Investigating the molecular basis of local adaptation to thermal stress: population differences in gene expression across the transcriptome of the copepod Tigriopus californicus

ABSTRACT: BACKGROUND: Geographic variation in the thermal environment impacts a broad range of biochemical and physiological processes and can be a major selective force leading to local population adaptation. In the intertidal copepod Tigriopus californicus, populations along the coast of California show differences in thermal tolerance that are consistent with adaptation, i.e., southern populations withstand thermal stresses that are lethal to northern populations. To understand the genetic basis of these physiological differences, we use an RNA-seq approach to compare genome-wide patterns of gene expression in two populations known to differ in thermal tolerance. RESULTS: Observed differences in gene expression between the southern (San Diego) and the northern (Santa Cruz) populations included both the number of affected loci as well as the identity of these loci. However, the most pronounced differences concerned the amplitude of upregulation of genes producing heat shock proteins (Hsps) and genes involved in ubiquitination and proteolysis. Among the hsp genes, orthologous pairs show markedly different thermal responses as the amplitude of hsp response was greatly elevated in the San Diego population, most notably in members of the hsp70 gene family. There was no evidence of accelerated evolution at the sequence level for hsp genes. Among other sets of genes, cuticle genes were up-regulated in SD but down-regulated in SC, and mitochondrial genes were down-regulated in both populations. CONCLUSIONS: Marked changes in gene expression were observed in response to acute sub-lethal thermal stress in the copepod T. californicus. Although some qualitative differences were observed between populations, the most pronounced differences involved the magnitude of induction of numerous hsp and ubiquitin genes. These differences in gene expression suggest that evolutionary divergence in the regulatory pathway(s) involved in acute temperature stress may offer at least a partial explanation of population differences in thermal tolerance observed in Tigriopus.     

Klar ensures thermal robustness of oskar localization by restraining RNP motility

Communication usually applies feedback loop–based filters and amplifiers to ensure undistorted delivery of messages. Such an amplifier acts during Drosophila melanogaster midoogenesis, when oskar messenger ribonucleic acid (mRNA) anchoring depends on its own locally translated protein product. We find that the motor regulator Klar β mediates a gain-control process that prevents saturation-based distortions in this positive feedback loop. We demonstrate that, like oskar mRNA, Klar β localizes to the posterior pole of oocytes in a kinesin-1–dependent manner. By live imaging and semiquantitative fluorescent in situ hybridization, we show that Klar β restrains oskar ribonucleoprotein motility and decreases the posterior-ward translocation of oskar mRNA, thereby adapting the rate of oskar delivery to the output of the anchoring machinery. This negative regulatory effect of Klar is particularly important for overriding temperature-induced changes in motility. We conclude that by preventing defects in oskar anchoring, this mechanism contributes to the developmental robustness of a poikilothermic organism living in a variable temperature environment.     

Focus: Addiction: Case Report: Internet Gaming Disorder Associated With Pornography Use

Internet gaming disorder (IGD) is not currently a recognized diagnosis in the Diagnostic and Statistical Manual for Mental Disorders-5 (DSM-5). However, IGD has been noted to warrant further research for possible future inclusion in the DSM. In many ways, IGD strongly resembles substance and gambling addictions. Such characteristics include tolerance, withdrawal, and social and occupational neglect resulting from increased time invested in video game use and acquisition. The use of similar or closely related media is also seen, which mirrors the natural course of substance and gambling addictions. We present a case of a 22-year-old man who exhibited IGD and problems associated with pornography use. This case report exemplifies the sequelae of IGD. Our paper also reviews the possible mechanisms of behavioral addiction, as well as the status of IGD as a potential subcategory of behavioral addiction. Additional research is needed to determine if IGD co-occurs with problematic use of pornography.     

An energy dissipation and cross shear time dependent computational wear model for the analysis of polyethylene wear in total knee replacements

The cost and time efficiency of computational polyethylene wear simulations may enable the optimization of total knee replacements for the reduction of polyethylene wear. The present study proposes an energy dissipation wear model for polyethylene which considers the time dependent molecular behavior of polyethylene, aspects of tractive rolling and contact pressure. This time dependent – energy dissipation wear model was evaluated, along with several other wear models, by comparison to pin-on-disk results, knee simulator wear test results under various kinematic conditions and knee simulator wear test results that were performed following the ISO 14243-3 standard. The proposed time dependent – energy dissipation wear model resulted in improved accuracy for the prediction of pin-on-disk and knee simulator wear test results compared with several previously published wear models.     

Reversed-phase ion-pair liquid chromatography analysis and purification of small interfering RNA

Small interfering RNA (siRNA)-induced gene silencing shows great promise in genomic research and therapeutic applications. siRNA duplexes are typically assembled from complementary synthetic oligonucleotides. High-purity single-stranded species are required for in vivo applications. Methods for separation, characterization, and purification of short RNA strands have been developed based on reversed-phase ion-pair liquid chromatography. The purification strategies were developed for both single-stranded and duplex RNA species. The method of duplex purification uses on-column annealing of complementary RNA strands, followed by separation of the target duplex from truncated duplexes and single-stranded RNA forms. The proposed method significantly reduces the purification time of synthetic siRNA.     

The contribution of cellular mechanotransduction to cardiomyocyte form and function

Myocardial development is regulated by an elegantly choreographed ensemble of signaling events mediated by a multitude of intermediates that take a variety of forms. Cellular differentiation and maturation are a subset of vertically integrated processes that extend over several spatial and temporal scales to create a well-defined collective of cells that are able to function cooperatively and reliably at the organ level. Early efforts to understand the molecular mechanisms of cardiomyocyte fate determination focused primarily on genetic and chemical mediators of this process. However, increasing evidence suggests that mechanical interactions between the extracellular matrix (ECM) and cell surface receptors as well as physical interactions between neighboring cells play important roles in regulating the signaling pathways controlling the developmental processes of the heart. Interdisciplinary efforts have made it apparent that the influence of the ECM on cellular behavior occurs through a multitude of physical mechanisms, such as ECM boundary conditions, elasticity, and the propagation of mechanical signals to intracellular compartments, such as the nucleus. In addition to experimental studies, a number of mathematical models have been developed that attempt to capture the interplay between cells and their local microenvironment and the influence these interactions have on cellular self-assembly and functional behavior. Nevertheless, many questions remain unanswered concerning the mechanism through which physical interactions between cardiomyocytes and their environment are translated into biochemical cellular responses and how these signaling modalities can be utilized in vitro to fabricate myocardial tissue constructs from stem cell-derived cardiomyocytes that more faithfully represent their in vivo counterpart. These studies represent a broad effort to characterize biological form as a conduit for information transfer that spans the nanometer length scale of proteins to the meter length scale of the patient and may yield new insights into the contribution of mechanotransduction into heart development and disease.     

Species formation and geographical range evolution in a genus of Central American cloud forest salamanders (Dendrotriton)

Aim Montane Central America offers an ideal system for testing geographical hypotheses of species diversification. We examined how the complex geological history of Nuclear Central America has shaped the diversification of a genus of cloud‐forest‐inhabiting salamanders (Dendrotriton). We applied parametric models of geographical range evolution to determine the predominant mode of species formation within the genus and to test existing hypotheses of geographical species formation in the region. Location Montane cloud forests of Nuclear Central America. Methods We estimated a species tree for Dendrotriton using a multi‐locus DNA sequence data set and several coalescent methods, and performed molecular dating for divergence events within the genus. We then applied the species‐tree estimate to a likelihood‐based time‐stratified model of geographical range evolution, based on current species distributions and available geological information for Central America. Results Species trees from all methods contain two groups, one corresponding to species from the Sierra de los Cuchumatanes and the other containing all remaining species. In most cases, species formation within the genus involved an even division of the geographical range of the ancestral species between descendant species. The ancestor of extant Dendrotriton species was estimated to have occurred in either the Sierra de los Cuchumatanes or the Sierra Madre de Chiapas, and both of these areas appear to have been important for diversification within the genus. The single species found in the Quaternary‐age Guatemalan volcanic cordillera dispersed to the volcanoes from an older highland area. Main conclusions Models of geographical range evolution, when combined with robust species‐tree estimates, provide insight into the historical biogeography of taxa not available from phylogenies or distributional data alone. Vicariant species formation, rather than peripatric or gradient speciation, appears to have been the dominant process of diversification, with most divergence events occurring within or between ancient highland areas. The apparent dispersal of Dendrotriton to the Quaternary‐age volcanoes raises the possibility that the rich salamander community there is composed of species that dispersed from geologically older areas. The Motagua Valley appears not to have been as important in vicariant species formation within Dendrotriton as it is within other groups.     

Microstructural White Matter Changes in the Corpus Callosum of Young People with Bipolar Disorder: A Diffusion Tensor Imaging Study

To date, most studies of white matter changes in Bipolar Disorder (BD) have been conducted in older subjects and with well-established disorders. Studies of young people who are closer to their illness onset may help to identify core neurobiological characteristics and separate these from consequences of repeated illness episodes or prolonged treatment. Diffusion tensor imaging (DTI) was used to examine white matter microstructural changes in 58 young patients with BD (mean age 23 years; range 16–30 years) and 40 controls. Whole brain voxelwise measures of fractional anisotropy (FA), parallel diffusivity (λ//) and radial diffusivity (λ⊥) were calculated for all subjects. White matter microstructure differences (decreased FA corrected p<.05) were found between the patients with BD and controls in the genu, body and splenium of the corpus callosum as well as the superior and anterior corona radiata. In addition, significantly increased radial diffusivity (p<.01) was found in the BD group. Neuroimaging studies of young patients with BD may help to clarify neurodevelopmental aspects of the illness and for identifying biomarkers of disease onset and progression. Our findings provide evidence of microstructural white matter changes early in the course of illness within the corpus callosum and the nature of these changes suggest they are associated with abnormalities in the myelination of axons.