Bluetongue Virus Serotype 1 Outbreak in the Basque Country (Northern Spain) 2007–2008. Data Support a Primary Vector Windborne Transport

BACKGROUND: Bluetongue (BT) is a vector-borne disease of ruminants that has expanded its traditional global distribution in the last decade. Recently, BTV-1 emerged in Southern Spain and caused several outbreaks in livestock reaching the north of the country. The aim of this paper was to review the emergence of BTV-1 in the Basque Country (Northern Spain) during 2007 and 2008 analyzing the possibility that infected Culicoides were introduced into Basque Country by winds from the infected areas of Southern Spain. METHODOLOGY/PRINCIPAL FINDINGS: We use a complex HYSPLIT (Hybrid Single-Particle Lagrangian Integrated Trajectory) model to draw wind roses and backward wind trajectories. The analysis of winds showed September 28 to October 2 as the only period for the introduction of infected midges in the Basque Country. These wind trajectories crossed through the areas affected by serotype 1 on those dates in the South of the Iberian Peninsula. Additionally meteorological data, including wind speed and humidity, and altitude along the trajectories showed suitable conditions for Culicoides survival and dispersion. CONCLUSIONS/SIGNIFICANCE: An active infection in medium-long distance regions, wind with suitable speed, altitude and trajectory, and appropriate weather can lead to outbreaks of BTV-1 by transport of Culicoides imicola, not only over the sea (as reported previously) but also over the land. This shows that an additional factor has to be taken into account for the control of the disease which is currently essentially based on the assumption that midges will only spread the virus in a series of short hops. Moreover, the epidemiological and serological data cannot rule out the involvement of other Culicoides species in the spread of the infection, especially at a local level

Discovery of a Glucocorticoid Receptor (GR) Activity Signature Using Selective GR Antagonism in ER-Negative Breast Cancer

Purpose: Although high glucocorticoid receptor (GR) expression in early-stage estrogen receptor (ER)-negative breast cancer is associated with shortened relapse-free survival (RFS), how associated GR transcriptional activity contributes to aggressive breast cancer behavior is not well understood. Using potent GR antagonists and primary tumor gene expression data, we sought to identify a tumor-relevant gene signature based on GR activity that would be more predictive than GR expression alone. Experimental Design: Global gene expression and GR ChIP-sequencing were performed to identify GR-regulated genes inhibited by two chemically distinct GR antagonists, mifepristone and CORT108297. Differentially expressed genes from MDA-MB-231 cells were cross-evaluated with significantly expressed genes in GR-high versus GR-low ER-negative primary breast cancers. The resulting subset of GR-targeted genes was analyzed in two independent ER-negative breast cancer cohorts to derive and then validate the GR activity signature (GRsig). Results: Gene expression pathway analysis of glucocorticoid-regulated genes (inhibited by GR antagonism) revealed cell survival and invasion functions. GR ChIP-seq analysis demonstrated that GR antagonists decreased GR chromatin association for a subset of genes. A GRsig that comprised n = 74 GR activation-associated genes (also reversed by GR antagonists) was derived from an adjuvant chemotherapy-treated Discovery cohort and found to predict probability of relapse in a separate Validation cohort (HR = 1.9; P = 0.012). Conclusions: The GRsig discovered herein identifies highrisk ER-negative/GR-positive breast cancers most likely to relapse despite administration of adjuvant chemotherapy. Because GR antagonism can reverse expression of these genes, we propose that addition of a GR antagonist to chemotherapy may improve outcome for these high-risk patients. (C) 2018 AACR

Recoletiones et quaestiones morales, ex vtraque facultate decerptae : in quibus breui et claro stylo proposita, et explicata littera Decretalis textus ... : quibus in fine additur explanatio propositionu damnataru, tam ab AlexandroVII quàm ab Innocentio XI ...

Sign.: [calderón]\p8\s, a-b\p8\s, A-Z\p8\s, 2A-2R\p8\s, 2S\p6\sTexto a dos colPort. orlada y con grab. xil. representando la Santísima Trinida

Recoletiones et quaestiones morales, et utraque facultate decerptae : in quibus brevi, et claro stylo proposita, et explicata littera decretalis textus...

Sign. : ¿¡8, a-b¡8, A-Z¡8, 2A-2K¡8, 2S¡6Error de pag., de p. 496 pasa a 499Texto a dos colPort. con orla tip. y grab. xilLetras capitales grab. xi

Título: Recoletionum moralium huius primi decretalium libri. Tomus secundus

Sign. : ¿¡4, 2¿¡2, A-Z¡8, 2A-2Z¡8, 3A¡6Texto a dos colPort. con orla tip. y grab. xilLetras capitales grab. xi