scholarly journals Molecular Biology of Rotavirus Entry and Replication

2009 ◽  
Vol 9 ◽  
pp. 1476-1497 ◽  
Author(s):  
Marie Christine Ruiz ◽  
Theresa Leon ◽  
Yuleima Diaz ◽  
Fabian Michelangeli
Keyword(s):  
Molecular Mechanisms ◽  
Rna Virus ◽  
Viral Proteins ◽  
Therapeutic Strategies ◽  
Viral Gastroenteritis ◽  
Structural Studies ◽  
Double Stranded Rna ◽  
The Individual ◽  
Remarkable Progress ◽  
Made In

Rotavirus is a nonenveloped, double-stranded, RNA virus belonging to the Reoviridae family and is the major etiological agent of viral gastroenteritis in young children and young animals. Remarkable progress in the understanding of the rotavirus cycle has been made in the last 10 years. The knowledge of viral replication thus far acquired is based on structural studies, the expression and coexpression of individual viral proteins, silencing of individual genes by siRNAs, and the effects that these manipulations have on the physiology of the infected cell. The functions of the individual rotavirus proteins have been largely dissected; however, the interactions between them and with cell proteins, and the molecular mechanisms of virus replication, are just beginning to be understood. These advancements represent the basis for the development of effective vaccination and rational therapeutic strategies to combat rotavirus infection and diarrhea syndromes. In this paper, we review and try to integrate the new knowledge about rotavirus entry, replication, and assembly, and pose some of the questions that remain to be solved.

scholarly journals Alpha-Synuclein: Mechanisms of Release and Pathology Progression in Synucleinopathies

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 375
Author(s):  
Inês C. Brás ◽  
Tiago F. Outeiro
Keyword(s):  
Molecular Mechanisms ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Therapeutic Strategies ◽  
Cell Protein ◽  
Protein Assemblies ◽  
Lewy Pathology ◽  
Tremendous Progress ◽  
The Brain ◽  
Made In

The accumulation of misfolded alpha-synuclein (aSyn) throughout the brain, as Lewy pathology, is a phenomenon central to Parkinson’s disease (PD) pathogenesis. The stereotypical distribution and evolution of the pathology during disease is often attributed to the cell-to-cell transmission of aSyn between interconnected brain regions. The spreading of conformationally distinct aSyn protein assemblies, commonly referred as strains, is thought to result in a variety of clinically and pathologically heterogenous diseases known as synucleinopathies. Although tremendous progress has been made in the field, the mechanisms involved in the transfer of these assemblies between interconnected neural networks and their role in driving PD progression are still unclear. Here, we present an update of the relevant discoveries supporting or challenging the prion-like spreading hypothesis. We also discuss the importance of aSyn strains in pathology progression and the various putative molecular mechanisms involved in cell-to-cell protein release. Understanding the pathways underlying aSyn propagation will contribute to determining the etiology of PD and related synucleinopathies but also assist in the development of new therapeutic strategies.

scholarly journals Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV

2020 ◽  
Author(s):  
Alexey Stukalov ◽  
Virginie Girault ◽  
Vincent Grass ◽  
Valter Bergant ◽  
Ozge Karayel ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Viral Proteins ◽  
Human Cell Line ◽  
Global Network ◽  
Cellular Interactions ◽  
Cellular Events ◽  
Host Signaling ◽  
Approved Drugs ◽  
The Individual

AbstractThe sudden global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several omics studies have extended our knowledge of COVID-19 pathophysiology, including some focused on proteomic aspects1–3. To understand how SARS-CoV-2 and related coronaviruses manipulate the host we here characterized interactome, proteome and signaling processes in a systems-wide manner. This identified connections between the corresponding cellular events, revealed functional effects of the individual viral proteins and put these findings into the context of host signaling pathways. We investigated the closely related SARS-CoV-2 and SARS-CoV viruses as well as the influence of SARS-CoV-2 on transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed relationships between the perturbations taking place upon SARS-CoV-2 infection at different layers and identified unique and common molecular mechanisms of SARS coronaviruses. The results highlight the functionality of individual proteins as well as vulnerability hotspots of SARS-CoV-2, which we targeted with clinically approved drugs. We exemplify this by identification of kinase inhibitors as well as MMPase inhibitors with significant antiviral effects against SARS-CoV-2.

scholarly journals The changing face of a rare disease: lymphangioleiomyomatosis

2015 ◽  
Vol 46 (5) ◽  
pp. 1471-1485 ◽  
Author(s):  
Sergio Harari ◽  
Olga Torre ◽  
Roberto Cassandro ◽  
Joel Moss
Keyword(s):  
Rare Disease ◽  
Tuberous Sclerosis Complex ◽  
Therapeutic Approach ◽  
Clinical Manifestations ◽  
Therapeutic Strategies ◽  
The Past ◽  
Lymphatic Abnormalities ◽  
Abdominal Tumours ◽  
Remarkable Progress ◽  
Made In

Lymphangioleiomyomatosis is a rare disease characterised by cystic destruction of the lung, lymphatic abnormalities and abdominal tumours. It affects almost exclusively females and can occur sporadically or in patients with tuberous sclerosis complex.In the past decade remarkable progress has been made in understanding of the pathogenesis of this disease leading to a new therapeutic approach. This review summarises recent advances regarding pathogenic mechanisms and clinical manifestations, and highlights the current and the most promising future therapeutic strategies.

A Handbook to Eddic Poetry: Myths and Legends of Early Scandinavia, ed. Carolyne Larrington, Judy Quinn, and Brittany Schorn. Cambridge: Cambridge University Press, 2016, xii, 413 pp., 12 b/w ill.

Mediaevistik ◽  
2018 ◽  
Vol 31 (1) ◽  
pp. 366-366
Author(s):  
Albrecht Classen
Keyword(s):  
Old Norse ◽  
Entire Volume ◽  
Cambridge University ◽  
Critical Studies ◽  
Individual Contributions ◽  
The Many ◽  
The Individual ◽  
Made In ◽  
Scandinavian Literature

Eddic poetry constitutes one of the most important genres in Old Norse or Scandinavian literature and has been studied since the earliest time of modern-day philology. The progress we have made in that field is impressive, considering the many excellent editions and translations, not to mention the countless critical studies in monographs and articles. Nevertheless, there is always a great need to revisit, to summarize, to review, and to digest the knowledge gained so far. The present handbook intends to address all those goals and does so, to spell it out right away, exceedingly well. But in contrast to traditional concepts, the individual contributions constitute fully developed critical article, each with a specialized topic elucidating it as comprehensively as possible, and concluding with a section of notes. Those are kept very brief, but the volume rounds it all off with an inclusive, comprehensive bibliography. And there is also a very useful index at the end. At the beginning, we find, following the table of contents, a list of the contributors, unfortunately without emails, a list of translations and abbreviations of the titles of Eddic poems in the Codex Regius and then elsewhere, and a very insightful and pleasant introduction by Carolyne Larrington. She briefly introduces the genre and then summarizes the essential points made by the individual authors. The entire volume is based on the Eddic Network established by the three editors in 2012, and on two workshops held at St. John’s College, Oxford in 2013 and 2014.

The Chemical Effect in Medicine Interaction Determining the Form and Speed of Psychical Involution in the Prosthetic Restauration in the Edentulous

2018 ◽  
Vol 69 (8) ◽  
pp. 2306-2310
Author(s):  
Aureliana Caraiane ◽  
Razvan Leata ◽  
Veronica Toba ◽  
Doina Vesa ◽  
Luana Andreea Macovei ◽  
...  
Keyword(s):  
Practical Importance ◽  
Psychosocial Problems ◽  
Well Being ◽  
The Elderly ◽  
Chemical Effect ◽  
Special Importance ◽  
Dramatic Form ◽  
Specific Disorders ◽  
The Individual ◽  
Made In

The progress made in dentistry during the latest decades is due, conceptually, to the new, systemic vision of man, which has also taken place in this field of medicine. In this context, the link between organic and psychic is indestructible. Thus illness is understood as a drama in which the somatic process has a psychic value, and the mental one has a body value. It is known that the morphological and functional integrity of the dental system, health and vigorousness, gives the individual a state of well-being that affects his somatic and psychic health, as any disturbance at this level entails repercussions in psychological and social behavior. Such a disruption is the total edification that seriously alters not only the dental system but the whole organism, putting various biological and psychosocial problems to the practitioner. The total expression represents not only a physical disability but also a psychological one. A special importance in studying psychological changes at total edentulous presents the psychological aspects of senile involution. This is not only a theoretical but also a practical importance due to the increase in the number of elderly people. Through the researches of the present paper we intend to present the reality of the psychological manifestations in the total edentation, which is objectified on different methods of psychodiagnosis in the first part, in order for the second part to be addressed to problems of prosthetic psychotherapy.The study comprises a group of 43 patients, of whom 24 were men and 19 women with total uni or bimaxilar edentation. Total edentation can be and is responsible for somatopsychic alterations, along with other pathogens, general, local, social, which sometimes can take a dramatic form, converting, where the area is also favorable, a pure somatic disease, for those who are not in psychopathy or even psychosis, although these latter cases are extremely rare and especially in youngsters, which would disrupt not only the person�s behavior as an individual, but also their status, function and social integrity. The treatment of dental and psychological complex is mandatory for any patient, but especially for the elderly, where recovery is more difficult, with disease-specific disorders adding to those of senescence.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

SARS-CoV-2 Biology Insights, Part I. Genome-wide structure and druggability: literature review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Host Cell ◽  
Nucleoside Analogs ◽  
Viral Proteins ◽  
Therapeutic Strategies ◽  
Adverse Side Effects ◽  
Viral Proteases ◽  
Genome Wide ◽  
Therapeutic Alternatives

BACKGROUND COVID-19 pandemic prompts the study of coronavirus biology and search of putative therapeutic strategies. OBJECTIVE To compare SARS-CoV-2 genome-wide structure and proteins with other coronaviruses, focusing on putative coronavirus-specific or SARS-CoV-2 specific therapeutic designs. METHODS The genome-wide structure of SARS-CoV-2 was compared to that of SARS and other coronaviruses in order to gain insights, doing a literature review through Google searches. RESULTS There are promising therapeutic alternatives. Host cell targets could be modulated to hamper viral replication, but targeting viral proteins directly would be a better therapeutic design, since fewer adverse side effects would be expected. CONCLUSIONS Therapeutic strategies (Figure 1) could include the modulation of host targets (PARPs, kinases) , competition with G-quadruplexes or nucleoside analogs to hamper RDRP. The nicest anti-CoV options include inhibitors of the conserved essential viral proteases and drugs that interfere ribosome slippage at the -1 PRF site.

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