Physiology

Expert Alert: Stress, Anxiety, and COVID-19 – UMM News, Sports & Events

UMD Expert Robert Lloyd, associate professor of Psychology, UMD College of Education and Human Service Professions.

Lloyd's faculty expertise includes evolutionary psychology, experimental methods and measurements, mind-body connection, neurophysiology, neurochemistry, and psychopharmacology.

"The coronavirus pandemic has caused many of us to experience persistent, high levels of stress. It is important to understand what this can do to us, and to know what steps we can take to reduce these harmful effects as we watch the scenario unfold."

Robert Lloyd says understanding how the brain functions gives us insight on actions people can take to stay emotionally healthy as well as physically healthy in the face of the coronavirus pandemic.

Prolonged stress works on the brain in a cycle. Stopping the cycle is key to surviving a crisis.

The brains amygdala, the part of the brain where we experience emotions, responds to threatening stimuli in the environment. When it becomes activated, it causes the release of the stress hormone cortisol and prepares the body for a fight-or-flight responses. However, when stress becomes chronic, a continuous elevation in cortisol results in depressed immunity and depression. The elevation in cortisol feeds back to, and excites, the amygdala, which, in turn, causes more cortisol to be released.

Periodic exposure to bad news about the coronavirus elevates cortisol in the feedback cycle and contributes to a blunted immune response, immune deficiency, and a depressive state characterized by rumination and withdrawal.

Lloyd cites specific restorative actions, such as reframing and wellness activities along with engaging in safe social engagements, that can break the cortisol production feedback cycle.

Publications

Lloyd's publications include: "Ketamine modulates TRH and TRH-like peptide turnover in brain and peripheral tissues of male rats," in the journal, Peptides, April 2015, authors A. E. Pekary, University of California, Los Angeles, Albert Sattin, University of California, Los Angeles and Robert Lloyd, University of Minnesota Duluth. "The Behavioral Physiology and Antidepressant Mechanisms of Electroconvulsive Shock," in The Journal of ECT, November 2014, authors Robert Lloyd, University of Minnesota Duluth and Albert Sattin, University of California, Los Angeles.

Contact Information

rlloyd@d.umn.edu

(218) 726-6799

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Expert Alert: Stress, Anxiety, and COVID-19 - UMM News, Sports & Events

Physiology

COVID-19: Is India equipped to carry out clinical trials on vaccines? – Down To Earth Magazine

Three India-based organisations are involved in studies to find a vaccine against the novel coronavirus disease (COVID-19). But none are being tested in here as the country does not have animals suitable for such pre-clinical trials.

Vaccines have to go through a series of trials before they are ready for the market. First preclinical trials on animals and then a series of trials on human beings. The animal models used have to be susceptible to the disease so that the efficacy of the vaccine can be determined. It has been seen that most of the usual experimental animals are not affected by the virus. Researchers in Australia have shown that ferrets are a good model for testing the vaccines as they seem to have lung physiology similar to that of humans. The group is using ferrets to test two vaccines developed by University of Oxford and Pennsylvania-based Inovio Pharmaceuticals. Other researchers are reviving the mouse model developed during the SARS epidemic to carry out experiments. At that time, the mice had been modified to carry humanised ACE2 genes. But this revival involves breeding of the animals which is expected to take at least 9 weeks. The lack of suitable experimental animals is said to be the biggest reason that could delay the research on vaccines.

As suitable animals models are not available in India, none of the preclinical trials are being carried out in India. The pandemic was sudden and we were not prepared with the animals, says Suresh Pothani, director in charge of the National Animal Resource Facility for Biomedical Research under the ICMR. While India has hamsters;ferrets or the modified mice are not available. Bharat Biotech had approached us for preclinical studies but we did not have the animals, says Pothani. Now these are being carried out in University of Wisconsin-Madison. The same is true for the vaccine developed by Serum Institute of India and Codagenix, Inc. is also being tested in the USA. Pothani reveals that the institute has requested the secretary to import the animals to ensure future studies.

India has invested in creating facilities for carrying out research on animals. The Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), established under the Prevention of Cruelty to Animals Act 1960 has registered 1748 supplier establishments including government organisations from where researchers can get experimental animals. These animals include mice, hamsters, rabbits, guinea pigs along with transgenic animals. The animal trials are governed by the Breeding of and experiments on animals (Control and Supervision) Rules, 1998 which were last amended in 2006.

Maintaining these facilities is important as the new drugs and clinical trials rules 2018 mandates that pre-clinical tests are carried out on both rodents and non rodents (dogs and monkeys) before moving on to human trials. It is said that animal testing in India is very difficult because of strict animal rights rules implemented by CPCSEA. To avoid these, Pharma companies prefer to conduct them outside the country. Fortunately for them, the new drugs and clinical trials rules 2018 accept animal trials done outside the country.

But it is important now to improve these facilities now. Experts fear that if clinical trials are outsourced, the resultant drugs and vaccines might not be available easily in India. Since moving to the product patent regime, very few new products have been developed in India. In case of vaccines, one example of success is the development of Hepatitis B vaccine by Shantha Biotechnics which used a novel technique to develop the vaccine and could reduce the price to less than $1/dose.

The government is also exploring technologies such as organs-on-a-chip to reduce the harm to animals. This would ensure that animals are used only when absolutely necessary. The United Kingdom and the United States have national road maps for developing non-animal technologies. Denmark, Brazil, Germany, Switzerland, Australia, China and Korea also have research programmes for developing alternative technologies. PETA has listed some technologies that researchers are using to avoid use of animals. In an article published on their site on April 9, they give an example of researchers at the University of Bristol in England who are growing the virus in cells to gain a better understanding of the way it spreads and causes sickness.

This would require an overhaul of the drug-approval process in India to remove the clause about animal testing.

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COVID-19: Is India equipped to carry out clinical trials on vaccines? - Down To Earth Magazine

Physiology

Research shows how stress changes structure of the brain – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Apr 14 2020

Research led by Si-Qiong June Liu, MD, Ph.D., Professor of Cell Biology and Anatomy at LSU Health New Orleans School of Medicine, has shown how stress changes the structure of the brain and reveals a potential therapeutic target to the prevent or reverse it. The findings are published in JNeurosci.

Working in a mouse model, Liu and her research team found that a single stressful event produced quick and long-lasting changes in astrocytes, the brain cells that clean up chemical messengers called neurotransmitters after they've communicated information between nerve cells. The stressful episode caused the branches of the astrocytes to shrink away from the synapses, the spaces across which information is transmitted from one cell to another.

The team also discovered a mechanism resulting in communication disruption. They found that during a stressful event, the stress hormone norepinephrine suppresses a molecular pathway that normally produces a protein, GluA1, without which nerve cells and astrocytes cannot communicate with each other.

Stress affects the structure and function of both neurons and astrocytes. Because astrocytes can directly modulate synaptic transmission and are critically involved in stress-related behavior, preventing or reversing the stress-induced change in astrocytes is a potential way to treat stress-related neurological disorders. We identified a molecular pathway that controls GluA1 synthesis and thereby astrocyte remodeling during stress. This suggests new pharmacological targets for possible prevention or reversal of stress-induced changes."

Dr. Si-Qiong June Liu, MD, Ph.D., Professor of Cell Biology and Anatomy at LSU Health New Orleans School of Medicine

She says that since many signaling pathways are conserved throughout evolution, the molecular pathways that lead to astrocyte structural remodeling and suppression of GluA1 production may also occur in humans who experience a stressful event.

"Stress alters brain function and produces lasting changes in human behavior and physiology," Liu adds. "The experience of traumatic events can lead to neuropsychiatric disorders including anxiety, depression and drug addiction. Investigation of the neurobiology of stress can reveal how stress affects neuronal connections and hence brain function. This knowledge is necessary for developing strategies to prevent or treat these common stress-related neurological disorders."

Source:

Journal reference:

Bender, C.L., et al. (2020) Emotional stress induces structural plasticity in Bergmann glial cells via an AC5-CPEB3-GluA1 pathway. The Journal of Neuroscience. doi.org/10.1523/JNEUROSCI.0013-19.2020.

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Research shows how stress changes structure of the brain - News-Medical.Net

Biochemistry

Eight Students Selected as Spring 2020 Rising Researchers | Office of News & Media Relations – UMass News and Media Relations

Eight undergraduates from across campus have received the spring 2020 Rising Researcher award.

The Rising Researcher program celebrates undergraduate students who excel in research, scholarship or creative activity.

The spring 2020 Rising Researchers are:

Taylor Cassidy, classics, Commonwealth Honors CollegeWilliam Johnson, biology, Commonwealth Honors CollegeColin Lemire, biochemistry and molecular biology, Commonwealth Honors CollegeJoseph McGaunn, biochemistry and molecular biology, psychology, Commonwealth Honors CollegeJack Merullo, computer science, Commonwealth Honors CollegeKit Newell, theaterMadeline Scott, mechanical engineeringElizabeth Voke, chemical engineering, Commonwealth Honors College

Visit the Research Next website to learn more about the Rising Researchers.

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Eight Students Selected as Spring 2020 Rising Researchers | Office of News & Media Relations - UMass News and Media Relations

Neuroscience

Class of 2020, COVID-19 and sports: Track season ends before Susy Meza beats her own best time – Reno Gazette Journal

Susy Mesa, on far left, runs in a track meet for Sparks High, during her junior year. This year's season was cut short as schools stay closed amid the coronavirus pandemic.(Photo: Provided by Susy Meza)

Susy's story: This is the second series of stories following Sparks High School senior Susy Meza. Susy, 17, will graduate in June. She is the student body president, played sports and was on the prom committee. Sheplans to study neuroscience at the University of Nevada, Reno in the fall. The next few months of high school weresupposed to be the culmination of all her hard work, and the chance to beat her own record in the 300 meter hurdles before life was interrupted by the coronavirus pandemic.

Susy Meza keeps a picture of a post it note on herphone.

On it she had written oneof her senior year goals.

"I'm going to beat my personal record in hurdles," she said.

Story 1: Susy Mesa talks about missing her senior prom.

Susy, 17, runs track for Sparks High School. It's just one of the three sports Suzyhas done in high school. She was team captain this year for two, including the school's tennis team and cheerleading squad.

But beating the one-minute mark in the 300 meter hurdles was at the top of her high school bucket list.

Susy Meza, center, leads a chant. The high school senior's won't finish her last season of sports as schools remain closed amid the coronavirus pandemic.(Photo: Provided by Susy Meza)

And as a senior, she would lead the team in stretches before practice every day after school.

Instead, spring sports are canceled in Nevadaand across the country amid the coronavirus pandemic.

"I'm not really competitive but I wanted to grow and get better," Susy said of a senior year of missed track meets. "A lot of people run it faster than I do so I just wanted to do better for myself."

She will study neuroscience at the University of Nevada, Reno in the fall and wants to be a doctor.

This track season was likely the last time she would do competitive sports.

Susy Mesa plays tennis for Sparks High. Susy, 17, played three sports for Sparks High but the track season was cut short amid the COVID-19 pandemic.(Photo: Provided by Susy Mesa)

And she would be awarded the Golden Spike, a cord she could wear over her graduation gown to honor her for playing three sportsfor all four years of high school.

She would have been given the honor at thehigh school's now-canceled spring awards banquet.

She would have been the only one in hersenior class of more than 300 to get the honor this year.

"I don't know what happens now," she said. "I just know I have loved hurdles. It's about perseverance."

Susy Mesa, second from left, poses with her cheer team. Susy, 17, was the captain of the cheer, tennis and track team her senior year, now cut short, at Sparks High.(Photo: PRovided by Susy Mesa)

Siobhan McAndrew tells stories about the people of Northern Nevada and covers education in Washoe County. Read her journalism right here. Consider supporting her work by subscribing to the Reno Gazette Journal.

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Class of 2020, COVID-19 and sports: Track season ends before Susy Meza beats her own best time - Reno Gazette Journal

Neuroscience

Kirsten Wade: Wading into the unknown – University of Pittsburgh The Pitt News

Kirsten Wade has a curious case of wanderlust.

Its a habit, the Pitt senior said. I like to go places I dont know, look around and see what I can learn, see if there are new people I can meet.

Thats true in a literal sense. Shes studied abroad four times in Italy, Spain, Switzerland, Germany and Colombia.

But wanderlust sums up Wades life when shes not studying abroad, too. It serves as a metaphor for her meandering interests her passion for art, science, social work and volunteering. In her four years as a Pitt student, Wade has assembled an exhaustive resume encompassing research, mentorship and a whole host of interdisciplinary projects more seamlessly than most people write a grocery list. Shes an urban studies and neuroscience double major with minors in Spanish and chemistry and a concentration in Latin American studies. Thats all landed her a finalist spot for the Rhodes Scholarship, too.

Lets see, Ive done labs for neuro. Ive mentored inner city kids. Ive done internships with urban planning Oh god, what else is on here? she said, grabbing her resume.

A lot, it turns out. Last summer, Wade went to Manizales, Colombia, on a research mission with Pitts Latin American Studies department. One of her favorite memories of the time is taking a spur-of-the moment trip into the idyllic Andes mountains.

But theres a catch.

[Manizales has] a very high risk of a wide variety of natural disasters, Wade said, nonchalantly. Theres an active volcano anything built on the slopes has a risk of landslides.

Wade promises she doesnt have a thirst for danger, just a longing for adventure. But that high risk of landslides and volcanic eruptions brought Wade to Manizales in the first place for research purposes, of course. Her project asked the question: how do people function in their daily lives, knowing that it could be upended by disaster at any time? To find an answer, she surveyed and interviewed people of all different backgrounds in Manizales politicians, Red Cross officials, ordinary citizens and those who had been directly displaced by disasters.

Theres definitely a very present awareness of disasters, Wade said. But most people, for varying reasons, insist it wont affect them.

Since returning from Manizales, Wade has frequented neuroscience labs, done social work at the Birmingham free clinic and taught classes on international urbanism.

Michelle Wade chalks up her little sisters versatility to her insatiable curiosity.

She would have five majors if she could, Michelle told me. Shes always on the hunt for new experiences and opportunities.

I interviewed Kirsten Wade for the first time last spring, when her myriad of interests left her feeling as lost as a wayward traveler are my interests too broad? I hope not, she said, anxiously. This past February, I interviewed her again, and it was like talking to a different person.

Previously, I think I viewed my own curiosity as something I needed to have an answer to all the time. I had curiosities, but I felt too mentally frozen to explore them, Wade said. Now, I realize that not having that answer is the whole point and my curiosity feels so much more real, livable, captivating and insatiable.

For the most part, Wades curiosity has shaped her into a creature of passion someone who wants to help the people she meets and learn everything she possibly can about the human condition. Thats partly how she cultivated an interest in neuroscience.

I remember jokingly telling people [in high school] that I wanted to study brains because of how weird they are, and four to five years later that still somewhat holds true, Wade said.

Wades always been fascinated by how humans come to understand themselves through interacting with the world, she says, and all of that understanding occurs through processes in the brain. But despite the understanding that can arise from studying neuro, scientists actually know very little about the brain, Wade said. Luckily, wading into the unknown is Wades speciality.

I love how frequently we arrive at points in class where the professor stands in front of us and says We honestly do not know, Wade said.

One activity that allows Wade to dig into her not-yet-realized interests is her role as program coordinator for Alumni Breakfast, where she invites speakers from different backgrounds to speak about the work they do.

We call it existential crisis Tuesday, Wade said. Because a lot of speakers come in with cool professions Ive never heard of. And I just say Oh no, am I gonna go into that field now?

I attended an Alumni Breakfast with Wade on a damp Tuesday morning in February. Even though it was 8 a.m. and the speaker had a job in engineering, one of the few fields Wade hasnt touched, she diligently scrawled away at her notes as he spoke, blue eyes sparkling with passion.

A couple years ago, one speaker in particular grabbed her attention. Jennie Dorris has done research at Carnegie Mellon University studying how patients with Alzheimer's and dementia reacted to certain stimuli namely exercise, art and music.

Arts and neuroscience put together! Wade said. It was my dream.

Arts and neuroscience put together is exactly what Wade does in her lab now. Shes an undergraduate research assistant in the department of neuroscience, studying the limbic system a set of structures in the brain that deal with emotion and memory in mice and humans.

Wade is part of the mouse team, and she specifically studies a cluster of cells near the amygdala to try to understand neurodevelopment in areas of the brain involved with emotional processing. To observe the cells, Wade and her colleagues stain mouse brain tissue with a plethora of different colors.

[The images] look like space, she said. I love it.

But despite Wades love for neuroscience, her first job actually had nothing to do with brains at all. As an Americorps member during the summers before her first two years of college, she mentored 30 low-income inner city students. The project shes most proud of was when she taught them about the dangers of climate change and what they could do to curb its effects.

We taught them the little things like Turn off the lights when youre not using them, Wade said. But we also had them memorize the greenhouse gases. I watched a lot of them educate their parents about greenhouse gases, actually.

Having grown up in a small town in Massachusetts and attending a Catholic school, Wade said a lot of the lessons werent as progressive or inclusive as they could have been. It wasnt until she attended a social justice camp the summer after her senior year of high school that she began to learn about intersectionality and the concept of privilege, which she tries to recognize in herself and use to lift up others.

Thats actually how I got interested in food policy. I learned about food deserts at camp, Wade said. How are people able to stay healthy if they dont even have access to healthy food?

Shelly Danko+Day, a food policy expert in the Department of City Planning, said interdisciplinary expertise could bring an interesting spin to the topic of food insecurity, a project for which she was actively recruiting interns two years ago.

This brought Wade, a Pitt student with a double major in neuroscience and urban studies, into her office.

I just immediately thought Wow, shes great, Danko+Day said. She presented a lot of ideas integrating her studies in neuroscience and urban planning with food policy I was so impressed. I remember assuming she was in grad school.

In her interview with Danko+Day, Wade emphasized the need to view the issue from a personal perspective. It was an idea Danko+Day had never heard before, she said, but Wade took the project and ran with it.

Over the course of a semester she fished out data from the health department and layered it with rates of food insecurity by district, then compiled everything into eight separate reports.

Most people tend to focus solely on the data when doing a quantitative analysis, Danko+Day said, but Wade actually viewed each data point as a person, and wanted to paint a picture of every individual she described in her graphs and charts.

When you talk about health and health access, its very important to realize there are real people youre talking about, feeling the effects of a certain policy, Wade said.

Wade lights up I love connecting with people, she says. But connecting with people has proven a lot easier than connecting all of her passions into a career path. Last year, after spending two hours rifling through all of her life accomplishments, I asked Wade what the future looked like.

That question haunts me, she said at the time.

This year, before packing up my things and shrugging on my coat, I ask her that question again. Wade furrows her brow and tucks a strand of curly red hair behind her ear. She definitely wants to explore neuroscience research, she says, and shell probably go to graduate school. But other than that, shes not completely sure.

She pauses, allowing herself a relaxed smile.

The simple truth is, Im not sure where Ill end up, Wade said. But I am excited for the work Ill do as I figure it out.

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Kirsten Wade: Wading into the unknown - University of Pittsburgh The Pitt News

Neuroscience

Large-scale analysis links glucose metabolism proteins in the brain to Alzheimer’s disease biology – National Institute on Aging

In the largest study to date of proteins related to Alzheimers disease, a team of researchers has identified disease-specific proteins and biological processes that could be developed into both new treatment targets and fluid biomarkers. The findings suggest that sets of proteins that regulate glucose metabolism, together with proteins related to a protective role of astrocytes and microglia the brains support cells are strongly associated with Alzheimers pathology and cognitive impairment.

The study, part of the Accelerating Medicines Partnership for Alzheimers Disease (AMP-AD), involved measuring the levels and analyzing the expression patterns of more than 3,000 proteins in a large number of brain and cerebrospinal fluid samples collected at multiple research centers across the United States. This research was funded by the National Institutes of Healths National Institute on Aging (NIA) and published April 13 in Nature Medicine.

This is an example of how the collaborative, open science platform of AMP-AD is creating a pipeline of discovery for new approaches to diagnosis, treatment and prevention of Alzheimers disease, said NIA Director Richard J. Hodes, M.D. This study exemplifies how research can be accelerated when multiple research groups share their biological samples and data resources.

The research team, led by Erik C.B. Johnson, M.D., Ph.D, Nicholas T. Seyfried, Ph.D., and Allan Levey, M.D., Ph.D., all at the Emory School of Medicine, Atlanta, analyzed patterns of protein expression in more than 2,000 human brain and nearly 400 cerebrospinal fluid samples from both healthy people and those with Alzheimers disease. The papers authors, which included Madhav Thambisetty, M.D., Ph.D., investigator and chief of the Clinical and Translational Neuroscience Section in the NIAs Laboratory of Behavioral Neuroscience, identified groups (or modules) of proteins that reflect biological processes in the brain.

The researchers then analyzed how the protein modules relate to various pathologic and clinical features of Alzheimers and other neurodegenerative disorders. They saw changes in proteins related to glucose metabolism and an anti-inflammatory response in glial cells in brain samples from both people with Alzheimers as well as in samples from individuals with documented brain pathology who were cognitively normal. This suggests, the researchers noted, that the anti-inflammatory processes designed to protect nerve cells may have been activated in response to the disease.

The researchers also set out to reproduce the findings in cerebrospinal fluid. The team found that, just like with brain tissue, the proteins involved in the way cells extract energy from glucose are increased in the spinal fluid from people with Alzheimers. Many of these proteins were also elevated in people with preclinical Alzheimers, i.e., individuals with brain pathology but without symptoms of cognitive decline. Importantly, the glucose metabolism/glial protein module was populated with proteins known to be genetic risk factors for Alzheimers, suggesting that the biological processes reflected by these protein families are involved in the actual disease process.

Weve been studying the possible links between abnormalities in the way the brain metabolizes glucose and Alzheimers-related changes for a while now, Thambisetty said. The latest analysis suggests that these proteins may also have potential as fluid biomarkers to detect the presence of early disease.

In a previous study, Thambisetty and colleagues, in collaboration with the Emory researchers, found a connection between abnormalities in how the brain breaks down glucose and the amount of the signature amyloid plaques and tangles in the brain, as well as the onset of symptoms such as problems with memory.

This large, comparative proteomic study points to massive changes across many biological processes in Alzheimers and offers new insights into the role of brain energy metabolism and neuroinflammation in the disease process, said Suzana Petanceska, Ph.D., program director at NIA overseeing the AMP-AD Target Discovery Program. The data and analyses from this study has already been made available to the research community and can be used as a rich source of new targets for the treatment and prevention of Alzheimers or serve as the foundation for developing fluid biomarkers.

Brain tissue samples came from autopsy of participants in Alzheimers disease research centers and several epidemiologic studies across the country, including the Baltimore Longitudinal Study of Aging (BLSA), Religious Orders Study (ROS) and Memory and Aging Project (MAP), and Adult Changes in Thought (ACT) initiatives. The brain collections also contained samples from individuals with six other neurodegenerative disorders as well as samples representing normal aging, which enabled the discovery of molecular signatures specific for Alzheimers. Cerebrospinal fluid samples were collected from study participants at the Emory Goizueta Alzheimers Disease Research Center. These and other datasets are available to the research community through the AD Knowledge Portal, the data repository for the AMP-AD Target Discovery Program, and other NIA supported team-science projects operating under open science principles.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

The research in this study is funded by NIH grants R01AG053960, R01AG057911, R01AG061800, RF1AG057471, RF1AG057470, R01AG061800, R01AG057911, R01AG057339, U01AG061357, P50AG025688, RF1AG057470, RF1AG051633, P30AG10161, R01AG15819, R01AG17917, U01AG61356, R01AG056533, K08NS099474, U01AG046170, RF1AG054014, RF1AG057440, R01AG057907, U01AG052411, P30AG10124, U01AG046161, R01AG050631, R01AG053960, R01AG057339, U01AG061357, P50AG005146, U24NS072026, and P30AG19610.

Reference: Johnson ECB et al. Large-scale proteomic analysis of Alzheimers disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nature Medicine. 2020 Apr 13. doi:10.1038/s41591-020-0815-6

About the National Institute on Aging (NIA): NIA leads the U.S. federal government effort to conduct and support research on aging and the health and well-being of older people. Learn more about age-related cognitive change and neurodegenerative diseases via NIAs Alzheimer's and related Dementias Education and Referral (ADEAR) Center website. For information about a broad range of aging topics, visit the main NIA website and stay connected.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

NIH...Turning Discovery Into Health

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Large-scale analysis links glucose metabolism proteins in the brain to Alzheimer's disease biology - National Institute on Aging

Neuroscience

Brown, Harvard, Yale. Pawtucket teen has been accepted to all 3, and more – The Providence Journal

PAWTUCKET The first acceptance letter came from Brown University. The next one from Harvard. When a thick envelope arrived from Yale University, Victoria Wijerathnayapa was totally blown away.

Wijerathnayapa is not only the first student from Blackstone Valley Prep to get into Harvard and Yale, she is the first one to be admitted to three Ivy League institutions.

Her first reaction?

"I was super happy," Wijerathnayapa said Thursday. "It was a really emotional experience, but a happy one."

The good news doesnt stop there. She was accepted at eight other colleges, including Brandeis, Swarthmore, Wellesley, Williams and Worcester Polytechnic Institute.

A first-generation college student whose mother is from Sri Lanka, Wijerathnayapa is not one to brag. She acknowledges that she doesnt fit the typical Ivy League mold. She didnt study abroad or attend a prestigious public or private school. In fact, shes never left New England.

She attributes her success to Blackstone Valley Prep, a cluster of charter schools in northern Rhode Island where college banners adorn classroom doors, where race and equity are part of the fabric of conversation.

In her Pawtucket elementary school, Wijerathnayapa says, she felt singled out for being bright.

In fifth grade, Wijerathnayapa won the lottery, literally. She was admitted to BVP, where her fortunes brightened.

"At BVP, my hard work and determination were not credited to my race but rather to my character," she said. "People here accepted me for who I was, not what I looked like."

Blackstone Valley Prep did more than encourage her academic brilliance. It allowed her to choose from a palette of enriching experiences, from attending a summer program at Brown University to taking a years worth of college classes at the Community College of Rhode Island, where she is currently taking cellular biology, English composition and public speaking.

At BVP, Wijerathnayapa said, she feels known. She ticked off the teachers who have been friends and mentors: Mr. Leger, her chemistry teacher and track coach; and Mr. Jose, one of her college and career counselors.

"Just this morning, I was stressed out about having to apply for scholarships, and online learning. So many things were coming at me," she said. "Being a first-generation student, not knowing how to navigate the system, I reached out to Ashley Gemma, my college counselor. We discussed how to arrange my time better. She helped me figure out what the next steps were."

Although she and her younger brother were born here, Wijerathnayapa still sees the world through an immigrants eyes, her mothers eyes.

"She sacrificed herself. She tells me theyve all been worth it."

Sri Lanka, a tropical island off the coast of India, was wracked by civil war for 26 years, from 1983 to 2009. In 2004, a typhoon killed some 30,000 residents.

"My mom is the rock in my life," she said. "Ever since I was born, she was pushing me to take advantage of all of the opportunities life gives you. I am eternally grateful to her."

A trip to the Museum of Science in Boston triggered Wijerathnayapas interest in neuroscience, her likely major in college. But an internship with the Rhode Island Board of Elections in eighth grade sent her in a separate direction: political science.

"I realized that youth voter apathy is a big problem," she said.

David Jose, the dean of BVPs college and careers, recalled how Wijerathnayapa walked around the cafeteria, imploring students to register to vote. Then she managed to get actual voting machines to the school for a student council election.

"She has so many interests," Jose said. "You could talk to her for hours about neuroscience and psychology. And you could talk to her for many hours about philosophy and political science."

Jose felt Wijerathnayapa was destined to have her choice of the most selective colleges. But he said getting admitted to an Ivy League school wasn't what motivated her.

"Her first goal was to learn as much as possible," Jose said. "That ethos drove her regardless. Nobody gets into three Ivies."

Her mother, he said, is her core influence.

"Her mom is a big cheerleader," he said. "But Victoria is also very connected to the Sri Lankan community. Its important for her to represent as much as possible the immigrant community. In a conversation we had the other day, she was asking, "What can I do to give back?"

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Brown, Harvard, Yale. Pawtucket teen has been accepted to all 3, and more - The Providence Journal

Neuroscience

Ed School Professor Kurt W. Fischer, a Champion of Kindness, Dies at 76 | News – Harvard Crimson

Jane T. Haltiwanger Fischer fell in love with her husband, Kurt W. Fischer, for his mind.

He was a brilliant, brilliant man, she said. I fell in love with him for his mind, but as the years went by, and certainly in the last years, it was very clear that what I loved the most about him was his heart.

Fischer was a professor at Harvards Graduate School of Education and the director of its Mind, Brain, and Education Program prior to his retirement in 2015. He died on March 30 at the age of 76. His cause of death remains unclear; he had Alzheimers disease and had come into contact with a staff member at his care facility who tested positive for COVID-19.

Fischer spent 27 years of his career at the Graduate School of Education.

One of his most notable academic accomplishments was integrating concepts from neuroscience and psychology with the study of education, creating a field he later called Mind, Brain, and Education.

Howard E. Gardner '65, a professor at the Graduate School of Education and longtime friend and colleague, said the idea to connect the three fields made Fischer a visionary.

Not only was that unique at Harvard, it was really unique in the world, Gardner said. There was nobody else yet who had coupled this stuff together.

Fischer also created the dynamic skill theory, a scale to analyze the complex manner in which humans construct knowledge and develop skills, depending on individual factors like mood, age, previous experience, and environmental factors, like level of support.

Mary Helen Immordino-Yang, who studied under Fischer and is now a professor at the University of Southern California, said that after founding the interdisciplinary field of Mind, Brain, and Education, dynamic skill theory is his most powerful legacy.

Rather than trying to reduce the complexities of human beings to statistics or simple averages, or group level metrics that are sometimes true on the whole, Kurt developed ways to appreciate the systematicity in the variation, Immordino-Yang said.

In addition to his theoretical work, Fischer was a proponent of expanding access to educational research for teachers and administrators. In 2006, Fischer helped develop the Usable Knowledge Program, a digital publication of education research that allows professionals to connect research to practice, according to its website.

Seth Fischer, his son, recently read through much of his fathers work, searching for the common theme.

I think that the through-line was that he wanted people to understand that children matter. Their circumstances matter. Listening to them matters. Their emotions matter, he said.

Dean of the Graduate School of Education Bridget Terry Long lauded Fischers lasting legacy as a cognitive psychologist in a remembrance published by the school.

From spearheading programming in neuroscience and education to his steadfast commitment to his students, we are a better community due to his influence and contributions, Long said.

Graduate School of Education lecturer Joseph Blatt said Fischer, for all his accomplishments, always remained generous and gentle.

Generous in the sense that he was always willing to do the extra bit to support me as a colleague, Blatt said. And gentle in that he always did it in a collegial and friendly way, not in a dictatorial way that he could have done as a tenured professor holding an endowed chair.

On top of his academic contributions, Fischers colleagues praised his patience and skill as a teacher and mentor.

He was very good with students whether they were brilliant and didn't need any help at all, or whether they had real learning challenges, Gardner said. He attracted, over the years, hundreds and hundreds of students who wanted to understand more about how to help kids.

Bryan Mascio was one of those students. Prior to his time at Harvard, he had worked as a teacher with students who struggled in traditional classrooms. Mascio said he felt out of place at Harvard until he worked with Fischer.

I honestly didn't feel like I really fit in. But Kurt made it very clear that that didn't mean that I didn't belong, Mascio said. He was very much embracing of teachers and the experience and the expertise that we bring to the table.

Like Mascio, Vanessa Rodriguez was a teacher before she came to Harvard. She was not originally in Fischers program, but after she explained her teaching philosophy to him, he invited her to study Mind, Brain, and Behavior.

He said to me, You're in the wrong program. You belong here, Rodriguez said. That was really powerful for me. As a Latina, it's not something anyone ever says to you.

At first, she was skeptical.

I said to him, No, I don't. I don't know anything about the mind, I don't know anything about the brain. I'm just a teacher, Rodriguez recalled. And he said to me, Of course you know about the mind and brain because you're a teacher. That's what you're an expert in.

Rodriguez and David B. Daniel, a professor at James Madison University, both said Fischer advocated for academics from underrepresented backgrounds.

He invited me to be a visiting scholar at Harvard. And in my mind, people like me just didn't ever get that opportunity. He gave me an opportunity, Daniel said.

Fischers mentorship was not limited to students and colleagues at Harvard. Students from across the world sought his guidance, and he readily gave it.

He was just the kindest, most generous, Daniel said. He gave his time to his students. And all these people in the field from all over the world who would just reach out to him and instead of blowing them off, he took an interest in them.

Seth Fischer said his father simply loved to help people.

He would want to help people, not because he thought he would get something out of it in the end. Not because he was trying to play some game of chess. Because he really just loved helping people, Seth Fischer said.

Kurt Fischer helped those around him through his humor, too.

When he was a graduate student at Harvard in the 1960s, one of his professors jokingly challenged his students to adopt a Rhesus monkey and take notes on its life. Fischer took him up on it.

He wanted to name it Frodo. But then he figured out that she was a woman, a girl, so he changed her name to Frodi, Seth Fischer said. He took care of it for as long as he safely could, raising her kind of as his child in graduate school, taking her everywhere with him, even once to Grand Central Station in New York.

Everyone around campus knew about Frodi and enjoyed Fischers whimsy, according to Gardner, who went to graduate school with Fischer.

Above all else, Seth Fischer called his father a champion of kindness.

In his work, in his family, that was sort of his core guiding principle, he said. He just also just loved ideas so much.

In the end, Fischer had more ideas than he had time to see through in his lifetime.

I know that he had more work that he wanted to do when he became ill and couldn't continue, Haltiwanger Fischer, his wife, said. That was very hard on him, but he also had very strong faith that his students are going to carry on.

His students did, in fact, carry on. Today, Mascio is a teacher educator and instructs his students on Fischers theories. Rodriguez is set to publish a major study on teacher wellbeing.

I'm using Kurt's legacy. It's all grounded in dynamic skill theory, Rodriguez said. And that's all based on the confidence and love and support and just undying belief in me that Kurt gave me.

Still, Seth Fisher wishes his father were around to see his legacy for himself.

He was just full of life and excitement about ideas and life and loving people. And I just feel like the world could really use him right now, he said.

Staff writer Camille G. Caldera can be reached at camille.caldera@thecrimson.com. Follow her on Twitter @camille_caldera.

Staff writer Kavya M. Shah can be reached at kavya.shah@thecrimson.com.

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Ed School Professor Kurt W. Fischer, a Champion of Kindness, Dies at 76 | News - Harvard Crimson

Neuroscience

Brain Discovery Could Have Important Implications for Neurodegenerative Diseases – University of Virginia

Improper removal of faulty brain cells during neurodevelopment may cause lifelong behavioral issues, new research from the University of Virginia School of Medicine suggests. The finding also could have important implications for a wide range of neurodegenerative diseases, such as Alzheimers and Parkinsons diseases.

UVA neuroscientists have discovered that an unexpected form of cellular cleanup takes place in developing brains. If this process goes wrong happening too little or too much it can cause permanent changes in the brains wiring. In lab mice, this results in anxiety-like behavior, and it may play a role in neurological conditions such as autism in humans.

You dont want [brain] cells to have genomic compromises. You dont want damaged DNA. So, this would be a normal mechanism to expel those cells from being incorporated into the central nervous system, researcher Catherine R. Lammert explained. When the damage isnt recognized, the cells that have DNA damage live on in the [central nervous system] and can be seen by accumulation of DNA damage in the brain.

The cellular cleaner the researchers spotted, the AIM2 inflammasome, has been associated primarily with the bodys immune response to infections, but has not been extensively studied in the brain. But there it plays a critical role in ensuring the developing brain is assembled properly and functions correctly, Lammert discovered in collaboration with principal investigator John Lukens.

Neurodevelopment is a very complicated process, said Lammert, a graduate student whose specialized skills were instrumental in the discovery. This form of cell death actually plays a role in removing unwanted cells from the brain to establish a healthy [central nervous system] with the correct connections and the right number of cells.

More than half the neurons created during brain development end up dying, so proper cleanup is essential, noted Lukens, of UVAs Department of Neuroscience. Too much or too little is thought to underlie everything from autism to intellectual disability any type of neurodevelopmental disorder, he said.

For example, ataxia is a condition that causes people to lose control of their movements. Theres a potential that this pathway could be contributing to the neuronal loss that is seen in ataxia, said Lukens, a researcher with UVAs Center for Brain Immunology and Glia, or BIG. On the one hand, you need it [the cleanup], but if you have too much of it, it can have negative consequences, like, potentially, ataxia. A lot of the early-onset neurodegenerative diseases are associated with mutations in DNA damage repair proteins, and this pathway could also be involved.

The discovery came about somewhat serendipitously, the result of an observation of the behavior of lab mice while the researchers were investigating traumatic brain injury. But following that unexpected lead has given scientists a better understanding of brain development, and that understanding may one day yield new treatments for neurological diseases.

Lukens, a member of UVAs Carter Immunology Center, cautioned that such treatments are likely a long way off, but he said a therapy based on the discovery might have widespread applications.

Hitting this pathway in the mature brain would likely provide a treatment strategy for any neurodegenerative disease associated with DNA damage, he said. And thats all the major heavy hitters: Alzheimers disease, Parkinsons, ALS.

The researchers havepublished their findings in the prestigious journal Nature. The studys authors were Lammert, Elizabeth L. Frost, Calli E. Bellinger, Ashley C. Bolte, Celia A. McKee, Mariah E. Hurt, Matt J. Paysour, Hannah E. Ennerfelt and Lukens.

The research was supported by the Hartwell Foundation; Rettsyndrome.org grant 22349; the Owens Family Foundation; and Brain & Behavior Research Foundation grant 27515. Lammert was supported by a predoctoral training grant from the National Institutes of Healths National Institute of General Medical Sciences and a Wagner Fellowship.

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Brain Discovery Could Have Important Implications for Neurodegenerative Diseases - University of Virginia