Effects of methamphetamine abuse and serotonin transporter gene variants on aggression and emotion-processing neurocircuitry.

Individuals who abuse methamphetamine (MA) exhibit heightened aggression, but the neurobiological underpinnings are poorly understood. As variability in the serotonin transporter (SERT) gene can influence aggression, this study assessed possible contributions of this gene to MA-related aggression. In all, 53 MA-dependent and 47 control participants provided self-reports of aggression, and underwent functional magnetic resonance imaging while viewing pictures of faces. Participants were genotyped at two functional polymorphic loci in the SERT gene: the SERT-linked polymorphic region (SERT-LPR) and the intron 2 variable number tandem repeat polymorphism (STin2 VNTR); participants were then classified as having high or low risk for aggression according to individual SERT risk allele combinations. Comparison of SERT risk allele loads between groups showed no difference between MA-dependent and control participants. Comparison of self-report scores showed greater aggression in MA-dependent than control participants, and in high genetic risk than low-risk participants. Signal change in the amygdala was lower in high genetic risk than low-risk participants, but showed no main effect of MA abuse; however, signal change correlated negatively with MA use measures. Whole-brain differences in activation were observed between MA-dependent and control groups in the occipital and prefrontal cortex, and between genetic high- and low-risk groups in the occipital, fusiform, supramarginal and prefrontal cortex, with effects overlapping in a small region in the right ventrolateral prefrontal cortex. The findings suggest that the investigated SERT risk allele loads are comparable between MA-dependent and healthy individuals, and that MA and genetic risk influence aggression independently, with minimal overlap in associated neural substrates

Respuesta de hipersensibilidad retardada en pacientes candidatos a artroplastia de cadera

Se estudiaron 100 pacientes escogidos de manera aleatoria de entre los candidatos a artroplastia de cadera (47 por fractura subcapital de fémur Garden IV, y 53 por coxartrosis). En el momento del ingresos se determinaron en sangre niveles de albúmina, proteínas totales y hemoglobina; y se midió la respuesta de hipersensibilidad retardada mediante la inoculación de siete antígenos de memoria con un aplicador Multitest® (Mérieux). La lectura de la reacción de induración se realizó a las 48 horas. Los pacientes fueron clasificados en: normoérgicos (+) a dos o más antígenos) y anérgicos (una o ninguna respuesta (+). La población normoérgica representó el 61% de los pacientes, con una edad 12,5 años menor que la población anérgica (p<0,001). Los pacientes normoérgicos presentaron cifras significativamente más altas de hemoglobina (p<0,001), proteínas totales (p<0,05) y albúmina (p<0,001). La situación de anergia fue más frecuente en el grupo de mujeres (29/57) frente al de hombres (10/43; p<0,001), y en el grupo de fracturas subcapitales (31/47) que en el de coxartrosis (8/53) (p<0,001). No se hallaron relaciones estadísticamente significativas entre los distintos parámetros estudiados y la aparición de infección en el postoperatorio. Las diferencias aparecidas reflejan alteraciones en la respuesta inmunológica que, sin embargo, no resultan pronósticas frente a la aparición de infección en nuestra serie.One hundred candidates for hip arthroplasty were chosen at random (47 Garden IV femoral neck fractures, and 53 osteoarthrosis). Before surgery, serum albumin, total proteins and haemoglobin were determined in peripheral blood. All patients were skin tested with seven memory antigens (Multitest®, Mérieux) in order to measure the delayed hypersensitivity response. The diameter of the resulting induration was measured 48 hours after injection. Patients were classified as reactive if they responded to one antigen or showed no response. Reactive patients supposed 61% of total, and anergic patients were 12,5 years older (p<0,001). Levels of haemoglobin (p<0,001), total proteins (p<0,05) and albumin (p<0,001) were higher in reactive patients. Anergy was more frequent in women (29/57) than in men (10/43; p<0,001), and in fractures (31/47) than in osteoarthrosis (8/53) (p<0,001). No association between the variables studied and postoperative infection was found. These differences show immunologic alterations. However, they have no prognostic value for postoperative infection in hip arthroplasty patients

Marcas de Agua: una Contribución a la Seguridad de Archivos Digitales

En las últimas dos décadas ha resurgido el arte de almacenar y transmitir información encubierta debido a los avances en las tecnologías de generación, almacenamiento y comunicación de contenidos digitales. El objetivo actual de este embebido de información, llamado marcado de agua digital, es proteger los archivos anfitriones y detectar adulteraciones. El marcado siempre produce una degradación del objeto contenedor (llamado host) de modo que las técnicas que no permiten recuperar el original causan un daño  irreversible. Por esta razón, en los últimos años se ha enfocado la investigación en el desarrollo de marcas reversibles en las que los legítimos usuarios pueden extraer la marca embebida y recuperar el archivo original, si es necesario. El propósito de este trabajo es difundir el conjunto de estos métodos que contribuyen a la seguridad informática por sí solos o, en la mayoría de los casos, reforzando técnicas criptográficas. Se pondrá énfasis en el caso de imágenes digitales con valor legal, sean médicas, forenses o militares, las que utilizan marcas reversibles. 

Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1

C.V. was recipient of an FPI-Severo Ochoa Fellowship from the Spanish Ministry of Economy and Competitiveness. Work in J.V. laboratory is supported by the European Research Council (ERC AdvG 670146), AGAUR, Spanish Ministry of Economy and Competitiveness (BFU 2017 89308-P) and the Centre of Excellence Severo Ochoa. Work in T.G.'s laboratory was supported by the European Research Council FP7/2007-2013 (ERC Synergy Grant 4D-Genome) the Ministerio de Educación y Ciencia (SAF.2012-37167) and AGAUR. We acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership and the CERCA Programme / Generalitat de Catalunya.UDTRIASBackground: Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we study the dynamics of alternative splicing changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells and compare them to those occurring during reprogramming of mouse embryonic fibroblasts. Results: We observe a significant overlap between alternative splicing changes detected in the two reprogramming systems, which are generally uncoupled from changes in transcriptional levels. Correlation between gene expression of potential regulators and specific clusters of alternative splicing changes enables the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of mouse embryonic fibroblasts reprogramming. We further find that these RNA-binding proteins control partially overlapping programs of splicing regulation, involving genes relevant for developmental and morphogenetic processes. Conclusions: Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process and their targets

Modelling germ cell development in vitro

Germ cells have a critical role in mediating the generation of genetic diversity and transmitting this information across generations. Furthermore, gametogenesis is unique as a developmental process in that it generates highly-specialized haploid gametes from diploid precursor stem cells through meiosis. Despite the importance of this process, progress in elucidating the molecular mechanisms underpinning mammalian germ cell development has been retarded by the lack of an efficient and reproducible system of in vitro culture for the expansion and trans-meiotic differentiation of germline cells. The dearth of such a culture system has rendered the study of germ cell biology refractory to the application of new high-throughput technologies such as RNA interference, leaving in vivo gene-targeting approaches as the only option to determine the function of genes believed to be involved in gametogenesis. Recent reports detailing the derivation of gametes in vitro from stem cells may provide the first steps in developing new tools to solve this problem. This review considers the developments made in modelling germ cell development using stem cells, and some of the challenges that need to be overcome to make this a useful tool for studying gametogenesis and to realize any future clinical application

Whole-genome fingerprint of the DNA methylome during chemically induced differentiation of the human AML cell line HL-60/S4

Epigenomic regulation plays a vital role in cell differentiation. The leukemic HL-60/S4 [human myeloid leukemic cell line HL-60/S4 (ATCC CRL-3306)] promyelocytic cell can be easily differentiated from its undifferentiated promyelocyte state into neutrophil- and macrophage-like cell states. In this study, we present the underlying genome and epigenome architecture of HL-60/S4 through its differentiation. We performed whole-genome bisulphite sequencing of HL-60/S4 cells and their differentiated counterparts. With the support of karyotyping, we show that HL-60/S4 maintains a stable genome throughout differentiation. Analysis of differential Cytosine-phosphate-Guanine dinucleotide methylation reveals that most methylation changes occur in the macrophage-like state. Differential methylation of promoters was associated with immune-related terms. Key immune genes, CEBPA, GFI1, MAFB and GATA1 showed differential expression and methylation. However, we observed the strongest enrichment of methylation changes in enhancers and CTCF binding sites, implying that methylation plays a major role in large-scale transcriptional reprogramming and chromatin reorganisation during differentiation. Correlation of differential expression and distal methylation with support from chromatin capture experiments allowed us to identify putative proximal and long-range enhancers for a number of immune cell differentiation genes, including CEBPA and CCNF. Integrating expression data, we present a model of HL-60/S4 differentiation in relation to the wider scope of myeloid differentiation

Immunogenetic characterization of clonal plasma cells in systemic light-chain amyloidosis

This study was supported by the Centro de Investigación Biomédica en Red—Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369; and CB16/12/00489), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI13/02196), Asociación Española Contra el Cáncer (GCB120981SAN and the Accelerator Award), CRIS against Cancer foundation grant 2014/0120, and the Black Swan Research Initiative of the International Myeloma Foundation.Peer reviewe

Genetics and Plant Development

There are only three grand theories in biology: the theory of the cell, the theory of the gene, and the theory of evolution. Two of these, the cell and gene theories, originated in the study of plants, with the third resulting in part from botanical considerations as well. Mendel's elucidation of the rules of inheritance was a result of his experiments on peas. The rediscovery of Mendel's work in 1900 was by the botanists de Vries, Correns, and Tschermak. It was only in subsequent years that animals were also shown to have segregation of genetic elements in the exact same manner as had been shown in plants. The story of developmental biology is different – while the development of plants has long been studied, the experimental and genetic approaches to developmental mechanism were developed via experiments on animals, and the importance of genes in development (e.g., Waddington, 1940) and their use for understanding developmental mechanisms came to botanical science much later – as late as the 1980s