Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

<p>Abstract</p> <p>Background:</p> <p>The <it>v-erbA </it>oncogene, carried by the Avian Erythroblastosis Virus, derives from the <it>c-erbAα </it>proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R). v-ErbA transforms erythroid progenitors <it>in vitro </it>by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor). However, v-ErbA target genes involved in its transforming activity still remain to be identified.</p> <p>Results:</p> <p>By using Serial Analysis of Gene Expression (SAGE), we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription) and unexpected (protein metabolism) functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA.</p> <p>Conclusion:</p> <p>This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.</p

Reuse of medical face masks in domestic and community settings without sacrificing safety: Ecological and economical lessons from the Covid-19 pandemic

The need for personal protective equipment increased exponentially in response to the Covid-19 pandemic. To cope with the mask shortage during springtime 2020, a French consortium was created to find ways to reuse medical and respiratory masks in healthcare departments. The consortium addressed the complex context of the balance between cleaning medical masks in a way that maintains their safety and functionality for reuse, with the environmental advantage to manage medical disposable waste despite the current mask designation as single-use by the regulatory frameworks. We report a Workflow that provides a quantitative basis to determine the safety and efficacy of a medical mask that is decontaminated for reuse. The type IIR polypropylene medical masks can be washed up to 10 times, washed 5 times and autoclaved 5 times, or washed then sterilized with radiations or ethylene oxide, without any degradation of their filtration or breathability properties. There is loss of the antiprojection properties. The Workflow rendered the medical masks to comply to the AFNOR S76-001 standard as “type 1 non-sanitory usage masks”. This qualification gives a legal status to the Workflow-treated masks and allows recommendation for the reuse of washed medical masks by the general population, with the significant public health advantage of providing better protection than cloth-tissue masks. Additionally, such a legal status provides a basis to perform a clinical trial to test the masks in real conditions, with full compliance with EN 14683 norm, for collective reuse. The rational reuse of medical mask and their end-of-life management is critical, particularly in pandemic periods when decisive turns can be taken. The reuse of masks in the general population, in industries, or in hospitals (but not for surgery) has significant advantages for the management of waste without degrading the safety of individuals wearing reused masks

Mécanismes moléculaires de la résistance des cancers colorectaux aux agressions chimiques

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Gene regulation by voltage-dependent calcium channels.

International audienceCa(2+) is the most widely used second messenger in cell biology and fulfills a plethora of essential cell functions. One of the most exciting findings of the last decades was the involvement of Ca(2+) in the regulation of long-term cell adaptation through its ability to control gene expression. This finding provided a link between cell excitation and gene expression. In this review, we chose to focus on the role of voltage-dependent calcium channels in mediating gene expression in response to membrane depolarization. We illustrate the different pathways by which these channels are involved in excitation-transcription coupling, including the most recent Ca(2+) ion-independent strategies that highlight the transcription factor role of calcium channels

Maurocalcine, a tool for the study of the excitation-contraction coupling process

Maurocalcine is a 33 amino-acid peptide that was first isolated from the venom of scorpio Maurus palmatus and then chemically produced as a synthetic peptide. It was shown to be active on the intracellular calcium channels ryanodine receptors. Ryanodine receptors permit Ca2+ release from endoplasmic reticulum in response to various stimuli, including membrane depolarization. In skeletal muscle, ryanodine receptors interaction with the voltage-gated calcium channel dyhydropyridine receptor is responsible for the triggering of the cell contraction following action potential, i.e. the excitation-contraction coupling. An interesting feature of maurocalcine is its partial sequence homology with a cytoplasmic domain (domain A) of the dihydropyridine receptor previously shown to interact with the ryanodine receptor. Maurocalcine directly interact with purified type 1 (skeletal), type 2 (cardiac) and type 3 ryanodine receptors. The type 1 and 2 ryanodine receptors sequences involved in maurocalcine binding have been mapped and correspond to the binding site of domain A. The functional effects of maurocalcine on skeletal ryanodine receptor were then characterized. While it strongly modifies the channel behaviour of type 1 ryanodine receptor, increase of the open probability and appearance of long lasting subconductance state, it shows no effect on type 2 ryanodine receptors. Studies on intact adult mammalian skeletal muscle fibres have shown that maurocalcine binding on ryanodine receptor depends on the coupling of ryanodine receptor with the dihydropyridine receptor and modifies specific steps of the excitationcontraction process

Nuclear life of the voltage-gated Cacnb4 subunit and its role in gene transcription regulation.

International audienceThe pore-forming subunit of voltage-gated calcium channels is associated to auxiliary subunits among which the cytoplasmic β subunit. The different isoforms of this subunit control both the plasma membrane targeting and the biophysical properties of the channel moiety. In a recent study, we demonstrated that the Cacnb4 (β 4) isoform is at the center of a new signaling pathway that connects neuronal excitability and gene transcription. This mechanism relies on nuclear targeting of β 4 triggered by neuronal electrical stimulation. This re-localization of β 4 is promoted by its interaction with Ppp2r5d a regulatory subunit of PP2A in complex with PP2A itself. The formation, as well as the nuclear translocation, of the β 4/ Ppp2r5d/ PP2A complex is totally impaired by the premature R482X stops mutation of β 4 that has been previously associated with juvenile epilepsy. Taking as a case study the tyrosine hydroxylase gene that is strongly upregulated in brain of lethargic mice, deficient for β 4 expression, we deciphered the molecular steps presiding to this signaling pathway. Here we show that expression of wild-type β 4 in HEK293 cells results in the regulation of several genes, while expression of the mutated β 4 (β 1-481) produces a different set of gene regulation. Several genes regulated by β 4 in HEK293 cells were also regulated upon neuronal differentiation of NG108-15 cells that induces nuclear translocation of β 4 suggesting a link between β 4 nuclear targeting and gene regulation