Subgenual Cingulum Microstructure Supports Control of Emotional Conflict

This is the final version of the article. Available from Oxford University Press via the DOI in this record.Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r= -0.53;P= 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimuli.P.A.K. was funded by the Higher Education Funding Council for Wales (HEFCW) and an Academy of Medical Sciences and Wellcome Trust Starter Grant (AJ17102004). M.M. received an EPSRC Doctoral Training Grant. This work was also supported by a Marie Curie fellowship to Marcel Meyer and received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 267171. D.K.J. was funded by HEFCW and received grants from the MS Society, a Wellcome Trust New Investigator Award, a Wellcome Trust Multi User Equipment Grant and Medical Research Council, and Wellcome Trust project grants. A.N.D. was supported by the Wellcome Trust PhD schemes. N.L. was funded by HEFCW. A.D.L. was funded by HEFCW. He also received grants from the ESRC, Wellcome Trust, and NISCHR. Funding to pay the Open Access publication charges for this article was provided by The Wellcome Trust

Francis Crick: A Singular Approach to Scientific Discovery.

Francis' office window (at the Salk) commanded a panorama of the Pacific. "This grand natural scene was a physical correlate of Francis's intellectual world: wide-ranging, brilliantly lit, a little overawing, but also immensely inviting and above all an exciting place to be." (Mitchison, 2004).Wellcome-Trus

K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect

Background-Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.Methods and Results-We have analyzed global changes in gone expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K-ATP channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.Conclusions-This is, to our knowledge, the first report of the altered expression of a K-ATP. channel subunit induced by a cardioprotective agent and demonstrates that K-ATP, channel opening is essential for the effect of this novel cardioprotective agent

Sex-biased expression of microRNAs in<i>Drosophila melanogaster</i>

Most animals have separate sexes. The differential expression of gene products, in particular that of gene regulators, is underlying sexual dimorphism. Analyses of sex-biased expression have focused mostly on protein-coding genes. Several lines of evidence indicate that microRNAs, a class of major gene regulators, are likely to have a significant role in sexual dimorphism. This role has not been systematically explored so far. Here, I study the sex-biased expression pattern of microRNAs in the model speciesDrosophila melanogaster. As with protein-coding genes, sex-biased microRNAs are associated with the reproductive function. Strikingly, contrary to protein-coding genes, male-biased microRNAs are enriched in the X chromosome, whereas female microRNAs are mostly autosomal. I propose that the chromosomal distribution is a consequence of high rates of de novo emergence, and a preference for new microRNAs to be expressed in the testis. I also suggest that demasculinization of the X chromosome may not affect microRNAs. Interestingly, female-biased microRNAs are often encoded within protein-coding genes that are also expressed in females. MicroRNAs with sex-biased expression do not preferentially target sex-biased gene transcripts. These results strongly suggest that the sex-biased expression of microRNAs is mainly a consequence of high rates of microRNA emergence in the X chromosome (male bias) or hitchhiked expression by host genes (female bias).</jats:p

The effect of sepsis and its inflammatory response on mechanical clot characteristics: a prospective observational study

Purpose: Sepsis and its progression are known to have a major influence on the coagulation system. Current coagulation tests are of limited use when assessing coagulation in sepsis patients. This study aims to assess the potential for a new functional biomarker of clot microstructure, fractal dimension, to identify changes in the mechanical properties of clot microstructure across the sepsis spectrum (sepsis, severe sepsis and septic shock). Methods: A total of 100 patients that presented acutely to a large teaching hospital were included in this prospective observational study (50 sepsis, 20 severe sepsis and 30 septic shock) against a matched control of 44 healthy volunteers. Fractal analysis was performed, as well as standard markers of coagulation, and six plasma markers of inflammation. Results: Fractal dimension was significantly higher in the sepsis and severe sepsis groups than the healthy control (1.78 ± 0.07 and 1.80 ± 0.05 respectively vs 1.74 ± 0.03) (p < 0.001), indicating a significant increase in mechanical clot strength and elasticity consistent with a hypercoagulable state. Conversely, fractal dimension was significantly lower in septic shock (1.66 ± 0.10, p < 0.001), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state. This corresponded with a significant increase in the inflammatory response. Conclusions: This study confirms that clot microstructure is significantly altered through the various stages of sepsis. Of particular importance was the marked change in clot development between severe sepsis and septic shock, which has not been previously reported