Miracle-dz/UniFAR-FTUs huggingface dataset:
High CO2 downregulates skeletal muscle protein anabolism via AMPKα2-mediated depressed ribosomal biogenesis.

High CO2 retention, or hypercapnia, is associated with worse outcomes in patients with chronic pulmonary diseases. Skeletal muscle wasting is also an independent predictor of poor outcomes in patients with acute and chronic pulmonary diseases. While previous evidence indicates that high CO2 accelerates skeletal muscle catabolism via AMPK-FoxO3a-MuRF1, little is known about the role of high CO2 in regulating skeletal muscle anabolism. In the present study we investigated the potential role of high CO2 in attenuating skeletal muscle protein synthesis. We found that locomotor muscles from patients with chronic CO2 retention demonstrate depressed ribosomal gene expression in comparison with non-CO2 retaining individuals, and analysis of muscle proteome from normo- and hypercapnic mice indicates reduction of important components of ribosomal structure and function. Indeed, mice chronically kept under a high CO2 environment show evidence of skeletal muscle downregulation of ribosomal biogenesis; and decreased protein synthesis as measured by the incorporation of puromycin to skeletal muscle. Hypercapnia did not regulate mTOR pathway and rapamycin-induced deactivation of mTOR did not cause decrease in ribosomal gene expression. Loss-of-function studies in cultured myotubes showed that AMPKα2 regulates CO2-mediated reductions in ribosomal gene expression and protein synthesis. While previous evidence has implicated transcription factor TIF-1A and the lysin demethylase KDM2A in AMPK-driven regulation of ribosomal gene expression, we found that these mediators are not required in the high CO2-induced depressed protein anabolism. Our research supports future studies targeting ribosomal biogenesis and protein synthesis to alleviate the effects of high CO2 on skeletal muscle turnover.
Sequence analysis COMPASS: the COMPletely Arbitrary Sequence Simulator

Summary: Simulated sequence alignments are frequently used to test bioinformatics tools, but current sequence simulators are limited to deﬁned state spaces. Here, we present the COMPletely Arbitrary Sequence Simulator (COMPASS), which is able to simulate the evolution of absolutely any discrete state space along a tree, for any form of time-reversible model. Availability and implementation: COMPASS is implemented in Python 2.7, and is freely available for all platforms with the Supplementary Information, as well as at http://labs.carleton. ca/eme/soft ware-and-data.
using chirp and click stimuli

Transient-evoked otoacoustic emission (TEOAE) responses (0.7–8 kHz) were measured in normal-hearing adult ears using click stimuli and chirps whose local frequency increased or decreased linearly with time over the stimulus duration. Chirp stimuli were created by allpass ﬁltering a click with relatively constant incident pressure level over frequency. Chirp TEOAEs were analyzed as a nonlinear residual signal by inverse allpass ﬁltering each chirp response into an equivalent click response. Multi-window spectral and temporal averaging reduced noise levels compared to a single-window average. Mean TEOAE levels using click and chirp stimuli were similar with respect to their standard errors in adult ears. TEOAE group delay, group spread, instantaneous frequency, and instantaneous bandwidth were similar overall for chirp and click conditions, except for small differences showing nonlinear interactions differing across stimulus conditions. These results support the theory of a similar generation mechanism on the basilar membrane for both click and chirp conditions based on coherent reﬂection within the tonotopic region. TEOAE temporal ﬁne structure was invariant across changes in stimulus level, which is analogous to the intensity invariance of click-evoked basilar-membrane displacement data. V C 2016 Acoustical Society of America .
High levels of antibody to Panton-Valentine leukocidin are not associated with resistance to Staphylococcus aureus skin and soft tissue infection

Background— Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) expressing Panton-Valentine Leukocidin (PVL) cause severe skin and soft tissue infections (SSTI), necrotizing pneumonia and other invasive infections. PVL toxin has been implicated as a virulence factor and antibody to a component of this toxin is under investigation as a vaccine candidate. The role of PVL in pathogenesis remains controversial and it is unknown if human serum antibody to PVL modulates infection. Methods— We determined antibody levels to PVL in sera from children aged 0-18 years presenting with PCR-confirmed PVL-positive MRSA SSTI with or without prior MRSA infection or SSTI, PVL-positive MRSA invasive infections, PVL-negative MRSA infections and uninfected controls. We also measured antibody-mediated neutralization of PVL-induced lysis of human polymorphonuclear cells. Results— Antibody to PVL was present in healthy children reaching adult levels by 4-6 years with a nadir at 4-6 months likely due to loss of maternal antibody. Children with a primary PVL-positive MRSA infection had moderate levels of antibody to PVL that increased following infection. Children with prior MRSA or SSTI infections had high levels of antibody to PVL at the onset of infection. There was no increase in antibody to PVL in this populations’ sera after the onset of infection. Sera from children with PVL-positive MRSA SSTIs, particularly those with prior MRSA or SSTI, and convalescent sera from children with invasive PVL-positive MRSA infection, potently inhibited PVL-induced lysis of PMNs. Conclusions— Neutralizing antibody to PVL does not protect children against primary or recurrent CA-MRSA Analyses were Correlations were
Factors Impacting the Implementation of Evidence-Based Strategies to Create Safe and Supportive School Environments for Sexual and Gender Minority Students

Purpose: The Centers for Disease Control and Prevention recommends six evidence-based strategies to improve safety and support for sexual and gender minority (SGM) youth in U.S. schools. However, only a small minority of schools implement all strategies. This study draws on implementation science to assess contextual challenges to strategy implementation. Methods: Semi-structured interviews were conducted with at least two stakeholders at each of 42 high schools in New Mexico. Interviews consisted of open-ended questions centered on attitudes toward, access to, and availability of school and community supports for SGM youth, school policies and practices, and organizational factors believed to impact implementation. Transcripts were imported into NVivo 11 for iterative coding and qualitative analysis. Results: We identified eleven overarching sets of factors related to the preparedness of schools to implement the evidence-based strategies: 1) political climate; 2) community context; 3) community resources; 4) policies and practices; 5) staff knowledge and exposure to SGM issues; 6) training deficits; 7) prevalence of neutrality discourses suggesting SGM students should not be singled out for “special treatment” or intervention; 8) student attitudes and support; 9) de facto safe spaces; 10) health education curricula; and 11) pragmatic considerations, such as time, staff turnover and workloads. Key factors believed to hinder implementation included lack of resources, staffing concerns, and knowledge deficits. Conclusions: These results can be used to inform the development of implementation strategies to modify school health systems from within to best support evidence-based practices for SGM youth and other stigmatized populations.
The impact of biofilm formation and multidrug resistance on environmental survival of clinical and environmental isolates of Acinetobacter baumannii .

Background. — Acinetobacter baumannii is a gram-negative, opportunistic pathogen. Its ability to form biofilm and increasing resistance to antibiotics present challenges for infection control. A better understanding of the impact of biofilm formation and antibiotic resistance on environmental persistence of A. baumannii in hospital settings is needed for more effective infection control. Methods. — A. baumannii strains isolated from patients and the hospital environment were identified via MALDI-TOF mass spectrometry, rep-PCR genotyped, and antibiotic resistance was determined using Vitek®2. Biofilm mass was quantified via microtiter plate method and desiccation tolerance determined up to 56 days. Results. — High biofilm forming, clinical, MDR positive strains were 50% less likely to die of desiccation than low biofilm, non-MDR strains. In contrast, environmental, MDR positive, low biofilm forming strains had a 2.7 times increase in risk of cell death due to desiccation compared to their MDR negative counterparts. MDR negative, high biofilm forming environmental strains had a 60% decrease in risk compared to their low biofilm forming counterparts. Conclusions. — The MDR positive phenotype was deleterious for environmental strains and the high biofilm phenotype was critical for survival. This study provides evidence of the trade-off between antibiotic resistance and desiccation tolerance, driven by condition-dependent adaptation, and establishes rationale for research into the genetic basis of the variation in fitness cost between clinical and environmental isolates. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Potential conflicts of interest . All authors report no conflicts of interest. been implicated for variations in phenotypic expressions The trade-offs in fitness imposed by the ability to form biofilms, tolerate desiccation and multidrug resistance are potentially different for A. baumannii strains that live primarily in the environment compared to clinical strains adapted to living in the human host. To test whether these trade-offs occur, we compared the biofilm formation, antibiotic susceptibility profiles and desiccation tolerance in a collection of A. baumannii strains isolated from patients and the hospital environment. Our results suggest that a trade-off between antibiotic resistance and desiccation tolerance occurs, and biofilm formation contributes significantly to the survival of these isolates.
I solation of antileishmanial, antimalarial and antimicrobial metabolites from J atropha multifida

A Objective: T o investigate the antileishmanial, antimicrobial and antimalarial activities of the pure metabolites from Jatropha multifida used in A frican ethnomedicine. Methods: T he methanolic stem bark extract of Jatropha multifida used in N igerian folk medicine as remedy against bacterial infections was subjected to column chromatography and HPLC analyses to obtain three known metabolites, microcyclic lathyrane diterpenoids ( 1 - 3 ) . S tructures were confirmed by comparison of 1 D and 2 D spectral data with literature. Results: T he three compounds exhibited inhibition of antileishmanial, antimalarial and antimicrobial actions against the tested organisms with compouds 2 and 3 active against Cryptococcus neoformans at IC 50 of 8 . 2 and 8 . 7 µ g/m L , respectively. Conclusions: T he research lends support to the ethnomedicinal use of the plant in combating microbial infections, leishmaniasis and malarial infections.
Conservative implicit schemes for the full potential equation applied to transonic flows

Implicit approximate factorization techniques (AF) were investigated for the solution of matrix equations resulting from finite difference approximations to the full potential equation in conservation form. For transonic flows, an artificial viscosity, required to maintain stability in supersonic regions, was introduced by an upwind bias of the density. Two implicit AF procedures are presented and their convergence performance is compared with that of the standard transonic solution procedure, successive line overrelaxation (SLOR). Subcritical and supercritical test cases are considered. The results indicate that the AF schemes are substantially faster than SLOR.
Degree of cognitive impairment does not signify early versus late MCI: Confirmation based on Alzheimer’s disease polygenic risk

Degree of memory impairment is often used to infer early versus late amnestic mild cognitive impairment (aMCI). Previously, 318 Alzheimer’s Disease Neuroimaging Initiative participants with aMCI – determined by a single memory test – were divided based on Rey Auditory Verbal Learning Task (AVLT) delayed recall: AVLT-impaired (n=225) and AVLT-normal (n=93). Equally consistent with differential progression or differential diagnosis, the AVLT-impaired group had more abnormal Alzheimer’s disease (AD) biomarkers, more neurodegeneration over time, and were more likely to develop AD. In the present study, higher AD polygenic risk scores were associated with increased odds of being AVLT-impaired (OR=1.8, P<0.001). Thus, impairment severity does not necessarily reflect early versus late aMCI because disease progression cannot alter polygenic risk. What is presumed to be earlier MCI is likely a heterogeneous category that includes excess false-positive diagnoses. The additional cognitive test improved diagnostic precision by reducing those false positives. Impairment severity may reflect differences in underlying disease risk but, based on cross-sectional data alone, it cannot be used to infer early versus late MCI status.
Genomic Characterization of the Filamentous Integrative Bacteriophages (cid:2) RSS1 and (cid:2) RSM1, Which Infect Ralstonia solanacearum (cid:1)

The genomic DNA sequences were determined for two ﬁlamentous integrative bacteriophages, (cid:1) RSS1 and (cid:1) RSM1, of the phytopathogen Ralstonia solanacearum . The 6,662-base sequence of (cid:1) RSS1 contained 11 open reading frames (ORFs). In the databases, this sequence showed high homology (95% identity) to the circular double-stranded DNA plasmid pJTPS1 (6,633 bp) isolated from a spontaneously occurring avirulent mutant of R . solanacearum . Two major differences between the two sequences were observed within (cid:1) RSS1 ORF7, corresponding to pIII, a minor coat protein required for host adsorption, and at the (cid:1) RSS1 intergenic (IG) region. The 9,004-base sequence of (cid:1) RSM1 showed 12 ORFs located on the same strand (plus strand) and 2 ORFs on the opposite strand. Compared with Ff-type phages, two insertions are obvious in the (cid:1) RSM1 replication module. Genomic DNA fragments containing the (cid:1) RSM integration junctions were cloned and sequenced from (cid:1) RSM lysogenic strain R . solanacearum MAFF211270. The att core sequence was identiﬁed as 5 (cid:1) -TGGCGGAGAGGGT-3 (cid:1) , corresponding to the 3 (cid:1) end of the serine tRNA (UCG) gene. Interestingly, ORF14, located next to the attP site on the (cid:1) RSM1 genome, showed high amino acid sequence homology with bacterial DNA recombinases and resolvases, different from XerCD recombinases. attP of (cid:1) RSS1 is within a sequence element of the IG region.
Nucleic Acids Research

Many immunoclobulin (Ig)-producinq cells retain the DNA that separates Ig variable (V) and constant (C) region genes in the germline. This "remnant" DNA must be moved during the recombination process that joins V and C genes via a joininq (J) segment. We have analyzed remnant DNAs in several Ig-producing cell lines. The nucleotide sequences of kappa (K) light chain remnant DNAs indicate close relationships to V-J joininq. We find fused VK and JK recognition sequences in five remnant DNAs, suggesting reciprocal relationsnips to the fused Vai and JK segments produced by V-J joininq.However, of sixteen plasmacytoma remnant DNAs analyzed, all involve only recombination with JK1. Thus, in most cell lines, remnant DNAs are not directly reciprocal to recombined K-genes. On the other hand, our-analyses of some myelomas do indicate indirect relationships between remnant DNAs and K-genes. Our results sihj~eTfhat multiple steps of DNA recombination occur during Ig-cene rearrangement. Because remnant DNA joining sites do not exhibit the flexibility that has been observed in Ig-gene V-J joining, our findings also suggest that the joining mechanism may involve endonuclease, exonuclease and ligase activities. INTRODUCTION Antibody genes require recombination of variable (V) and constant (C) region gene segments to produce a functional transcription unit. This recombination involves the joining of one of many V qenes to a C gene via one of several J (for joininq) segments (for a review see ref. 1). Whereas a number of possible models for the recombinational mechanism involved in the juxtaposition and joining of V and J segments can be formulated, early evidence favored a simple "excision-deletion" model, in which the DNA between V and J segments was simply excised and lost from the genome (2,3). More recently, in conflict with this excision-deletion model, several reports have indicated that the DNA initially separating V and J genes in the germline is not always absent from the genomes of antibody producing cells (4-8). Studies have shown that this "remnant" DNA, unexpectedly remaining in the genome when a simple excision-deletion model would predict its absence, has a structural © I R L Press Limited, Oxford, England. Nucleic Acids Research
Estimating regression functions and their derivatives by the kernel method

A kernel estimate is introduced for obtaining a nonparametric estimate of a regression function, as well as of its derivatives. In many fields of engineering and biomedicine, the estimation of velocity and acceleration is of great importance in addition to obtaining a smoothed curve from the measurements themselves. Some asymptotic properties, as, for example, weak and strong consistency and asymptotic normality are derived, as well as asymptotic expressions for bias and variance. A solution for treating the extremities of the data is investigated in order to obtain the asymptotic integrated mean squared error, and also in order to facilitate data analysis over the range of abscissae investigated. Some finite sample results, and two examples of application in biomedicine, render some insight into the potential usefulness of this approach.
Prenatal Exposures to Pollutants Effects of prenatal exposure to ambient air pollutant PM 10 on ultrasound-measured fetal growth

Background: Limited epidemiological studies have investigated the relationship between prenatal exposure to ambient particulate matter and risk of abnormal fetal growth, and have reached inconclusive results. No study has been conducted in areas with very high air pollution levels. We investigated the hypothesis that exposure to high levels of particulate matter with aerodynamic diameter no larger than 10 m m (PM 10 ) during pregnancy increases the risk of abnormal fetal growth. Methods: A birth cohort study was performed in Lanzhou, China, 2010–12, including 8877 pregnant women with 18 583 ultrasound measurements of four fetal growth parameters during pregnancy, including biparietal diameter (BPD), femur length (FL), head circumference (HC) and abdominal circumference (AC). Mixed-effects modelling was used to examine the associations between PM 10 exposure and risk of abnormal fetal growth. Results: When average PM 10 exposure from conception until the ultrasound examination exceeded 150 m g/m 3 , there were signiﬁcant increases in standardized FL ( b ¼ 0.095, P ¼ 0.0012) and HC ( b ¼ 0.090, P ¼ 0.0078) measures. When average PM 10 exposure was treated as continuous variable, we found a signiﬁcant decrease in standardized BPD ( b ¼ (cid:2) 0.018, P ¼ 0.0016) as per 10 m g/m 3 increase in PM 10 . After examining the associations by various exposure windows, positive associations between higher levels of PM 10 and fetal overgrowth were consistently seen for HC measures. Conclusions: Our study suggested that prenatal exposure to high levels of ambient PM 10 increased the risk of abnormal fetal growth. The ﬁndings from our study have important public health implications and also call for future studies to explore the underlying mechanisms and post-natal consequences of these ﬁndings.
Electrically driven single photon source based on a site-controlled quantum dot with self-aligned cu

Electrical operation of single photon emitting devices employing site-controlled quantum dot (QD) growth is demonstrated. An oxide aperture acting as a buried stressor structure is forcing site-controlled QD growth, leading to both QD self-alignment with respect to the current path in vertical injection pin-diodes and narrow, jitter-free emission lines. Emissions from a neutral exciton, a neutral bi-exciton, and a charged exciton are unambiguously identified. Polarization-dependent measurements yield an exciton fine-structure splitting of (84 ± 2) μeV at photon energies of 1.28–1.29 eV. Single-photon emission is proven by Hanbury Brown and Twiss experiments yielding an anti-bunching value of g(2)(0) = 0.05 under direct current injection.
Altered corticolimbic control of the nucleus accumbens by chronic Δ 9 -THC

Background: Decriminalization, legalization and expansion of medical cannabis has led to an increase in its use and availability of high-potency strains. Cannabis potency is determined by the concentration of Δ 9 -tetrahydrocannabinol (Δ 9 -THC), a psychoactive constituent that activates CB1 and CB2 cannabinoid receptors (CB1R, CB2R), and use of high-potency cannabis is associated with cannabis use disorder (CUD) and increased susceptibility to psychiatric illness. The nucleus accumbens (NAc) is part of a brain reward circuit affected by Δ 9 -THC through modulation of glutamate afferents arising from corticolimbic brain areas implicated in drug addiction and psychiatric disorders. Moreover, brain imaging studies show alterations in corticolimbic and NAc properties in human cannabis users. Methods: Using in vitro electrophysiology and optogenetics, we examine how Δ 9 -THC alters corticolimbic input to the NAc in rats. Results: We find that chronic Δ 9 -THC weakens prefrontal cortex glutamate input to the NAc shell (NAcs) and strengthens input from basolateral amygdala and ventral hippocampus. Further, whereas chronic Δ 9 -THC had no effect on net strength of glutamatergic nput to NAcs arising from midbrain DA neurons, it alters fundamental properties of these synapses. Conclusions: Chronic Δ 9 -THC shifts control of the NAcs from cortical to limbic input likely contributing to cognitive and psychiatric dysfunction associated with cannabis use. indicate that 9 -THC exposure leads to altered NAc excitatory synaptic transmission and synaptic plasticity but the of these afferents not identified, and changes in distinct NAc pathways remain Here, we examined patterns of altered function in several glutamatergic inputs to the NAc after chronic -THC in rats. We find that chronic 9 -THC shifts the strength of glutamatergic activation of NAc from to limbic sites, and we hypothesize that to the was significant
A method to bioassay onion thrips, 'Thrips tabaci' Lindeman (Thysanoptera: Thripidae) for pesticide response

Onion thrips, 'Thrips tabaci' Lindeman, is a major pest of Australian field onion with chemical control limited to organophosphate insecticides. Following grower complaints of field failure we aimed to establish a bioassay capability for onion thrips and develop a method that could accurately measure small differences in response to insecticides with a view to resistance detection. LC99.9, extrapolation indicated a discriminating concentration of 1.25 g ai L-1 for diazinon, 0.40 g ai L-1 for dimethoatc. 0.40 g ai L-1 for methidathion, 0.11 g ai L-1 for omethoatc and 3.50 g ai L-1 for malathion.