Category Archives: Cell Biology

Cell Biology

Researchers determine the atomic structure of protein that helps coronavirus to evade immune cells – News-Medical.net

A team of HIV researchers, cellular biologists, and biophysicists who banded together to support COVID-19 science determined the atomic structure of a coronavirus protein thought to help the pathogen evade and dampen response from human immune cells.

The structural map - which is now published in the journal PNAS, but has been open-access for the scientific community since August - has laid the groundwork for new antiviral treatments tailored specifically to SARS-CoV-2, and enabled further investigations into how the newly emerged virus ravages the human body.

Using X-ray crystallography, we built an atomic model of ORF8, and it highlighted two unique regions: one that is only present in SARS-CoV-2 and its immediate bat ancestor, and one that is absent from any other coronavirus. These regions stabilize the protein - which is a secreted protein, not bound to the membrane like the virus's characteristic spike proteins - and create new intermolecular interfaces. We, and others in the research community, believe these interfaces are involved in reactions that somehow make SARS-CoV-2 more pathogenic than the strains it evolved from."

James Hurley, Lead Author, Professor, UC Berkeley, Former Faculty Scientist, Lawrence Berkeley National Laboratory (Berkeley Lab)

Generating protein structure maps is always labor intensive, as scientists have to engineer bacteria that can pump out large quantities of the molecule, manipulate the molecules into a pure crystalline form, and then take many, many X-ray diffraction images of the crystals. These images - produced as X-ray beams bounce off atoms in the crystals and pass through gaps in the lattice, generating a pattern of spots - are combined and analyzed via special software to determine the location of every individual atom. This painstaking process can take years, depending on the complexity of the protein.

For many proteins, the process of building a map is helped along by comparing the unsolved molecule's structure to other proteins with similar amino acid sequences that have already been mapped, allowing scientists to make informed guesses about how the protein folds into its 3D shape.

But for ORF8, the team had to start from scratch. ORF8's amino acid sequence is so unlike any other protein that scientists had no reference for its overall shape, and it is the 3D shape of a protein that determines its function.

Hurley and his UC Berkeley colleagues, experienced in structural analysis of HIV proteins, worked with Marc Allaire, a biophysicist and crystallography expert at the Berkeley Center for Structural Biology, located at Berkeley Lab's Advanced Light Source (ALS). Together, the team worked in overdrive for six months - Hurley's lab generated crystal samples and passed them to Allaire, who would use the ALS's X-ray beamlines to take the diffraction images. It took hundreds of crystals with multiple versions of the protein and thousands of diffraction images analyzed by special computer algorithms to puzzle together ORF8's structure.

"Coronaviruses mutate differently than viruses like influenza or HIV, which quickly accumulate many little changes through a process called hypermutation. In coronaviruses, big chunks of nucleic acids sometimes move around through recombination," explained Hurley. When this happens, big, new regions of proteins can appear.

Genetic analyses conducted very early in the SARS-CoV-2 pandemic revealed that this new strain had evolved from a coronavirus that infects bats, and that a significant recombination mutation had occurred in the area of the genome that codes for a protein, called ORF7, found in many coronaviruses. The new form of ORF7, named ORF8, quickly gained the attention of virologists and epidemiologists because significant genetic divergence events like the one seen for ORF8 are often the cause of a new strain's virulence.

"Basically, this mutation caused the protein to double in size, and the stuff that doubled was not related to any known fold," added Hurley. "There's a core of about half of it that's related to a known fold type in a solved structure from earlier coronaviruses, but the other half was completely new."

Like so many scientists working on COVID-19 research, Hurley and his colleagues opted to share their findings before the data could be published in a peer-reviewed journal, allowing others to begin impactful follow-up studies months earlier than the traditional publication process would have allowed. As Allaire explained, the all-hands-on-deck crisis caused by the pandemic shifted everyone in the research community into a pragmatic mindset. Rather than worrying about who accomplished something first, or sticking to the confines of their specific areas of study, scientists shared data early and often, and took on new projects when they had the resources and expertise needed.

In this case, Hurley's UC Berkeley co-authors had the viral protein and crystallography expertise, and Allaire, a longtime collaborator, was right up the hill, also with crystallography expertise and, critically, a beamline that was still operational. The ALS had received special funding from the CARES Act to remain operational for COVID-19 investigations. The team knew from reviewing the SARS-CoV-2 genomic analysis posted in January that ORF8 was an important piece of the (then much hazier) pandemic puzzle, so they set to work.

The authors have since all moved on to other projects, satisfied that they laid the groundwork for other groups to study ORF8 in more detail. (Currently, there are several investigations underway focused on how ORF8 interacts with cell receptors and how it interacts with antibodies, as infected individuals appear to produce antibodies that bind to ORF8 in addition to antibodies specific to the virus's surface proteins.)

"When we started this, other projects had been put on hold, and we had this unique opportunity to hunker down and solve an urgent problem," said Allaire, who is part of Berkeley Lab's Molecular Biophysics and Integrated Bioimaging Division. "We worked very closely, with a lot of back and forth, until we got it right. It really has been one of the best collaborations of my career."

Source:

Journal reference:

Flower, T.G., et al. (2021) Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2021785118.

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Researchers determine the atomic structure of protein that helps coronavirus to evade immune cells - News-Medical.net

Cell Biology

Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases – News-Medical.Net

The abundant presence of an enzyme known as low molecular weight protein tyrosine phosphatase (LMWPTP) in tumor cells has long been considered an indicator of cancer aggressiveness and metastatic potential. It is also known to perform important functions in cells under normal conditions, participating in both the proliferation process and the regulation of intracellular systems. Research continues on its role in cancer progression.

In Brazil, a group of researchers at the University of Campinas's In Vitro Bioassay and Signal Transduction Laboratory led by Professor Carmen Verssima Ferreira-Halder are studying the possibility of inhibiting this protein phosphatase to create novel opportunities for monitoring and treatment of cancer and other diseases.

We believe inhibition of LMWPTP could contribute to the treatment of several diseases. In our case, the focus is on cancer, but research shows it's also associated with autoimmune diseases and diabetes, among others."

Carmen Verssima Ferreira-Halder, Professor, In Vitro Bioassay and Signal Transduction Laboratory, University of Campinas

Ferreira-Halder was principal investigator for the Thematic Project "Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation", supported by FAPESP and completed in June 2020.The phosphatase favors the action of intratumor proteins that help tumors divide, migrate and establish metastasis. "For this reason we say it's a 'hub', in the sense that it controls several processes which together make tumor cells resistant to treatment and able to migrate and establish metastasis," she said.

A review article by the group published in Cellular and Molecular Life Sciences outlines 14 years of research on LMWPTP and its contribution to cancer treatment. "Our group was one of the first to show that this enzyme contributes to chemotherapy resistance in leukemia cells," Ferreira-Halder said. "We also found that the more advanced the stage of the tumor, the larger the amount of the enzyme.

With these discoveries as a basis, research conducted in collaboration with the group led by Professor Maikel Peppelenbosch at Erasmus University Medical Center in Rotterdam [Erasmus MC, Netherlands] validated the significance of LMWPTP to other types of cancer, such as prostate, colorectal and stomach cancer. This research showed us that LMWPTP not only weakens the response to chemotherapy drugs but is also associated with a greater capacity for metastasis."

The review article, whose first author is Alessandra Valria de Sousa Faria, also discusses the available substances that inhibit LMWPTP and the characteristics that make it difficult for drugs to be designed against it. Ferreira-Halder believes it is not yet possible to speak of treatment based on inhibition of LMWPTP, but the strategy can be used for other purposes.

"Our initial aim is to use this enzyme as a biomarker for the purpose of monitoring treatment, and also to use it to classify patients in terms of the severity of disease. In my view this can be done in a relatively short time," she said. "As for treatment, a lot more work remains to be done. Professor Nunzio Bottini at the University of California San Diego [USA] has filed for a patent on a highly effective inhibitor that can be administered orally. Actually he and his group have synthesized several inhibitors, but they have only published one. Maybe we're in for a surprise and a drug will be developed faster. Who knows?"

The main challenges to be faced in developing inhibitors are specificity the drug must act specifically on LMWPTP, which is part of a family of some 100 highly similar phosphatases and stability, so that the drug remains active in the organism. "Until Bottini and his group filed their patent application, all inhibitors acted on several members of the family," Ferreira-Halder said.

Some of the substances mentioned in the review were developed for other purposes but also inhibit LMWPTP and could be used to treat cancer, according to Faria, who recently defended her doctoral thesis on how LMWPTP affects platelets, small cell fragments in the bloodstream that play a key role in clotting.

Faria's research on LMWPTP began with its role in colorectal cancer and platelet reaction in this microenvironment. "As our investigation of platelet biology progressed, we realized how much more knowledge of the enzyme's action on platelets was needed," she said.

The first part of the study consisted of verifying the action of LMWPTP and the protein tyrosine phosphatase 1B (PTP1B) on platelets, with regard to both metabolism and function. The second focused on the influence of platelets on the expression of LMWPTP in cells.

"The goal was to find out to what extent tumor cells may 'educate' platelets to support certain events, such as metastasis, for example, and conversely how far platelets 'educate' tumor cells to assure their survival and proliferation," Faria explained.

For Ferreira-Halder, the relationship appears to be two-way. "However, the action of tumor cells probably predominates. They practically program platelets to work in their favor," she said.

Ferreira-Halder and her group have collaborated with Peppelenbosch's since 2004, but work on the Thematic Project completed in June began only 2016, she recalled, adding that experiments conducted by Emanuella Maria Barreto Fonseca and Cludia de Lourdes Soraggi at Peppelenbosch's laboratory provided a vitally important foundation for the initial hypotheses. Fonseca was supported by a postdoctoral fellowship from FAPESP. Soraggi was able to attend an overseas training course thanks to support from the University of Campinas (UNICAMP) via its Executive Vice Rectorship for International Relations.

"In our Thematic Project research, we were able to investigate the action of this phosphatase from various angles and validate the hypothesis of its role in other tumors besides chronic myeloid leukemia," Ferreira-Halder said. "We wanted to uncover the mechanism of its action, and we now have a great deal of information about this action not just inside but also outside the tumor, because we set out to see if LMWPTP also influenced the tumor's microenvironment external to the cancer cells."

Other research interests for the group during the project included: extracellular vesicles (nanometer-sized structures that play an important role in intercellular communication), with Stefano Piatto Clerici supported by FAPESP showing that LMWPTP regulates these vesicles; platelets, studied by Faria, also with a scholarship from FAPESP; and the TGF-beta signaling pathway, which is involved in many cellular processes such as proliferation and differentiation and was studied by Helon Guimares Cordeiro.

The network of collaborators continued to expand, adding an expert in platelet biology (Sheila Siqueira Andrade at PlateInnove Biotech), and a hematologist and an oncologist at Erasmus MC (Moniek de Maat and Gwenny Fuhler respectively).

According to Ferreira-Halder, the Thematic Project has so far spawned 15 publications (eight articles and two book chapters, as well as five articles under peer review), and several other research fronts. A new project in the same line of research is currently being designed.

Source:

Journal reference:

Faria, A.V. S., et al. (2020) Low molecular weight protein tyrosine phosphatase as signaling hub of cancer hallmarks. Cellular and Molecular Life Sciences. doi.org/10.1007/s00018-020-03657-x.

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Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases - News-Medical.Net

Cell Biology

Aviceda Therapeutics Announces Formation of Executive Team – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Aviceda Therapeutics, a late-stage, pre-clinical biotech company focused on developing the next generation of immuno-modulators by harnessing the power of glycobiology to manipulate the innate immune system and chronic, non-resolving inflammation, is announcing the composition of the Executive Team that will guide the company through ongoing development of breakthrough, first-in-class therapeutics and continued growth opportunities as a business entity.

Serving in key leadership roles on Avicedas Executive Leadership Team will be:

Aviceda is extremely proud of the world-class team of internationally renowned experts we have assembled to guide the company in the next phases of growth. In addition to offering keen scientific insight into product development, each member of the Executive Team also brings with them previous experience in key leadership positions in the pharmaceutical industry. Being able to tap into this knowledge base will undoubtedly pay huge dividends as Aviceda pursues an aggressive but realistic growth and product development strategy, said Dr. Genead, who is a Co-Founder of Aviceda.

A serial life-sciences entrepreneur, senior innovative biopharma executive, inventor, and consultant to many ophthalmic biotechnology companies and healthcare venture firms, Dr. Genead is widely regarded as a global executive and senior leader with 20-plus years experience in pharmaceutical drug and business development with execution from discovery to late development and commercial phases. He has played key roles in executing global approvals and launches and driving sales growth in country, regional and global development positions together with direct reporting teams.

Dr. Genead previously served as Chief Medical Officer and Executive Vice-President for GenSight Biologics where he led the clinical team to multiple phase I-III trials leveraging a disruptive ocular gene therapy and optogenetics platforms in patients with retinal degenerative diseases. Prior to GenSight, Dr. Genead was Biogens Head of Ophthalmology and Retina Gene Therapy. Dr. Genead has also held leadership positions with Allegro Ophthalmics, where he led the global clinical development teams for the Risuteganib (anti-integrin) platform, and Allergan, where he was Global Medical Director and Clinical Team Lead for Retina Therapeutic area. Dr. Genead is a Co-founder of several start-ups, has been instrumental in the raising of over $500M in venture and institutional capital for numerous life sciences biotech companies and is currently a board member of several ophthalmic organizations and scientific advisory boards. Dr. Genead is a board-certified ophthalmologist/retina specialist by training, having completed a vitreoretinal fellowship at the Department of Ophthalmology and Visual Sciences of the University of Illinois in Chicago and Medical College of Wisconsin. He has served as a principal Investigator with a proven record of success in developing and launching global blockbuster therapeutics. He was the primary and key author for numerous peer-reviewed manuscripts in high impact factor scientific journals (more than 100 manuscripts and presentations) focusing on clinical research and novel therapeutics.

Dr. Callanan is a board-certified ophthalmologist, a clinical Professor at the University of Texas Southwestern Medical School in Dallas, Texas and surgeon with Texas Retina Associates, specializing in vitreoretinal diseases including uveitis, diabetic retinopathy and age-related macular degeneration.

Dr. Callanan earned his medical degree at the University of Iowa College of Medicine and completed his ophthalmology residency at Parkland Memorial Hospital, University of Texas Southwestern Medical Center. He received a National Research Service Award from the National Institutes of Health for the study of Ocular Immunology with Dr. Jerry Niederkorn. He was a Heed Ophthalmic Foundation Fellow at the prestigious Bascom Palmer Eye Institute in Miami, Florida. He completed fellowships in medical retina with legendary Dr. J. Donald M. Gass and vitreoretinal surgery with the Bascom Palmer faculty. Dr. Callanan also received additional training in uveitis with Dr. Robert Nussenblatt at the National Eye Institute in Bethesda, over 60 peer reviewed articles and several book chapters, Dr. Callanan is widely regarded as a respected leader in his field. Throughout his career he has actively conducted clinical research and has played an instrumental role in several ophthalmic drug approvals. In addition to his clinical and academic responsibilities, Dr. Callanan also serves on the board of directors of the Retina Foundation of the Southwest and is a member of numerous professional and honorary societies, including the American Academy of Ophthalmology, The Association for Research in Vision and Ophthalmology, The Macula Society, The American Uveitis Society, and the American Society of Retina Specialists, among others.

I am thrilled to join Aviceda at an exciting time for the company and its portfolio of pipeline candidates. Glyco-immune therapeutics offers the prospect of a truly transformational approach to treating a variety of underserved immune mediated inflammatory conditions that do not have adequate therapeutic options. While our immediate focus will be on ophthalmic conditions, there is tremendous potential to improve treatment options for a wide assortment of conditions affecting the innate immune system, said Dr. Callanan.

Dr. Kunimoto, who is a co-Founder of Aviceda, holds a medical degree with honors from Harvard Medical School and a law degree with honors from Oxford University, which he attended on a Rhodes Scholarship. He was a medicine intern at Massachusetts General Hospital and completed his residency at Wills Eye Hospital in Philadelphia, where he served as co-chief resident. Dr. Kunimoto was recognized as a Heed and Michaels Fellow. He worked as a consultant with the management consultancy, McKinsey & Co. Dr. Kunimoto has authored numerous peer-reviewed publications, two major ophthalmology textbooks, and has been invited to speak at ophthalmology conferences, both nationally and internationally. Dr. Kunimoto has been very active in the clinical research of retinal diseases, acting as Investigator or Principal Investigator in over 150 global clinical trials. A recipient of numerous honors for academic and research achievements, Dr. Kunimoto served as Managing Partner of Retinal Consultants of Arizona, where he lead efforts to grow the practice to 35 locations, develop a nutraceutical franchise, and establish an Aviation Department for transportation and patient coverage at outlying satellite offices. He also served as Manager of the Retina Research Institute. Dr. Kunimoto is a founding member and served as Founding President of the Vit-Buckle Society, served as Chair of the Medical Student Governing Council in the Massachusetts Medical Society, and as a member on the Council on Constitution and Bylaws of the American Medical Association. Outside of medicine, Dr. Kunimoto serves on the Board of Directors of the Association of American Rhodes Scholars.

Prior to graduating with a medical degree from the University of Massachusetts, Dr. Tolentino performed research on retinal degeneration at the Schepens Eye Research Institute and the Berman Gund Lab (both at Harvard Medical School), as well as the National Eye Institute. After Medical School, Dr. Tolentino did a post-doctoral angiogenesis research fellowship in the lab of Dr. Judah Folkman, where he helped develop a cancer/xenograft model to screen for angiogenic inhibitors, work that demonstrated the role of Vascular Endothelial Growth Factor (VEGF) in macular degeneration, diabetic retinopathy and vein occlusion. During this time he purified Bevacizumab (Avastin), a drug designed for oncologic applications, and demonstrated intravitreal application could inhibit ocular neovascularization, a discovery that led to the eventual development of anti-VEGF therapeutics for retinal disease. After finishing his Ophthalmology Residency, Dr. Tolentino joined the retina and molecular ophthalmology faculty at the University of Pennsylvania, where he ran a lab funded by the National Institutes of Health working on gene, cell and RNAi therapy. Among his many accomplishments is the invention of a new class of gene silencing molecules called small interfering RNA (siRNA) against anti-angiogenic targets. He has 3 issued patents on the composition and methods of use of these molecules in vertebrate organisms for treating neovascular diseases. The discovery of siRNA and its mechanisms in invertebrate worms resulted in the Nobel prize in Medicine for Craig Mello and Andrew Fire in 2006. Dr. Tolentino co-founded and served as the interim CEO/CSO for Acuity Pharmaceuticals, where he was able to herald the first siRNA therapeutic into human clinical trials. Acuity eventually merged with Exegenic Inc to form OPKO health (NYSE: OPK), a publicly traded biopharmaceutical company. Over the course of his career, Dr. Tolentino has been very active in the clinical research of retinal diseases, acting as principal investigator in over 150 clinical trials that led to multiple global approvals for retinal therapeutics. He has authored over 100 publications and delivered over 200 international lectures. He has served as a consultant/scientific advisor for numerous pharma/biotech companies.

Prof. Scott, Aviceda Scientific Co-Founder, is Director of the Patrick G Johnston Centre for Cancer Research and Cell Biology at Queens University Belfast. He is internationally renowned for his work in development of novel approaches in the field of antibody and nanomedicine-based therapies for the treatment of cancer and other conditions. Prof. Scott has a background in both the pharmaceutical industry and academia and was a founding scientist of Fusion Antibodies Plc. Research in his laboratory is funded by agencies such as Medical Research Council, UK charities and various industrial sources. He also held a Royal Society Industrial Fellowship with GSK from 2012 to 2015 and won the Vice Chancellors Prize for Innovation in 2015 with his groups work on developing a novel Siglec targeting nanomedicine for the treatment of sepsis and other inflammatory conditions.

About Aviceda Therapeutics

Founded in 2018 and based in Cambridge, Massachusetts, Aviceda Therapeutics is a late-stage, pre-clinical biotechnology company with a mission to develop the next generation of glyco-immune therapeutics (GITs) utilizing a proprietary technology platform to modulate the innate immune system and chronic, non-resolving inflammation. Aviceda has assembled a world-class, cross-disciplinary team of recognized scientists, clinicians and drug developers to tackle devastating ocular and systemic degenerative, fibrotic, oncologic and immuno-inflammatory diseases. At Aviceda, we exploit a unique family of receptors expressed on all innate immune cells and their associated glycobiological interactions to develop transformative medicines. Combining the power of our biology with our innovative cell-based high-throughput screening platform and proprietary nanoparticle technology, we can modulate the innate immune response specifically and profoundly. Aviceda is developing a pipeline of GITs that are delivered via biodegradable nanoparticles and which safely and effectively target numerous immune-inflammatory conditions. Avicedas lead ophthalmic optimized nanoparticle, as an intravitreal formulation, AVD-104, is being developed to target various immune system responses that contribute to the pathology associated with age-related macular degeneration (AMD).

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Aviceda Therapeutics Announces Formation of Executive Team - Business Wire

Cell Biology

RNA molecules are masters of their own destiny – MIT News

At any given moment in the human body, in about 30 trillion cells, DNA is being read into molecules of messenger RNA, the intermediary step between DNA and proteins, in a process called transcription.

Scientists have a pretty good idea of how transcription gets started: Proteins called RNA polymerases are recruited to specific regions of the DNA molecules and begin skimming their way down the strand, synthesizing mRNA molecules as they go. But part of this process is less-well understood: How does the cell know when to stop transcribing?

Now, new work from the labs of Richard Young, Whitehead Institute for Biomedical Research member and MIT professor of biology, and Arup K. Chakraborty, professor of chemical engineering, physics, and chemistry at MIT, suggests that RNA molecules themselves are responsible for regulating their formation through a feedback loop. Too few RNA molecules, and the cell initiates transcription to create more. Then, at a certain threshold, too many RNA molecules cause transcription to draw to a halt.

The research, published in Cell on Dec. 16, 2020, represents a collaboration between biologists and physicists, and provides some insight into the potential roles of the thousands of RNAs that are not translated into any proteins, called noncoding RNAs, which are common in mammals and have mystified scientists for decades.

A question of condensates

Previous work in Youngs lab has focused on transcriptional condensates, small cellular droplets that bring together the molecules needed to transcribe DNA to RNA. Scientists in the lab discovered the transcriptional droplets in 2018, noticing that they typically formed when transcription began and dissolved a few seconds or minutes later, when the process was finished.

The researchers wondered if the force that governed the dissolution of the transcriptional condensates could be related to the chemical properties of the RNA they produced specifically, its highly negative charge. If this were the case, it would be the latest example of cellular processes being regulated via a feedback mechanism an elegant, efficient system used in the cell to control biological functions such as red blood cell production and DNA repair.

As an initial test, the researchers used an in vitro experiment to test whether the amount of RNA had an effect on condensate formation. They found that within the range of physiological levels observed in cells, low levels of RNA encouraged droplet formation and high levels of RNA discouraged it.

Thinking outside the biology box

With these results in mind, Young lab postdocs and co-first authors Ozgur Oksuz and Jon Henninger teamed up with physicist and co-first author Krishna Shrinivas, a graduate student in Arup Chakrabortys lab, to investigate what physical forces were at play.

Shrinivas proposed that the team build a computational model to study the physical and chemical interactions between actively transcribed RNA and condensates formed by transcriptional proteins. The goal of the model was not to simply reproduce existing results, but to create a platform with which to test a variety of situations.

The way most people study these kinds of problems is to take mixtures of molecules in a test tube, shake it and see what happens, Shrinivas says. That is as far away from what happens in a cell as one can imagine. Our thought was, Can we try to study this problem in its biological context, which is this out-of-equilibrium, complex process?

Studying the problem from a physics perspective allowed the researchers to take a step back from traditional biology methods. As a biologist, it's difficult to come up with new hypotheses, new approaches to understanding how things work from available data, Henninger says. You can do screens, you can identify new players, new proteins, new RNAs that may be involved in a process, but you're still limited by our classical understanding of how all these things interact. Whereas when talking with a physicist, you're in this theoretical space extending beyond what the data can currently give you. Physicists love to think about how something would behave, given certain parameters.

Once the model was complete, the researchers could ask it questions about situations that may arise in cells for instance, what happens to condensates when RNAs of different lengths are produced at different rates as time ensues? and then follow it up with an experiment at the lab bench. We ended up with a very nice convergence of model and experiment, Henninger says. To me, it's like the model helps distill the simplest features of this type of system, and then you can do more predictive experiments in cells to see if it fits that model.

The charge is in charge

Through a series of modeling and experiments at the lab bench, the researchers were able to confirm their hypothesis that the effect of RNA on transcription is due to RNAs molecules highly negative charge. Furthermore, it was predicted that initial low levels of RNA enhance and subsequent higher levels dissolve condensates formed by transcriptional proteins. Because the charge is carried by the RNAs phosphate backbone, the effective charge of a given RNA molecule is directly proportional to its length.

In order to test this finding in a living cell, the researchers engineered mouse embryonic stem cells to have glowing condensates, then treated them with a chemical to disrupt the elongation phase of transcription. Consistent with the models predictions, the resulting dearth of condensate-dissolving RNA molecules increased the size and lifetime of condensates in the cell. Conversely, when the researchers engineered cells to induce the production of extra RNAs, transcriptional condensates at these sites dissolved. These results highlight the importance of understanding how non-equilibrium feedback mechanisms regulate the functions of the biomolecular condensates present in cells, says Chakraborty.

Confirmation of this feedback mechanism might help answer a longstanding mystery of the mammalian genome: the purpose of non-coding RNAs, which make up a large portion of genetic material. While we know a lot about how proteins work, there are tens of thousands of noncoding RNA species, and we dont know the functions of most of these molecules, says Young. The finding that RNA molecules can regulate transcriptional condensates makes us wonder if many of the noncoding species just function locally to tune gene expression throughout the genome. Then this giant mystery of what all these RNAs do has a potential solution.

The researchers are optimistic that understanding this new role for RNA in the cell could inform therapies for a wide range of diseases. Some diseases are actually caused by increased or decreased expression of a single gene, says Oksuz, a co-first author. We now know that if you modulate the levels of RNA, you have a predictable effect on condensates. So you could hypothetically tune up or down the expression of a disease gene to restore the expression and possibly restore the phenotype that you want, in order to treat a disease.

Young adds that a deeper understanding of RNA behavior could inform therapeutics more generally. In the past 10 years, a variety of drugs have been developed that directly target RNA successfully. RNA is an important target, Young says. Understanding mechanistically how RNA molecules regulate gene expression bridges the gap between gene dysregulation in disease and new therapeutic approaches that target RNA.

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RNA molecules are masters of their own destiny - MIT News

Cell Biology

What are longevity supplements, and are they safe? – MarketWatch

Aches and pains. A growing waistline. Diminishing eyesight, hearing loss, memory lapses. These are the woes of growing older for some people, once considered inevitable. But recent, exciting discoveries in the fast-growing field of longevity science have some doctors and researchers pronouncing that these symptoms of aging may one day be treatable with pharmaceuticals, gene therapies or other yet-to-be-discovered medical technologies.

Many people havent been content to wait, though. Dozens of commercial producers are selling hundreds of so-called longevity supplements right now, and sales data suggest anawful lot of peopleare trying them. But do they work? Are they even safe?

To find out, we scoured the latest research and interviewed two top scientists in the field. What we learned suggests that you may want to hold off on ordering a supply, or at least do your research very carefully.

There is a solid handful of compounds that look very promising in the scientific quest to slow the aging process. One of the most exciting is nicotinamide adenine dinucleotide, or NAD, which has been shown to extend both the lifespans and youthful function of yeast and animals in clinical trials. Human trials are ongoing, with only a handful published to date.

NAD (also often written as NAD+) is a substance found in every cell in your body, which controls all kinds of metabolic processes, including the regulation of sirtuins, the so-called longevity genes. As you age, your NAD+ levels decline, and scientists think it is perhapsthisdecline that leads toall sortsof other age-related declines.

Also read: Should you invest in the new longevity funds?

The working theory, then, is that if we can boost our NAD+ levels as we age, we can slow our decline tremendously. Lab studies on yeast and rodentslend strong supportto that theory. The most recent studies have primarily involved the administration of either nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), which is then converted into NAD in the body.

To learn more about NAD, Next Avenue talked to Dr. Shin-Ichiro Imai, professor of developmental biology at the Washington University School of Medicine in St. Louis. Along with Leonard Guarente, Imai discovered the link between NAD and sirtuin control in 1999. Hes been studying the molecule ever since.

There have been 10 human clinical trials using NR, most at very high dose, with no safety issues, Imai said. Most of those trials, however, lasted for a duration of weeks or months at most.

Is it safe to take NAD-boosting supplements continuously, for years?

NMN and NR have already been available in Japan and the U.S. since 2015, and some people have been taking it since then, Imai noted. Anecdotally, I havent heard of any side effects from the taking of these supplements.

Some trials, however, have recorded mild side effects including headaches, nausea, diarrhea and skin flushing.

See: 3 aging experts tell how they decided on where to grow older

More troubling, however, is the conclusion of a 2019 study that showed a possible link between elevated levels of NAD and tumor growth in isolated cells and animals. Rugang Zhang, deputy director at the nonprofit Wistar Institute Cancer Center in Philadelphia, was the lead researcher on that study.The study, published in the UK journal Nature Cell Biology, did not find that NAD causes cancer, rather that elevated levelsappeared to accelerateoncogenesis (tumor formation) already in motion.

We dont want to oversell the results of our study, Zhang said. Lots of studies in the literature have clearly demonstrated that as normal cells age, there is lower NAD. So, supplementing NAD could be beneficial. Its possible that NAD boosters could help people live longer and healthier. Were not saying that if people take NAD boosters they will get cancer. This was a very early study on mouse models, and more study is needed.

He suggests a course of action grounded in a deep preponderance of evidence: At the end of the day, we just need more knowledge, through more research. We need the scientific community to come to a consensus. The risk to potential benefit remains to be seen.

Mucking up the risk/benefit ratio further is the fact that supplements are onlyvery lightly regulatedby the U.S. Food and Drug Administration, with the testing, evaluation and labeling of such products left up to manufacturers. This presents another dilemma for those considering longevity supplements: theres no sure way of knowing exactly what youre getting.

The results of the few published human clinical trials to date unequivocally show that taking NR boosts levels of NAD in the body. But apparently, more NAD doesnt translate to more youthful function.

See: There are six types of retirees which are you?

Unfortunately, those studies have not yet shown any significant efficacy, Imai said.

And thats when the substance administered is of lab-grade purity. So what about the typical supplements available online?

There are so many products out there, Imai lamented, particularly for NMN, but Im concerned about the quality.

Indeed, a 2020meta-analysisof NAD trials surmised: it seems likely that side effects linked to interventions that target NAD metabolism more likely arise from impurities rather than the supplements themselves, since this industry generally operates without rigorous control of quality and standardization.

Imais lab has evaluated a number of commercially available NAD-boosting supplements, but found only two of lab-grade purity. Imai wouldnt disclose the names of the products (both Japanese-made), as he doesnt endorse supplements. But he did note that they are extremely expensive.

Dont miss: What is the secret to aging well?

Finally, we asked someone whod taken an NAD-booster to share her experience. Kim Oberdorfer, an air-traffic controller in Oakland, Calif., wasnt impressed.

I took [a popular NR supplement] for about two months and it just gave me these dull headaches. I was having hot flashes last February, and when I told my sister Im 47, shes 53 about how horrified I was to be having them so young, she goes, Are you sure its not just a reaction to an NAD supplement? said Oberdorfer. At the time I wasnt really working out much, but my sleep schedule was really messed up and I heard it was good for that as well. I didnt think it helped at all.

Rashelle Brownis a longtime fitness professional and freelance writer with hundreds of bylines in print and online. She is a regular contributor for NextAvenue and the Active Network, and is the author of Reboot Your Body: Unlocking the Genetic Secrets to Permanent Weight Loss (Turner Publishing). Connect with her on Twitter and Instagram @RashelleBrownMN.

This article is reprinted by permission fromNextAvenue.org, 2021 Twin Cities Public Television, Inc. All rights reserved.

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What are longevity supplements, and are they safe? - MarketWatch

Cell Biology

Champions Oncology Announces the Expansion of Lumin Bioinformatics: Now Featuring a Highly Valuable Set of Proteomic Data and Analytics – BioSpace

HACKENSACK, NJ / ACCESSWIRE / January 5, 2021 / Champions Oncology, Inc.. (NASDAQ:CSBR), a leading global oncology technology company that is transforming drug discovery and development through data-driven research strategies, announced today the expansion of its SaaS program, Lumin Bioinformatics. Since its launch, Champions has been adding to the data and functionality housed within Lumin, which now features 20,000+ datasets including rare and valuable quantitative phospho-proteomics. To aid in the analysis of this proteomic data, engineers at Champions have also developed a unique and sophisticated set of analysis tools that enable researchers to unlock the power of this proteomic data.

Importantly, each proteomic dataset contained within Lumin has associated data from the matching tumor, including whole exome sequencing, RNA sequencing, clinical and in vivo drug responses, phenotypic evaluations, clinical annotations of the tumor, and much more. Users of Lumin will have the ability to upload their own proteomic datasets and leverage the various tools available for processing and analysis, as well as to use the large proteomic dataset available in Lumin as a reference. This extremely valuable combination of proteomic data, analytics and visualizations will empower scientists to gain a more accurate depiction of tumor cell biology and will provide unparalleled insights into the mechanisms of cellular transformation and therapeutic resistance.

Ronnie Morris, MD, President and CEO, said "The addition of proteomics to Lumin has been an extremely exciting moment for the scientists at Champions. One of the major advantages of our dataset is the depth to which each tumor is characterized. Adding proteomics to this growing dataset will enable scientists to gain a very deep understanding of what is actually happening at the molecular level of a tumor. We will no longer need to rely on the predicted nature of protein expression or intracellular pathway activity from DNA and RNA sequencing, nor we will need to try and predict the subcellular expression level of proteins. We now have this information directly at our fingertips, and we have unleashed the power of this data through Lumin. We are truly excited at how this will transform cancer research moving forward."

"Our Lumin proteomics initiative is a game changer for cancer biologists across the world", said Michael Ritchie, PhD, MBA, Chief Commercial Officer at Champions Oncology. "Aside from the sheer magnitude of the dataset that we have made available, the tools that have been included for analysis make the use of proteomics possible to a very broad audience. Most biologists do not have the background necessary to perform the proteomic pre-processing nor the ability to build analysis tools needed to leverage this truly valuable data, so it is rarely used. Instead, sequencing of DNA and RNA is performed as a surrogate, even though our protein predictions from this data type is often inaccurate. Now that proteomic analyses are accessible with Lumin, we're excited to see researchers use this powerful data on a regular basis."

About Champions OncologyChampions Oncology is a data-driven research organization that leverages an oncology research center of excellence to develop transformative technology and accelerate oncology research and development. This technology ranges from computational-based discovery platforms, unique oncology software solutions, and innovative and proprietary experimental tools such as in vivo, ex vivo and biomarker platforms. For more information, please visit http://www.ChampionsOncology.com.

Media Contact:Rachel Bunting, MS, MBASr. Director, Head of MarketingMarketing@ChampionsOncology.com

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Champions Oncology Announces the Expansion of Lumin Bioinformatics: Now Featuring a Highly Valuable Set of Proteomic Data and Analytics - BioSpace

Cell Biology

Your nose knows you have COVID before you do. Is a scratch-and-sniff card the best tool for mass testing? – The Colorado Sun

It may be clich, in this time of heightened stress and frenzy, to remind you to stop and smell the roses. But seriously: Stop. And. Smell. The. Roses. You might find out you have COVID-19.

Anosmia, the loss of your sense of smell, is by now a well-known symptom of a coronavirus infection. Studies have estimated its prevalence among people with COVID-19 at as much as 80%, which would make it as common of a symptom as cough or fever among symptomatic patients.

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But unlike those other two symptoms, anosmia also occurs at high rates in people with coronavirus infections that are otherwise asymptomatic. And its also an unusual symptom there arent a lot of other illnesses that cause it. So that makes it more predictive than cough or fever, both of which can be caused by many other kinds of other illnesses.

For all these reasons, two researchers at the University of Colorado and a Yale School of Medicine professor who grew up in Boulder think theyve sniffed out a better way to conduct mass testing for coronavirus infections.

Forget the nose swabs, the temperature guns, the overwhelmed testing labs. What if the solution to conducting a comprehensive surveillance program at places like offices or college campuses was as simple as a stack of 50-cent scratch-and-sniff cards and a phone app?

If youve lost your sense of smell unexpectedly, that should be a signal to make sure the mask is on tight, said Daniel Larremore, a professor at CU who is one of the three researchers.

In a paper posted earlier this month on the preprint server medRxiv, the researchers use a mathematical model to argue that conducting sniff tests three times a week would be as effective in curtailing virus spread as conducting weekly PCR tests. The server has become a common place during the pandemic for scientists to post hot-off-the-workbench studies before they have gone through peer review.

Its not so much that the sniff tests are super-accurate. PCR tests are still considered the gold standard for accuracy in detecting coronavirus infections.

But, when it comes to mass testing, frequency is just as important as accuracy. And PCR tests are cumbersome to administer and analyze. Theyre also costly something that can add up quickly when organizations are trying to conduct testing on a large scale.

Thus, a cheaper and simpler, although less accurate, test that can be conducted more frequently can be just as valuable.

Your lack in accuracy is more than made up in frequency, said Derek Toomre, a professor of cell biology at the Yale School of Medicine who was an author on the study, along with Larremore and CU professor Roy Parker.

And thats how the u-Smell-it test (slogan: Do you smell it?) was born.

The test is part science and part elementary school arts and crafts. It involves a card with five unmarked scratch-and-sniff spots on it as well as a QR code. Test-takers use a smartphone app to scan the QR code. Then they scratch the spots and answer multiple-choice questions in the app about what they smelled mint, vanilla, strawberry or other common scents. Theres also an option to say you smelled nothing.

The whole process takes about 45 seconds, at the end of which the app will tell you if youve passed or failed.

Toomre, who grew up in Boulder and went to CU for undergrad, said a dedicated, blind sniff test for coronavirus has significant advantages over just telling people to mind their nose. The first is that people who are infected often dont realize theyve lost their sense of smell other studies have found around 45% to 50% of people infected with coronavirus report a loss of smell when surveyed, but that number rises to around 80% when people are actually administered a smell test, Larremore said.

And Toomre said its also important for the test to be blind to avoid tricks of the mind. If, for instance, you are used to sticking your nose down into your cup of coffee every morning, your brain might continue smelling that coffee even if your nose cant. So Toomre said, in order for the test to work best, people cant know in advance what they are supposed to be smelling.

Toomre has asked the federal Food and Drug Administration to approve the test, allowing it to be used for coronavirus surveillance testing. Its not meant to be a diagnostic test, Toomre said. People who fail the sniff test should follow up with a PCR test.

But it could be valuable to workplaces or college campuses looking to conduct mass testing programs, and it could also be useful for people to have around the house, especially if they think they might be coming down with other symptoms and want to know if they should go get a PCR test.

This idea, though quirky, is not exclusive to Toomre, Larremore and Parker. Researchers at Penn State University have also explored the idea.

Toomre said hes talking with manufacturers, with the hope of producing hundreds of millions of cards that can be sold for 50 cents or less, assuming it receives federal approval. He said he also plans to donate large numbers of tests to nonprofits.

Its a long way from his pre-pandemic work, which focused on cellular imaging.

I am comfortable being uncomfortable, Toomre said, which I definitely am in this area.

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Your nose knows you have COVID before you do. Is a scratch-and-sniff card the best tool for mass testing? - The Colorado Sun

Cell Biology

Bioniz Announces Positive End of Phase 2 Meeting with the FDA for BNZ-1 for the Treatment of Refractory Cutaneous T-Cell Lymphoma – Yahoo Finance

TipRanks

A new year, a new addition to the stock portfolio what can make more sense than that? The right time to buy, of course, is when stocks are priced at the bottom. Buying low and selling high may be a bit hackneyed, but its true, and truth has staying power.But the markets are up. The NASDAQ rose 43% in 2020, and the S&P 500 showed a gain of 16%. With a market environment like that, finding stocks that are caught in the doldrums is harder than it looks. That's where the Wall Street pros can lend a hand.We used TipRanks' database to pinpoint three stocks that fit a profile: a share price that has dropped over 30% in the last 12 months, but with at least double-digit upside potential, according to analysts. Not to mention each has earned a Moderate or Strong Buy consensus rating.Esperion (ESPR)We will start with Esperion, a company that specializes in therapies for the treatment of elevated low-density lipoprotein cholesterol levels a major factor contributing to heart disease. The companys main product, bempedoic acid, is now available in tablet form under the brand names Nexletol and Nexlizet.In February 2020, both Nexletol and Nexlizet were approved as oral treatments to lower LDL-C. Bempedoic acid remains in clinical trials of its efficacy in risk reduction for cardiovascular disease. The trial, called CLEAR Outcomes, is a large-scale, long-term study, tracking more than 14,000 patients with top-line data expected in the second half of 2022. The study covers 1,400 locations in 32 countries around the world.Esperion shares peaked last February, after the FDA approvals, but since then, the stock has declined. Shares are down 65% since their peak. Along with the drop in share value, the company showed a fall in revenue from Q2 to Q3, with the top line collapsing from $212 million to $3.8 million. Since the Q3 report, Esperion announced pricing on a $250 million offer of senior subordinated notes, at 4%, due in 2025. The offering gives the company a boost in available capital for further work on its development pipeline and its marketing efforts for bempedoic acid.Chad Messer, covering ESPR for Needham, sees the note offering as a net positive for Esperion. We believe this cash position will be sufficient to support Esperion through 2021 and to profitability in 2022... We believe this financing should help put to rest concerns regarding Esperion's balance sheet. Despite a challenging launch for NEXLETOL and NEXLIZET, product growth has continued in 3Q against the backdrop of a contracting LDL-C market. This growth trajectory suggests potential for a rapid acceleration when conditions improve," Messer wrote.To this end, Messer rates ESPR shares a Strong Buy, and his price target, at $158, suggests the stock has room for huge growth this year up to 481% from current levels. (To watch Messers track record, click here)Overall, Esperion has 6 recent reviews on record, with a breakdown of 5 Buys and 1 Hold to give the stock a Strong Buy rating from the analyst consensus. The shares, trading at $27.16, have an average price target of $63.33, implying a one-year upside of 133%. (See ESPR stock analysis on TipRanks)Intercept Pharma (ICPT)Liver disease is a serious health threat, and Intercept Pharma is focused on developing treatments for some of the more dangerous chronic liver conditions, including nonalcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC). Intercept has a research pipeline based on FXR, a regulator of bile acid pathways in the hepatic system.FXRs action affects not just the bile acid metabolism, but also the glucose and lipid metabolisms, and inflammation and fibrosis around the liver. The lead compound, obeticholic acid (OCA), is an analog of the bile acid CDCA, and as such can take a role in the FXR pathways and receptors implicated in chronic liver disease. Treating liver disease through the FXR biology has direct applications for PBC, and is showing promise treating complications from NASH.ICPT shares dropped sharply last summer, when the FDA rejected the companys application to approve OCA for treatment of NASH-related liver fibrosis. This delays the drugs potential entry to a lucrative market; there is no current treatment for NASH, and the first drug to win approval will have the lead in reaching a market estimated at $2 billion to $5 billion in potential annual sales. The effect on the stock is still felt, and ICPT remains at its 52-week low point.In reaction, in December of 2020, Intercept announced major changes in top-level management, as CEO and President Mark Pruzanski announced he's stepping down effective January 1 of this year. He is succeeded by Jerome Durso, formerly the companys COO, who will also take a post on the Board of Directors. Pruzanski will remain as an advisor, and will hold a directors position on the companys Board.Piper Sandler analyst Yasmeen Rahimi takes a deep dive into Intercepts continuing efforts to expand applications of OCA and to resubmits its New Drug Application to the FDA. She sees the leadership transition as part of these efforts, and writes, [We] believe that Dr. Pruzanski's dedication to transform the liver space is still strong, and that he will continue to guide ICPT's progress as an advisor and Board member. Additionally, we have had the pleasure of working closely with Jerry Durso and believe that he will transform the company and lead ICPT's success in growing the PBC market and the path to potential approval and commercial launch of OCA in NASH.Rahimi takes a long-term bullish stance on ICPT, giving the stock an Overweight (i.e. Buy) rating and an $82 price target. This figure indicates an impressive 220% upside for the next 12 months. (To watch Rahimis track record, click here)Wall Street is somewhat more divided on the drug maker. ICPT's Moderate Buy consensus rating is based on 17 reviews, including 8 Buys and 9 Holds. Shares are priced at $25.82, and the average price target of $59.19 suggests an upside potential of 132% for the next 12 months. (See ICPT stock analysis on TipRanks)Gilead Sciences (GILD)Gilead has had a year like a firework fast up and fast down. The gains came in 1H20, when it appeared that the companys antiviral drug remdesivir would become a prime treatment for COVID-19. By November, however, even though remdesivir had been approved, the World Health Organization (WHO) was recommending against its use, and the COVID vaccines now on the market have made remdesivir irrelevant to the pandemic.This was only one of Gileads recent headwinds. The company has been working, in conjunction with Galapagos (GLPG), on development of filgotinib as a treatment for rheumatoid arthritis. While the drug received EU and Japanese approval in September 2020, the FDA has withheld approval and Gilead announced in December that it was suspending US development efforts on the drug.Even so, Gilead retains a diverse and active research pipeline, with over 70 research candidates at varying stages of the development and approval process for a wide range of diseases and conditions, including HIV/AIDS, inflammatory & respiratory diseases, cardiovascular disease, and hematology/oncology.On a positive note, Gilead posted Q3 earnings above estimates, with the top line revenue, of $6.58 billion, beating the forecast by 6% and growing 17% year-over-year. The company updated its full-year 2020 guidance on product sales from $23 billion to $23.5 billion.Among the bulls is Oppenheimer analyst Hartaj Singh, who gives GILD shares an Outperform (i.e. Buy) rating and $100 price target. Investors stand to pocket a 69% gain should the analysts thesis play out. (To watch Singhs track record, click here)Backing his stance, Singh writes, We continue to believe in our thesis of (1) a dependable remdesivir/other medicines business against SARS-CoV flares, (2) a base business (HIV/oncology/HCV) growing low-single digits over the next couple of years, (3) operating leverage providing greater earnings growth, and (4) a 3-4% dividend yield. What does the rest of the Street think? Looking at the consensus breakdown, opinions from other analysts are more spread out. 10 Buys, 12 Holds and 1 Sell add up to a Moderate Buy consensus. In addition, the $73.94 average price target indicates 25% upside potential from current levels. (See GILD stock analysis on TipRanks)To find good ideas for beaten-down stocks trading at attractive valuations, visit TipRanks Best Stocks to Buy, a newly launched tool that unites all of TipRanks equity insights.Disclaimer: The opinions expressed in this article are solely those of the featured analysts. The content is intended to be used for informational purposes only. It is very important to do your own analysis before making any investment.

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Bioniz Announces Positive End of Phase 2 Meeting with the FDA for BNZ-1 for the Treatment of Refractory Cutaneous T-Cell Lymphoma - Yahoo Finance

Cell Biology

Research Roundup: Different Antibody Responses to COVID-19 and More – BioSpace

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Antibodies Respond Differently to Severe Versus Mild COVID-19

Researchers at Stanford Medicine found that COVID-19 antibodies preferentially target different parts of the SARS-CoV-2 virus in mild COVID-19 cases than they do in severe cases. In addition, they fade differently based on the severity of the case. People with severe COVID-19 have low proportions of antibodies that target the spike protein. In milder cases, the antibodies seem to do a better job of binding to the spike protein. The spike protein binds to the ACE2 receptor on human cells, which allows the virus to enter the cell. Once inside, the virus gets rid of its outer coat, takes over the cells protein-making machinery and churns out more viral particles that then infect other cells. Antibodies that bind to the spike protein block the ability to bind to ACE2. Antibodies that bind to other parts of the virus dont seem to prevent viral spread.

Antibody responses are not likely to be the sole determinant of someones outcome, said Scott Boyd, associate professor of pathology at Stanford. Among people with severe disease, some die and some recover. Some of these patients mount a vigorous immune response, and others have a more moderate response. So, there are a lot of other things going on. There are also other branches of the immune system involved. Its important to note that our results identify correlations but dont prove causation.

Understanding Brain Plasticity in Adults

When brains develop, they constantly grow new neuronal connectionssynapsesas they learn and remember. Important connects are nurtured and reinforced while seemingly unnecessary ones are pruned. Adult brains undergo similar treatment, but its not well understood why adult synapses are eliminated. A group of researchers at The Korean Advanced Institute of Science and Technology (KAIST) have found the underlying mechanism of plasticity, which could be related to neurological disorders in adult brains. The brains gray matter contains microglia and astrocytes. Microglia are a frontline immune defensethey eat pathogens and dead cells. Astrocytes are star-shaped cells that help structure the brain and maintain homeostasis with involvement in neuronal signaling. It was long thought that microglial eat synapses as part of their clean-up effort, a process called phagocytosis. But their research, using a new molecular sensor, found that it was actually the astrocytes that are constantly eliminating excessive and unnecessary adult excitatory synaptic connections.

New Class of Antibiotic Works Against Range of Bacteria

Investigators withThe Wistar Institute have identified a new class of antibiotics that have a broad range of antibacterial effects, including against microbes with antimicrobial resistance (AMR). They focused on a metabolic pathway essential for bacteria but absent in humans, called methyl-D-erythritol phosphate (MEP) or non-mevalonate pathway, which is responsible for biosynthesis of isoprenoids. Isoprenoids are required for cell survival in most pathogenic bacteria. The researchers targeted the IspH enzyme, essential in isoprenoid biosynthesis. They screened several million commercially available compounds using computer models to find ones that could bind with the enzyme and chose the most potent ones. Most IspH inhibitors cant penetrate the bacterial cell wall, so the researchers worked to identify and synthesize novel IspH inhibitors that could get inside the bacteria.

Rhesus Macaque Genome Reference Includes 85 Million Genetic Variants

Researchers at Baylor College of Medicine, the University of Missouri and the University of Washington created a new reference genome assembly, identifying more than 85 million genetic variants in the rhesus macaque. This makes it the largest database of genetic variation for any single nonhuman primate species. It is a big improvement over the first reference assembled in 2007, and they believe it can help analyze and answer fundamental questions in molecular genetics, cell biology and physiology, not just in rhesus macaques, but in humans and other primates and mammals.

This is a major step forward in the amount of information we have about genetic variation in the rhesus macaque, said Jeffrey Rogers, associate professor at the Human Genome Sequencing Center and Department of Molecular and Human Genetics at Baylor. We have actually identified thousands of new mutations in the population of research animals. Now colleagues all over the country who are investigating various aspects of health and disease using rhesus macaques can begin to make use of that information.

Common Diabetes Drug Linked to Rare COVID-19 Complications

Although diabetes is a known risk factor for COVID-19, researchers with Brigham and Women's Hospital have identified a rare COVID-19 complication with common diabetes drugs. The side effect is called euDKA, or euglycemic diabetic ketoacidosis. DKA occurs when the bodys cells do not absorb enough glucose and begin metabolizing fats instead, which results in a build-up of ketones. EuDKA is marked by lower blood sugar levels, making it harder to diagnose. The researchers evaluated five unusual euDKA cases that was a significantly higher level of incidence, all seen in COVID-19 patients taking sodium-glucose cotransporter 2 inhibitors (SLGLT2i). They believe that COVID-19 may increase the risk of euDKA by binding to cells on the pancreas that produce insulin. The three SGLT2 inhibitors approved by the FDA are Janssens Invokana (canagliflozin), AstraZenecas Farxiga (dapagliflozin) and Eli Lilly and Boehringer Ingelheims Jardiance (empagliflozin).

Whats Going on in the International Space Station?

The Expedition 64 crew took the day off for Christmas, but immediately afterwards went back to work on a variety of biological and medical research. Two studies evaluated new treatments for joint injuries and cancerone looked at bone, cartilage and synovium in artificial gravity chambers to better understand bone loss and joint damage; the second studied protein crystals grown in space and their ability to target cancer cells. A different study on several dozen mice evaluated the vascular changes in space on eyesight functionabout 40% of people working in space have vision changes from fluid shifts and radiation. Another experiment studied genetic changes in space and their impact on the growth and deterioration of bone tissue.

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Research Roundup: Different Antibody Responses to COVID-19 and More - BioSpace

Cell Biology

Global Cell And Tissue Analysis Products Market Growth Graph To Demonstrate Inclination Towards Positive Axis By 2026 – The Courier

The primary aim of the globalCell And Tissue Analysis Products Marketresearch report is to evaluate, describe, and forecast the Cell And Tissue Analysis Products market globally based on the various factors like organization size, region, service, application, segments, deployment mode, and verticals. The global Cell And Tissue Analysis Products market research report distinctly evaluates every segment {Cell & Tissue Characterization Products, Bio specimens, Cell Separation Products}; {Drug Discovery and Development, Stem Cell Research, Cell Biology, Other Research Practices} influencing the growth factors, restraining factors for the growth, contribution to the total Cell And Tissue Analysis Products market and the future developments.

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Cell And Tissue Analysis Products Market COVID-19 Impact Analysis

The outbreak of COVID-19 was sudden and was not at all considered so dangerous when it first struck at Wuhan city of China. Although, everything in that city was closed but the coronavirus infection had wide spread in China as a wild fire. Within months it spread to the neighboring countries and then to every single country in the world. The World Health Organization announced it as a pandemic and till then it had created huge losses in several countries.

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The global Cell And Tissue Analysis Products market research report gives a comprehensive data and analysis about the worldwide market. The report further gives the data that one could rely on; which comes with in-depth analysis of Cell And Tissue Analysis Products market. Different factors like in-depth description of Cell And Tissue Analysis Products market, growth factors, segmentation, regional analysis, sales, supply, demand, manufacture analysis, recent trends, and competing companies are included in the Cell And Tissue Analysis Products report. The exquisite data provided in global Cell And Tissue Analysis Products market research report is explanatory in terms of quantity as well as quality.

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All the major players Danaher, Luminex, EMD Millipore Corporation, PARTEC, GE Healthcare, Thermo Fisher Scientific, BD, Mindray, PerkinElmer, Miltenyi Biotec leading in the Cell And Tissue Analysis Products market are mentioned in the report along with their regions-wise dominance.

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Global Cell And Tissue Analysis Products Market Growth Graph To Demonstrate Inclination Towards Positive Axis By 2026 - The Courier