Caspase-2 Mediated Apoptotic and Necrotic Murine Macrophage Cell Death Induced by Rough Brucella abortus

Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK). Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella pathogenesis and protective Brucella immunity is discussed

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Conocimiento sobre el fenómeno de las drogas en entre estudiantes y docentes de la Facultad de Medicina Universidad Mayor de San Andrés, La Paz, Bolivia Conhecimento sobre o fenômeno das drogas entre estudantes e docentes da Faculdade de Medicina da Universidade Mayor de San Andrés, La Paz, Bolívia Knowledge on drugs phenomenon by students and faculty from the Medical School at Universidad Mayor de San Andrés, La Paz, Bolivia

El objetivo de este estudio fue identificar el grado de conocimiento de los estudiantes y docentes de salud sobre drogas lícitas e ilícitas, relacionadas a: tipo, clasificación, acción, mecanismos, daños, consecuencias y efectos adversos además del uso y consumo. El diseño metodológico fue de "corte transversal, con una muestra de 172 estudiantes, profesores y residentes de las áreas de medicina y enfermería de la Universidad Mayor de San Andrés (UMSA), en Bolivia. Los resultados revelan que existe una debilidad en cuanto al conocimiento en relación a la clasificación de sustancias psicotrópicas de acuerdo con la estructura, propiedad química y efectos que producen en la salud, destacándose una diferencia significativa del conocimiento sobre drogas lícitas, como el alcohol y tabaco, con las drogas ilícitas. Se resalta el desconocimiento en todo el grupo estudiado sobre drogas lícitas e ilícitas, consecuencias y efectos adversos, lo que confirma la necesidad de mejorar la enseñanza en este contenido en las escuelas de salud.<br>O objetivo deste estudo foi identificar o grau de conhecimento dos estudantes e professores da área da saúde sobre drogas lícitas e ilícitas, em relação ao tipo, classificação, mecanismos de ação, danos, consequências e efeitos adversos, decorrentes de seu consumo. Trata-se de estudo de coorte transversal, com amostra de 172 estudantes, professores e residentes das áreas de medicina e enfermagem da Universidad Mayor de San Andrés (UMSA), Bolívia. Os resultados revelam baixo nível de conhecimento dos sujeitos da investigação, relacionado à classificação de substâncias psicotrópicas, quanto à estrutura, propriedade química e efeitos que produzem na saúde, destacando-se diferença significativa entre o conhecimento sobre drogas lícitas, como álcool e tabaco, e drogas ilícitas. Ressalta-se o desconhecimento de todos os sujeitos da investigação sobre drogas lícitas e ilícitas, quanto às consequências e efeitos adversos à saúde, o que indica a necessidade de se promover melhoria do ensino desse conteúdo em escolas da área da saúde.<br>The goal of this study was to identify the degree of knowledge of students and health educators on licit and illicit drugs, related to the type, classification, action, mechanisms damages, consequences and adverse effects, besides use and consumption. A cross-sectional methodological design was used, with a sample of 172 students, professors and residents in medicine and nursing at Universidad Mayor de San Andrés (UMSA), Bolivia. The results reveal weak knowledge on the classification of psychotropic substances according to structure, chemical property and effects for health, highlighting significant difference with knowledge on licit and illicit drugs use, with high percentages. In conclusion, there is lack of knowledge in all groups studied on licit and illicit drugs regarding the consequences and adverse effects. This confirms the need to improve teaching on this content in health schools