Interferon-gamma promoter hypomethylation and increased expression in chronic periodontitis: IFNG hypomethylation in periodontal disease

The goal of this investigation was to determine whether epigenetic modifications in the IFNG promoter are associated with an increase of IFNG transcription in different stages of periodontal diseases

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Alloreactive T Cell Receptor Diversity against Structurally Similar or Dissimilar HLA-DP Antigens Assessed by Deep Sequencing

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

The use of visual methods to explore how children construct and assign meaning to the ''self'' within two urban communities in the Western Cape, South Africa

This study aimed to explore how children construct and assign meaning to the ''self'' within two urban communities of Cape Town in South Africa. Using a child participation methodological framework data were collected using Photovoice and community maps with 54 participants between the ages of 9 and 12. Feelings of safety, social connectedness, and children's spaces were found to be central to the ways in which the participants constructed and assigned meaning to the ''self.'' The study provides implications for intervention programmes aimed at improving children's well-being to be inclusive of activities aimed at improving children's self-concept, including the construction of safe spaces for children to play, learn, and form meaningful relationships

Etica y política en la novela y el ensayo de José Saramago

Al plantear la dimensión ético-política de un texto se presupone un análisis axiológico de los valores que sostiene y sustrae en su emergencia discursiva, esto es la imagen de mundo, la concepción filosófica en que se sustenta y la voluntad práctica que propicia. Una lectura ético-política de un texto –en este orden– supone «usarlo» (al menos en el sentido que Humberto Eco le concede) al «autotelizarlo», es decir, transformarlo en vehículo de una reflexión colectiva. Potenciarlo en sus posibilidades y tornarlo acontecimiento de lenguaje; pragmatizarlo en su intención para leerlo documentaria y documentalmente, sin dejar de reconocerlo como ente en sí mismo. Se está haciendo referencia –claro está– a las implicancias ético-culturales y ético-políticas que los textos literarios presuponen, pero también a una dimensión productiva que opera en su enunciación, aquella que Saramago refiere cuando proclama la necesidad de una «insurrección ética» que devuelva a los seres humanos la capacidad de responsabilizarse de su lugar en el mundo. De allí el imperativo categórico que se imprime en sus textos y que al Equipo Saramaguiano de Teoría y Crítica Literarias le interesa explicitar. La lectura propuesta por el Equipo de investigación, además de explorar las potencialidades significativas de los textos, pretende contribuir a través de ellas a una segunda lectura, de orden refractaria esta última, es decir, inscripta en una dimensión situada: la perspectiva latinoamericana. No se trata de explorar el significado en sí mismo ni de ordenarlo conforme a una coordenada que le es referencialmente precisa, sino de aportar reflexiva y responsablemente a un análisis más profundo de la realidad inmediata en la que habitamos como investigadores. Se busca –en suma– potenciar los procedimientos heurísticos al máximo pero hacerlos conscientes de una mirada propia, al costurarlos con «nuestro» aquí y ahora de universitarios latinoamericanos.Fil: Koleff, Miguel Alberto. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentin

Alternative Splicing of Spg7, a Gene Involved in Hereditary Spastic Paraplegia, Encodes a Variant of Paraplegin Targeted to the Endoplasmic Reticulum

BACKGROUND: Hereditary spastic paraplegia defines a group of genetically heterogeneous diseases characterized by weakness and spasticity of the lower limbs owing to retrograde degeneration of corticospinal axons. One autosomal recessive form of the disease is caused by mutation in the SPG7 gene. Paraplegin, the product of SPG7, is a component of the m-AAA protease, a high molecular weight complex that resides in the mitochondrial inner membrane, and performs crucial quality control and biogenesis functions in mitochondria. PRINCIPAL FINDINGS: Here we show the existence in the mouse of a novel isoform of paraplegin, which we name paraplegin-2, encoded by alternative splicing of Spg7 through usage of an alternative first exon. Paraplegin-2 lacks the mitochondrial targeting sequence, and is identical to the mature mitochondrial protein. Remarkably, paraplegin-2 is targeted to the endoplasmic reticulum. We find that paraplegin-2 exposes the catalytic domains to the lumen of the endoplasmic reticulum. Moreover, endogenous paraplegin-2 accumulates in microsomal fractions prepared from mouse brain and retina. Finally, we show that the previously generated mouse model of Spg7-linked hereditary spastic paraplegia is an isoform-specific knock-out, in which mitochondrial paraplegin is specifically ablated, while expression of paraplegin-2 is retained. CONCLUSIONS/SIGNIFICANCE: These data suggest a possible additional role of AAA proteases outside mitochondria and open the question of their implication in neurodegeneration

Impact of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis

Transforming growth factor beta (TGF-ß) plays an important role in carcinogenesis. Two polymorphisms in the TGF-ß1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-ß1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-ß1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-ß1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.This work was supported by Fundação para a Ciência e Tecnologia, Portugal (PTDC/SAU-GMG/113795/2009 and SFRH/BPD/33612/2009 to B.M.C.; SFRH/BD/88121/2012 to J.V.C.; SFRH/BD/92786/2013 to C.S.G.; PTDC/SAU-ONC/115513/2009 to R.R.)

Magnesium based materials for hydrogen based energy storage: Past, present and future

Magnesium hydride owns the largest share of publications on solid materials for hydrogen storage. The “Magnesium group” of international experts contributing to IEA Task 32 “Hydrogen Based Energy Storage” recently published two review papers presenting the activities of the group focused on magnesium hydride based materials and on Mg based compounds for hydrogen and energy storage. This review article not only overviews the latest activities on both fundamental aspects of Mg-based hydrides and their applications, but also presents a historic overview on the topic and outlines projected future developments. Particular attention is paid to the theoretical and experimental studies of Mg-H system at extreme pressures, kinetics and thermodynamics of the systems based on MgH2, nanostructuring, new Mg-based compounds and novel composites, and catalysis in the Mg based H storage systems. Finally, thermal energy storage and upscaled H storage systems accommodating MgH2 are presented

Can Sophie's Choice Be Adequately Captured by Cold Computation of Minimizing Losses? An fMRI Study of Vital Loss Decisions

The vast majority of decision-making research is performed under the assumption of the value maximizing principle. This principle implies that when making decisions, individuals try to optimize outcomes on the basis of cold mathematical equations. However, decisions are emotion-laden rather than cool and analytic when they tap into life-threatening considerations. Using functional magnetic resonance imaging (fMRI), this study investigated the neural mechanisms underlying vital loss decisions. Participants were asked to make a forced choice between two losses across three conditions: both losses are trivial (trivial-trivial), both losses are vital (vital-vital), or one loss is trivial and the other is vital (vital-trivial). Our results revealed that the amygdala was more active and correlated positively with self-reported negative emotion associated with choice during vital-vital loss decisions, when compared to trivial-trivial loss decisions. The rostral anterior cingulate cortex was also more active and correlated positively with self-reported difficulty of choice during vital-vital loss decisions. Compared to the activity observed during trivial-trivial loss decisions, the orbitofrontal cortex and ventral striatum were more active and correlated positively with self-reported positive emotion of choice during vital-trivial loss decisions. Our findings suggest that vital loss decisions involve emotions and cannot be adequately captured by cold computation of minimizing losses. This research will shed light on how people make vital loss decisions