Category Archives: Cell Biology

Cell Biology

Project positions at Translational Health Science and Technology Institute – Mathrubhumi English

Translational Health Science and Technology Institute (THSTI), an Autonomous Institute of the Department of Biotechnology, Govt. of India; NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, P.O. Box No. 04, Faridabad-121001, has notified various Project positions at the Institute.

Projects and Positions are as follows:

Project: Preclinical and Pharmacokinetics Evaluations of select AYUSH Herbal Extracts/Formulations for Mitigating SARS-CoV2 Associated Pathologies

Project Associate: Masters Degree in any branch of Life Science or Pharmacology with 2 years experience in Animal Cell Culture and Molecular Biology Techniques

Project: Adaptive Molecular Diagnostics

Research Fellow: M.Sc in Chemistry/Biochemistry/Microbiology with one year of Post qualification research experience in Cell Biology or Microbiology or Genomics from a R&D Institute

Project: Structure Determination of targeting of ubiquitously expressed membrane integrated form of Chloride Intracellular channels (CLICs) for discovery of small molecular anti-cancer therapeutics

Research Associate: PhD in Organic Chemistry/Medicinal Chemistry or equivalent

Project: Development, Characterization and Evaluation of protective efficacy of self-amplifying mRNA vaccine candidates against the severe acute respiratory syndrome coronavirus 2 (SARS CoV 2)

Project Scientist: PhD In any branch of Life Science with 2 years post qualification research experience in animal cell culture and molecular Biology techniques

Senior Project Associate: Ph.D In any branch of Life Science with 1 year post qualification research experience in mouse/hamster handling and experimentation

Project Associate: Masters Degree in any branch of Life Science or Pharmacology with 2 years experience in animal cell culture and molecular Biology techniques and/or mouse/hamster handling and experimentation

Details of the Project, selection procedure, last date for applying and other terms and conditions are available in the detailed notification at https://thsti.in/application/jobs.php

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Project positions at Translational Health Science and Technology Institute - Mathrubhumi English

Cell Biology

Coronavirus: The 40-year-old drug that could stop people getting sick from COVID-19 – The Australian Financial Review

On Tuesday, one its co-founders, Pierre Kory, appeared before a US Senate Homeland Security and governmental affairs committee, saying there was more evidence.

He reminded the hearing on Early Outpatient Treatment: An Essential Part of a COVID-19 Solution that in May, against widespread opposition, he had recommended corticosteroids be used to treat COVID-19.

That turned out to be a lifesaving recommendation," Associate Professor Kory told the hearing. "I am here today with a new recommendation.

He said four large randomised controlled trials involving more than 1500 patients had demonstrated Ivermectins effectiveness as a safe prophylactic agent in COVID 19, when used in early outpatient treatment.

He noted discoveries related to Invermectin had won two researchers the Nobel Prize for Physiology or Medicine in 2015.

All I ask is for the National Institutes of Health to review our data, he said.

At an alliance press conference in the US last week, Professor Kory said that as vaccines would not be distributed fast enough to save lives, something was needed in the interim.

COVID-19 is a runaway train barrelling down the tracks, and if youre on those tracks, Ivermectin can help lift you out of harms way," he said.

Paul Marik, co-founder of the alliance, said Ivemectin had been used safely by 3.7 billion people.

It had high activity fighting the SARS-CoV-2 virus as well as the inflammation produced in all stages of COVID-19.

It works pre-and post-exposure, the early symptoms phase and late-stage disease," Professor Marik said.

Australia was first to identify the drug's potential against COVID-19, says Stephen Turner, head of the Department of Microbiology at Monash. Monash

In April, the Monash and Doherty study indicated Ivermectin resulted in the loss of nearly all viral material within 48 hours, with no toxicity, in non-human cells.

But in May, another study found the design of this study made it difficult to extrapolate to humans.

Ivermectin works by interfering with the life cycle of pathogens, disrupting some basic cell biology. So it needs to be used at low enough doses to minimise side effects in patients, says Stephen Turner, head of the Department of Microbiology at Monash.

Now the researchers are looking at safe dosing that could still get the protective effect while limiting side effects. Their trials are under way and, until they report, the jury is still out.

Allen Cheng, professor of infectious diseases epidemiology at Monash and a member of Australias National COVID Evidence Taskforce, which keeps an eye on all the available evidence, agrees the jury is still out.

He says the taskforce currently recommends against the use of Ivermectin as treatment outside of trials and has no recommendation for its use in prevention.

The taskforce has a list of almost 30 other treatments that have not been found to work, which reinforces that treatments need to be tested rigorously in clinical trials," Professor Cheng says.

"Obviously, evidence is constantly changing, so if evidence emerges that Ivermectin (or any other treatment) works, these recommendations would change.

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Coronavirus: The 40-year-old drug that could stop people getting sick from COVID-19 - The Australian Financial Review

Cell Biology

Magenta Therapeutics and bluebird bio Announce a Phase 2 Clinical Trial Collaboration to Evaluate Magenta’s MGTA-145 for Mobilizing and Collecting…

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20201204005134/en/

We are excited to build upon our leading position in the field of ex-vivo gene therapy and the promising clinical data with LentiGlobin in SCD with a collaboration focused on achieving improved stem cell mobilization, said Dave Davidson, M.D., chief medical officer, bluebird bio. In this initial study, we hope to establish whether the combination of plerixafor with MGTA-145 can generate appropriate CD34+ stem cells with a single round of mobilization. If successful, we hope to evaluate this novel mobilization regimen with LentiGlobin to make another step forward in the treatment of patients with SCD.

Achieving reliable and rapid stem cell mobilization and a simplified collection process can ensure the entire patient experience is optimal with respect to therapeutic outcome. The incorporation of bluebird bios experience in this area of treatment will be immensely valuable in further developing MGTA-145 plus plerixafor to address the remaining unmet needs in gene therapy approaches for diseases like sickle cell disease, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics. We look forward to collaborating with bluebird bio to evaluate MGTA-145 as the preferred mobilization option for people with sickle cell disease.

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events (VOEs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complicationssuch as acute chest syndrome (ACS), stroke, and infections, which can contribute to early mortality in these patients.

Currently available mobilization drugs, including granulocyte-colony stimulating factor (G-CSF), a commonly used mobilization agent administered over the course of five to seven days in other transplant settings, is not used in sickle cell disease because it can trigger vaso-occlusive crises and even death in adults and adolescents. Plerixafor is used to mobilize a patients stem cells for collection prior to transplant and while an available treatment option, multiple cycles of apheresis and collection may sometimes be required to generate sufficient stem cells for gene therapy. Magenta is developing MGTA-145, in combination with plerixafor, to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells (HSCs) to improve stem cell transplantation outcomes in multiple disease areas, including genetic diseases such as sickle cell disease, as well as blood cancers and autoimmune diseases.

About Magenta Therapeutics MGTA-145

MGTA-145, in combination with plerixafor, has demonstrated, in a recently completed Phase 1 study in healthy volunteers, it can rapidly and reliably mobilize high numbers of functional stem cells in a single day, without the need for G-CSF. MGTA-145 works in combination with plerixafor to harness a physiological mechanism of stem cell mobilization to rapidly and reliably mobilize HSCs for collection and transplant across multiple indications.

Additionally, as shown in preclinical studies, stem cells mobilized with MGTA-145 can be efficiently gene-modified and are able to engraft, potentially allowing for safer and more efficient mobilization for gene therapy approaches to treat sickle cell disease and other genetic diseases.

Magenta completed its Phase 1 trial of MGTA-145 in healthy volunteers, demonstrating MGTA-145 was well tolerated and enables same-day dosing, mobilization and simplified collection of sufficient stem cells for transplant, meeting all primary and secondary endpoints.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavour, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, and in bluebird bios Annual Report on Form 10-K filed on February 18, 2020, as updated by each companys most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta and bluebird bio believe that the expectations reflected in the forward-looking statements are reasonable, neither Magenta nor bluebird bio can guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta or bluebird bio, nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. Neither Magenta nor bluebird undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics and bluebird bio Announce a Phase 2 Clinical Trial Collaboration to Evaluate Magenta's MGTA-145 for Mobilizing and Collecting...

Cell Biology

Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145…

Dec. 7, 2020 13:00 UTC

Enrollment commenced in the MGTA-145 Phase 2 clinical trial of autologous transplant of multiple myeloma patients at Stanford University

Oral presentation of Phase 1 clinical data presented at the 62nd American Society of Hematology (ASH) Annual Meeting confirming MGTA-145 achieved proof-of concept: all safety and efficacy endpoints met and mobilized cells demonstrated functional superiority over other mobilization approaches in preclinical studies

Preclinical data from MGTA-117, the first targeted antibody-drug conjugate (ADC) from the Magenta platform, continue to indicate that it is an effective, potent conditioning agent with the potential to improve transplant outcomes in patients with blood cancers and genetic diseases

Magenta expects to provide additional updates on its programs and clinical plans in early 2021

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, today announced final clinical results from its earlier completed Phase 1 clinical trial as well as development updates for its MGTA-145 stem cell mobilization therapy, including commencement of enrollment in a Phase 2 clinical trial in multiple myeloma, and its plans for a Phase 2 clinical trial in allogeneic stem cell transplant for patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS). The company also previously announced a clinical collaboration with bluebird bio to evaluate MGTA-145 for mobilizing and collecting stem cells in adults and adolescents with sickle cell disease (SCD). Additional preclinical results were also presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020, on the Magenta conditioning platform, including MGTA-117 program, which is a targeted antibody-drug conjugate (ADC) to prepare patients for stem cell transplant.

MGTA-145 Advancement to Phase 2 Development in Blood Cancers

The company announced that enrollment has started and is ongoing in a Phase 2 clinical trial of MGTA-145, used in combination with plerixafor, to mobilize and collect stem cells for autologous stem cell transplantation of multiple myeloma patients at Stanford University. Magenta expects that this trial will provide patient-level data on stem cell mobilization and collection, characteristics of the mobilized graft and engraftment in patients with multiple myeloma.

Additionally, through a collaboration with the National Marrow Donor Program/Be The Match, a global leader in facilitating allogeneic hematopoietic stem cell transplantation, Magenta plans to initiate a Phase 2 clinical trial in early 2021 using MGTA-145 to mobilize and collect stem cells from allogeneic donors for transplant in patients with AML, ALL and MDS. Allogeneic stem cell transplant provides a potentially curative therapeutic option for patients with these diseases. This clinical trial will evaluate stem cell mobilization, collection, cell quality, engraftment and the potential for reduced Graft-versus-Host Disease (GvHD), which is of particular importance in the allogeneic transplant setting.

MGTA-145 in Sickle Cell Disease

Magenta Therapeutics recently announced an exclusive clinical collaboration with bluebird bio to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in adults and adolescents with SCD.

The data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. bluebird bios experience with plerixafor as a mobilization agent in SCD aligns with Magentas combination therapy approach, utilizing MGTA-145 plus plerixafor with potential for safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

MGTA-145 Presentations at ASH

Magenta presented final clinical data from its MGTA-145 stem cell mobilization Phase 1 clinical trial in healthy volunteers at the ASH Annual Meeting. All primary and secondary endpoints were met in the study completed earlier this year.

The results demonstrate that a single dose of MGTA-145, in combination with plerixafor, rapidly and reliably mobilized high numbers of stem cells in a single day without the need for G-CSF for potential use in diseases that can benefit from autologous and/or allogeneic stem cell transplantation. The additional data also offer further confirmation that MGTA-145, in combination with plerixafor, was well tolerated and provides a rapid and reliable method to obtain large numbers of hematopoietic stem cells. Transplant of these cells in preclinical models resulted in enhanced, durable engraftment, in addition to highly immunosuppressive properties, leading to reduced GvHD.

Results from this study provide a robust dataset and proof of concept that MGTA-145, in combination with plerixafor, provides rapid and robust mobilization of stem cells and that these cells have better engraftment potential, are able to be gene modified and engraft and reduce GvHD in preclinical models compared to cells mobilized with other available agents. The data reinforce the availability of compelling opportunities for development in both the autologous and allogeneic transplant settings, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics.

The data were presented by Steven M. Devine, MD, Chief Medical Officer of the National Marrow Donor Program/Be The Match and Associate Scientific Director of the CIBMTR (Center for International Blood and Marrow Transplant Research).

Conditioning Program (MGTA-117 and CD45-ADC) Presentations at ASH

Magenta also provided updates on its conditioning platform at the ASH Annual Meeting, including MGTA-117 and CD45-ADC programs. Preclinical data from a study of MGTA-117 demonstrate that it is an effective, potent conditioning agent for transplant with anti-leukemic activity, significantly decreasing tumor burdens, leading to delayed tumor growth and increased median survival rates in animal models of AML. Ongoing GLP toxicology and GMP manufacturing progress continue to be supportive of advancing MGTA-117 towards an IND filing in AML and MDS.

Additionally, preclinical data from a study of Magentas CD45-ADC, a CD45-targeted conditioning agent designed to remove the cells that cause autoimmune diseases to enable curative immune reset, demonstrated the ability to achieve successful outcomes as a single agent in the most challenging disease model through fully mismatched allogeneic hematopoietic stem cell transplant, where only radiation or combinations of toxic chemotherapies are available, potentially providing patients the option of a reduced toxicity conditioning regimen. The company continues to evaluate this program preclinically.

About MGTA-145

MGTA-145 is being developed in combination with plerixafor to harness complementary chemokine mechanisms to mobilize hematopoietic stem cells for collection and transplantation. This new combination has the potential to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells to improve outcomes in autologous and allogeneic stem cell transplantation, which can rebuild a healthy immune system for patients with blood cancers, genetic diseases and autoimmune disorders.

MGTA-145 has the potential to replace the current standard of care for patients and allogeneic donors who currently rely on the use of granulocyte-colony stimulating factor (G-CSF) alone or in combination with plerixafor, which can take up to five days or longer to mobilize sufficient numbers of stem cells, often resulting in significant bone pain and other side effects.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with blood cancer, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145...

Cell Biology

White blood cells may cause tumor cell death but thats not necessarily a good thing – Newswise

Newswise White blood cells are part of many immune system responses in the human body. New research shows that a specific type of those cells may cause brain cancer tissues to die but thats not good news, according to researchers at Penn State College of Medicine and Penn State Cancer Institute. They said that higher amounts of this tissue death have been associated with poor survival in patients with aggressive glioblastomas, a deadly type of brain cancer that is common in adults.

Wei Li, assistant professor of pediatrics and biochemistry and molecular biology, studied the causes of this tissue death, called necrosis. Scientists have suggested that a lack of oxygen due to poor blood supply from rapid tumor growth may cause necrosis, but Li and a team of researchers investigated the molecular processes that cause this tissue death to occur. Their findings were published in Nature Communications.

Glioblastoma patients with higher degrees of necrosis have a poor chance of survival, Li said. We hope insight into the processes that drive this tissue death can help us develop new therapeutics to improve outcomes for these patients.

Li and the research team, including medical scientist training program student Patricia Yee, found that ferroptosis, a specific type of regulated cell death, caused tissue death. They examined tumor tissue samples from animal models of glioblastoma under a microscope and found that neutrophils, a type of white blood cell, were present in the same areas as dead tumor cells.

To establish whether these cells were part of the tissue death process, they decreased the amount of neutrophils in animal models, which then decreased the amount of necrosis in those cancer models. They also isolated these white blood cells and tested them against cancer cells in a lab and found that the presence of neutrophils prevented the cancer cells from thriving.

We confirmed our theory on the role of neutrophils in necrosis by evaluating glioblastoma patient data, Li said. A high number of neutrophils and the presence of genetic signals of ferroptosis were associated with pathological evidence of necrosis and predicted poor survival in patients.

Although they had a better idea of the key factor driving the tissue death, Li and colleagues were unsure why the tissue death was beneficial to tumor progression. They studied glioblastoma patient data sets and found that the dead cells secrete molecular signals that may help tumor cells grow.

Li said future studies will investigate how the white blood cells that spur on the tissue death arrive at the tumor to begin with. He suspects that tissue damage from the tumor growth may be causing the neutrophils to arrive, but that further studies are needed. He also said more research is needed to better understand how necrosis promotes cancer growth.

If we can develop therapeutic approaches for preventing necrosis, theres a chance those tumors might be less aggressive, which could be beneficial to glioblastoma patients, Li said.

Dawit Aregawi, Michael Glantz, Brad Zacharia and Hong-Gang Wang of Penn State Cancer Institute; Krishnamoorthy Thamburaj of Penn State Neuroscience Institute; Stephen Chih of Penn State College of Medicine Medical Scientist Training Program; and Yiju Wei, Soo-Yeon Kim, Tong Lu, Cynthia Lawson, Miaolu Tang, Zhijun Liu, Benjamin Anderson, Megan Young and Charles Specht of Penn State College of Medicine also contributed to this research.

This research was supported by the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

This research was also supported by the Meghan Rose Bradley Foundation, the American Cancer Society, Four Diamonds, and Penn State College of Medicines Medical Scientist Training Program.

The authors declare no conflicts of interest.

About Penn State College of MedicineLocated on the campus ofPenn State Health Milton S. Hershey Medical Centerin Hershey, Pa.,Penn State College of Medicineboasts a portfolio of more than $100 million in funded research. Projects range from development of artificial organs and advanced diagnostics to groundbreaking cancer treatments and understanding the fundamental causes of disease. Enrolling its first students in 1967, the College of Medicine has more than 1,700 students and trainees in medicine, nursing, the health professions and biomedical research on its two campuses.

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White blood cells may cause tumor cell death but thats not necessarily a good thing - Newswise

Cell Biology

Scientists Look to Animals and Find Out What May Make Certain People More Vulnerable to COVID-19 – SciTechDaily

What makes certain groups more vulnerable to COVID-19? Researchers look to animals to find clues in proteins involved in infection.

What makes the elderly and people with underlying conditions more vulnerable to COVID-19? According to a new study led by McGill University researchers, clues can be found in the proteins involved in initiating infection, as the virus binds to host cells of different animals. Greater cellular oxidation with aging and sickness may explain why seniors and people with chronic illness get infected more often and more severely.

Over 60 million people have been infected and around 1.5 million have died from COVID-19. The virus is disrupting economies and food supply chains all over the world. Understanding why some animals get infected and others do not could be the key to unlocking new treatments and therapies. In a study published in Computational and Structural Biotechnology Journal, researchers analyzed available protein sequences of the virus and host cell receptors across different spices to find out why.

In analyzing the proteins and their amino acid building blocks, the researchers found that animals susceptible to the virus have a few things in common. They have two cysteine amino acids that form a special disulfide bond held together by an oxidizing cellular environment. This disulfide bond creates an anchor for the virus. Credit: Jaswinder Singh

We know that the virus can infect humans, cats, dogs and ferrets but not bovine and swine. Also, COVID-19 hits the elderly and people with underlying conditions more severely than the young and healthy ones. Until nowreasons for this were unclear, says McGill Professor Jaswinder Singh.

The research was conducted by a multidisciplinary team of scientists led by Professor Singh. The team includes Professor Rajinder Dhindsa (McGill University), Professor Baljit Singh (University of Calgary) and Professor Vikram Misra (University of Saskatchewan).

Once inside a host cell, the virus hijacks the cells metabolic machinery to replicate and spread. The viruss protein spikes attach to a protein receptor on the surface of the host cell called ACE2, fusing the membranes around the cell and the virus together. This process allows the virus to enter the cell and co-opt its protein-making machinery to make new copies of itself. The copies then go on to infect other healthy cells.

In analyzing the proteins and their amino acid building blocks, the researchers found that animals susceptible to the virus have a few things in common. Such animals like humans, cats, and dogs have two cysteine amino acids that form a special disulfide bond held together by an oxidizing cellular environment. This disulfide bond creates an anchor for the virus. Our analysis suggests that greater cellular oxidation in the elderly or those with underlying health conditions could predispose them to more vigorous infection, replication and disease, says co-author Rajinder Dhindsa, an emeritus professor of biology at McGill University.

In the case of animals resistant to the virus, like pigs and cows, one of these two cysteine amino acids is missing, and the disulfide bond cannot be formed. As a result, the virus cannot anchor on to the cell.

According to the researchers, preventing the anchor from forming could be the key to unlocking new treatments for COVID-19. One strategy, they suggest, could be to disrupt the oxidizing environment that keeps the disulfide bonds intact. Antioxidants could decrease the severity of COVID-19 by interfering with entry of the virus into host cells and its survival afterwards in establishing further infection, says Professor Singh.

In terms of next steps, the researchers say CRISPR technology could be used to edit protein sequences and test out their theory. The researchers are also looking into other proteins near the ACE2 receptor that may facilitate entry of the virus to see if they behave the same way.

Reference: SARS-CoV2 infectivity is potentially modulated by host redox status by Jaswinder Singh, Rajinder S. Dhindsa, Vikram Misra and Baljit Singh, 20 November 2020, Computational and Structural Biotechnology Journal.DOI: 10.1016/j.csbj.2020.11.016

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Scientists Look to Animals and Find Out What May Make Certain People More Vulnerable to COVID-19 - SciTechDaily

Cell Biology

Stunning imagery on display in 2020 ASCB Image and Video Contest – Newswise

Newswise The American Society for Cell Biology (ASCB) hosted its second image and video contest, and we could not be more delighted with all entries that were submitted this year. We received 55 submissions in total, and they represent some of the most stunning cell biology visualizations and imaging techniques you can imagine.

Congratulations to the winners (see below) of the 2020 Cell Bio Image & Video Contest! Click here to see a video of all the winning images and videos.

Entries were judged by members of the ASCB Public Information Committee. Choosing winners was a difficult task. They looked for striking images that feature any aspect of cell biological research, including light and electron micrographs, movies, images of gels or other assays, data visualization, and computer simulations. Submissions were either still images or short (up to 15 seconds) videos. Click to see a gallery of all the submissions here.

Image Winners

1st place (tie) Aidan Fenix, University of Washington: Through the Worm Hole

1st place (tie) James Hayes and Dylan Burnette, Vanderbilt University: The Incredible Hulk of Cells: The Cardiac Myocyte

1st place (tie) Nilay Taneja, Vanderbilt University: Human Cardiac Myocyte

2nd place Dylan Burnette, Vanderbilt University: Actin Filaments, Mitochondria, and Golgi Apparatus

3rd place James Hayes and Dylan Burnette, Vanderbilt University: Natures Disco Ball

Video Winners

1st place Andrew Moore, Howard Hughes Medical Institute: Actin Dynamics in an Interphase HeLa Cell

2nd place Grace Hsu and Janet Iwasa, University of Utah: TRIM5 Forming a Lattice around HIV Capsid

3rd place Dylan Burnette, Vanderbilt University: Actin Filaments in a Mouse Embryonic Fibroblast Z Series

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Stunning imagery on display in 2020 ASCB Image and Video Contest - Newswise

Cell Biology

Planet of the Apes redux? Human brain gene inserted into monkey fetuses enlarged their brains, raising ethical concerns – Genetic Literacy Project

Researchers from Germanys Max Planck Institute of Molecular Cell Biology and Genetics in Germany and Japans Central Institute for Experimental Animals introduced a specifically human gene,ARHGAP11B, into the fetus of a common marmoset monkey, causing the enlargement of its brains neocortex. The scientistsreported their findings in Science.

The neocortex is the newest part of the brain to evolve. Its in the nameneo meaning new, and cortex meaning, well, the bark of a tree. This outer shell makes up more than 75 percent of the human brain and is responsible for many of the perks and quirks that make us uniquely human, including reasoning and complex language.

The scientists call these human-monkey hybrids transgenic non-human primates, which may be enough to ring the alarm of any doomsdayer. It certainly raises a lot of ethical questions when doing experiments on primates, let alone when introducing human genes into other animals.

For this reason, the researchers limited their study to monkey fetuses, which were taken out by C-section after growing for 100 days. Allowing the experiment to go past the fetal phase and let the human gene-carrying monkeys to be born would beirresponsible and unethical, study coauthor Wieland Huttner said in the press release.

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Planet of the Apes redux? Human brain gene inserted into monkey fetuses enlarged their brains, raising ethical concerns - Genetic Literacy Project

Cell Biology

Georgia Tech faculty member: I didnt think I connected with my students online. They disagreed. – Atlanta Journal Constitution

My students love not knowing me

The view from my virtual classroom is bleak. My desk -- a table salvaged from the basement -- sits in an unused corner of a spare bedroom that looks out over a radiator, a pull-out sofa, and the cats litter box. The curated science-themed bookshelf is behind me, a faade of normalcy. It is from here that I recorded dozens of videos for my cell biology course last semester. I spent my days alone with intracellular signaling pathways, motor proteins, and the cytoskeleton. I spoke to no one but my webcam. Each Sunday I sent the videos into the void and hoped some of the 60 students enrolled in my class would watch them.

Were my students even there?

Before the first exam, I held an online review session. One student showed up, connecting from the lodge at Yellowstone where she was vacationing with her family. She didnt have any questions, but it was raining outside so she decided to log in and meet me. We spoke for about 10 minutes, and she told me she didnt know anyone else in the class. I held other online office hours that no one attended. I held a review session for the final exam, and three people logged on. Within two weeks of the end of the semester, I forgot the names of everyone in the class.

Georgia Tech professor Jennifer Leavey

Credit: Christopher Moore

Credit: Christopher Moore

For me, this unexpectedly online course was a disappointment. This course was supposed to be taught at a study abroad program in Lyon, France, where I have been part of the faculty for five years. Most years, the class is small. We have seminar-style discussions. We take field trips to local tech companies so students have a sense of what research looks like in an industrial setting. I invite groups of students to my rented apartment where we get to know each other over home cooked meals I create with ingredients from the daily fresh market down the street.

We have conversations about the students hopes and dreams, and I help connect them with research advisors who share their interests. On occasion, I write them letters of recommendation for things like medical school or the Fulbright scholars program.

This semester, I didnt get to know anyone.

When my end-of-semester anonymous course evaluations arrived, I clicked the link with dread. Surely this semester would leave a stain, much like the rest of 2020. But as I started to read, it became clear that my students perception of our relationship was very different than my own. One student said, Dr. Leavey was always incredibly helpful when I ran into any issues I really appreciated her concern for us and our well-being! Another said, She respected her students and was very available for help.

Yet another said, She was very accessible and willing to go above and beyond to help students. She was very caring and considerate, especially as these are difficult and uncertain times for us all. How could this be? Somehow, I must have been conveying compassiondigitally.

I looked through my weekly class announcements for signs that I cared. Some of my notes reflected my own fears, like if you are in Georgia be safe out there. COVID-19 is worse now than it ever has been and Please stay safe and protect others by staying socially distant and wearing a mask. Other messages suggested I was available and accessible, and perhaps even desperate to connect: feel free to email me or any the TAs any time and Let me know if you would like to get together and discuss the course (or anything).

While I wasnt hearing from very many students in any given week, they must have been hearing me loud and clear.

Is it possible that remote learning can feel even more personal for the student than in-person instruction does? In a normal semester, I would be at the front of the room. Depending on where my students sit, they may not be able to see or hear me very well. But my remote class was somehow intimate. I was arriving in my students inbox every day. My face was on a screen in their lap. My voice was in their earbuds. The unused corner of my spare bedroom was in their house, no matter where they were in the world. And maybe my students knew me better than they ever have before. If only I knew them.

About the Author

Maureen Downey has written editorials and opinion pieces about local, state and federal education policy since the 1990s.

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Georgia Tech faculty member: I didnt think I connected with my students online. They disagreed. - Atlanta Journal Constitution

Cell Biology

Differential Effects of Fingolimod and Natalizumab on B Cell Repertoires in Multiple Sclerosis Patients – DocWire News

This article was originally published here

Neurotherapeutics. 2020 Nov 30. doi: 10.1007/s13311-020-00975-7. Online ahead of print.

ABSTRACT

Natalizumab and fingolimod are effective multiple sclerosis (MS) therapies that disrupt lymphocyte migration but have differential effects on B cell maturation and trafficking. We investigated their effects on peripheral blood (PB) and cerebrospinal fluid (CSF) B cell repertoires using next-generation deep sequencing. Paired CSF and PB B cell subsets (nave, CD27+ memory, and CD27IgD double-negative B cells and plasmablasts) were collected by applying flow cytometry at baseline and after 6 months of treatment and their respective heavy-chain variable region repertoires assessed by Illumina MiSeq. Treatment with fingolimod contracted, whereas natalizumab expanded circulating PB B cells. CSF B cell numbers remained stable following fingolimod treatment but decreased with natalizumab therapy. Clonal overlap between CSF and PB B cells was reduced with natalizumab treatment but remained stable with fingolimod therapy. Lineage analyses of pre- and posttreatment CSF B cell repertoires revealed large, clonally expanded B cell clusters in natalizumab-treated MS patients but no intrathecal clonal expansion following fingolimod therapy. Our findings suggest that natalizumab diminishes the exchange of peripheral and intrathecal B cells without impacting intrathecal clonal expansion. In contrast, fingolimod treatment fails to alter blood-brain barrier B cell exchange but diminishes intrathecal clonal expansion. Sphingosine-1 phosphate receptor inhibition may alter intrathecal B cell biology in MS.

PMID:33258072 | DOI:10.1007/s13311-020-00975-7

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Differential Effects of Fingolimod and Natalizumab on B Cell Repertoires in Multiple Sclerosis Patients - DocWire News