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

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

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

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

Fine-tuning the electrostatic properties of an alkali-linked organic adlayer on a metal substrate

The performance of modern organic electronic devices is often determined by the electronic level alignment at a metal–organic interface. This property can be controlled by introducing an interfacial electrostatic dipole via the insertion of a stable interlayer between the metallic and the organic phases. Here, we use density functional theory to investigate the electrostatic properties of an assembled structure formed by alkali metals coadsorbed with 7,7,8,8-tetracyanoquinodimethane (TCNQ) molecules on a Ag(100) substrate. We find that the interfacial dipole buildup is regulated by the interplay of adsorption energetics, steric constraints and charge transfer effects, so that choosing chemical substitutions within TCNQ and different alkali metals provides a rich playground to control the systems’ electrostatics and in particular fine-tune its work-function shift