An evaluation of the social validity of the Aberrant Behavior Checklist - Community

Purpose – This paper aims to evaluate the social validity of the Aberrant Behavior Checklist - Communit y (ABC-C). Design/methodology/approach – Thirty-six participants completed a questionnaire in which they identified and commented on items of the ABC-C they saw as problematic. Thematic analysis was conducted on the comments made. Findings – All participants identified at least one item of the ABC-C as problematic with six items being so identified by over half the participants. A number of themes were identified in participant comments including ambiguity, judgemental language, child-focussed language, lack of attention to behavioural function and repetition. Research limitations/implications – More research is required using empirically based methodologies on measures used to assess people with learning disabilities. This should involve ascertaining the social validity of such measures by soliciting the views of both those being assessed and those assessing. Originality/value – This study is the first of its kind to evaluate the social validity of one of the most widely used measures of challenging behaviour for people with learning disabilities

Circumpolar Diversity and Geographic Differentiation of mtDNA in the Critically Endangered Antarctic Blue Whale (Balaenoptera musculus intermedia)

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work.\ud This is the publisher’s final pdf. The published article is copyrighted by the Public Library of Science and can be found at: http://www.plosone.org/home.action.The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131 degrees longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968 +/- 0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F-ST = 0.032, p<0.005) and microsatellite alleles (F-ST = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

Circumpolar Diversity and Geographic Differentiation of mtDNA in the Critically Endangered Antarctic Blue Whale (Balaenoptera musculus intermedia)

The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131 degrees longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968 +/- 0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F-ST = 0.032, p<0.005) and microsatellite alleles (F-ST = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales

Investigation of Testosterone, Androstenone, and Estradiol Metabolism in HepG2 Cells and Primary Culture Pig Hepatocytes and Their Effects on 17βHSD7 Gene Expression

Steroid metabolism is important in various species. The accumulation of androgen metabolite, androstenone, in pig adipose tissue is negatively associated with pork flavor, odour and makes the meat unfit for human consumption. The 17β-hydroxysteroid dehydrogenase type 7 (17βHSD7) expressed abundantly in porcine liver, and it was previously suggested to be associated with androstenone levels. Understanding the enzymes and metabolic pathways responsible for androstenone as well as other steroids metabolism is important for improving the meat quality. At the same time, metabolism of steroids is known to be species- and tissue-specific. Therefore it is important to investigate between-species variations in the hepatic steroid metabolism and to elucidate the role of 17βHSD7 in this process. Here we used an effective methodological approach, liquid chromatography coupled with mass spectrometry, to investigate species-specific metabolism of androstenone, testosterone and beta-estradiol in HepG2 cell line, and pig cultured hepatocytes. Species- and concentration-depended effect of steroids on 17βHSD7 gene expression was also investigated. It was demonstrated that the investigated steroids can regulate the 17βHSD7 gene expression in HepG2 and primary cultured porcine hepatocytes in a concentration-dependent and species-dependent pattern. Investigation of steroid metabolites demonstrated that androstenone formed a 3′-hydroxy compound 3β-hydroxy-5α-androst-16-ene. Testosterone was metabolized to 4-androstene-3,17-dione. Estrone was found as the metabolite for β-estradiol. Inhibition study with 17βHSD inhibitor apigenin showed that apigenin didn't affect androstenone metabolism. Apigenin at high concentration (50 μM) tends to inhibit testosterone metabolism but this inhibition effect was negligible. Beta-estradiol metabolism was notably inhibited with apigenin at high concentration. The study also established that the level of testosterone and β-estradiol metabolites was markedly increased after co-incubation with high concentration of apigenin. This study established that 17βHSD7 is not the key enzyme responsible for androstenone and testosterone metabolism in porcine liver cells. © 2012 Chen et al

SISALv2: A comprehensive speleothem isotope database with multiple age-depth models

Characterizing the temporal uncertainty in palaeoclimate records is crucial for analysing past climate change, correlating climate events between records, assessing climate periodicities, identifying potential triggers and evaluating climate model simulations. The first global compilation of speleothem isotope records by the SISAL (Speleothem Isotope Synthesis and Analysis) working group showed that age model uncertainties are not systematically reported in the published literature, and these are only available for a limited number of records (ca. 15 %, n = 107=691). To improve the usefulness of the SISAL database, we have (i) improved the database's spatiooral coverage and (ii) created new chronologies using seven different approaches for age depth modelling. We have applied these alternative chronologies to the records from the first version of the SISAL database (SISALv1) and to new records compiled since the release of SISALv1. This paper documents the necessary changes in the structure of the SISAL database to accommodate the inclusion of the new age models and their uncertainties as well as the expansion of the database to include new records and the qualitycontrol measures applied. This paper also documents the age depth model approaches used to calculate the new chronologies. The updated version of the SISAL database (SISALv2) contains isotopic data from 691 speleothem records from 294 cave sites and new age depth models, including age depth temporal uncertainties for 512 speleothems. SISALv2 is available at https://doi.org/10.17864/1947.256 (Comas-Bru et al., 2020a). © 2020 Author(s)

Genome sequences of four cluster P mycobacteriophages

Four bacteriophages infecting Mycobacterium smegmatis mc2155 (three belonging to subcluster P1 and one belonging to subcluster P2) were isolated from soil and sequenced. All four phages are similar in the left arm of their genomes, but the P2 phage differs in the right arm. All four genomes contain features of temperate phages

A Computational Investigation on the Connection between Dynamics Properties of Ribosomal Proteins and Ribosome Assembly

Assembly of the ribosome from its protein and RNA constituents has been studied extensively over the past 50 years, and experimental evidence suggests that prokaryotic ribosomal proteins undergo conformational changes during assembly. However, to date, no studies have attempted to elucidate these conformational changes. The present work utilizes computational methods to analyze protein dynamics and to investigate the linkage between dynamics and binding of these proteins during the assembly of the ribosome. Ribosomal proteins are known to be positively charged and we find the percentage of positive residues in r-proteins to be about twice that of the average protein: Lys+Arg is 18.7% for E. coli and 21.2% for T. thermophilus. Also, positive residues constitute a large proportion of RNA contacting residues: 39% for E. coli and 46% for T. thermophilus. This affirms the known importance of charge-charge interactions in the assembly of the ribosome. We studied the dynamics of three primary proteins from E. coli and T. thermophilus 30S subunits that bind early in the assembly (S15, S17, and S20) with atomic molecular dynamic simulations, followed by a study of all r-proteins using elastic network models. Molecular dynamics simulations show that solvent-exposed proteins (S15 and S17) tend to adopt more stable solution conformations than an RNA-embedded protein (S20). We also find protein residues that contact the 16S rRNA are generally more mobile in comparison with the other residues. This is because there is a larger proportion of contacting residues located in flexible loop regions. By the use of elastic network models, which are computationally more efficient, we show that this trend holds for most of the 30S r-proteins

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22–1·10]; d=0·46 [0·16–0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association