scholarly journals Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by neutron scattering

2021 ◽  
Author(s):  
Andreas Santamaria ◽  
Krishna Chaithanya Batchu ◽  
Olga Matsarskaia ◽  
Sylvain F Prevost ◽  
Daniela Russo ◽  
...  
Keyword(s):  
Neutron Scattering ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Spin Echo ◽  
Respiratory Illness ◽  
Fusion Peptides ◽  
Molecular Events ◽  
Host Plasma Membrane ◽  
Fusion Domain

Coronavirus disease-2019 (COVID-19), a lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of the SARS-CoV-2 Spike protein, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium however re-orients the protein to the lipid leaflet in contact with the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed.

scholarly journals Molecular Events Involved in Influenza A Virus-Induced Cell Death

2022 ◽  
Vol 12 ◽  
Author(s):  
Rui Gui ◽  
Quanjiao Chen
Keyword(s):  
Cell Death ◽  
Influenza A Virus ◽  
Influenza A ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Tissue Destruction ◽  
Inflammatory Reactions ◽  
Molecular Events ◽  
Host Death

Viral infection usually leads to cell death. Moderate cell death is a protective innate immune response. By contrast, excessive, uncontrolled cell death causes tissue destruction, cytokine storm, or even host death. Thus, the struggle between the host and virus determines whether the host survives. Influenza A virus (IAV) infection in humans can lead to unbridled hyper-inflammatory reactions and cause serious illnesses and even death. A full understanding of the molecular mechanisms and regulatory networks through which IAVs induce cell death could facilitate the development of more effective antiviral treatments. In this review, we discuss current progress in research on cell death induced by IAV infection and evaluate the role of cell death in IAV replication and disease prognosis.

scholarly journals Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽  
2020 ◽  
Author(s):  
Kaitlyn A Dorsett ◽  
Michael P Marciel ◽  
Jihye Hwang ◽  
Katherine E Ankenbauer ◽  
Nikita Bhalerao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sialic Acids ◽  
Invasion Resistance ◽  
Cell Behaviors ◽  
Molecular Events ◽  
Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

scholarly journals Oxidative stress and ageing of the post-ovulatory oocyte

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. R217-R227 ◽  
Author(s):  
Tessa Lord ◽  
R John Aitken
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Embryo Quality ◽  
Fertilization Rates ◽  
Molecular Events ◽  
Post Implantation ◽  
Potential Use

With extended periods of time following ovulation, the metaphase II stage oocyte experiences deterioration in quality referred to as post-ovulatory oocyte ageing. Post-ovulatory ageing occurs both in vivo and in vitro and has been associated with reduced fertilization rates, poor embryo quality, post-implantation errors and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been established, the molecular mechanisms controlling this process are not well defined. This review analyses the relationships between biochemical changes exhibited by the ageing oocyte and the symptoms associated with the ageing phenotype. We also discuss molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We propose that oxidative stress may act as the initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to cause a decline in levels of critical cell cycle factors such as maturation-promoting factor, impair calcium homoeostasis, induce mitochondrial dysfunction and directly damage multiple intracellular components of the oocyte such as lipids, proteins and DNA. Finally, this review addresses current strategies for delaying post-ovulatory oocyte ageing with a particular focus on the potential use of compounds such as caffeine or selected antioxidants in the development of more refined media for the preservation of oocyte integrity during IVF procedures.

scholarly journals Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication

2020 ◽  
Vol 7 (1) ◽  
pp. 289-307 ◽  
Author(s):  
Wei Liu ◽  
Jianxin You
Keyword(s):  
Molecular Mechanisms ◽  
Human Tumor ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Virus Family ◽  
The Past ◽  
Molecular Events ◽  
Cellular Tropism ◽  
Novel Virus

Viral infection underlies a significant share of the global cancer burden. Merkel cell polyomavirus (MCPyV) is the newest member of the human oncogenic virus family. Its discovery over a decade ago marked the beginning of an exciting era in human tumor virology. Since then, significant evidence has emerged to support the etiologic role of MCPyV in Merkel cell carcinoma (MCC), an extremely lethal form of skin cancer. MCPyV infection is widespread in the general population. MCC diagnoses have tripled over the past 20 years, but effective treatments are currently lacking. In this review, we highlight recent discoveries that have shaped our understanding of MCPyV oncogenic mechanism and host cellular tropism, as well as the molecular events occurring in the viral infectious life cycle. These insights will guide future efforts in developing novel virus-targeted therapeutic strategies for treating the devastating human cancers associated with this new tumorigenic virus.

Acquired cholesteatoma: summary of the cascade of molecular events

2013 ◽  
Vol 127 (6) ◽  
pp. 542-549 ◽  
Author(s):  
L Louw
Keyword(s):  
Molecular Mechanisms ◽  
Bone Erosion ◽  
Chronic Otitis Media ◽  
Future Directions ◽  
Molecular Events ◽  
Matrix Interactions ◽  
Proliferation And Apoptosis ◽  
Acquired Cholesteatoma ◽  
Role Players

AbstractBackground:Cholesteatoma is considered a benign, gradually expanding and destructive epithelial lesion of the temporal bone. The pathogenesis of different classifications of cholesteatoma is marked by similar underlying cellular and molecular processes. Stepwise explanations of the histopathogenesis have been described previously. The current paper focuses on expounding the molecular events of cholesteatoma.Method and results:Cholesteatoma pathogenesis encompasses a complex network of signalling pathways during: epidermal hyperplasia, perimatrix–matrix interactions and mucosal disease. This paper presents a review of the molecular events driven by inflammatory mediators and enzymes during: cholesteatoma growth (cell proliferation and apoptosis); maintenance and deterioration (angiogenesis and hypoxia, oxidative stress and toxicity); and complications (bone erosion and hearing loss). The cascade of molecular events applicable to atelectasis and cholesteatoma that coexist with chronic otitis media and bone erosion as sequelae is summarised.Conclusion:The role of lipids in this disease is relatively unexplored, but there is evidence in support of fatty acid role-players that needs confirmation. Future directions in lipid research to delineate molecular mechanisms are proposed.

The role of macrophage-derived TGF-β1 on SiO2-induced pulmonary fibrosis: A review

2021 ◽  
pp. 074823372198989
Author(s):  
Zhao-qiang Zhang ◽  
Hai-tao Tian ◽  
Hu Liu ◽  
Ruining Xie
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Silica Dust ◽  
Molecular Events ◽  
Fibrotic Lung Disease ◽  
Different Sources ◽  
Tgf Β1

Silicosis is an occupational fibrotic lung disease caused by inhaling large amounts of crystalline silica dust. Transforming growth factor-β1 (TGF-β1), which is secreted from macrophages, has an important role in the development of this disease. Macrophages can recognize and capture silicon dust, undergo M2 polarization, synthesize TGF-β1 precursors, and secrete them out of the cell where they are activated. Activated TGF-β1 induces cells from different sources, transforming them into myofibroblasts through autocrine and paracrine mechanisms, ultimately causing silicosis. These processes involve complex molecular events, which are not yet fully understood. This systematic summary may further elucidate the location and development of pulmonary fibrosis in the formation of silicosis. In this review, we discussed the proposed cellular and molecular mechanisms of production, secretion, activation of TGF-β1, as well as the mechanisms through which TGF-β1 induces cells from three different sources into myofibroblasts during the pathogenesis of silicosis. This study furthers the medical understanding of the pathogenesis and theoretical basis for diagnosing silicosis, thereby promoting silicosis prevention and treatment.

scholarly journals Role of CD1A and HSP60 in the antitumoral response of oesophageal cancer

2011 ◽  
pp. 225-232
Author(s):  
Simona Corrao ◽  
Giampiero La Rocca ◽  
Rita Anzalone ◽  
Lorenzo Marasà ◽  
Felicia Farina ◽  
...  
Keyword(s):  
Oesophageal Cancer ◽  
Molecular Mechanisms ◽  
Tumor Antigens ◽  
Normal Epithelium ◽  
Improve Treatment ◽  
Molecular Events ◽  
New Strategies ◽  
Stimulation Of

Oesophageal cancer (OC) is one of the most common and severe forms of tumor. A wider knowledge of molecular mechanisms which lead to a normal epithelium becoming a neoplasm may reveal new strategies to improve treatment and outcome of this disease. In this review, we report recent findings concerning molecular events which take place during carcinogenesis of the oesophagus. In particular, we focus on the role of two molecules, CD1a and Hsp60, which are overexpressed in oesophageal and many other types of tumor. Both molecules may present tumor antigens and promote in situ the stimulation of an antitumoral immune activity. We suggest there is a synergistic action between these molecules. Further knowledge about their intracellular pathways and extracellular roles may help develop new antitumoral tools for OC.

scholarly journals Microarray analysis reveals the role of matrix metalloproteinases in mouse experimental autoimmune myocarditis induced by cardiac myosin peptides

2007 ◽  
Vol 12 (2) ◽  
Author(s):  
Qizhu Tang ◽  
Ji Huang ◽  
Haiyan Qian ◽  
Ran Xiong ◽  
Difei Shen ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Global Changes ◽  
Autoimmune Myocarditis ◽  
Molecular Events ◽  
Specific Antigens ◽  
Experimental Mouse ◽  
Insight Into

AbstractAutoimmune myocarditis develops after the presentation of heart-specific antigens to autoaggressive CD4+ T cells and after inflammation has infiltrated the tissues. To shed light on global changes in the gene expression of autoimmune myocarditis and to gain further insight into the molecular mechanisms underlying the genesis of myocarditis, we conducted a comprehensive microarray analysis of mRNA using an experimental mouse autoimmune myocarditis model via immunization with α-myosin heavy chain-derived peptides. Of over 39,000 transcripts on a high density oligonucleotide microarray, 466 were under-expressed and 241 over-expressed by ≥ 1.5-fold compared with the controls in BALB/C mouse with autoimmune myocarditis. In this paper, we list the top 50 up-regulated genes related to the immune response. These altered genes encode for leukocyte-specific markers and receptors, the histocompatibility complex, cytokines/receptors, chemokines/receptors, adhesion molecules, components of the complement cascade, and signal transduction-related molecules. Interestingly, matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 were up-regulated, as further revealed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. This indicates that MMPs may act as major regulators of the cytokine profile. Together, these findings provide new insight into the molecular events associated with the mechanism of the autoimmune genesis of myocarditis.

scholarly journals Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

2020 ◽  
Author(s):  
Nilesh Kumar ◽  
Bharat Mishra ◽  
Adeel Mehmood ◽  
Mohammad Athar ◽  
M. Shahid Mukhtar
Keyword(s):  
Viral Entry ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Respiratory Illness ◽  
Network Biology ◽  
Lung Epithelial Cells ◽  
Pathway Enrichment Analysis ◽  
Modeling Framework ◽  
Human Interactome ◽  
Molecular Events

AbstractCOVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrated multiomics data pertaining to lung epithelial cells-specific coexpression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity.

Role of microRNAs in immunity and organ transplantation

2011 ◽  
Vol 13 ◽  
Author(s):  
Janine C. Spiegel ◽  
Johan M. Lorenzen ◽  
Thomas Thum
Keyword(s):  
Organ Transplantation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Implications ◽  
Rna Molecules ◽  
Small Regulatory Rna ◽  
Molecular Events ◽  
Noninvasive Biomarkers

Organ transplantation has evolved rapidly and there is now widespread use of donated organs for the treatment of end-stage organ failure. Although the therapeutic options achieving long-term graft survival have improved, acute and chronic rejections are still a major problem. Studies to identify noninvasive biomarkers for rejection and underlying molecular events have increased significantly in the past decade, but a major breakthrough is still missing. The recent discovery of small regulatory RNA molecules (microRNAs) resulted in a new and improved understanding of the mechanisms of gene regulation and also led to the development of the first new microRNA (miRNA)-based therapies. miRNAs are endogenous, single-stranded RNAs consisting of about 19–25 noncoding nucleotides, which have an important role in regulating gene expression. Additionally, circulating miRNAs that might be useful as novel disease biomarkers were detected. Here, we summarise current knowledge about the role of miRNAs in immunology and transplantation medicine and their role as potential biomarkers. We also focus on the molecular mechanisms and therapeutic implications of the use of miRNA-based therapeutic strategies to improve long-term allograft survival.

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