Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction

TP53INP2 at the crossroad of apoptosis and autophagy in death receptor signaling

The binding of ligands to death receptors elicits distinct outcomes, such as apoptosis, inflammation and necroptosis, depending on the cellular context. We have recently described that the autophagic protein TP53INP2 favors apoptosis upon death receptor signaling and is a potential biomarker of responsiveness to TRAIL treatment

Knock, knock, knocking on muscle doors. Visions of the transport of substrates across the plasma membrane in muscle

El múscul té un paper central en el metabolisme. Així, el múscul utilitza quantitats substancials de glucosa durant l'estat absortiu, i els canvis en la captació muscular de la glucosa provoquen alteracions en la utilització global de la glucosa per l'organisme sencer. El múscul constitueix també el principal reservori corporal d'aminoàcids i de proteïnes. A més, el metabolisme muscular és mantingut mitjantçant l'activitat de molts diferents transportadors localitzats a la membrana plasmàtica, com són els transportadors de glucosa, carnitina, creatina o aminoàcids; aquests transportadors capten o alliberen, a través de la membrana plasmàtica de la cèl·lula muscular, diferents substrats o metabòlits. L'objectiu d'aquesta revisió consisteix en la caracterització molecular de les principals proteïnes transportadores presents a la membrana plasmàtica de les cèl·lules musculars, així com l'anàlisi de les seves propietats reguladores.Muscle is a major player in metabolism. It uses large amounts of glucose in the absorptive state and changes in muscle insulin-stimulated glucose uptake alter whole-body glucose disposal. Lipid substrates such as fatty acids or ketone bodies are preferentially used by muscle in certain physiological conditions. Muscle is also the main reservoir of amino acids and protein. The activity of many different plasma membrane transporters such as glucose carriers, carnitine, creatine or amino acid transporters maintain muscle metabolism by taking up or releasing substrates or metabolites across the cell surface. The goal of this review is the molecular characterization of muscle membrane transporter proteins and the analysis of their regulatory roles

dDOR Is an EcR Coactivator that Forms a Feed-Forward Loop Connecting Insulin and Ecdysone Signaling

SummaryBackgroundMammalian DOR was discovered as a gene whose expression is misregulated in muscle of Zucker diabetic rats. Because no DOR loss-of-function mammalian models are available, we analyze here the in vivo function of DOR by studying flies mutant for Drosophila DOR (dDOR).ResultsWe show that dDOR is a novel coactivator of ecdysone receptor (EcR) that is needed during metamorphosis. dDOR binds EcR and is required for maximal EcR transcriptional activity. In the absence of dDOR, flies display a number of ecdysone loss-of-function phenotypes such as impaired spiracle eversion, impaired salivary gland degradation, and pupal lethality. Furthermore, dDOR knockout flies are lean. We find that dDOR expression is inhibited by insulin signaling via FOXO.ConclusionThis work uncovers dDOR as a novel EcR coactivator. It also establishes a mutual antagonistic relationship between ecdysone and insulin signaling in the fly fat body. Furthermore, because ecdysone signaling inhibits insulin signaling in the fat body, this also uncovers a feed-forward mechanism whereby ecdysone potentiates its own signaling via dDOR

Stochastic modulation evidences a transitory EGF-Ras-ERK MAPK activity induced by PRMT5

The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway involves a three-step cascade of kinases that transduce signals and promote processes such as cell growth, development, and apoptosis. An aberrant response of this pathway is related to the proliferation of cell diseases and tumors. By using simulation modeling, we document that the protein arginine methyltransferase 5 (PRMT5) modulates the MAPK pathway and thus avoids an aberrant behavior. PRMT5 methylates the Raf kinase, reducing its catalytic activity and thereby, reducing the activation of ERK in time and amplitude. Two minimal computational models of the epidermal growth factor (EGF)-Ras-ERK MAPK pathway influenced by PRMT5 were proposed: a first model in which PRMT5 is activated by EGF and a second one in which PRMT5 is stimulated by the cascade response. The reported results show that PRMT5 reduces the time duration and the expression of the activated ERK in both cases, but only in the first model PRMT5 limits the EGF range that generates an ERK activation. Based on our data, we propose the protein PRMT5 as a regulatory factor to develop strategies to fight against an excessive activity of the MAPK pathway, which could be of use in chronic diseases and cancer

Application of Gamification in Industrial Engineering subjects in University of La Rioja

La gamificación es una herramienta potente para conseguir un aprendizaje activo y dinámico. La formación universitaria es un campo adecuado para incluir herramientas y estrategias que mejoren la calidad de la docencia desde aspectos más lúdicos. La experiencia que aquí se presenta, pretende mostrar su utilidad en tres asignaturas de la rama de conocimiento de Ingeniería Industrial. Se han utilizado tres herramientas informáticas como son Blackboard, Quizizz y Socrative, que permiten la construcción de cuestionarios que deben contestar los alumnos, incorporando, las dos últimas, aspectos de gamificación. La inmediatez en la detección de posibles faltas en la formación previa de los alumnos ha sido clave para la detección temprana. La clase se ha vuelto más dinámica y más cercana a las necesidades del alumno. La construcción de algunos cuestionarios en lengua inglesa ha conseguido mejorar las destrezas técnicas en dicha lengua, y acercarle más a su realidad profesional. Los test han recogido aspectos teóricos y análisis de casos prácticos, evitando la simple memorización, y sirviendo como fuente de información, tanto para los alumnos como para los profesores. Dentro de la estrategia de digitalización, también se han colocado cuestionarios accesibles para el alumno, para su formación fuera del horario presencial.Gamification is a powerful tool for archiving active and dynamic learning. University education is a suitable field to include tools and strategies that improve the quality of teaching from more gaming aspects. Experience presented here, aims to show its usefulness in three subjects of Industrial Engineering field. Three informatic tools has been included: Blackboard, Quizizz and Socrative, which allow the construction of quizzes, to be answered by students. As Quiziz, as Socrative, include gamification aspects. Automatic feedback of faults in previous knowledge, has been key to early detection. Class has become more dynamic and closer to the needs of students. Construction of some questionnaires in English, has improved technical skills in that language, and brought them closer to their professional reality. Quizzes have included theoretical aspects and analysis of practical cases, avoiding simple memorization, and serving as feedback for both students and teachers. As part of the digitalization strategy, quizzes have also been made available to students for training outside classroom hours

Utililzación de glucosa durante la vida fetal y su relación nutricional

Utililzación de glucosa durante la vida fetal y su relación nutricional

DOR undergoes nucleo-cytoplasmic shuttling, which involves passage through the nucleolus

AbstractDOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress–response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption

Supportive periodontal therapy and periodontal biotype as prognostic factors in implants placed in patients with a history of periodontitis

Objectives: To evaluate bone loss around implants placed in patients with a history of treated chronic periodontitis and who did or did not attend supportive periodontal therapy, after one year in function. Furthermore, the influence of periodontal biotype and level of plaque was also evaluated. Material and Methods: Forty-nine patients participated voluntarily in the study. All subjects had a history of chronic periodontitis, which had been previously treated. After the active treatment, 27 patients attended supportive periodontal therapy (SPT) and the rest did not (No SPT). The O'Leary plaque index and periodontal biotype were recorded for each subject and 246 Astra Tech® OsseospeedTM implants were radiographically analysed (123 placed in SPT patients and 123 in No SPT patients) at the time of loading and one year later, measuring marginal bone loss with the program Dental Studio NX 6.0®. The statistical analysis was performed with Windows SPSS, applying Pearson's correlation index and the Kruskal- Wallis and U-Mann Whitney non-parametric tests. Results: Six patients were found to have periimplantitis and sixteen mucositis. The survival rate was 99.59% (100% SPT and 99.18% No SPT). Mean bone loss was 0.39 mm (range [-0.71 - 8.05]). Among SPT patients, 95% of the implants had losses less than or equal to the mean (mean bone loss of 0.16 mm) compared to 53.7% for the No SPT group (mean bone loss of 0.62 mm). A statistically significant relationship was demonstrated between bone loss around the implant and the patient's periodontal biotype and plaque index. Conclusions: The marginal bone loss around implants in patients with treated chronic periodontitis is minimal if they are in a controlled SPT programme and there is individual control of plaque index. Moreover, the presence of a thin periodontal biotype represents a risk factor for additional bone loss