Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice

Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP), develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection. Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice

DESFIBRILADORES EXTERNOS SEMIAUTOMÁTICOS (DESA). EL PROFESIONAL DE ENFERMERÍA COMO INSTRUCTOR DE PERSONAL NO SANITARIO

The main cause of cardiac arrest in adults in out-of-hospital setting is Ventricular Fibrillation (VF). This chaotic heart rhythm represents 75-80 % of sudden cardiac deaths. The possibility of survival decreases by 10 % each minute of delay, therefore emergency action must take place almost immediately in this situation. An early defibrillation could save the life of a person with a VF, above all in the case of being witnessed. One of the most important goals in the Cardiopulmonary Resuscitation (CPR) is incorporating defibrillation into the Basic Life Support. Semiautomatic External Defibrillators (AED) are designed to be used by people without medical backgrounds. Decree 220/2007 of November 2 of the Council of the Government of Valencia regulates the use of AED by non medical personnel. Its objective is the regulation of the use of AED by non health care personnel within the region of Valencia. Nursing professionals must take part of the training team of the use of AED by non health care personnel.La causa principal de parada cardiorrespiratoria (PCR) en el adulto en el medio extrahospitalario es la Fibrilación Ventricular (FV); este ritmo caótico, representa el 75-80% de las muertes súbitas de origen cardíaco. Por cada minuto que se retrasa el tratamiento se reduce un 10% la posibilidad de supervivencia de la persona; se hace necesaria, por tanto, una atención precoz en esta situación. Una desfibrilación precoz podría salvar la vida de una persona con una fibrilación ventricular, sobretodo en el caso de ser presenciada. Uno de los objetivos más importantes en la reanimación cardiopulmonar es el de acercar la desfibrilación al soporte vital básico (SVB). Los desfibriladores externos semiautomáticos (DESA) están preparados para ser utilizados por personal no sanitario. El Decreto 220/2007, de 2 de noviembre del Consell del Gobierno Valenciano, regula la utilización de desfibriladores semiautomáticos externos por personal no médico y tiene como objeto la regulación del uso del DESA por personal no sanitario en el territorio de la CV. El profesional de enfermería puede y debe formar parte de los equipos docentes para formación de utilización de DESA para personal no sanitario

Transcriptome profiling of grapevine seedless segregants during berry development reveals candidate genes associated with berry weight

Indexación: Web of Science; PubMedBackground Berry size is considered as one of the main selection criteria in table grape breeding programs. However, this is a quantitative and polygenic trait, and its genetic determination is still poorly understood. Considering its economic importance, it is relevant to determine its genetic architecture and elucidate the mechanisms involved in its expression. To approach this issue, an RNA-Seq experiment based on Illumina platform was performed (14 libraries), including seedless segregants with contrasting phenotypes for berry weight at fruit setting (FST) and 6–8 mm berries (B68) phenological stages. Results A group of 526 differentially expressed (DE) genes were identified, by comparing seedless segregants with contrasting phenotypes for berry weight: 101 genes from the FST stage and 463 from the B68 stage. Also, we integrated differential expression, principal components analysis (PCA), correlations and network co-expression analyses to characterize the transcriptome profiling observed in segregants with contrasting phenotypes for berry weight. After this, 68 DE genes were selected as candidate genes, and seven candidate genes were validated by real time-PCR, confirming their expression profiles. Conclusions We have carried out the first transcriptome analysis focused on table grape seedless segregants with contrasting phenotypes for berry weight. Our findings contributed to the understanding of the mechanisms involved in berry weight determination. Also, this comparative transcriptome profiling revealed candidate genes for berry weight which could be evaluated as selection tools in table grape breeding programs.http://bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-016-0789-

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4×10-48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3×10-43 cm2 (7.1×10-42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

The cadherin–catenin complex in nasopharyngeal carcinoma

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in nasopharyngeal carcinoma. The aim of this study was to analyze β-Catenin cellular location and E-cadherin expression levels in nasopharyngeal carcinoma. E-cadherin expression levels were also correlated with clinical data and underlying pathology. β-Catenin and E-cadherin expression were examined in 18 nasopharyngeal carcinoma and 7 non-tumoral inflammatory pharynx tissues using immunohistochemical methods. Patient clinical data were collected, and histological evaluation was performed by hematoxylin/eosin staining. β-catenin was detected in membrane and cytoplasm in all cases of nasopharyngeal carcinoma, regardless of histological type; in non-tumoral tissues, however, β-catenin was observed only in the membrane. As for E-cadherin expression levels, strong staining was observed in most non-tumoral tissues, but staining was only moderate in nasopharyngeal carcinoma tissues. E-cadherin expression was associated with β-catenin localization, study group, metastatic disease, and patient outcomes. Reduced levels of E-cadherin protein observed in nasopharyngeal carinoma may play an important role in invasion and metastasis. Cytoplasmic β-catenin in nasopharyngeal carcinoma may impair cell–cell adhesion, promoting invasive behavior and a metastatic tumor phenotype

Simulations of events for the LUX-ZEPLIN (LZ) dark matter experiment

The LUX-ZEPLIN dark matter search aims to achieve a sensitivity to the WIMP-nucleon spin-independent cross-section down to (1–2)×10−12 pb at a WIMP mass of 40 GeV/c2. This paper describes the simulations framework that, along with radioactivity measurements, was used to support this projection, and also to provide mock data for validating reconstruction and analysis software. Of particular note are the event generators, which allow us to model the background radiation, and the detector response physics used in the production of raw signals, which can be converted into digitized waveforms similar to data from the operational detector. Inclusion of the detector response allows us to process simulated data using the same analysis routines as developed to process the experimental data

Projected sensitivity of the LUX-ZEPLIN experiment to the 0νββ decay of Xe 136

The LUX-ZEPLIN (LZ) experiment will enable a neutrinoless double β decay search in parallel to the main science goal of discovering dark matter particle interactions. We report the expected LZ sensitivity to Xe136 neutrinoless double β decay, taking advantage of the significant (>600 kg) Xe136 mass contained within the active volume of LZ without isotopic enrichment. After 1000 live-days, the median exclusion sensitivity to the half-life of Xe136 is projected to be 1.06×1026 years (90% confidence level), similar to existing constraints. We also report the expected sensitivity of a possible subsequent dedicated exposure using 90% enrichment with Xe136 at 1.06×1027 years

Corrigendum: Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy.

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P\u2009=\u20097.54E-07; ORGCA\u2009=\u20091.19, ORTAK\u2009=\u20091.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA\u2009=\u20095.52E-04, ORGCA\u2009=\u20091.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus