Miracle-dz/UniFAR-FTUs huggingface dataset:
How “simple” methodological decisions affect interpretation of population structure based on reduced representation library DNA sequencing: A case study using the lake whitefish

Reduced representation (RRL) sequencing approaches (e.g., RADSeq, genotyping by sequencing) require decisions about how much to invest in genome coverage and sequencing depth, as well as choices of values for adjustable bioinformatics parameters. To empirically explore the importance of these “simple” methodological decisions, we generated two independent sequencing libraries for the same 142 individual lake whitefish (Coregonus clupeaformis) using a nextRAD RRL approach: (1) a larger number of loci at low sequencing depth based on a 9mer (library A); and (2) fewer loci at higher sequencing depth based on a 10mer (library B). The fish were selected from populations with different levels of expected genetic subdivision. Each library was analyzed using the STACKS pipeline followed by three types of population structure assessment (FST, DAPC and ADMIXTURE) with iterative increases in the stringency of sequencing depth and missing data requirements, as well as more specific a priori population maps. Library B was always able to resolve strong population differentiation in all three types of assessment regardless of the selected parameters, largely due to retention of more loci in analyses. In contrast, library A produced more variable results; increasing the minimum sequencing depth threshold (-m) resulted in a reduced number of retained loci, and therefore lost resolution at high -m values for FST and ADMIXTURE, but not DAPC. When detecting fine population differentiation, the population map influenced the number of loci and missing data, which generated artefacts in all downstream analyses tested. Similarly, when examining fine scale population subdivision, library B was robust to changing parameters but library A lost resolution depending on the parameter set. We used library B to examine actual subdivision in our study populations. All three types of analysis found complete subdivision among populations in Lake Huron, ON and Dore Lake, SK, Canada using 10,640 SNP loci. Weak population subdivision was detected in Lake Huron with fish from sites in the north-west, Search Bay, North Point and Hammond Bay, showing slight differentiation. Overall, we show that apparently simple decisions about library construction and bioinformatics parameters can have important impacts on the interpretation of population subdivision. Although potentially more costly on a per-locus basis, early investment in striking a balance between the number of loci and sequencing effort is well worth the reduced genomic coverage for population genetics studies. More conservative stringency settings on STACKS parameters lead to a final dataset that was more consistent and robust when examining both weak and strong population differentiation. Overall, we recommend that researchers approach “simple” methodological decisions with caution, especially when working on non-model species for the first time.
Serotonin transporter dependent modulation of food-seeking behavior

The olfactory pathway integrates the odor information required to generate correct behavioral responses. To address how changes of serotonin signaling in two contralaterally projecting, serotonin-immunoreactive deutocerebral neurons impacts key odorant attraction in Drosophila melanogaster, we selectively alter serotonin signaling using the serotonin transporter with mutated serotonin binding sites in these neurons and analyzed the consequence on odorant-guided food seeking. The expression of the mutated serotonin transporter selectively changed the odorant attraction in an odorant-specific manner. The shift in attraction was not influenced by more up-stream serotonergic mechanisms mediating behavioral inhibition. The expression of the mutated serotonin transporter in CSD neurons did not influence other behaviors associated with food seeking such as olfactory learning and memory or food consumption. We provide evidence that the change in the attraction by serotonin transporter function might be achieved by increased serotonin signaling and by different serotonin receptors. The 5-HT1B receptor positively regulated the attraction to low and negatively regulated the attraction to high concentrations of acetic acid. In contrast, 5-HT1A and 5-HT2A receptors negatively regulated the attraction in projection neurons to high acetic acid concentrations. These results provide insights into how serotonin signaling in two serotonergic neurons selectively regulates the behavioral response to key odorants during food seeking.
A multiplexed in vitro assay system for evaluating human skeletal muscle functionality in response to drug treatment

In vitro systems that mimic organ functionality have become increasingly important tools in drug development studies. Systems that measure the functional properties of skeletal muscle are beneficial to compound screening studies and also for integration into multiorgan devices. To date, no studies have investigated human skeletal muscle responses to drug treatments at the single myotube level in vitro. This report details a microscale cantilever chip‐based assay system for culturing individual human myotubes. The cantilevers, along with a laser and photo‐detector system, enable measurement of myotube contractions in response to broad‐field electrical stimulation. This system was used to obtain baseline functional parameters for untreated human myotubes, including peak contractile force and time‐to‐fatigue data. The cultured myotubes were then treated with known myotoxic compounds and the resulting functional changes were compared to baseline measurements as well as known physiological responses in vivo. The collected data demonstrate the system's capacity for screening direct effects of compound action on individual human skeletal myotubes in a reliable, reproducible, and noninvasive manner. Furthermore, it has the potential to be utilized for high‐content screening, disease modeling, and exercise studies of human skeletal muscle performance utilizing iPSCs derived from specific patient populations such as the muscular dystrophies.
Exploring factors influencing whether residents participate in square dancing using social cognitive theory

Abstract Physical inactivity is a worldwide public health problem, and it is a risk factor for several chronic diseases. Square dancing nightly may be an efficient way to promote physical activity among Chinese residents. This study aims to explore factors that affect resident participation in square dancing on the basis of social cognitive theory constructs (outcome expectations, outcome expectancies, self-efficacy, self-control, and environment) that may provide a scientific basis for designing interventions to promote physical activity in the future. Forty squares near neighborhood communities in Chongqing were randomly selected. A sample of 1732 residents who came to these squares at 18:00–21:00 were interviewed using a social cognitive theory questionnaire jointly developed by researchers from Chongqing Medical University and Jackson State University. Among 1732 respondents, 279 (16.1%) were male and 1457 (83.9%) were female. A total of 939 (54.2%) of the respondents were square dancers. The mean age of the dancers was 58.6 (SD = 9.1) years. Of the dancers, 825 (87.9%) danced at least 150 minutes every week, and 792 (84.2%) indicated that they had danced for more than 1 year. All the constructs of social cognitive theory were significantly different between residents whether they danced or not (P < .001 for all). Women (OR = 1.54, 95% CI: 1.03–2.31) were more likely to dance. Nonretired residents (OR = 0.53, 95% CI: 0.39–0.74) were less likely to dance. Residents with income of more than CNY 4000 per month were less likely to dance (OR = 0.44, 95% CI: 0.23–0.86). Residents with high self-efficacy (OR = 2.01, 95% CI: 1.81–2.22), and high self-control (OR = 1.26, 95% CI: 1.18–1.34) were more likely to dance. This study provides salient implications for developing interventions to promote square dancing by using social cognitive theory. Gender, retirement, income, and self-efficacy would be the factors influencing whether residents participate in square dancing.
Role of the Built and Online Social Environments on Expression of Dining on Instagram

Online social communities are becoming windows for learning more about the health of populations, through information about our health-related behaviors and outcomes from daily life. At the same time, just as public health data and theory has shown that aspects of the built environment can affect our health-related behaviors and outcomes, it is also possible that online social environments (e.g., posts and other attributes of our online social networks) can also shape facets of our life. Given the important role of the online environment in public health research and implications, factors which contribute to the generation of such data must be well understood. Here we study the role of the built and online social environments in the expression of dining on Instagram in Abu Dhabi; a ubiquitous social media platform, city with a vibrant dining culture, and a topic (food posts) which has been studied in relation to public health outcomes. Our study uses available data on user Instagram profiles and their Instagram networks, as well as the local food environment measured through the dining types (e.g., casual dining restaurants, food court restaurants, lounges etc.) by neighborhood. We find evidence that factors of the online social environment (profiles that post about dining versus profiles that do not post about dining) have different influences on the relationship between a user’s built environment and the social dining expression, with effects also varying by dining types in the environment and time of day. We examine the mechanism of the relationships via moderation and mediation analyses. Overall, this study provides evidence that the interplay of online and built environments depend on attributes of said environments and can also vary by time of day. We discuss implications of this synergy for precisely-targeting public health interventions, as well as on using online data for public health research.
DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-1

Key Points DHEA limits leukocyte recruitment. DHEA restores endothelial DEL-1 expression in inflammation. This effect involves regulation of C/EBPβ in a TRKA/AKT-dependent manner. Leukocytes are rapidly recruited to sites of inflammation via interactions with the vascular endothelium. The steroid hormone dehydroepiandrosterone (DHEA) exerts anti-inflammatory properties; however, the underlying mechanisms are poorly understood. In this study, we show that an anti-inflammatory mechanism of DHEA involves the regulation of developmental endothelial locus 1 (DEL-1) expression. DEL-1 is a secreted homeostatic factor that inhibits β2-integrin–dependent leukocyte adhesion, and the subsequent leukocyte recruitment and its expression is downregulated upon inflammation. Similarly, DHEA inhibited leukocyte adhesion to the endothelium in venules of the inflamed mouse cremaster muscle. Importantly, in a model of lung inflammation, DHEA limited neutrophil recruitment in a DEL-1–dependent manner. Mechanistically, DHEA counteracted the inhibitory effect of inflammation on DEL-1 expression. Indeed, whereas TNF reduced DEL-1 expression and secretion in endothelial cells by diminishing C/EBPβ binding to the DEL-1 gene promoter, DHEA counteracted the inhibitory effect of TNF via activation of tropomyosin receptor kinase A (TRKA) and downstream PI3K/AKT signaling that restored C/EBPβ binding to the DEL-1 promoter. In conclusion, DHEA restrains neutrophil recruitment by reversing inflammation-induced downregulation of DEL-1 expression. Therefore, the anti-inflammatory DHEA/DEL-1 axis could be harnessed therapeutically in the context of inflammatory diseases.
Stratified meta-analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was associated with coronary artery disease in Asians, but not in Caucasians

Abstract Background: Previous studies demonstrated that ADRB3, beta-3 adrenergic receptor, participated in lipolysis and thermogenesis in adipose tissue. Consequently, this gene has attracted an increasing number of genetic studies examining its association with coronary artery disease (CAD) in different ethnicities in recent years, but no conclusion has been reached so far. The aim of this study was to explore whether the well-studied locus ADRB3 Trp64Arg in this gene confers a race-specific effect to CAD by conducting a stratified meta-analysis involving 15 independent studies and 11,802 subjects. Methods: Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. Publication bias was quantified and examined with Begg's funnel plot test and Egger's linear regression method. The overall meta-analysis or stratified meta-analysis by ethnicity was performed by using STATA 12.0 software. Results: A total of 15 eligible studies involving 5779 CAD cases and 6023 health controls were included in this meta-analysis. The pooled results indicated that ADRB3 Trp64Arg polymorphism was significantly associated with an increased risk of CAD. Further stratified analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was significantly associated with CAD in Asians (allelic: OR = 1.48, 95%CI 1.13–1.94, P = .005; homozygous: OR = 2.66, 95%CI 1.87–3.77, P < .001; recessive: OR = 2.46, 95%CI 1.74–3.47, P < .001), but not in Caucasians (allelic: OR = 1.09, 95%CI 0.93–1.27, P = .290; homozygous: OR = 1.31, 95%CI 0.61–2.86, P = .490; recessive: OR = 1.31, 95%CI 0.60–2.84, P = 2.494). Conclusions: This meta-analysis suggests that ADRB3 Trp64Arg polymorphism confers a race-specific effect to CAD.
An Electrochemical Immunosensor Based on a Self-Assembled Monolayer Modified Electrode for Label-Free Detection of α-Synuclein

This research demonstrated the development of a simple, cost-effective, and label-free immunosensor for the detection of α-synuclein (α-Syn) based on a cystamine (CYS) self-assembled monolayer (SAM) decorated fluorine-doped tin oxide (FTO) electrode. CYS-SAM was formed onto the FTO electrode by the adsorption of CYS molecules through the head sulfur groups. The free amine (–NH2) groups at the tail of the CYS-SAM enabled the immobilization of anti-α-Syn-antibody, which concurrently allowed the formation of immunocomplex by covalent bonding with α-Syn-antigen. The variation of the concentrations of the attached α-Syn at the immunosensor probe induced the alternation of the current and the charge transfer resistance (Rct) for the redox response of [Fe(CN)6]3−/4−, which displayed a linear dynamic range from 10 to 1000 ng/mL with a low detection limit (S/N = 3) of ca. 3.62 and 1.13 ng/mL in differential pulse voltammetry (DPV) and electrochemical impedance spectra (EIS) measurements, respectively. The immunosensor displayed good reproducibility, anti-interference ability, and good recoveries of α-Syn detection in diluted human serum samples. The proposed immunosensor is a promising platform to detect α-Syn for the early diagnose of Parkinson’s disease, which can be extended for the determination of other biologically important biomarkers.
Development and evaluation of a panel of multiplex one‐tube nested real time PCR assay for simultaneous detection of 14 respiratory viruses in five reactions

Multiplex real‐time quantitative polymerase chain reaction (mRT‐qPCR) assay is commonly used to detect respiratory viruses, however, the sensitivity is limited for most reports. A panel of locked nucleic acid based multiplex closed one‐tube nested real‐time PCR (mOTNRT‐PCR) assay consisting of five separate internally controlled RT‐qPCR assays was developed for detection of 14 respiratory viruses. The sensitivity and reproducibility of mOTNRT‐PCR panel were evaluated using plasmid standards and the specificity was evaluated using clinical samples. The clinical performance of mOTNRT‐PCR panel was further evaluated with 468 samples collected from patients with an acute respiratory infection and compared with individual real‐time PCR (RT‐qPCR) assay. The analytical sensitivities of mOTNRT‐PCR panel ranged from 2 to 20 copies/reaction, and no cross‐reaction with common respiratory viruses was observed. The coefficients of variation of intra‐assay and inter‐assay were between 0.35% and 8.29%. Totally 35 clinical samples detected by mOTNRT‐PCR assay panel were missed by RT‐qPCR and confirmed true positive by sequencing of nested PCR products. The mOTNRT‐PCR assay panel provides a more sensitive and high‐throughput method for the detection of 14 respiratory viruses.
Prediction of Smoking Abstinence in Women Living With Human Immunodeficiency Virus Infection

Background This study examined whether baseline negative emotional states (depression and anxiety) would predict craving for cigarettes and other nicotine withdrawal symptoms in early abstinence and whether those emotional states and withdrawal symptoms would predict failure in quitting smoking at 3 months postquit among U.S. women living with the human immunodeficiency virus (HIV). Method The study is a secondary analysis of data from two smoking cessation studies of women living with HIV. Craving for cigarettes and other withdrawal symptoms were assessed weekly with a total of 229 observations during the first 4 weeks following quit day. Descriptive statistics were used to examine baseline characteristics of the participants. A random growth curve model was used to estimate between-person differences in a within-person trend of changes in the withdrawal symptoms. A binary logistic regression analysis was performed to identify predictors of short-term smoking abstinence. Results Baseline anxiety was a predictor of postquit nicotine withdrawal symptoms but baseline depression was not. Neither baseline anxiety nor depression predicted postquit craving for cigarettes. Participants who received an HIV-tailored smoking cessation intervention showed a greater decline in craving symptom than those who received an attention-controlled intervention. HIV-tailored intervention and less craving predicted smoking abstinence at 3-month follow-up. Discussion Compared to an attention-controlled intervention, an HIV-tailored intervention effectively decreased craving for cigarette smoking after quitting—which effectively increased the rate of short-term smoking abstinence in women living with HIV.
Evaluation of an Improved Model of Middle Cerebral Artery Occlusion in the Rat by Intraluminal Suture

Aim:To evaluate a modified method of intraluminal suture occlusion of the middle cerebral artery (MCA) on the neurobehavioral function and on the volume of brain infarction in rats subjected to a temporary focal cerebral ischemic insult. Methods: Sprague-Damley rats were subjected to 2 h temporary MCA occlusion (MACO) with poly-L-lysine coated suture (0.1%)and conventional suture. Behavioral motor functions were evaluated at 180 min,24,48,and 72 h after reperfusion by eight-point behavioral rating scale and postural reflex. Brains were perfusion-fixed and infarct volume were measured at the time of 72 h after reperfusion. The results were compared between two groups. Results:9 of 20 rats with uncoated suture had infarct,while in the group with poly-L-lysine-coated suture,15 of 20 rates had infarct. Our results demonstrate a liner relationship between motor functional impairment and lesion volume. Infarct volumes were significantly larger in rats with poly-L-lysine-coated suture group than without poly-L-lysine-coated suture group.Infarct volume in the uncoated sutures tended to be smaller and more inconsistent compared with the group in which sutures were coated with poly-L-lysine. Conclusion:Eight-point behavioral rating scale and postural reflex tests of motor performance provide quantitative,objective measures of functional impairment of rats following an ischemic insult. MCAO in which a poly-L-lysine-coated intralumianl suture used was proved to be a reliable and effective modification of this technique.
Ofatumumab for multirelapsing membranous nephropathy complicated by rituximab-induced serum-sickness

Rituximab (375 mg/m2) achieved remission of the first episode and six relapses of nephrotic syndrome (NS) in a young male patient with podocyte phospholipase A2 receptor (PLA2R)-related membranous nephropathy (MN) refractory to steroids and cyclosporine. Between-treatments interval averaged 17.4±4.2 months. The seventh infusion was complicated by delayed serum-sickness, which resolved with steroids. On subsequent relapse, the fully human anti-CD20 monoclonal antibody ofatumumab (300 mg) achieved remission of the NS, without significant side effects. Circulating CD19+ B cells were depleted, proteinuria decreased from 10.9 to 1.3 g/day, and serum albumin, immunoglobulin levels and glomerular filtration rate normalised. Twenty-eight months later, despite transient anti-PLA2R depletion, ofatumumab (100 mg) failed to induce remission of the eighth relapse. Remission was safely achieved 5 months later with repeated ofatumumab infusion (300 mg). This treatment (€723) was less expensive than rituximab (€1801). Ofatumumab could be a safe and cost/effective rescue therapy for patients with MN sensitised against rituximab.
The F1534C voltage‐sensitive sodium channel mutation confers 7‐ to 16‐fold resistance to pyrethroid insecticides in Aedes aegypti

Abstract BACKGROUND Recent outbreaks of dengue and Zika have emphasized the importance to effectively control Aedes aegypti, which vectors the viruses causing these diseases. Pyrethroid insecticides are primarily used to control adult A. aegypti, especially during disease outbreaks. However, pyrethroid resistance in A. aegypti is an increasing problem. Mutations in the voltage‐sensitive sodium channel (Vssc) are a common mechanism of pyrethroid resistance. The F1534C mutation is common and distributed globally in A. aegypti populations, but previous studies disagree about the role of this mutation in conferring resistance to pyrethroid insecticides. RESULTS We isolated a congenic strain (1534C:ROCK) which was closely related to a susceptible strain Rockefeller (ROCK), but was homozygous for the 1534C Vssc allele. We determined resistance levels against eight insecticides that target the VSSC: six pyrethroids, DDT and DCJW (the bioactivated metabolite of indoxacarb). The resistance levels ranged from 7‐ to 16‐fold, and resistance was inherited as an incompletely recessive trait. We also found a novel 367I+1520I+1534C allele, in addition to the 1534C and 1520I+1534C alleles, in mosquitoes from Thailand. The T1520I mutation did not increase pyrethroid resistance beyond what was conferred by the F1534C mutation alone. CONCLUSION The F1534C Vssc mutation is common in A. aegypti populations and confers 7‐ to 16‐fold resistance to pyrethroids, DDT, and DCJW in Aedes aegypti. These resistance levels are considerably less than previously reported for the S989P+V1016G mutations. Our results provide useful information for resistance management, specifically the levels of resistance conferred by the most common Vssc mutation in A. aegypti. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.