scholarly journals Thioester-Containing Protein-4 Regulates the Drosophila Immune Signaling and Function against the Pathogen Photorhabdus

2016 ◽  
Vol 9 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Upasana Shokal ◽  
Ioannis Eleftherianos
Keyword(s):  
Immune Response ◽  
Photorhabdus Luminescens ◽  
Human Pathogen ◽  
Loss Of Function ◽  
Phenoloxidase Activity ◽  
Microbial Infections ◽  
Immune Pathways ◽  
And Function ◽  
Important Progress

Despite important progress in identifying the molecules that participate in the immune response of Drosophila melanogaster to microbial infections, the involvement of thioester-containing proteins (TEPs) in the antibacterial immunity of the fly is not fully clarified. Previous studies mostly focused on identifying the function of TEP2, TEP3 and TEP6 molecules in the D. melanogaster immune system. Here, we investigated the role of TEP4 in the regulation and function of D. melanogaster host defense against 2 virulent pathogens from the genus Photorhabdus, i.e. the insect pathogenic bacterium Photorhabdus luminescens and the emerging human pathogen P. asymbiotica. We demonstrate that Tep4 is strongly upregulated in adult flies following the injection of Photorhabdus bacteria. We also show that Tep4 loss-of-function mutants are resistant to P. luminescens but not to P. asymbiotica infection. In addition, we find that inactivation of Tep4 results in the upregulation of the Toll and Imd immune pathways, and the downregulation of the Jak/Stat and Jnk pathways upon Photorhabdus infection. We document that loss of Tep4 promotes melanization and phenoloxidase activity in the mutant flies infected with Photorhabdus. Together, these findings generate novel insights into the immune role of TEP4 as a regulator and effector of the D. melanogaster antibacterial immune response.

PIN-FORMED 1 regulates cell fate at the periphery of the shoot apical meristem

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5157-5165 ◽  
Author(s):  
T. Vernoux ◽  
J. Kronenberger ◽  
O. Grandjean ◽  
P. Laufs ◽  
J. Traas
Keyword(s):  
Cell Fate ◽  
Apical Meristem ◽  
Transmembrane Protein ◽  
Loss Of Function ◽  
Hybrid Identity ◽  
Hormone Transport ◽  
Early Markers ◽  
Ideal Tool ◽  
And Function

The process of organ positioning has been addressed, using the pin-formed 1 (pin1) mutant as a tool. PIN1 is a transmembrane protein involved in auxin transport in Arabidopsis. Loss of function severely affects organ initiation, and pin1 mutants are characterised by an inflorescence meristem that does not initiate any flowers, resulting in the formation of a naked inflorescence stem. This phenotype, combined with the proposed role of PIN1 in hormone transport, makes the mutant an ideal tool to study organ formation and phyllotaxis, and here we present a detailed analysis of the molecular modifications at the shoot apex caused by the mutation. We show that meristem structure and function are not severely affected in the mutant. Major alterations, however, are observed at the periphery of the pin1 meristem, where organ initiation should occur. Although two very early markers of organ initiation, LEAFY and AINTEGUMENTA, are expressed at the periphery of the mutant meristem, the cells are not recruited into distinct primordia. Instead a ring-like domain expressing those primordium specific genes is observed around the meristem. This ring-like domain also expresses a boundary marker, CUP-SHAPED COTYLEDON 2, involved in organ separation, showing that the zone at the meristem periphery has a hybrid identity. This implies that PIN1 is not only involved in organ outgrowth, but that it is also necessary for organ separation and positioning. A model is presented in which PIN1 and the local distribution of auxin control phyllotaxis.

scholarly journals VACCINATION TO PROMOTE HEALTH THROUGHOUT LIFE AS A HEALTHY AGING STRATEGY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S211-S211
Author(s):  
Leonard Friedland
Keyword(s):  
Immune Response ◽  
Healthy Aging ◽  
New Technologies ◽  
Older Age ◽  
Target Antigen ◽  
Older Individuals ◽  
Demographic Shift ◽  
Age Related ◽  
Important Progress

Abstract This symposium addresses the role of vaccination to promote healthy aging, the process of developing and maintaining the functional ability that enables wellbeing in older age. Life-span immunization of adults across all age categories can help to reduce morbidity and mortality. Healthy aging is critical for our global society to counter the surge in healthcare costs that is coming as a result of the demographic shift to older age. Immune system function and response to vaccination declines with advancing age. Generating effective immune responses against new infectious disease targets can be difficult in older individuals. Important progress has been made in understanding the mechanisms underlying immunosenescence, the age-related decline of the immune response to infections and vaccinations. Innovative research and the development of new technologies, such as adjuvants, substances that can enhance and shape the immune response to the target antigen(s), has facilitated the development of vaccines specially tailored for adults. This evidence-based approach to the development of innovative vaccines addressing immunosenescence is an important clinically relevant healthy aging strategy to promote health throughout life.

scholarly journals Viperin catalyzes methionine oxidation to promote protein expression and function of helicases

2019 ◽  
Vol 5 (8) ◽  
pp. eaax1031 ◽  
Author(s):  
Lei Bai ◽  
Jiazhen Dong ◽  
Zhenqiu Liu ◽  
Youliang Rao ◽  
Pinghui Feng ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Methionine Oxidation ◽  
Biological Processes ◽  
Loss Of Function ◽  
Rna Helicases ◽  
Dna And Rna ◽  
Biochemical Studies ◽  
The Stability ◽  
And Function

Helicases play pivotal roles in fundamental biological processes, and posttranslational modifications regulate the localization, function, and stability of helicases. Here, we report that methionine oxidation of representative helicases, including DNA and RNA helicases of viral (ORF44 of KSHV) and cellular (MCM7 and RIG-I) origin, promotes their expression and functions. Cellular viperin, a major antiviral interferon-stimulated gene whose functions beyond host defense remain largely unknown, catalyzes the methionine oxidation of these helicases. Moreover, biochemical studies entailing loss-of-function mutations of helicases and a pharmacological inhibitor interfering with lipid metabolism and, hence, decreasing viperin activity indicate that methionine oxidation potently increases the stability and enzyme activity of these helicases that are critical for DNA replication and immune activation. Our work uncovers a pivotal role of viperin in catalyzing the methionine oxidation of helicases that are implicated in diverse fundamental biological processes.

scholarly journals Role of Cytokines and Toll-Like Receptors in the Immunopathogenesis of Guillain-Barré Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kishan Kumar Nyati ◽  
Kashi Nath Prasad
Keyword(s):  
Immune Response ◽  
Single Agent ◽  
Host Factors ◽  
Guillain Barre Syndrome ◽  
Toll Like Receptors ◽  
Guillain Barré Syndrome ◽  
Microbial Infections ◽  
Inflammatory Processes ◽  
Guillain Barré

Guillain-Barré syndrome (GBS) is an autoimmune disease of the peripheral nervous system, mostly triggered by an aberrant immune response to an infectious pathogen. Although several infections have been implicated in the pathogenesis of GBS, not all such infected individuals develop this disease. Moreover, infection with a single agent might also lead to different subtypes of GBS emphasizing the role of host factors in the development of GBS. The host factors regulate a broad range of inflammatory processes that are involved in the pathogenesis of autoimmune diseases including GBS. Evidences suggest that systemically and locally released cytokines and their involvement in immune-mediated demyelination and axonal damage of peripheral nerves are important in the pathogenesis of GBS. Toll-like receptors (TLRs) link innate and adaptive immunity through transcription of several proinflammatory cytokines. TLR genes may increase susceptibility to microbial infections; an attenuated immune response towards antigen and downregulation of cytokines occurs due to mutation in the gene. Herein, we discuss the crucial role of host factors such as cytokines and TLRs that activate the immune response and are involved in the pathogenesis of the disease.

scholarly journals Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity

2020 ◽  
Vol 7 ◽  
Author(s):  
José João Name ◽  
Ana Carolina Remondi Souza ◽  
Andrea Rodrigues Vasconcelos ◽  
Pietra Sacramento Prado ◽  
Carolina Parga Martins Pereira
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Adequate Intake ◽  
High Demand ◽  
Comprehensive Overview ◽  
Disease Prognosis ◽  
Mucous Membranes ◽  
And Function

Some nutrients play key roles in maintaining the integrity and function of the immune system, presenting synergistic actions in steps determinant for the immune response. Among these elements, zinc and vitamins C and D stand out for having immunomodulatory functions and for playing roles in preserving physical tissue barriers. Considering the COVID-19 pandemic, nutrients that can optimize the immune system to prevent or lower the risk of severe progression and prognosis of this viral infection become relevant. Thus, the present review aims to provide a comprehensive overview of the roles of zinc and vitamins C and D in the immune response to viral infections, focusing on the synergistic action of these nutrients in the maintenance of physical tissue barriers, such as the skin and mucous membranes. The evidence found in the literature shows that deficiency of one or more of these three elements compromises the immune response, making an individual more vulnerable to viral infections and to a worse disease prognosis. Thus, during the COVID-19 pandemic, the adequate intake of zinc and vitamins C and D may represent a promising pharmacological tool due to the high demand for these nutrients in the case of contact with the virus and onset of the inflammatory process. Ongoing clinical trials will help to clarify the role of these nutrients for COVID-19 management.

scholarly journals Regulatory Roles of Six-Transmembrane Epithelial Antigen of the Prostate Family Members in the Occurrence and Development of Malignant Tumors

2021 ◽  
Vol 9 ◽  
Author(s):  
Wen-Jia Chen ◽  
Hua-Tao Wu ◽  
Chun-Lan Li ◽  
Yi-Ke Lin ◽  
Ze-Xuan Fang ◽  
...  
Keyword(s):  
Immune Response ◽  
Theoretical Basis ◽  
Malignant Tumors ◽  
Expression Patterns ◽  
Molecular Transport ◽  
Therapeutic Resistance ◽  
Biological Processes ◽  
Different Types ◽  
And Function

The human six-transmembrane epithelial antigen of the prostate (STEAP) proteins, which include STEAP1–4 and atypical STEAP1B, contain six transmembrane domains and are located in the cell membrane. STEAPs are considered archaeal metal oxidoreductases, based on their heme groups and F420H2:NADP+ oxidoreductase (FNO)-like structures, and play an important role in cell metal metabolism. Interestingly, STEAPs not only participate in biological processes, such as molecular transport, cell cycling, immune response, and intracellular and extracellular activities, but also are closely related to the occurrence and development of several diseases, especially malignant tumors. Up to now, the expression patterns of STEAPs have been found to be diverse in different types of tumors, with controversial participation in different aspects of malignancy, such as cell proliferation, migration, invasion, apoptosis, and therapeutic resistance. It is clinically important to explore the potential roles of STEAPs as new immunotherapeutic targets for the treatment of different malignant tumors. Therefore, this review focuses on the molecular mechanism and function of STEAPs in the occurrence and development of different cancers in order to understand the role of STEAPs in cancer and provide a new theoretical basis for the treatment of diverse cancers.

scholarly journals Targeting the Microtubule EB1-CLASP2 Complex Modulates Na V 1.5 at Intercalated Discs

2021 ◽  
Author(s):  
Gerard A Marchal ◽  
Mariam Jouni ◽  
David Y Chiang ◽  
Marta Pérez-Hernández Duran ◽  
Svitlana Podliesna ◽  
...  
Keyword(s):  
Sodium Current ◽  
Induced Pluripotent Stem Cell ◽  
Loss Of Function ◽  
Whole Cell ◽  
Intercalated Discs ◽  
Cardiac Sodium Channel ◽  
Optical Reconstruction ◽  
Induced Pluripotent ◽  
And Function

Rationale: Loss-of-function of the cardiac sodium channel Na V 1.5 causes conduction slowing and arrhythmias. Na V 1.5 is differentially distributed within subcellular domains of cardiomyocytes, with sodium current (I Na ) being enriched at the intercalated discs (ID). Various pathophysiological conditions associated with lethal arrhythmias display ID-specific I Na reduction, but the mechanisms underlying microdomain-specific targeting of Na V 1.5 remain largely unknown. Objective: To investigate the role of the microtubule (MT) plus-end tracking proteins end binding protein 1 (EB1) and CLIP-associated protein 2 (CLASP2) in mediating Na V 1.5 trafficking and subcellular distribution in cardiomyocytes. Methods and Results: EB1 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) resulted in enhanced whole-cell I Na , increased action potential (AP) upstroke velocity (V max ), and enhanced Na V 1.5 localization at the plasma membrane as detected by multi-color stochastic optical reconstruction microscopy (STORM). Fluorescence recovery after photobleaching (FRAP) experiments in HEK293A cells demonstrated that EB1 overexpression promoted Na V 1.5 forward trafficking. Knockout of MAPRE1 in hiPSC-CMs led to reduced whole-cell I Na , decreased V max and AP duration (APD) prolongation. Similarly, acute knockout of the MAPRE1 homolog in zebrafish (mapre1b) resulted in decreased ventricular conduction velocity and V max as well as increased APD. STORM imaging and macropatch I Na measurements showed that subacute treatment (2-3 hours) with SB216763 (SB2), a GSK3β inhibitor known to modulate CLASP2-EB1 interaction, reduced GSK3β localization and increased Na V 1.5 and I Na preferentially at the ID region of wild type murine ventricular cardiomyocytes. By contrast, SB2 did not affect whole cell I Na or Na V 1.5 localization in cardiomyocytes from Clasp2-deficient mice, uncovering the crucial role of CLASP2 in SB2-mediated modulation of NaV1.5 at the ID. Conclusions: Our findings demonstrate the modulatory effect of the MT plus-end tracking protein EB1 on Na V 1.5 trafficking and function, and identify the EB1-CLASP2 complex as a target for preferential modulation of I Na within the ID region of cardiomyocytes.

scholarly journals Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens

2011 ◽  
Vol 79 (8) ◽  
pp. 2964-2973 ◽  
Author(s):  
Joshua C. Cyktor ◽  
Joanne Turner
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Interleukin 10 ◽  
Parasitic Infections ◽  
Intracellular Pathogens ◽  
Effective Immune Response ◽  
Infection Models ◽  
And Function

ABSTRACTThe generation of an effective immune response against an infection while also limiting tissue damage requires a delicate balance between pro- and anti-inflammatory responses. Interleukin-10 (IL-10) has potent immunosuppressive effects and is essential for regulation of immune responses. However, the immunosuppressive properties of IL-10 can also be exploited by pathogens to facilitate their own survival. In this minireview, we discuss the role of IL-10 in modulating intracellular bacterial, fungal, and parasitic infections. Using information from several different infection models, we bring together and highlight some common pathways for IL-10 regulation and function that cannot be fully appreciated by studies of a single pathogen.

Diversity and function of soil microbes on montane gradients: the state of knowledge in a changing world

2020 ◽  
Vol 96 (9) ◽  
Author(s):  
Caitlin I Looby ◽  
Patrick H Martin
Keyword(s):  
Microbial Diversity ◽  
Microbial Communities ◽  
Functional Groups ◽  
Soil Microbes ◽  
Diversity Indices ◽  
Saprotrophic Fungi ◽  
Microbial Biogeography ◽  
And Function ◽  
Important Progress

ABSTRACT Mountains have a long history in the study of diversity. Like macroscopic taxa, soil microbes are hypothesized to be strongly structured by montane gradients, and recently there has been important progress in understanding how microbes are shaped by these conditions. Here, we summarize this literature and synthesize patterns of microbial diversity on mountains. Unlike flora and fauna that often display a mid-elevation peak in diversity, we found a decline (34% of the time) or no trend (33%) in total microbial diversity with increasing elevation. Diversity of functional groups also varied with elevation (e.g. saprotrophic fungi declined 83% of the time). Most studies (82%) found that climate and soils (especially pH) were the primary mechanisms driving shifts in composition, and drivers differed across taxa—fungi were mostly determined by climate, while bacteria (48%) and archaea (71%) were structured primarily by soils. We hypothesize that the central role of soils—which can vary independently of other abiotic and geographic gradients—in structuring microbial communities weakens diversity patterns expected on montane gradients. Moving forward, we need improved cross-study comparability of microbial diversity indices (i.e. standardizing sequencing) and more geographic replication using experiments to broaden our knowledge of microbial biogeography on global gradients.

scholarly journals Endothelial Aldehyde Dehydrogenase 2 as a Target to Maintain Vascular Wellness and Function in Ageing

Biomedicines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 4 ◽  
Author(s):  
Ginevra Nannelli ◽  
Marina Ziche ◽  
Sandra Donnini ◽  
Lucia Morbidelli
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Low Grade ◽  
Loss Of Function ◽  
Aldehyde Dehydrogenase 2 ◽  
Main Determinants ◽  
And Function ◽  
Low Grade Inflammation

Endothelial cells are the main determinants of vascular function, since their dysfunction in response to a series of cardiovascular risk factors is responsible for disease progression and further consequences. Endothelial dysfunction, if not resolved, further aggravates the oxidative status and vessel wall inflammation, thus igniting a vicious cycle. We have furthermore to consider the physiological manifestation of vascular dysfunction and chronic low-grade inflammation during ageing, also known as inflammageing. Based on these considerations, knowledge of the molecular mechanism(s) responsible for endothelial loss-of-function can be pivotal to identify novel targets of intervention with the aim of maintaining endothelial wellness and vessel trophism and function. In this review we have examined the role of the detoxifying enzyme aldehyde dehydrogenase 2 (ALDH2) in the maintenance of endothelial function. Its impairment indeed is associated with oxidative stress and ageing, and in the development of atherosclerosis and neurodegenerative diseases. Strategies to improve its expression and activity may be beneficial in these largely diffused disorders.

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