scholarly journals The Dynamic SecYEG Translocon

2021 ◽  
Vol 8 ◽  
Author(s):  
Julia Oswald ◽  
Robert Njenga ◽  
Ana Natriashvili ◽  
Pinku Sarmah ◽  
Hans-Georg Koch
Keyword(s):  
Protein Transport ◽  
Current Knowledge ◽  
Model Organism ◽  
Protein Composition ◽  
Protein Homeostasis ◽  
Transport Mechanisms ◽  
Multiple Partner ◽  
Outer Membranes ◽  
Recent Developments ◽  
Partner Proteins

The spatial and temporal coordination of protein transport is an essential cornerstone of the bacterial adaptation to different environmental conditions. By adjusting the protein composition of extra-cytosolic compartments, like the inner and outer membranes or the periplasmic space, protein transport mechanisms help shaping protein homeostasis in response to various metabolic cues. The universally conserved SecYEG translocon acts at the center of bacterial protein transport and mediates the translocation of newly synthesized proteins into and across the cytoplasmic membrane. The ability of the SecYEG translocon to transport an enormous variety of different substrates is in part determined by its ability to interact with multiple targeting factors, chaperones and accessory proteins. These interactions are crucial for the assisted passage of newly synthesized proteins from the cytosol into the different bacterial compartments. In this review, we summarize the current knowledge about SecYEG-mediated protein transport, primarily in the model organism Escherichia coli, and describe the dynamic interaction of the SecYEG translocon with its multiple partner proteins. We furthermore highlight how protein transport is regulated and explore recent developments in using the SecYEG translocon as an antimicrobial target.

Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells

2017 ◽  
Vol 8 (2) ◽  
pp. 93-104 ◽  
Author(s):  
Myriam Lazard ◽  
Marc Dauplais ◽  
Sylvain Blanquet ◽  
Pierre Plateau
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Model Organism ◽  
Protein Homeostasis ◽  
Recent Advances ◽  
Inorganic Selenium ◽  
Protein Thiols ◽  
Selenoamino Acids ◽  
High Doses

AbstractSelenium is an essential trace element due to its incorporation into selenoproteins with important biological functions. However, at high doses it is toxic. Selenium toxicity is generally attributed to the induction of oxidative stress. However, it has become apparent that the mode of action of seleno-compounds varies, depending on its chemical form and speciation. Recent studies in various eukaryotic systems, in particular the model organism Saccharomyces cerevisiae, provide new insights on the cytotoxic mechanisms of selenomethionine and selenocysteine. This review first summarizes current knowledge on reactive oxygen species (ROS)-induced genotoxicity of inorganic selenium species. Then, we discuss recent advances on our understanding of the molecular mechanisms of selenocysteine and selenomethionine cytotoxicity. We present evidences indicating that both oxidative stress and ROS-independent mechanisms contribute to selenoamino acids cytotoxicity. These latter mechanisms include disruption of protein homeostasis by selenocysteine misincorporation in proteins and/or reaction of selenols with protein thiols.

scholarly journals The Multiple Functions of Rho GTPases in Fission Yeasts

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1422
Author(s):  
Jero Vicente-Soler ◽  
Teresa Soto ◽  
Alejandro Franco ◽  
José Cansado ◽  
Marisa Madrid
Keyword(s):  
Fission Yeast ◽  
Rho Gtpases ◽  
Current Knowledge ◽  
Model Organism ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors ◽  
Physiological Processes ◽  
Evolutionary Changes ◽  
Rho Family

The Rho family of GTPases represents highly conserved molecular switches involved in a plethora of physiological processes. Fission yeast Schizosaccharomyces pombe has become a fundamental model organism to study the functions of Rho GTPases over the past few decades. In recent years, another fission yeast species, Schizosaccharomyces japonicus, has come into focus offering insight into evolutionary changes within the genus. Both fission yeasts contain only six Rho-type GTPases that are spatiotemporally controlled by multiple guanine–nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and whose intricate regulation in response to external cues is starting to be uncovered. In the present review, we will outline and discuss the current knowledge and recent advances on how the fission yeasts Rho family GTPases regulate essential physiological processes such as morphogenesis and polarity, cellular integrity, cytokinesis and cellular differentiation.

Ribosomally synthesized peptides, foreground players in microbial interactions: recent developments and unanswered questions

2021 ◽  
Author(s):  
Sylvie Rebuffat
Keyword(s):  
Current Knowledge ◽  
Complex Interaction ◽  
Microbial Interactions ◽  
Interaction Networks ◽  
Recent Developments

This review unveils current knowledge on the complex interaction networks involving ribosomally synthesized peptides, either modified or not, being at play in microbial interactions and symbioses.

scholarly journals T regulatory cells in childhood arthritis – novel insights

2013 ◽  
Vol 15 ◽  
Author(s):  
Anne M. Pesenacker ◽  
Lucy R. Wedderburn
Keyword(s):  
T Cells ◽  
Juvenile Idiopathic Arthritis ◽  
Regulatory T Cells ◽  
T Regulatory Cells ◽  
Current Knowledge ◽  
Autoimmune Arthritis ◽  
Regulatory Cells ◽  
New Developments ◽  
Childhood Arthritis ◽  
Recent Developments

In recent years, there have been many new developments in the field of regulatory T cells (Treg), challenging the consensus on their behaviour, classification and role(s) in disease. The role Treg might play in autoimmune disease appears to be more complex than previously thought. Here, we discuss the current knowledge of regulatory T cells through animal and human research and illustrate the recent developments in childhood autoimmune arthritis (juvenile idiopathic arthritis (JIA)). Furthermore, this review summarises our understanding of the fields and assesses current and future implications for Treg in the treatment of JIA.

scholarly journals More actors in ammonia absorption by the thick ascending limb

2012 ◽  
Vol 302 (3) ◽  
pp. F293-F297 ◽  
Author(s):  
Pascal Houillier ◽  
Soline Bourgeois
Keyword(s):  
Current Knowledge ◽  
Collecting Duct ◽  
Ammonia Excretion ◽  
Hydrogen Ion ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Transport Mechanisms ◽  
Sodium Hydrogen ◽  
Ammonia Transport ◽  
Ammonia Absorption

This review will briefly summarize current knowledge on the basolateral ammonia transport mechanisms in the thick ascending limb (TAL) of the loop of Henle. This segment transports ammonia against a concentration gradient and is responsible for the accumulation of ammonia in the medullary interstitium, which, in turn, favors ammonia secretion across the collecting duct. Experimental data indicate that the sodium/hydrogen ion exchanger isoform 4 (NHE4; Scl9a4) is a sodium/ammonia exchanger and plays a major role in this process. Disruption of murine NHE4 leads to metabolic acidosis with inappropriate urinary ammonia excretion and decreases the ability of the TAL to absorb ammonia and to build the corticopapillary ammonia gradient. However, NHE4 does not account for the entirety of ammonia absorption by the TAL, indicating that, at least, one more transporter is involved.

The Salivary miRNome: A Promising Biomarker of Disease

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sara Tomei ◽  
Harshitha Shobha Manjunath ◽  
Selvasankar Murugesan ◽  
Souhaila Al Khodor
Keyword(s):  
Current Knowledge ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Circulating Mirnas ◽  
Disease Pathogenesis ◽  
Technical Aspects ◽  
Recent Developments ◽  
Health And Disease ◽  
Non Coding Rnas

: MicroRNAs (miRNAs) are non-coding RNAs ranging from 18-24 nucleotides also known to regulate the human genome mainly at the post-transcriptional level. MiRNAs were shown to play an important role in most biological processes such as apoptosis and in the pathogenesis of many diseases such as cardiovascular diseases and cancer. Recent developments of advanced molecular high-throughput technologies have enhanced our knowledge of miRNAs. MiRNAs can now be discovered, interrogated, and quantified in various body fluids, and hence can serve as diagnostic and therapeutic markers for many diseases. While most studies use blood as a sample source to measure circulating miRNAs as possible biomarkers for disease pathogenesis, fewer studies have assessed the role of salivary miRNAs in health and disease. This review aims at providing an overview of the current knowledge of the salivary miRNome, addressing the technical aspects of saliva sampling and highlighting the applicability of miRNA screening to clinical practice.

Cloud Crime and Fraud

2019 ◽  
pp. 1159-1175
Author(s):  
Nimisha Singh
Keyword(s):  
Cloud Computing ◽  
Law Enforcement ◽  
Current Knowledge ◽  
Organizational Level ◽  
Law Enforcement Agencies ◽  
Policy Makers ◽  
Security Breaches ◽  
Recent Developments ◽  
Standards And Guidelines ◽  
Developed Nations

Changing trends in IT industry are opening new avenues. With the scalability, flexibility, and economic advantage offered by cloud computing, more and more organizations are moving towards cloud for their applications. With all the benefits of cloud computing, it poses a danger of digital crime and security breaches. These challenges are compounded by the fact that cybercrime and the transgressors transcend geographical boundaries while the law enforcement does not. This paper tries to focus on how cloud computing is rising to the challenges thrown in from cyber space and recent developments to avoid and mitigate cloud fraud and abuse. Taking counter measures at organizational level, will alleviate and up to an extent eliminate security breaches. With current knowledge on policy and standards adopted by developed nations, the policy makers and law enforcement agencies in developing countries can work towards formulating standards and guidelines for awareness on threats, vulnerabilities and effectiveness of security controls to respond to risk.

Cloud Crime and Fraud

2018 ◽  
pp. 1334-1350
Author(s):  
Nimisha Singh
Keyword(s):  
Cloud Computing ◽  
Law Enforcement ◽  
Current Knowledge ◽  
Organizational Level ◽  
Law Enforcement Agencies ◽  
Policy Makers ◽  
Security Breaches ◽  
Recent Developments ◽  
Standards And Guidelines ◽  
Developed Nations

Changing trends in IT industry are opening new avenues. With the scalability, flexibility, and economic advantage offered by cloud computing, more and more organizations are moving towards cloud for their applications. With all the benefits of cloud computing, it poses a danger of digital crime and security breaches. These challenges are compounded by the fact that cybercrime and the transgressors transcend geographical boundaries while the law enforcement does not. This paper tries to focus on how cloud computing is rising to the challenges thrown in from cyber space and recent developments to avoid and mitigate cloud fraud and abuse. Taking counter measures at organizational level, will alleviate and up to an extent eliminate security breaches. With current knowledge on policy and standards adopted by developed nations, the policy makers and law enforcement agencies in developing countries can work towards formulating standards and guidelines for awareness on threats, vulnerabilities and effectiveness of security controls to respond to risk.

scholarly journals GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

2020 ◽  
Vol 21 (17) ◽  
pp. 6213
Author(s):  
Andrés Felipe Leal ◽  
Eliana Benincore-Flórez ◽  
Daniela Solano-Galarza ◽  
Rafael Guillermo Garzón Jaramillo ◽  
Olga Yaneth Echeverri-Peña ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Transport ◽  
Current Knowledge ◽  
Sandhoff Disease ◽  
Substrate Reduction Therapy ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Central Nervous System Dysfunction ◽  
Gm2 Gangliosidoses

GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay–Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood–brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g., intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidoses, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.

scholarly journals Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

Membranes ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 181 ◽  
Author(s):  
Carole Ayoub Moubareck
Keyword(s):  
Current Knowledge ◽  
Acquired Resistance ◽  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Antibiotic Development ◽  
Outer Membranes ◽  
Initial Discovery ◽  
Clinical Interest

Following their initial discovery in the 1940s, polymyxin antibiotics fell into disfavor due to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the rising global prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria have both rejuvenated clinical interest in these polypeptide antibiotics. Parallel to the revival of their use, investigations into the mechanisms of action and resistance to polymyxins have intensified. With an initial known effect on biological membranes, research has uncovered the detailed molecular and chemical interactions that polymyxins have with Gram-negative outer membranes and lipopolysaccharide structure. In addition, genetic and epidemiological studies have revealed the basis of resistance to these agents. Nowadays, resistance to polymyxins in MDR Gram-negative pathogens is well elucidated, with chromosomal as well as plasmid-encoded, transferrable pathways. The aims of the current review are to highlight the important chemical, microbiological, and pharmacological properties of polymyxins, to discuss their mechanistic effects on bacterial membranes, and to revise the current knowledge about Gram-negative acquired resistance to these agents. Finally, recent research, directed towards new perspectives for improving these old agents utilized in the 21st century, to combat drug-resistant pathogens, is summarized.

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