Cross-Lagged Relations Between Motives and Substance Use: Can Use Strengthen Your Motivation Over Time?

Motives for substance use have garnered considerable attention due to the strong predictive utility of this construct, both in terms of use and problems associated with use. The current study examined the cross-lagged relations between alcohol use and motives, and marijuana use and motives over three yearly assessment periods in a large sample (N = 526, 48% male) of college students. The relations between substance use and motives were assessed at each time point, allowing for the examination of these inter-relations over time. Results indicated different trends based on the type of substance. For alcohol use, cross-lagged trends were found between freshman and sophomore year for coping, social, and conformity motives with cross-lagged relations between enhancement motives and alcohol use across all years. However, outside of enhancement motives, cross-lagged relations were not found between sophomore and junior year. In contrast, cross-lagged effects were found for marijuana use and coping, enhancement, and expansion motives between sophomore and junior year, but not freshman year. These results suggest that people’s expectations that drinking or smoking marijuana makes activities more reinforcing and helps them cope with distress may perpetuate use. In turn, use itself may enhance these expectations over time. Results have direct implications for treatment, with recommended focus on motives, behavior activation, and healthy coping skills in order to interrupt the cycle of substance use

Aberrant Ca2+ signaling by IP3Rs in adipocytes links inflammation to metabolic dysregulation in obesity.

Chronic metabolic inflammation is a key feature of obesity, insulin resistance, and diabetes. Here, we showed that altered regulation of the Ca2+ channel inositol trisphosphate receptor (IP3R) was an adipocyte-intrinsic event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation induced by cytokine exposure in vitro or by obesity in vivo led to increases in the abundance and activity of IP3Rs and in the phosphorylation of the Ca2+-dependent kinase CaMKII in adipocytes in a manner dependent on the kinase JNK. In mice, adipocyte-specific loss of IP3R1/2 protected against adipose tissue inflammation and insulin resistance, despite the mice exhibiting substantial diet-induced weight gain. Thus, this work suggests that increased IP3R activity is a key link between obesity, inflammation, and insulin resistance. These data also suggest that approaches to target IP3R-mediated Ca2+ homeostasis in adipocytes may offer new therapeutic opportunities against metabolic diseases, especially because GWAS studies also implicate this locus in human obesity

Aberrant Ca2+ homeostasis in adipocytes links inflammation to metabolic dysregulation in obesity [preprint]

Chronic metabolic inflammation is a key feature of obesity, insulin resistance and diabetes, although the initiation and propagation mechanisms of metaflammation are not fully established, particularly in the adipose tissue. Here we show that in adipocytes, altered regulation of the Ca2+ channel inositol triphosphate receptor (IP3Rs) is a key, adipocyte-intrinsic, event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation, either induced by cytokine exposure in vitro or by obesity in vivo lead to increased expression and activity of IP3Rs in adipocytes in a JNK-dependent manner. This results in increased cytosolic Ca2+ and impaired insulin action. In mice, adipocyte-specific loss of IP3R1/2 protected against adipose tissue inflammation and insulin resistance despite significant diet-induced weight gain. Thus, this work reveals that IP3R over-activation and the resulting increase in cytosolic Ca2+ is a key link between obesity, inflammation and insulin resistance, and suggests that approaches to target adipocyte Ca2+ homeostasis may offer new therapeutic opportunities against metabolic diseases, especially since GWAS studies also implicate this locus in human obesity

WormBase: a comprehensive resource for nematode research

WormBase (http://www.wormbase.org) is a central data repository for nematode biology. Initially created as a service to the Caenorhabditis elegans research field, WormBase has evolved into a powerful research tool in its own right. In the past 2 years, we expanded WormBase to include the complete genomic sequence, gene predictions and orthology assignments from a range of related nematodes. This comparative data enrich the C. elegans data with improved gene predictions and a better understanding of gene function. In turn, they bring the wealth of experimental knowledge of C. elegans to other systems of medical and agricultural importance. Here, we describe new species and data types now available at WormBase. In addition, we detail enhancements to our curatorial pipeline and website infrastructure to accommodate new genomes and an extensive user base

Transcription factor Pit-1 affects transcriptional timing in the dual-promoter human prolactin gene

Gene transcription occurs in short bursts interspersed with silent periods, and these kinetics can be altered by promoter structure. The effect of alternate promoter architecture on transcription bursting is not known. We studied the human prolactin (hPRL) gene that contains two promoters, a pituitary-specific promoter that requires the transcription factor Pit-1, and displays dramatic transcriptional bursting activity, and an alternate upstream promoter that is active in non-pituitary tissues. We studied large hPRL genomic fragments with luciferase reporters, and used bacterial artificial chromosome (BAC) recombineering to manipulate critical promoter regions. Stochastic switch mathematical modelling of single-cell time-lapse luminescence image data revealed that the Pit-1-dependent promoter showed longer, higher-amplitude transcriptional bursts. Knockdown studies confirmed that the presence of Pit-1 stabilised and prolonged periods of active transcription. Pit-1 therefore plays an active role in establishing the timing of transcription cycles, in addition to its cell-specific functions

Alterations to chromatin in intestinal macrophages link IL-10 deficiency to inappropriate inflammatory responses

Intestinal macrophages are uniquely programmed to tolerate exposure to bacteria without mounting potent inflammatory responses. The cytokine IL-10 maintains the macrophage anti-inflammatory response such that loss of IL-10 results in chronic intestinal inflammation. To investigate how IL-10-deficiency alters intestinal macrophage programming and bacterial tolerance, we studied changes in chromatin accessibility in response to bacteria in macrophages from two distinct niches, the intestine and bone-marrow, from both wild-type and IL-10-deficient mice. In both bone-marrow-derived and intestinal macrophages, we identified chromatin accessibility changes associated with bacterial exposure and IL-10-deficiency. Surprisingly, IL-10-deficient intestinal macrophages adopted chromatin and gene expression patterns characteristic of an inflammatory response, even in the absence of bacteria. Further, if IL-10 protein was added to cells that had previously been IL-10-deficient, it could not revert the chromatin landscape to a normal state. Our results demonstrate that IL-10 deficiency results in stable chromatin alterations in macrophages, even in the absence of bacteria. This supports a model where IL-10-deficiency leads to chromatin alterations that contribute to a loss of intestinal macrophage tolerance to bacteria, which is a primary initiating event in chronic intestinal inflammation

The green valley is a red herring : Galaxy Zoo reveals two evolutionary pathways towards quenching of star formation in early-and late-type galaxies

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Monthly Notices of the Royal Astronomical Society following peer review. The version of record [Kevin Schawinski, et al, 'The green valley is a red herring: Galaxy Zoo reveals two evolutionary pathways towards quenching of star formation in early- and late-type galaxies' MNRAS, Vol. 440(1): 889-907, May 2014] is available online at: https://doi.org/10.1093/mnras/stu327.We use SDSS+GALEX+Galaxy Zoo data to study the quenching of star formation in lowredshift galaxies. We show that the green valley between the blue cloud of star-forming galaxies and the red sequence of quiescent galaxies in the colour-mass diagram is not a single transitional state through which most blue galaxies evolve into red galaxies. Rather, an analysis that takes morphology into account makes clear that only a small population of blue early-type galaxies move rapidly across the green valley after the morphologies are transformed from disc to spheroid and star formation is quenched rapidly. In contrast, the majority of blue star-forming galaxies have significant discs, and they retain their late-type morphologies as their star formation rates decline very slowly. We summarize a range of observations that lead to these conclusions, including UV-optical colours and halo masses, which both show a striking dependence on morphological type. We interpret these results in terms of the evolution of cosmic gas supply and gas reservoirs. We conclude that late-type galaxies are consistent with a scenario where the cosmic supply of gas is shut off, perhaps at a critical halo mass, followed by a slow exhaustion of the remaining gas over several Gyr, driven by secular and/or environmental processes. In contrast, early-type galaxies require a scenario where the gas supply and gas reservoir are destroyed virtually instantaneously, with rapid quenching accompanied by a morphological transformation from disc to spheroid. This gas reservoir destruction could be the consequence of a major merger, which in most cases transforms galaxies from disc to elliptical morphology, and mergers could play a role in inducing black hole accretion and possibly active galactic nuclei feedback.Peer reviewe

WALLABY Pre-Pilot and Pilot Survey: the Tully Fisher Relation in Eridanus, Hydra, Norma and NGC4636 fields

The WALLABY pilot survey has been conducted using the Australian SKA Pathfinder (ASKAP). The integrated 21-cm HI line spectra are formed in a very different manner compared to usual single-dish spectra Tully-Fisher measurements. It is thus extremely important to ensure that slight differences (e.g. biases due to missing flux) are quantified and understood in order to maximise the use of the large amount of data becoming available soon. This article is based on four fields for which the data are scientifically interesting by themselves. The pilot data discussed here consist of 614 galaxy spectra at a rest wavelength of 21cm. Of these spectra, 472 are of high enough quality to be used to potentially derive distances using the Tully-Fisher relation. We further restrict the sample to the 251 galaxies whose inclination is sufficiently close to edge-on. For these, we derive Tully-Fisher distances using the deprojected WALLABY velocity widths combined with infrared (WISE W1) magnitudes. The resulting Tully-Fisher distances for the Eridanus, Hydra, Norma and NGC 4636 clusters are 21.5, 53.5, 69.4 and 23.0 Mpc respectively, with uncertainties of 5–10%, which are better or equivalent to the ones obtained in studies using data obtained with giant single dish telescopes. The pilot survey data show the benefits of WALLABY over previous giant single-dish telescope surveys. WALLABY is expected to detect around half a million galaxies with a mean redshift of 푧 = 0.05(200푀 푝푐). This study suggests that about 200,000 Tully-Fisher distances might result from the survey