Search

Prohibitins (PHB) form a multimeric structure at the mitochondrial inner membrane. PHB deficiency shortens the lifespan of wild type Caenorhabditis elegans nematodes, but dramatically extends that of insulin signalling receptor (daf-2) mutants. This phenotype is accompanied by a differential induction of the mitochondrial Unfolded Protein Response (UPRmt) that is attenuated in daf-2 mutants. We identified Heterochromatin Protein Like 1 (HPL-1) as a new regulator of the UPRmt and mediator of the opposing longevity phenotype caused by PHB depletion. We report functional and structural impairments of mitochondria when HP1 is depleted from worm and human cells, showing a conservation of function. We uncovered ~70% of differently bound genes by HPL-1 upon mitochondrial stress and determined HPL-1-dependent tissue-specific alterations in gene expression in hypodermal cells. Our data shows for the first time a role for HP1 proteins in controlling gene expression in response to mitochondrial dysfunction to modulate lifespan.

Prohibitins (PHB) form a multimeric structure at the mitochondrial inner membrane. PHB deficiency shortens the lifespan of wild type Caenorhabditis elegans nematodes, but dramatically extends that of insulin signalling receptor (daf-2) mutants. This phenotype is accompanied by a differential induction of the mitochondrial Unfolded Protein Response (UPRmt) that is attenuated in daf-2 mutants. In a genome wide RNAi screen, we identified Heterochromatin Protein Like 1 (HPL-1) as a new regulator of the UPRmt. Under normal conditions, hpl-1 null mutants live longer than wild type worms and show a mild induction of the UPRmt, which depends on canonical UPRmt transcription factors. We observed mitochondrial fragmentation and reduced respiration in hpl-1 mutants, which together with a marked sensitivity to mitochondrial translation inhibition suggests a mitochondrial dysfunction. Remarkably, under mitochondrial stress by PHB depletion, hpl-1 null mutants showed an increased lifespan compared to wild type animals and a reduced UPRmt. Moreover, the reduced respiration of PHB depleted animals was fully recovered in hpl-1 null mutants. Interestingly, HPL-1 was required for the increased lifespan and the attenuated UPRmt of daf-2 PHB-depleted worms. Upon PHB depletion, HPL-1 protein levels increase in hypodermal tissue, supporting the relevance of HPL-1 in mounting the stress response. Additionally, in the absence of stress HPL-1 levels increase as animals age, suggesting a role in longevity regulation. In order to study genes targeted by HPL-1, we examined its binding profile in hypodermal tissue by DamID under non-stress and mitochondrial stress conditions in wild type and daf-2 mutants. HPL-1 associates to coding and upstream regions with and without stress. We uncovered ~40% and 70% of HPL-1-unique bound genes upon mitochondrial stress in wild type and insulin signalling mutants, respectively. Among them, a significant group of genes are commonly regulated by HPL-1 and key s

Consistent evidence from both experimental and human studies indicates that Type 2 diabetes mellitus (T2DM) is a complex disease resulting from the interaction of genetic, epigenetic, environmental, and lifestyle factors. Nutrients and dietary patterns are important environmental factors to consider in the prevention, development and treatment of this disease. Nutritional genomics focuses on the interaction between bioactive food components and the genome and includes studies of nutrigenetics, nutrigenomics and epigenetic modifications caused by nutrients. There is evidence supporting the existence of nutrient-gene and T2DM interactions coming from animal studies and family-based intervention studies. Moreover, many case-control, cohort, cross-sectional cohort studies and clinical trials have identified relationships between individual genetic load, diet and T2DM. Some of these studies were on a large scale. In addition, studies with animal models and human observational studies, in different countries over periods of time, support a causative relationship between adverse nutritional conditions during in utero development, persistent epigenetic changes and T2DM. This review provides comprehensive information on the current state of nutrient-gene interactions and their role in T2DM pathogenesis, the relationship between individual genetic load and diet, and the importance of epigenetic factors in influencing gene expression and defining the individual risk of T2DM.

[Introduction]: Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR. [Methods]: Utero-placental insufficiency was induced by meso-ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry. [Results]: Placental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus. [Conclusions]: The results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.

Phosphorylation of proteins is an important regulatory mechanism that controls numerous biological processes. Vaccinia-Related Kinase 1 (VRK1) is a conserved protein kinase that is related to cell proliferation and survival. In mammals, loss of VRK1 leads to sterility and may cause neurological disorders. VRK1 is known to phosphorylate chromatin proteins, such as BAF and histones H2A and H3 as well as the transcription factors p53, c-Jun, ATF2 and CREB. To characterize the dynamics of VRK1 we have generated VRK1 single-copy transgenic Caenorhabditis elegans strains and human cell lines. We have mapped a short localization domain of both, C. elegans and human VRK1 that is sufficient to localize the protein to condensed chromosomes in mitosis. Our novel C. elegans transgenic strains, in contrast to previous observations, show expression of VRK-1 in all cell types including proliferating and post-mitotic cells. During C. elegans vulval development, a specialized gonadal cell, called the anchor cell (AC), fuses with uterine cells to form the utse syncytium. Defects in utse formation cause in adults a protruding vulva phenotype. Our data show that VRK-1 is required for AC fusion with neighboring cells to form the utse syncytium. To identify interaction partners we expressed and purified VRK1 from human cells followed by high-resolution mass spectrometry. Among top candidate proteins are several nuclear envelope proteins, including the LEM-domain protein emerin, which was subsequently confirmed by Y2H assays. In addition, we have developed a bicistronic system to study protein-protein interactions by Bimolecular Fluorescence Complementation (BiFC) analysis. This system enables us to test for VRK1 in vivo interactions at physiological expression levels but the system can be adapted to any other protein pair.

BACKGROUND Alcoholic fermentation of fruits has generated novel products with high concentrations of bioactive compounds and moderate alcohol content. The aim of this study was to evaluate the potential effect on cardiovascular risk factors of the regular consumption by healthy humans of a beverage obtained by alcoholic fermentation and pasteurization of orange juice. RESULTS Thirty healthy volunteers were enrolled in a randomized controlled study. The experimental group (n = 15) drank 500 mL orange beverage (OB) per day for 2 weeks (intervention phase), followed by a 3-week washout phase. Blood samples were collected at baseline (E-T0) and at the end of the intervention (E-T1) and washout (E-T2) phases. Controls (n = 15) did not consume OB during a 2-week period. OB intake significantly increased oxygen radical absorbance capacity (43.9%) and reduced uric acid (−8.9%), catalase (CAT) (−23.2%), thiobarbituric acid reactive substances (TBARS) (−30.2%) and C-reactive protein (−2.1%) (E-T1 vs. E-T0). These effects may represent longer-term benefits, given the decreased uric acid (−8.9%), CAT (−34.6%), TBARS (−48.4%) and oxidized low-density lipoprotein (−23.9%) values recorded after the washout phase (E-T2 vs. E-T0). CONCLUSION The regular consumption of OB improved antioxidant status and decreased inflammation state, lipid peroxidation and uric acid levels. Thus OB may protect the cardiovascular system in healthy humans and be considered a novel functional beverage. © 2017 Society of Chemical Industry

The consumption of fruits prevents the risk of cardiovascular diseases. Alcoholic fermentation has been carried out in fruits resulting in products which provide high concentration of bioactive compounds and variable alcohol content. The aim of this study was to assess the potential beneficial effect of an orange beverage obtained by alcoholic fermentation and pasteurization of orange juice on cardiovascular risk biomarkers. For this purpose, four mice groups (n = 8) ingested orange beverage (equivalent volume to 250 mL/day in human), orange juice, alcoholic solution (at the proportional amount of orange beverage) or water during 12 weeks. The equivalent amount to double serving of orange beverage (500 mL/day) was administered to mice in a subsequent intervention, and a control group was also evaluated. Orange beverage consumption increased levels of glutathione and uric acid, improved lipid profile, decreased oxidized LDL and maintained levels of IL-6 and C-reactive protein. Synergistic effects between the bioactive compounds and the alcohol content of orange beverage may occur. The intake of double serving also increased antioxidant enzyme activities, bilirubin content and plasma antioxidant capacity. These results suggest that orange beverage may produce greater protection against cardiovascular risk factors than orange juice in healthy mice.

Los alumnos del Grado de Nutrición Humana y Dietética aprenden que una alimentación equilibrada es necesaria en todas las edades y estados fisiológicos para gozar de una buena calidad de vida. Es por tanto, fundamental en la formación del alumnado la adquisición de los conocimientos necesarios para ser capaz de informar a la población de la importancia de una alimentación saludable. Parte del profesorado del Área de Nutrición y Bromatología de la Universidad Pablo de Olavide llevó a cabo durante el curso académico 2012-2013 un Proyecto dentro del Plan de Innovación y Desarrollo Docente que perseguía dicho objetivo. El proyecto se llevó a cabo simultáneamente en varias asignaturas de segundo y tercer curso, contemplando distintos puntos de vista de la “Alimentación Saludable”: dietético, nutricional, educativo, higiénico y culinario y, considerando tanto situaciones fisiológicas como patológicas, con el fin de poner de manifiesto los conocimientos adquiridos por los estudiantes en todas las asignaturas implicadas. Los alumnos de 2º y 3er curso participaron con una gran implicación en la propuesta. La mayoría de los materiales elaborados fueron trípticos (55%), seguidos por carteles (40%) y vídeos (5%). Los materiales elaborados se diseñaron según el colectivo de la población al que va dirigido, tratando de hacer llegar la información de la forma más eficaz posible. Los trabajos realizados fueron de muy buena calidad en base a las rúbricas establecidas para su evaluación.

Genetic and molecular data have implicated the Drosophila gene female-lethal (2)d (fl (2)d) in alternative splicing regulation of genes involved in sexual determination. Sex-specific splicing is under the control of the female-specific regulatory protein sex-lethal (SXL). Co-immunoprecipitation and mass spectrometry results indicate that SXL and FL (2)D form a complex and that the protein VIRILIZER and a Ran-binding protein implicated in protein nuclear import are also present in complexes containing FL (2)D. A human homolog of FL (2)D was identified and cloned. Interestingly, this gene encodes a protein (WTAP) that was previously found to interact with the Wilms' tumor suppressor-1 (WT1), an isoform of which binds to and co-localizes with splicing factors. Alternative splicing of transformer pre-mRNA, a target of SXL regulation, was affected by immunodepletion of hFL (2)D/WTAP from HeLa nuclear extracts, thus arguing for a biochemical function of FL (2)D/WTAP proteins in splicing regulation.

Como parte del grupo de trabajo creado en el Hospital Infantil Universitario Virgen del Rocío de Sevilla para el estudio de las malformaciones en la infancia, se inició este trabajo sobre las MALFORMACIONES ASOCIADAS A LAS CARDIOPATIAS CONGENITAS, por su alta incidencia y su gran importancia y relevancia dentro de las causas globales de morbi-mortalidad infantil (especialmente neonatal y perinatal). Se estudian 237 casos de cardiopatías congénitas entre un total de 779 autopsias infantiles, realizadas entre los años 1980 y 1993, procediendo todos del Hospital Infantil y Centro Maternal de Sevilla. Todos los casos debían ser exitus y en todos se realizó estudio necrósico completo, siendo la base de nuestro trabajo los datos anatomo-clínicos de estas malformaciones. Las cardiopatías se estudiaron por el método del análisis segmentario y se clasificaron por la lesión de mayor importancia, y las malformaciones asociadas mediante estudio macroscópico de las piezas en cada órgano correspondiente. Del resumen de a historia clínica y de la autopsia, se analizan un total de 34 variables, algunas clínicas (tales como: peso, sexo, edad gestacional, edad materna, paridad, etc.) y otras anatomo-patológicas (tipos de cardiopatías congénitas, anomalías extracardíacas), agrupadas a su vez en distintas categorías. Obtenemos un ligero predominio de varones sobre las hembras (con una relación de 1.07), siendo más frecuentes los casos de recién nacidos a término (un 55.2%) y con peso adecuado a su edad gestacional (un 47.2%). En cuanto a datos maternos, destacan el grupo de madres entre 25-35 años (un 22.3%), y con 2-3 partos (un 30%), lo cual entra dentro de los habitual en la población general. Encontramos una incidencia de malformaciones extracardíacas en este estudio de un 60.33%, siendo las más frecuentes las malformaciones menores externas (un 32%), y por órganos las genito- urinarias (28%), digestivas y menores internas (20% cada una), del sistema nervioso central (19%) y por úl