Studies Into β-Glucan Recognition in Fish Suggests a Key Role for the C-Type Lectin Pathway

Immune-modulatory effects of β-glucans are generally considered beneficial to fish health. Despite the frequent application of β-glucans in aquaculture practice, the exact receptors and downstream signalling remains to be described for fish. In mammals, Dectin-1 is a member of the C-type lectin receptor (CLR) family and the best-described receptor for β-glucans. In fish genomes, no clear homologue of Dectin-1 could be identified so far. Yet, in previous studies we could activate carp macrophages with curdlan, considered a Dectin-1-specific β-(1,3)-glucan ligand in mammals. It was therefore proposed that immune-modulatory effects of β-glucan in carp macrophages could be triggered by a member of the CLR family activating the classical CLR signalling pathway, different from Dectin-1. In the current study, we used primary macrophages of common carp to examine immune modulation by β-glucans using transcriptome analysis of RNA isolated 6 h after stimulation with two different β-glucan preparations. Pathway analysis of differentially expressed genes (DEGs) showed that both β-glucans regulate a comparable signalling pathway typical of CLR activation. Carp genome analysis identified 239 genes encoding for proteins with at least one C-type Lectin Domains (CTLD). Narrowing the search for candidate β-glucan receptors, based on the presence of a conserved glucan-binding motif, identified 13 genes encoding a WxH sugar-binding motif in their CTLD. These genes, however, were not expressed in macrophages. Instead, among the β-glucan-stimulated DEGs, a total of six CTLD-encoding genes were significantly regulated, all of which were down-regulated in carp macrophages. Several candidates had a protein architecture similar to Dectin-1, therefore potential conservation of synteny of the mammalian Dectin-1 region was investigated by mining the zebrafish genome. Partial conservation of synteny with a region on the zebrafish chromosome 16 highlighted two genes as candidate β-glucan receptor. Altogether, the regulation of a gene expression profile typical of a signalling pathway associated with CLR activation and, the identification of several candidate β-glucan receptors, suggest that immune-modulatory effects of β-glucan in carp macrophages could be a result of signalling mediated by a member of the CLR family

Genome streamlining via complete loss of introns has occurred multiple times in lichenized fungal mitochondria.

Reductions in genome size and complexity are a hallmark of obligate symbioses. The mitochondrial genome displays clear examples of these reductions, with the ancestral alpha-proteobacterial genome size and gene number having been reduced by orders of magnitude in most descendent modern mitochondrial genomes. Here, we examine patterns of mitochondrial evolution specifically looking at intron size, number, and position across 58 species from 21 genera of lichenized Ascomycete fungi, representing a broad range of fungal diversity and niches. Our results show that th

What life course theoretical models best explain the relationship between exposure to childhood adversity and psychopathology symptoms: Recency, accumulation, or sensitive periods?

Copyright © Cambridge University Press 2018Â. Background Although childhood adversity is a potent determinant of psychopathology, relatively little is known about how the characteristics of adversity exposure, including its developmental timing or duration, influence subsequent mental health outcomes. This study compared three models from life course theory (recency, accumulation, sensitive period) to determine which one(s) best explained this relationship.Methods Prospective data came from the Avon Longitudinal Study of Parents and Children (n = 7476). Four adversities commonly linked to psychopathology (caregiver physical/emotional abuse; sexual/physical abuse; financial stress; parent legal problems) were measured repeatedly from birth to age 8. Using a statistical modeling approach grounded in least angle regression, we determined the theoretical model(s) explaining the most variability (r2) in psychopathology symptoms measured at age 8 using the Strengths and Difficulties Questionnaire and evaluated the magnitude of each association.Results Recency was the best fitting theoretical model for the effect of physical/sexual abuse (girls r2 = 2.35%; boys r2 = 1.68%). Both recency (girls r2 = 1.55%) and accumulation (boys r2 = 1.71%) were the best fitting models for caregiver physical/emotional abuse. Sensitive period models were chosen alone (parent legal problems in boys r2 = 0.29%) and with accumulation (financial stress in girls r2 = 3.08%) more rarely. Substantial effect sizes were observed (standardized mean differences = 0.22-1.18).Conclusions Child psychopathology symptoms are primarily explained by recency and accumulation models. Evidence for sensitive periods did not emerge strongly in these data. These findings underscore the need to measure the characteristics of adversity, which can aid in understanding disease mechanisms and determining how best to reduce the consequences of exposure to adversity

Efficacy and Tolerability of Pharmacotherapies to Aid Smoking Cessation in Adolescents

Abstract Adolescent smoking remains a public health problem. Despite concerns regarding adolescent nicotine dependence, few well-designed smoking cessation studies have been conducted with teen smokers. This is particularly true regarding pharmacological treatments for nicotine dependence. Currently, pharmacological aids are not recommended for treating adolescent nicotine dependence, as efficacy has not been shown in this population. This review includes studies that have examined the efficacy of pharmacotherapy for smoking abstinence and/or reduction in cigarette consumption among adolescent smokers who want to quit smoking, lab-based adolescent studies that have examined the effectiveness of these medications in reducing cravings and/or withdrawal symptoms, and/or studies that have assessed the tolerability of medications for smoking cessation in adolescent smokers. This review provides information on the pharmacologic action of each medication, the efficacy of each medication for adolescent smoking cessation, the tolerability of each medication based on reported adverse events, and compliance with the medication protocols. Thirteen relevant articles were identified and included in the review. Nicotine patch, nicotine gum, nicotine nasal spray, bupropion, and varenicline have been studied in adolescent smokers. The adverse events reported in the studies on pharmacology for adolescent smoking suggest that the side effect profiles for nicotine replacement therapy, bupropion, and varenicline are similar to those reported in adult studies. There is some evidence of efficacy of nicotine patch and bupropion at end of treatment (efficacy of varenicline has not been assessed), but none of the medications included in this review were efficacious in promoting long-term smoking cessation among adolescent smokers. It is noted that many of the study protocols did not follow the recommended dose or length of pharmacotherapy for adults, rendering it difficult to determine the true efficacy of medication for adolescent smoking cessation. Future efficacy studies are warranted before recommending pharmacotherapy for adolescent smoking cessation. Adolescent Smoking and Pharmacotherapy Adolescent smoking remains a high priority public health concern. The U.S. Department of Health and Human Services has retained the goal of reducing adolescent smoking rates in the Healthy People 2020 initiative. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Considering that over 80% of adult smokers begin smoking prior to age of 18, Relatively few well-designed smoking cessation studies have been conducted with teen smokers. This is particularly true regarding pharmacological treatments for nicotine dependence. To date, nicotine replacement, bupropion (Zyban), and varenicline have been approved as therapies for adult smokers and the recommended treatment for adult nicotine dependence is a combination of psychotherapy and pharmacotherapy. Methods Study Identification and Inclusion Searches were conducted through the PubMed and PsycINFO online databases (through May 2011) and were limited to "English Language" and "Human." The following keywords were used in the initial search "smoking cessation", "adolescent OR teen" and then limited by the separate use of the following terms: "bupropion", "Zyban", "nicotine replacement therapy", "varenicline", "Chantix", "nicotine patch", "nicotine gum", "nicotine nasal spray", and "pharmacotherapy." Only studies that targeted adolescent smokers for recruitment and enrollment were included. In addition, studies referenced in relevant review articles, metaanalyses, and all selected articles were examined. The searches yielded 14 relevant studies that included pharmacotherapy for adolescent nicotine dependence. One study was excluded from the review because the focus was on reduction of smoking among adolescents that did not want to quit and did not include data on adverse events. Nicotine replacement therapy This review focuses on nicotine replacement therapy (NRT) that has been evaluated for smoking cessation among adolescent smokers (nicotine patch, gum, and spray); however, there are other nicotine replacement products approved for smoking cessation, including a nicotine inhaler, a nicotine lozenge and, in some countries outside of the United States, a nicotine sublingual tablet. Nicotine replacement therapy (NRT) replaces the nicotine delivered while smoking to reduce craving and withdrawal symptoms and is available in different forms and dosages depending on the number of cigarettes smoked. Open-label studies- The earliest study to use NRT with adolescent smokers was conducted by Smith and colleagues in 1996. No adverse events were associated with discontinuation of patch therapy. Hurt et al. conducted a larger open-label study (n = 101) that coupled six weeks of 15 mg/ 16-hour NP therapy with an optional brief individual counseling session at the first clinic visit. Randomized clinical trials (RCT)- The first randomized, double-blind, placebocontrolled study of NRT was conducted by Hanson et al. in 2003. [16] Initial dose and titration schedules were based on the teens' level of cigarette consumption. Participants (n = 100) received 10 weeks of NP therapy and cognitive-behavioral therapy and a contingency management procedure. There were no significant differences between groups in biologically verified, 7-day point prevalence abstinence at end of treatment (Week 10) (28.0% NP vs. 24.0% placebo), 30-day point prevalence abstinence (20.0% NP vs. 18.0% placebo), or continuous abstinence from the quit date. Compared to the placebo patch group, the active NP group experienced a significantly lower craving score and overall withdrawal symptom score. Participants in the placebo patch group reported more headaches than those in the active NP group (75.6% vs. 56.3%, respectively). None reported dropping out as a result of an adverse event and no significant differences in dropout rates or medication compliance were observed across the treatment groups. A community-based, double-blind pilot RCT was conducted by Roddy and colleagues with 98 regular smokers (defined as > 1 cigarette per day or < 1 cigarette per day but reported past or anticipated withdrawal). Moolchan and colleagues Finally, Rubinstein et al. conducted a pilot randomized trial of nicotine nasal spray (NNS) in 40 adolescent smokers. Summary of efficacy See Safety/tolerability None of the studies reported any severe or life-threatening side effects. The adverse events reported by adolescents for NRT were similar to those reported by adult smokers. Of the NRT studies, only three reported discontinuation of study medication during treatment due to an adverse event. Special considerations for use in adolescent smokers Controversy remains over the use of NRT in adolescents. Studies with animals indicate that nicotine can elicit neuronal damage and long-term changes in synaptic function, suggesting that there could be long-term adverse consequences of nicotine exposure in adolescence. Bupropion Bupropion was initially marketed as an atypical antidepressant and was approved in 1997, under the name Zyban, as the first non-nicotine medication to aid in smoking cessation for adults. Bupropion inhibits the reuptake of dopamine and norepinephrine in the central nervous system Randomized clinical trials (RCT)-Four RCTs have assessed the efficacy of bupropion for smoking cessation with adolescents. In the only study to examine bupropion SR in combination with NP therapy, Killen and colleagues randomized adolescent smokers (n = 211) to receive eight weeks of NP therapy and nine weeks of either 150 mg/day bupropion SR or placebo pills. Finally, Gray and colleagues examined the efficacy of 300 mg/day bupropion SR and contingency management (CM). Summary of efficacy See None of the studies with 300 mg/day bupropion SR were longer than six weeks in duration. The full dose was well tolerated by adolescent smokers and resulted in higher end of treatment abstinence than 150 mg/day bupropion SR in the only adolescent multi-dose study. However, similar to the few multi-dose studies in adults, the higher dose did not produce a better outcome at follow-up. Paediatr Drugs. Author manuscript; available in PMC 2012 April 4. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Given that none of the studies that have examined the use of bupropion SR for adolescent nicotine dependence followed the dosage recommendations for adult smokers, a future study that adheres to these guidelines is warranted. Safety/tolerability The most common adverse events reported by adolescent smokers were similar to those reported by their adult counterparts Although bupropion SR was generally well tolerated by adolescent smokers, hospitalizations occurred on three occasions. One was due to the intentional ingestion of Jimson weed in combination with bupropion SR, resulting in an anticholinergic crisis. Compliance rates Three of the five studies provided compliance data, but the methods used to assess compliance varied across the three studies. Special considerations for use in adolescent smokers Zyban contains the same active ingredient as the antidepressant medications Wellbutrin, Wellbutrin SR, and Wellbutrin XL. In 2004, the FDA directed manufacturers to add a "black box" to the health professional label of all antidepressants warning that antidepressants increased the risk compared to placebo of suicidal thinking and suicidal behavior in NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders. In the RCTs with bupropion SR for smoking cessation in adolescent smokers, two adverse events were deemed to be intentional suicide attempts. Varenicline In 2006, the United States FDA approved varenicline as a prescription-only pharmacological aid for adult smoking cessation. It is also an approved smoking cessation aid in some countries outside of the U.S. Varenicline is a selective nicotinic acetylcholine receptor partial antagonist that binds to the α 4 β 2 receptor subtype, thereby reducing the reinforcing effects of nicotine. Due to its mixed agonist-antagonist properties, varenicline is effective at relieving craving and withdrawal during abstinence and blocking the reinforcing effects of smoking. Literature on varenicline in adolescent smokers One RCT examined the pharmacokinetics, safety and tolerability of varenicline in adolescent smokers

Psychosocial Factors Associated with Patterns of Smoking Surrounding Pregnancy in Fragile Families

Although research has documented factors associated with maternal smoking, we need a more in-depth understanding of the risk factors associated with changes in smoking behaviors during the postpartum period. We investigate smoking patterns during pregnancy and 1 year postpartum as a function of relevant psychosocial factors. We use data on 3,522 postpartum mothers from the Fragile Families and Child Wellbeing Study to analyze the predictors of smoking among mothers who did not smoke during pregnancy but smoked at 1 year postpartum, mothers who smoked both during pregnancy and postpartum, and mothers who did not smoke during either period. Our covariates are grouped into four categories of risk factors for smoking: socioeconomic status, health care, life course and health, and partner and social support. Postpartum mothers in our sample were more likely to smoke throughout or after their pregnancies if they had only a high school education or less, had a household income three or more times below the poverty line, had public or no health insurance, breastfed for less than 5 months, were not married to the infant’s father, if the infant’s father currently smoked, and if they attended religious services less than once a week. Mental health problems were consistently associated with an increased risk of constant and postpartum smoking relative to non-smoking. Psychosocial factors play a role in postpartum smoking, but they have a stronger effect in predicting smoking that persists throughout pregnancy and the first year postpartum

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations in the Data Release 9 Spectroscopic Galaxy Sample

We present measurements of galaxy clustering from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III). These use the Data Release 9 (DR9) CMASS sample, which contains 264,283 massive galaxies covering 3275 square degrees with an effective redshift z=0.57 and redshift range 0.43 < z < 0.7. Assuming a concordance Lambda-CDM cosmological model, this sample covers an effective volume of 2.2 Gpc^3, and represents the largest sample of the Universe ever surveyed at this density, n = 3 x 10^-4 h^-3 Mpc^3. We measure the angle-averaged galaxy correlation function and power spectrum, including density-field reconstruction of the baryon acoustic oscillation (BAO) feature. The acoustic features are detected at a significance of 5\sigma in both the correlation function and power spectrum. Combining with the SDSS-II Luminous Red Galaxy Sample, the detection significance increases to 6.7\sigma. Fitting for the position of the acoustic features measures the distance to z=0.57 relative to the sound horizon DV /rs = 13.67 +/- 0.22 at z=0.57. Assuming a fiducial sound horizon of 153.19 Mpc, which matches cosmic microwave background constraints, this corresponds to a distance DV(z=0.57) = 2094 +/- 34 Mpc. At 1.7 per cent, this is the most precise distance constraint ever obtained from a galaxy survey. We place this result alongside previous BAO measurements in a cosmological distance ladder and find excellent agreement with the current supernova measurements. We use these distance measurements to constrain various cosmological models, finding continuing support for a flat Universe with a cosmological constant.Comment: 33 page

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: measurements of the growth of structure and expansion rate at z=0.57 from anisotropic clustering

We analyze the anisotropic clustering of massive galaxies from the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 9 (DR9) sample, which consists of 264,283 galaxies in the redshift range 0.43 < z < 0.7 spanning 3,275 square degrees. Both peculiar velocities and errors in the assumed redshift-distance relation ("Alcock-Paczynski effect") generate correlations between clustering amplitude and orientation with respect to the line-of-sight. Together with the sharp baryon acoustic oscillation (BAO) standard ruler, our measurements of the broadband shape of the monopole and quadrupole correlation functions simultaneously constrain the comoving angular diameter distance (2190 +/- 61 Mpc) to z=0.57, the Hubble expansion rate at z=0.57 (92.4 +/- 4.5 km/s/Mpc), and the growth rate of structure at that same redshift (d sigma8/d ln a = 0.43 +/- 0.069). Our analysis provides the best current direct determination of both DA and H in galaxy clustering data using this technique. If we further assume a LCDM expansion history, our growth constraint tightens to d sigma8/d ln a = 0.415 +/- 0.034. In combination with the cosmic microwave background, our measurements of DA, H, and growth all separately require dark energy at z > 0.57, and when combined imply \Omega_{\Lambda} = 0.74 +/- 0.016, independent of the Universe's evolution at z<0.57. In our companion paper (Samushia et al. prep), we explore further cosmological implications of these observations.Comment: 19 pages, 11 figures, submitted to MNRAS, comments welcom

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr