Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structures of disordered Z-type helices

Abstract The X-ray crystal structures of a decamer sequence d(CGCGTACGCG)2 and a tetradecamer sequence d(CGCGCGTACGCGCG)2 are presented here. Both sequences are alternating pyrimidine-purine repeat sequences and they form disordered, pseudo-continuous left handed Z-type helices. They demonstrate interesting variants of the ‘bundles of columns of helices’ mode of packing.
Brain Gray Matter Volume Is Modulated by Visual Input and Overall Learning Success but Not by Time Spent on Learning a Complex Balancing Task

To better understand the process of neuroplasticity, this study assesses brain changes observed by voxel-based morphometry (VBM) in response to two different learning conditions. Twenty-two young, healthy subjects learned slacklining, a complex balancing task, with either their eyes open (EO, n = 11) or their eyes closed (EC, n = 11). The learning took place three times per week for four weeks, with learning periods of 1 hour, providing a total of 12 hours of learning. The scanning and testing protocols were applied at three time-points: (1) immediately before learning (baseline), (2) immediately afterwards (post-test), and (3) two months afterwards (follow-up). The EO group performed better on the task-specific test. Significant group*time interaction effects were found in sensory-motor areas at the post-test, with increases in the EO group only. The results suggest that VBM-observed brain changes in response to learning a complex balancing task vary depending on the learning success and the availability of visual input, and not solely on the amount of time spent on learning. These findings should be taken into account by future studies using similar methodologies.
ADAR1 Is Required for Dendritic Cell Subset Homeostasis and Alveolar Macrophage Function

RNA editing by adenosine deaminases acting on dsRNA (ADAR) has become of increasing medical relevance, particularly because aberrant ADAR1 activity has been associated with autoimmunity and malignancies. However, the role of ADAR1 in dendritic cells (DC), representing critical professional APCs, is unknown. We have established conditional murine CD11c Cre-mediated ADAR1 gene ablation, which did not induce general apoptosis in CD11c+ cells but instead manifests in cell type–specific effects in DC subpopulations. Bone marrow–derived DC subset analysis revealed an incapacity to differentiate CD103 DC+ in both bulk bone marrow and purified pre-DC lineage progenitor assays. ADAR1 deficiency further resulted in a preferential systemic loss of CD8+/CD103+ DCs, revealing critical dependency on ADAR1, whereas other DC subpopulations were moderately affected or unaffected. Additionally, alveolar macrophages were depleted and dysfunctional, resembling pulmonary alveolar proteinosis. These results reveal an unrecognized role of ADAR1 in DC subset homeostasis and unveils the cell type–specific effects of RNA editing.
Relationships between Challenge Tour golfers’ clubhead velocity and force producing capabilities during a countermovement jump and isometric mid-thigh pull

ABSTRACT A number of field-based investigations have evidenced practically significant relationships between clubhead velocity (CHV), vertical jump performance and maximum strength. Unfortunately, whilst these investigations provide a great deal of external validity, they are unable to ascertain vertical ground reaction force (vGRF) variables that may relate to golfers’ CHVs. This investigation aimed to assess if the variance in European Challenge Tour golfers’ CHVs could be predicted by countermovement jump (CMJ) positive impulse (PI), isometric mid-thigh pull (IMTP) peak force (PF) and rate of force development (RFD) from 0–50 ms, 0–100 ms, 0–150 ms and 0–200 ms. Thirty-one elite level European Challenge Tour golfers performed a CMJ and IMTP on dual force plates at a tournament venue, with CHV measured on a driving range. Hierarchical multiple regression results indicated that the variance in CHV was significantly predicted by all four models (model one R2 = 0.379; model two R2 = 0.392, model three R2 = 0.422, model four R2 = 0.480), with Akaike’s information criterion indicating that model one was the best fit. Individual standardised beta coefficients revealed that CMJ PI was the only significant variable, accounting for 37.9% of the variance in European Challenge Tour Golfers’ CHVs.
Hepatocyte and stellate cell deletion of liver fatty acid binding protein reveals distinct roles in fibrogenic injury

Liver fatty acid binding protein (L‐Fabp) modulates lipid trafficking in enterocytes, hepatocytes, and hepatic stellate cells (HSCs). We examined hepatocyte vs. HSC L‐Fabp deletion in hepatic metabolic adaptation and fibrotic injury. Floxed L‐Fabp mice were bred to different transgenic Cre mice or injected with adeno‐associated virus type 8 (AAV8) Cre and fed diets to promote steatosis and fibrosis or were subjected to either bile duct ligation or CCl4 injury. Albumin‐Cre‐mediated L‐Fabp deletion revealed recombination in hepatocytes and HSCs; these findings were confirmed with 2 other floxed alleles. Glial fibrillary acid protein‐Cre and platelet‐derived growth factor receptor β‐Cre‐mediated L‐Fabp deletion demonstrated recombination only in HSCs. Mice with albumin promoter‐driven Cre recombinase (Alb‐Cre)‐mediated or AAV8‐mediated L‐Fabp deletion were protected against food withdrawal‐induced steatosis. Mice with Alb‐Cre‐mediated L‐Fabp deletion were protected against high saturated fat‐induced steatosis and fibrosis, phenocopying germline L‐Fabp−/− mice. Mice with HSC‐specific L‐Fabp deletion exhibited retinyl ester depletion yet demonstrated no alterations in fibrosis. On the other hand, fibrogenic resolution after CCl4 administration was impaired in mice with Alb‐Cre‐mediated L‐Fabp deletion. These findings suggest cell type‐specific roles for L‐Fabp in mitigating hepatic steatosis and in modulating fibrogenic injury and reversal. —Newberry, E. P., Xie, Y. , Lodeiro, C. , Solis, R. , Moritz, W. , Kennedy, S. , Barron, L. , Onufer, E. , Alpini, G. , Zhou, T. , Blaner, W. S. , Chen, A. , Davidson, N. O. Hepatocyte and stellate cell deletion of liver fatty acid binding protein reveal distinct roles in fibrogenic injury. FASEB J. 33, 4610–4625 (2019). www.fasebj. org
Deletion of both centrin 2 (CETN2) and CETN3 destabilizes the distal connecting cilium of mouse photoreceptors

Centrins (CETN1–4) are ubiquitous and conserved EF-hand–family Ca2+-binding proteins associated with the centrosome, basal body, and transition zone. Deletion of CETN1 or CETN2 in mice causes male infertility or dysosmia, respectively, without affecting photoreceptor function. However, it remains unclear to what extent centrins are redundant with each other in photoreceptors. Here, to explore centrin redundancy, we generated Cetn3GT/GT single-knockout and Cetn2−/−;Cetn3GT/GT double-knockout mice. Whereas the Cetn3 deletion alone did not affect photoreceptor function, simultaneous ablation of Cetn2 and Cetn3 resulted in attenuated scotopic and photopic electroretinography (ERG) responses in mice at 3 months of age, with nearly complete retina degeneration at 1 year. Removal of CETN2 and CETN3 activity from the lumen of the connecting cilium (CC) destabilized the photoreceptor axoneme and reduced the CC length as early as postnatal day 22 (P22). In Cetn2−/−;Cetn3GT/GT double-knockout mice, spermatogenesis-associated 7 (SPATA7), a key organizer of the photoreceptor-specific distal CC, was depleted gradually, and CETN1 was condensed to the mid-segment of the CC. Ultrastructural analysis revealed that in this double knockout, the axoneme of the CC expanded radially at the distal end, with vertically misaligned outer segment discs and membrane whorls. These observations suggest that CETN2 and CETN3 cooperate in stabilizing the CC/axoneme structure.
Atomic Fe Dispersed on N‐Doped Carbon Hollow Nanospheres for High‐Efficiency Electrocatalytic Oxygen Reduction

Exploration of high‐efficiency, economical, and ultrastable electrocatalysts for the oxygen reduction reaction (ORR) to substitute precious Pt is of great significance in electrochemical energy conversion devices. Single‐atom catalysts (SACs) have sparked tremendous interest for their maximum atom‐utilization efficiency and fascinating properties. Therefore, the development of effective synthetic methodology toward SACs becomes highly imperative yet still remains greatly challenging. Herein, a reliable SiO2‐templated strategy is elaborately designed to synthesize atomically dispersed Fe atoms anchored on N‐doped carbon nanospheres (denoted as Fe–N–C HNSs) using the cheap and sustainable biomaterial of histidine (His) as the N and C precursor. By virtue of the numerous atomically dispersed Fe–N4 moieties and unique spherical hollow architecture, the as‐fabricated Fe–N–C HNSs exhibit excellent ORR performance in alkaline medium with outstanding activity, high long‐term stability, and superior tolerance to methanol crossover, exceeding the commercial Pt/C catalyst and most previously reported non‐precious‐metal catalysts. This present synthetic strategy will provide new inspiration to the fabrication of various high‐efficiency single‐atom catalysts for diverse applications.
Barrier to Resistance of Dolutegravir in Two-Drug Combinations

A major concern when using two-drug anti-HIV regimens is the risk of viral resistance. However, no techniques to evaluate the barrier to resistance of two-drug combinations in vitro have been reported. ABSTRACT A major concern when using two-drug anti-HIV regimens is the risk of viral resistance. However, no techniques to evaluate the barrier to resistance of two-drug combinations in vitro have been reported. We evaluated the emergence of drug-resistant mutants in a passage study with constant concentrations of two drugs simultaneously. The barrier to resistance of dolutegravir-containing two-drug combinations was higher than the other combinations evaluated in this study.
CSHAP: efficient haplotype frequency estimation based on sparse representation

Motivation Estimating haplotype frequencies from genotype data plays an important role in genetic analysis. In silico methods are usually computationally involved since phase information is not available. Due to tight linkage disequilibrium (LD) and low recombination rates, the number of haplotypes observed in human populations is far less than all the possibilities. This motivates us to solve the estimation problem by maximizing the sparsity of existing haplotypes. Here we propose a new algorithm by applying the compressive sensing (CS) theory in the field of signal processing, CSHAP, to solve the sparse representation of haplotype frequencies based on allele frequencies and between-allele covariances. Results Our proposed approach can handle both individual genotype data and pooled DNA data with hundreds of loci. The CSHAP exhibits the same accuracy compared to the state-of-the-art methods, but runs several orders of magnitude faster. CSHAP can also handle with missing genotype data imputations efficiently. Availability and Implementation The CSHAP is implemented in R, the source code and the testing datasets are available at http://home.ustc. edu.cn/~zhouys/CSHAP/. Supplementary information Supplementary data are available at Bioinformatics online.
Evaluation of the psychometric properties of the social isolation measure (SIM) in adults with hearing loss

Abstract Objective: This study aimed to evaluate the psychometric properties of a brief, hearing-specific outcome measure: the Social Isolation Measure (SIM). Design: In Phase 1, adults with hearing loss were invited to complete an online survey that contained the SIM, a hearing-specific participation questionnaire, a generic activity and participation questionnaire, and a generic loneliness questionnaire. In Phase 2, the participants were asked to complete the SIM for a second time 2–3 weeks following Phase 1. Study Sample: One hundred and sixteen adults with hearing loss completed Phase 1. Ninety-five participants also completed Phase 2. Twenty-nine participants were excluded from the Phase 2 data analysis because they reported that their hearing had changed since Phase 1 or because they completed Phase 2 outside of the 2–3 week interval following Phase 1. Results: In support of its construct validity, the SIM had a strong correlation with the hearing-specific questionnaire and moderate correlations with the generic questionnaires. The findings also supported the internal consistency, interpretability and test-retest reliability of the SIM. Conclusions: The SIM was found to have strong psychometric properties. It could serve as a brief measure of perceived social isolation in research or clinical practice.
Determination of size dependent carrier capture in InGaN/GaN quantum nanowires by femto-second transient absorption spectroscopy: effect of optical phonon, electron–electron scattering and diffusion

Understanding the ultrafast processes corresponding to carrier capture, thermalization and relaxation is essential to design high speed optoelectronic devices. Here, we have investigated a size dependent carrier capture process in InGaN/GaN 20, 50 nm nanowires and quantum well systems. Femto-second transient absorption spectroscopy reveals that the carrier capture is a two-step process. The carriers are captured in the barrier by polar optical phonon (POP) scattering. They further scatter into the active region by electron–electron and POP scatterings. The capture is found to slow down for quantum confined structures. A significant number of carriers are found to disappear from the barrier during the diffusion process. All the experimental observations are explained in a simulation framework depicting various scattering mechanisms.
Metacaspase involvement in programmed cell death of the marine cyanobacterium Trichodesmium

Metacaspases are cysteine specific proteases implicated in cell-signalling, stress acclimation and programmed cell death (PCD) pathways in plants, fungi, protozoa, bacteria and algae. We investigated metacaspase-like gene expression and biochemical activity in the bloom-forming, N2 -fixing, marine cyanobacterium Trichodesmium, which undergoes PCD under low iron and high-light stress. We examined these patterns with respect to in-silico analyses of protein domain architectures that revealed a diverse array of regulatory domains within Trichodesmium metacaspases-like (TeMC) proteins. Experimental manipulations of laboratory cultures and oceanic surface blooms of Trichodesmium from the South Pacific Ocean triggered PCD under Fe-limitation and high light along with enhanced TeMC activity and upregulated expression of diverse TeMC representatives containing different regulatory domains. Furthermore, TeMC activity was significantly and positively correlated with caspase-like activity, which has been routinely observed to increase with PCD induction in Trichodesmium. Although both TeMC and caspase-like activities were stimulated upon PCD induction, inhibitor treatments of these proteolytic activities provided further evidence of largely distinct substrate specificities, even though some inhibitory crossover was observed. Our findings are the first results linking metacaspase expression and activity in PCD induced mortality in Trichodesmium. Yet, the role/s and specific activities of these different proteins remain to be elucidated.
Three-Dimensional Stable Alginate-Nanocellulose Gels for Biomedical Applications: Towards Tunable Mechanical Properties and Cell Growing

Hydrogels have been studied as promising materials in different biomedical applications such as cell culture in tissue engineering or in wound healing. In this work, we synthesized different nanocellulose-alginate hydrogels containing cellulose nanocrystals, TEMPO-oxidized cellulose nanocrystals (CNCTs), cellulose nanofibers or TEMPO-oxidized cellulose nanofibers (CNFTs). The hydrogels were freeze-dried and named as gels. The nanocelluloses and the gels were characterized by different techniques such as Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and dynamic mechanical thermal analysis (DMTA), while the biological features were characterized by cytotoxicity and cell growth assays. The addition of CNCTs or CNFTs in alginate gels contributed to the formation of porous structure (diameter of pores in the range between 40 and 150 μm). TEMPO-oxidized cellulose nanofibers have proven to play a crucial role in improving the dimensional stability of the samples when compared to the pure alginate gels, mainly after a thermal post-treatment of these gels containing 50 wt % of CNFT, which significantly increased the Ca2+ crosslinking density in the gel structure. The morphological characteristics, the mechanical properties, and the non-cytotoxic behavior of the CNFT-alginate gels improved bioadhesion, growth, and proliferation of the cells onto the gels. Thus, the alginate-nanocellulose gels might find applications in tissue engineering field, as for instance, in tissue repair or wound healing applications.
Effects of early adversity on the brain: Larger-volume anterior cingulate cortex in AIDS orphans

Multiple studies have revealed that adolescent AIDS orphans have more psychosocial problems than healthy adolescents. However, little is known about whether and how the brain structures of adolescent AIDS orphans differ from those of healthy adolescents. Here, we used magnetic resonance imaging to compare adolescent AIDS orphans reared in institutions (N = 20) with a sex- and age-matched group of healthy adolescents reared in families (N = 20) in China using a voxel-based morphometry analysis. First, we found that both total gray- and white-matter volumes did not differ between groups. Second, after correcting for age, sex, and total gray-matter volume, the AIDS orphan group demonstrated smaller hippocampal volumes, larger anterior cingulate cortex (ACC) volumes, and no differences in the amygdala. Third, a whole-brain analysis identified higher gray-matter volume of the ACC in the AIDS orphan group than in the control group. The preliminary findings of this study highlight the need for future research to confirm the sensitivity of the hippocampus and ACC to early adversity.
Protein Phosphatase 2A Reduces Cigarette Smoke-Induced Cathepsin S and Loss of Lung Function.

RATIONALE Cathepsin S (CTSS) is a cysteine protease that is observed at higher concentrations in bronchoalveolar lavage fluid and plasma of chronic obstructive pulmonary disease (COPD) subjects. OBJECTIVES The objective of this study was to investigate whether CTSS is involved in the pathogenesis of cigarette smoke-induced COPD and determine whether targeting upstream signaling could prevent the disease. METHODS CTSS expression was investigated in animal and human tissue and cell models of COPD. Ctss-/- mice were exposed to long-term cigarette smoke and forced oscillation and expiratory measurements were recorded. Animals were administered chemical modulators of protein phosphatase 2A (PP2A) activity. MEASUREMENTS AND MAIN RESULTS Here we observed enhanced CTSS expression and activity in mouse lungs following exposure to cigarette smoke. Ctss-/- mice were resistant to cigarette smoke-induced inflammation, airway hyperresponsiveness, airspace enlargements and loss of lung function. CTSS expression was negatively regulated by PP2A in human bronchial epithelial cells isolated from healthy non-smokers and COPD donors and in monocyte-derived macrophages. Modulating PP2A expression or activity, with silencer short interfering RNA or a chemical inhibitor or activator, during acute smoke exposure in mice altered inflammatory responses and CTSS expression and activity in the lung. Enhancement of PP2A activity prevented chronic smoke-induced COPD in mice. CONCLUSIONS Our study indicates that the decrease in PP2A activity that occurs in COPD contributes to elevated CTSS expression in the lungs and results in impaired lung function. Enhancing PP2A activity represents a feasible therapeutic approach to reduce CTSS activity and counter smoke-induced lung disease.
Police-Related Correlates of Client-Perpetrated Violence Among Female Sex Workers in Baltimore City, Maryland.

OBJECTIVES To characterize interactions that female sex workers (FSWs) have with the police and explore associations with client-perpetrated violence. METHODS Baseline data were collected April 2016 to January 2017 from 250 FSWs from the Sex Workers and Police Promoting Health in Risky Environments (SAPPHIRE) study based in Baltimore, Maryland. Interviewer-administered questionnaires captured different patrol or enforcement and abusive police encounters, experiences of client-perpetrated violence, and other risk factors, including drug use. We conducted bivariate and multivariable analysis in Stata/SE version 14.2 (StataCorp LP, College Station, TX). RESULTS Of participants, 78% reported lifetime abusive police encounters, 41% reported daily or weekly encounters of any type. In the previous 3 months, 22% experienced client-perpetrated violence. Heroin users (70% of participants) reported more abusive encounters (2.5 vs 1.6; P < .001) and more client-perpetrated violence (26% vs 12%; P = .02) than others. In multivariable analysis, each additional type of abusive interaction was associated with 1.3 times (95% confidence interval [CI] = 1.1, 1.5) increased odds of client-perpetrated violence. For patrol or enforcement encounters, this value was 1.3 (95% CI = 1.0, 1.7). CONCLUSIONS Frequent exposures to abusive police practices appear to contribute to an environment where client-perpetrated violence is regularly experienced. For FSWs who inject drugs, police exposure and client-perpetrated violence appear amplified. Public Health Implications. Structural interventions that address police-FSW interactions will help alleviate police's negative impact on FSWs' work environment.
Effect of Mental Health Screening and Integrated Mental Health on Adolescent Depression–Coded Visits

Adolescent depression causes morbidity and is underdiagnosed. It is unclear how mental health screening and integrated mental health practitioners change adolescent depression identification. We conducted a retrospective primary care network natural cohort study where 10 out of 19 practices implemented mental health screening, followed by the remaining 9 practices implementing mental health screening with less coaching and support. Afterward, a different subset of 8 practices implemented integrated mental health practitioners. Percentages of depression-coded adolescent visits were compared between practices (1) with and without mental health screening and (2) with and without integrated mental health practitioners, using difference-in-differences analyses. The incidence of depression-coded visits increased more in practices that performed mental health screening (ratio of odds ratios = 1.22; 95% confidence interval =1.00-1.49) and more in practices with integrated mental health practitioners (ratio of odds ratios = 1.58; 95% confidence interval = 1.30-1.93). Adolescent mental health screening and integrated mental health practitioners increase depression-coded visits in primary care.
Efficient estimation of a linear transformation model for current status data via penalized splines

We propose a flexible and computationally efficient penalized estimation method for a semi-parametric linear transformation model with current status data. To facilitate model fitting, the unknown monotone function is approximated by monotone B-splines, and a computationally efficient hybrid algorithm involving the Fisher scoring algorithm and the isotonic regression is developed. A goodness-of-fit test and model diagnostics are also considered. The asymptotic properties of the penalized estimators are established, including the optimal rate of convergence for the function estimator and the semi-parametric efficiency for the regression parameter estimators. An extensive numerical experiment is conducted to evaluate the finite-sample properties of the penalized estimators, and the methodology is further illustrated with two real studies.