Mitochondria in endothelial cells: Sensors and integrators of environmental cues

The involvement of angiogenesis in disease and its potential as a therapeutic target have been firmly established over recent decades. Endothelial cells (ECs) are central elements in vessel homeostasis and regulate the passage of material and cells into and out of the bloodstream. EC proliferation and migration are modified by alterations to mitochondrial biogenesis and dynamics resulting from several signals and environmental cues, such as oxygen, hemodynamics, and nutrients. As intermediary signals, mitochondrial ROS are released as important downstream modulators of the expression of angiogenesis-related genes. In this review, we discuss the physiological actions of these signals and aberrant responses during vascular disorders.We thank M. M. Munoz-Hernandez and Dr Concepcion Jimenez for technical assistance, Keren Lopez Fernandez for the artwork in Fig. 1 and Simon Bartlett for English editing. This study was supported by MINECO: SAF2015-65633-R MSCA-COFUND-DP Doctoral programmes 2014. The CNIC is supported by MINECO and Pro-CNIC Foundation, and is a SO-MINECO (award SEV-2015-0505).S

The function of the respiratory supercomplexes: the plasticity model

Mitochondria are important organelles not only as efficient ATP generators but also in controlling and regulating many cellular processes. Mitochondria are dynamic compartments that rearrange under stress response and changes in food availability or oxygen concentrations. The mitochondrial electron transport chain parallels these rearrangements to achieve an optimum performance and therefore requires a plastic organization within the inner mitochondrial membrane. This consists in a balanced distribution between free respiratory complexes and supercomplexes. The mechanisms by which the distribution and organization of supercomplexes can be adjusted to the needs of the cells are still poorly understood. The aim of this review is to focus on the functional role of the respiratory supercomplexes and its relevance in physiology. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.This study was supported by grants from the Ministerio de Ciencia e Innovación (SAF2012-32776 & CSD200700020); the Comunidad de Madrid (CAM/API1009); and the Marie Curie Career Integration Grant (UEO/MCA1108). RA-P is an investigator of the Ramon y Cajal research program from the Ministerio de Economía y Competitividad. The CNIC is supported by the Ministerio de Economía y Competitividad and the Pro-CNIC Foundation.S

Generation of Reactive Oxygen Species by Mitochondria.

Reactive oxygen species (ROS) are series of chemical products originated from one or several electron reductions of oxygen. ROS are involved in physiology and disease and can also be both cause and consequence of many biological scenarios. Mitochondria are the main source of ROS in the cell and, particularly, the enzymes in the electron transport chain are the major contributors to this phenomenon. Here, we comprehensively review the modes by which ROS are produced by mitochondria at a molecular level of detail, discuss recent advances in the field involving signalling and disease, and the involvement of supercomplexes in these mechanisms. Given the importance of mitochondrial ROS, we also provide a schematic guide aimed to help in deciphering the mechanisms involved in their production in a variety of physiological and pathological settings.This study was supported by MINECO: SAF2015-65633-R, RTI2018-099357-B-I00, HFSP (RGP0016/2018) and CIBER (CB16/10/00282). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). His research has been financed by Spanish Government grants (ISCIII and AEI agencies, partially funded by the European Union FEDER/ERDF)S

Regulation and functional role of the electron transport chain supercomplexes

Mitochondria are one of the most exhaustively investigated organelles in the cell and most attention has been paid to the components of the mitochondrial electron transport chain (ETC) in the last 100 years. The ETC collects electrons from NADH or FADH2 and transfers them through a series of electron carriers within multiprotein respiratory complexes (complex I to IV) to oxygen, therefore generating an electrochemical gradient that can be used by the F1-F0-ATP synthase (also named complex V) in the mitochondrial inner membrane to synthesize ATP. The organization and function of the ETC is a continuous source of surprises. One of the latest is the discovery that the respiratory complexes can assemble to form a variety of larger structures called super-complexes (SCs). This opened an unexpected level of complexity in this well-known and fundamental biological process. This review will focus on the current evidence for the formation of different SCs and will explore how they modulate the ETC organization according to the metabolic state. Since the field is rapidly growing, we also comment on the experimental techniques used to describe these SC and hope that this overview may inspire new technologies that will help to advance the fiel

Impacto Del Programa Presupuestal Articulado Nutricional En La Desnutrición Crónica Infantil En Menores De 5 Años, En La Unidad Ejecutora Geresa Lambayeque En El Periodo 2012 - 2016.

Objetivo: Determinar la Impacto del Programa Presupuestal Articulado Nutricional en la Desnutrición Crónica infantil en menores de 5 años, en la Unidad Ejecutora GERESA Lambayeque en el periodo 2012 - 2016. Metodología: Fue Cuantitativa, descriptiva, transversal. Instrumento de recolección de datos: Se utilizó una ficha de registro de datos. Los resultados: La proporción de menores de 5 años con desnutrición crónica en la Unidad Ejecutora GERESA Lambayeque fue de 11.8% en el 2016, observándose una disminución de 2 puntos porcentuales en comparación con el año 2012 que la proporción fue de 14.0% en la población de la misma edad. Las intervenciones efectivas de carácter preventivo promocional para la disminución de la desnutrición crónica nos muestran que, la proporción de menores de 36 meses con vacunas básicas completas se tuvo en 2012 el 70.8%, disminuyendo hacia el año 2016 en 5.4 puntos porcentuales (65.4%), la proporción de menores de 36 meses con controles de crecimiento y desarrollo completo, se obtuvo en el 2012 el 41.1% mientras que en el 2016 aumento en 3.3 puntos porcentuales (44.4%), y la proporción de hogares con acceso al agua tratada, se obtuvo en el 2012 el 90.3% mientras que en el 2016 aumento en 4.8 puntos porcentuales (95.1%).Se concluye que el programa articulado nutricional en la Unidad Ejecutora GERESA- Lambayeque tiene un impacto positivo en la disminución de desnutrición crónica en menores de 5 años. En todo momento se han considerado los criterios de rigor científico y ético

“Gestión administrativa y su influencia en la calidad de servicio de la empresa Pegasus consultores S.A.C., Callao, 2018”

La investigación tuvo como objetivo determinar cómo la gestión administrativa influye en la calidad de servicio en la empresa Pegasus Consultores S.A.C., distrito del Callao en el año 2018. El método de estudio en la investigación fue hipotético deductivo, de tipo aplicada, diseño no experimental, de corte transversal, con nivel explicativo-causal, la población de 32 colaboradores, censal. La técnica utilizada fue la encuesta, teniendo como instrumento un cuestionario conformado por 18 preguntas de la variable independiente “Gestión Administrativa” y 17 preguntas de la variable dependiente “Calidad de Servicio”, para la medición se utilizó la Escala de Likert. Para el procesamiento de la información se utilizó el SPSS 24 y se pudo determinar la confiabilidad del instrumento mediante el uso del alfa de Cronbach, asimismo para medir la influencia de las variables se utilizó Chi cuadrado de Pearson. Finalmente se determinó que la gestión administrativa influye significativamente en la calidad de servicio en la empresa Pegasus Consultores S.A.C., Callao, 2018

Revisión crítica : intervenciones de enfermería en el paciente con infarto agudo de miocardio en el servicio de emergencia

La presente investigación tuvo como objetivo identificar las intervenciones de enfermería sobre el paciente con infarto agudo de miocardio, llevándonos a reflexionar sobre ¿que intervenciones de enfermería se deben realizar en el paciente con infarto agudo de miocardio en el servicio de emergencia?. Se realizó la búsqueda de artículos y guías de alto contenido científico (Pubmed, Dialnet,BVS,Scielo, Digapihc, Sciencie Direct y Google académico). Realizando para ello una selección sistemática de 10 artículos de los cuales a través de la Guía de Gálvez Toro pasaron 4 la revisión. El estudio a partir del cual se emitirá la crítica, es una investigación secundaria: Guía de Práctica Clínica denominada “Intervenciones de Enfermería en la atención del paciente con infarto agudo de miocardio”. Su instrumento de evaluación fue el AGREE II, con un nivel de evidencia II–2 y un grado de recomendación “B”. Finalmente dando repuesta a la pregunta planteada ¿cuáles son las intervenciones de enfermería en el paciente con infarto agudo de miocardio en el servicio de emergencia?, la guía de práctica clínica brinda cuidados generales adaptables al I, II y III nivel de atención, de ellos se infiere los aplicables al servicio de emergencia: valoración de la intensidad del dolor (aplicando la escala), la toma del EKG, administración de oxigenoterapia, tratamiento antiplaquetario VO, monitorización de los signos vitales, contar con dos vías EV periféricas de buen calibre permeables, entre otros

Nuclear transcription factors in mammalian mitochondria

Nuclear transcription factors have been detected in mammalian mitochondria and may directly regulate mitochondrial gene expression. Emerging genomics techniques may overcome outstanding challenges in this field

The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNASer(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression

The pathogenetic mechanism of the deafness-associated mitochondrial DNA (mtDNA) T7445C mutation has been investigated in several lymphoblastoid cell lines from members of a New Zealand pedigree exhibiting the mutation in homoplasmic form and from control individuals. We show here that the mutation flanks the 3' end of the tRNASer(UCN) gene sequence and affects the rate but not the sites of processing of the tRNA precursor. This causes an average reduction of ~70% in the tRNASer(UCN) level and a decrease of ~45% in protein synthesis rate in the cell lines analyzed. The data show a sharp threshold in the capacity of tRNASer(UCN) to support the wild-type protein synthesis rate, which corresponds to ~40% of the control level of this tRNA. Strikingly, a 7445 mutation-associated marked reduction has been observed in the level of the mRNA for the NADH dehydrogenase (complex I) ND6 subunit gene, which is located ~7 kbp upstream and is cotranscribed with the tRNASer(UCN) gene, with strong evidence pointing to a mechanistic link with the tRNA precursor processing defect. Such reduction significantly affects the rate of synthesis of the ND6 subunit and plays a determinant role in the deafness-associated respiratory phenotype of the mutant cell lines. In particular, it accounts for their specific, very significant decrease in glutamate- or malate-dependent O2 consumption. Furthermore, several homoplasmic mtDNA mutations affecting subunits of NADH dehydrogenase may play a synergistic role in the establishment of the respiratory phenotype of the mutant cells

Variant pathogenic prediction by locus variability: the importance of the current picture of evolution.

Accurate detection of pathogenic single nucleotide variants (SNVs) is a key challenge in whole exome and whole genome sequencing studies. To date, several in silico tools have been developed to predict deleterious variants from this type of data. However, these tools have limited power to detect new pathogenic variants, especially in non-coding regions. In this study, we evaluate the use of a new metric, the Shannon Entropy of Locus Variability (SELV), calculated as the Shannon entropy of the variant frequencies reported in genome-wide population studies at a given locus, as a new predictor of potentially pathogenic variants in non-coding nuclear and mitochondrial DNA and also in coding regions with a selective pressure other than that imposed by the genetic code, e.g splice-sites. For benchmarking, SELV was compared to predictors of pathogenicity in different genomic contexts. In nuclear non-coding DNA, SELV outperformed CDTS (AUCSELV = 0.97 in ROC curve and PR-AUCSELV = 0.96 in Precision-recall curve). For non-coding mitochondrial variants (AUCSELV = 0.98 in ROC curve and PR-AUCSELV = 1.00 in Precision-recall curve) SELV outperformed HmtVar. Moreover, SELV was compared against two state-of-the-art ensemble predictors of pathogenicity in splice-sites, ada-score, and rf-score, matching their overall performance both in ROC (AUCSELV = 0.95) and Precision-recall curves (PR-AUC = 0.97), with the advantage that SELV can be easily calculated for every position in the genome, as opposite to ada-score and rf-score. Therefore, we suggest that the information about the observed genetic variability in a locus reported from large scale population studies could improve the prioritization of SNVs in splice-sites and in non-coding regions.FSC is supported by the Ministerio de Ciencia, Innovación, y Universidades (MCIU) [grant no. RTI2018-102084-B-I00]. JAE is supported by the MCIU (RTI2018-099357-BI00), Human Frontier Science Program (RGP0016/2018), CIBERFES16/10/00282 and RED2018-102576-T. The CNIC is supported by MCIU and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence [MCIU award SEV-XXX].”S