Kir4.1 channels contribute to astrocyte CO2/H+-sensitivity and the drive to breathe

Astrocytes in the retrotrapezoid nucleus (RTN) stimulate breathing in response to CO2/H+, however, it is not clear how these cells detect changes in CO2/H+. Considering Kir4.1/5.1 channels are CO2/H+-sensitive and important for several astrocyte-dependent processes, we consider Kir4.1/5.1 a leading candidate CO2/H+ sensor in RTN astrocytes. To address this, we show that RTN astrocytes express Kir4.1 and Kir5.1 transcripts. We also characterized respiratory function in astrocyte-specific inducible Kir4.1 knockout mice (Kir4.1 cKO); these mice breathe normally under room air conditions but show a blunted ventilatory response to high levels of CO2, which could be partly rescued by viral mediated re-expression of Kir4.1 in RTN astrocytes. At the cellular level, astrocytes in slices from astrocyte-specific inducible Kir4.1 knockout mice are less responsive to CO2/H+ and show a diminished capacity for paracrine modulation of respiratory neurons. These results suggest Kir4.1/5.1 channels in RTN astrocytes contribute to respiratory behavior

Prevention of insulin resistance in adolescents at risk for type 2 diabetes with depressive symptoms: 1-year follow-up of a randomized trial

Background: Depression is associated with poor insulin sensitivity. We evaluated the long-term effects of a cognitive behavioral therapy (CBT) program for prevention of depression on insulin sensitivity in adolescents at risk for type 2 diabetes (T2D) with depressive symptoms. Methods: One-hundred nineteen adolescent females with overweight/obesity,T2Dfamily history, and mild-to-moderate depressive symptoms were randomized to a 6-week CBT group (n = 61) or 6-week health education (HE) control group (n = 58). At baseline, posttreatment, and 1 year, depressive symptoms were assessed, and whole body insulin sensitivity (WBISI) was estimated from oral glucose tolerance tests.Dual energy X-ray absorptiometry assessed fat mass at baseline and 1 year. Primary outcomes were 1-year changes in depression and insulin sensitivity, adjusting for adiposity and other relevant covariates. Secondary outcomeswere fasting and 2-hr insulin and glucose.We also evaluated the moderating effect of baseline depressive symptom severity. Results: Depressive symptoms decreased in both groups (P \u3c .001). Insulin sensitivity was stable inCBTandHE(ΔWBISI: .1 vs. .3) and did not differ between groups (P=.63).However, among girls with greater (moderate) baseline depressive symptoms (N = 78), those in CBT developed lower 2- hr insulin than those in HE (Δ-16 vs. 16 �IU/mL, P \u3c .05). Additional metabolic benefits of CBT were seen for this subgroup in post hoc analyses of posttreatment to 1-year change. Conclusions: Adolescent females at risk for T2D decreased depressive symptoms and stabilized insulin sensitivity 1 year following brief CBT or HE. Further studies are required to determine if adolescents with moderate depression show metabolic benefits after CBT

Political strategies of external support for democratization

Political strategies of external support to democratization are contrasted and critically examined in respect of the United States and European Union. The analysis begins by defining its terms of reference and addresses the question of what it means to have a strategy. The account briefly notes the goals lying behind democratization support and their relationship with the wider foreign policy process, before considering what a successful strategy would look like and how that relates to the selection of candidates. The literature's attempts to identify strategy and its recommendations for better strategies are compared and assessed. Overall, the article argues that the question of political strategies of external support for democratization raises several distinct but related issues including the who?, what?, why?, and how? On one level, strategic choices can be expected to echo the comparative advantage of the "supporter." On a different level, the strategies cannot be divorced from the larger foreign policy framework. While it is correct to say that any sound strategy for support should be grounded in a theoretical understanding of democratization, the literature on strategies reveals something even more fundamental: divergent views about the nature of politics itself. The recommendations there certainly pinpoint weaknesses in the actual strategies of the United States and Europe but they have their own limitations too. In particular, in a world of increasing multi-level governance strategies for supporting democratization should go beyond preoccupation with just an "outside-in" approach

A randomized, comparative pilot trial of family-based interpersonal psychotherapy for reducing psychosocial symptoms, disordered-eating, and excess weight gain in at-risk preadolescents with loss-of-control-eating: SHOMAKER et al.

Preadolescent loss-of-control-eating (LOC-eating) is a risk factor for excess weight gain and binge-eating-disorder. We evaluated feasibility and acceptability of a preventive family-based interpersonal psychotherapy (FB-IPT) program. FB-IPT was compared to family-based health education (FB-HE) to evaluate changes in children’s psychosocial functioning, LOC-eating, and body mass

Nonparametric Simulation of Signal Transduction Networks with Semi-Synchronized Update

Simulating signal transduction in cellular signaling networks provides predictions of network dynamics by quantifying the changes in concentration and activity-level of the individual proteins. Since numerical values of kinetic parameters might be difficult to obtain, it is imperative to develop non-parametric approaches that combine the connectivity of a network with the response of individual proteins to signals which travel through the network. The activity levels of signaling proteins computed through existing non-parametric modeling tools do not show significant correlations with the observed values in experimental results. In this work we developed a non-parametric computational framework to describe the profile of the evolving process and the time course of the proportion of active form of molecules in the signal transduction networks. The model is also capable of incorporating perturbations. The model was validated on four signaling networks showing that it can effectively uncover the activity levels and trends of response during signal transduction process

Advances in studying brain morphology: the benefits of open-access data

Until recently, neuroimaging data for a research study needed to be collected within one’s own lab. However, when studying inter-individual differences in brain structure, a large sample of participants is necessary. Given the financial costs involved in collecting neuroimaging data from hundreds or thousands of participants, large-scale studies of brain morphology could previously only be conducted by well-funded laboratories with access to MRI facilities and to large samples of participants. With the advent of broad open-access data-sharing initiatives, this has recently changed–here the primary goal of the study is to collect large datasets to be shared, rather than sharing of the data as an afterthought. This paradigm shift is evident as increase in the pace of discovery, leading to a rapid rate of advances in our characterization of brain structure. The utility of open-access brain morphology data is numerous, ranging from observing novel patterns of agerelated differences in subcortical structures to the development of more robust cortical parcellation atlases, with these advances being translatable to improved methods for characterizing clinical disorders (see Figure 1 for an illustration). Moreover, structural MRIs are generally more robust than functional MRIs, relative to potential artifacts and in being not task-dependent, resulting in large potential yields. While the benefits of open-access data have been discussed more broadly within the field of cognitive neuroscience elsewhere (Van Horn and Gazzaniga, 2013; Poldrack and Gorgolewski, 2014; Van Horn and Toga, 2014; Vogelstein et al., 2016; Voytek, 2016; Gilmore et al., 2017), as well as in other fields (Choudhury et al., 2014; Ascoli et al., 2017; Davies et al., 2017), this opinion paper is focused specifically on the implications of open data to brain morphology research

Differential Response of High-Elevation Planktonic Bacterial Community Structure and Metabolism to Experimental Nutrient Enrichment

Nutrient enrichment of high-elevation freshwater ecosystems by atmospheric deposition is increasing worldwide, and bacteria are a key conduit for the metabolism of organic matter in these oligotrophic environments. We conducted two distinct in situ microcosm experiments in a high-elevation lake (Emerald Lake, Sierra Nevada, California, USA) to evaluate responses in bacterioplankton growth, carbon utilization, and community structure to short-term enrichment by nitrate and phosphate. The first experiment, conducted just following ice-off, employed dark dilution culture to directly assess the impact of nutrients on bacterioplankton growth and consumption of terrigenous dissolved organic matter during snowmelt. The second experiment, conducted in transparent microcosms during autumn overturn, examined how bacterioplankton in unmanipulated microbial communities responded to nutrients concomitant with increasing phytoplankton-derived organic matter. In both experiments, phosphate enrichment (but not nitrate) caused significant increases in bacterioplankton growth, changed particulate organic stoichiometry, and induced shifts in bacterial community composition, including consistent declines in the relative abundance of Actinobacteria. The dark dilution culture showed a significant increase in dissolved organic carbon removal in response to phosphate enrichment. In transparent microcosms nutrient enrichment had no effect on concentrations of chlorophyll, carbon, or the fluorescence characteristics of dissolved organic matter, suggesting that bacterioplankton responses were independent of phytoplankton responses. These results demonstrate that bacterioplankton communities in unproductive high-elevation habitats can rapidly alter their taxonomic composition and metabolism in response to short-term phosphate enrichment. Our results reinforce the key role that phosphorus plays in oligotrophic lake ecosystems, clarify the nature of bacterioplankton nutrient limitation, and emphasize that evaluation of eutrophication in these habitats should incorporate heterotrophic microbial communities and processes

eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5'UTR

Background: Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood. Results: Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5′UTR of target mRNAs directly upstream of the AUG start codon. Conclusions: Our data support a model whereby purine motifs towards the 3′ end of the 5′UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding