352 research outputs found

    Bidirectional associations between body dissatisfaction and depressive symptoms from adolescence through early adulthood

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    Body dissatisfaction and depressive symptoms are commonly experienced during adolescence and increase the risk of adverse health outcomes, especially eating disorders. However, the dominant temporal associations between these two experiences (i.e., whether one is a risk factor for the other or the two are mutually reinforcing) has yet to be fully explored. We examined the associations between body dissatisfaction and depressive symptoms assessed at baseline and 5- and 10-year follow-up in younger (M age = 12.9 years at baseline, 56% female, n = 577) and older (M age = 15.9 years at baseline, 57% female, n = 1,325) adolescent cohorts assessed as part of Project Eating Among Teens and Young Adults. Associations between body dissatisfaction and depressive symptoms were examined using cross-lagged models. For females, the dominant directionality was for body dissatisfaction predicting later depressive symptoms. For males, the picture was more complex, with developmentally sensitive associations in which depressive symptoms predicted later body dissatisfaction in early adolescence and early adulthood, but the reverse association was dominant during middle adolescence. These findings suggest that interventions should be tailored to dynamic risk profiles that shift over adolescence and early adulthood, and that targeting body dissatisfaction at key periods during development may have downstream impacts on depressive symptoms

    Pharmacological characterisation of MDI-222, a novel AMPA receptor positive allosteric modulator with an improved safety profile

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    There is considerable interest in positive allosteric modulators (PAMs) of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) subtype of ionotropic glutamate receptors as therapeutic agents for a range of cognitive and mood disorders. However, the challenge is to increase AMPA receptor (AMPAR) function sufficient to enhance cognitive function but not to the extent that there are mechanism-related pro-convulsant or convulsant side effects. In this present study, we report the preclinical pharmacology data for MDI-222, an AMPAR PAM which enhances cognition but has a much reduced side-effect (i.e. convulsant) liability relative to other molecules of this mechanism

    The need for a far-infrared cold space telescope to understand the chemistry of planet formation

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    At a time when ALMA produces spectacular high resolution images of gas and dust in circumstellar disks, the next observational frontier in our understanding of planet formation and the chemistry of planet-forming material may be found in the mid- to far-infrared wavelength range. A large, actively cooled far-infrared telescope in space will offer enormous spectroscopic sensitivity improvements of 3-4 orders of magnitude, making it possible to uniquely survey certain fundamental properties of planet formation. Specifically, the Origins Space Telescope (OST), a NASA flagship concept to be submitted to the 2020 decadal survey, will provide a platform that allows complete surveys of warm and cold water around young stars of all masses and across all evolutionary stages, and to measure their total planet-forming gas mass using the ground-state line of HD. While this white paper is formulated in the context of the NASA Origins Space Telescope concept, it can be applied in general to inform any future space-based, cold far-infrared observatory

    DNA and Inflammatory Mediators in Bronchoalveolar Lavage Fluid From Children With Acute Inhalational Injuries:

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    Assess the feasibility of using serial bronchoalveolar lavage fluids (BALF) to characterize the course of cell damage and inflammation in airways of pediatric patients with acute burn or inhalation injury

    Evidence of a small, island-associated population of common bottlenose dolphins in the Mariana Islands

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    Small, island-associated populations of cetaceans have evolved around numerous oceanic islands, likely due to habitat discontinuities between nearshore and offshore waters. However, little is known about the ecology and structure of cetacean populations around the Mariana Islands, a remote archipelago in the western Pacific Ocean. We present sighting, photo-identification, and genetic data collected during twelve years of surveys around these islands that reveal the existence of a small, island-associated population of bottlenose dolphins. Nearly half of the photo-identified individuals were encountered in more than one year. Both haplotypic and nuclear genetic diversity among sampled individuals was low (haplotypic diversity = 0.701, nuclear heterozygosity = 0.658), suggesting low abundance. We used mark-recapture analysis of photo-identification data to estimate yearly abundance in the southern portion of the population’s range from 2011 to 2018. Each abundance estimate was less than 54 individuals, with each upper 95% confidence interval below 100. Additional survey effort is necessary to generate a full population abundance estimate. We found extensive introgression of Fraser’s dolphin DNA into both the mitochondrial and nuclear genomes of the population, suggesting at least two hybridization events more than two generations in the past. The Mariana Islands are used extensively by the U.S. military for land and sea training operations. Thus, this unique bottlenose dolphin population likely faces high exposure to multiple threats

    Effect of ABCG2/BCRP Expression on Efflux and Uptake of Gefitinib in NSCLC Cell Lines

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    BCRP/ABCG2 emerged as an important multidrug resistance protein, because it confers resistance to several classes of cancer chemotherapeutic agents and to a number of novel molecularly-targeted therapeutics such as tyrosine kinase inhibitors. Gefitinib is an orally active, selective EGFR tyrosine kinase inhibitor used in the treatment of patients with advanced non small cell lung cancer (NSCLC) carrying activating EGFR mutations. Membrane transporters may affect the distribution and accumulation of gefitinib in tumour cells; in particular a reduced intracellular level of the drug may result from poor uptake, enhanced efflux or increased metabolism

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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