Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.

Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors

Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs

The DNA repair proteins poly(ADP-ribose) polymerase-1 (PARP-1), Ku86, and catalytic subunit of DNA-PK (DNA-PKcs) have been involved in telomere metabolism. To genetically dissect the impact of these activities on telomere function, as well as organismal cancer and aging, we have generated mice doubly deficient for both telomerase and any of the mentioned DNA repair proteins, PARP-1, Ku86, or DNA-PKcs. First, we show that abrogation of PARP-1 in the absence of telomerase does not affect the rate of telomere shortening, telomere capping, or organismal viability compared with single telomerase-deficient controls. Thus, PARP-1 does not have a major role in telomere metabolism, not even in the context of telomerase deficiency. In contrast, mice doubly deficient for telomerase and either Ku86 or DNA-PKcs manifest accelerated loss of organismal viability compared with single telomerase-deficient mice. Interestingly, this loss of organismal viability correlates with proliferative defects and age-related pathologies, but not with increased incidence of cancer. These results support the notion that absence of telomerase and short telomeres in combination with DNA repair deficiencies accelerate the aging process without impacting on tumorigenesis

The first occurrence of Cobitis paludica (de Buen, 1930) in the Segura River Basin (SE Iberian Peninsula)

The aim of the present report is to describe the establishment of viable populations of Cobitis paludica (de Buen, 1930) in the Segura River Basin. We found two isolated populations: one located in the upper part of the Segura River and the mouth of its tributary, the Zumeta River, and another in the Mundo River, between the Talave and Camarillas reservoirs. We hypothesised that the introduction of this species may be attributable to the deliberate or accidental introduction by anglers or fish translocation from the Tajo-Segura interbasin water transfer system. C. paludica is a threatened endemic fish species from the Iberian Peninsula, and it exhibits sharply declining populations. Therefore, further investigation is needed to assess the genetic origin of the populations reported in this report and to monitor the population trends to determine the population status and the appropriate management plan in the Segura River Basin.El presente trabajo constituye la primera referencia al establecimiento de poblaciones viables de Cobitis paludica (de Buen, 1930) en la cuenca del río Segura. Se han detectado dos poblaciones separadas geográficamente: una localizada en la zona alta del río Segura y la desembocadura del río Zumeta, y otra en el río Mundo, entre los embalses de Talave y Camarillas. Su presencia puede ser debida a la introducción deliberada o accidental por parte de los pescadores, o a la translocación de ejemplares a través del trasvase Tajo-Segura. C. paludica es una especie amenazada endémica de la Península Ibérica cuyas poblaciones se encuentran actualmente en declive. En este sentido, es necesario realizar estudios genéticos que confirmen el origen de estas poblaciones y desarrollar protocolos de seguimiento para establecer su estado poblacional y el plan de gestión de esta especie en la cuenca del río Segura

A Randomized Study of Food Pictures-Influenced Decision-Making Under Ambiguity in Individuals With Morbid Obesity

Background and Aims In addition to craving responses to salient food cues, the anticipation of short-term rewarding consumption of palatable food may overrun the anticipation of long-term negative consequences of obesity. The present investigation addressed the potential interplay of food cravings and decision-making abilities in individuals with obesity. Method Study 1 included 107 bariatric surgery candidates with class 2/3 obesity (OB-group) and study 2 included 54 individuals with normal weight/pre-obesity (nonOB-group). In both studies, standardized questionnaires concerning food cravings, food addiction, and psychopathology were administered. A cue-reactivity paradigm was used to measure craving responses toward semi-individualized images of highly palatable, processed food/fruit (appetitive food cues) compared to images of raw vegetables (non-appetitive food cues). Decision-making was measured with a modified computerized version of the Iowa Gambling Task (IGT) with food pictures. Both groups were divided into two subgroups that were randomized to different IGT conditions. In one IGT condition the advantageous IGT card decks were covered by pictures of palatable, processed food or fruit and the disadvantageous decks by images of raw vegetables (= congruent condition), and in the other IGT conditionvice versa. Results Participants in the OB-group admitted on average higher craving responses toward palatable, processed food or fruit cues compared to pictures of raw vegetables. This was not the case in the nonOB-group. Contrary to our hypothesis, decision-making performance in both groups was worse when pictures of palatable, processed food or fruit were associated with advantageous IGT card decks compared to performance when those pictures were linked to the disadvantageous decks. The interference effect of food pictures processing on advantageous decision-making has been observed particularly in those individuals of the OB-group who exhibited high craving responses toward palatable, processed food cues or high levels of food addiction. Discussion The results indicate that food pictures processing interferes with decision-making, regardless of weight status. Opposed to the hypothesis, stronger tendencies to avoid than to approach pictures presenting processed, tasty food were observed. Further research should examine how cognitive avoidance tendencies toward processed, high energy food and approach tendencies toward healthy food can be transferred to real life situations

Evaluación de la reacción de las lineas avanzadas de soya Glycine max (L) Merril frente al patógeno Cylindrocladium scoparium (morgan).

El artículo presenta el desarrollo de la investigación con lo cual se pretendía identificar materiales tolerantes para zonas afectadas por la enfermedad. Encontramos la metodología, las variables de sanidad, los métodos de inoculación, los resultados y discusiones, la descripción de los grupos para las variables de sanidad y las conclusiones y recomendaciones.Soya-Soja- Glycine ma

Identification of NEK3 and MOK as novel targets for lithium

Lithium ion, commonly used as the carbonate salt in the treatment of bipolar disorders, has been identified as an inhibitor of several kinases, including Glycogen Synthase Kinase-3ß, for almost 20 years. However, both the exact mechanism of enzymatic inhibition and its apparent specificity for certain metalloenzymes are still a matter of debate. A data-driven hypothesis is presented that accounts for the specificity profile of kinase inhibition by lithium in terms of the presence of a unique protein environment in the magnesium-binding site. This hypothesis has been validated by the discovery of two novel potential targets for lithium, namely NEK3 and MOK, which are related to neuronal function.Ministerio de Economía y Competitivida