Sexual Phenotype Differences in zic2 mRNA Abundance in the Preoptic Area of a Protogynous Teleost, Thalassoma bifasciatum

The highly conserved members of the zic family of zinc-finger transcription factors are primarily known for their roles in embryonic signaling pathways and regulation of cellular proliferation and differentiation. This study describes sexual phenotype differences in abundances of zic2 mRNA in the preoptic area of the hypothalamus, a region strongly implicated in sexual behavior and function, in an adult teleost, Thalassoma bifasciatum. The bluehead wrasse (Thalassoma bifasciatum) is a valuable model for studying neuroendocrine processes because it displays two discrete male phenotypes, initial phase (IP) males and territorial, terminal phase (TP) males, and undergoes socially-controlled protogynous sex change. Previously generated microarray-based comparisons suggested that zic2 was upregulated in the brains of terminal phase males relative to initial phase males. To further explore this difference, we cloned a 727 bp sequence for neural zic2 from field-collected animals. Riboprobe-based in situ hybridization was employed to localize zic2 signal in adult bluehead brains and assess the relative abundance of brain zic2 mRNA across sexual phenotypes. We found zic2 mRNA expression was extremely abundant in the granular cells of the cerebellum and widespread in other brain regions including in the thalamus, hypothalamus, habenula, torus semicircularis, torus longitudinalis, medial longitudinal fascicle and telencephalic areas. Quantitative autoradiography and phosphorimaging showed zic2 mRNA hybridization signal in the preoptic area of the hypothalamus was significantly higher in terminal phase males relative to both initial phase males and females, and silver grain analysis confirmed this relationship between phenotypes. No significant difference in abundance was found in zic2 signal across phenotypes in the habenula, a brain region not implicated in the control of sexual behavior, or cerebellum

A Serum Factor Induces Insulin-Independent Translocation of GLUT4 to the Cell Surface which Is Maintained in Insulin Resistance

In response to insulin, glucose transporter GLUT4 translocates from intracellular compartments towards the plasma membrane where it enhances cellular glucose uptake. Here, we show that sera from various species contain a factor that dose-dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes, human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate that the serum-induced increase in cell surface GLUT4 levels is not due to inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that of insulin, while it also sensitizes the cells to insulin. In accordance with these findings, serum does not appear to activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 translocation. We conclude that in addition to insulin, at least one other biological proteinaceous factor exists that contributes to GLUT4 regulation and still functions in insulin resistance. The challenge now is to identify this factor

Muscle and reflex changes with varying joint angle in hemiparetic stroke

<p>Abstract</p> <p>Background</p> <p>Despite intensive investigation, the origins of the neuromuscular abnormalities associated with spasticity are not well understood. In particular, the mechanical properties induced by stretch reflex activity have been especially difficult to study because of a lack of accurate tools separating reflex torque from torque generated by musculo-tendinous structures. The present study addresses this deficit by characterizing the contribution of neural and muscular components to the abnormally high stiffness of the spastic joint.</p> <p>Methods</p> <p>Using system identification techniques, we characterized the neuromuscular abnormalities associated with spasticity of ankle muscles in chronic hemiparetic stroke survivors. In particular, we systematically tracked changes in muscle mechanical properties and in stretch reflex activity during changes in ankle joint angle. Modulation of mechanical properties was assessed by applying perturbations at different initial angles, over the entire range of motion (ROM). Experiments were performed on both paretic and non-paretic sides of stroke survivors, and in healthy controls.</p> <p>Results</p> <p>Both reflex and intrinsic muscle stiffnesses were significantly greater in the spastic/paretic ankle than on the non-paretic side, and these changes were strongly position dependent. The major reflex contributions were observed over the central portion of the angular range, while the intrinsic contributions were most pronounced with the ankle in the dorsiflexed position.</p> <p>Conclusion</p> <p>In spastic ankle muscles, the abnormalities in intrinsic and reflex components of joint torque varied systematically with changing position over the full angular range of motion, indicating that clinical perceptions of increased tone may have quite different origins depending upon the angle where the tests are initiated.</p> <p>Furthermore, reflex stiffness was considerably larger in the non-paretic limb of stroke patients than in healthy control subjects, suggesting that the non-paretic limb may not be a suitable control for studying neuromuscular properties of the ankle joint.</p> <p>Our findings will help elucidate the origins of the neuromuscular abnormalities associated with stroke-induced spasticity.</p

Development and Analysis of an Adverse Outcome Pathway Network for Human Neurotoxicity

An adverse outcome pathway (AOP) network is an attempt to represent the complexity of systems toxicology. This study illustrates how an AOP network can be derived and analysed in terms of its topological features to guide research and support chemical risk assessment. A four-step workflow describing general design principles and applied design principles were established and implemented. An AOP network linking nine linear AOPs was mapped and made available in AOPXplorer. The resultant AOP network was modelled and analysed in terms of its topological features, including level of degree, eccentricity and betweenness centrality. Several well connected KEs were identified, and cell injury/death was established as the most hyperlinked KE across the network. The derived network expands the utility of linear AOPs to better understand signalling pathways involved in developmental and adult/aging neurotoxicity. The results provide a solid basis to guide the development of in vitro test method batteries, as well as further quantitative modelling of key events (KEs) and key event relationships (KERs) in the AOP network, with an eventual aim to support hazard characterisation and chemical risk assessment

Brain Transcriptional Profiles of Male Alternative Reproductive Tactics and Females in Bluegill Sunfish

We thank Scott Colborne for his help in collecting bluegill, Dave Bridges for providing the R script to convert Ensemble IDs to stickleback homologs, and David Winter and Jeramia Ory for providing Python script used in the bioinformatics analyses. We thank Doug Haywick for producing Fig 1. We also thank Shawn Garner, Tim Hain, Lauren Kordonowy, and Lindsay Havens, and three anonymous reviewers for helpful comments on the manuscript.Bluegill sunfish (Lepomis macrochirus) are one of the classic systems for studying male alternative reproductive tactics (ARTs) in teleost fishes. In this species, there are two distinct life histories: parental and cuckolder, encompassing three reproductive tactics, parental, satellite, and sneaker. The parental life history is fixed, whereas individuals who enter the cuckolder life history transition from sneaker to satellite tactic as they grow. For this study, we used RNAseq to characterize the brain transcriptome of the three male tactics and females during spawning to identify gene ontology (GO) categories and potential candidate genes associated with each tactic. We found that sneaker males had higher levels of gene expression differentiation compared to the other two male tactics. Sneaker males also had higher expression in ionotropic glutamate receptor genes, specifically AMPA receptors, compared to other males, which may be important for increased spatial working memory while attempting to cuckold parental males at their nests. Larger differences in gene expression also occurred among male tactics than between males and females. We found significant expression differences in several candidate genes that were previously identified in other species with ARTs and suggest a previously undescribed role for cAMP-responsive element modulator (crem) in influencing parental male behaviors during spawning.Yeshttp://www.plosone.org/static/editorial#pee