scholarly journals Endocytosis: A Turnover Mechanism Controlling Ion Channel Function

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1833
Author(s):  
Irene Estadella ◽  
Oriol Pedrós-Gámez ◽  
Magalí Colomer-Molera ◽  
Manel Bosch ◽  
Alexander Sorkin ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Transmembrane Proteins ◽  
Receptor Activation ◽  
Vital Role ◽  
Rab Proteins ◽  
Cellular Internalization ◽  
Molecular Determinants ◽  
Health And Disease ◽  
Endocytic Pathways

Ion channels (IChs) are transmembrane proteins that selectively drive ions across membranes. The function of IChs partially relies on their abundance and proper location in the cell, fine-tuned by the delicate balance between secretory, endocytic, and degradative pathways. The disruption of this balance is associated with several diseases, such as Liddle’s and long QT syndromes. Because of the vital role of these proteins in human health and disease, knowledge of ICh turnover is essential. Clathrin-dependent and -independent mechanisms have been the primary mechanisms identified with ICh endocytosis and degradation. Several molecular determinants recognized by the cellular internalization machinery have been discovered. Moreover, specific conditions can trigger the endocytosis of many IChs, such as the activation of certain receptors, hypokalemia, and some drugs. Ligand-dependent receptor activation primarily results in the posttranslational modification of IChs and the recruitment of important mediators, such as β-arrestins and ubiquitin ligases. However, endocytosis is not a final fate. Once internalized into endosomes, IChs are either sorted to lysosomes for degradation or recycled back to the plasma membrane. Rab proteins are crucial participants during these turnover steps. In this review, we describe the major ICh endocytic pathways, the signaling inputs triggering ICh internalization, and the key mediators of this essential cellular process.

scholarly journals Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Chiara Fedeli ◽  
Giulia Torriani ◽  
Clara Galan-Navarro ◽  
Marie-Laurence Moraz ◽  
Hector Moreno ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antiviral Therapy ◽  
Posttranslational Modification ◽  
Public Health Problem ◽  
Receptor Activation ◽  
Tissue Tropism ◽  
Lassa Virus ◽  
Highly Pathogenic ◽  
Low Levels

ABSTRACT Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan. Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo . The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates. However, their role in LASV entry is not entirely understood. Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG. To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model. We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using “apoptotic mimicry” in a way similar to that of other enveloped viruses. We further show that Axl-dependent LASV entry requires receptor activation and involves a pathway resembling macropinocytosis. Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor. In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry. In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy. IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa. Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism. The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear. Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification. We found that in the absence of functional DG, Axl can mediate LASV entry via apoptotic mimicry. Productive entry requires virus-induced receptor activation, involves macropinocytosis, and critically depends on LAMP-1. In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry. In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.

scholarly journals The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1679 ◽  
Author(s):  
Tulasi Yadati ◽  
Tom Houben ◽  
Albert Bitorina ◽  
Ronit Shiri-Sverdlov
Keyword(s):  
Vital Role ◽  
Intracellular Protein ◽  
Pathological Conditions ◽  
Wide Range ◽  
Intracellular Protein Degradation ◽  
Health And Disease ◽  
Lysosomal Proteases ◽  
Shed Light ◽  
Physiological Substrates

Cathepsins are the most abundant lysosomal proteases that are mainly found in acidicendo/lysosomal compartments where they play a vital role in intracellular protein degradation,energy metabolism, and immune responses among a host of other functions. The discovery thatcathepsins are secreted and remain functionally active outside of the lysosome has caused a paradigmshift. Contemporary research has unraveled many versatile functions of cathepsins in extralysosomallocations including cytosol and extracellular space. Nevertheless, extracellular cathepsins are majorlyupregulated in pathological states and are implicated in a wide range of diseases including cancerand cardiovascular diseases. Taking advantage of the dierential expression of the cathepsinsduring pathological conditions, much research is focused on using cathepsins as diagnostic markersand therapeutic targets. A tailored therapeutic approach using selective cathepsin inhibitors isconstantly emerging to be safe and ecient. Moreover, recent development of proteomic-basedapproaches for the identification of novel physiological substrates oers a major opportunity tounderstand the mechanism of cathepsin action. In this review, we summarize the available evidenceregarding the role of cathepsins in health and disease, discuss their potential as biomarkers ofdisease progression, and shed light on the potential of extracellular cathepsin inhibitors as safetherapeutic tools.

scholarly journals Vaccine Interactions With the Infant Microbiome: Do They Define Health and Disease?

2020 ◽  
Vol 8 ◽  
Author(s):  
Candice E. Ruck ◽  
Oludare A. Odumade ◽  
Kinga K. Smolen
Keyword(s):  
Precise Determination ◽  
Vital Role ◽  
Therapeutic Interventions ◽  
Research Strategies ◽  
Vaccine Responses ◽  
The Past ◽  
Early Results ◽  
Health And Disease

Over the past decade, there has been a growing awareness of the vital role of the microbiome in the function of the immune system. Recently, several studies have demonstrated a relationship between the composition of the microbiome and the vaccine-specific immune response. As a result of these findings, the administration of probiotics has been proposed as a means of boosting vaccine-specific immunity. Early results have so far been highly inconsistent, with little evidence of sustained benefit. To date, a precise determination of the aspects of the microbiome that impact immunity is still lacking, and the mechanisms of action are also unknown. Further investigations into these questions are necessary to effectively manipulate the microbiome for the purpose of boosting immunity and enhancing vaccine-specific responses in infants. In this review, we summarize recent studies aimed at altering the neonatal gut microbiome to enhance vaccine responses and highlight gaps in knowledge and understanding. We also discuss research strategies aimed at filling these gaps and developing potential therapeutic interventions.

Asiana Airlines Flight 214

2014 ◽  
Vol 4 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Stephanie Chow ◽  
Stephen Yortsos ◽  
Najmedin Meshkati
Keyword(s):  
Human Factors ◽  
Aviation Safety ◽  
Cultural Factors ◽  
Vital Role ◽  
Cultural Issues ◽  
Flight Crew ◽  
Pilot Performance ◽  
Engineering Designs ◽  
Flight Deck

This article focuses on a major human factors–related issue that includes the undeniable role of cultural factors and cockpit automation and their serious impact on flight crew performance, communication, and aviation safety. The report concentrates on the flight crew performance of the Boeing 777–Asiana Airlines Flight 214 accident, by exploring issues concerning mode confusion and autothrottle systems. It also further reviews the vital role of cultural factors in aviation safety and provides a brief overview of past, related accidents. Automation progressions have been created in an attempt to design an error-free flight deck. However, to do that, the pilot must still thoroughly understand every component of the flight deck – most importantly, the automation. Otherwise, if pilots are not completely competent in terms of their automation, the slightest errors can lead to fatal accidents. As seen in the case of Asiana Flight 214, even though engineering designs and pilot training have greatly evolved over the years, there are many cultural, design, and communication factors that affect pilot performance. It is concluded that aviation systems designers, in cooperation with pilots and regulatory bodies, should lead the strategic effort of systematically addressing the serious issues of cockpit automation, human factors, and cultural issues, including their interactions, which will certainly lead to better solutions for safer flights.

Energy Efficiency Analysis in ERA using NFL-BA Algorithm

2020 ◽  
pp. 340-348
Author(s):  
Palky Mehta ◽  
H. L. Sharma
Keyword(s):  
Cluster Head ◽  
Vital Role ◽  
Wireless Sensor ◽  
Energy Usage ◽  
Cluster Heads ◽  
Comparison Results ◽  
Current Scenario ◽  
Energy Efficiency Analysis ◽  
Selection Of

In the current scenario of Wireless Sensor Network (WSN), power consumption is the major issue associated with nodes in WSN. LEACH technique plays a vital role of clustering in WSN and reduces the energy usage effectively. But LEACH has its own limitation in order to search cluster head nodes which are randomly distributed over the network. In this paper, ERA-NFL- BA algorithm is being proposed for selects the cluster heads in WSN. This algorithm help in selection of cluster heads can freely transform from global search to local search. At the end, a comparison has been done with earlier researcher using protocol ERA-NFL, which clearly shown that proposed Algorithm is best suited and from comparison results that ERA-NFL-BA has given better performance.

Tertiary English-majored Students’ Perceptions toward the Role of Pronunciation in English Language Learning and their Practicing Strategies

2020 ◽  
Vol 6 (2) ◽  
pp. 264-279
Keyword(s):  
Language Learning ◽  
English Language ◽  
Vital Role ◽  
English Language Learning ◽  
Structured Interviews ◽  
Efl Learners ◽  
The University

Accurate pronunciation has a vital role in English language learning as it can help learners to avoid misunderstanding in communication. However, EFL learners in many contexts, especially at the University of Phan Thiet, still encounter many difficulties in pronouncing English correctly. Therefore, this study endeavors to explore English-majored students’ perceptions towards the role of pronunciation in English language learning and examine their pronunciation practicing strategies (PPS). It involved 155 English-majored students at the University of Phan Thiet who answered closed-ended questionnaires and 18 English-majored students who participated in semi-structured interviews. The findings revealed that students strongly believed in the important role of pronunciation in English language learning; however, they sometimes employed PPS for their pronunciation improvement. Furthermore, the results showed that participants tended to use naturalistic practicing strategies and formal practicing strategies with sounds, but they overlooked strategies such as asking for help and cooperating with peers. Such findings could contribute further to the understanding of how students perceive the role of pronunciation and their PPS use in the research’s context and other similar ones. Received 10th June 2019; Revised 12th March 2020; Accepted 12th April 2020

The role of Record of Rights (Khatian) in determining title or possession: An overview

IIUC Studies ◽  
2020 ◽  
Vol 15 ◽  
pp. 33-46
Author(s):  
Kalim Ullah
Keyword(s):  
Human Life ◽  
Vital Role ◽  
Critical Element ◽  
Human Beings ◽  
Supportive Evidence ◽  
Land Administration ◽  
Holy Quran ◽  
The Holy Quran ◽  
Religious Systems

Human beings are deeply related to land. Human beings take birth on land, live on land, die on land and mixes with land ultimately. As stated in the holy Quran: ‘We (Allah) created you (human beings) from the soil, we shall make you return to the soil and We shall call you back again from the soil’ (20:55). Human life is surrounded by soil i.e. land. So, land is a highly completed issue of human life involving economic, social, political, cultural and often religious systems. Land administration is thus a critical element and often a pre-condition for peaceful society and sustainable development. In administrating land, Khatian or record of rights plays a vital role to determine the rights and interests of the respective parties as supportive evidence. In this article, discussion is mainly made on the fact that Khatian or record of rights is not a document of title solely but it may be an evidence of title as well as possession. IIUC Studies Vol.15(0) December 2018: 33-46

A Court in Decline? Examining the Regality Court Records of Melrose, Roxburghshire, 1657–84

2020 ◽  
Vol 40 (1) ◽  
pp. 1-16
Author(s):  
Vivienne Dunstan
Keyword(s):  
Seventeenth Century ◽  
Local Community ◽  
Local Population ◽  
Local Area ◽  
Vital Role ◽  
Local Communities ◽  
Court Records ◽  
Seminal Work

McIntyre, in his seminal work on Scottish franchise courts, argues that these courts were in decline in this period, and of little relevance to their local population. 1 But was that really the case? This paper explores that question, using a particularly rich set of local court records. By analysing the functions and significance of one particular court it assesses the role of this one court within its local area, and considers whether it really was in decline at this time, or if it continued to perform a vital role in its local community. The period studied is the mid to late seventeenth century, a period of considerable upheaval in Scottish life, that has attracted considerable attention from scholars, though often less on the experiences of local communities and people.

Risk and Protective Factors in the Life of Youth in Relation to Resilience

2018 ◽  
Vol 52 (1) ◽  
pp. 50-59
Author(s):  
Silvia Barnová ◽  
Viola Tamášová
Keyword(s):  
Social Support ◽  
Protective Factors ◽  
School Psychologists ◽  
Social Environment ◽  
Social Services ◽  
Service Providers ◽  
Vital Role ◽  
Great Role ◽  
Health Service Providers

Abstract Introduction: A certain degree of stress is present in everyone’s life and young people are not an exception. Most of them show a certain degree of resilience and can cope with stressful situations without any difficulties, however there is a group of youth who live in toxic environments and need help. If there is a risk of failure due to the intensity of stressors; external formal and informal support have a great role to play as they have the potential to prevent negative developmental outcomes. Purpose: The authors’ intention was to make a review of available literature on the current issues of resilience research with a focus on the importance of protective factors in young people’s lives – especially when they are exposed to adversity. An emphasis is placed on the vital role of social support to individuals provided by schools as well as social services. Methods: In the presented literature review, multiple formal search methods including hand searching of key journals; electronic searching of journal databases and subject specific websites; reference scanning; and citation tracking were used. Conclusion: Individuals commonly demonstrate some level of resilience, yet most of them are able to deal with stressful situations without any harm. On the other hand, if the adversity is too high, the presence of social support provided by their social environment is important. In this context, good relationships in general and sufficient external protective factors provided by their social environment (schools, school psychologists, institutional social and health service providers) are important.

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