Structure-function studies of the Parkinsonism-linked protein DJ-1

DJ-1 is a multifunctional protein linked to familial Parkinson’s disease. DJ-1 has been suggested to exert its cytoprotective function, in part, by acting as a copper carrier that can sequester the reactive metal and/or provide the copper cofactor for the activation of the Cu-Zn superoxide dismutase (SOD1). Using absorption spectroscopy and mass spectrometry, we found that DJ-1 binds one Cu(I) ion per DJ-1 homodimer. The structure of Cu(I)-bound DJ-1 reveals a new biscysteinate metal binding motif formed by juxtaposed Cys-53 at the homodimer interface. We calculated a subfemtomolar dissociation constant (Kd = 6.41 x 10-16 M) for Cu(I) that supports the physiological intracellular retention of the metal. Cu(I)-bound DJ-1 was not capable of interacting and activating SOD1 in vitro. We posit that DJ-1 sequester copper to protect against metal-induced cytotoxicity. Our results illuminate the molecular basis on how disease-linked mutations that impairs homodimerisation could disrupt the metal binding site. In the second part of this dissertation, we sought to determine the impact of a Parkinsonism-linked A107P mutation on DJ-1 structure and glyoxalase activity. The A107P variant abrogates the ability of DJ-1 to protect against glyoxal-induced cytotoxicity and carboxymethyllysine protein modification. A crystal structure of DJ-1 C106S variant with glycerol and sulphate bound in the active site suggests that Ala-107 is critical for the stabilization of the transition state of the nucleophilic addition step. In our hands, the protein levels of DJ-1 A107P mutant in SH-SH5Y cells were ostensibly similar to the wild-type level but reduced levels were found in HEK 293E and MEF cells. Using CD and NMR spectroscopy, we found that the structural defect caused by the mutation extends beyond the active site. The A107P mutation resulted in a remarkable misfolding of the protein providing a basis for the reduced intracellular protein level and the abrogation of enzymatic activity

Hybridization between wild and cultivated potato species in the Peruvian Andes and biosafety implications for deployment of GM potatoes

The nature and extent of past and current hybridization between cultivated potato and wild relatives in nature is of interest to crop evolutionists, taxonomists, breeders and recently to molecular biologists because of the possibilities of inverse gene flow in the deployment of genetically-modified (GM) crops. This research proves that natural hybridization occurs in areas of potato diversity in the Andes, the possibilities for survival of these new hybrids, and shows a possible way forward in case of GM potatoes should prove advantageous in such areas

A holistic approach to enhance the use of neglected and underutilized species: the case of Andean grains in Bolivia and Peru

The IFAD-NUS project, implemented over the course of a decade in two phases, represents the first UN-supported global effort on neglected and underutilized species (NUS). This initiative, deployed and tested a holistic and innovative value chain framework using multi-stakeholder, participatory, inter-disciplinary, pro-poor gender- and nutrition-sensitive approaches. The project has been linking aspects often dealt with separately by R&D, such as genetic diversity, selection, cultivation, harvest, value addition, marketing, and final use, with the goal to contribute to conservation, better incomes, and improved nutrition and strengthened livelihood resilience. The project contributed to the greater conservation of Andean grains and their associated indigenous knowledge, through promoting wider use of their diversity by value chain actors, adoption of best cultivation practices, development of improved varieties, dissemination of high quality seed, and capacity development. Reduced drudgery in harvest and postharvest operations, and increased food safety were achieved through technological innovations. Development of innovative food products and inclusion of Andean grains in school meal programs is projected to have had a positive nutrition outcome for targeted communities. Increased income was recorded for all value chain actors, along with strengthened networking skills and self-reliance in marketing. The holistic approach taken in this study is advocated as an effective strategy to enhance the use of other neglected and underutilized species for conservation and livelihood benefits

Hybridization between wild and cultivated potato species in the Peruvian Andes and biosafety implications for deployment of GM potatoes

The nature and extent of past and current hybridization between cultivated potato and wild relatives in nature is of interest to crop evolutionists, taxonomists, breeders and recently to molecular biologists because of the possibilities of inverse gene flow in the deployment of genetically-modified (GM) crops. This research proves that natural hybridization occurs in areas of potato diversity in the Andes, the possibilities for survival of these new hybrids, and shows a possible way forward in case of GM potatoes should prove advantageous in such areas

Revisiting the Andean butterfly Eryphanis zolvizora group (Lepidoptera, Nymphalidae) : one or several species?

Eryphanis zolvizora (Hewitson, 1877) is a rare Andean endemic butterfly, described from Bolivia, which has been historically classified either as a unique species, or as part of a group of three allopatric species from Bolivia, Ecuador and Colombia. In this paper, the group is revised using more than 200 specimens housed in 35 European and North and South American public and private collections. For the first time, the presence of the group in Western Ecuador and Venezuela is confirmed, and important data on Peruvian populations are provided. In some populations, individual variations of genitalia are observed. Nevertheless, male genitalia allow the distinction of four geographical groups. Considering also habitus characters, eight taxa are distinguished and considered to be subspecies, of which five are new: Eryphanis zolvizora inca ssp. nov., Eryphanis zolvizora chachapoya ssp. nov., Eryphanis zolvizora casagrande ssp. nov., Eryphanis zolvizora reyi ssp. nov., and Eryphanis zolvizora isabelae ssp. nov. In the present state of knowledge, these taxa are allopatric, except for a possible geographic overlap in central Peru, where data are insufficient to prove sympatry. The “several subspecies vs. several species” dilemma is discussed, considering its impact for conservation action and policies

Puno : ¿cómo vamos en educación?

Reúne información estadística relevante de la situación actual de la educación de la región Puno, ha sido hecho para servir como una guía informativa amigable de todos aquellos actores de la región que puedan influir positivamente en su realidad educativa. Entre 2004 y 2013, ha habido una tendencia de aumento a una tasa media de crecimiento anual del gasto público educativo por alumno de 21.2% en inicial, 14.4% en primaria y 9.3% en secundaria. Sin embargo, cuando se observa el gasto en educación, respecto al GPT (Gasto Público Total), pasa lo contrario, hay una tendencia a la baja. Ambas situaciones no particularidades de Puno sino características a nivel nacional. A nivel distrital, hay distritos como Tinicachi con el 100% de locales educativos con los tres servicios básicos, mientras que otros como Achaya no tienen ningún local con los tres servicios. Esto ilustra la heterogeneidad de la región. En 2014, el indicador de la región Puno asciende a 29.9% frente a un 41.5% para todo el Perú. El porcentaje de escuelas con acceso a Internet tanto a nivel nacional como de la región Puno registra un crecimiento sostenido en los últimos diez años, en particular en el caso de secundaria, que en Puno pasó de tener en el 2005 solo el 9% de escuelas con Internet a más de la tercera parte (40.8%) en 2014. Sin embargo, tanto en primaria como en secundaria, este indicador está muy por debajo del nivel nacional (10 puntos porcentuales por debajo para primaria y 12.8 puntos porcentuales para secundaria). La tasa neta de asistencia en primaria, inicial y secundaria en Puno en comparación con el nivel nacional tiende a ser estadísticamente igual, no existiendo diferencias significativas en comparación con los porcentajes nacionales. El acceso a educación en el nivel de primaria e inicial se ha mantenido estadísticamente estable entre 2004 y 2013 en un valor promedio de 92.5% y 81.9 respectivamente; mientras que por su parte la tasa en inicial tienden a crecer, pasando de 48.1% en 2004 a 73.4% en 2013. En 2014, el indicador de alumno por docente de Puno resulta ser mejor en comparación con el indicador nacional (en la región: 14, 10 y 11 en inicial, primaria y secundaria, frente al nacional: 16, 14 y 11, respectivamente). Los valores de la mayoría de distritos se sitúa en dos grupos que se encuentran comprendidos entre 7.4 y 22 alumnos por profesor. Puno presenta menores tasas de desaprobación en primaria y secundaria y de retiro y atraso en primaria con respecto a todo el país, mientras que en atraso y retiro de secundaria sus tasas son mayores siendo que mientras en el nivel nacional los porcentajes de atraso y de retiro son de 13.7% y 3.6%, en Puno estos valores son de 14.3% y 4.4% respectivamente. El porcentaje de desaprobados en primaria fluctúa desde 1.8% para Chucuito hasta 11.1% para Azángaro. Respecto al atraso escolar, todos los distritos en primaria se ubican en el quintil más bajo (menor a 20%) mientras que en secundaria todos salvo uno están distribuidos entre el primer y segundo quintil (menores a 40%)

A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway.

The invasion-associated type III secretion system (T3SS-1) of Salmonella enterica serotype Typhimurium (S. Typhimurium) activates the transcription factor NF-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacterial delivery or ectopic expression of SipA, a T3SS-1-translocated protein, led to the activation of the NOD1/NOD2 signaling pathway and consequent RIP2-mediated induction of NF-κB-dependent inflammatory responses. SipA-mediated activation of NOD1/NOD2 signaling was independent of bacterial invasion in vitro but required an intact T3SS-1. In the mouse colitis model, SipA triggered mucosal inflammation in wild-type mice but not in NOD1/NOD2-deficient mice. These findings implicate SipA-driven activation of the NOD1/NOD2 signaling pathway as a mechanism by which the T3SS-1 induces inflammatory responses in vitro and in vivo

目次

TRUCHA ARCOÍRIS DIMORFISMO SEXUAL SANIDAD, BIOSEGURIDAD Y PATOLOGÍA PROPIEDADES DE LA TRUCHA CICLO DE PRODUCCIÓN DE LA TRUCHA MARCO JURÍDCO DE ACCESO E INVERSIÓN PARA EL CULTIVO DE TRUCHA LA TRUCHA EN EL PERÚ PRINCIPALES ZONAS DE ACTIVIDAD TRUCHÍCOLA EN LA REGIÓN PUNO LA TRUCHA EN LA REGIÓN PUNO CONSUMO PERCÁPITA DE TRUCHA COMERCIALIZACIÓN ASPECTOS ECONÓMICOS PARTIDA ARANCELARIAS DE LA TRUCHA ANÁLISIS NET-SHARE DE LOS MERCADOS INTERNACIONALES ANÁLISIS DE MERCADOS PRE-SELECCIONADOS DE INTERÉS MATRIZ DE SELECCIÓN CUALITATIVA ANÁLISIS FODA: PRODUCCIÓN DE TRUCHA ARCOÍRIS DE LAS PISCIGRANJAS EN LA REGIÓ