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Herpesvirus Triggers Cervical Cancer Affecting Nearly One in Four Adult Sea Lions; May Be Key Model for Understanding How Virally-Induced Cancers Develop

After more than three decades of research, scientists have proven that the cancer affecting up to one in four adult California sea lions necrospied at The Marine Mammal Center in Sausalito, California, is caused by a sexually transmitted herpesvirus. The cancer, known as sea lion urogenital carcinoma, has clear parallels to cervical cancer in humans and provides a helpful model for human cancer study. Scientists have long suspected this cancer was associated with a virus, but this is the first study to prove this theory. The study, which was published online on February 13, 2021 in Animals, an open-access, peer-reviewed journal, concluded that genital herpesvirus is a driving factor in the development of sea lion urogenital carcinoma. The research also suggests there is an underlying trigger or event that causes the virus to induce cancer in some infected sea lions and not others. Wild California sea lions have among the highest prevalence of a single type of cancer in any mammal, including humans. The Animals article is titled “Unlocking the Role of a Genital Herpesvirus, Otarine Herpesvirus 1, in California Sea Lion Cervical Cancer” (https://www.mdpi.com/2076-2615/11/2/491). A recently published news article (“Sea Lions Are Dying from a Mysterious Cancer,” Los Angeles Times, January 31, 2021-- https://www.latimes.com/environment/story/2021-01-31/california-sea-lion...) described work led by the same team which showed that pollutants such as PCBs and DDT play a significant role as co-factors in the development of this cancer.

Eminent Physician-Scientist Issues Open Letter Response to March 30 WHO Report; States That Five Undisputed Facts Support Laboratory Origin of COVID Virus; Suggests “Gain-of-Function” Research at Fault and Believes Moratorium Should Be Re-Considered

An Open Letter concerning the just-released WHO Report on the origin of the COVID virus was published today (March 30, 2021) by Steven Quay (photo), MD, PhD, CEO of Atossa Therapeutics, Inc. (NASDAQ: ATOS), and former Assistant Professor, Department of Pathology, Stanford University School of Medicine. The letter is titled "To Stop the Next Pandemic, Evidence That Is Undisputed Favoring Lab Origin of COVID Needs to Be Acknowledged." The Open Letter can be downloaded from Zenodo, a general-purpose open-access repository operated by CERN, here: Open Letter to the WHO (https://zenodo.org/record/4643871#.YGN-Mz9OlPY). A short “explainer” video about the letter can be found here: Open Letter - Video Explainer (https://www.youtube.com/watch?v=3jT-ZqpuQNw). The purpose of the Open Letter is to help readers of the WHO report understand the five facts that scientists agree on and which support the conclusion that an accidental laboratory-acquired infection was likely responsible for the COVID pandemic. According to Dr. Quay, the five undisputed facts are: 1. COVID-19 wasn't smoldering in the community before the epidemic broke out, as was observed with previous coronavirus epidemics. 2. Despite an intense search, neither the COVID virus, nor any close relative, has yet been found in nature, unlike prior natural zoonoses. The closest viral relative is from the laboratories of the Wuhan Institute of Virology, near the epicenter of the first cases. 3. The COVID virus had little genetic diversity at the outset, unlike prior natural zoonoses. It was genetically pure, like the man-made vaccines being rolled out. 4. The COVID virus's powerful infectious trigger isn't found anywhere in its related viral group in nature, but has been repeatedly inserted into viruses by laboratory scientists, including at the Wuhan Institute of Virology. 5.

WHO Report Calls for Further Studies and More Data on Origin of SARS-Cov-2 Virus; Report Reiterates That All Hypotheses Remain Open; Mystery of Virus Origin Unsolved and Controversy Swirls Over Possible Chinese Bias in WHO-Organized Investigation

The report of the international team on its Wuhan, China field visit, from 14 January 14 to February 10, 2021, was published today (March 30, 2021) (https://www.who.int/health-topics/coronavirus/origins-of-the-virus), as WHO Director-General Dr. Tedros Adhanom Ghebreyesus called for further studies. The report stems from a Member State resolution adopted by consensus at the World Health Assembly in May 2020 and calling on WHO “to identify the zoonotic source of the virus and the route of introduction to the human population, including the possible role of intermediate hosts, including through efforts such as scientific and collaborative field missions.” In remarks to Member States today, Dr. Tedros, who received the full report on the weekend, thanked the team for its tireless work. He said it advances our understanding in important ways, while raising questions that will need to be addressed by further studies, as noted in the report. “As far as WHO is concerned, all hypotheses remain on the table. This report is a very important beginning, but it is not the end. We have not yet found the source of the virus, and we must continue to follow the science and leave no stone unturned as we do,” said Dr. Tedros. “Finding the origin of a virus takes time and we owe it to the world to find the source so we can collectively take steps to reduce the risk of this happening again. No single research trip can provide all the answers.” The WHO report is available on this webpage: https://www.who.int/health-topics/coronavirus/origins-of-the-virus.

Report by Eminent US Scientist Concludes That SARS-CoV-2 Was Most Likely Laboratory-Derived, Not Result of Natural Zoonosis; In-Depth Statistical Analysis Suggests 99.8% Chance That Virus Came from Lab

A paper published on January 29, 2021, by Steven Quay (photo), MD, PhD, CEO of Atossa Therapeutics, Inc. (NASDAQ: ATOS), entitled, "A Bayesian Analysis Concludes Beyond a Reasonable Doubt That SARS-Cov-2 Is Not a Natural Zoonosis But Instead Is Laboratory Derived." The 193-page paper can be downloaded from Zenodo, a general-purpose open-access repository operated by CERN (The European Organization for Nuclear Research), here: https://zenodo.org/record/4477081#. A short “explainer” video about the paper is here: https://zenodo.org/record/4477212#. The purpose of the analysis was to determine the origin of SARS-CoV-2, the virus that causes COVID-19. Beginning with a likelihood of 98.2% that it was a zoonotic jump from nature with only a 1.2% probability it was a laboratory escape, twenty-six different, independent facts and evidence concerning the virus were examined systematically. These included the three key pro-zoonotic papers published early on in the pandemic, the lack of posterior genetic diversity in SARS-CoV-2, the lack of a furin cleavage site in any of the ~1,000 other corona viruses in the same subgenera as SARS-CoV-2 (the Spike protein of SARS-CoV-2 must be cleaved by the host furin enzyme to gain entry to the human cell), and a canvas of 410 animals showing that humans and primates are the best and bats are the worst for ACE2-Spike protein interaction. The final conclusion of the Dr. Quay’s Bayesian statistical analysis is that it is a 99.8% probability SARS-CoV-2 came from a laboratory and only a 0.2% likelihood it came from nature. "Like many others, I am concerned about what appear to be significant conflicts of interest between members of the WHO team and scientists and doctors in China and how much this will impede an unbiased examination of the origin of SARS-CoV-2," said Dr. Quay.

Potential COVID-19 Treatment Identified in UCLA-Led Lab Study; Kinase Inhibitor (Berzosertib) Already in Human Trials As Cancer Therapy Appears to Disrupt Coronavirus Replication

A collaboration among scientists from UCLA and other universities in California, Delaware, and Germany, as well as a German pharmaceutical company, has singled out a compound that shows promise for treating SARS-CoV-2, the virus that causes COVID-19. In a series of experiments using different types of cells in lab dishes, the researchers found that berzosertib was effective in blocking the coronavirus’s ability to replicate and did not cause significant harm to cells. Berzosertib, which is licensed by Merck KGaA, Darmstadt, Germany, is being investigated in separate early- and mid-stage clinical trials, in combination with chemotherapy, as a possible treatment for small-cell lung cancer, ovarian cancer, and other types of tumors. The study, published online on March 17, 2021 in Cell Reports, was led by corresponding authors Robert Damoiseaux, PhD, a UCLA Professor of Molecular and Medical Pharmacology and of Bioengineering, and Vaithilingaraja Arumugaswami, PhD, a UCLA Associate Professor of Molecular and Medical Pharmacology and a member of the UCLA Broad Stem Cell Research Center. Both are members of the California NanoSystems Institute (CNSI) at UCLA. The Cell Reports article is titled “Antiviral Drug Screen Identifies DNA-Damage Response Inhibitor as Potent Blocker of SARS-CoV-2 Replication” (https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00254-0). “Currently, there are no effective small-molecule drug therapies against COVID-19,” said Gustavo Garcia Jr., the study’s first author and a UCLA staff research associate. “This study identified a new potential therapy that could help the global fight against COVID-19 and support populations that have been disproportionately affected by this deadly disease.”

MIT Scientists Identify Genes Linked to Abnormal Repetitive Behaviors Often Seen in Models of Addiction and Schizophrenia

Extreme repetitive behaviors such as hand-flapping, body-rocking, skin-picking, and sniffing are common to a number of brain disorders including autism, schizophrenia, Huntington’s disease, and drug addiction. These behaviors, termed stereotypies, are also apparent in animal models of drug addiction and autism. In a new study published online on March 23, 2021 in the European Journal of Neuroscience, researchers at MIT’s McGovern Institute for Brain Research have identified genes that are activated in the brain prior to the initiation of these severe repetitive behaviors. The article is titled “Striatal transcriptome changes linked to drug‐induced repetitive behaviors” (https://onlinelibrary.wiley.com/doi/10.1111/ejn.15116). “Our lab has found a small set of genes that are regulated in relation to the development of stereotypic behaviors in an animal model of drug addiction,” says MIT Institute Professor Ann Graybiel, PhD, who is the senior author of the paper. “We were surprised and interested to see that one of these genes is a susceptibility gene for schizophrenia. This finding might help to understand the biological basis of repetitive, stereotypic behaviors as seen in a range of neurologic and neuropsychiatric disorders, and in otherwise ‘typical’ people under stress.” In work led by Research Scientist Jill Crittenden (photo), PhD, scientists in the Graybiel lab exposed mice to amphetamine, a psychomotor stimulant that drives hyperactivity and confined stereotypies in humans and in laboratory animals and that is used to model symptoms of schizophrenia.

New Structure That Mimics Blastocysts Could Aid Research into Early Human Development, UTSW Researchers Say in Nature Article

A University of Texas Southwestern (UTSW) research team has generated biological structures that resemble blastocysts--the structures that form from the early development of fertilized eggs in mammals. They did this using previously established human embryonic stem cells derived from embryos donated for research and human-induced pluripotent stem cells generated from adult cells-- collectively known as human pluripotent stem cells. The findings, published online on March 17, 2021 in Nature, could offer a new way to study early human development, pregnancy loss, and developmental defects. The Nature article is titled “Blastocyst-like structures generated from human pluripotent stem cells” (https://www.nature.com/articles/s41586-021-03356-y). Despite their similar morphology to blastocysts, blastocyte-like structures cannot develop into fetuses, says study leader Jun Wu (https://profiles.utsouthwestern.edu/profile/175076/jun-wu.html), PhD, an Assistant Professor of Molecular Biology at UTSW. “Having an in vitro biological model for blastocyst development is critically important to fill the gap for understanding human development without relying extensively on human embryos,” Dr. Wu says. Human pluripotent stem cells--cells at one of the earliest stages of development--have the potential to become nearly all of the body’s many tissue types. However, it was not known what molecular signals were important to get them to develop into blastocysts, hollow ball-shaped early embryos that form about five days after conception before implanting into the uterine wall. Studies of this stage of human development have largely relied on discarded/donated embryos from fertility treatments, a scarce resource that has ethical concerns, Dr. Wu says. Blastocysts contain three main cell types: epiblasts, hypoblasts, and trophoblasts.

Scientists Detect Cancer Stem Cell (CSC) Biomarkers in Exosomes from Patients with Malignant Melanoma; Work May Lead to Earlier Diagnosis and Inform Prognosis

A new study has shown that exosomes released by cancer stem cells (CSCs) from patients with malignant melanoma (MM) have a different molecular composition from that of exosomes from differentiated MM cells. These differential molecules were also found to be detectable in exosomes present in the blood, and they presented differences in patients with malignant melanoma compared to healthy individuals. This makes them potentially suitable as biomarkers for the diagnosis and prognosis of this disease. The results were published online on October 14, 2020 in Molecular Oncology. The open-access article is titled “Metabolomic Profile of Cancer Stem Cell‐Derived Exosomes from Patients with Malignant Melanoma” (https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.12823). MM is one of the most aggressive types of skin cancer and its prevalence has been increasing worldwide in recent years. Among the factors that contribute to the life-threatening nature and severity of this disease are the late appearance of the first symptoms, the lack of effective treatments, its high metastasis capacity, and also the difficulty of detecting this particular cancer. Unfortunately, the diagnosis of MM therefore continues to be problematic due to the lack of indicators--known as biomarkers--to accurately signal the early stages of this disease and predict how it might evolve in a given patient, once detected. These characteristics, which make this type of cancer such a serious disease, may be partly attributable to so-called cancer stem cells (CSCs), a sub-population of cells that exist in tumors and that present the typical characteristics of stem cells. These CSCs are responsible for tumor initiation, maintenance, and progression, as well as metastasis and recurrence--even years after a tumor has been eradicated.

Display of “Eat-Me” Signal on Cell Surfaces of Unwanted Cells Requires Activation of a Lipid-Scrambling Protein by a Nuclear Protein Fragment

Scientists at the Institute for Integrated Cell-Material Sciences (iCeMS) (Kyoto University) and colleagues in Japan have revealed molecular mechanisms involved in eliminating unwanted cells in the body. A nuclear protein fragment released into the cytoplasm activates a plasma membrane protein to display a lipid on the cell surface, signaling other cells to get rid of it (see small image at left and enlarged image below). The findings were published online on March 15, 2021 in journal Molecular Cell. The article is titled “Caspase cleavage releases a nuclear protein fragment that stimulates phospholipid scrambling at the plasma membrane” (https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00135-0). "Every day, ten billion cells die and are engulfed by blood cells called phagocytes. If this didn't happen, dead cells would burst, triggering an auto-immune reaction," explains iCeMS biochemist Jun Suzuki, PhD, Professor, Deputy Director of Medical Biochemistry and Cell Membrane Biology, who led the study. "It is important to understand how dead cells are eliminated as part of our body's maintenance." Scientists already know that dead cells display an “eat me” signal on their surface that is recognized by phagocytes. During this process, lipids are flipped between the inner and outer parts of the cell membrane via a variety of proteins called scramblases. Dr. Suzuki and his team have already identified several of these lipid-scrambling proteins, but some of their activation mechanisms have been unclear. To solve this, the team used an array of screening approaches to study the scrambling protein called Xkr4. The broad aim was to single out the genes that are active during cell death and to specifically zoom in on Xkr4 and its associated proteins to understand how they interact.

Case Study of Critically Ill Person with COVID-19 and on ECMO for 66 Days Successfully Treated with CytoDyn’s Anti-CCR5 Monoclonal Antibody Leronlimab

Several cases have recently been reported suggesting that treatment with CytoDyn’s leronlimab restores immune function and achieves clinical improvement in people with critical COVID-19 (https://www.sciencedirect.com/science/article/pii/S2589909021000034) (https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1583/59...). A new article, published online on March 23, 2021 in the Journal of Translational Autoimmuity, reports on an additional case of a critically ill COVID-19 person who was successfully treated with leronlimab. This person had been on extracorporeal membrane oxygenation (ECMO) for an extended period of time (66 days) before receiving four doses of leronlimab. The male subject received his first dose of leronlimab on Day 79 of hospitalization. He was weaned off ECMO by Day 84 and discharged from the ECMO intensive care unit on Day 91. He continues to improve and is currently in rehabilitation. The case was reported by corresponding author, Soheir Elneil, MD, PhD, University College London, National Hospital for Neurology and Neurosurgery, London, UK; Jacob Lalezari, MD, CEO & Director, Quest Diagnostis Services, San Francisco, California; and Nader Pourhassan, PhD, CEO & President & Director, CytoDyn, Seattle, Washington. In their abstract, the authors noted that the number of confirmed cases of infection with SARS-CoV-2, the virus causing coronavirus disease 2019 (COVID-19), continues to increase and is associated with substantial morbidity and mortality in virtually every country in the world. The authors noted that, “although in the long-term mass vaccinations remains the most promising approach to control the pandemic, evidence suggests that new variants of the virus have emerged that may be able to evade the immune responses triggered by current vaccines.

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