be related to a placebo effect because of high patient expectations and conditioning, but even that can be considered as a therapeutic effect. It has to be stressed, though, that our findings are based on subjective patient reports and that clinically appropriate studies are urgently needed," he concluded.

Bastiaan R. Bloem, MD, PhD, Director, Radboudumc Center of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands, and Co-Editor-in Chief of the Journal of Parkinson's Disease, added: "These findings are interesting in that they confirm a widespread interest among patients in the use of cannabis as a potential treatment for people living with PD. It is important to emphasize that more research is needed before cannabis can be prescribed as a treatment, and that guidelines currently recommend against the use of cannabis, even as self-medication, because the efficacy is not well established, and because there are safety concerns (adverse effects include among others sedation and hallucinations). As such, the present paper mainly serves to emphasize the need for carefully controlled clinical trials to further establish both the efficacy and safety of cannabis treatment."

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IOS Press

Mouse study: gabapentin prevents harmful structural changes in spinal cord

image: Phillip Popovich is a professor and chair of Ohio State's Department of Neuroscience and Executive Director of the Belford Center for Spinal Cord Injury at The Ohio State University College of Medicine.

Image: 
The Ohio State University Wexner Medical Center

COLUMBUS, Ohio - Research led by The Ohio State University Wexner Medical Center and College of Medicine found that the widely prescribed pain-relief drug gabapentin can prevent harmful structural changes in the injured spinal cords of mice, and also block cardiovascular changes and immune suppression caused by spinal cord injury.

"Gabapentin is often prescribed as a treatment for pain, but if it is given early after injury - before symptoms develop - it can also limit structural changes in nerve cells. We show that these benefits remain even one month after stopping gabapentin treatment in spinal injured mice. We believe that gabapentin could be repurposed as a prophylactic therapy that can prevent autonomic dysfunction in people affected by spinal cord injuries," said Phillip Popovich, senior author and chair of Ohio State's Department of Neuroscience.

Study findings are published online in the journal Cell Reports.

"This is the first time a treatment has been shown to prevent the development of autonomic dysfunction, rather than manage the symptoms caused by autonomic dysfunction. In response to stress or danger, autonomic nerve cells in the spinal cord trigger a 'fight or flight' response. This is a normal and helpful response that increases blood pressure and releases hormones like adrenaline and cortisol," said lead author Faith Brennan, research scientist in Ohio State's department of neuroscience.

But, after traumatic spinal cord injury, massive structural changes occur within spinal autonomic nerve centers that control the fight or flight response, and these changes cause uncontrolled autonomic reflexes.

For example, normally harmless stimuli, such as the bladder filling, will trigger the fight or flight response. But because of the spinal cord injury, the response is uncontrolled and can cause several health problems, including severe high blood pressure, heart rate slowing and long-term immune suppression.

"Autonomic dysfunction is a major problem for people living with a spinal cord injury. The cardiovascular complications can lead to severe morbidities like heart attack and stroke while long-term immune suppression can lead to serious recurrent infections like pneumonia," Popovich said.

Currently, these symptoms can only be managed, (regular bowel/bladder voiding regimens, for example), but there is no treatment.

"The possibility of repurposing gabapentin as a prophylactic therapy to prevent the development of autonomic dysfunction could significantly improve the quality of life for individuals living with spinal cord injuries, including greater independence in society, reduced caregiver reliance, reduced infection susceptibility and increased life expectancy," Brennan said. "Gabapentin is FDA-approved, and is already widely used to manage neuropathic pain caused by spinal cord injuries. If patients are treated early after their injuries, gabapentin could prevent the harmful structural changes that are inevitable in most severe spinal cord injuries."

This study builds on Ohio State's previous research showing that autonomic dysfunction directly drives immune suppression, said Popovich, who also is a researcher in Ohio State's Neurological Institute and the Belford Center for Spinal Cord Injury.

"We don't know how long treatment can be delayed after injury and still maintain the beneficial effects. Ongoing studies in the Belford Center are optimizing this treatment onset window. We also don't know if gabapentin targets other cells/organs in the body, so we'll investigate the effects of this therapy on other tissues beyond the spinal cord," Popovich said.

Credit: 
Ohio State University Wexner Medical Center

Hybrid closed-loop insulin therapy improves glycemic control

image: Journal that covers new technology and new products for the treatment, monitoring, diagnosis, and prevention of diabetes and its complications.

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, January 26, 2021--Hybrid closed-loop insulin therapy improved glycemic control in adolescents and young adults with type 1 diabetes. These outcomes, derived from the International Diabetes Closed-Loop (iDCL) Trial, are reported in the peer-reviewed journal Diabetes Technology & Therapeutics (DTT). Click here to read the article now.

Adolescents and young adults with a mean age of 17 years were randomly assigned to a closed-loop control (CLC) insulin delivery system or a sensor augmented pump (SAP) with a continuous glucose monitoring system over a 6-month period. The Time in Range increased by 13% for the CLC group, compared to a decrease of 1% with SAP, for a group difference of +3.1 hours/day. This reflected a reduction in time spent at >180 mg/dL. The use of CLC was especially effective at increasing Time in Range overnight.

"Notably, we found that this sample of adolescents and young adults successfully used the CGM more than 90% of the time during the 6-month trial and the closed-loop system was active 89% of the time," stated John Lum, Jaeb Center for Health Research, and the iDCL Trial Research Group.

"Multiple Automated Insulin Delivery (AID) systems using different algorithms have been developed in the past decade for patients with type 1 diabetes. Almost all of the systems have shown significant reductions in nocturnal hypoglycemia. The iDCL multicenter trial done in young adults and adolescents with T1D reported in this issue of DTT further advances the use of hybrid closed-loop system by increasing the time-in-range, especially during the night," says Satish Garg, MD, University of Colorado Denver and Editor-in-Chief of Diabetes Technology & Therapeutics.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

Satellite data reveals bonds between emissions, pollution and economy

image: The city of Denver, Colorado, blanketed by smog.

Image: 
National Oceanic and Atmospheric Administration

Burning fossil fuels has long powered world economies while contributing to air pollution and the buildup of greenhouse gases. A new analysis of nearly two decades of satellite data shows that economic development, fossil-fuel combustion and air quality are closely linked on the continental and national scales, but can be decoupled at the national level, according to Penn State scientists.

"We know air pollution and economic development are linked, but we want to know how tightly and whether our actions can change this," said Ruixue Lei, a post-doctoral researcher in the Department of Meteorology and Atmospheric Science. "We found they are not inherently bonded and can be decoupled under favorable policies."

While previous research has explored the connections between air pollution, fossil-fuel emissions and economic growth, the study is the first to examine all three jointly to determine their long-term, global relationships, the scientists said.

"The significance of this study is that data from satellites was used for the first time to prove that we actually do not need to sacrifice our environment while at the same time having a growth economy," said Sha Feng, assistant research professor of meteorology and atmospheric science. "This relationship can be detangled, but countries may need infrastructure or policy support to make it happen."

The team analyzed 18 years of satellite data measuring the amounts of anthropogenic aerosols in the atmosphere and fossil-fuel carbon dioxide emission estimates from the Open-Data Inventory for Anthropogenic Carbon product to determine anthropogenic emissions on continental and national scales. They then compared those findings to gross domestic product data for individual countries.

Their data showed the fastest growing nations suffer the most severe pollution while countries like the United States were able to grow their economies while slowing emissions, the scientists said. The team developed a filter that allowed them to focus on cities and other areas where emissions result from human activities.

"We found the linkage between fossil-fuel combustion and air quality is not how much you emitted, it is how fast the annual increase of the combustion was," Lei said. "Maybe at this stage all countries cannot unbound these factors, but we still see good examples that give us hope."

There are different types of pollutants associated with the burning of fossil fuels, and the satellite data also indicated that these varied widely by country, the scientists said.

The results, published in the journal Environmental Research Letters, indicate that certain types of pollutants may be more associated with one economic system than another, and that those may change as a nation goes through phases of development, the scientists said.

"This paper is a first step to look at fossil-fuel emissions using satellite data at a national scale and to provide information for policy makers who face difficult challenges in balancing economic growth and reducing fossil-fuel emissions," Feng said.

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Penn State

Researchers simplify the study of gene-environment interactions

Researchers at Weill Cornell Medicine and Cornell University's Ithaca campus have developed a new computational method for studying genetic and environmental interactions and how they influence disease risk.

The research, published Jan. 7 in The American Journal of Human Genetics, makes the process of finding these interactions much less difficult and demonstrates their importance in determining body mass index and diabetes risk.

"Our study demonstrates that your genes matter and the environment matters and that the interaction of the two can increase risk for disease," said co-senior author, Dr. Olivier Elemento, who is professor of computational genomics in computational biomedicine, professor of physiology and biophysics, associate director of the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, and director of the Caryl and Israel Englander Institute for Precision Medicine at Weill Cornell Medicine.

Typically, studying gene-environment interactions creates a huge computational challenge, said lead author Andrew Marderstein, a doctoral candidate in the Weill Cornell Graduate School of Medical Sciences whose research was conducted both in Dr. Elemento's lab in New York City and Dr. Andrew Clark's lab in Ithaca, enabling him to have immediate access to computational biology and population health expertise.

"Genotype-environment interaction can be thought of as the situation where some genotypes are much more sensitive to environmental insults than others," said Dr. Clark, co-senior author and Jacob Gould Schurman Professor of Population Genetics in the Department of Molecular Biology and Genetics in the College of Arts & Sciences and a Nancy and Peter Meinig Family Investigator at Cornell University. "These are exactly the cases where changes in the diet or other exposures might have the biggest improvement in health, but only for a subset of individuals."

The millions of genetic variants, or inherited genetic differences found between individuals in a population, and different lifestyle and environmental factors, such as smoking, exercise, different eating habits, can be analyzed for combined effects in numerous ways. When researchers test for gene-environment interactions, they typically analyze millions of data points in a pairwise fashion, meaning they assess one genetic variant and its interaction with one environmental factor at a time. This type of analysis can become quite labor intensive, said Marderstein.

The new computational method prioritizes and assesses a smaller number of variants in the genome--or the complete set of genetic material found in the body--for gene-environment interactions. "We condensed a problem with analyzing 10 million different genetic variants to essentially analyzing only tens of variants in different regions of the genome," Marderstein said.

While a standard genetic association study might look at whether a single genetic variant could lead to an average change in body mass index (BMI), this study assessed which genetic variants were associated with individuals being more likely to have a higher BMI or lower BMI. The researchers found that looking for sections of DNA associated with the variance in a human characteristic, called a variance quantitative trait locus or vQTL, enabled them to more readily identify gene-environment interactions. Notably, the vQTLs associated with body mass index were also more likely to be associated with diseases that have large environmental influences.

Another area of study where the new computational method might useful is determining how an individual might respond to a specific drug based on gene-environment interactions, said Marderstein. Analysis of social determinants of health, meaning a person's environmental and social conditions, such as poverty level and educational attainment, is a third area that the researchers are interesting in pursuing, according to Dr. Elemento.

Overall, scientists in the precision medicine field are realizing they can sequence a person's DNA, in addition to assessing environmental factors such air quality and physical activity, to better understand whether the individual is at risk of developing a specific disease. "The idea down the line is to use these concepts in the clinic," said Dr. Elemento. "This is part of the evolution of precision medicine, where we can now sequence somebody's genome very easily and then potentially analyze all of the variants in the genetic landscape that correlate with the risk of developing particular conditions."

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Weill Cornell Medicine

Smart algorithm cleans up images by searching for clues buried in noise

To enter the world of the fantastically small, the main currency is either a ray of light or electrons.

Strong beams, which yield clearer images, are damaging to specimens. On the other hand, weak beams can give noisy, low-resolution images.

In a new study published in Nature Machine Intelligence, researchers at Texas A&M University describe a machine learning-based algorithm that can reduce graininess in low-resolution images and reveal new details that were otherwise buried within the noise.

"Images taken with low-powered beams can be noisy, which can hide interesting and valuable visual details of biological specimens," said Shuiwang Ji, associate professor in the Department of Computer Science and Engineering. "To solve this problem, we use a pure computational approach to create higher-resolution images, and we have shown in this study that we can improve the resolution up to an extent very similar to what you might obtain using a high beam."

Ji added that unlike other denoising algorithms that can only use information coming from a small patch of pixels within a low-resolution image, their smart algorithm can identify pixel patterns that may be spread across the entire noisy image, increasing its efficacy as a denoising tool.

Instead of solely relying on microscope hardware to improve the images' resolution, a technique known as augmented microscopy uses a combination of software and hardware to enhance the quality of images. Here, a regular image taken on a microscope is superimposed on a computer-generated digital image. This image processing method holds promise to not just cut down costs but also automatize medical image analysis and reveal details that the eye can sometimes miss.

Currently, a type of software based on a machine-learning algorithm called deep learning has been shown to be effective at removing the blurriness or noise in images. These algorithms can be visualized as consisting of many interconnected layers or processing steps that take in a low-resolution input image and generate a high-resolution output image.

In conventional deep-learning-based image processing techniques, the number and network between layers decide how many pixels in the input image contribute to the value of a single pixel in the output image. This value is immutable after the deep-learning algorithm has been trained and is ready to denoise new images. However, Ji said fixing the number for the input pixels, technically called the receptive field, limits the performance of the algorithm.

"Imagine a piece of specimen having a repeating motif, like a honeycomb pattern. Most deep-learning algorithms only use local information to fill in the gaps in the image created by the noise," Ji said. "But this is inefficient because the algorithm is, in essence, blind to the repeating pattern within the image since the receptive field is fixed. Instead, deep-learning algorithms need to have adaptive receptive fields that can capture the information in the overall image structure."

To overcome this hurdle, Ji and his students developed another deep-learning algorithm that can dynamically change the size of the receptive field. In other words, unlike earlier algorithms that can only aggregate information from a small number of pixels, their new algorithm, called global voxel transformer networks (GVTNets), can pool information from a larger area of the image if required.

When they analyzed their algorithm's performance against other deep-learning software, the researchers found that GVTNets required less training data and could denoise images better than other deep-learning algorithms. Furthermore, the high-resolution images obtained were comparable to those obtained using a high-energy light beam.

The researchers noted that their new algorithm can easily be adapted to other applications in addition to denoising, such as label-free fluorescence imaging and 3D to 2D conversions for computer graphics.

"Our research contributes to the emerging area of a smart microscopy, where artificial intelligence is seamlessly integrated into the microscope," Ji said. "Deep-learning algorithms such as ours will allow us to potentially transcend the physical limit posed by light that was not possible before. This can be extremely valuable for a myriad of applications, including clinical ones, like estimating the stage of cancer progression and distinguishing between cell types for disease prognosis."

Credit: 
Texas A&M University

Concordia researchers find melatonin is effective against polycystic kidney disease

image: Chiara Gamberi (left) and Cassandra Millet-Boureima: "I hope there will be more research on the drugs we tested and that we get more results that will help the polycystic kidney disease community."

Image: 
Concordia University

A hormone commonly associated with sleep-wake regulation has been found to reduce cysts in fruit flies, according to Concordia researchers. It's a finding that may affect the way we treat some kidney diseases and reduce the need for kidney transplants.

In a new paper published in the journal Molecules, alum Cassandra Millet-Boureima (MSc 19) and Chiara Gamberi, affiliate assistant professor of biology, write that melatonin was found to reduce cysts in the renal tubules of fruit flies. These tubules are also found in more complex mammals, including humans, where they are called nephrons. This study, which builds on previous studies by Millet-Boureima and Gamberi, was co-authored by Roman Rozencwaig and Felix Polyak of BH Bioscience in Montreal.

The researchers hope that their findings can be applied to treating people suffering from autosomal dominant polycystic kidney disease. ADPKD is a genetic chronic and progressive disease characterized by the growth of dozens of cysts in the nephrons. It is incurable and affects approximately 12.5 million worldwide.

Similarities big and small

Because nephrons in vertebrates are embedded in other tissue, the researchers experimented on Drosophila -- the common fruit fly.

"Drosophila conserves many of the renal pathway components found in vertebrates and have anatomically isolated renal tubes," Gamberi explains. "With microdissection, we can isolate the tubules and conduct biochemical and molecular analysis."

The researchers bred fruit flies bearing the Bicaudal C gene mutation. It is known to cause kidney cysts in all manner of living beings, from flies to frogs to mice to humans.

Over 18 days, Millet-Boureima administered melatonin to 50 Drosophila and ethanol to a control group. She then dissected the flies and scored their cysts, a process yielding a cystic index. She found that the melatonin-treated flies had much fewer and smaller cysts than the control. Because Millet-Boureima was skilled at dissecting the insects and evaluating the recovered renal tubules, she was able to avoid bias in the count.

She was also able to distinguish three separate sections of the Drosophila tubule, each with its own unique function, and assign the cysts to a particular section. After testing several compounds on the same family of cells, she observed different activities along the length of the tubule. The researchers realized that they could potentially develop targeted treatment depending on the location of the cysts in a patient's nephrons.

"Biologically speaking, this has a lot of potential that we will obviously develop," Gamberi says.

Helping without harming

Though Gamberi says melatonin has not been previously used to treat PKD, she does think it holds some promise. PKD is a chronic disease, so treatment cannot include any toxic components. This rules out chemotherapy and tumour-killing antineoplastics used in oncology, for instance. However, melatonin is entirely non-toxic and shares certain properties with antineoplastics and anti-inflammatory agents.

"We know from oncology that melatonin has two effects when it is administered with chemotherapy," Gamberi explains. "First, it acts as a drug adjuvant to the chemotherapy, making it work more effectively against cancer cells. Second, it appears to protect healthy cells from the toxicity of the chemotherapy. Basically, melatonin increases the specificity of the chemotherapy. We hope that it can have a similar positive effect when used with an anti-ADPKD drug like tolvaptan, which can damage the liver."

The researchers are keen to share their findings as quickly as possible.

"I hope there will be more research on the drugs we tested and that we get more results that will help the PKD community," Millet-Boureima says.

Credit: 
Concordia University

Story tips from Johns Hopkins experts on Covid-19

STUDY PROFILES IMMUNE CELLS FIGHTING COVID-19, MAY HELP GUIDE NEXT-GEN VACCINE DEVELOPMENT

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

Even as the first vaccines for SARS-CoV-2, the virus that causes COVID-19, are being distributed, scientists and clinicians around the world have remained steadfast in their efforts to better understand how the human immune system responds to the virus and protects people against it. Now, a research team -- led by Johns Hopkins Medicine and in collaboration with ImmunoScape, a U.S.-Singapore biotechnology company -- has published one of the most comprehensive characterizations to date of a critical contributor to that protection: the response of immune system cells called T lymphocytes (more commonly known as T cells) in people who have recovered from SARS-CoV-2 infection.

The researchers, whose findings were posted online Jan. 11, 2021, in The Journal of Clinical Investigation, say that better defining which T cells interact with which specific portions of the SARS-CoV-2 virus -- as well as how those interactions can provide long-lasting immunity against COVID-19 -- may help spur development of the next generation of vaccines.

"We already knew that plasma from convalescent patients with COVID-19 -- those who have recovered from a SARS-CoV-2 infection -- can contain antibodies that neutralize the virus, which can then be used to help other patients with active infection," says study senior author Thomas Quinn, M.D., professor of medicine at the Johns Hopkins University School of Medicine and National Institutes of Health distinguished investigator at the National Institute of Allergy and Infectious Diseases. "Our study was designed to assess which T cells react to specific proteins of SARS-CoV-2, how they might complement neutralizing antibodies in recovery from infection and what can be done to optimize the process for long-term protection."

The T cells of interest to Quinn and his colleagues are known as CD8+ T cells, also called cytotoxic or killer T cells for their ability to eliminate foreign invaders such as bacteria and viruses from the body. To analyze them, the researchers collected blood samples from 30 convalescent patients who had recovered from mild cases of COVID-19. The six human leukocyte antigens (HLAs, as they are more commonly known, are cell-surface proteins that regulate the immune system and are part of each person's genetic profile) of the donors studied, Quinn says, are representative of some 73% of the continental U.S. population, meaning the study results have broad significance.

The samples were taken from 26 to 62 days after the donors stopped having COVID-19 symptoms, so that "their immune response would be fully matured in response to the virus and have primed certain CD8+ T cells against it," says Quinn. The Johns Hopkins Medicine researchers measured the level of neutralizing antibodies in the donors at various times post-recovery and stored samples for deeper analysis.

That assessment occurred when the donor samples were sent to ImmunoScape for the difficult task of identifying which T cells had responded to SARS-CoV-2. More specifically, the company's deep immune cell profiling method could show toward which virus proteins the T cells directed that response -- data that could provide valuable insight into the T cells' functional properties.

In a first-of-its-kind analysis, the ImmunoScape team used its highly sensitive HLA-SARS-CoV-2 tetramers -- laboratory-produced proteins that bind exclusively to their T cell targets -- to tag and identify the types of virus-recognizing CD8+ T cells. The samples were probed with 408 SARS-CoV-2 epitopes -- proteins that may elicit an immune response -- from the spikes on the virus surface, from the virus capsule and from nonstructural proteins inside the virus. The researchers then looked to see which T cells matched up with which epitopes.

"We found that 52 of the 408 epitopes were recognized by the T cells from the convalescent donors, with 18 of these epitope matchings previously unreported," says study co-author Aaron Tobian, M.D., Ph.D., director of the transfusion medicine division and professor of pathology at the Johns Hopkins University School of Medicine.
"Of these, 23% were derived from spike proteins -- the types targeted by the currently available COVID-19 vaccines -- while 14% were from capsule proteins and 63% were from nonstructural proteins that normally would not elicit an immune response."

Looking at the specific types of CD8+ T cells present at different times following recovery from COVID-19, the researchers found that as the levels of neutralizing antibodies increased in the convalescent plasma, so did the number of memory CD8+ T cells that recognized SARS-CoV-2 epitopes.

"That's good because those are the T cells you want to be primed in case you are exposed to SARS-CoV-2 a second time as they 'remember' the first infection and quickly direct the immune system to fight the virus before it takes root again," says Quinn.

Characterizing the CD8+ T cells in blood samples from convalescent patients that are specific to SARS-CoV-2 and, more importantly, specific to which viral epitopes, is an important achievement, Tobian adds.

"With this knowledge, we will be better equipped to design COVID-19 vaccines that produce a strong immune response and likely provide years of defense against SARS-CoV-2," he says.

Quinn and Tobian are available for interviews.

JOHNS HOPKINS MEDICINE RESEARCHER PART OF TEAM THAT QUANTIFIED 'PANDEMIC FATIGUE'

Media Contact: Danny Jacobs, djacob41@jhmi.edu

Anecdotal evidence of "pandemic fatigue" -- defined by the World Health Organization as "a lack of motivation to follow recommended COVID-19 protection behaviors" -- has been reported and shared almost as long as physical distancing guidelines have been around to fight the spread of the disease. Now, a research team, including a Johns Hopkins medical student, has the data to prove it.

The researchers analyzed almost nine months of survey responses to the University of Southern California's Understanding America Study, during which, twice each month, nearly 8,000 people across the United States were asked if they were practicing nonpharmaceutical interventions (NPIs), including physical distancing, frequent handwashing and wearing a mask.

The researchers used the data to develop a national NPI adherence index, detailed in a research letter published Jan. 22, 2021, in the Journal of the American Medical Association. The index, they report, started at 70 (out of 100, which would be total adherence) in early April 2020, dropped and plateaued in the high 50s in June, and increased slightly to 60 by Thanksgiving. The decrease was consistent across every region in the country.

"The plateau we see for overall NPI adherence in the results likely reflects some stability in the risk perception of different activities," says study lead author Matthew Crane, a second-year medical student at the Johns Hopkins University School of Medicine. "It's good to see adherence isn't continuing to drop at the initial rate because that would be terrible. But it's also disconcerting that protective behaviors overall have become relatively stable no matter what the national state of COVID-19 prevalence is. Given new, more transmissible variants of the virus that are arising globally, we really might need greater adherence to keep people safe."

The NPIs that had the largest decreases were remaining at home except for essential activities and exercise (79.6% of respondents did so in April 2020 compared with 41.1% by November), having no close contact with non-household members (63.5% decreased to 37.8%), not having visitors at their homes (80.3% decreased to 57.6%) and avoiding eating at restaurants (87.3% decreased to 65.8%).

"I was surprised [NPI adherence] wasn't more responsive to surges in COVID-19 cases," Crane says. "I thought it would fluctuate based on headlines and public health advisories."

The biggest increase was in mask wearing, which went from 39.2% to 88.6%. But Crane notes the survey asks if respondents have done or not done a specific action in the last seven days. That means a person might have worn a mask because it was required to visit a grocery store or another public space but was still opposed in principle to the rule.

"It might not be an endorsement of mask wearing," Crane says.

Crane hopes to continue to track NPI adherence and break down the survey data further, providing more insight for public health professionals to create targeted messaging to change behaviors.

"Until vaccines are very widely distributed, these protective behaviors will be the cornerstone of our national response. It's really what is going to get us through this, the NPIs," he says.

Crane is available for interviews.

MACHINE LEARNING TOOL GIVES EARLY WARNING OF CARDIAC ISSUES FOR PATIENTS WITH COVID-19

Media Contact: Danny Jacobs, djacob41@jhmi.edu

A team of Johns Hopkins University biomedical engineers and Johns Hopkins Medicine heart specialists have developed an algorithm that warns doctors several hours before patients hospitalized with COVID-19 experience cardiac arrest or blood clots.

The COVID-HEART predictor can forecast cardiac arrest for patients who have COVID-19 with a median early warning time of 18 hours, and it can predict blood clots three days in advance. It was developed with data from 2,178 patients treated at the five hospitals in the Johns Hopkins Health System between March 1 and Sept. 27, 2020.

"It's an early warning system to predict in real time these two outcomes in hospitalized COVID patients," said study senior author Natalia Trayanova, M.S., Ph.D., the Murray B. Sachs Professor of Biomedical Engineering and Medicine at the Johns Hopkins University School of Medicine. "The continuously updating predictor can help hospitals allocate the appropriate resources and proper interventions to attain the best outcomes for patients."

The paper was posted online Jan. 10, 2021, on the preprint website MedRxiv where scientists have been sharing urgent research related to COVID-19 throughout the pandemic. Trayanova's lab began the research in April 2020 with one of the first grants awarded from the National Science Foundation's Rapid Response Research effort.

Julie Shade, the study's lead author and a doctoral student in biomedical engineering at The Johns Hopkins University, built the machine-learning algorithm with more than 100 clinical data points, demographic information and laboratory results obtained from the JH-CROWN registry that Johns Hopkins established to collect COVID-19 data from every patient in the hospital system. Shade added other variables that she found reported by doctors on Twitter and from other preprint papers.

For example, the team did not anticipate that electrocardiogram (ECG) data would play a critical role in the prediction of blood clotting. But once it was added, the ECG data became one of the most accurate indicators for the condition, Trayanova said.

The researchers' next step is to develop the best method for setting up the technology in hospitals to aid in the care of patients with COVID-19.

Trayanova is available for interviews.

STUDY SHOWS PANDEMIC STRESS AFFECTS HOW PARENTS FEED THEIR CHILDREN

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

The COVID-19 pandemic has dramatically affected the lives of families everywhere. Household routines have changed, with families forced to spend more time than usual at home. School-aged children may have to prepare their own snacks and meals in between virtual classes, and parents might have less time to cook family meals because of their work-from-home schedules. Also, some parents have lost income, reducing family food budgets and changing the ability to afford healthy foods.

Johns Hopkins Medicine researchers surveyed families across the United States to learn how stress related to the pandemic is affecting the ways parents feed their children and in turn, what the children are eating.

A report on the findings was posted online as part of the journal Appetite's January 2021 special issue about COVID-19 impacts on food intake, appetite and weight status.

"Providing healthy meals and snacks to our kids can be a challenge even when we're not experiencing a pandemic," says study senior author Susan Carnell, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "The pandemic has massively disrupted families and caused a lot of stress, and this has naturally affected interactions around food."

In the Johns Hopkins Medicine study, 318 parents of children ages 2-12 answered survey questions about interactions with their children regarding meals and snacks, and their youngsters' diets during the pandemic. During the survey, parents were asked about stress related to the COVID-19 pandemic, pre-COVID-19 stress, financial stress (e.g. food insecurity), their feeding practices as parents and how frequently children ate snacks.

The results showed that parents who reported higher levels of stress due to the pandemic also were more likely to use food to manage children's emotions and behaviors. For example, they might offer less nutritious food and snacks, such as cookies, as rewards. These findings are consistent with those of previous research studies showing that parental stress levels and a family's inadequate access to food impact the behaviors of parents when feeding their kids. COVID-19-specific stress also was linked to children eating more sweet and savory snacks throughout the day.

However, other results suggest positive effects of pandemic disruption. For example, the researchers say that 75% of families reported their children had regular breakfast, lunch and dinner times, and less consistent snack times. Lower reported stress also was associated with consistent mealtimes and routines, and positive interactions regarding food, such as parents eating or engaging with their children around mealtimes. This, the researchers say, likely reflects the effects of parents and children spending more time at home and having more chances to interact regarding food.

"The pandemic seems to have produced both negative and positive impacts on food parenting practices," says study lead author Elena Jansen, Ph.D., a postdoctoral fellow in psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "We look forward to learning how new routines will become habitual as the pandemic progresses."

To help ensure healthier children during the COVID-19 pandemic and beyond, the researchers recommend that parents follow proven practices, such as establishing regular meal times, involving children in meal preparation, arranging to eat together as a family without television and other distractions, modeling healthy eating habits for children, and being responsive to the hunger and fullness levels of their children when offering food.

The researchers say their ongoing research across socioeconomically diverse families will investigate how parent-child mealtime interactions and child snack intake evolve as the pandemic continues and eventually resolves.

Carnell and Jansen are available for interviews.

Credit: 
Johns Hopkins Medicine

When push comes to shove, what counts as a fight?

image: Monk parakeets are gregarious colonial-nesting birds that live in a social hierarchy. They are invasive species in the United States.

Image: 
Michael Miller

Biologists often study animal sociality by collecting observations about several types of behavioral interactions. These interactions can be things like severe fights, minor fights, cooperative food sharing, or grooming each other.

But to analyze animal behavior, researchers need to make decisions about how to categorize these interactions and how to code these behaviors during data collection. Turns out, this question can be complicated.

Researchers at the University of Cincinnati dug into this tricky question while studying monk parakeets. In new research, published in the journal Current Zoology, the team asked: How do you properly categorize two seemingly similar behaviors? The study was led by UC postdoctoral researcher Annemarie van der Marel who worked with UC PhD students Sanjay Prasher, Claire O'Connell, and Chelsea Carminito and UC Assistant Professor Elizabeth Hobson.

"Biologists have to deal with this question: are the behaviors that we categorize as unique actually perceived as unique by the animals?" Hobson said. "How do the animals classify those behaviors?"

Biases can easily lead researchers astray in making these judgement calls. "If you look at chimpanzees, smiling is an aggressive behavior. But in humans, smiling is friendly," said van der Marel. "The behaviors look similar to us but the nuances of how the behaviors are used are very different."

Monk parakeets are highly social parrots that live in large colonies where they often interact with other individuals. The parakeets spend a large proportion of the day fighting, especially top-ranked birds, which makes it easy to distinguish them from birds ranked lower in the dominance hierarchy, said O'Connell. The birds demonstrate aggression in many ways. They bite, of course. But monk parakeets also like to take another parrot's perch through menace or sheer force.

UC biologists observed two types of this "king of the hill" behavior: "displacements", where one bird lunges at another bird and can bite to force that bird away, and "crowding", where a threatened bird moves before an aggressor is within biting range. The team coded these behaviors as distinct because they appeared to differ in the level of aggression, with displacements appearing as a more severe form of aggression with a higher potential for injury. 

The parakeets also used these behaviors somewhat differently, with displacements occurring much more often than the crowding.

The question is: were these behaviors essentially used in the same ways by the birds, so that they could be treated as the same types of events in later analyses?

Pooling two behaviors has major research benefits such as creating a richer dataset for future analyses. But pooling also carries a risk -- by generalizing, scientists could be losing nuances of behaviors that convey important information when considered alone, Hobson said.

To get to the bottom of this question, the team turned to computational analysis. They created a new computer model that compared the real aggression patterns to ones that were randomized. This approach allowed the team to test whether treating the two behaviors as interchangeable caused any changes in the social structure. "On top of being a great lab bonding experience, it was an exciting opportunity to learn how to use simulations to help answer research questions" Prasher said.

In the UC study, their computational analysis supported pooling the two behaviors. For the UC team, these results will help them plan their future analyses as they work to understand the complex social lives of these parakeets. More broadly, van der Marel said the new framework can also help other animal-behavior researchers make informed and data-driven decisions about when to pool together behaviors and when to separate them.

Credit: 
University of Cincinnati

Mouse study identifies novel compound that may help develop diabetes drugs

image: Dr. Rama K. Mallampalli is professor and chair of the Department of Internal Medicine at The Ohio State University Wexner Medical Center and The Ohio State University College of Medicine.

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The Ohio State University Wexner Medical Center

COLUMBUS, Ohio - Research led by The Ohio State University Wexner Medical Center and College of Medicine identified a new compound that might serve as a basis for developing a new class of drugs for diabetes.

Study findings are published online in the journal Nature Chemical Biology.

The adenosine monophosphate-activated protein kinase (Ampk) is a crucial enzyme involved in sensing the body's energy stores in cells. Impaired energy metabolism is seen in obesity, which is a risk factor for diabetes. Some medications used to treat diabetes, such as metformin, work by increasing the activity of Ampk.

"In our study, we discovered a protein that is involved in removing Ampk from cells called Fbxo48. We designed and tested a compound termed, BC1618, that blocks Fbxo48 and was much more potent than metformin in increasing Ampk function. BC1618 improved responses to insulin, a measure of effectiveness for diabetes medicines, in obese mice," said Dr. Rama K. Mallampalli, senior author and chair of the department of internal medicine at Ohio State.

Mallampalli began this research at The University of Pittsburgh before joining Ohio State, and continued collaborating with researchers there to complete the study.

"This study builds on our prior research to understand how critical proteins in the body are removed or degraded. The research team had previously designed and produced a family of anti-inflammatory drugs that are FDA approved and are poised to enter Phase 1 studies," Mallampalli said. "Using this new compound as a backbone, our team including Dr. Bill Chen and Dr. Yuan Liu at Pittsburgh will make other compounds that are more potent and safe in animal models and then test them in diabetes animal models. Eventually we aim to obtain FDA approval for human testing."

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Ohio State University Wexner Medical Center

Study sheds new light on the behaviour of the giant carnivorous dinosaur Spinosaurus

image: Reconstructed skeleton of a moderately sized Spinosaurus showing its famous sail-back and tail plume. Scale bar is 1 m.

Image: 
Image by Genya Masukawa who retains the copyright but this is free to use in conjunction with this story.

New research from Queen Mary University of London and the University of Maryland, has reignited the debate around the behaviour of the giant dinosaur Spinosaurus.

Since its discovery in 1915, the biology and behaviour of the enormous Spinosaurus has puzzled palaeontologists worldwide. It was recently argued that the dinosaur was largely an aquatic predator, using its large tail to swim and actively pursue fish in the water.

The new study, published today in Palaeontologia Electronica, challenges this recent view of Spinosaurus suggesting that whilst it likely fed from the water, and may have swum, it wasn't well adapted to the life of an aquatic pursuit predator. Instead it was like a giant (if flightless) heron or stork - snatching at fish from the shoreline while also taking any other small available prey on land or in water.

The researchers compared the features of Spinosaurus with the skulls and skeletons of other dinosaurs and various living and extinct reptiles that lived on land, in the water or did both. They found that whilst there were several pieces of evidence that contradicted the aquatic pursuit predator concept, none contradicted the wading heron-like model, and various lines of evidence actively supported it.

Dr David Hone, Senior Lecturer at Queen Mary and lead author on the project said: "The biology and ecology of Spinosaurus has been troubling palaeontologists for decades. Some recent studies have suggested that it was actively chasing fish in water but while they could swim, they would not have been fast or efficient enough to do this effectively. Our findings suggest that the wading idea is much better supported, even if it is slightly less exciting."

Co-author Tom Holtz, Principal Lecturer in Vertebrae Paleontology, University of Maryland, said: "Spinosaurus was a bizarre animal even by dinosaur standards, and unlike anything alive today, so trying to understand its ecology will always be difficult. We sought to use what evidence we have to best approximate its way of life. And what we found did not match the attributes one would expect in an aquatic pursuit predator in the manner of an otter, sea lion, or short-necked plesiosaur."

One of the key pieces of evidence unearthed by the researchers related to the dinosaur's ability to swim. Spinosaurus was already shown to be a less efficient swimmer than a crocodile, but also has fewer tail muscles than a crocodile, and due to its size would have a lot more drag in the water.

Dr Hone said: "Crocodiles are excellent in water compared to land animals, but are not that specialised for aquatic life and are not able to actively chase after fish. If Spinosaurus had fewer muscles on the tail, less efficiency and more drag then it's hard to see how these dinosaurs could be chasing fish in a way that crocodiles cannot."

Dr Holtz added: "We certainly add that the evidence points to Spinosaurus feeding partly, even mostly, in the water, probably more so than any other large dinosaur. But that is a different claim than it being a rapid swimmer chasing after aquatic prey." Though as Dr Hone concludes: "Whilst our study provides us with a clearer picture of the ecology and behaviour of Spinosaurus, there are still many outstanding questions and details to examine for future study and we must continue to review our ideas as we accumulate further evidence and data on these unique dinosaurs. This won't be the last word on the biology of these amazing animals."

Originally found in Egypt, Spinosaurus is thought to be one of the largest carnivorous dinosaurs to exist probably reaching over 15 m in length. The first known Spinosaurus fossils were destroyed by Allied bombing during World War II, which has hampered palaeontologist's attempts to understand these unusual creatures. More recently the dinosaur found fame in the 2001 film Jurassic Park III, where it battles and defeats a Tyrannosaurus rex.

Credit: 
Queen Mary University of London

Can dogs rapidly learn words?

image: The Family Dog Project research team is investigating on these exceptionally talented dogs

Image: 
Photo by Claudia Fugazza

A new study found that talented dogs can learn new words after hearing them only four times.

While preliminary evidence seems to show that most dogs do not learn words (i.e. names of objects), unless eventually very extensively trained, a few individuals have shown some exceptional abilities.

The Family Dog Project research team at the Department of Ethology, Eötvös Loránd University, Budapest is investigating on these exceptionally talented dogs who seem to learn words in the absence of any formal training, but simply by being exposed to playing with their owners in the typical way owners do, in a human family.

Video abstract of the study: https://youtu.be/Wr_P5NR1A3k

A new study, just published in Scientific Reports, has provided surprising results about how quickly the gifted dogs can learn new words. Two gifted dogs, a Border Collie named Whisky, from Norway, already famous for her spontaneous categorization skills and a Yorkshire terrier named Vicky Nina, from Brazil, participated in this experiment. Their ability to learn a new word after hearing it only four times was tested.

While it is natural to think that dogs, like human children, would learn words mostly in a social context, previous studies tested the ability of talented dogs to learn object names during an exclusion-based task. In such task the dog was confronted with a setup in which seven familiar, already named dog toys were present, together with a novel one and his ability to choose the novel object upon hearing a novel name was tested.

"We wanted to know under which conditions the gifted dogs may learn novel words. To test this, we exposed Whisky and Vicky Nina to the new words in two different conditions" explains Claudia Fugazza, first author of the study, "during an exclusion-based task and in a social playful context with their owners. Importantly, in both conditions the dogs heard the name of the new toy only 4 times".

In the exclusion-based task, the dogs showed that they were able to select the new toy when their owner spoke a new name, confirming that dogs can choose by exclusion - i.e., excluding all the other toys because they already have a name, and selecting the only one that does not. However, this was not the way they would learn the name of the toy. In fact, when tested on their ability to recognize the toy by its name, as this was confronted with another equally novel name, the dogs failed.

The other condition, the social one, where the dogs played with their owners who pronounced the name of the toy while playing with the dog, proved to be the successful way to learn the name of the toy, even after hearing it only 4 times. Whisky and Vicky Nina were able to select the toys based on their names when they had learned the names this way.

"Such rapid learning seems to be similar to the way human children acquire their vocabulary around 2-3 years of age", comments Adam Miklósi, head of the Department of Ethology and co-author of the study.

To test whether most dogs would learn words this way, other 20 dogs were tested in the same condition, but none of them showed any evidence of learning the toy names, confirming that the capacity to learn words rapidly, in the absence of formal training is very rare and is only present in few gifted dogs.

After such few exposures, however, Whisky's and Vicky Nina's memory of the learned words decayed quite fast. While in the first test, conducted a couple of minutes after hearing the toy names, the dogs were successful, they did not succeed in most of the tests conducted after 10 minutes and 1 hour.

To find out more about the number of words that the gifted dogs can learn in a short timeframe, the researchers of Eötvös Loránd University have also recently launched the Genius Dog Challenge a project that became viral in the social media.

Vicky Nina, unfortunately, passed away in the meantime and could not take part in the Genius Dog Challenge. Whisky is participating in it, together with other five talented dogs that the scientists found all over the world in the past two years of search.

Credit: 
Eötvös Loránd University

Toddlers who use touchscreens may be more distractible

Toddlers with high daily touchscreen use are quicker to look at objects when they appear and are less able to resist distraction compared to toddlers with no or low touchscreen use - according to new research from Birkbeck, University of London, King's College London and University of Bath.

The research team say the findings are important for the growing debate around the role of screen time on toddlers' development especially given the increased levels of screen time seen during the COVID-19 pandemic.

Lead researcher Professor Tim Smith, from Birkbeck's Centre for Brain and Cognitive Development, said: "The use of smartphones and tablets by babies and toddlers has accelerated rapidly in recent years. The first few years of life are critical for children to learn how to control their attention and ignore distraction, early skills that are known to be important for later academic achievement. There has been growing concern that toddler touchscreen use may negatively impact their developing attention but previously there was no empirical evidence to support this."

To provide such evidence, Professor Smith's TABLET Project, at Birkbeck's Centre for Brain and Cognitive Development, recruited 12-month-old infants who had different levels of touchscreen usage. The study followed them over the next 2.5 years, bringing them into the lab three times, at 12 months, 18 months and 3.5 years. During each visit the toddlers took part in computer tasks with an eye-tracker to measure their attention. Objects appeared in different screen locations. How quickly toddlers looked at the objects and how well they could ignore distracting objects were measured.

Professor Smith states: "We found that infants and toddlers with high touchscreen use were faster to look at objects when they appeared and were less able to ignore distracting objects compared to the low users."

Dr Ana Maria Portugal, main researcher on the project points out "We are currently unable to conclude that the touchscreen use caused the differences in attention as it could also be that children who are more distractible may be more attracted to the attention-grabbing features of touchscreen devices than those who are not."

Co-investigator Dr Rachael Bedford, from the Department of Psychology at University of Bath commented: "What we need to know next is how this pattern of increased looking to distracting objects on screens relates to attention in the real-world: is it a positive sign that the children have adapted to the multitasking demands of their complex everyday environment or does it relate to difficulties during tasks that require concentration?"

Credit: 
University of Bath

Highly specific synaptic plasticity in addiction

image: One step of the methodology used to isolate and measure the MMP activity.

Image: 
Elsevier

Philadelphia, January 26, 2021 - Addiction, or substance use disorder (SUD), is a complex neurological condition that includes drug-seeking behavior among other cognitive, emotional and behavioral features. Synaptic plasticity, or changes in the way neurons communicate with one another, drives these addictive behaviors. These lasting brain changes are at the crux of why addiction is so hard to treat.

A new study in Biological Psychiatry, published by Elsevier, now shows that players in the extracellular environment - not just at neuronal interfaces - contribute to addiction plasticity. Neurons in a brain area called the nucleus accumbens are known to undergo addiction-related plasticity. Specifically, changes at synapses of medium spiny neurons (MSN), which sense the neurotransmitter dopamine, have been associated with drug-seeking and extinction behaviors.

Previous research had shown that plasticity at MSNs expressing the D1-type of dopamine receptor is linked to drug-seeking, whereas extinction of drug-seeking involves plasticity at MSNs containing the D2-type dopamine receptor. Now, research led by Peter Kalivas, PhD, and Vivian Chioma, PhD, shows that distinct enzymes working at D1- and D2-type MSNs underlie drug-seeking and extinction behaviors.

The researchers trained rats to self-administer heroin by pushing a lever for 10 days, followed by a 10-day withdrawal period. They then carefully examined the rats' brains under a microscope to detect enzymatic activity around the MSN synapses.

The study focused on the activity of extracellular enzymes called metalloproteinases (MMP). MMPs break down proteins that constitute the extracellular matrix around nerve cells. This matrix of proteins supports synaptic connections, but it also constrains the remodeling of synaptic connections in response to experience. Therefore, MMP activity directly impacts cells' ability to manifest neuroplastic changes.

To assess activity of the MMPs, the researchers used a technique called in vivo zymography, in which the rats' brains were injected with a fluorescent dye encapsulated in a protective gelatin coat at various points during the drug-training regimen. Once broken open by MMP enzymes, the dye becomes visible, allowing the investigators to observe cells' morphology as well as the enzymes' activity around specific cell types and sub-cellular locations.

"We found that drug cues increased MMP activity on one cell type in the nucleus accumbens," said Dr. Kalivas, referring to D1-type MSNs, "and they decreased activity on another cell type," the D2-type MSNs. "By showing this cellular specificity of MMP activation and inactivation by cues, we have identified novel molecules that may be potential targets for drug development in treating drug addiction," he added.

"This paper highlights the exquisite selectivity of addiction-related neuroplasticity," said John Krystal, MD, Editor of Biological Psychiatry. "In this study, cues associated with heroin delivery activated MMPs near dopamine D1 receptor-containing MSNs in the nucleus accumbens, promoting plasticity in key cells implicated in addiction. Rather than reducing this addiction-related effect on plasticity, extinction training instead increased MMP activity close to neighboring dopamine D2 receptor-containing MSNs – cells implicated in protection against addiction."

Importantly, the researchers also saw MMP activity associated with cells adjacent to the MSNs called astrocytes, a type of glial cell. The astrocytes, the extracellular matrix, and the two neurons forming a synapse are all part of what is termed the tetrapartite, or four-part, synaptic complex.

"Our work investigating cell-type specific synaptic neuroadaptations in the nucleus accumbens provides evidence of novel advances in our understanding of tetrapartite synaptic activity during heroin seeking," said Dr. Chioma. "This research demonstrates how integration of components of the tetrapartite synapse regulate specific addiction phenotypes."

Dr. Krystal added, "This finding suggests that recovery from addiction is not simply a reversal of addiction-related changes in the brain, but rather it also involves the laying down of new anti-addiction changes that protect against substance use."

Credit: 
Elsevier

How did Florida fail to respond to a coral disease epizootic and what's to follow?

image: A colony of the large grooved brain coral, Colpophyllia natans, infected by Stony Coral Tissue Loss Disease. The photo shows the progressive, rapid advance of disease, left-to-right, across the colony.

Image: 
William Precht

By 2020, massive losses of large populations of corals have been observed throughout Florida and into the greater Caribbean basin. Taking into account the high mortality and the large number of susceptible species affected, this is likely the most lethal case of Stony Coral Tissue Loss Disease (SCTLD) ever recorded in modern history.

However, for too long, the tremendous decline in coral reefs has wrongly been attributed to the local dredge project, which had been ongoing at the time of the initial reports. In a recent Perspectives paper, published in the open-access peer-reviewed journal Rethinking Ecology, William Precht, a carbonate sedimentologist by training and currently the Director of Marine and Coastal Programs for the independent environmental consulting firm Dial Cordy and Associates Inc., provides an overview about what went wrong and how Florida ended up in a situation, where the best that could be done is the rescue of genetic material from coral species already at risk of regional extinction.

In fact, the coral disease was first observed in September 2014 near Virginia Key, Florida, and is, unfortunately, still active throughout the Caribbean to this date.

Initially, the resource managers in Southeast Florida missed the short time window to respond to the emerging epidemic before it spreads. Once it began to reach into the greater Caribbean, many, including the mass media, were quick to blame the ongoing Port Miami Dredge Project for the coral reef losses, even though its activities, meant to widen or deepen existing ship channels, while minimising damage to coral reef resources, had already been under a thorough scrutiny by government agencies and intensive monitoring, conducted by trained scientific divers. Nevertheless, dredging has typically been assumed to be bad for corals. Furthermore, these events coincided with the State of Florida's prohibition for government employees to acknowledge global warming in their work.

In the meantime, SCTLD, a disease initiated by a regional thermal anomaly and coral bleaching event, was killing off the same suite of coral species in the same fashion throughout the region, well beyond the dredge site.

"Finally, when the agencies responded to the outbreak, their efforts were too little and much too late to make a meaningful difference. While eradication of the disease was never a possibility, early control measures may have slowed its spread, or allowed for the rescue of significant numbers of large colonies of iconic species. Because of the languid management response to this outbreak, we are now sadly faced with a situation where much of our management efforts are focused on the rescue of genetic material from coral species already at risk of regional extinction," explains Precht.

"Why was the response to the loss of our coral reefs to a coral disease epidemic such a massive failure? This includes our failure as scientists, regulators, resource managers, local media, and policy makers alike," he adds.

Credit: 
Pensoft Publishers