Auditory Conflict Resolution Correlates with Medial–Lateral Frontal Theta/Alpha Phase Synchrony

When multiple persons speak simultaneously, it may be difficult for the listener to direct attention to correct sound objects among conflicting ones. This could occur, for example, in an emergency situation in which one hears conflicting instructions and the loudest, instead of the wisest, voice prevails. Here, we used cortically-constrained oscillatory MEG/EEG estimates to examine how different brain regions, including caudal anterior cingulate (cACC) and dorsolateral prefrontal cortices (DLPFC), work together to resolve these kinds of auditory conflicts. During an auditory flanker interference task, subjects were presented with sound patterns consisting of three different voices, from three different directions (45° left, straight ahead, 45° right), sounding out either the letters “A” or “O”. They were asked to discriminate which sound was presented centrally and ignore the flanking distracters that were phonetically either congruent (50%) or incongruent (50%) with the target. Our cortical MEG/EEG oscillatory estimates demonstrated a direct relationship between performance and brain activity, showing that efficient conflict resolution, as measured with reduced conflict-induced RT lags, is predicted by theta/alpha phase coupling between cACC and right lateral frontal cortex regions intersecting the right frontal eye fields (FEF) and DLPFC, as well as by increased pre-stimulus gamma (60–110 Hz) power in the left inferior fontal cortex. Notably, cACC connectivity patterns that correlated with behavioral conflict-resolution measures were found during both the pre-stimulus and the pre-response periods. Our data provide evidence that, instead of being only transiently activated upon conflict detection, cACC is involved in sustained engagement of attentional resources required for effective sound object selection performance

Developing a method for estimating subject-specific trunk muscle morphometry

Spinal injury and pain can often be debilitating, leading to a significant decrease in quality of life. The development of these spinal conditions may be explained by changes spinal loading patterns. Since spinal loading patterns cannot be analyzed in vivo, biomechanical musculoskeletal models have been developed to estimate them. Incorporating muscle parameters such as cross sectional area and moment arms improves the accuracy of musculoskeletal models, but no current resource provides a comprehensive set of muscle parameters for a wide variety of subjects. This study aims to develop a method for estimating trunk muscle parameters from clinically attainable variables such as age, sex, height, weight, trunk width, and trunk depth. The regression models built in this study drew from in-vivo CT-based cross sectional area and moment arms measurements of an age- and sex- stratified community-based population. The base regression model used the independent variables age, sex, height, and weight, while subsequent models examined the differences when trunk depth or trunk width was incorporated. 27% of cross sectional area regressions were improved with the addition of trunk weight or trunk width; 26.6% of medial lateral moment arm regressions were improved with the addition of trunk width; 50% of anterior posterior moment arm regressions were improved with the addition of trunk depth. Although the addition of trunk depth or width improved model fit especially in moment arm regressions, the R2 values of regressions were not increased greatly. It is suspected that muscle position as related to distribution of fat may explain the mismatched contribution of trunk measurements to moment arm estimates in different muscles. Further investigation is needed to examine the effects of fat distribution on muscle parameter estimation

Brain Networks of Novelty-Driven Involuntary and Cued Voluntary Auditory Attention Shifting

In everyday life, we need a capacity to flexibly shift attention between alternative sound sources. However, relatively little work has been done to elucidate the mechanisms of attention shifting in the auditory domain. Here, we used a mixed event-related/sparse-sampling fMRI approach to investigate this essential cognitive function. In each 10-sec trial, subjects were instructed to wait for an auditory “cue” signaling the location where a subsequent “target” sound was likely to be presented. The target was occasionally replaced by an unexpected “novel” sound in the uncued ear, to trigger involuntary attention shifting. To maximize the attention effects, cues, targets, and novels were embedded within dichotic 800-Hz vs. 1500-Hz pure-tone “standard” trains. The sound of clustered fMRI acquisition (starting at t = 7.82 sec) served as a controlled trial-end signal. Our approach revealed notable activation differences between the conditions. Cued voluntary attention shifting activated the superior intra­­parietal sulcus (IPS), whereas novelty-triggered involuntary orienting activated the inferior IPS and certain subareas of the precuneus. Clearly more widespread activations were observed during voluntary than involuntary orienting in the premotor cortex, including the frontal eye fields. Moreover, we found ­evidence for a frontoinsular-cingular attentional control network, consisting of the anterior insula, inferior frontal cortex, and medial frontal cortices, which were activated during both target discrimination and voluntary attention shifting. Finally, novels and targets activated much wider areas of superior temporal auditory cortices than shifting cues

A Parallel Study of mRNA and microRNA Profiling of Peripheral Blood in Young Adult Women

Background: Aging is a complex process that involves the interplay of genetic, epigenetic, and environmental factors. Identifying aging-related biomarkers holds great potential for improving our understanding of complex physiological changes, thereby providing a means to investigate the mechanism by which aging influences various diseases. Method and Results: We performed a parallel study of microRNA and gene expression profiling of peripheral blood in a group of healthy young adult women, among which 13 were aged 22–25 and 9 were aged 36–39 years old. We identified a significantly distinct pattern of microRNA, but not gene expression profiling, between these two young adult women groups. We also performed correlation analysis of expression levels between all pairs of age-associated microRNAs and genes and identified a weak global correlation between these two types of expression levels. A significant involvement of estrogen regulation was observed by pathway analysis of the most differentially expressed microRNAs that included miR-155, -18a, -142, -340, -363, -195, and -24. Conclusion: Our results suggest that the change in global microRNA expression in the peripheral blood is associated with normal aging in young adult women. This change may precede global gene expression changes. Future studies are needed to investigate the regulatory mechanism of the estrogen-related microRNAs and associated diseases

Estimation of GFR using β-trace protein in children

Background and objectives Sexmay affect the performance of smallmolecularweight proteins as markers of GFR because of differences in fat mass between the two sexes. The hypothesis was that the diagnostic performance of b-trace protein, a novel marker of GFR, would be significantly better in boys than in girls. Design, setting, participants, & measurements GFR, height, weight, serum creatinine, and β-trace protein were measured in 755 children and adolescents (331 girls) undergoing 99technetium diethylenetriamine penta–acetic acid renal scans from July of 1999 to July of 2006. Boys and girls were separated into formula generation cohorts (284 boys and 220 girls) and formula validation cohorts (140 boys and 111 girls). GFRestimating formulas on the basis of β-trace protein, creatinine, and height were derived using stepwise linear regression analysis of log-transformed data. The slope of the regression lines of the sex-specific eGFRswere compared. Bland–Altman analysis was used for testing agreement between 99technetium diethylenetriamine penta–acetic acid GFR and calculated GFR both with this equation in boys and girls as well as previously established Benlamri, White, and Schwartz formulas. Results In the stepwise regression analysis, β-trace protein (R2=0.73 for boys and R2=0.65 for girls) was more important than creatinine (which increased R2 to 0.81 for boys and R2 to 0.75 for girls) and height (which increased R2 to 0.88 for boys and R2 to 0.80 for girls) in the data generation groups. GFR can be calculated using the following formulas: formula present Bland–Altman analysis showed better performance in boys than in girls. The new formulas performed significantly better than the previous Benlamri, White, and Schwartz formulas with respect to bias, precision, and accuracy. Conclusions Improved and sex-specific formulas for the estimation of GFR in children on the basis of β-trace protein, serum creatinine, and height are now available

Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling.

Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.Medical Research Counci