keyword
https://read.qxmd.com/read/36854760/clic-and-membrane-wound-repair-pathways-enable-pandemic-norovirus-entry-and-infection
#21
JOURNAL ARTICLE
B Vijayalakshmi Ayyar, Khalil Ettayebi, Wilhelm Salmen, Umesh C Karandikar, Frederick H Neill, Victoria R Tenge, Sue E Crawford, Erhard Bieberich, B V Venkataram Prasad, Robert L Atmar, Mary K Estes
Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways...
February 28, 2023: Nature Communications
https://read.qxmd.com/read/36833954/impact-of-covid-19-pandemic-on-caregivers-of-people-with-an-intellectual-disability-in-comparison-to-carers-of-those-with-other-disabilities-and-with-mental-health-issues-a-multicountry-study
#22
JOURNAL ARTICLE
Andrew Wormald, Eimear McGlinchey, Maureen D'Eath, Iracema Leroi, Brian Lawlor, Philip McCallion, Mary McCarron, Roger O'Sullivan, Yaohua Chen
Carers supporting people with an intellectual disability often rely on others to manage the burden of care. This research aims to compare the differences between carer groups and understand the predictors of loneliness changes and burden for carers of people with an intellectual disability. Data from the international CLIC study were analysed. In total, 3930 carers responded from four groups; people who care for those with mental health difficulties ( n = 491), dementia ( n = 1888), physical disabilities ( n = 1147), and Intellectual disabilities ( n = 404)...
February 13, 2023: International Journal of Environmental Research and Public Health
https://read.qxmd.com/read/36821411/sterol-structural-features-impact-on-the-spontaneous-membrane-insertion-of-clic1-into-artificial-lipid-membranes
#23
JOURNAL ARTICLE
Khondker R Hossain, Daniel R Turkewitz, Stephen A Holt, Anton P Le Brun, Stella M Valenzuela
Background : A membrane protein interaction with lipids shows distinct specificity in terms of the sterol structure. The structure of the sterol's polar headgroup, steroidal rings, and aliphatic side chains have all been shown to influence protein membrane interactions, including the initial binding and subsequent oligomerization to form functional channels. Previous studies have provided some insights into the regulatory role that cholesterol plays in the spontaneous membrane insertion of the chloride intracellular ion channel protein, CLIC1...
February 23, 2023: Langmuir: the ACS Journal of Surfaces and Colloids
https://read.qxmd.com/read/36758493/automated-method-using-direct-immersion-solid-phase-microextraction-and-on-fiber-derivatization-coupled-with-comprehensive-two-dimensional-gas-chromatography-high-resolution-mass-spectrometry-for-profiling-naphthenic-acids-in-produced-water
#24
JOURNAL ARTICLE
Juliana Crucello, Naiara Mfm Sampaio, Iris Medeiros Junior, Rogerio Mesquita Carvalho, Emanuela Gionfriddo, Philip J Marriott, Leandro Wang Hantao
Naphthenic acids (NAs) are naturally occurring organic acids in petroleum and are found in waste waters generated during oil production (produced water, PW). Profiling this class of compounds is important due to flow assurance during oil exploration. Compositional analysis of PW is also relevant for waste treatment to reduce negative impacts on the environment. Here, comprehensive two-dimensional gas chromatography coupled with high-resolution mass spectrometry (GC×GC-HRMS) was applied as an ideal platform for qualitative analysis of NAs by combining the high peak capacity of the composite system with automated scripts for group-type identification based on accurate mass measurements and fragmentation patterns...
February 1, 2023: Journal of Chromatography. A
https://read.qxmd.com/read/36659928/structure-based-discovery-and-in-vitro-validation-of-inhibitors-of-chloride-intracellular-channel-4-protein
#25
JOURNAL ARTICLE
Fisayo Olotu, Encarnacion Medina-Carmona, Angela Serrano-Sanchez, Felipe Ossa, Abdelaziz El-Hamdaoui, Özlem Tastan Bishop, Jose L Ortega-Roldan, Vahitha B Abdul-Salam
The use of computer-aided methods have continued to propel accelerated drug discovery across various disease models, interestingly allowing the specific inhibition of pathogenic targets. Chloride Intracellular Channel Protein 4 (CLIC4) is a novel class of intracellular ion channel highly implicated in tumor and vascular biology. It regulates cell proliferation, apoptosis and angiogenesis; and is involved in multiple pathologic signaling pathways. Absence of specific inhibitors however impedes its advancement to translational research...
2023: Computational and Structural Biotechnology Journal
https://read.qxmd.com/read/36398726/a-metazoan-specific-c-terminal-motif-in-exc-4-and-g%C3%AE-rho-rac-signaling-regulate-cell-outgrowth-during-tubulogenesis-in-c-elegans
#26
JOURNAL ARTICLE
Anthony F Arena, Julianna Escudero, Daniel D Shaye
Chloride intracellular channels (CLICs) are conserved proteins for which the cellular and molecular functions remain mysterious. An important insight into CLIC function came from the discovery that Caenorhabditis elegans EXC-4/CLIC regulates morphogenesis of the excretory canal (ExCa) cell, a single-cell tube. Subsequent work showed that mammalian CLICs regulate vascular development and angiogenesis, and human CLIC1 can rescue exc-4 mutants, suggesting conserved function in biological tube formation (tubulogenesis) and maintenance...
December 15, 2022: Development
https://read.qxmd.com/read/36337997/geriatric-emergency-medicine-providing-older-missourians-with-the-care-they-need-and-deserve
#27
JOURNAL ARTICLE
Samuel A Ockner, Edward L Fieg
Emergency care of older adults evolved in an effort to meet the needs of our aging population. The pace of improving the quality and cost-effectiveness of emergency department (ED) care for older adults is accelerating with the development of Geriatric Emergency Department Accreditation (GEDA) and research initiatives forged by the Center for Leading Innovation and Collaboration (CLIC) and Geriatric Emergency care Applied Research (GEAR). The innovations of two Missouri EDs are highlighted, including how each approached fall risk and quality improvement efforts for aging populations with multimorbidity...
September 2022: Missouri Medicine
https://read.qxmd.com/read/36264759/intracellular-chloride-channels-regulate-endothelial-metabolic-reprogramming-in-pulmonary-arterial-hypertension
#28
JOURNAL ARTICLE
Mai M Alzaydi, Vahitha B Abdul-Salam, Harry J Whitwell, Giusy Russomanno, Angelos Glynos, Daria Capece, Gyorgy Szabadkai, Martin R Wilkins, Beata Wojciak-Stothard
Mitochondrial fission and a metabolic switch from oxidative phosphorylation to glycolysis are key features of vascular pathology in pulmonary arterial hypertension (PAH) and are associated with exuberant endothelial proliferation and apoptosis. The underlying mechanisms are poorly understood. We describe the contribution of two intracellular chloride channel proteins, CLIC1 and CLIC4, both highly expressed in PAH and cancer, to mitochondrial dysfunction and energy metabolism in PAH endothelium. Pathological overexpression of CLIC proteins induces mitochondrial fragmentation, inhibits mitochondrial cristae formation, and induces metabolic shift toward glycolysis in human pulmonary artery endothelial cells, consistent with changes observed in patient-derived cells...
January 2023: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/36264062/caveolae-couple-mechanical-stress-to-integrin-recycling-and-activation
#29
JOURNAL ARTICLE
Fidel-Nicolás Lolo, Dácil María Pavón, Araceli Grande, Alberto Elósegui Artola, Valeria Inés Segatori, Sara Sánchez, Xavier Trepat, Pere Roca-Cusachs, Miguel Ángel Del Pozo
Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts...
October 20, 2022: ELife
https://read.qxmd.com/read/36252017/regulated-restructuring-of-mucins-during-secretory-granule-maturation-in-vivo
#30
JOURNAL ARTICLE
Zulfeqhar A Syed, Liping Zhang, Duy T Tran, Christopher K E Bleck, Kelly G Ten Hagen
Mucins are large, highly glycosylated transmembrane and secreted proteins that line and protect epithelial surfaces. However, the details of mucin biosynthesis and packaging in vivo are largely unknown. Here, we demonstrate that multiple distinct mucins undergo intragranular restructuring during secretory granule maturation in vivo, forming unique structures that are spatially segregated within the same granule. We further identify temporally-regulated genes that influence mucin restructuring, including those controlling pH ( Vha16-1 ), Ca2+ ions ( fwe ) and Cl- ions ( Clic and ClC-c )...
October 25, 2022: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/36230813/chloride-intracellular-channel-proteins-clics-and-malignant-tumor-progression-a-focus-on-the-preventive-role-of-clic2-in-invasion-and-metastasis
#31
REVIEW
Saya Ozaki, Kanta Mikami, Takeharu Kunieda, Junya Tanaka
CLICs are the dimorphic protein present in both soluble and membrane fractions. As an integral membrane protein, CLICs potentially possess ion channel activity. However, it is not fully clarified what kinds of roles CLICs play in physiological and pathological conditions. In vertebrates, CLICs are classified into six classes: CLIC1, 2, 3, 4, 5, and 6. Recently, in silico analyses have revealed that the expression level of CLICs may have prognostic significance in cancer. In this review, we focus on CLIC2, which has received less attention than other CLICs, and discuss its role in the metastasis and invasion of malignant tumor cells...
October 6, 2022: Cancers
https://read.qxmd.com/read/36175369/nuclear-localisation-sequences-of-chloride-intracellular-channels-1-and-4-facilitate-nuclear-import-via-interactions-with-import-mediator-importin-%C3%AE-an-empirical-and-theoretical-perspective
#32
JOURNAL ARTICLE
Olga Faerch, Roland Worth, Ikechukwu Achilonu, Heini Dirr
Chloride intracellular channel proteins (CLICs) display ubiquitous expression, with each member exhibiting specific subcellular localisation. While all CLICs, except CLIC3, exhibit a highly conserved putative nuclear localisation sequence (NLS), only CLIC1, CLIC3 and CLIC4 exist within the nucleus. The CLIC4 NLS, 199-KVVAKKYR-206, appears crucial for nuclear entry and interacts with mouse nuclear import mediator Impα isoform 1, omitting the IBB domain (mImpα1ΔIBB). The essential nature of the basic residues in the CLIC4 NLS has been established by the fact that mutating out these residues inhibits nuclear import, which in turn is linked to cutaneous squamous cell cancer...
September 29, 2022: Journal of Molecular Recognition: JMR
https://read.qxmd.com/read/35908390/parental-occupational-exposure-to-combustion-products-metals-silica-and-asbestos-and-risk-of-childhood-leukaemia-findings-from-the-childhood-cancer-and-leukaemia-international-consortium-clic
#33
JOURNAL ARTICLE
Felix M Onyije, Ann Olsson, Friederike Erdmann, Corrado Magnani, Eleni Petridou, Jacqueline Clavel, Lucia Miligi, Audrey Bonaventure, Daniela Ferrante, Sara Piro, Susan Peters, Roel Vermeulen, Hans Kromhout, Joachim Schüz
Parental occupational exposures around conception (father) or during pregnancy (mother) have been hypothesized as potential predisposing factors for childhood leukaemia. We investigated parental exposure to several known occupational carcinogens and childhood leukaemia risk. We conducted a pooled analysis using case-control data from four European countries (3362 childhood leukemia cases and 6268 controls). Parental occupational exposures to polycyclic aromatic hydrocarbons (PAH), diesel engine exhaust (DEE), chromium, nickel, crystalline silica, and asbestos were assessed by a general population job-exposure matrix...
July 20, 2022: Environment International
https://read.qxmd.com/read/35863434/the-oxidoreductase-clic4-is-required-to-maintain-mitochondrial-function-and-resistance-to-exogenous-oxidants-in-breast-cancer-cells
#34
JOURNAL ARTICLE
Heba Al Khamici, Vanesa C Sanchez, Hualong Yan, Christophe Cataisson, Aleksandra M Michalowski, Howard H Yang, Luowei Li, Maxwell P Lee, Jing Huang, Stuart H Yuspa
The chloride intracellular channel-4 (CLIC4) is one of the six highly conserved proteins in the CLIC family that share high structural homology with GST-omega in the GST superfamily. While CLIC4 is a multifunctional protein that resides in multiple cellular compartments, the discovery of its enzymatic glutaredoxin-like activity in vitro suggested that it could function as an antioxidant. Here, we found that deleting CLIC4 from murine 6DT1 breast tumor cells using CRISPR enhanced the accumulation of reactive oxygen species (ROS) and sensitized cells to apoptosis in response to H2 O2 as a ROS-inducing agent...
September 2022: Journal of Biological Chemistry
https://read.qxmd.com/read/35849798/%C3%AE-ester-functionalized-1-1-dicyanomethylene-3-indanone-end-capped-nonfullerene-acceptors-for-high-performance-annealing-free-organic-solar-cells
#35
JOURNAL ARTICLE
Seunglok Lee, Geunhyung Park, Mingyu Jeong, Byongkyu Lee, Seonghun Jeong, Jeewon Park, Yongjoon Cho, Seung Man Noh, Changduk Yang
Modifying the end-capping groups in nonfullerene acceptors (NFAs) is an effective strategy for modulating their properties and that of the entire NFAs. This study reports the synthesis of a novel γ-ester-functionalized IC end-capping group (IC-γe) and its incorporation into the benzothiadiazole-fused central core, yielding isomer-free IC-γe end-capped NFAs, such as Y-IC-γe, Y-FIC-γe, and Y-ClIC-γe. The resultant NFAs exhibited similar absorption profiles but upshifted the lowest unoccupied molecular orbital energy level compared with those of the ester-free analogues, such as Y6 and Y7...
July 18, 2022: ACS Applied Materials & Interfaces
https://read.qxmd.com/read/35836791/moving-beyond-annual-data-reports-a-blueprint-for-communicating-and-disseminating-actionable-intelligence
#36
JOURNAL ARTICLE
Raquel Ruiz, Ann Schwartz, Elissa Orlando, Deborah Ossip, Martin S Zand, Ann Dozier
Identifying and disseminating actionable intelligence is a challenging task that requires thoughtful planning. The National Center for Advancing Translational Sciences instituted the Common Metrics Initiative with the goal of evaluating the Clinical and Translational Science Awards (CTSA) Programs using a standard set of metrics. Initially managed by Tufts University, the Center for Leading Innovation and Collaboration (CLIC) at the University of Rochester began leading this initiative in 2017. In directing this work, CLIC created a framework for communicating and disseminating data insights...
2022: Journal of Clinical and Translational Science
https://read.qxmd.com/read/35833483/a-zn2-triggered-two-step-mechanism-of-clic1-membrane-insertion-and-activation-into-chloride-channels
#37
JOURNAL ARTICLE
Lorena Varela, Alex C Hendry, Joseph Cassar, Ruben Martin-Escolano, Diego Cantoni, Felipe Ossa, John C Edwards, Vahitha Abdul-Salam, Jose L Ortega-Roldan
The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation. Here, cellular Cl- efflux assays and immunofluorescence microscopy studies have identified intracellular Zn2+ release as the trigger for CLIC1 activation and membrane insertion...
August 1, 2022: Journal of Cell Science
https://read.qxmd.com/read/35622156/endocytic-trafficking-of-gas6-axl-complexes-is-associated-with-sustained-akt-activation
#38
JOURNAL ARTICLE
Agata Poświata, Kamila Kozik, Marta Miączyńska, Daria Zdżalik-Bielecka
AXL, a TAM receptor tyrosine kinase (RTK), and its ligand growth arrest-specific 6 (GAS6) are implicated in cancer metastasis and drug resistance, and cellular entry of viruses. Given this, AXL is an attractive therapeutic target, and its inhibitors are being tested in cancer and COVID-19 clinical trials. Still, astonishingly little is known about intracellular mechanisms that control its function. Here, we characterized endocytosis of AXL, a process known to regulate intracellular functions of RTKs. Consistent with the notion that AXL is a primary receptor for GAS6, its depletion was sufficient to block GAS6 internalization...
May 27, 2022: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/35551697/orchestrated-intragranular-restructuring-of-mucins-during-secretory-granule-maturation
#39
JOURNAL ARTICLE
Kelly G Ten Hagen, Zulfeqhar A Syed, Liping Zhang, Duy T Tran, Christopher K E Bleck
Regulated secretion is an essential process where proteins are packaged into membranous secretory vesicles. However, the details of cargo packaging and secretory granule maturation are largely unknown. Here, we demonstrate that multiple distinct proteins undergo orchestrated intragranular restructuring during secretory granule maturation in vivo, to allow spatial segregation of distinct components within the same granule. Furthermore, through a combination of genetics and multimodality imaging, we demonstrate the molecular identity of each distinct intragranular structure...
May 2022: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/35549041/diffusion-of-short-semiflexible-dna-polymer-chains-in-strong-and-moderate-confinement
#40
JOURNAL ARTICLE
Gregory T Morrin, Daniel F Kienle, Daniel K Schwartz
In many technological applications, DNA is confined within nanoenvironments that are smaller than the size of the unconfined polymer in solution. However, the dependence of the diffusion coefficient on molecular weight and characteristic confinement dimension remains poorly understood in this regime. Here, convex lens-induced confinement (CLiC) was leveraged to examine how the diffusion of short DNA fragments varied as a function of slit height by using single-molecule fluorescence tracking microscopy. The diffusion coefficient followed approximate power law behavior versus confinement height, with exponents of 0...
October 19, 2021: ACS Macro Letters
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