Category Archives: Cell Biology

Mantarray: Scalable Human-relevant 3D Engineered Cardiac and Skeletal Muscle Tissues for Therapeutics Discovery Upcoming Webinar Hosted by Xtalks -…

October 5, 2021 medical

Learn how these advanced 3D tissue models generated on the Mantarray platform can improve the physiological relevance of preclinical cardiac and skeletal muscle models, accelerating the discovery of new medicines.

TORONTO (PRWEB) October 05, 2021

3D cellular models and organs-on-chips are poised to add tremendous value by providing human data earlier in the drug discovery pipeline. There is intense interest in adopting these 3D models in preclinical and translational research, but their complex implementation has remained a roadblock for many labs.

In this webinar, Curi Bio will present its Mantarray platform, which represents an easy-to-use, flexible, and scalable system for generating 3D EMTs at high-throughput with the ability to measure contractility in parallel. The platform features a novel method of casting 3D tissues that can be easily performed by nearly any cell biology researcher and can be readily adapted to a variety of cell lines and extracellular matrices. In addition, Mantarrays novel magnetic sensing modality permits contractility measurement of 24 tissues in parallel and in real time, while the cloud data analysis portal takes the guesswork out of analyzing and comparing results across experiments.

Register for this webinar to hear an overview of the technology, along with application examples across various use cases, including:

Join Dr. Nicholas Geisse, Chief Science Officer at Curi Bio, for the live webinar on Friday, October 22, 2021 at 1pm EDT.

For more information, or to register for this event, visit Mantarray: Scalable Human-Relevant 3D-Engineered Cardiac and Skeletal Muscle Tissues for Safety and Efficacy Studies.

ABOUT XTALKS

Xtalks, powered by Honeycomb Worldwide Inc., is a leading provider of educational webinars to the global life science, food and medical device community. Every year, thousands of industry practitioners (from life science, food and medical device companies, private & academic research institutions, healthcare centers, etc.) turn to Xtalks for access to quality content. Xtalks helps Life Science professionals stay current with industry developments, trends and regulations. Xtalks webinars also provide perspectives on key issues from top industry thought leaders and service providers.

To learn more about Xtalks visit http://xtalks.comFor information about hosting a webinar visit http://xtalks.com/why-host-a-webinar/

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Cell Biology

October: Henrietta Lacks statue | News and features – University of Bristol

October 5, 2021 medical

A life-size bronze statue of Henrietta Lacks, a Black American woman whose cells were the first ever to survive and multiply outside the body, and whose use changed the course of modern medicine, has been unveiled at the University of Bristol by members of her family to honour the 70th anniversary of her cells first being used.

Her sonLawrence Lacks, who was 17 when his mother passed away,was joined by her grandson Alan Wilks and his wife Pam, granddaughter Jeri Lacks-Whye and great-granddaughters Victoria Baptiste and Veronica Robinson for the unveiling this afternoon Monday 4 October 2021.

The statue,commissioned by the University earlier this year,is located inthe heart of thecampusprecinct next to Royal Fort House. It is thework of Bristol artist HelenWilson-Roeand is the first public statue of a Black woman made by a Black woman to be permanently installed in the UK.

It follows the exhibiting of two of Helens portraits of Henrietta Lacks and Cllr Cleo Lake, Bristols first Black female Lord Mayor, which have been on display in the Wills Memorial Buildingsince October2020.

Henrietta Lacks wasa young wife and motherwhodiedin 1951of an unusually aggressive form of cervical cancer. During surgery, a sample of cells was taken from the tumour and was sent to a laboratory where they were found to be thefirst living human cells ever to survive and multiply outside the human body.Henriettas cells weretaken without her or her family's knowledge or consent,and it was only in 1975 that by chance the family found out about her legacy.

Because Henriettas cells were able to proliferate indefinitely, they formed the first scientifically definedimmortalhuman cell line, opening the door to all kinds of experiments and research on cell behaviour.

These cells madepossible some of the most important medical advances of all time including the development of the polio vaccine, chemotherapy, gene-mapping, IVF and cloning.

They became known as HeLa cells - taking the first two letters of Henriettas first and last names. HeLa cells are used in almost every major hospital and science-based University in the world, including the University of Bristol where they have been used most recently, for COVID-19 research.

The Universitys Faculty of Life Sciences has been working with students and staff to look at how it can diversify its teaching curriculum with one focus being to highlight previously overlooked figures which will include Henrietta Lacks and the important ethical issues and debates that are part of her story.

The University is also announcing the launch of The Henrietta Lacks Studentship - a six-week paid summer internship for an undergraduate student to work in its laboratories on cell biology and, with the support of the Lacks Family, is planning free in-person visits to the University for KS4 and KS5 pupils to learn more about cell biology. Other education science events in collaboration with the Lacks family both in the UK and overseas are underway.

The University is collaborating with the Lacks family-ledHELA 100: The Henrietta Lacks Initiative, which began during her centennial year and features aworldwide education and advocacy tour. The statue unveiling will also be live streamed around the world as part of the HELA100 Colloquium, commemorating 70 years since Henriettas incredible HeLa cells changed the world and her untimely death on 4 October 1951.

Attendees will learn about the worldwide advancements made bythe cellsand Henriettas descendants to educate future generations on the impact of her immortal HeLa cells while promoting health equity and social justice.

Jeri Lacks-Whye, Henrietta Lacks Granddaughter, said:As the worldcommemorates 70 years since Henrietta Lacks HeLa cells changed the world,we also reflect on my grandmother's untimely passing. It is only fitting that she be memorialised to educate future generations on her legacy and the importance of advancing health equity and social justice for all. The Lacks Family is honoured to begin our HELA100 worldwide tour with the University of Bristol and Helen Wilson Roe for the unveiling of this historic statue.

Helen Wilson-Roe said: Henriettas statue will be the first public statue of a Black woman made by a Black woman in the UK and will be installed permanently on the University of Bristol campus. May our ancestors continue to show us the way to walk.

As a child growing up in Bristol there were no statues of Black women that I could identify with.So,knowing that my children and their grandchildren and great grandchildren will be able to see Henrietta's statue, is just fantastic, especially at this time when Bristol is starting to address its past.

I have been researching about Henrietta Lacks independently for over 20 years. My mission now is to finish painting all 24 portraits of the Lacks family and gift the portraits to the family so that they retain full control of their legacy.

Professor Jeremy Tavare, Dean of theFaculty of Life Sciencesat the University of Bristol,who is also a biochemist,added: Many of our biomedical science researcherswhose work uses human cellshave used Henriettas cells in their research or with collaborators, including myself.We all owe Henrietta an enormous debt of gratitude.

I am absolutely delighted to be able to host this beautiful statue of Henrietta on our campus so we can visually honour her contribution to important discoveries we have made in Bristol over the last 70 years. I feel intensely proud that her family have been so supportive in our doing so. Her statue will do so much to raise her profile with our students and also with children in our local communities.

Professor Judith Squires, Deputy Vice-Chancellor and Provost, said: Henrietta Lacks legacy to science research and health care globally cannot be underestimated.Thisstatuecelebratesthe impact her cells have made to our research here in Bristol, and indeed research around the world.

The Lacks family have a unique relationship with Helen Wilson-Roe, who is a local artist and wished for her statue to be in Bristol.We are pleased to be able to give it a permanent home right here on our campus.

The statue also marks a significant step in addressing the lack of representation of women, and women of colour, in public artwork in our diverse multicultural city. As public art, the local community are most welcome to visit to see this wonderful statue for themselves and learn more about Henrietta Lacks and her legacy.

EMBL and University of Tartu sign MoU to boost scientific collaboration – Science Business

October 5, 2021 medical

Since June 2019, Estonia has been a prospect member state of the European Molecular Biology Laboratory (EMBL). A memorandum of understanding (MoU) has now been signed between EMBL and the University of Tartu, a leading centre of research and training. The MoU aims to strengthen cooperation between EMBL and the life science research community in Estonia, building on the very successful links in the context of the prospect membership.

This MoU also formalises previous exchanges and research collaborations between the two institutions. In February 2021, EMBL and the Estonian Research Council organised a joint workshop in which many Estonian researchers were actively involved, including participants and speakers from the University of Tartu. On this occasion, EMBL Director General Edith Heard presented the next EMBL Programme, Molecules to Ecosystems, which has the aim of understanding life in its natural context. EMBLs scientific plans for the next five years (20222026) is the first pan-European molecular biology programme for environmental and human health and has collaboration across disciplines and sectors at its core.

Confronted with global challenges and urgent societal and environmental needs, fostering cooperation and integrating European life science have become essential endeavours. Estonia has been a very engaged prospect member of EMBL since 2019, and I view the signing of the MoU with the University of Tartu as a catalyst for collaboration between the two organisations, says Edith Heard. The MoU stands as a firm commitment to enhancing cutting-edge scientific research, knowledge sharing, and training, especially in the context of the new EMBL Programme. This will benefit Estonias life science landscape as we prepare for the countrys accession to EMBL as a full member state.

During the workshop in February, EMBL Deputy Director General Ewan Birney highlighted the work of EMBLs European Bioinformatics Institute (EMBL-EBI) in human genetics and personalised medicine. Other talks by EMBL Heads of Faculty touched upon bioinformatics training opportunities and some of the themes in the new EMBL Programme. Possibilities for joint collaboration were also discussed, particularly on several of the programmes new transversal themes, such as Human Ecosystems, Planetary Biology, Microbial Ecosystems, and Data Science.

Estonia has shown great success in attracting talent, so we really look forward to collaborating with all those excellent researchers. Im thrilled to see what discoveries come from this exciting new alliance says Ewan Birney.

This formalised collaboration between EMBL and the University of Tartu is already helping to forge stronger links between EMBL and the science landscape in Estonia. Estonian researchers have had individual contacts with EMBL, but through the MoU we are now committed to advance the joint undertakings at more systematic and strategic levels to help to boost the career of young Estonian talent, further the development of joint scientific infrastructures and increase the overall volume of interactions and activities both in experimental biology as well as biological data management and analysis, says Jaak Vilo, one of the EMBL Council delegates from Estonia and current Head of the Institute of Computer Science at the University of Tartu.

Toivo Maimets, Professor of Cell Biology at the University of Tartu and former president of the European Molecular Biology Conference (EMBC)* of which Estonia has been a member since 2006, sees the MoU between the University of Tartu and EMBL as the next important step to carry on the rapid developments of Estonian science. Tighter collaboration between the EMBL and our university will accelerate our full membership in EMBL and bring even more possibilities to gain from these top-level international professional networks, says Maimets.

*The European Molecular Biology Conference (EMBC) is an intergovernmental organisation that provides a framework for European cooperation in the field of molecular biology and closely-related research areas.

This article was first published on October 4 by University of Tartu.

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EMBL and University of Tartu sign MoU to boost scientific collaboration - Science Business

Cell Biology

Study reveals the underlying mechanisms behind obesity and type 2 diabetes link – News-Medical.Net

October 5, 2021 medical

It is well known that obesity affects the body's insulin production and over time risks leading to type 2 diabetes and several other metabolic diseases. Now researchers at Karolinska Institutet in Sweden have found further explanation for why fat cells cause metabolic morbidity. The study, published in Nature Medicine, may have an impact on the treatment of comorbidity in obesity with already available drugs.

Obesity is a rapidly growing global public health problem, not least among children and young people. Many metabolic diseases, among them type 2 diabetes, are strongly associated with obesity. In order to reverse the trend, more knowledge is needed, among other things, about how fat cells (adipocytes) contribute to various harmful processes in tissues and organs.

When fat cells are enlarged, they begin to secrete factors that cause inflammation of the adipose tissue. Fat cell enlargement is also associated with insulin resistance, when cells in the body do not respond to insulin as they should. The important task of insulin is to regulate energy, glucose, for the body's cells. When that function is disturbed, as with insulin resistance, the risk of type 2 diabetes increases.

This relationship is well documented, but there has been a lack of knowledge about the underlying mechanisms behind enlarged fat cells (fat cell hypertrophy) and the secretion of pro-inflammatory substances.

Now researchers at Karolinska Institutet have shown that in obesity and insulin resistance, the cell activity of fat cells changes. As fat cells increase in cell size, nuclear size and nuclear DNA content also increases.

The process of cells not dividing but increasing in DNA content and cell size (endoreplication) is common among plants and animals. In contrast, the process has not been described for human fat cells (adipocytes), which can increase in size more than 200 times over their lifespan."

Qian Li, Researcher, Department of Cell and Molecular Biology, Karolinska Institutet, and Joint First Author

The natural process of fat cells increasing in size has several negative effects on health. The authors demonstrate that elevated levels of insulin in the blood cause premature aging, senescence, in some cells in the adipose tissue.

"Our results show that senescent fat cells increase the secretion of pro-inflammatory factors, and drive inflammation and pathology in human adipose tissue. This in turn affects the health of the whole body," says Carolina Hagberg, researcher at the Department of Medicine, Solna at Karolinska Institutet, and joint first author.

The results are based on analysis of adipose tissue from 63 people with BMI under 30 who underwent umbilical hernia surgery or cholecysectomy for gallstone disease, as well as 196 people with BMI over 30 who underwent bariatric surgery for obesity in Stockholm.

Using a commonly prescribed drug for type 2 diabetes, the researchers were able to block the formation of senescent fat cells and reduce the secretion of fat cell-based pro-inflammatory factors.

"These studies identify an unappreciated aspect of human adipocyte biology, the activation of a cell cycle program in obesity and hyperinsulinemia, which could pave the way for novel treatment strategies for obesity and associated co-morbidities, such as type 2 diabetes," says Kirsty Spalding, researcher at the Department of Cell and Molecular Biology, Karolinska Institutet, and the study's last author.

Source:

Journal reference:

Li, Q., et al. (2021) Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Nature Medicine. doi.org/10.1038/s41591-021-01501-8.

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Study reveals the underlying mechanisms behind obesity and type 2 diabetes link - News-Medical.Net

Cell Biology

Gene Identified in Mice and Monkeys Acts as Natural Antiviral Against HIV, Ebola, and Other Deadly Infections – Genetic Engineering &…

October 5, 2021 medical

A research team led by scientists at the University of Utah (U of U) Health and the Rockefeller University has determined how a genetic mutation found in mice and in some New World monkeys interferes with how viruses such as HIV and Ebola infect cells. The gene, called RetroCHMP3, encodes an altered protein that disrupts the ability of certain viruses to exit an infected cell, and so prevents it from going on to infect other cells. The researchers suggest that the finding could help inform the future development of strategies for human therapeutics.

This was an unexpected discovery, said Nels Elde, PhD, senior author of the study and an evolutionary geneticist in the department of human genetics at U of U Health. We were surprised that slowing down our cell biology just a little bit throws virus replication off its game.

The team reported its findings in Cell, in a paper titled, RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis.

In humans and other animals, a protein called charged multivesicular body protein 3, or CHMP3, is well known for playing a key part in cellular mechanisms that are vital for maintaining cellular membrane integrity, intercellular signaling, and cell division. The endosomal sorting complexes required for transport (ESCRT) pathway mediates essential cellular membrane fission events such as multivesicular body formation, cytokinetic abscission, and resealing of the post-mitotic nuclear envelope, the authors explained. Some viruses, including HIV, which are known as enveloped viruses, hijack this ESCRT pathway to exit infected cells, which they do by encasing themselves in the cell membrane and then budding off from the host cell.

The new study has found that the variant version of CHMP3, known as RetroCHMP3, which is found in monkeys and mice, delays that process long enough that the virus can no longer escape. RetroCHMP3 originated as a duplicated copy of CHMP3. So while humans only have the original CHMP3, species such as monkeys, mice, and other animals, have retroCHMP3 or other variants.

Based on their research, Elde and his colleagues suspected that the duplications of CHMP3 that they discovered in primates and mice blocked the ability of enveloped viruses to co-opt the ESCRT pathway into their escape mechanism, as protection against viruses like HIV and other viral diseases.

Building on their hypothesis, Elde and other scientists began exploring whether variants of CHMP3 might work as an antiviral. In laboratory experiments conducted elsewhere, a shorter, altered version of human CHMP3 successfully prevented HIV from budding off cells. There was, however, a glitch: the modified protein also disrupted important cellular functions, causing the cells to die.

Unlike other researchers, Elde and his colleagues at U of U Health had naturally occurring variants of CHMP3 from other animals available. So, working in collaboration with Sanford Simon, PhD, co-author and professor of cellular biophysics at the Rockefeller University, along with Phuong Tieu Schmitt, PharmD, research associate and Anthony Schmitt, PhD, professor of molecular virology, both at Pennsylvania State University, they tried a different approach.

Using genetic tools, they coaxed human cells to produce the version of retroCHMP3 found in squirrel monkeys. When they then infected the cells with HIV, they found that the virus had difficulty budding off from the cells, essentially stopping them in their tracks. When expressed in human cells, these retroCHMP3 proteins potently inhibit the release of retroviruses, paramyxoviruses, and filoviruses, the investigators wrote. And this occurred without disrupting metabolic signaling or related cellular functions that can cause cell death. Remarkably, retroCHMP3 proteins have evolved to reduce interactions with other ESCRT-III factors and have little effect on cellular ESCRT processes, revealing routes for decoupling cellular ESCRT functions from viral exploitation, the team noted.

The scientists also suggested that an antiviral approach based on exploiting retroCHMP may prove more durable than existing antiviral strategies. Additionally,the observation that retroCHMP3 alters ESCRT pathway function instead of targeting a viral protein raises theintriguing possibility that retroCHMP3 may be more resistant to viral counter-adaptations than other antiviral proteins that directly inhibit viral replication, they stated.

Were excited about the work because we showed some time ago that many different enveloped viruses use this pathway, called the ESCRT pathway, to escape cells, said Wes Sundquist, PhD, co-corresponding author of the study and chair of the department of biochemistry at the University of Utah. We always thought that this might be a point at which cells could defend themselves against such viruses, but we didnt see how that could happen without interfering with other very important cellular functions.

From an evolutionary perspective, Elde believes this represents a new type of immunity that can arise quickly to protect against short-lived threats. We thought the ESCRT pathway was an Achilles heel that viruses like HIV and Ebola could always exploit as they bud off and infect new cells, Elde said. RetroCHMP3 flipped the script, making the viruses vulnerable. Moving forward, we hope to learn from this lesson and use it to counter viral diseases.

More specifically, that lesson raises the possibility that an intervention that slows down the process may be inconsequential for the host, but provide us with a new anti-retroviral, added Simon.

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Gene Identified in Mice and Monkeys Acts as Natural Antiviral Against HIV, Ebola, and Other Deadly Infections - Genetic Engineering &...

Cell Biology

Aging-US: Cellular senescence in lymphoid organs and immunosenescence – EurekAlert

October 5, 2021 medical

image:With advancing age, the stromal cells in the lining of sinuses, that demarcate follicular zone from the marginal zone, become less organized accompanied with an altered localization of various cell types. The inflammatory environment created by the accumulation of SnCs impairs the functionality of several cells residing in the spleen. This functional impairment mediated improper antigen presenting capabilities lead to the establishment of an inadequate T-cell response against pathogenic invasion. Abbreviations: SnC: Senescent cell; SASP: Senescence associated secretory phenotype; ROS: Reactive Oxygen Species. view more

Credit: Correspondence to: Daohong Zhou email: zhoudaohong@cop.ufl.edu

Aging-USpublished "Cellular senescence in lymphoid organs and immunosenescence" which reported that immunosenescence is a multi-faceted phenomenon at the root of age-associated immune dysfunction.

Though both cellular senescence and immunosenescence have been studied extensively and implicated in various pathologies, their relationship has not been greatly explored. In the wake of an ongoing pandemic that disproportionately affects the elderly, immunosenescence as a function of age has become a topic of great importance.

The goal of this review is to explore the role of cellular senescence in age-associated lymphoid organ dysfunction and immunosenescence, and provide a framework to explore therapies to rejuvenate the aged immune system.

Dr. Daohong Zhou fromThe University of Floridasaid, "Aging is the gradual process of organismal deterioration which is associated with a multitude of age-related disorders and diseases that make one wonder if aging itself is a disease that needs to be addressed."

A shadow is cast on the benefits of longevity if the elderly are faced with the possibility of a decline in their quality of life. The world currently has over 700 million people who are over the age of 65, a number that is projected to grow rapidly in the near future. As advancing age is strongly correlated to decreased quality of life and increased risk of several age-related diseases, these demographics seem more dismal in prospering countries, with the USA and the UK having about 1618% of their population over the age of 65.

The silver lining to this otherwise tragic situation is that results from recent studies indicate that the aging process and the pace of organismal deterioration is malleable and can be influenced greatly by physiological, genetic, dietary and pharmaceutical interventions.

The Zhou Research Team concluded in theirAging-US Research Output, "The increasing array of genetic models of SnC clearance along with a growing panel of senolytic and senostatic agents, provide a unique opportunity for scientists to answer these questions to lay a strong foundation to this new avenue of research in immunosenescence. Ultimately, gaining a deeper understanding of the interaction between cellular senescence and immunosenescence will help in the development of improved therapeutics that will aid in the conservation of our vitality as we age."

Full Text -https://www.aging-us.com/article/203405/text

Correspondence to: Daohong Zhouemail:zhoudaohong@cop.ufl.edu

Keywords:cellular senescence,immunosenescence,immune senescence,senescence associated secretory phenotype (SASP),thymus

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.

To learn more about Aging-US, please visithttp://www.Aging-US.comor connect with@AgingJrnl

Aging-US is published byImpact Journals, LLCplease visithttp://www.ImpactJournals.comor connect with@ImpactJrnls

Media Contact18009220957x105MEDIA@IMPACTJOURNALS.COM

Cellular senescence in lymphoid organs and immunosenescence

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Aging-US: Cellular senescence in lymphoid organs and immunosenescence - EurekAlert

Cell Biology

Study: Gene therapy can restore vision after stroke – EurekAlert

October 5, 2021 medical

Key research finding

Most strokes happen when an artery in the brain becomes blocked. Blood flow to the neural tissue stops, and those tissues typically die. Because of the locations of the major arteries in the brain, many strokes affect motor function. Some affect vision, however, causing patients to lose their vision or find it compromised or diminished. A research team led by Purdue Universitys Alexander Chubykin, an associate professor of biological sciences in the College of Science, in collaboration with the team led by Gong Chen at Jinan University, China, has discovered a way to use gene therapy to turn glial brain cells into neurons, restoring visual function and offering hope for a way to restore motor function.

Neurons dont regenerate. The brain can sometimes remap its neural pathways enough to restore some visual function after a stroke, but that process is slow, its inefficient, and for some patients, it never happens at all. Stem cell therapy, which can help, relies on finding an immune match and is cumbersome and difficult. This new gene therapy, as demonstrated in a mouse model, is more efficient and much more promising.

We are directly reprogramming the local glial cells into neurons, Chubykin said. We dont have to implant new cells, so theres no immunogenic rejection. This process is easier to do than stem cell therapy, and theres less damage to the brain. We are helping the brain heal itself. We can see the connections between the old neurons and the newly reprogrammed neurons get reestablished. We can watch the mice get their vision back.

Chubykins research is especially important because visual function is easier than motor skills to measure accurately, using techniques including optical imaging in live mice to track the development and maturation of the newly converted neurons over the course of weeks. Perfecting and understanding this technique could lead to a similar technique reestablishing motor function. This research bridges the gap in understanding between the basic interpretation of the neurons and the function of the organs.

Purdue professors expertise

Chubykin is an expert in how neurons respond to visual experiences, as well as conditions including autism and ischemic stroke. He is affiliated with the Purdue Institute for Integrative Neuroscience and the Purdue Autism Research Center.

###

Journal name

Frontiers in Cell and Developmental Biology. The article is available online.

Funding

National Institute of Mental Health grant RF1 MH123401

Brief summary of methods

The team simulated an ischemic stroke affecting the visual centers in the brains of mice, mapping and measuring the extent of the neural and visual damage. Then, they used adeno-associated viruses to deliver NeuroD1 to glial cells in the affected part of the brain. They watched and measured as the glial cells were reprogrammed into neurons and were integrated into the visual cortex. After that, they measured the responses of these cells to visual stimulus and mapped the development of the visual cortex to measure the recovery of visual function.

Writer/Media contact: Brittany Steff, bsteff@purdue.edu

Source: Alexander Chubykin, chubykin@purdue.edu

Frontiers in Cell and Developmental Biology

Experimental study

Animals

Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy

18-Aug-2021

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Study: Gene therapy can restore vision after stroke - EurekAlert

Cell Biology

NextCure Announces New Appointments to its Board of Directors – GlobeNewswire

October 5, 2021 medical

BELTSVILLE, Md., Oct. 04, 2021 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases, today announced the appointments of Ellen G. Feigal, M.D., and Anne Borgman, M.D., to its Board of Directors.

I am thrilled to welcome two new members to NextCures Board of Directors, said Michael Richman, NextCures president and chief executive officer. Both Dr. Feigal and Dr. Borgman bring extensive experience in clinical and biopharmaceutical settings. Their insights will be valuable as NextCure continues to advance multiple clinical programs and investigate and develop new immunomedicines for cancer patients. These appointments follow the resignation of Stella Xu, Ph.D. from the board as previously announced. In addition, we would like to thank Stella Xu for her commitment and support in building NextCure.

Dr. Feigal is currently a Partner and Head of the Biologics Practice at NDA Partners LLC, a life sciences consulting and contract development organization, where she leads efforts in designing and executing product development and regulatory strategies in the areas of cell therapies, medical imaging, hematology and oncology. Dr. Feigal is also adjunct faculty at the Sandra Day O'Connor College of Law, Arizona State University, where she teaches FDA drug law and medical research ethics and law. Her career includes over thirty years in clinical drug development, with roles spanning industry and academic medicine, including at the National Cancer Institute, where she served as Acting Director, Division of Cancer Treatment/Diagnosis during her tenure; Senior Vice President of Research and Development at the California Institute of Regenerative Medicine, and Executive Medical Director, global development at Amgen. She currently serves as a board member for Xencor. She earned her M.D. from the University of California, Davis, completed an internal medicine residency at Stanford University and a hematology/oncology fellowship at the University of California, San Francisco.

Dr. Borgman is currently Vice President and Global Therapeutic Area Lead, Hematology-Oncology, at Jazz Pharmaceuticals, where she is responsible for global development of the companys oncology and hematology drugs, including four marketed products. Previously, Dr. Borgman was Vice President, Clinical Research & Development, at Exelixis, where she was a Clinical Lead in the global development for cabozantinib in oncology indications including renal cell, hepatocellular and thyroid carcinoma. Earlier she was Chief Medical Officer and Vice President of Hana Biosciences (Talon Therapeutics), where she oversaw all aspects of the companys drug development operations. In addition, Dr. Borgman has worked as Associate Chief Medical Officer at KaloBios Pharmaceuticals, and she was formerly a Global Development Head at Abbott Pharmaceuticals (now AbbVie) where she was responsible for the early drug development of the PARP inhibitor, antimitotic, and Bcl-2/Bcl-XL platforms. Dr. Borgman continues clinical involvement, as a Consulting Associate Professor at Stanford University School of Medicines Stem Cell Transplant & Cell Biology program, and as a Clinical Associate at University of Chicagos Department of Pediatric Oncology and Stem Cell Research. Dr. Borgman completed her fellowship in pediatric hematology - oncology and stem cell transplant at UCLA David Geffen School of Medicine, trained in pediatrics at Texas Children's Hospital, Baylor College of Medicine, and earned her M.D. from Loyola University of Chicagos Stritch School of Medicine.

About NextCure, Inc.NextCure is a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases. Through our proprietary FIND-IO platform, we study various immune cells to discover and understand targets and structural components of immune cells and their functional impact in order to develop immunomedicines. Our initial focus is to bring hope and new treatments to patients who do not respond to current cancer therapies, patients whose cancer progresses despite treatment and patients with cancer types not adequately addressed by available therapies. http://www.nextcure.com

Cautionary Statement Regarding Forward-Looking StatementsStatements made in this press release that are not historical facts are forward-looking statements. Words such as expects, believes, intends, hope, forward and similar expressions are intended to identify forward-looking statements. Examples of forward-looking statements in this press release include, among others, statements about NextCures plans, objectives and intentions with respect to the discovery of immunomedicine targets and the discovery and development of immunomedicines. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those projected in any forward-looking statement. Such risks and uncertainties include, among others: our limited operating history and no products approved for commercial sale; our history of significant losses; our need to obtain additional financing; risks related to clinical development, marketing approval and commercialization; and the unproven approach to the discovery and development of product candidates based on our FIND-IO platform. More detailed information on these and additional factors that could affect NextCures actual results are described in NextCures filings with the Securities and Exchange Commission (the SEC), including NextCures most recent Form 10-K and subsequent Form 10-Q. You should not place undue reliance on any forward-looking statements. NextCure assumes no obligation to update any forward-looking statements, even if expectations change.

Investor InquiriesTimothy Mayer, Ph.D.NextCure, Inc.Chief Operating Officer(240) 762-6486IR@nextcure.com

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NextCure Announces New Appointments to its Board of Directors - GlobeNewswire

Cell Biology

Stunning Images Captured Using the Glowing Properties of Plant Cells – SciTechDaily

October 5, 2021 medical

Formaldehyde fixation improves fluorescence patterns of tissues within maize (Zea mays) leaf cross sections. Treatment with a paraformaldehyde fixative solution revealed distinctive blue/green fluorescence of epidermis, trichomes, xylem, phloem, and bulliform cells resulting from aldehyde-induced fluorescence. By comparison, red autofluorescence of chlorophyll was observed in bundle sheath cells and mesophyll of leaf cross sections. This sample was prepared using a formaldehyde fixation and confocal imaging technique described by Pegg et al. in Algae to Angiosperms: Autofluorescence for rapid visualization of plant anatomy among diverse taxa in this issue. Formaldehyde fixation of Viridiplantae taxa samples such as Zea mays generates useful structural data while requiring no additional histological staining or clearing. In addition, image acquisition requires only minimal specialized equipment in the form of fluorescence-capable microscopes. Credit: Timothy J. Pegg

Scientists have come a long way since Antonie van Leeuwenhoek discovered teeming colonies of previously invisible bacteria and protozoa while peering through his custom-made microscopes. The architecture of cells, organelles, proteins, and even molecules has since been illuminated across the tree of life. Yet despite these advances, barriers still remain to comprehensively mapping the microscopic world. Before they can be viewed under a microscope, tissues and cell components must first be stained with dyes and fixatives and subjected to a lengthy preparation process.

In a new study published in the journal Applications in Plant Sciences, scientists obviate the need for specimen staining by tapping into the natural autofluorescence of tissues in species across the plant tree of life.

Our work provides a cost-effective, generalized protocol for plant sample preparation and visualization that is equally applicable to large research institutions and smaller plant science groups, said Dr. Timothy Pegg, a visiting assistant professor at Marietta College and lead author on the study.

When certain tissue types in both plants and animals absorb light, electrons in their atoms get a jolt of energy that bumps them into an excited state. In plant leaves, these electrons become so unstable that they break free from their atoms and are used by the plant to power photosynthesis. In other tissues, the excess energy is re-emitted in the form of low-frequency light bright enough to be detected with specialized microscopes.

Autofluorescence hasnt always been viewed as a good thing. In cases where researchers have to use stains to visualize specific structures, the light-emitting properties of nearby tissues can interfere by decreasing the contrast between different cell types.

But it can also be an indispensable resource for discovery. Autofluorescence has been used to detect early onset cancers, as well as other diseases and pathologies. Its been used to study how insects use their tongues and antennae to taste food, the mechanisms underlying tail regeneration in lizards, and to analyze the diversity of microscopic plankton in marine environments.

Autofluorescence is equally useful in plants, where it shows up in everything from the hard tissues that give woody plants their stability, to the water-wicking residue covering spores and pollen, to the diverse arsenal of toxic compounds plants produce to ward off would-be predators.

Up until now, however, researchers have lacked a one-size-fits-all protocol for detecting autofluorescent light in plants. The lack of a unified, standard approach is understandable, given there are nearly half-a-million living species of land plants and algae, but Pegg and his colleagues remained undeterred. They selected 12 species from several key plant groups separated by more than 500 million years of evolutionary history, including pines, bryophytes, flowering plants, and algae.

Using these representatives, they developed a cost-efficient method of tissue preservation without the need for stains or dyes.

While autofluorescence can often be directly visualized with confocal microscopes, it can also be induced or enhanced with different fixatives, including alcohols, ethanol, and compounds called aldehydes. Pegg and his colleagues chose five of the most effective among these to test their plant specimens. After marinating in fixative for 24 hours, the plants were rinsed, chopped to the width of a human hair, and mounted on a transparent slide for visualization.

When the researchers looked through the microscope, the miniature world of plant cells and organelles was brought into sharp focus. The rigid lines of cell walls stood out in bas-relief from the tightly packed chlorophyll inside. By honing in on particular wavelengths of light emitted by proteins, they could distinguish between the dense features of nuclei and the water- and sugar-conducting tissue snaking their way between cells.

Most fixatives performed well in the representative plants, with striking results, but algae proved to be an exception. Most land plants have thick, buttressing cell walls that help prevent water loss while providing structural support, qualities that algae lack. Due to their flimsier cellular scaffolding, ethanol and alcohol fixatives quickly penetrated the cell walls of algae and the sole liverwort (a plant closely related to mosses) used in the study, causing the organelles to wrinkle and deform. For these specimens, Pegg recommends sticking to aldehyde fixatives or reducing the amount of time used in the specimen preparation stages.

Most research labs also dont own the high-powered confocal microscopes required to view cellular structures at fine scales, instead paying hourly rates to use the equipment provided by their institution, an issue which Pegg and his colleagues hope their protocol can address.

Our simple sample preparation technique can cut down on the amount of time researchers need to spend visualizing samples on advanced microscopes, said Dr. Robert Baker, assistant professor of biology at Miami University and senior author on the study.

All of the chemicals and reagents used in the study are similarly inexpensive and readily available, meaning that just about anyone at a research institution can use this protocol to study subcellular interactions in plants.

Reference: Algae to angiosperms: Autofluorescence for rapid visualization of plant anatomy among diverse taxa by Timothy J. Pegg, Daniel K. Gladish and Robert L. Baker, 2 July 2021, Applications in Plant Sciences.DOI: 10.1002/aps3.11437

Cell Biology

Nicotinic acetylcholine receptor redux: Discovery of accessories opens therapeutic vistas – Science

August 13, 2021 medical

Accessory proteins and nicotinic receptors

Acetylcholine was the first neurotransmitter identified, and nicotinic acetylcholine receptors (nAChRs) were the first neurotransmitter receptors isolated. Recent studies have identified a multitude of molecules and mechanisms that regulate nAChRs in different tissues. In a Review, Matta et al. discuss these discoveries and their implications for the cell biology and medicinal pharmacology of nACHRs. Many accessory factors promote the assembly and function of diverse nAChRs. Some factors are small molecules, some are proteins, some control receptor biogenesis, and some regulate channel gating. These protein chaperones and auxiliary subunits elucidate the pharmacological and physiological processes regulated by acetylcholine.

Science, abg6539, this issue p. eabg6539

One hundred years ago, experiments on beating frog hearts identified acetylcholine (ACh) as the seminal neurotransmitter. Sixty years later, fractionation of the eel electroplax isolated nicotinic ACh receptors (nAChRs) as the first purified ion channel. We now appreciate that a family of nAChRs are differentially expressed in numerous tissues, including the brain, skeletal muscle, white blood cells, and cochlear hair cells. Paralleling this wide distribution, nAChRs mediate diverse physiological functions, including cognition, muscle contraction, immunomodulation, and sound discrimination. Neuronal nAChRs also account for the psychoactive and addictive properties of tobacco and are the primary genetic risk factors for lung cancer. Therapeutically, nAChRs provide pharmacological targets of approved medicines for cardiovascular and neurological disorders.

Nicotinic AChRs comprise multiple subunits whose molecular folding and surface trafficking involve complex and tightly regulated processes. As nAChRs often require tissue-specific factors for functional expression, many subtypes fail to create receptor channels in recombinant systems. Our limited understanding of nAChR assembly has impeded basic research and drug development.

Studies in the 1970s found that smokers have increased nAChR density in the brain owing to receptor stabilization by nicotinea process that likely contributes to tobacco addiction. Recent applications of proteomics, genetics, and expression cloning have identified a bevy of partner proteins and metabolites essential for nAChR function. These accessories act at multiple steps in nAChR biogenesis. Within the endoplasmic reticulum, chaperones mediate nAChR subunit folding and assembly. Other factors then promote nAChR trafficking to the plasma membrane. Finally, auxiliary subunits associated with surface nAChRs modulate channel activation. These chaperones and auxiliary subunits include both nAChR-specific regulators and more pleiotropic factors. On the one hand, NACHO (a neuronal endoplasmic reticulumresident protein) serves as a client-specific chaperone for neuronal nAChRs. By contrast, transmembrane inner ear protein contributes to both hair cell nAChRs and mechanosensitive channels, which modulate cochlear amplification and transduce sound waves, respectively. Interplay between nAChR accessory components can further regulate receptor distribution and function.

Discovery of these molecules and mechanisms is transforming basic and translational science concerning nAChRs. Inclusion of appropriate chaperones during protein production is enabling structural studies of nAChR subtypes. Accessory components are also permitting biophysical studies of nAChR channel properties. Furthermore, understanding mechanisms that control trafficking and subunit composition is defining roles for nAChRs in biological processes and disease.

This research also provides therapeutic opportunities. The dearth of pharmacological agents for certain nAChRs results from challenges in recombinant expression of many receptor types. The ability to express complex nAChR subunit combinations in cell lines unlocks them for the chemical screening that initiates drug discovery. Auxiliary subunits can themselves provide pharmacological targets. Furthermore, drugging chaperone pathways may benefit myasthenia gravis and other diseases associated with aberrant nAChR levels.

Despite being the archetypal neurotransmitter receptor, much remains unknown about nAChRs. The identification of molecular partners and elucidation of regulatory mechanisms provide a cell biological renaissance and can suggest avenues for treating diseases associated with nAChR dysfunction.

Throughout the body, nAChRs are differentially expressed in neurons, myocytes, leukocytes, and cochlear and vestibular hair cells. An array of nAChR chaperones and auxiliary subunits (inset) mediate endoplasmic reticulum folding and assembly, intracellular trafficking, and plasma membrane activation. The recent identification of receptor accessories enables drug discovery for these nAChRs, which provide compelling targets for neurological, psychiatric, immunological, and auditory disorders.

The neurotransmitter acetylcholine (ACh) acts in part through a family of nicotinic ACh receptors (nAChRs), which mediate diverse physiological processes including muscle contraction, neurotransmission, and sensory transduction. Pharmacologically, nAChRs are responsible for tobacco addiction and are targeted by medicines for hypertension and dementia. Nicotinic AChRs were the first ion channels to be isolated. Recent studies have identified molecules that control nAChR biogenesis, trafficking, and function. These nAChR accessories include protein and chemical chaperones as well as auxiliary subunits. Whereas some factors act on many nAChRs, others are receptor specific. Discovery of these regulatory mechanisms is transforming nAChR research in cells and tissues ranging from central neurons to spinal ganglia to cochlear hair cells. Nicotinic AChRspecific accessories also enable drug discovery on high-confidence targets for psychiatric, neurological, and auditory disorders.

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Nicotinic acetylcholine receptor redux: Discovery of accessories opens therapeutic vistas - Science