Surfactant protein D increases fusion of Mycobacterium tuberculosis- containing phagosomes with lysosomes in human macrophages

Lung surfactant protein D (SP-D) binds to Mycobacterium tuberculosis surface lipoarabinomannan and results in bacterial agglutination, reduced uptake, and inhibition of growth in human macrophages. Here we show that SP-D limits the intracellular growth of bacilli in macrophages by increasing phagosome-lysosome fusion but not by generating a respiratory burst

Tree-ring stable isotopes record the impact of a foliar fungal pathogen on CO₂ assimilation and growth in Douglas-fir

Swiss needle cast (SNC) is a fungal disease of Douglas-fir (Pseudotsuga menziesii) that has recently become prevalent in coastal areas of the Pacific Northwest. We used growth measurements and stable isotopes of carbon and oxygen in tree-rings of Douglas-fir and a non-susceptible reference species (western hemlock, Tsuga heterophylla) to evaluate their use as proxies for variation in past SNC infection, particularly in relation to potential explanatory climate factors. We sampled trees from an Oregon site where a fungicide trial took place from 1996 to 2000, which enabled the comparison of stable isotope values between trees with and without disease. Carbon stable isotope discrimination (Δ¹³C) of treated Douglas-fir tree-rings was greater than that of untreated Douglas-fir tree-rings during the fungicide treatment period. Both annual growth and tree-ring Δ¹³C increased with treatment such that treated Douglas-fir had values similar to co-occurring western hemlock during the treatment period. There was no difference in the tree-ring oxygen stable isotope ratio between treated and untreated Douglas-fir. Tree-ring Δ¹³C of diseased Douglas-fir was negatively correlated with relative humidity during the two previous summers, consistent with increased leaf colonization by SNC under high humidity conditions that leads to greater disease severity in following years.Keywords: Swiss needle cast, Stable isotopes, Phaeocryptopus gaeumannii, Pseudotsuga menziesii, Tree-ring

Impacts of dwarf mistletoe on the physiology of host Tsuga heterophylla trees as recorded in tree-ring C and O stable isotopes

See article for Abstract. Keywords: mesophyll conductance, effective path lengt

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.Peer reviewe

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.Peer reviewe

Annual Change in Opioid Prescribing and Concomitant Medications from an Urban Academic Emergency Department from 2011-2016

Objectives Primary Objective Describe change in annual opioid prescribing rates written for patients discharged from an urban academic ED Secondary Objectives Investigate variation in types of opioids prescribed over time Report on medications co-prescribed with opioid

Systematic literature review on the effect of antidepressants on sleep impairment in major depressive disorder

Major Depressive Disorder (MDD) is a prevalent, chronic mood disorder that affects more than 300 million people globally (World Health Organization, 2017). One of the specific symptoms of MDD is fatigue due to insomnia or hypersomnia. It is estimated that the prevalence of lifetime insomnia in people with MDD may be as high as 90% (Soehner, 2014; Seow 2016). Insomnia has adverse effects on daytime functioning and overall functional recovery, even when severity of depression symptoms is mitigated or resolved (O’Brien, 2011; Xiao, 2018). The lack of evidence-based treatments for insomnia in individuals with MDD is an unmet need in clinical practice. As new pharmacologic treatments are being studied specifically for sleep impairment within context of MDD, it is important for policymakers and formulary decision makers to understand the current landscape of how FDA-approved antidepressants affect sleep symptoms to make informed coverage decisions for emerging therapies. This systematic literature review sought to assess how FDA approved antidepressants affect sleep symptoms in adults with major depressive disorder. This review showed that a prolific body of evidence exists to evaluate the effect of antidepressants approved for MDD in the US; however, a variety of outcomes can be used to evaluate effect on sleep and there is not one standard measure. Additional research could be conducted to quantify the qualitative assessment done here, either in the form of a meta-analysis or indirect treatment comparisons. The findings here should be taken into context relative to the overall efficacy and safety profile of each antidepressant agent, outside of its effect on sleep. The findings from this review are generally consistent with antidepressant agents thought to have positive effects on sleep impairment in MDD (i.e. quetiapine, mirtazapine, trazodone)

Tree-ring stable isotopes record the impact of a foliar fungal pathogen on CO\u3csub\u3e2\u3c/sub\u3e assimilation and growth in Douglas-fir

Swiss needle cast (SNC) is a fungal disease of Douglas-fir (Pseudotsuga menziesii) that has recently become prevalent in coastal areas of the Pacific Northwest. We used growth measurements and stable isotopes of carbon and oxygen in tree-rings of Douglas-fir and a non-susceptible reference species (western hemlock, Tsuga heterophylla) to evaluate their use as proxies for variation in past SNC infection, particularly in relation to potential explanatory climate factors. We sampled trees from an Oregon site where a fungicide trial took place from 1996 to 2000, which enabled the comparison of stable isotope values between trees with and without disease. Carbon stable isotope discrimination (Δ13C) of treated Douglas-fir tree-rings was greater than that of untreated Douglas-fir tree-rings during the fungicide treatment period. Both annual growth and tree-ring Δ13C increased with treatment such that treated Douglas-fir had values similar to co-occurring western hemlock during the treatment period. There was no difference in the tree-ring oxygen stable isotope ratio between treated and untreated Douglas-fir. Tree-ring Δ13C of diseased Douglas-fir was negatively correlated with relative humidity during the two previous summers, consistent with increased leaf colonization by SNC under high humidity conditions that leads to greater disease severity in following years

An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in \u3ci\u3eSaccharomyces cerevisiae\u3c/i\u3e

Background: The machinery for interorganelle phosphatidylserine (PtdSer) transport is poorly defined at the molecular level. Results: Molecular interaction studies identify specific protein-protein and protein-lipid interactions in PtdSer transport. Conclusion: A protein and lipid interaction network defines key participants in PS transport to the locus of PtdSer-decarboxylase 2. Significance: This study identifies important molecular participants involved in non-vesicular phospholipid traffic