Grief matters最新文献

{"title":"Synergistic toxicity between glyphosate and 2,4-dinitrophenol on budding yeast is not due to H2O2-mediated oxidative stress","authors":"Antoine Daviere, Maximilien Sotomski, A. Audibert, P. Carol, S. Hubert, S. Lebreton, S. Louvet-Vallée, J. Pédron, J. Puyaubert, Y. Kraepiel, J. Lacoste","doi":"10.19185/MATTERS.201903000030","DOIUrl":"https://doi.org/10.19185/MATTERS.201903000030","url":null,"abstract":"Glyphosate is a widely-used herbicide that is frequently found as a pollutant of soil and water runoffs. Glyphosate toxicity is controversial but a toxic synergy with other molecules could result in deleterious consequences for living organisms and for the human health. Using budding yeast (Saccharomyces cerevisiae) as a eukaryotic model organism, we report here a strong toxic synergy between glyphosate and 2,4-dinitrophenol (DNP), a phenolic compound derived from diesel engine’s combustion and industrial pollutant found frequently in surface water and rainfall. Glyphosate concentrations below 600 mg/L did not affect yeast growth but exhibit dose-dependent toxicity in the presence of non-toxic DNP concentrations (below 1 mM). This so-called ‘cocktail effect’ increases with DNP concentration. Yeast growth is totally abolished in the presence of the highest concentration of both molecules. We explored the implication of oxidative stress in this synergistic effect of glyphosate and DNP, by measuring H2O2 concentrations in the culture media, and by comparing cta1∆/ctt1∆ catalase double-mutant with wild-type yeast. We did not find any glyphosate-DNP enhanced susceptibility for the catalase mutant and did not observe any clear increase of H2O2 in the presence of the pollutant mixture. All these data suggest that the redox homeostasis is not involved in this toxic synergy, that remains to be explained.","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74959754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphomimetic mutations modulate the ability of HIV-1 Rev to bind human Importin β in vitro","authors":"Nadia Ben Fadhel, L. Signor, C. Petosa, M. Noirclerc-Savoye","doi":"10.19185/MATTERS.201903000032","DOIUrl":"https://doi.org/10.19185/MATTERS.201903000032","url":null,"abstract":"The HIV-1 Rev (Regulator of Expression of Virion) protein, an RNA-binding protein essential for viral replication, is imported into the host cell nucleus by human Importin β (Impβ). Rev is phosphorylated in vivo on serine residues by a nuclear kinase. In this study, we introduced glutamate substitution mutations that mimic phosphorylation at serine positions previously identified as potential phosphorylation sites and assessed their impact on the ability of Rev to bind Impβ in thermal shift, gel shift, and fluorescence polarization assays. Phosphomimetic mutations introduced in either the N-terminal tail, helical hairpin domain or C-terminal domain of Rev had a small but reproducible stabilizing effect on the Impβ/Rev complex. Moreover, the mutation of Rev residue Ser56, which localizes to one face of the helical hairpin domain, had a greater stabilizing effect than that of Ser54 located on the opposite face, suggesting that the helical hairpin orients its Ser56-containing face towards Impβ. Taken together, our results suggest that phosphorylation can significantly modulate the ability of Rev to associate with Impβ.","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79993669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The posterior limit of the area pellucida (pPL) as a reliable proxy for the end of the primitive streak in chick elongation studies","authors":"Ana C Maia-Fernandes, T. P. D. Azevedo, A. Marreiros, I. Palmeirim, R. P. Andrade","doi":"10.19185/MATTERS.201903000031","DOIUrl":"https://doi.org/10.19185/MATTERS.201903000031","url":null,"abstract":"Early embryo elongation involves coordinated cellular and tissue behaviors that are readily observable in the chick embryo vertebrate model system. Easily identifiable morphological landmarks are crucial to obtain reliable morphometric data, particularly when assessing tissue elongation over time. The posterior end of the primitive streak marks the caudal end of the chick embryonic tissue. However, the identification of its precise location is ambiguous, especially to the untrained eye. Herein, we assessed if the posterior limit of the area pellucida (pPL), which is readily recognizable due to the optical contrast with the area opaca, is a valid proxy for the caudal limit of the primitive streak. Measurements of total embryo length were performed in multiple images of chick embryos over time using both caudal landmarks. We found that the pPL offered greater precision and a higher degree of inter-user reproducibility, when compared to the end of the primitive streak. Importantly, our work uncovers a quantitative proportionality between embryo length measurements using the end of the primitive streak and the pPL as caudal landmarks. We have thus validated the pPL as a reliable morphological proxy for the end of the primitive streak in chick embryo elongation studies.","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84800598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The occluding junction protein Neurexin-IV is required for tissue integrity in the Drosophila wing disc epithelium","authors":"Susana Ponte, Antonio Jacinto Prof., Lara Carvalho","doi":"10.19185/MATTERS.201903000014","DOIUrl":"https://doi.org/10.19185/MATTERS.201903000014","url":null,"abstract":"Epithelia are essential tissues in all multicellular organisms to establish a barrier against the external environment. To exert this vital function, epithelial cells need to be tightly connected to each other while at the same time they allow for complex tissue and cell shapes to arise. Occluding Junctions (OJs) have evolved to become epithelia’s gatekeepersthey seal intercellular spaces but also provide selective permeability. Recent studies have also proposed that OJs regulate epithelial morphogenesis and polarity, but themechanisms are still poorly understood. Herewe explored novel functions of OJs by investigating the function of Neurexin-IV (Nrx-IV), a conserved transmembrane protein of the Neurexin/Contactin family localized at invertebrate OJs, using theDrosophila melanogaster larval epithelium as a model system. By knocking down the expression of this protein in a specific subset of epithelial cells and in a time-controlled manner, we show that Nrx-IV is required for proper epithelial tissue organization and survival. This suggests that OJs play a more important role in epithelial morphogenesis than previously anticipated. As Nrx-IV is also present in invertebrate glial OJs and in vertebrate axo-glial junctions this work not only increases our knowledge about epithelia but can also have implications in nervous system biology.","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84107837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Environmental Factors rescues spine defects of Eps8 KO mice","authors":"S. Ferrara, S. Zambetti, D. Braida, R. Morini, M. Sala, M. Matteoli, E. Menna","doi":"10.19185/MATTERS.201903000024","DOIUrl":"https://doi.org/10.19185/MATTERS.201903000024","url":null,"abstract":"Several neuropsychiatric diseases, including autism spectrum disorders (ASD) and intellectual disability (ID) are characterized by synaptic dysfunctions, such as, altered number and shape of dendritic spines, and defective synaptic signalling and plasticity. The actin regulatory protein, Eps8, plays a key role in spine morphogenesis and plasticity since neurons lacking Eps8 show defective spine morphology and density and fail to undergo long term potentiation. Consistently, Eps8 KO mice display increased density of immature spines in CA1 hippocampal region and cognitive defects. Also, lower levels of Eps8 have been detected in the brain of a cohort of ASD patients. Preclinical studies showed that environmental factors, such as mice exposure to environmental enrichment (EE) or neuron exposure to increased extracellular Mg2+, may have a “plasticizing action” resulting in improved cognitive functions and higher cellular plasticity. Here, we tested whether early EE or high Mg2+ exposure may rescue the structural synaptic defects of Eps8 KO mice and neurons. Results of this study indicate that the early EE treatment in mice and elevated extracellular Mg2+ concentration in neurons restore normal dendritic morphology and synaptic plasticity in Eps8 KO mice and neurons. These data suggest that early “plasticizing” interventions can be beneficial on synaptic defects and their efficacy in the treatment of neuro-developmental diseases is worth to be investigated.","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82970819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chasing tail: putative pre-copulatory behaviour in free-living zebra sharks (Stegostoma fasciatum)","authors":"Matthew J Birt Mr, Todd Bond Mr, Michael Taylor Mr, Dianne L McLean Dr, Timothy J Langlois Dr","doi":"10.19185/MATTERS.201903000016","DOIUrl":"https://doi.org/10.19185/MATTERS.201903000016","url":null,"abstract":"","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74722408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell surface expression of integrin β4-subunit in the absence of α6-subunit","authors":"Satu-Marja Myllymäki, A. Manninen","doi":"10.19185/MATTERS.201902000007","DOIUrl":"https://doi.org/10.19185/MATTERS.201902000007","url":null,"abstract":"Laminin-rich basement membrane (BM) guides epithelial cell polarity, regulates epithelial cell behavior and maintains the integrity of epithelial tissues. αβ1and α6β4-integrins both contribute to laminin adhesion and signaling via the assembly of integrin adhesion complexes that help to orient the apico-basal polarity axis. β4-integrin differs from other integrin subunits due to its large cytoplasmic domain that connects to cellular intermediate filament (IF) networks in specialized adhesions called hemidesmosomes (HD). β4-integrin is only known to form a heterodimer with the α6-subunit. In normal tissues, β4-integrin is expressed in cells that also express the α6-subunit. However, in most cells analyzed, β4-integrin is expressed in large excess over α6-integrin and in some tumor cells, β4-integrin appears to promote tumorigenic signaling despite loss of HDs formation. The fate of free β4-subunit and its potential functions in cells have not been extensively studied. Here, we have studied subcellular localization and potential surface delivery of β4-integrin in the absence of its heterodimer partner α6. We provide evidence that a significant fraction of β4-subunit can reach the cell surface without α6-subunit. We also report that β4 is cleaved at its extracellular domain to produce a membrane-bound proteolytic product with an intact cytoplasmic domain. The processed β4-integrin did not co-precipitate with α6-subunit. Taken together, our data suggest that β4-integrin might have functions that are independent of heterodimer formation.","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90078175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonbinary branching of myelinated dendrites at nodal networks on afferent terminal arbors in paddlefish electroreceptors","authors":"D. F. Russell, Desmon E. Rogers, Lilia L. Neiman","doi":"10.19185/MATTERS.201812000003","DOIUrl":"https://doi.org/10.19185/MATTERS.201812000003","url":null,"abstract":"The branching of vertebrate neuronal processes, axons or dendrites, is predominantly binary, where a proximal neuronal process bifurcates into two distal progeny. Here, we illustrate counterexamples where neuronal processes branched into more than 2, up to 6, progeny branches, in one step. These were branch points of myelinated dendrites in the peripheral terminals of ALLn cranial nerve afferents innervating the Lorenziniantype ampullary electroreceptors on the rostrum of paddlefish, Polyodon spathula. We imaged afferent terminals fluorescently (in widefield stacks, with deconvolution) after immunolabling of afferent terminals for neuronal cytoplasmic neurofilament-H (NEFH), myelin markers (MBP, P0), or nodal ion channels (Nav1.x, Kv1.1), or after migration of DiI in dendrite membranes. Branched afferent terminals formed a laminar radial radiation beneath a receptive field, parallel to the skin surface, with two serial stages: (1) Starting at each afferent’s centric first branchpoint, each of a small group of 2–4 (most often 3) afferents branched radially into 2–4 (usually 3) generations of myelinated dendrites, whose internodes were covered by sheaths immunoreactive for antigenic markers of myelin (MBP+/P0+), ending distally at ~15 heminode presumed spike initiation zones. (2) From the latter, bundles of unmyelinated (MBP-/P0-) sensory neuron (NEFH+) processes projected distally to innervate electrosensory neuroepithelia of adjacent ampullary organs. The nonbinary branch points that we imaged were in stage-1, on myelinated dendrites. Branch points always coincided with composite systems of nodes, in which each progeny dendrite started at a narrowed nodal segment expressing voltage gated sodium ion channels at high density. These narrowed nodal segments of multiple progeny branched in parallel from a parent’s blunt distal end. Hence the branch point nodal complexes formed multisite excitable systems, likely strongly coupled due to proximity.","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78510872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De quoi la « guerre contre le terrorisme » est-elle le nom ?","authors":"D. Fonseca","doi":"10.3917/grief.192.0057","DOIUrl":"https://doi.org/10.3917/grief.192.0057","url":null,"abstract":"","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89623330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Destabilisation of Argonaute 2 generates a truncated protein: halfAgo2","authors":"Sarah Bajan, M. Johnston, G. Hutvagner","doi":"10.19185/MATTERS.201811000001","DOIUrl":"https://doi.org/10.19185/MATTERS.201811000001","url":null,"abstract":"The Argonaute 2 (Ago2) protein is an essential effector protein in miRNA-mediated mechanisms that regulate gene expression. Ago2 directly binds to the miRNA, forming the RISC. RISC function is critical to controlling key biological processes and when dysregulated can result in disease pathogenesis. Understanding Ago2 protein stability and turnover will further our understanding in how RISC function is regulated. In human cells, we discovered a previously unidentified ~55 kDa protein that is a truncated form of Ago2, that is formed from proteolytic cleavage of the full length Ago2 protein. Further experiments are needed to determine (i) the detailed mechanism that forms halfAgo2 (ii) the cellular or environmental triggers or stresses that initiate halfAgo2 production and (iii) if halfAgo2 has a potentially new role in gene regulation. Introduction miRNAs are endogenous small molecules that are essential regulators of human development. miRNAs function by targeting the post-transcriptional stages of gene expression, via several distinct mechanisms [1]. miRNA regulatory function depends on the miRNA directly binding to an Argonaute (Ago) protein, forming the RNA Induced Silencing Complex (RISC). In this complex the miRNA acts a guide, by binding to a complementary site within mRNA and bringing the RISC, and its associated regulatory proteins, to the target [2] [3]. RISC regulates key biological processes, therefore any disruption to RISC function can have severe consequences, and misregulation of RISC is implicated in the development of disease [4]. It is therefore important that the stability of RISC and accordingly its components, miRNA andAgo, are controlled. There are several knownmechanisms that mediatemiRNA stability and turnover, including homeostatic and feedbackmechanisms that coordinate miRNA levels with Ago levels [5] [6] [7] [8]. However, we have only limited understanding into mechanisms that regulate the turnover of Ago proteins and the RISC complex. There is emerging evidence that Ago function and stability is mediated by a variety of post-translational modifications of the protein, which occurs as a consequence of complex signalling pathways [9] [10] [11] [12] [13]. These modifications can alter protein function, stability, and localisation. Depending on the modification, these changes can be permanent or reversible. Therefore Ago levels are potentially highly dynamic and are responsive to internal and external stimuli. While the 4 human Ago proteins (1–4) display some functional redundancy, Ago2 is the most abundant in commonly used human cell lines [14] and the most studied in miRNA regulation. Objective While analysing the protein expression of full-length (FL), endogenous, Ago2 (~85 kDa) in HeLa cell lysate, we observed that an Ago2-specific monoclonal antibody targeted to the N-terminus of the protein [15], also bound to a previously unidentified protein of approximately 55 kDa. The objective of this study was to investigate thi","PeriodicalId":90172,"journal":{"name":"Grief matters","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88167427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}