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

Estructura, logros y desafíos del Grupo de Estudios Didácticos de la Educación Superior en Salud / Structure, achievements and challenges of the Didactic Study Group in the High Education in Health

La Universidad Médica Pinareña, inmersa en dar respuesta a las demandas que el proceso formativo requiere, ha precisado lograr un clima institucional Didáctico - Pedagógico que diera respuesta a la formación de su claustro profesoral para enfrentar los retos que las condiciones actuales demandan, lo que hizo necesario proponer una estrategia de desarrollo que permitiese una estructura funcional de un Grupo de Estudios Didáctico para la Educación Médica, determinando su misión, visión y funciones. Para ello se tomaron en consideración los métodos teóricos y empíricos, que permitieron dar sustento a partir de la detección de los problemas didácticos que se presentaban en la Universidad de Ciencias Médicas Dr. Ernesto Che Guevara de la Serna de Pinar del Río. El trabajo demostró los logros alcanzados por el Grupo durante la etapa que se analiza, estableciendo los desafíos, que como retos, culminarán en paso de Grupo a Centro de Estudios Didácticos de la Educación Médica Superior para las Carreras de la Salud. Palabras Clave: educación médica/métodos, universidades.ABSTRACT Pinar del Rio Medical University is concerned about those demands that the educative process requires and it has created a didactic- pedagogical method for the professorial staff in order to face those challenges demanded by the current conditions, so it was necessary to propose an strategy being able to create a functional structure by a didactic study group in the medical education for determining its purpose, its objective and functions. With this purpose, those theoretical and empirical methods capable of allowing the detection of the didactic problems present in Pinar del Rio "Ernesto Che Guevara de la Serna" Medical School were considered. It was demonstrated the achievements obtained by this group of professors and it was established the challenges that will permit the change from a group to a centre of high medica education for health majors. Key words: medical education/methods, universitie

Estructura, logros y desafíos del Grupo de Estudios Didácticos de la Educación Superior en Salud / Structure, achievements and challenges of the Didactic Study Group in the High Education in Health

La Universidad Médica Pinareña, inmersa en dar respuesta a las demandas que el proceso formativo requiere, ha precisado lograr un clima institucional Didáctico - Pedagógico que diera respuesta a la formación de su claustro profesoral para enfrentar los retos que las condiciones actuales demandan, lo que hizo necesario proponer una estrategia de desarrollo que permitiese una estructura funcional de un Grupo de Estudios Didáctico para la Educación Médica, determinando su misión, visión y funciones. Para ello se tomaron en consideración los métodos teóricos y empíricos, que permitieron dar sustento a partir de la detección de los problemas didácticos que se presentaban en la Universidad de Ciencias Médicas Dr. Ernesto Che Guevara de la Serna de Pinar del Río. El trabajo demostró los logros alcanzados por el Grupo durante la etapa que se analiza, estableciendo los desafíos, que como retos, culminarán en paso de Grupo a Centro de Estudios Didácticos de la Educación Médica Superior para las Carreras de la Salud. Palabras Clave: educación médica/métodos, universidades.ABSTRACT Pinar del Rio Medical University is concerned about those demands that the educative process requires and it has created a didactic- pedagogical method for the professorial staff in order to face those challenges demanded by the current conditions, so it was necessary to propose an strategy being able to create a functional structure by a didactic study group in the medical education for determining its purpose, its objective and functions. With this purpose, those theoretical and empirical methods capable of allowing the detection of the didactic problems present in Pinar del Rio "Ernesto Che Guevara de la Serna" Medical School were considered. It was demonstrated the achievements obtained by this group of professors and it was established the challenges that will permit the change from a group to a centre of high medica education for health majors. Key words: medical education/methods, universitie

IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog, MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ (a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and miRNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins (p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity. These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epitheliaThis work was funded by project PI17/00578, from the “Instituto de Salud Carlos III” (Ministry of Science, Innovation and Universities) and co-funded by the European Regional Development Fund, and approved by the Ethics Committee of our Institution. It has been founded also by projects CB16/12/00228, PI16/00161, RD16/0011/0011, RD12/0019/0023 and SAF2017–84248-PS

Resistance of Trichoplusia ni to Bacillus thuringiensis Toxin Cry1Ac Is Independent of Alteration of the Cadherin-Like Receptor for Cry Toxins

Alteration of binding sites for Bacillus thuringiensis (Bt) toxins in insect midgut is the major mechanism of high-level resistance to Bt toxins in insects. The midgut cadherin is known to be a major binding protein for Bt Cry1A toxins and linkage of Bt-resistance to cadherin gene mutations has been identified in lepidopterans. The resistance to Bt toxin Cry1Ac evolved in greenhouse populations of Trichoplusia ni has been identified to be associated with the down-regulation of an aminopeptidase N (APN1) gene by a trans-regulatory mechanism and the resistance gene has been mapped to the locus of an ABC transporter (ABCC2) gene. However, whether cadherin is also involved with Cry1Ac-resistance in T. ni requires to be understood. Here we report that the Cry1Ac-resistance in T. ni is independent of alteration of the cadherin. The T. ni cadherin cDNA was cloned and the cadherin sequence showed characteristic features known to cadherins from Lepidoptera. Various T. ni cadherin gene alleles were identified and genetic linkage analysis of the cadherin alleles with Cry1Ac-resistance showed no association of the cadherin gene with the Cry1Ac-resistance in T. ni. Analysis of cadherin transcripts showed no quantitative difference between the susceptible and Cry1Ac-resistant T. ni larvae. Quantitative proteomic analysis of midgut BBMV proteins by iTRAQ-2D-LC-MS/MS determined that there was no quantitative difference in cadherin content between the susceptible and the resistant larvae and the cadherin only accounted for 0.0014% (mol%) of the midgut BBMV proteins, which is 1/300 of APN1 in molar ratio. The cadherin from both the susceptible and resistant larvae showed as a 200-kDa Cry1Ac-binding protein by toxin overlay binding analysis, and nano-LC-MS/MS analysis of the 200-kDa cadherin determined that there is no quantitative difference between the susceptible and resistant larvae. Results from this study indicate that the Cry1Ac-resistance in T. ni is independent of cadherin alteration

Actualistic taphonomic study of the rodents digested by the Achala culpeo fox (Lycalopex culpaeus smithersi) in the highlands of central Argentina

We present the first actualistic study of the rodents consumed by the South American foxLycalopex culpaeus smithersi (Achala culpeo fox), a subspecies of the culpeo fox that is endemicto the highlands of central Argentina. We provide a taphonomic characterization of this canidbased on digested micromammal bones, and compare it to other carnivores. We studied over 1000bones derived from 83 scats collected in Quebrada del Condorito National Park, Córdobaprovince, Argentina, corresponding to caviomorph and myomorph rodents. Galea leucoblepharawas the main prey (59.8% MNI, 93.1% biomass). Average relative abundance for the totalassemblage was 26.7. Cranial and, to a lesser extent, proximal limb bones were the most abundantelements. A high degree of breakage was observed in cranial elements and, to a lesser extent, inlimb bones. A high proportion of heavy and extreme digestion was inferred, while some elementsbear light or no digestion traces at all. Overall, the Achala culpeo fox fits best with othermammalian carnivores in the category of extreme modification, and shows types and proportionsof taphonomic attributes similar to other South American mammalian predators. These resultscontribute to the understanding of regional taphonomic processes and of digestivemodifications by Lycalopex foxes generally, and are thus relevant to interpreting the presence of micromammal remains in the archaeological and palaeontological recordsand the impact of these foxes in their formation.Fil: Coll, Daiana Geraldine. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Montalvo, Claudia Inés. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Fernández, Fernando Julián. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pia, Monica Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: Mondini, Nora Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Antropología de Córdoba. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Instituto de Antropología de Córdoba; Argentin

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011