$1.7M MPower Grant to Support UMCP, UMB Health Research Collaborations – Maryland Today

A new grant will provide $1.725 million over three years to support research collaborations between the University of Maryland, College Park (UMCP) and the University of Maryland, Baltimore (UMB) aiming to improve health care.

The grant from the University of Maryland Strategic Partnership, MPowering the State, and accompanying cooperative agreement will allow researchers across the College Park campus to partner with UMBs Institute for Clinical and Translational Research (ICTR). The institute focuses on putting health-related scientific findings to work, and offers expert patient- and community-centered services; biostatistical support for study design, implementation, and interpretation; and pre- and postdoctoral training awards.

The MPower award will help researchers access resources for clinical training, reduce barriers to patient recruitment and open new avenues for human-subject research at UMCP.

The effort is co-led by Dr. Stephen N. Davis, the Dr. Theodore E. Woodward Chair of the Department of Medicine at the University of Maryland School of Medicine and director of the ICTR in Baltimore, and Professor Elizabeth Quinlan, the Clark Leadership Chair in Neuroscience, Department of Biology, and director of the Brain and Behavior Instituteat UMCP.

Access to ICTR resources will enable the translation of high-impact research from the laboratory to the clinic, said Quinlan. The MPower funding to establish this strategic partnership reflects the commitment to training and will accelerate new bi-campus collaborations.

The ICTR, supported by funding from the National Institutes of Health, was established at UMB in 2017 as a universitywide, interdisciplinary hub with a mission to turn basic research findings into novel technologies and practices with communitywide impact. Through the MPower funding, College Park faculty researchers in the life sciences, public health, neuroscience, bioengineering and other disciplines related to clinical and translational research are now eligible to submit proposals for services provided by the ICTR. In addition, College Park students, postdocs and faculty will be invited to compete for career development and mentoring funding. College Park faculty are also eligible to apply for the ICTR Accelerated Translational Incubator Pilot voucher program.

To further strengthen this partnership, MPower funds will continue to develop UMBs bioinformatic infrastructure, which applies computational analysis to biological and health information.

These resources will scale up the ICTRs informatics capabilities and help generate compelling data that demonstrate the effective and seamless clinical research partnership of the two campuses, said Davis. The MPower agreement will create a clinical research network across Maryland that benefits both the population of the state and faculty in Baltimore and College Park.

The MPower announcement follows the news earlier this year that the University of Maryland achieved its highest-ever ranking in the National Science Foundations Higher Education Research and Development survey, as a result of Baltimore and College Park research enterprise being linked together for the first time.

"This will create exciting new opportunities for our researchers to collaborate and deepen the impact of our combined research productivity across our College Park and Baltimore campuses," said Interim Vice President for Research Amitabh Varshney. "For College Park researchers new to the ICTR, the program will provide a high-quality environment for clinical and translational research and will foster innovation in research methods and training."

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$1.7M MPower Grant to Support UMCP, UMB Health Research Collaborations - Maryland Today

Female-Led Team Investigates Increased Alzheimer’s Risk in Women – Duke Today

This MRI scan of a mouse brain, enhanced with manganese, shows 332 regions of the brain. Quantifying volumes and texture helps reveal vulnerable regions and circuits.

By Dana Adcock 22

For Duke faculty members Christina Williams and Alexandra Badea, their research on Alzheimers disease feels deeply personal.

I have seen what Alzheimers is like in the family, so I think Im particularly fortunate to be able to contribute to Alzheimers research, said Badea, an associate professor in radiology and neurology. Even if this is just pushing the field forwards by half of a millimeter, Im very grateful for this chance.

Williams, who is a professor of psychology and neuroscience, agreed. Ive seen the effects of Alzheimers on real people, people I love and care about, she noted. Being able to actually do something, and as Alex said, moving the field forward, is something that we all feel anxious to do. Any little contribution we can make is one that we think is valuable.

The two researchers combined expertise in neuroscience and radiology has paired well together throughout the years.

Alex and I came together in large part because were both interested in memory and in Alzheimers disease, said Williams. Alex is particularly interested in using imaging technology to look at the sizes of different things in the brains of mice, and also levels of activity and connectivity of brain circuits. She looks at the circuit and system level, whereas the work in my lab tends to look more specifically at individual cell types that are affected by Alzheimers disease in particular brain regions.

Immunohistochemistry stains of Alzheimers plaque and microglia in mouse brains. Microglia are important for maintaining a healthy central nervous system.

Williams and Badeas overarching goal is to combine their techniques to get at what is changing in the brain from Alzheimers. Along with that, theyre interested in how environmental factors, such as estrogen loss and exercise, alter the course of the disease.

For the past five years, they have led Bass Connections teams to involve undergraduate and graduate students in tackling this issue. Their current team, Alzheimers Disease: Exercise Therapy and Brain Networks, is focusing on the disease in women.

One of the things thats lesser known about Alzheimers disease is that women are considerably more vulnerable.

Two thirds of the patients with Alzheimers are women, and the disease progresses more rapidly in women, said Williams. Some of the symptoms are a little bit different in women than in men. The question of why women are more vulnerable is one of the questions that were interested in asking and trying to get answers to.

The team uses mouse models to examine the impact of exercise and estrogen loss on Alzheimers disease. Some of the mouse models demonstrate familial Alzheimer's, which is the early onset type and genetically determined. Others mimic the later onset type, which is more common but has fewer known causes. They utilize technologies like fMRI scans and immunohistochemistry to visualize the progression of the disease in the mices brains.

Ph.D. candidate Janai Williams

Psychology & Neuroscience Ph.D. candidate Janai Williams serves as the teams project manager. Joining the project a year after its inception, she embraced the chance to learn from continuing members.

I was able to build my knowledge from the undergraduates who are brilliant and have such great skills, said Williams. Once I got a stronghold of the project, the diverse knowledge and thought helped me build on my own questions within this project [and bring them into] what Im planning to do for my future dissertation project and what Ive presented for my thesis.

Undergraduate Divya Reddy

Undergraduates work in subteams, tackling different aspects of the project. My role in the project lies more within the exercise therapy aspect of the team, Divya Reddy (Biology 23) explained. Her subteam is using mouse models to look at the effects of chronic exercise as opposed to sedentary mice or non-chronic exercise.

Meanwhile, Eileen Wen(24) is using immunohistochemistry to test whether the teams menopause models actually are working effectively and whether they have categorized the mice into the right cycling or non-cycling female group.

Undergraduate Eileen Wen

The project team includes eight other undergraduate members: Akhil Bedapudi, Nikhil Gadiraju, Melinda Guo, Kyra Hoskin, Jasmine King, Pradnesh Kolluru, Anna MacFarlane and Isabella Pansini.

Despite focusing on different research areas, students say they still feel connected to the rest of the team. With Bass Connections, the whole goal is to try and make sure that you always feel supported and feel like youre in the know with everyone elses project, said Pansini (Neuroscience 23). It becomes easier to integrate everyones information and everyones project together because ultimately we are working toward the same goal.

The team plans to analyze and compare brain imaging data from mouse models of Alzheimers disease to brain neuropathology, behavioral data and databases of human brain imaging from Alzheimers patients. Team members will contribute to publications and posters and present these to the research community and clinical consumers. They also hope to create a website to share their findings with the public.

Duke University senior Dana Adcock is a Bass Connections communications assistant who is majoring in Environmental Sciences & Policy.

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Female-Led Team Investigates Increased Alzheimer's Risk in Women - Duke Today

Exicure to Present at Upcoming Scientific Conferences – Business Wire

CHICAGO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Exicure, Inc. (NASDAQ: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) technology, today announced presentations at the following scientific conferences during the month of November:

TIDES EUTitle: "Development of Spherical Nucleic Acids Targeting SCN9A For the Treatment of Neuropathic Pain"Presented by: Bart Anderson, Senior Director, R&DDate: November 16, 2021Time: 8:45am CET / 1:45am U.S. CST

Neuroscience 2021 (The Society for Neuroscience)Poster 1: "Spherical Nucleic Acids Targeting FXN Induce Frataxin Expression in Models of Friedreichs Ataxia"Presented by: Grant Corbett, Group Lead, NeurosciencePoster 2: "Biodistribution of Spherical Nucleic Acids in the Mouse CNS Following ICV, ICM and IT Delivery"Presented by: Lauren Moore, Senior Scientist, NeuroscienceNovember 8-11, 2021

About Exicure, Inc.

Exicure, Inc. is a clinical-stage biotechnology company developing therapeutics for neurology, immuno-oncology, inflammatory diseases and other genetic disorders based on its proprietary Spherical Nucleic Acid, or SNA technology. Exicure believes that its proprietary SNA architecture has distinct chemical and biological properties that may provide advantages over other nucleic acid therapeutics and may have therapeutic potential to target diseases not typically addressed with other nucleic acid therapeutics. Exicure is in preclinical development of XCUR-FXN, a lipid-nanoparticle SNAbased therapeutic candidate, for the intrathecal treatment of Friedreichs ataxia (FA). Exicures therapeutic candidate cavrotolimod (AST-008) is in a Phase 1b/2 clinical trial in patients with advanced solid tumors. Exicure is based in Chicago, IL and in Cambridge, MA. http://www.exicuretx.com

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Exicure to Present at Upcoming Scientific Conferences - Business Wire

Neuroscience Antibodies and Assays Market 2021 Outlook, Demand, Regional Analysis, Industry Value Chain | Operating Vendors: Thermo Fisher, Abcam,…

The latest research report on the Global Neuroscience Antibodies and Assays Market provides the cumulative study on the COVID-19 outbreak to provide the latest information on the key features of the Neuroscience Antibodies and Assays market. This intelligence report contains investigations based on current scenarios, historical records and future forecasts. The report contains various market forecasts related to market size, revenue, production, CAGR, consumption, gross margin in the form of charts, graphs, pie charts, tables and more. While emphasizing the main driving and restraining forces in this market, the report also offers a comprehensive study of future trends and developments in the market. It also examines the role of the major market players involved in the industry, including their business overview, financial summary and SWOT analysis. It provides a 360-degree overview of the industries competitive landscape. Neuroscience Antibodies and Assays Market shows steady growth and CAGR is expected to improve during the forecast period.

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Neuroscience Antibodies and Assays Market Segmentation:

Neuroscience Antibodies and Assays Market, By Application (2016-2027)

Neuroscience Antibodies and Assays Market, By Product (2016-2027)

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Company Profiles This is a very important section of the report that contains accurate and detailed profiles for the major players in the global Neuroscience Antibodies and Assays market. It provides information on the main business, markets, gross margin, revenue, price, production and other factors that define the market development of the players studied in the Neuroscience Antibodies and Assays market report.

Global Neuroscience Antibodies and Assays Market: Regional Segments

The different section on regional segmentation gives the regional aspects of the worldwide Neuroscience Antibodies and Assays market. This chapter describes the regulatory structure that is likely to impact the complete market. It highlights the political landscape in the market and predicts its influence on the Neuroscience Antibodies and Assays market globally.

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This report includes the estimation of market size for value (million USD) and volume (K Units). Both top-down and bottom-up approaches have been used to estimate and validate the market size of Neuroscience Antibodies and Assays market, to estimate the size of various other dependent submarkets in the overall market. Key players in the market have been identified through secondary research, and their market shares have been determined through primary and secondary research. All percentage shares, splits, and breakdowns have been determined using secondary sources and verified primary sources.

Some Major Points from Table of Contents:

Chapter 1. Research Methodology & Data Sources

Chapter 2. Executive Summary

Chapter 3. Neuroscience Antibodies and Assays Market: Industry Analysis

Chapter 4. Neuroscience Antibodies and Assays Market: Product Insights

Chapter 5. Neuroscience Antibodies and Assays Market: Application Insights

Chapter 6. Neuroscience Antibodies and Assays Market: Regional Insights

Chapter 7. Neuroscience Antibodies and Assays Market: Competitive Landscape

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Neuroscience Antibodies and Assays Market 2021 Outlook, Demand, Regional Analysis, Industry Value Chain | Operating Vendors: Thermo Fisher, Abcam,...

Neuroscience Market:Industry Analysis and Forecast 2021-2027| Key Players Doric Lenses . GE Healthcare , Siemens Healthineers , Laserglow Technologies…

Neuroscience Marketis the study of the nervous system and it is concerned with assessing and imaging brain function. Neuroscience is a comprehensive term that refers to the study of the nervous systems molecular, cellular, developmental, structural, functional, evolutionary, computing, psychological, and medicinal components.

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List of Key players: Following are the number of key players studied to understand theNeuroscience Market:

Doric Lenses GE Healthcare Siemens Healthineers Laserglow Technologies Mightex Systems NEURALINK Kernel BrainCo, Inc. MindMaze Paradromics NeuroPro NeuroSky EMOTIV Cercare Medical A/S Plexon, Inc. Noldus Information Technology bv Femtonics Ltd. Neuralynx

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This study estimates the size of theNeuroscience Marketin terms of both value and volume. It includes a thorough examination of the markets major drivers, restraints, and opportunities. Through the Porters five forces analysis, the study examines the major elements that contribute to the growth of theNeuroscience Market. Furthermore, the market participants have been profiled, with a particular emphasis on their product offers.

The research also includes data in the form of statistics, facts, and figures, as well as contact information and sales contact information for the global markets leading players. There is a full picture of the global Silk industrys competitive landscape, with all information gathered and deepened with the SWOT analysis. Opportunities for possible industrial expansion have been identified, as have the competitive threats associated.

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The introduction of new goods and the research involved in the development of innovative products is one of the primary components that is likely to have an impact on theNeuroscience Market.The study provides information on the sales and market growth of various markets on a regional and national scale. This report is to provide a market analysis in terms of growth patterns, prospects, and market players contributions to market development. The research also examines market demand growth estimates for products and services.

OBJECTIVES OF THE STUDY

Our Research Methodology:

This research study involves the use of extensive secondary sources such as encyclopedia, directories, and databases to identify and collect information useful for this technical, market-oriented, and commercial study of theNeuroscience Market. Primary sources that include selected experts from related industries and selected suppliers have been interviewed to obtain and verify important information as well as to assess future prospects. As a part of the secondary research process, various sources have been referred to for identifying and collecting information for this study. Secondary sources include annual reports, press releases, and investor presentations of companies; white papers; certified publications, articles from recognized authors; and gold & silver standard websites.

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Neuroscience Market: Global Industry Analysis And Forecast (2022-2029)

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Neuroscience Market:Industry Analysis and Forecast 2021-2027| Key Players Doric Lenses . GE Healthcare , Siemens Healthineers , Laserglow Technologies...

Xen by Neuvana: First-of-its-kind Vagus Nerve Stimulation Device Now Shipping to the United Kingdom and European Union – PRNewswire

Xen by Neuvana is a pocket-sized device that connects to your mobile phone through an app and sends a gentle electrical signal through patented earbuds to stimulate the vagus nerve in the ear. Invented by a leading cardiac surgeon and supported by science, Xen's innovative design targets the vagus nerve, the longest cranial nerve in the body, which acts as the information highway from the brain to most of the body's major organs. When stimulated, the vagus nerve activates the parasympathetic nervous system by signaling the brain to release calming neurotransmitters such as acetylcholine and norepinephrine. This natural chemical process can help the body feel calmer, more focused, increase mood, and achieve better sleep too.

"We have had an outpouring of interest from consumers outside of the U.S. wanting to try Xen and experience the health benefits users have shared that improve their day-to-day lifestyle," said Vince Manopoli, CEO of Neuvana. "We are excited to continue to expand the company's footprint to our friends overseas and deliver Xen into the hands of people who are looking for alternative ways to manage the health impact of stress, anxiety, and poor sleep "

Initially launched in the United States in 2019, Xen was specifically designed to meet the high standards of product safety testing and certification in order to bring the product to consumers overseas. It has earned the esteemed CE marked certification, which applies to products intended for the European market that have been tested and found to comply with each country's high safety requirements.

"With the safety of our customers always at the forefront, we continue to work diligently to meet the most stringent guidelines for our products according to each country's specific requirements," said Manopoli. "Furthermore, it's important to us that we do so without compromising the product's health benefits or diminishing the overall customer experience. Thanks to an incredible team of engineers and scientists behind our product, we have successfully accomplished just that."

Starting this week, consumers can preorder their Xen product starting at 444.70 EUR online at http://www.neuvanalife.com. The company will start shipping to all EU countries and the UK beginning November 15.

Science Behind Vagus Nerve Stimulation (VNS)

The vagus nerve controls part of the body's automatic responsesthe parasympathetic nervous system. The term "vagus" is named after the Latin word for "wandering," as it starts at the brain, and travels near the ear, and on to every major organ in the body. As a result, it controls a vast range of functions and communicates sensory information between the brain and the organs. The vagus nerve is crucial for activating the body's relaxation response and helping to regulate tension. Just like a muscle, when toned or strengthened regularly, the functions of the vagus nerve can be amplified and its response can help a person recover quicker from stressful events.

Backed by Research

Neuvana is considered a leader in neuroscience technology, specifically in the vagus nerve stimulation (VNS) category. As a company, its focus is centered around pairing neuroscience and technology to develop innovative products to better people's health and everyday lifestyle. As part of this process, Neuvana is involved in research surrounding VNS with the following institutions: Walter Reed National Military Medical Center, Air Force Research Laboratory (AFRL), Defense Advanced Research Projects Agency (DARPA), University of Maryland, Thomas Jefferson University Hospital, Defense Language Institute Foreign Language Center, among others.

About Neuvana LLC

Neuvana, LLC is a South Florida-based company at the intersection of wellness and technology, with a focus on Neuroscience. Founded in 2014 by Richard Cartledge, MD, an inventor and chief of cardiovascular surgery at Boca Raton Regional Hospital, the company is comprised of engineers, clinicians, experienced business professionals and a world-class scientific advisory board with a shared goal: to create a platform to make the wellness benefits of neuroscience safe, easy and accessible to everyone. In late 2019, Neuvana released its flagship product, Xen, which stimulates the vagus nerve system through patented earbuds to help reduce stress, boost sleep and improve focus. For more information about Neuvana, its board members and product details, visit http://www.neuvanalife.com.

Press Contact: Sarah Cooke, 5613156946

SOURCE Neuvana LLC

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Xen by Neuvana: First-of-its-kind Vagus Nerve Stimulation Device Now Shipping to the United Kingdom and European Union - PRNewswire

Neuroscientist Paxinos’ 21-year odyssey is over with publication of first novel – Neos Kosmos

Over a long and distinguished career in neuroscience, Prof George Paxinos has identified more areas of the brain than anyone else in history, he has also written 57 books on the subject. Now he has dipped into the waters of fiction with the publication of his first novel A River Divided.

It took him 21 years and countless revisions to publish the book, a process that was harder than anything he had attempted before.

The central idea came to me one night in 1999, of identical twins raised apart and I filled in the plot over the years, Paxinos told Neos Kosmos. The rest was sheer persistence as he set about writing and revising the book to his ultimate satisfaction.

The idea developed in the book so that the identical twins are cloned from the remains of a man found near Masada, the Jewish fortress near the Dead Sea that resisted a Roman siege to the death.

The remains are those of the biblical Jesus. The clone is accidentally divided into two identical embryos which are transferred to two host mothers. One grows up in Australia the other in completely different circumstances in South America. The twins meet again as adults confronting each other from very different positions.

The novel guided by the story grapples with important ethical and moral issues, with the environmental crisis at its heart. In the 1980s Paxinos was a key advocate for the founding the Light Rail Association to bring back the tram to Sydney and in 2015 he was the Australian Cyclists Party candidate in the New South Wales state elections.

The issue of our time today is the environment. I try to penetrate what Christ would have said today. In Christs time the issue was justice. We must not give the next generation, the burden of a damaged environment, Paxinos said.

READ MORE: George Paxinos launches new book: The Brain Atlas

If Christians get over the initial shock of the finding (and cloning) Christs remains, I think they will find it was a choice made from affection for Christ and the ideas he produced. I hope they will not find this idea disagreeable.

A book needs heart, soul and mind, the book has all three elements but it is also (about) reflection, conflict and internal debate. It grapples with some important issues.

The books title, A River Divided refers to the confluence of two very different rivers, the lighter coloured muddier colder Rio Solimes and the darker, warmer Rio Negro. The rivers which meet near the city Manaus and retain their individual character until they eventually blend 25km downstream to become the mighty Amazon River. Plans to dam a river in the region, draw the twins who are in opposite ends of the situation.

The action of the book runs through various settings from Israel, to Australia, the Vatican and South America and the author visited each place as part of his research in writing the novel.

When he wrote The Brain Atlas he put in 110 hours a week for several months in order to complete it.

I gave more to this than my scientific works, Paxinos said.

Literature is hard. I would not let my scientific books go (for publication) until I could not add anything more. I did not feel that way for this book and up until the last moment I felt I was improving the manuscript. A book must hang together with the right flow, expression and emotions, it must not be inappropriate.

His academic books are highly acclaimed in the field of neuroscience with his first one The Rat Brain in Stereotaxic Coordinates, as the most cited publication in neuroscience and was the third-most cited work in all of science for several decades.

In teaching undergraduates and post graduates over the years helped him to gauge what would work for readers of the novel- unlike his academic books, a novel should not be didactic or preach, the story and the characters guides the flow of the book.

Some key concepts of neuroscience to weave their way into the A River Divided: the role of our genetic endowment versus the influence of our environment in sculpting our character being one example.

Had the brain been smaller then we would not have had technology, had our brain been larger and better functioning then we would have solved many of the problems that affect us now. Unfortunately, the brain is just not the right size, Paxinos said.

I used my neuroscientist background to craft the characters. I visited the places reflected in the novel and received a lot of help from scientists. It is accurate and comprehensible scientifically to the point that a Greek kindergarten teacher diagnosed the symptoms of Temporal Lobe Glioma in one of her friends on the basis of the description of the symptoms in one of the characters in the novel.

READ MORE: Groundbreaking discovery in neuroscience by Greek researcher

He had tried to first get the book published in Australia but conveying what it was about with its complexity of themes was a problem. He took the manuscript to Greece in 2015 where Livanis Publications took it up and translated into the Greek under the title In His Image.

The publisher in Greece said: Dont tell me anything, just read me the last page.

The lady cried and I thought a publisher will normally only cry if the book does not sell, Paxinos joked.

Having seen the book in his native language, he obtained a better understanding of the emotions of the characters he had created and spent another six years improving the English version.

Every time I revised the book, I would make many corrections but each time they improved the book.

The persistence that is his trademark has paid off but Paxinos says his next novel should be titled How to write a novel in less than 25 years.

A River Divided by George Paxinos is published in Australia by Heads and Tales will be available from Mid-November in Booktopia and good book stores.

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Neuroscientist Paxinos' 21-year odyssey is over with publication of first novel - Neos Kosmos

A Nobel Prize with a connection to UB research – UB Now: News and views for UB faculty and staff – University at Buffalo Reporter

On Oct. 4, the Nobel Prize for Physiology or Medicine was awarded to two researchers for their work in identifying the proteins responsible for providing our ability to sense heat and touch.

These were milestones to commemorate, and well-deserved by the researchers who made the discoveries: Dr. David Julius at the University of California, San Francisco, and Dr. Ardem Patapoutian at Scripps Research in La Jolla, California.

With regard to sensing touch, Dr. Patapoutian won the prize for identifying Piezo proteins, which are a type of ion channel on the surface of cells that respond to pressure and stretching.

This can be the pressure or stretching felt as we slide our finger across the surface of a table, or the pressure in our arteries that occurs with each heartbeat. It can be the stretch felt in our lungs when we take a deep breath, or the pain felt by the inflammation caused by a mosquito bite.

The touch sensitivity award is significant to the UB community because the category of ion channels that provide this sensitivity were first observed right here in Buffalo.

Forty years ago, Dr. Frederick Sachs, SUNY Distinguished Professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB, used miniature glass pipettes to suck on the surface of skeletal muscle cells. And in so doing he recorded for the first time the tiny electrical currents that were produced by mechanosensitive ion channels that were most likely Piezo channels.

This seminal publication (Journal of Physiology, London, 1984, 352, 685-701) opened the door to the field of touch-pressure sensitivity. And this first paper was followed by many publications by Dr. Sachs and others over the next 25 years, using his technique to investigate how mechanosensitive ion channels provide many different cell types with the ability to feel their surroundings.

Additional publications by Dr. Sachs and colleagues showed the role of these ion channels in pathology for diseases like vascular disease, cardiac arrhythmias, muscular dystrophy, sickle cell anemia and cancer. Scientists soon realized that disease in any form can change the way tissues and cells respond to stretch and pressure in a variety of ways through pressure from a growing tumor pressing on the surrounding healthy tissue; through a heart arrhythmia that causes the heart muscle to contract with unsynchronized force; or through long-term stiffening of arteries that are under prolonged increased blood pressure from stress.

For many years these channels were being studied in normal physiology and disease using Dr. Sachs technique, but without knowing the identity of the protein that actually provided the ability to respond to stretch and pressure.

It wasnt until Dr. Patapoutian discovered the amino acid sequence of these channels that we knew their identity. And this discovery allowed researchers to investigate how expression of the channels in different tissues changes during normal development and their abnormal function contributes to disease. It also allowed more detailed studies of how the channels respond to stretch forces in different environments.

The role of these channels in disease led Dr. Sachs to search for blockers as a way to ameliorate negative effects of the overactivity of these channels.

Dr. Sachs teamed with me and Dr. Philip Gottlieb, also researchers in the Department of Physiology and Biophysics, to search for compounds that could block the channels. We hunted for compounds in spider and scorpion venom, and discovered an effective blocker of Piezo channels in the venom of the Chilean Rose tarantula and called it GsMTx4.

We then discovered the compounds unusual method of blocking, which so far has proven difficult to duplicate. To improve the lives of patients suffering from disease, we launched a biomedical company called Tonus Therapeutics to develop this blocker, which is now made as a synthetic version of the original tarantula venom compound.

The Sachs/Suchyna/Gottlieb lab continues to study pressure/touch sensitivity here at UB. We use a variety of novel techniques to provide new insights into the role of Piezo channels in living systems and into the development of therapeutic strategies to treat disease. The recognition of the Nobel award committee to pressure/touch sensitivity as a milestone in biology and medicine will bring welcomed exposure to the field for funding and help to attract young scientists into this important area of research.

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A Nobel Prize with a connection to UB research - UB Now: News and views for UB faculty and staff - University at Buffalo Reporter

The trouble of being tall – Vet Candy

The giraffe is a truly puzzling animal. With its exceptional anatomy and suite of evolutionary adaptations, the giraffe is an outstanding case of animal evolution and physiology. Now, an international team of researchers from the University of Copenhagen and Northwestern Polytechnical University in China have produced a high-quality genome from the giraffe and investigated which genes are likely to be responsible for its unique biological features.

The extraordinary stature of the giraffe has led to a long list of physiological co-adaptations. The blood pressure of the giraffe, for instance, is twice as high as in humans and most other mammals to allow a steady blood supply to the lofty head. How does the giraffe avoid the usual side effects of high blood pressure, such as severe damage to the cardiovascular system or strokes?

The team discovered a particular gene - known as FGFRL1 - that has undergone many changes in the giraffe compared to all other animals. Using sophisticated gene editing techniques they introduced giraffe-specific FGFRL1 mutations into lab mice. Interestingly, the giraffe-type mice differed from normal mice in two important aspects: they suffered less cardiovascular and organ damage when treated with a blood pressure increasing drug, and they grew more compact and denser bones.

- "Both of these changes are directly related to the unique physiological features of the giraffe - coping with high blood pressure and maintaining compact and strong bones, despite growing them faster than any other mammal, to form the elongated neck and legs.", says Rasmus Heller from the Department of Biology, University of Copenhagen, one of the lead authors on the study.

Giraffe's can't get no sleep

While jumping out of bed for (some) humans might be an effortless and elegant affair, this is definitely not the case for the giraffe. Merely standing up is an a lengthy and awkward procedure, let alone getting up and running away from a ferocious predator. Therefore, giraffes have evolved into spending much less time sleeping than most other mammals.

- Rasmus Heller elaborates: "We found that key genes regulating the circadian rhythm and sleep were under strong selection in giraffes, possibly allowing the giraffe a more interrupted sleep-wake cycle than other mammals".

In line with research in other animals an evolutionary trade-off also seem to be determining their sensory perception, Rasmus continues:

- "Giraffes are in general very alert and exploit their height advantage to scan the horizon using their excellent eyesight. Conversely, they have lost many genes related to olfaction, which is probably related to a radically diluted presence of scents at 5m compared to ground level".

A model of evolutionary mechanisms--and perhaps even human medicine?

These findings provide insights into basic modes of evolution. The dual effects of the strongly selected FGFRL1 gene are compatible with the phenomenon that one gene can affect several different aspects of the phenotype, so called evolutionary pleiotropy. Pleiotropy is particularly relevant for explaining unusually large phenotypic changes, because such changes often require that a suite of traits are changed within a short evolutionary time. Therefore, pleiotropy could provide one solution to the riddle of how evolution could achieve the many co-dependent changes needed to form an animal as extreme as a giraffe. Furthermore, the findings even identifies FGFRL1 as a possible target of research in human cardiovascular disease.

- "These results showcase that animals are interesting models, not only to understand the basic principles of evolution, but also to help us understand which genes influence some of the phenotypes we are really interested in - such as those related to disease. However, it's worth pointing out that genetic variants do not necessarily have the same phenotypic effect in different species, and that phenotypes are affected by many other things than variation in coding regions.", says Qiang Qiu from Northwestern Polytechnical University, another lead author on the study.

The results have just been published in the prestigious scientific journal,Science Advances.

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Penn study illuminates the biology of common heart disorder – EurekAlert

Researchers at Penn Medicine have made a major advance in understanding the biology of a common, puzzling, and often fatal heart disorder, dilated cardiomyopathy (DCM), which features the enlargement of the heart and a progressive decrease in its function, for reasons other than cardiovascular disease. DCM is estimated to affect at least hundreds of thousands of people in the United States. The largest single known cause, accounting for an estimated 10 to 20 percent of cases, involves the mutation of the gene that encodes a key heart-muscle protein called titin.

Titin (pronounced titan) is a giant among proteins, and unfortunately its enormity has made it hard to study. How titin mutations lead to DCM has therefore been largely a mystery. But the Penn Medicine researchers, who report their findings today in Science Translational Medicine[LB1], used an array of sophisticated methods to overcome the usual technical hurdles. They found that titin mutations in DCM patients lead to two key abnormalities in heart muscle cells: a shortage of normal-length titin, and the accumulation of mutant, truncated titin fragmentspointing to the possibility that both of these abnormalities drive heart dysfunction in DCM.

These findings change how we look at this genetic form of DCM and give us new directions to pursue for possible future therapies, said study co-senior author Zoltan Arany, MD, PhD, Samuel Bellet Professor of Cardiology at the Perelman School of Medicine at the University of Pennsylvania. Aranys co-senior author is Benjamin L. Prosser, PhD, an associate professor of Physiology.

There is a strong need for a disease-specific treatment for DCM, since the disorder is both common and lethal. It often leads, within a few years, to heart failure, and only about half of DCM patients live five years after their diagnosis. Many who survive do so by receiving heart transplants.

Developing an effective therapy has been a real challenge, however, given the lack of understanding of DCMs underlying biology. Pregnancy, the use of alcohol and other recreational drugs, certain types of infection, and gene mutations, have all been linked to DCMand there are hints that in many cases a combination of factors triggers this diseasebut the precise causes in most individual cases are obscure. Even the mechanism by which titin gene mutations cause DCM has been unclear.

In principle, these causative mutations offer researchers an opportunity to discover the details of how DCM arises. In practice, the size of the affected protein, titin, the largest known protein in biologyhundreds of times larger than many other common proteinshas made it uniquely hard to study. In particular, prior research has been unable to determine whether titin mutations in DCM patients cause heart disease through some direct toxic effect of mutant titin protein, or due to a shortage of normal titin protein.

In the new study, Arany and his colleagues tackled this question, and found evidence supporting both of these mechanisms.

A pathbreaking study

The titin mutations that are often linked to DCM are in the titin-encoding gene TTN, and are called truncatingshortenedvariants in TTN, or TTNtvs. Most genes in our genomes are inherited as a pair, one copy from the mother and one from the father, and DCM patients with TTNtvs typically have one normal copy of TTN to go with the abnormal copy.

Arany and his colleagues examined 184 failing hearts taken out of DCM patients during transplants by co-author Kenneth Margulies, MD, research director of Heart Failure/Transplantation and a professor of Medicine and Physiology at Penn. The researchers found TTNtvs in 22 of the hearts and, with an innovative set of techniques, detected abundant truncated titin fragments, even though prior studies of TTNtv hearts did not find them. That discovery reopens the possibility that these fragments are contributing to DCM by harming heart muscle cells.

In another novel finding, the researchers determined that levels of normal titin were about 30 percent lower in TTNtv-containing heart muscle, suggesting that a shortage of normal titin may also be a contributor to disease.

The study yielded many other findings, such as the observation that the severity of DCM doesnt seem to depend on the parts of titin affected by TTNtv mutations. Altogether, the study represents a leap forward in this fieldone that sends researchers along many new lines of investigation, which could ultimately yield the first DCM-specific treatments.

If it turns out that these chopped titin proteins are the chief cause of trouble, for example, wed want to design therapies to get rid of those proteins, Arany said. With these findings, were aiming in a different direction.

The research was supported by grants from the National Institutes of Health (R01-HL133080, R01-HL126797, AR 53461-12, R01 AG17022, R01 HL089847, R01 HL105993, R01 HL13308), the Gund Family Fund, and the Department of Defense (W81XWH18-1-0503).

Science Translational Medicine

Observational study

Human tissue samples

Truncated titin proteins in dilated cardiomyopathy

3-Nov-2021

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