SIV(SM)/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells

BACKGROUND: Vpx is a non-structural protein coded by members of the SIV(SM)/HIV-2 lineage that is believed to have originated by duplication of the common vpr gene present in primate lentiviruses. Vpx is incorporated into virion particles and is thus present during the early steps of viral infection, where it is thought to drive nuclear import of viral nucleoprotein complexes. We have previously shown that Vpx is required for SIV(MAC)-derived lentiviral vectors (LVs) infection of human monocyte-derived dendritic cells (DCs). However, since the requirement for Vpx is specific for DCs and not for other non-dividing cell types, this suggests that Vpx may play a role other than nuclear import. RESULTS: Here, we show that the function of Vpx in the infection of DCs is conserved exclusively within the SIV(SM)/HIV-2 lineage. At a molecular level, Vpx acts by promoting the accumulation of full length viral DNA. Furthermore, when supplied in target cells prior to infection, Vpx exerts a similar effect following infection of DCs with retroviruses as divergent as primate and feline lentiviruses and gammaretroviruses. Lastly, the effect of Vpx overlaps with that of the proteasome inhibitor MG132 in DCs. CONCLUSION: Overall, our results support the notion that Vpx modifies the intracellular milieu of target DCs to facilitate lentiviral infection. The data suggest that this is achieved by promoting viral escape from a proteasome-dependent pathway especially detrimental to viral infection in DCs

One hundred fifty years of total laryngectomies

The inaugural total laryngectomy in history was conducted by Billroth in 1873. Nevertheless, significant enhancements to the technique were achieved through the contributions of Gluck, Sorensen, and various other surgeons. Throughout the twentieth century, advancements in anesthesia, infectious disease, hospital hygiene, antibiotic therapy, resuscitation, and the expertise of numerous laryngologists elevated total laryngectomy to a pivotal surgical intervention in head and neck surgery. The latter half of the twentieth century witnessed a paradigm shift with the emergence of organ preservation protocols. Total laryngectomy became the preferred choice for patients experiencing radiotherapy failure. However, the widespread use of laryngeal conservative treatments appears to be correlated with a decline in overall survival rates in the United States and Europe. The evolution of new minimally invasive surgical approaches in the twenty-first century may usher in a revolutionary era in the management of laryngeal carcinoma, offering the potential for improved survival and functional outcomes

La révélation dans les nouvelles de Raymond Carver

This study is focused on five of Raymond Carver's collections of short stories. It explores the question of revelation and from this perspective, it also deals with Carver's so-called minimalist style and the evolution of his work. The world in which Carver's characters are evolving is at the same time familiar, common and threatening. Most of the characters are silent, alienated, lost and dehumanized. They are on the edge of a crisis and therefore, they are waiting to be freed or eager for answers about themselves and their future. Thanks to a minimalist style and to the frame of his short stories, Carver is able to combine simplicity and mystery, inviting readers to interact with the text and to go beyond the surface so the text may reveal itself to them. Thus, the question of revelation is at the centre of Carver's work since characters and readers are waiting for things to be unveiled. The aim of this work is to study what kind of revelation the reader, the author and the characters are confronted with and if revelations do take place then, under which conditions.Cette étude se focalise sur cinq des recueils de nouvelles de Raymond Carver et propose d'en démontrer le caractère épiphanique tout en explorant le style dit minimaliste de Carver et son évolution. L'univers carverien est menaçant avec ses personnages silencieux, isolés, perdus, qui se retrouvent en pleine crise et, ainsi, à un tournant de leur existence. Directement liés à la notion de révélation, l'isolement, la question d'identité ainsi que la renaissance sont des thèmes récurrents importants auxquels les personnages carveriens sont rattachés. Le lecteur se retrouve, quant à lui, confronté à une écriture à la fois simple et mystérieuse. Le cadre des nouvelles, avec leurs fins ouvertes et leurs nombreux détournements ne font qu'entretenir un certain suspense pour le lecteur qui va devoir décortiquer et interagir avec le texte afin d'accéder à une révélation. La question d'épiphanie est alors au centre de l'oeuvre puisque de par son contenu et sa forme, le style carverien va placer ses personnages et ses lecteurs dans l'attente d'une révélation tout en les incitant à se questionner. L'objectif de cette recherche est donc d'étudier quels types de révélations s'offrent à la fois au lecteur, à l'auteur ainsi qu'aux personnages, et sous quelle forme

Characterization of the Early Steps of Infection of Primary Blood Monocytes by Human Immunodeficiency Virus Type 1▿

Blood-circulating monocytes migrate in tissues in response to danger stimuli and differentiate there into two major actors of the immune system: macrophages and dendritic cells. Given their migratory behavior and their pivotal role in the orchestration of immune responses, it is not surprising that cells of the monocyte lineage are the target of several viruses, including human immunodeficiency virus type 1 (HIV-1). HIV-1 replicates in monocytoid cells to an extent that is influenced by their differentiation status and modulated by exogenous stimulations. Unstimulated monocytes display a relative resistance to HIV infection mostly exerted during the early steps of the viral life cycle. Despite intensive studies, the identity of the affected step remains controversial, although it is generally assumed to take place after viral entry. We reexamine here the early steps of viral infection of unstimulated monocytes using vesicular stomatitis virus G protein-pseudotyped HIV-1 virions. Our data indicate that a first block to the early steps of infection of monocytes with these particles occurs at the level of viral entry. After entry, reverse transcription and integration proceed with extremely slow kinetics rather than being blocked. Once completed, viral DNA molecules delay entry into the nucleus and integration for up to 5 to 6 days. The inefficacy of these steps accounts for the resistance of monocytes to HIV-1 during the early steps of infection

Incorporación de mayor valor en la cadena de la miel y productos derivados de la colmena en el Pacífico Central, Costa Rica

En este documento se ofrece una propuesta para el fortalecimiento de la cadena de valor de la miel de abeja y para la incorporación de valor agregado a los productos derivados de la colmena en la región del Pacífico Central costarricense. El proceso se llevó a cabo mediante un acuerdo de cooperación técnica entre el Ministerio de Economía, Industria y Comercio de Costa Rica (MEIC) y la Sede Subregional de la Comisión Económica para América Latina y el Caribe (CEPAL) en México, en el marco de las actividades del proyecto CEPAL-CRUSA “Fortalecimiento de dos cadenas de valor con alto potencial de encadenamientos para PYME en el Pacífico Central costarricense”.Resumen .-- Introducción .-- I. Aspectos generales de la cadena de la miel .-- II. Caracterización de la cadena de la miel en el Pacífico Central .-- III. Oportunidades para incrementar el valor agregado de la cadena .-- IV. Gobernanza .-- V. Análisis de la sostenibilidad ambiental .-- VI. Restricciones .-- VII. Buenas prácticas .-- VIII. Estrategia para fortalecer la cadena de la miel y productos derivados de la colmena a partir de la generación de productos de mayor valor agregado .-- IX. Conclusiones

Additional file 2: of Gap junctions contribute to anchorage-independent clustering of breast cancer cells

Figure S2. Effect of the combination of latrunculin A and meclofenamate on the clustering of MCF7 cancer cells and on calcein transfer. (A) Variation of the area occupied by MCF7 cells during the clustering assay with cells incubated or not (n = 21) with 100 nM latrunculin A (n = 22), 300 μM meclofenamate (n = 26), or latrunculin A + meclofenamate (n = 27). Results are the mean ± SD of 4 independent experiments. Mann-Whitney non-parametric tests, except for NT versus latrunculin A + meclofenamate: unpaired two-tailed t-test at 2 h, ***p < 0.0005. (B) Transfer of calcein during the clustering assay from donor positive cells to negative cells incubated or not with different compounds as in (A). The percentage of receiver positive cells is indicated. Results are the mean ± SD of 4 independent experiments (3 replicates for each condition in each experiment). Unpaired two-tailed t-tests, at 2 h, 5 h and 10 h; differences are not statistically significant (N.S.). (PDF 575 kb

Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells

International audienceThe protocadherin proteins are cell adhesion molecules at the crossroad of signaling pathways playing a major role in neuronal development. It is now understood that their role as signaling hubs is not only important for the normal physiology of cells but also for the regulation of hallmarks of cancerogenesis. Importantly, protocadherins form a cluster of genes that are regulated by DNA methylation. We have identified for the first time that PCDHB15 gene is DNA-hypermethylated on its unique exon in the metastatic melanoma-derived cell lines and patients’ metastases compared to primary tumors. This DNA hypermethylation silences the gene, and treatment with the DNA demethylating agent 5-aza-2′-deoxycytidine reinduces its expression. We explored the role of PCDHB15 in melanoma aggressiveness and showed that overexpression impairs invasiveness and aggregation of metastatic melanoma cells in vitro and formation of lung metastasis in vivo. These findings highlight important modifications of the methylation of the PCDHβ genes in melanoma and support a functional role of PCDHB15 silencing in melanoma aggressiveness

Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells

International audienceThe protocadherin proteins are cell adhesion molecules at the crossroad of signaling pathways playing a major role in neuronal development. It is now understood that their role as signaling hubs is not only important for the normal physiology of cells but also for the regulation of hallmarks of cancerogenesis. Importantly, protocadherins form a cluster of genes that are regulated by DNA methylation. We have identified for the first time that PCDHB15 gene is DNA-hypermethylated on its unique exon in the metastatic melanoma-derived cell lines and patients’ metastases compared to primary tumors. This DNA hypermethylation silences the gene, and treatment with the DNA demethylating agent 5-aza-2′-deoxycytidine reinduces its expression. We explored the role of PCDHB15 in melanoma aggressiveness and showed that overexpression impairs invasiveness and aggregation of metastatic melanoma cells in vitro and formation of lung metastasis in vivo. These findings highlight important modifications of the methylation of the PCDHβ genes in melanoma and support a functional role of PCDHB15 silencing in melanoma aggressiveness

« Grâce à elle(s) ? » : le rôle des femmes dans la construction du Canada

Ce numéro 88 fait suite au Congrès annuel de l’Association française d’études canadiennes qui s’est tenu à Bordeaux du 12 au 14 juin 2019 sur le thème « Grâce à elle(s) ? » : le rôle des femmes dans la construction du Canada. À une époque où le Canada s’enorgueillit d’adopter « une politique d’aide internationale féministe » pour promouvoir l’égalité des sexes et contribuer au renforcement du pouvoir des femmes et des filles dans le monde, il apparait particulièrement opportun d’examiner les faits et les questions relatifs aux femmes et à la manière (sous-évaluée ?) dont elles ont contribué à la construction du Canada. À travers une sélection d’articles représentatifs, ce nuérmo reflète la richesse et la diversité des contributions que cette thématique a inspirées