A. V. Alimov, E. P. Igonina, I. V. Feldblyum, V. Chalapa, Y. Zakharova
{"title":"Current status of healthcare-associated enteroviral (non-polio) infections","authors":"A. V. Alimov, E. P. Igonina, I. V. Feldblyum, V. Chalapa, Y. Zakharova","doi":"10.15789/10.15789/2220-7619-csf-1161","DOIUrl":"https://doi.org/10.15789/10.15789/2220-7619-csf-1161","url":null,"abstract":"Here we present the data on foreign research publications describing healthcare-associated enteroviral (nonpolio) infections (HAI) sought in the Worldwide Database for Nosocomial Outbreaks (Institut für Hygiene und Umweltmedizin, Universitȁtmedizincomplex “Charite”, Germany) as well as PubMed search engine (The United States National Library), covering 1936–2017 timeframe. The publications retrieved contained the data on 28 nosocomial outbreaks caused by Enterovirus A (EV-A71), В (Echoviruses 11, 17, 18, 30, 31, 33, Coxsackie viruses А9, В2, В5) and D (EV-D68). It was discovered that the majority of the nosocomial enteroviral (non-polio) outbreaks occurred in obstetric hospitals and neonatal units so that children were mainly maternally infected. In addition, a case associated with intrauterine infection was described. It was shown that outbreaks might be started by an infected child at the incubation period. Single publications reported nosocomial outbreaks in geriatric hospitals. Generally, nosocomial enteroviral (non-polio) outbreaks were characterized by polymorphic clinical picture caused by any certain pathogen serotype and within a single site of the infection. Few lethal outcomes were recorded. Enterovirus B species dominated among identified etiological agents. Violated hospital hygiene and infection control contributing to spread of infection were among those found in neonatal units: putting used diapers out on baby bed prior disposal, sharing bathtub, toys and household objects as well as poor hand hygiene in medical workers. One of the measures recommended to improve diagnostics of enteroviral (non-polio) infections was virology screening of children with suspected sepsis in case of unidentified etiology. It was established that etiological decoding of nosocomial outbreaks was impossible without applying pathogen-specific diagnostic tools, mainly nested RT-PCR and direct sequencing of followed by subsequent phylogenetic analysis.","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"1 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2020-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67098552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Visualization of Procollagen IV Reveals ER-to-Golgi Transport by ERGIC-independent Carriers.","authors":"Yuto Matsui, Yukihiro Hirata, Ikuo Wada, Nobuko Hosokawa","doi":"10.1247/csf.20025","DOIUrl":"10.1247/csf.20025","url":null,"abstract":"<p><p>Collagen is the most abundant protein in animal tissues and is critical for their proper organization. Nascent procollagens in the endoplasmic reticulum (ER) are considered too large to be loaded into coat protein complex II (COPII) vesicles, which have a diameter of 60-80 nm, for exit from the ER and transport to the Golgi complex. To study the transport mechanism of procollagen IV, which generates basement membranes, we introduced a cysteine-free GFP tag at the N-terminus of the triple helical region of the α1(IV) chain (cfSGFP2-col4a1), and examined the dynamics of this protein in HT-1080 cells, which produce endogenous collagen IV. cfSGFP2-col4a1 was transported from the ER to the Golgi by vesicles, which were a similar size as small cargo carriers. However, mCherry-ERGIC53 was recruited to α<sub>1</sub>-antitrypsin-containing vesicles, but not to cfSGFP2-col4a1-containing vesicles. Knockdown analysis revealed that Sar1 and SLY1/SCFD1 were required for transport of cfSGFP2-col4a1. TANGO1, CUL3, and KLHL12 were not necessary for the ER-to-Golgi trafficking of procollagen IV. Our data suggest that procollagen IV is exported from the ER via an enlarged COPII coat carrier and is transported to the Golgi by unique transport vesicles without recruitment of ER-Golgi intermediate compartment membranes.Key words: collagen, procollagen IV, endoplasmic reticulum, ER-to-Golgi transport, ERGIC.</p>","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"45 2","pages":"107-119"},"PeriodicalIF":1.5,"publicationDate":"2020-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.20025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38064000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MON2 Guides Wntless Transport to the Golgi through Recycling Endosomes.","authors":"Shen-Bao Zhao, Neta Dean, Xiao-Dong Gao, Morihisa Fujita","doi":"10.1247/csf.20012","DOIUrl":"10.1247/csf.20012","url":null,"abstract":"<p><p>Endocytic cargos are transported to recycling endosomes (RE) but how these sorting platforms are generated is not well understood. Here we describe our biochemical and live imaging studies of the conserved MON2-DOPEY complex in RE formation. MON2 mainly co-localized with RE marker RAB4B in peripheral dots and perinuclear region. The peripheral RE approached, interacted with, and separated from sorting nexin 3 (SNX3)-positive early endosomes (EE). Membrane-bound DOPEY2 was recruited to RE dependent upon MON2 expression, and showed binding abilities to kinesin and dynein/dynactin motor proteins. MON2-knockout impaired segregation of RE from EE and led to a decreased tubular recycling endosomal network, whereas RE was accumulated at perinuclear regions in DOPEY2-knockout cells. MON2 depletion also impaired intracellular transferrin receptor recycling, as well as retrograde transport of Wntless during its passage through RE before delivery from EE to the Golgi. Together, these data suggest that the MON2 drives separation of RE from EE and is required for efficient transport of endocytic cargo molecules.Key words: membrane trafficking, MON2, recycling endosomes, Wntless.</p>","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"45 1","pages":"77-92"},"PeriodicalIF":1.5,"publicationDate":"2020-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.20012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37933683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of the Translation Initiation Factor eIF2α Phosphorylation in Cell Structure and Function.","authors":"Sung Hoon Back","doi":"10.1247/csf.20013","DOIUrl":"10.1247/csf.20013","url":null,"abstract":"<p><p>It is often assumed that α-subunit phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) complex is just a mechanism to control protein synthesis. However, eIF2α phosphorylation induced by multiple kinases can recognize various intracellular and extracellular stress conditions, and it is involved in various other cellular processes beyond protein synthesis. This review introduces the roles of eIF2α phosphorylation in translational regulation, the generation of reactive oxygen species, changes in mitochondria structure and shape, and mitochondrial retrograde signaling pathways in response to diverse stress conditions.Key words: eIF2α phosphorylation, Translation, Unfolded Protein Response, Reactive Oxygen Species, Mitochondria.</p>","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"45 1","pages":"65-76"},"PeriodicalIF":1.5,"publicationDate":"2020-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.20013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37885120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes.","authors":"Yutaka Takeda, Kanako Kuroki, Takumi Chinen, Daiju Kitagawa","doi":"10.1247/csf.20007","DOIUrl":"10.1247/csf.20007","url":null,"abstract":"<p><p>Centrosomes are highly conserved organelles that act as the major microtubule-organizing center (MTOC) in animal somatic cells. Through their MTOC activity, centrosomes play various roles throughout the cell cycle, such as supporting cell migration in interphase and spindle organization and positioning in mitosis. Various approaches for removing centrosomes from somatic cells have been developed and applied over the past few decades to understand the precise roles of centrosomes. Centrinone, a reversible and selective PLK4 (polo-like kinase 4) inhibitor, has recently emerged as an efficient approach to eliminate centrosomes. In this review, we describe the latest findings on centrosome function that have been revealed using various centrosome-eliminating approaches. In addition, we discuss our recent findings on the mechanism of centrosome-independent spindle bipolarization, discovered through the use of centrinone.Key words: centrosome, centrinone, mitotic spindle, bipolarity, NuMA.</p>","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"45 1","pages":"57-64"},"PeriodicalIF":1.5,"publicationDate":"2020-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.20007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37816624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rab7B/42 Is Functionally Involved in Protein Degradation on Melanosomes in Keratinocytes.","authors":"Soujiro Marubashi, Mitsunori Fukuda","doi":"10.1247/csf.19039","DOIUrl":"10.1247/csf.19039","url":null,"abstract":"<p><p>Keratinocytes uptake melanosomes from melanocytes and retain them in the perinuclear region, where they form melanin caps. Although these processes are crucial to protecting nuclear DNA against ultraviolet injury, the molecular basis of melanosome uptake and decomposition in keratinocytes is poorly understood. One of the major reasons for its being poorly understood is the lack of a specific marker protein that can be used to visualize or monitor melanosomes (or melanosome-containing compartments) that have been incorporated into keratinocytes. In this study, we performed a comprehensive localization screening for mammalian Rab family small GTPases (Rab1-45) and succeeded in identifying 11 Rabs that were enriched around melanosomes that had been incorporated into keratinocytes. We also established a new assay by using a recently developed melanosome probe (called M-INK) as a means of quantitatively assessing the degradation of proteins on incorporated melanosomes in control and each of a series of Rab-knockdown keratinocytes. The results showed that knockdown or CRISPR/Cas9-mediated knockout of Rab7B (also identified as Rab42) in keratinocytes caused strong inhibition of protein degradation on melanosomes. Our findings indicated that Rab7B/42 is recruited to melanosome-containing compartments and that it promotes protein degradation on melanosomes in keratinocytes.Key words: degradation, keratinocytes, melanocytes, melanosome, Rab small GTPase.</p>","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"45 1","pages":"45-55"},"PeriodicalIF":1.5,"publicationDate":"2020-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.19039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37625986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hierarchical Development of Motile Polarity in Durotactic Cells Just Crossing an Elasticity Boundary.","authors":"Thasaneeya Kuboki, Hiroyuki Ebata, Tomoki Matsuda, Yoshiyuki Arai, Takeharu Nagai, Satoru Kidoaki","doi":"10.1247/csf.19040","DOIUrl":"10.1247/csf.19040","url":null,"abstract":"<p><p>Cellular durotaxis has been extensively studied in the field of mechanobiology. In principle, asymmetric mechanical field of a stiffness gradient generates motile polarity in a cell, which is a driving factor of durotaxis. However, the actual process by which the motile polarity in durotaxis develops is still unclear. In this study, to clarify the details of the kinetics of the development of durotactic polarity, we investigated the dynamics of both cell-shaping and the microscopic turnover of focal adhesions (FAs) for Venus-paxillin-expressing fibroblasts just crossing an elasticity boundary prepared on microelastically patterned gels. The Fourier mode analysis of cell-shaping based on a persistent random deformation model revealed that motile polarity at a cell-body scale was established within the first few hours after the leading edges of a moving cell passed through the boundary from the soft to the stiff regions. A fluorescence recovery after photobleaching (FRAP) analysis showed that the mobile fractions of paxillin at FAs in the anterior part of the cells exhibited an asymmetric increase within several tens of minutes after cells entered the stiff region. The results demonstrated that motile polarity in durotactic cells is established through the hierarchical step-wise development of different types of asymmetricity in the kinetics of FAs activity and cell-shaping with a several-hour time lag.Key words: Microelasticity patterned gel, durotaxis, cell polarity, focal adhesions, paxillin.</p>","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"45 1","pages":"33-43"},"PeriodicalIF":1.5,"publicationDate":"2020-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10739161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37513057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Byungseok Jin, Tokiro Ishikawa, Mai Taniguchi, Satoshi Ninagawa, Tetsuya Okada, Shigehide Kagaya, Kazutoshi Mori
{"title":"Development of a Rapid in vivo Assay to Evaluate the Efficacy of IRE1-specific Inhibitors of the Unfolded Protein Response Using Medaka Fish.","authors":"Byungseok Jin, Tokiro Ishikawa, Mai Taniguchi, Satoshi Ninagawa, Tetsuya Okada, Shigehide Kagaya, Kazutoshi Mori","doi":"10.1247/csf.19032","DOIUrl":"10.1247/csf.19032","url":null,"abstract":"<p><p>Three types of transmembrane protein, IRE1α/IRE1β, PERK, and ATF6α/ATF6β, are expressed ubiquitously in vertebrates as transducers of the unfolded protein response (UPR), which maintains the homeostasis of the endoplasmic reticulum. IRE1 is highly conserved from yeast to mammals, and transmits a signal by a unique mechanism, namely splicing of mRNA encoding XBP1, the transcription factor downstream of IRE1 in metazoans. IRE1 contains a ribonuclease domain in its cytoplasmic region which initiates splicing reaction by direct cleavage of XBP1 mRNA at the two stem loop structures. As the UPR is considered to be involved in the development and progression of various diseases, as well as in the survival and growth of tumor cells, UPR inhibitors have been sought. To date, IRE1 inhibitors have been screened using cell-based reporter assays and fluorescent-based in vitro cleavage assays. Here, we used medaka fish to develop an in vivo assay for IRE1α inhibitors. IRE1α, IRE1β, ATF6α and ATF6β are ubiquitously expressed in medaka. We found that IRE1α/ATF6α-double knockout is lethal, similarly to IRE1α/IRE1β- and ATF6α/ATF6β-double knockout. Therefore, IRE1 inhibitors are expected to confer lethality to ATF6α-knockout medaka but not to wild-type medaka. One compound named K114 was obtained from 1,280 compounds using this phenotypic screening. K114 inhibited ER stress-induced splicing of XBP1 mRNA as well as reporter luciferase expression in HCT116 cells derived from human colorectal carcinoma, and inhibited ribonuclease activity of human IRE1α in vitro. Thus, this phenotypic assay can be used as a quick test for the efficacy of IRE1α inhibitors in vivo.Key words: endoplasmic reticulum, inhibitor screening, mRNA splicing, phenotypic assay, unfolded protein response.</p>","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"45 1","pages":"23-31"},"PeriodicalIF":1.5,"publicationDate":"2020-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1247/csf.19032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37489908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myogenesis","authors":"Y. Shimada, E. Ozawa","doi":"10.1007/978-1-61779-343-1","DOIUrl":"https://doi.org/10.1007/978-1-61779-343-1","url":null,"abstract":"","PeriodicalId":9927,"journal":{"name":"Cell structure and function","volume":"9 Suppl 1","pages":"s111-5"},"PeriodicalIF":1.5,"publicationDate":"2020-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-1-61779-343-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49591363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}