19 research outputs found

    It’s the Economy, Stupid: Applying (Micro)economic Principles to Microbiome Science

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    A key challenge in microbiome science is the scale mismatch problem, which arises when the scale at which microbial communities are sampled, interrogated, and averaged is different from the scale at which individual microorganisms within those communities interact with each other and with their environment. Profiling the microbial communities in a teaspoon of soil, from a scoop of fecal matter, or along a plant leaf surface represents a scale mismatch of multiple orders of magnitude, which may limit our ability to interpret or predict species interactions and community assembly within such samples. In this Perspective, we explore how economists, who are historically and topically split along the lines of micro- and macroeconomics, deal with the scale mismatch problem, and how taking clues from (micro)economists could benefit the field of microbiomics

    The MEC1 and MEC2 lines represent two CLL subclones in different stages of progression towards prolymphocytic leukemia.

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    The EBV carrying lines MEC1 and MEC2 were established earlier from explants of blood derived cells of a chronic lymphocytic leukemia (CLL) patient at different stages of progression to prolymphocytoid transformation (PLL). This pair of lines is unique in several respects. Their common clonal origin was proven by the rearrangement of the immunoglobulin genes. The cells were driven to proliferation in vitro by the same indigenous EBV strain. They are phenotypically different and represent subsequent subclones emerging in the CLL population. Furthermore they reflect the clinical progression of the disease. We emphasize that the support for the expression of the EBV encoded growth program is an important differentiation marker of the CLL cells of origin that was shared by the two subclones. It can be surmised that proliferation of EBV carrying cells in vitro, but not in vivo, reflects the efficient surveillance that functions even in the severe leukemic condition. The MEC1 line arose before the aggressive clinical stage from an EBV carrying cell within the subclone that was in the early prolymphocytic transformation stage while the MEC2 line originated one year later, from the subsequent subclone with overt PLL characteristics. At this time the disease was disseminated and the blood lymphocyte count was considerably elevated. The EBV induced proliferation of the MEC cells belonging to the subclones with markers of PLL agrees with earlier reports in which cells of PLL disease were infected in vitro and immortalized to LCL. They prove also that the expression of EBV encoded set of proteins can be determined at the event of infection. This pair of lines is particularly important as they provide in vitro cells that represent the subclonal evolution of the CLL disease. Furthermore, the phenotype of the MEC1 cells shares several characteristics of ex vivo CLL cells

    PROFIL DES UTILISATEURS DU PREMIER KIT DE DÉPISTAGE PAR AUTOPRÉLÈVEMENT DU PROGRAMME MÉMODÉPISTAGES PROPOSÉ AUX HSH MULTIPARTENAIRES EN FRANCE EN 2018

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    International audienceIn 2017, the French National Authority for Health’s guidelines for HIV screening stated that men who havesex with men (MSM) should be screened every three months. This pace was defined to reduce the intervalbetween infection and diagnosis and the proportion of undiagnosed people for HIV. To support the implementationof these guidelines, a wide range of screening options were available – laboratory, anonymousscreening centers, self-administered tests, community screening– but there were fewer options for othersexually transmitted infections (STIs). To help MSM repeat the HIV screening while taking into considerationthe STIs issue, Santé publique France developed the MemoDepistages program designed for multi-partnerMSM. Advertised online in spring 2018, the program offered MSM with multiple partners a self-samplingkit (SSK) for HIV, HBV, HCV, syphilis, and gonococcal and chlamydia infections. Among the 7,158 men whowere offered the kit, 27.2% used it to make at least one of the four tests proposed. Users lived mainly in bigcities, were highly educated and frequent users of gay meeting venues. Sociodemographic factors (age,diploma) were strongly associated with using the kit. SSK was used by 30% of our sample with small variationbetween the different groups, and addressed a diverse population regarding socio-demographic and HIVscreening habits at baseline.En 2017, la Haute Autorité de Santé (HAS) a fixé à trois mois la fréquence optimale de dépistage pour le VIHdes hommes ayant des relations sexuelles avec d’autres hommes (HSH) afin de réduire le délai entre la datede l’infection et le diagnostic et la part des personnes vivant avec le VIH non diagnostiquées. Ces objectifss’appuientsur une offre variée de dépistage du VIH – laboratoires, centres de dépistages anonymes, autotests,dépistages communautaires – mais moins diversifiée pour les autres infections sexuellement transmissibles (IST).Afin d’encouragerle dépistage répété du VIH tout en tenant compte des enjeux relatifs au dépistage des autresIST, Santé publique France a construit le programme MémoDépistages à destination de HSH multipartenaires.Promu en ligne au printemps 2018, ce programme proposait un kit d’autoprélèvement pour réaliser le dépistagedu VIH, du VHB, du VHC, de la syphilis, des infections à chlamydia et à gonocoques. Parmi les 7 158 hommeséligibles auxquels un kit d’autoprélèvement a été proposé, 27,2% l’ont utilisé pour réaliser au moins l’un desquatre prélèvements proposés. Il s’agissait majoritairement d’hommes citadins, avec un haut niveau d’étude,familiers des lieux de convivialité gay. Ce sont principalement les facteurs sociodémographiques (âge, niveaud’étude) qui étaient associés à un taux élevé d’utilisation de l’autoprélèvement dans l’étude. Utilisé par près de30% des hommes auxquels il est proposé, le kit d’autoprélèvement permet d’amener au dépistage une populationdiversifiée tant en termes sociodémographiques qu’en termes de comportements face au dépistage

    Comparison of the MEC1 and MEC2 cells.

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    <p>(A) Expression of EBV encoded proteins EBNA-2 and LMP-1 by immunofluorescence; magnification (×100), scale bar 25 µm. Note: the MEC2 cells are larger. (B) Expression of EBNA-2 and LMP-1 by immunoblotting; positive control: CBM1-Ral-STO, negative control: Ramos. 1.5×10<sup>5</sup> cells were loaded in control lanes and 5×10<sup>5</sup> were loaded in MEC1 and MEC2 lanes. Note MEC2 expresses higher amount of EBNA-2. (C) Expression of Bright and BARF1 by Q-PCR. (D) FACS analysis of surface markers that are differently expressed in the 2 lines.</p

    The effect of IL-21 and CD40L exposure on MEC1 and MEC2 cells.

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    <p>Expression of EBNA-2 and LMP-1 in IL-21 treated cells (A, B). (A) Simultaneous immunofluorescence staining of EBNA-2 (Green) and LMP-1 (Red); magnification (×100), scale bar 25 µm. Note the downregulation of EBNA-2 and upregultion of LMP-1 after IL-21 treatment. (B) Expression of EBNA-2, LMP-1 and Blimp-1 by immunoblotting; positive control: CBM1-Ral-STO, negative control: Ramos. 1.5×10<sup>5</sup> cells were loaded in the control lanes and 5×10<sup>5</sup> were loaded in both untreated and IL-21 treated MEC1 and MEC2 lanes. Note low expression of EBNA-2 and high expression of LMP-1 after IL-21 treatment and induction of Blimp-1 after IL-21 treatment. (C) Activity of the W and C promoters that regulate EBNA-2 expression and LMP-1 mRNA expression by Q-PCR. Note the difference in EBNA-2 regulation; the MEC2 cell uses both Wp and Cp while in MEC1 only Wp is active. (D) Expression of EBNA-2 and LMP-1 in cells exposed to CD40L. Simultaneous immunofluorescence staining; for details see (A). Note: EBNA-2 and LMP-1 are downregulated by CD40L in both lines. (E) CD40L induced modulation of surface marker by FACS analysis.</p

    Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial

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