Embryology

Tauranga man walks to Wellington with pink casket – The Bay’s News First – SunLive

Tauranga man Peter van Zweeden is setting out on foot for Wellington today, with a little pink casket strapped to his back.

He wants to raise awareness of a health bill passed prior to lockdown in March.

Peter is calling for the Abortion Legislation Act to be altered to reflect the fact that all New Zealanders, born or yet to be, should treated with respect and valued.

The Abortion Legislation Bill passed its third reading in Parliament in March, meaning the procedure was removed from the Crimes Act.

It passed 68 votes to 51 - a much narrower margin than at the second reading.

At the time, Justice Minister Andrew Little says for more than 40 years, abortion had been the only medical procedure considered a crime in New Zealand. Read more here.

Peter, who owns a local health-care clinic, left from the Mount Surf Club at 8am flanked by several supporters also walking the first leg.

While the idea of walking 525km carrying a tiny coffin is admittedly strange, the 58-year-old is just a regular guy: he employs four people, coaches his youngest sons football team, and, along with his wife, provides respite foster-care at their Welcome Bay home.

A chiropractor with a science degree in genetics and embryology, he says most people were understandably focused on preparing for lockdown when the bill came before Parliament - and believes it passed largely unnoticed.

People are shocked when they realise theres no legal requirement to make sure a foetus does not feel pain during a termination and that if a baby is inadvertently born alive after an attempted abortion procedure, it can be left to die.

MPs voted down amendments to the bill which would have fixed both those issues.

Peter emphasises he is not advocating that women should be criminalised for abortion.

Women who choose to terminate a pregnancy generally do so after a lot of thought and with much angst.

Often they see it as their only valid choice. As a society, we need to offer them much more support, both before and after abortion, along with information on all their options.

I am calling for the law to be altered to reflect the fact that all New Zealanders, born or yet to be, should treated with respect and valued and for politicians seeking election to listen to what people think about the legislation as it stands currently. We can do so much better.

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Tauranga man walks to Wellington with pink casket - The Bay's News First - SunLive

Cell Biology

Propofol Affects Non-Small-Cell Lung Cancer Cell Biology By Regulating the miR-21/PTEN/AKT Pathway In Vitro and In Vivo – DocWire News

Anesth Analg. 2020 Oct;131(4):1270-1280. doi: 10.1213/ANE.0000000000004778.

ABSTRACT

BACKGROUND: Propofol is a common sedative-hypnotic drug traditionally used for inducing and maintaining general anesthesia. Recent studies have drawn attention to the nonanesthetic effects of propofol, but the potential mechanism by which propofol suppresses non-small-cell lung cancer (NSCLC) progression has not been fully elucidated.

METHODS: For the in vitro experiments, we used propofol (0, 2, 5, and 10 g/mL) to treat A549 cells for 1, 4, and 12 hours and Cell Counting Kit-8 (CCK-8) to detect proliferation. Apoptosis was measured with flow cytometry. We also transfected A549 cells with an microribonucleic acid-21 (miR-21) mimic or negative control ribonucleic acid (RNA) duplex and phosphatase and tensin homolog, deleted on chromosome 10 (PTEN) small interfering ribonucleic acid (siRNA) or negative control. PTEN, phosphorylated protein kinase B (pAKT), and protein kinase B (AKT) expression were detected using Western blotting, whereas miR-21 expression was examined by real-time polymerase chain reaction (RT-PCR). In vivo, nude mice were given injections of A549 cells to grow xenograft tumors; 8 days later, the mice were intraperitoneally injected with propofol (35 mg/kg) or soybean oil. Tumors were then collected from mice and analyzed by immunohistochemistry and Western blotting.

RESULTS: Propofol inhibited growth (1 hour, P = .001; 4 hours, P .0001; 12 hours, P = .0004) and miR-21 expression (P .0001) and induced apoptosis (1 hour, P = .0022; 4 hours, P = .0005; 12 hours, P .0001) in A549 cells in a time and concentration-dependent manner. MiR-21 mimic and PTEN siRNA transfection antagonized the suppressive effects of propofol on A549 cells by decreasing PTEN protein expression (mean differences [MD] [95% confidence interval {CI}], -0.51 [-0.86 to 0.16], P = .0058; MD [95% CI], 0.81 [0.07-1.55], P = .0349, respectively), resulting in an increase in pAKT levels (MD [95% CI] = -0.82 [-1.46 to -0.18], P = .0133) following propofol exposure. In vivo, propofol treatment reduced NSCLC tumor growth (MD [95% CI] = -109.47 [-167.03 to -51.91], P .0001) and promoted apoptosis (MD [95% CI] = 38.53 [11.69-65.36], P = .0093).

CONCLUSIONS: Our study indicated that propofol inhibited A549 cell growth, accelerated apoptosis via the miR-21/PTEN/AKT pathway in vitro, suppressed NSCLC tumor cell growth, and promoted apoptosis in vivo. Our findings provide new implications for propofol in cancer therapy and indicate that propofol is extremely advantageous in surgical treatment.

PMID:32925348 | DOI:10.1213/ANE.0000000000004778

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Propofol Affects Non-Small-Cell Lung Cancer Cell Biology By Regulating the miR-21/PTEN/AKT Pathway In Vitro and In Vivo - DocWire News

Cell Biology

Beyond the bench: how inclusion and exclusion make us the scientists we are – DocWire News

This article was originally published here

Mol Biol Cell. 2020 Sep 15;31(20):2164-2167. doi: 10.1091/mbc.E20-06-0374.

ABSTRACT

Recent events encompassing social injustices, healthcare disparities, and police brutality against Black citizens highlight the continued need to strive toward unbiased and inclusive practices in all realms of the world. Our voices as cell biologists are powerful tools that can be used to combat inequities in the scientific landscape. In this inaugural Voices essay, we discuss how exclusion and inclusion events have contributed to our scientific journeys and how scientists can work to create an inclusive environment for our trainees and colleagues. As underrepresented minority scientists in the early and late stages of our scientific training, we frame the trainee experience to provide insight from unique perspectives. This essay also provides actionable items that the cell biology community can implement to promote inclusivity. We anticipate that initiating an open dialogue focused on diversity and inclusion will promote growth in the field of cell biology and enable scientists to assess and assume their role in creating welcoming environments. We believe that scientists at all stages in their careers can make meaningful and habitual contributions to supporting inclusivity in cell biology, thereby creating a future where diversity, equity, and inclusion are expected, not requested.

PMID:32924843 | DOI:10.1091/mbc.E20-06-0374

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Beyond the bench: how inclusion and exclusion make us the scientists we are - DocWire News

Cell Biology

The art of science: Olympus launches second global image of the year award – News-Medical.net

Sep 16 2020

Following the success of the first Global Image of the Year Life Science Light Microscopy Award, Olympus has launched its second annual Global Image of the Year Award to recognize the best in life science imaging. Those interested in participating can enter through Jan. 10, 2021 by uploading up to three images, with a description of the equipment used, at Olympus-LifeScience.com/IOTY. Winners will be selected by a jury panel and announced in March 2021.

Prizes include an Olympus SZX7 stereo microscope with a DP27 digital camera for the global winner and an Olympus CX23 upright microscope for the regional winners in Asia, Europe and the Americas.

The jury consists of global representatives from both science and the arts, including Wendy Salmon, a light microscopy specialist at Whitehead Institute for Biomedical Research at MIT; Geoff Williams, the manager of the Leduc BioImaging Facility at Brown University; Harini Sreenivasappa, the microscopy facility manager of the Cell Imaging Center at Drexel University; Safa Shehab, a professor at United Arab Emirates University; Sin Culley, a postdoctoral research associate at the MRC Laboratory for Molecular Cell Biology at UCL; Stefan Terjung, the operational manager of the Advanced Light Microscopy Facility at EMBL Heidelberg; Xiang Yu, a professor in the School of Life Sciences at Peking University and investigator of the Peking-Tsinghua Center for Life Sciences and the McGovern Institute for Brain Research; Graham Wright, the chief technology officer at A*STARs Research Support Centre; and Ikuko Koyama-Honda, the project lecturer of the Graduate School and Faculty of Medicine, the University of Tokyo.

All entries will be evaluated based on artistic and visual aspects, scientific impact and microscope proficiency.

Olympus IOTY Award began in 2017 as the Image of the Year European Life Science Light Microscopy Award with the aim to celebrate both the artistic and scientific value of microscopy images. Today, the competition stays true to this mission by encouraging people across the world to look at scientific images in a new way, appreciate their beauty and share images with others.

More information about the Global Image of the Year Life Science Light Microscopy Award, including jury members biographies, last years winning images and the full terms and conditions, can be found at Olympus-LifeScience.com/IOTY.

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The art of science: Olympus launches second global image of the year award - News-Medical.net

Cell Biology

A cell culture master class: What your cells wish they could tell you – Science Magazine

Cell culturethe controlled growing of cells outside their natural environmentmay be commonplace in molecular biology laboratories, but one thing that strikes fear in both novices and experts using these techniques is contamination. Whether it occurs via chemicals (impurities in media, sera, and water) or biological components (bacteria, viruses, and mycoplasma), contamination can bring research to a halt, wasting both time and money and possibly raising doubts about the validity of a laboratorys findings. Studies have shown that up to 30% of animal cell cultures are contaminated by either microorganisms or other cells.While no researcher is immune to this common problem, an introduction to and/or refresher on good aseptic techniques can help reduce the occurrence of contamination and possibly its severity. This webinar will be a master class for all those who perform primary and immortalized cell culture. It will discuss best practices and common pitfalls, with a special section dedicated to the dangers of contamination and ways to avoid it. An additional section will be devoted to protein expression in suspension. This webinar should be equally beneficial to both novices and experts in cell culture.

During the webinar, the speakers will:

This webinar will last for approximately 60 minutes.

Johns Hopkins School of MedicineBaltimore, MD

Stowers Medical InstituteKansas City, MO

Dr. Zhao, originally from Henan Province, China, graduated from Zhengzhou University with an M.D. degree. She earned her Ph.D. in veterinary pathobiology from the University of Missouri-Columbia, then completed a 2-year certification in science management at the University of Kansas. In 2012 she joined the Stowers Institute of Medical Research in Kansas City, Missouri, as a research coordinator. In 2019, she was promoted to head of Tissue Culture at Stowers and in 2020 was named head of Tissue Culture and Media Prep. With 15 years of experience in cell culture, including 3D organoid culture, primary cell culture, virus work, and gene editing, Dr. Zhao collaborates with Stowers researchers to develop new products and technologies in the cell-culture field.

Science/AAASWashington, DC

Dr. Oberst did her undergraduate training at the University of Maryland, College Park, and her Ph.D. in Tumor Biology at Georgetown University, Washington D.C. She combined her interests in science and writing by pursuing an M.A. in Journalism from the Philip Merrill College of Journalism at the University of Maryland, College Park. Dr. Oberst joined Science/AAAS in 2016 as the Assistant Editor for Custom Publishing. Before then she worked at Nature magazine, the Howard Hughes Medical Institute, The Endocrine Society, and the National Institutes of Mental Health.

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A cell culture master class: What your cells wish they could tell you - Science Magazine

Cell Biology

S2 Genomics Announces Asia-Pacific Distribution Partnerships for the Singulator 100 System With SCRUM, PharmiGene, LnCBio, Thunderbio Science, and…

S2 Genomics, Inc., today announced that it has entered into distribution agreements with SCRUM, PharmiGene, LnCBio, Thunderbio Science, and TrendBio for the promotion, sales, and support of S2s Singulator 100 System and associated products for single-cell genomics and cell biology applications in the Asia-Pacific region.

The distribution agreements cover Japan (SCRUM), South Korea (LnCBio and Thunderbio Science), Taiwan (PharmiGene), and Australia and New Zealand (TrendBio).

The Asia-Pacific region is experiencing significant growth in single-cell genomic and cell biology analyses, and that is driving a need for improved sample preparation solutions, said Dr. Stevan Jovanovich, S2 Genomics Chief Executive Officer. We are excited to welcome SCRUM, PharmiGene, LnCBio, Thunderbio Science, and TrendBio as key partners for S2 Genomics. Each of these distributors has significant expertise in life sciences, and especially in genomics. Expanding our commercialization efforts into the Asia-Pacific region represents a significant milestone for S2 Genomics.

S2 Genomics Singulator 100 system enables consistent isolation of single cells or nuclei from solid tissue samples, essential to producing high-quality single-cell data from difficult tissue types. The Singulator 100 system uses single-use disposable cartridges and proprietary reagents to automate tissue dissociation in a convenient workflow. In addition, the system allows users to create their own dissociation protocols, use their own reagents, and dissociate tissue at low temperature to minimize changes to cell transcriptomes.

Takemitsu Furuta, President and CEO of SCRUM noted, Its exciting for SCRUM to be working with S2 and expand our product portfolio in cell biology, especially single cell genomics. This is also an important area of current life science studies in Japan. I strongly believe the value of this platform will facilitate our customers research studies and greatly improve their experimental efficiency.

S2 Genomics distributor information can be found at http://www.S2Genomics.com/distributors.

About S2 Genomics, Inc.

S2 Genomics, founded in 2016, is a leading developer of laboratory automation solutions for processing solid tissues for single-cell applications. S2 Genomics technology platforms integrate advanced fluidics, optics, and biochemistry to produce automated sample preparation solutions for single-cell sequencing and cell biology markets, enabling discovery and innovation in life science research, healthcare, and agriculture. For more information, visit https://S2Genomics.com.

For Research Use Only. Not for use in diagnostic procedures.

S2 Genomics, the S2 Genomics logo, and Singulator are trademarks of S2 Genomics, Inc.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200909005030/en/

Dr. John Bashkin, VP Business Development, S2 Genomics, Inquiries@s2genomics.com

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S2 Genomics Announces Asia-Pacific Distribution Partnerships for the Singulator 100 System With SCRUM, PharmiGene, LnCBio, Thunderbio Science, and...

Cell Biology

10x Genomics First to Market With Product to Simultaneously Capture Epigenome and TranscriptomeChromium Single Cell Multiome ATAC + Gene Expression…

PLEASANTON, Calif., Sept. 15, 2020 (GLOBE NEWSWIRE) --10x Genomics (Nasdaq: TXG) today announced it has begun shipping its Chromium Single Cell Multiome ATAC + Gene Expression solution to customers, marking the first commercial release of a product capable of simultaneously profiling the epigenome and transcriptome from the same single cell. This multi-omic approach provides customers with the ability to link a cells epigenetic program to its transcriptional output, enabling a better understanding of cell functionality and bypassing the need to infer relationships through computer simulations.

This is one of our most ambitious undertakings at the company, said Ben Hindson, co-founder and Chief Scientific Officer of 10x Genomics. By introducing the first solution that captures ATAC and gene expression simultaneously, researchers can gain even more clarity by combining two already powerful methods to profile biological systems at single cell resolution simultaneously for the first time.

The new solution builds on an array of new products launched by the company this year for both its Chromium platform for single cell analysis as well as its Visium platform for spatial genomics. Early customers already working with Chromium Single Cell Multiome ATAC + Gene Expression include Stanford University School of Medicine, Icahn School of Medicine at Mt. Sinai and Spains Centro Nacional de Anlisis Genmico.

My lab is interested in understanding why some immune cell types fail to fight the cancer, said Dr. Ansuman Satpathy, Assistant Professor of Pathology, Stanford University School of Medicine. We plan to use 10x Genomics' new assay to understand the epigenetic and transcriptional regulation of immune cell dysfunction directly in patient samples, and to use this information to precisely engineer more effective immunotherapies in the future.

Until now, we have relied on computational prediction to match a cell's epigenome to a single-cell gene expression profile, said Dr. Holger Heyn, leader of the single cell genomics team at Spains Centro Nacional de Anlisis Genmico that is working on delineating the dynamics underlying B-cell differentiation and activation. 10x Genomics new multiome assay will allow us to directly measure what before could only be predicted, and offers a new gold standard that will confirm how accurate these predictions had been.

"With this new technology, we can better understand the mechanisms affected by the non-coding risk genetic variation across a wide range of neuropsychiatric diseases, including Alzheimers, Parkinsons, Schizophrenia, bipolar disorder and major depression, along with different severity of neuropathology and clinical symptomatology," added Dr. Panagiotis Roussos, Associate Professor of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai.

By using Chromium Single Cell Multiome ATAC + Gene Expression, researchers can:

Chromium Single Cell Multiome ATAC + Gene Expression is shipping to customers. To learn more, visit https://www.10xgenomics.com/products/single-cell-multiome-atac-plus-gene-expression.

About 10x Genomics10x Genomics is a life science technology company building products to interrogate, understand and master biology to advance human health. The companys integrated solutions include instruments, consumables and software for analyzing biological systems at a resolution and scale that matches the complexity of biology. 10x Genomics products have been adopted by researchers around the world including 97 of the top 100 global research institutions and 19 of the top 20 global pharmaceutical companies, and have been cited in over 1,500 research papers on discoveries ranging from oncology to immunology and neuroscience. The companys patent portfolio comprises more than 775 issued patents and patent applications.

Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements generally can be identified by the use of forward-looking terminology such as may, will, should, expect, plan, anticipate, could, intend, target, project contemplate, believe, estimate, predict, potential or continue or the negatives of these terms or variations of them or similar terminology. These forward-looking statements include statements regarding 10x Genomics, Inc.s partnership activities, which involve risks and uncertainties that could cause 10x Genomics, Inc.s actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on managements current expectations, forecasts, beliefs, assumptions and information currently available to management, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect 10x Genomics, Inc.s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere in the documents 10x Genomics, Inc. files with the Securities and Exchange Commission from time to time. The forward-looking statements in this press release are based on information available to 10x Genomics, Inc. as of the date hereof, and 10x Genomics, Inc. disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing 10x Genomics, Inc.s views as of any date subsequent to the date of this press release.

Disclosure Information10x Genomics uses filings with the Securities and Exchange Commission, its website (www.10xgenomics.com), press releases, public conference calls, public webcasts and its social media accounts as means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

ContactsMedia:media@10xgenomics.comInvestors:investors@10xgenomics.com

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10x Genomics First to Market With Product to Simultaneously Capture Epigenome and TranscriptomeChromium Single Cell Multiome ATAC + Gene Expression...

Immunology

Attempting to bounce back after mid-stage flop, Novus pivots to immunology with CD40L-focused acquisition of Anelixis – Endpoints News

Following a mid-stage failure of its acute otitis media candidate back in June that sent its shares deep into penny stock territory, Novus Therapeutics has found what it believes to be a new, exciting path forward in immunology.

The Irvine, CA-based company, originally called Tokai Pharmaceuticals, announced Monday afternoon the acquisition of Anelixis Therapeutics a biotech that was spun out of the ALS Therapy Development Institute in Boston in 2015 as well as $108 million in private placement funding led by BVF Partners. Anelixis lead program AT-1501, an anti-CD40L antibody, will be central to Novus new focus, and the company is bringing along David-Alexandre Gros to steer the ship as new CEO.

The concept and discussions were around not only how to continue to move this asset forward in ALS, but also recognizing the broader potential of the CD40 ligand and beginning to think about how one could develop the asset more broadly, Gros, who joins the company after co-founding Imbria, told Endpoints News.

Novus new funding will get AT-1501 through four Phase II trials in renal transplantation, islet cell transplantation, autoimmune nephritis and ALS. Several other investors participated in the private placement, including Cormorant Asset Management, Ecor1, Logos, Fidelity Management and Research, Adage, Woodline, Ridgeback Capital, Janus Henderson, and Samsara BioCapital.

Joining Gros at Novus is Steven Perrin, the founder and CEO of Anelixis, who will work as the companys new president and CSO. When Anelixis was founded, the biotech spent its resources studying AT-1501s effect in the treatment of ALS, managing to complete a Phase I trial evaluating the compounds safety.

CD40 has a long history of research, Perrin said, and blocking the pathway can induce profound effects in the biology of both B cells and T cells, creating potential opportunities for drugs to treat a host of autoimmune disorders like multiple sclerosis, rheumatoid arthritis and type 1 diabetes. But in earlier efforts by companies to create anti-CD40 drugs, several instances of blood clots arose, putting early but exciting clinical programs on hold.

Prominently, in 2018, a UCB and Biogen anti-CD40L program designed to treat lupus flopped in a Phase IIb trial. Lupus, however, has been a challenging indication for years as the field has seen one FDA approval in GSKs Benlysta. AstraZeneca spinout Viela Bio is also working on an anti-CD40L in kidney transplant rejection, currently in a Phase II trial.

Novus hopes to set itself apart from the competition by focusing on the CD40 ligand, rather than the receptor, as part of an emerging new generation of transplant rejection therapies. The opportunity to join this pack is one of the main reasons why the program is being expanded from an initial ALS target into other indications, Perrin said.

The most important part of the historical data is that to this day, blocking CD40 ligand signaling is the most effective way to prevent transplant rejection in multiple animal models, Perrin said. Thats why theres been a long-term focus on this pathway; it could really be a transformational way to treat autoimmune indications and transplants.

From Anelixis business perspective, Perrin and his team decided to go against the traditional fundraising and eventual IPO route after wrapping up the programs Phase I at the end of 2019. Anelixis wanted to further AT-1501 development as the company was excited by their data, but needed more than just cash. Novus existing infrastructure, both from an administrative and operational standpoint, made the pairing a suitable match, Perrin said.

Next up are the Phase II trials, after which Novus will determine future steps.

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Attempting to bounce back after mid-stage flop, Novus pivots to immunology with CD40L-focused acquisition of Anelixis - Endpoints News

Immunology

Immunologists analyze types of immune response to predict an effective COVID-19 vaccine – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 15 2020

Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition. It is especially important now when multiple vaccines against COVID-19 are being developed. The top immunologists analyze types of immune response to predict what kind of vaccine would be the best.

The COVID-19 pandemic is still ongoing, and it is a major challenge for healthcare professionals worldwide.

Currently, there are several strategies of preventing the spread of the disease caused by the SARS-CoV-2 virus, including confinement or quarantine measures, social distancing, use of face masks, and good hygiene -- with frequent hand washing and application of antiseptics. However, it is clear that such restrictions affect our personal and professional lives.

This is why vaccines against SARS-CoV-2 are being developed across the globe, as vaccination could help stop the pandemic. But these vaccines can be designed in a number of ways, and immune responses may be different.

The recent keynote paper by Sechenov University scientists and their Swiss colleagues analyses which type of immune reaction would be more favorable so the vaccine could be effective. The study has been published in International Archives of Allergy and Immunology.

The vaccine, as expected, should efficiently induce high-affinity neutralizing antibodies which would target SARS-CoV-2. At the same time, there are concerns that infection after vaccination might lead to eosinophilic lung disease and eosinophil associated Th2 immunopotentiation.

Eosinophils are white blood cells involved in conditions such as bronchial asthma, eosinophilic oesophagitis, and hypereosinophilic syndromes. Currently, despite the limited available data, there is no indication that eosinophils play a protective or pathogenic role in COVID-19 infection.

However, eosinophils might still get involved when a person is vaccinated. For example, the research on potential vaccines against SARS-CoV-1, a closely related virus which caused an epidemic in 2002-2004, showed that pulmonary eosinophilia was induced in ferrets, monkeys, and mice after viral challenge.

This fact suggests that vaccines against SARS-CoV-2 could also cause a similar immunopathology. Another source of complications might be the induced antibodies that promote viral uptake via Fc receptors.

According to the authors of the study, the most advantageous strategy should focus on vaccines that would induce the production of high-affinity virus-neutralizing antibodies.

These antibodies should block the interaction of SARS-CoV-2 with its cellular receptor -- angiotensin-converting enzyme 2 (ACE2). Successful vaccines are expected to polarize the T-cell response towards type 1 immunity and prevent the stimulation of cytokines which induce T-helper 2 immunity.

From our experience with the SARS-1 vaccine, we know that mice which received the whole spike protein (responsible for ACE2 binding) exhibited some eosinophilic complications due to the Th-2 polarisation of the immune response."

Alexander Karaulov, Study Author and Head of the Department of Clinical Immunology and Allergology, Sechenov University

'At the same time, if the injected vaccine contained not the whole spike protein, but rather its receptor-binding domain which is directly involved in interactions with ACE2, immune-mediated pathologies (hypereosinophilic syndrome) could be avoided because of the high immunogenicity and high antibody titre. I believe this to be an important aspect, which remains poorly investigated'.

The article is the result of a collaboration between Sechenov University and the University of Bern (Switzerland).

Source:

Journal reference:

Simon H.-U., et al. (2020) Strategies to Prevent SARS-CoV-2-Mediated Eosinophilic Disease in Association with COVID-19 Vaccination and Infection. International Archives of Allergy and Immunology. doi.org/10.1159/000509368.

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Immunologists analyze types of immune response to predict an effective COVID-19 vaccine - News-Medical.Net

Immunology

Antibiotic Molecule Enables HIV Infected Cells To Be Killed by the Immune System – Technology Networks

Ever since the first cases of a mysterious disease in the early 1980s exploded into the HIV/AIDS pandemic, researchers have been searching for ways to outsmart the deadly virus. Now thanks to anti-retroviral therapy, people living with HIV can live relatively normal lifespansas long as they take their medications every day.

If they ever stop, in short order the virus rebounds and resets at the high levels seen before starting and that seems to be the case even after decades of therapy, says Mark Painter, Ph.D., a graduate student in the University of Michigan Medical Schools department of microbiology and immunology.

The reason is that HIV can hide inside the human genome, lying dormant and ready to emerge at any time. Because of this, a true cure for HIV relies on waking the latent virus and eliminating it before it has a chance to again take hold of the bodys cells, an approach known as shock and kill.

Working with a team under the direction of Kathleen Collins, M.D., Ph.D., they set out to find a weapon to kill HIV by targeting a protein called Nef. In 1998, Collins, who is a professor of internal medicine and microbiology and immunology, discovered that HIV uses Nef to evade the bodys immune system by overriding the functioning of a protein on a cells surface that lets immune cells know that the cell is infected and in need of elimination. By disabling this protein, called MHC-I, infected cells are able to proliferate.

The research tried determine if there was an FDA-approved drug or molecule already on the market that could override Nef, restore the functioning of MHC-I and allow the bodys own immune system, specifically cells known as cytotoxic T lymphocytes, to recognize the HIV-infected cells and destroy them.

We started out screening a library of 200,000 small molecules and found none inhibited Nef, says Painter. Undeterred, they approached David Sherman, Ph.D. of the U-M Life Sciences Institute, whose lab studies the biosynthesis of natural products from microbes, such as cyanobacteria.

Often synthetic molecules have quite a low molecular weight, meaning they are fairly small. And if you need to disrupt a large protein surface or interface, such as with Nef, a small molecule wont work well or at all, explains Sherman. A natural products library like the one at the LSI, on the other hand, is going to have molecules with a large range of weights and sizes.

After screening approximately 30,000 molecules, they discovered that a class of antibiotic molecules called pleicomacrolides inhibited Nef.

Pleicomacrolides are widely used in lab experiments when you want to shut down the lysosome. Because of this, they are considered toxic and risky to use as drugs, says Painter. The lysosome is an essential cell organelle used to break down worn out cell parts, viruses and bacteria.

However, the team determined that a pleicomacrolide called concanamycin A inhibits Nef at much lower concentrations than those needed to inhibit the lysosome. As a lead compound for drug development, its fairly exciting because we can use a very low dose, and inhibit Nef without short-term toxicity to the cells, said Painter.

In a proof of concept experiment, they treated HIV-infected, Nef expressing cells with concanamycin A and found that cytotoxic T cells were able to clear the infected T cells.

Its been extremely gratifying for this project, which began in my lab over a decade ago to finally come to fruition. I had hoped we would find something that worked as well as this compound does but it was never a guarantee that we would actually be successful. This type of research is risky but extremely important because of the potential reward, says Collins. But, she adds, the molecule is not yet ready to be used as a drug for treatment of HIV infected people. More research will be needed to optimize the compound. We will need to further separate the potent Nef inhibitory activity from the more toxic effect on lysosomal function to make it a viable therapy.

Collins, Painter and their colleagues are continuing work on refining the chemistry of concanamycin A to make it even more viable as a potential therapy. When combined with ART and future treatments that shock latent HIV awake, Painter notes the therapy could be used to clear any remaining virus, essentially curing HIV.

ReferencePainter M et al. Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes, PNAS. September 11, 2020. https://doi.org/10.1073/pnas.2008615117

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Antibiotic Molecule Enables HIV Infected Cells To Be Killed by the Immune System - Technology Networks