Comparative genomic analysis of the arthropod muscle myosin heavy chain genes allows ancestral gene reconstruction and reveals a new type of 'partially' processed pseudogene

<p>Abstract</p> <p>Background</p> <p>Alternative splicing of mutually exclusive exons is an important mechanism for increasing protein diversity in eukaryotes. The insect <it>Mhc </it>(myosin heavy chain) gene produces all different muscle myosins as a result of alternative splicing in contrast to most other organisms of the Metazoa lineage, that have a family of muscle genes with each gene coding for a protein specialized for a functional niche.</p> <p>Results</p> <p>The muscle myosin heavy chain genes of 22 species of the Arthropoda ranging from the waterflea to wasp and <it>Drosophila </it>have been annotated. The analysis of the gene structures allowed the reconstruction of an ancient muscle myosin heavy chain gene and showed that during evolution of the arthropods introns have mainly been lost in these genes although intron gain might have happened in a few cases. Surprisingly, the genome of <it>Aedes aegypti </it>contains another and that of <it>Culex pipiens quinquefasciatus </it>two further muscle myosin heavy chain genes, called <it>Mhc3 </it>and <it>Mhc4</it>, that contain only one variant of the corresponding alternative exons of the <it>Mhc1 </it>gene. <it>Mhc3 </it>transcription in <it>Aedes aegypti </it>is documented by EST data. <it>Mhc3 </it>and <it>Mhc4 </it>inserted in the <it>Aedes </it>and <it>Culex </it>genomes either by gene duplication followed by the loss of all but one variant of the alternative exons, or by incorporation of a transcript of which all other variants have been spliced out retaining the exon-intron structure. The second and more likely possibility represents a new type of a 'partially' processed pseudogene.</p> <p>Conclusion</p> <p>Based on the comparative genomic analysis of the alternatively spliced arthropod muscle myosin heavy chain genes we propose that the splicing process operates sequentially on the transcript. The process consists of the splicing of the mutually exclusive exons until one exon out of the cluster remains while retaining surrounding intronic sequence. In a second step splicing of introns takes place. A related mechanism could be responsible for the splicing of other genes containing mutually exclusive exons.</p

Developmental Considerations for Assessment and Treatment of Impulsivity in Older Adults

Impulsivity is an important factor in many clinical disorders, especially alcohol and substance use disorders. Most of the research on impulsivity in this domain has focused on adolescence and young adulthood, as this developmental period is characterized by onset of and escalation in alcohol and substance use, likely driven in part by brain development patterns. Although many individuals eventually “mature out” of these behaviors in middle adulthood, a critical subset of people do not. The role of impulsivity in middle-to-older adulthood, when certain individuals transition from normative to disordered substance use, has not been carefully examined. The goal of this paper is to review the literature on measuring and modifying impulsivity from adolescence through older adulthood, with a special focus on middle-to-older adulthood. We propose that impulsivity research should include data on middle-to-older adulthood as an important time of transition to disordered use. We consider how impulsivity might have unique meaning at different stages of the adult lifespan and suggest modifications for assessing and treating impulsivity in older adults

Hsf1 Activation Inhibits Rapamycin Resistance and TOR Signaling in Yeast Revealed by Combined Proteomic and Genetic Analysis

TOR kinases integrate environmental and nutritional signals to regulate cell growth in eukaryotic organisms. Here, we describe results from a study combining quantitative proteomics and comparative expression analysis in the budding yeast, S. cerevisiae, to gain insights into TOR function and regulation. We profiled protein abundance changes under conditions of TOR inhibition by rapamycin treatment, and compared this data to existing expression information for corresponding gene products measured under a variety of conditions in yeast. Among proteins showing abundance changes upon rapamycin treatment, almost 90% of them demonstrated homodirectional (i.e., in similar direction) transcriptomic changes under conditions of heat/oxidative stress. Because the known downstream responses regulated by Tor1/2 did not fully explain the extent of overlap between these two conditions, we tested for novel connections between the major regulators of heat/oxidative stress response and the TOR pathway. Specifically, we hypothesized that activation of regulator(s) of heat/oxidative stress responses phenocopied TOR inhibition and sought to identify these putative TOR inhibitor(s). Among the stress regulators tested, we found that cells (hsf1-R206S, F256S and ssa1-3 ssa2-2) constitutively activated for heat shock transcription factor 1, Hsf1, inhibited rapamycin resistance. Further analysis of the hsf1-R206S, F256S allele revealed that these cells also displayed multiple phenotypes consistent with reduced TOR signaling. Among the multiple Hsf1 targets elevated in hsf1-R206S, F256S cells, deletion of PIR3 and YRO2 suppressed the TOR-regulated phenotypes. In contrast to our observations in cells activated for Hsf1, constitutive activation of other regulators of heat/oxidative stress responses, such as Msn2/4 and Hyr1, did not inhibit TOR signaling. Thus, we propose that activated Hsf1 inhibits rapamycin resistance and TOR signaling via elevated expression of specific target genes in S. cerevisiae. Additionally, these results highlight the value of comparative expression analyses between large-scale proteomic and transcriptomic datasets to reveal new regulatory connections

Problematic Facebook use and problematic video gaming as mediators of relationship between impulsivity and life satisfaction among female and male gamers

Over the past few decades, many new technologies have emerged, such as portable computers, the internet and smartphones, which have contributed to improving the lives of individuals. While the benefits of these new technologies are overwhelmingly positive, negative consequences are experienced by a minority of individuals. One possible negative aspect of new technologies is their problematic use due to impulsive use which may lead to lower life satisfaction. The present study investigated the mediating role of problematic video gaming (PVG) and problematic Facebook use (PFU) in the relationship between impulsivity dimensions and life satisfaction as well as the relationship between impulsivity dimensions and problematic behaviors. Additionally, the potential impact of gender differences was also examined. The study comprised 673 gamers (391 females) aged 17–38 years (M = 21.25 years, SD = 2.67) selected from 1365 individuals who completed an offline survey. PFU was assessed using the Facebook Intrusion Scale, and PVG was assessed using the nine-item Internet Gaming Disorder Scale–Short-Form (IGDS9-SF). Impulsivity dimensions such as attention, cognitive instability, motor, perseverance, self-control, and cognitive complexity were assessed using the Barratt Impulsiveness Scale (BIS-11), and life satisfaction was assessed using the Satisfaction With Life Scale (SWLS). Depending on the specific impulsivity dimension, findings showed both positive and negative relationships between impulsivity and life satisfaction. Attention and perseverance subtypes of impulsivity were primarily associated with problematic behaviors. Additionally, cognitive complexity was associated with PFU among female gamers, whereas cognitive instability was associated with PVG among male gamers. Additionally, PVG was primarily associated with lower life satisfaction. However, there was no mediation effects between impulsivity dimensions and life satisfaction via PFU or PVG. These findings provide a better understanding of the relationship between problematic behaviors, life satisfaction, and impulsivity among gamers and the differences between male and female gamers