The Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-to-ER Retrograde Transport

Ubiquitination regulates several biological processes, however the role of specific members of the ubiquitinome on intracellular membrane trafficking is not yet fully understood. Here, we search for ubiquitin-related genes implicated in protein membrane trafficking performing a High-Content siRNA Screening including 1187 genes of the human “ubiquitinome” using amyloid precursor protein (APP) as a reporter. We identified the deubiquitinating enzyme PSMD14, a subunit of the 19S regulatory particle of the proteasome, specific for K63-Ub chains in cells, as a novel regulator of Golgi-to-endoplasmic reticulum (ER) retrograde transport. Silencing or pharmacological inhibition of PSMD14 with Capzimin (CZM) caused a robust increase in APP levels at the Golgi apparatus and the swelling of this organelle. We showed that this phenotype is the result of rapid inhibition of Golgi-to-ER retrograde transport, a pathway implicated in the early steps of the autophagosomal formation. Indeed, we observed that inhibition of PSMD14 with CZM acts as a potent blocker of macroautophagy by a mechanism related to the retention of Atg9A and Rab1A at the Golgi apparatus. As pharmacological inhibition of the proteolytic core of the 20S proteasome did not recapitulate these effects, we concluded that PSMD14, and the K63-Ub chains, act as a crucial regulatory factor for macroautophagy by controlling Golgi-to-ER retrograde transport

Incidence and mortality rates of selected infection-related cancers in Puerto Rico and in the United States

<p>Abstract</p> <p>Background</p> <p>In 2002, 17.8% of the global cancer burden was attributable to infections. This study assessed the age-standardized incidence and mortality rates of stomach, liver, and cervical cancer in Puerto Rico (PR) for the period 1992-2003 and compared them to those of Hispanics (USH), non-Hispanic Whites (NHW), and non-Hispanic Blacks (NHB) in the United States (US).</p> <p>Methods</p> <p>Age-standardized rates [ASR(World)] were calculated based on cancer incidence and mortality data from the PR Cancer Central Registry and SEER, using the direct method and the world population as the standard. Annual percent changes (APC) were calculated using the Poisson regression model from 1992-2003.</p> <p>Results</p> <p>The incidence and mortality rates from stomach, liver and cervical cancer were lower in NHW than PR; with the exception of mortality from cervical cancer which was similar in both populations. Meanwhile, the incidence rates of stomach, liver and cervical cancers were similar between NHB and PR; except for NHB women who had a lower incidence rate of liver cancer than women in PR. NHB had a lower mortality from liver cancer than persons in PR, and similar mortality from stomach cancer.</p> <p>Conclusions</p> <p>The burden of liver, stomach, and cervical cancer in PR compares to that of USH and NHB and continues to be a public health priority. Public health efforts are necessary to further decrease the burden of cancers associated to infections in these groups, the largest minority population groups in the US. Future studies need to identify factors that may prevent infections with cancer-related agents in these populations. Strategies to increase the use of preventive strategies, such as vaccination and screening, among minority populations should also be developed.</p

Comparación de alternativas de manejo para plagas convencional e integrado (MIP) en el cultivo del sorgo (Sorghum bicolor (L) Moench), en época de postrera en las localidades Guanacastillo - Masaya y CNIA-INTA, Managua 2004

Este trabajo se realizó en dos localidades; finca El Paraíso ubicada en el km 38 carretera Masaya-Tipitapa; Comarca Guanacastillo municipio de Masaya y Centro Nacional de Investigación Agropecuaria (CNIA-INTA), ubicada en el km 14 carretera norte departamento de Managua. Con el objetivo de generar alternativas de manejo de plagas insectíles y enfermedades en el cultivo del sorgo. El diseño experimental utilizado fue bloque completos al azar (BCA), con cuatro tratamientos y cinco repeticiones: T1 (una aplicación de cypermetrina, phyton, benomil en etapa vegetativa y reproductiva), T2 (dos aplicaciones de cypermetrina, phyton, benomil en etapa vegetativa y reproductiva), T3 (una aplicación de dipel, caldo sulfocalcico en etapa vegetativa y reproductiva), T4 (dos aplicaciones de dipel, caldo sulfocalcico en etapa vegetativa y reproductiva). Las variables evaluadas fueron: incidencia de daño fresco por cogollero, severidad de enfermedades foliares e incidencia de mohos de la panoja y rendimiento. Se realizó análisis de varianza (ANDEVA) y separación de medias por Duncan con ( α = 5%). Para el gusano cogollero el análisis estadístico indica que se encontró diferencia significativa entre los diferentes tratamientos en ambas localidades. Presentando los menores porcentajes de daños los tratamientos dipel y caldo sulfocá lcico. El análisis de varianza realizado para raya tiznada y mohos de la panoja mostró diferencias estadísticas en ambas localidades, no así para ohos de la panoja en la localidad finca El Paraíso. Para la variable rendimiento el análisis indica que no se encontró diferencia estadística entre los tratamientos en ambas localidades, obteniendo los mayores rendimientos los tratamientos T3 y T4, con 2520 y 2626 kg ha-1(finca El Paraíso), 2762 y 2814 kg ha-1(CNIA-INTA) respectivamente. En el análisis económico los menores costos variables se obtuvo en el tratamiento T3 en ambas localidades y la mayor rentabilidad con 965.86 % (finca El Paraíso) y 1068.19 % (CNIA- INTA)

ARNECON, SA.-León, la influencia que tiene en el desarrollo socioeconómico de sus trabajadores, 2008-2009

Tesis (Lic. en Ciencias de la Educación con Mención en Ciencias Sociales)-Universidad Nacional Autónoma de Nicaragua, León.UNAN-Leó

Steatotic livers. Can we use them in OLTX? Outcome data from a prospective baseline liver biopsy study

Introduction. Steatotic livers have been associated with greater risk of allograft dysfunction in liver transplantation. Our aim was to determinate the prevalence of steatosis in grafts from deceased donors in Chile and to assess the utility of a protocol-bench biopsy as an outcome predictor of steatotic grafts in our transplant program.Material and methods. We prospectively performed protocol-bench graft biopsies from March 2004 to January 2009. Biopsies were analyzed and classified by two independent pathologists. Steatosis severity was graded as normal from absent to 33-66% and grade 3: > 66%.Results. We analyzed 58 liver grafts from deceased donors. Twenty-nine grafts (50%) were steatotic; 9 of them (16%) with grade 3. Donor age (p < 0.001) and BMI over 25 kg/m2 (p = 0.012) were significantly associated with the presence of steatosis. There were two primary non-functions (PNF); both in a grade 3 steatotic graft. The 3-year overall survival was lower among recipients with macrovesicular steatotic graft (57%) than recipients with microvesicular (85%) or non-steatotic grafts (95%) (p = 0.026).Conclusion. Macro-vesicular steatosis was associated with a poor outcome in this series. A protocol bench-biopsy would be useful to identify these grafts