scholarly journals Chaperoning the Mononegavirales: Current Knowledge and Future Directions

2018 ◽  
Author(s):  
Victor Latorre ◽  
Florian Mattenberger ◽  
Ron Geller
Keyword(s):  
Molecular Chaperones ◽  
Current Knowledge ◽  
Small Subset ◽  
Protein Homeostasis ◽  
Emerging Infections ◽  
Therapeutic Approaches ◽  
Future Directions ◽  
Antiviral Therapies ◽  
Cellular Machinery ◽  
Cellular Pathways

The order Mononegavirales harbors numerous viruses of significant relevance for human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the mononegavirales interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals.

scholarly journals Chaperoning the Mononegavirales: Current Knowledge and Future Directions

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 699 ◽  
Author(s):  
Victor Latorre ◽  
Florian Mattenberger ◽  
Ron Geller
Keyword(s):  
Molecular Chaperones ◽  
Current Knowledge ◽  
Small Subset ◽  
Protein Homeostasis ◽  
Emerging Infections ◽  
Therapeutic Approaches ◽  
Future Directions ◽  
Antiviral Therapies ◽  
Cellular Machinery ◽  
Cellular Pathways

The order Mononegavirales harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses, and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the Mononegavirales interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals.

Free Fatty Acid Receptors as New Potential Targets in Colorectal Cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 1397-1404
Author(s):  
Adrian Bartoszek ◽  
Jakub Fichna ◽  
Aleksandra Tarasiuk ◽  
Agata Binienda ◽  
Adam Fabisiak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Current Knowledge ◽  
Developed Countries ◽  
Future Directions ◽  
Screening Programs ◽  
Pharmacological Targets ◽  
The Family ◽  
Free Fatty Acid Receptors

Colorectal cancer (CRC) is one of the most common cancers worldwide. In developed countries, its mortality remains high, yet the prevalence has established owing to effective screening programs; however due to the westernization of lifestyle, the incidences in many other countries have increased. Although the treatment of CRC has improved in the last few years, the side effects of these approaches cannot be neglected. Recently, members of the family of free fatty acid receptors (FFARs) have become attractive pharmacological targets in many diseases, including asthma; studies also point to their role in carcinogenesis. Here, we discuss current knowledge and future directions in FFAR research related to CRC. Contradictory results of FFARs modulation may derive from the pleiotropic effects of FFAR ligands, receptor distribution and different signal transduction. Hence, we indicate directions of further studies to fully use the potential of FFARs in CRC.

Alcohol Consumption and Risk of Uterine Fibroids

2020 ◽  
Vol 20 (4) ◽  
pp. 247-258 ◽  
Author(s):  
Hajra Takala ◽  
Qiwei Yang ◽  
Ahmed M. Abd El Razek ◽  
Mohamed Ali ◽  
Ayman Al-Hendy
Keyword(s):  
Alcohol Consumption ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Legal Status ◽  
Current Knowledge ◽  
Uterine Fibroids ◽  
Future Directions ◽  
Working Adults ◽  
The Us ◽  
Alcohol Related Problems

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well.

scholarly journals Current Knowledge and Future Directions for Improving Subsoiling Quality and Reducing Energy Consumption in Conservation Fields

Agriculture ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 575
Author(s):  
Shangyi Lou ◽  
Jin He ◽  
Hongwen Li ◽  
Qingjie Wang ◽  
Caiyun Lu ◽  
...  
Keyword(s):  
Energy Consumption ◽  
Cover Crops ◽  
Current Knowledge ◽  
High Energy ◽  
Field Application ◽  
Research Progress ◽  
Monitoring And Control ◽  
Future Directions ◽  
Tillage Depth ◽  
And Control

Subsoiling has been acknowledged worldwide to break compacted hardpan, improve soil permeability and water storage capacity, and promote topsoil deepening and root growth. However, there exist certain factors which limit the wide in-field application of subsoiling machines. Of these factors, the main two are poor subsoiling quality and high energy consumption, especially the undesired tillage depth obtained in the field with cover crops. Based on the analysis of global adoption and benefits of subsoiling technology, and application status of subsoiling machines, this article reviewed the research methods, technical characteristics, and developing trends in five key aspects, including subsoiling shovel design, anti-drag technologies, technologies of tillage depth detection and control, and research on soil mechanical interaction. Combined with the research progress and application requirements of subsoiling machines across the globe, current problems and technical difficulties were analyzed and summarized. Aiming to solve these problems, improve subsoiling quality, and reduce energy consumption, this article proposed future directions for the development of subsoiling machines, including optimizing the soil model in computer simulation, strengthening research on the subsoiling mechanism and comprehensive effect, developing new tillage depth monitoring and control systems, and improving wear-resisting properties of subsoiling shovels.

scholarly journals Fusarium basal rot: profile of an increasingly important disease in Allium spp.

2021 ◽  
Author(s):  
Dung Le ◽  
Kris Audenaert ◽  
Geert Haesaert
Keyword(s):  
Disease Management ◽  
Cultural Practices ◽  
Current Knowledge ◽  
Management Strategies ◽  
Future Directions ◽  
Basal Rot ◽  
Major Constraint ◽  
Fusarium Basal Rot ◽  
Chemical Pesticides ◽  
Important Disease

AbstractFusarium basal rot (FBR) is a soil-borne disease that affects Allium species worldwide. Although FBR has long been recognized as a major constraint to the production of economically important Allium species, information that could support disease management remains scattered. In this review, the current knowledge on the causal agents, symptomology and epidemiology, impact, and management strategies of FBR is synthesized. We highlight that FPR is associated with different complexes of several Fusarium species, of which Fusarium oxysporum and F. proliferatum are the most prevalent. These pathogenic complexes vary in composition and virulence, depending on sites and hosts, which can be challenging for disease management. Research to improve disease management using chemical pesticides, resistance cultivars, biocontrol agents, and cultural practices has achieved both promising results and limitations. Finally, research needs and future directions are proposed for the development of effective FBR management strategies.

scholarly journals Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 723
Author(s):  
Hafid Ait-Oufella ◽  
Jean-Rémi Lavillegrand ◽  
Alain Tedgui
Keyword(s):  
T Cell ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Therapeutic Approaches ◽  
Coronary Patients ◽  
Cell Subpopulations ◽  
Atherosclerotic Process ◽  
T Cell Subpopulations ◽  
Disease Analysis

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke
Keyword(s):  
Current Knowledge ◽  
Future Research ◽  
Transcriptional Level ◽  
Cellular Functions ◽  
Multiple Functions ◽  
Open Questions ◽  
G Quadruplex ◽  
Cellular Pathways ◽  
Nucleic Acid Structures ◽  
Dependent Processes

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

scholarly journals The Fourth IOCDC

CNS Spectrums ◽  
2000 ◽  
Vol 5 (S4) ◽  
pp. 4-4
Author(s):  
Eric Hollander ◽  
Joseph Zohar ◽  
Donatella Marazziti
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Current Knowledge ◽  
Active Role ◽  
Cortical Inhibition ◽  
Obsessive Compulsive ◽  
Future Directions ◽  
Compulsive Disorder ◽  
Ablative Surgery

The Fourth International Obsessive Compulsive Disorder Conference (IOCDC) was held February 10–12, 2000, on the beautiful island of St. Thomas. The IOCDC is an annual meeting which brings together the world's leading experts in obsessive-compulsive disorder (OCD) and related disorders in a small workshop setting to present recent research advances, discuss gaps in our current knowledge, and plan or international approaches that address these knowledge gaps. The IOCDC meetings have been held on islands on both sides of the Atlantic—Capri, Guadeloupe, Madeira, and now St. Thomas.The International Organizing Committee consists of Eric Hollander, MD (USA), Joseph Zohar, MD (Israel), and Donatella Marazziti, MD (Italy). The proceedings are generously supported by an unrestricted educational grant from Solvay Pharmaceuticals Inc. and Solvay Pharmaceuticals, and we would like to acknowledge the very important contributions of Chantal Vekens and Mary Blangiardo of Solvay. Also, an mportant part of the success of these meetings stems from the very active role of the chairpersons and cochairpersons of the workshops who lead the discussions, who synthesize the future directions and prepare the manuscripts that result from these discussions that appear in this academic supplement.The meeting led off with a state-of-the-art plenary address by Mark George, MD (USA), describing how new methods of brain stimulation are improving research and therapy in OCD and promise to revolutionize neuropsychiatric research and herapy over the next decade. He describes how transcranial magnetic stimulation (TMS) is used to test the circuits in OCD and test electrophysiologic evaluations of cortical inhibition n OCD. Newer techniques that are less invasive than ablative surgery and appear promising in OCD therapy include vagus nerve stimulation and deep brain stimulation.

scholarly journals Sleep Disorders in Adults with Down Syndrome

2021 ◽  
Vol 10 (14) ◽  
pp. 3012
Author(s):  
Sandra Giménez ◽  
Miren Altuna ◽  
Esther Blessing ◽  
Ricardo M. Osorio ◽  
Juan Fortea
Keyword(s):  
Quality Of Life ◽  
Mental Health ◽  
Down Syndrome ◽  
Sleep Disorders ◽  
Negative Impact ◽  
Current Knowledge ◽  
Sleep Disruption ◽  
Physical And Mental Health ◽  
Future Directions

Sleep disorders, despite being very frequent in adults with Down syndrome (DS), are often overlooked due to a lack of awareness by families and physicians and the absence of specific clinical sleep guidelines. Untreated sleep disorders have a negative impact on physical and mental health, behavior, and cognitive performance. Growing evidence suggests that sleep disruption may also accelerate the progression to symptomatic Alzheimer’s disease (AD) in this population. It is therefore imperative to have a better understanding of the sleep disorders associated with DS in order to treat them, and in doing so, improve cognition and quality of life, and prevent related comorbidities. This paper reviews the current knowledge of the main sleep disorders in adults with DS, including evaluation and management. It highlights the existing gaps in knowledge and discusses future directions to achieve earlier diagnosis and better treatment of sleep disorders most frequently found in this population.

scholarly journals Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 757
Author(s):  
João Diogo Dias ◽  
Nazim Sarica ◽  
Christine Neuveut
Keyword(s):  
Hepatitis B ◽  
Nuclear Import ◽  
Current Knowledge ◽  
Hbv Infection ◽  
Health Concern ◽  
Infected People ◽  
Antiviral Therapies ◽  
Improve Liver Function ◽  
Control Virus ◽  
Episomal Dna

Hepatitis B virus (HBV) remains a major public health concern, with more than 250 million chronically infected people who are at high risk of developing liver diseases, including cirrhosis and hepatocellular carcinoma. Although antiviral treatments efficiently control virus replication and improve liver function, they cannot cure HBV infection. Viral persistence is due to the maintenance of the viral circular episomal DNA, called covalently closed circular DNA (cccDNA), in the nuclei of infected cells. cccDNA not only resists antiviral therapies, but also escapes innate antiviral surveillance. This viral DNA intermediate plays a central role in HBV replication, as cccDNA is the template for the transcription of all viral RNAs, including pregenomic RNA (pgRNA), which in turn feeds the formation of cccDNA through a step of reverse transcription. The establishment and/or expression of cccDNA is thus a prime target for the eradication of HBV. In this review, we provide an update on the current knowledge on the initial steps of HBV infection, from the nuclear import of the nucleocapsid to the formation of the cccDNA.

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