bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental Self-Control as a Moderator of the Association Between Family Conflict and Type 1 Diabetes Management
Authors: Campbell MaryJane S , Berg Cynthia A , Wiebe Deborah J 
Published: May 2019

Abstract

Objective
To examine whether parental self-control (i.e., parents’ ability to regulate their emotions, cognitions, and behaviors) moderates the detrimental association between type 1 diabetes (T1D)-specific family conflict and adherence and HbA1c, such that conflict is most detrimental when parental self-control is low.

Methods
One hundred and forty-nine adolescents diagnosed with T1D (Mage = 14.09; 53% female) reported on their T1D-specific conflict with their mothers and fathers and their adherence to the T1D regimen at two time points (6 months apart). Mothers and fathers reported on their self-control. Glycated hemoglobin (HbA1c) was obtained from the medical record at both time points.

Results
Higher adolescent-reported conflict with father was associated concurrently with higher HbA1c and lower adherence only for fathers with low self-control (ps < .05). Higher adolescent-reported conflict with mother was also associated concurrently with lower adherence only for mothers with lower self-control (p < .05); no significant moderation was found for mothers’ self-control in predicting HbA1c. Longitudinal analyses indicated family conflict with mother predicted changes in adherence and HbA1c, but there were no significant moderating effects of either mother or father self-control.

Conclusions
Lower parental self-control may prevent parents from handling diabetes-related family conflict in a productive manner. We discuss the implications of parental self-control as an intervention target for health care professionals working with adolescents with T1D and their families.
Detecting baryon acoustic oscillations in dark matter from kinematic weak lensing surveys
Authors: Ding Zhejie , Seo Hee-Jong , Huff Eric , Saito Shun , Clowe Douglas 
Published: May 2019

Abstract
We investigate the feasibility of extracting baryon acoustic oscillations (BAO) from cosmic shear tomography. We particularly focus on the BAO scale precision that can be achieved by future spectroscopy-based, kinematic weak lensing (KWL) surveys in comparison to the traditional photometry-based weak lensing surveys. We simulate cosmic shear tomography data of such surveys with a few simple assumptions to focus on the BAO information, extract the spatial power spectrum, and constrain the recovered BAO feature. Due to the small shape noise and the shape of the lensing kernel, we find that a Dark Energy Task Force Stage IV version of such KWL survey can detect the BAO feature in dark matter by 3σ and measure the BAO scale at the precision level of 4 per cent, while it will be difficult to detect the feature in photometry-based weak lensing surveys. With a more optimistic assumption, a KWL-Stage IV could achieve a ${\sim } 2{{\ \rm per\ cent}}$ BAO scale measurement with 4.9σ confidence. A built-in spectroscopic galaxy survey within such KWL survey will allow cross-correlation between galaxies and cosmic shear, which will tighten the constraint beyond the lower limit we present in this paper and therefore possibly allow a detection of the BAO scale bias between galaxies and dark matter.
Intraspecific Variation in Microsatellite Mutation Profiles in Daphnia magna
Authors: Ho Eddie K H , Macrae Fenner , Latta Leigh C , Benner Maia J , Sun Cheng , Ebert Dieter , Schaack Sarah 
Published: May 2019

AbstractMicrosatellite loci (tandem repeats of short nucleotide motifs) are highly abundant in eukaryotic genomes and often used as genetic markers because they can exhibit variation both within and between populations. Although widely recognized for their mutability and utility, the mutation rates of microsatellites have only been empirically estimated in a few species, and have rarely been compared across genotypes and populations within a species. Here, we investigate the dynamics of microsatellite mutation over long- and short-time periods by quantifying the starting abundance and mutation rates for microsatellites for six different genotypes of Daphnia magna, an aquatic microcrustacean, collected from three populations (Finland, Germany, and Israel). Using whole-genome sequences of these six starting genotypes, descendent mutation accumulation (MA) lines, and large population controls (non-MA lines), we find each genotype exhibits a distinctive initial microsatellite profile which clusters according to the population-of-origin. During the period of MA, we observe motif-specific, highly variable, and rapid microsatellite mutation rates across genotypes of D. magna, the average of which is order of magnitude greater than the recently reported rate observed in a single genotype of the congener, Daphnia pulex. In our experiment, genotypes with more microsatellites starting out exhibit greater losses and those with fewer microsatellites starting out exhibit greater gains—a context-dependent mutation bias that has not been reported previously. We discuss how genotype-specific mutation rates and spectra, in conjunction with evolutionary forces, can shape both the differential accumulation of repeat content in the genome and the evolution of mutation rates.
DNAvisualization.org: a serverless web tool for DNA sequence visualization
Authors: Lee Benjamin D , Timony Michael A , Ruiz Pablo 
Published: May 2019

AbstractRaw DNA sequences contain an immense amount of meaningful biological information. However, these sequences are hard for humans to intuitively interpret. To solve this problem, a number of methods have been proposed to transform DNA sequences into two-dimensional visualizations. DNAvisualization.org implements several of these methods in a cost effective and performant manner via a novel, entirely serverless architecture. By taking advantage of recent developments in serverless parallel computing and selective data retrieval, the website is able to offer users the ability to visualize up to thirty 4.5 Mb DNA sequences simultaneously using one of five supported methods and to export these visualizations in a variety of publication-ready formats.
Validation of the GARD™skin Assay for Assessment of Chemical Skin Sensitizers: Ring Trial Results of Predictive Performance and Reproducibility
Authors: Johansson Henrik , Gradin Robin , Johansson Angelica , Adriaens Els , Edwards Amber , Zuckerstätter Veronika , Jerre Anders , Burleson Florence , Gehrke Helge , Roggen Erwin L 
Published: May 2019

AbstractProactive identification of chemicals with skin sensitizing properties is a key toxicological endpoint within chemical safety assessment, as required by legislation for registration of chemicals. In order to meet demands of increased animal welfare and facilitate increased testing efficiency also in nonregulatory settings, considerable efforts have been made to develop nonanimal approaches to replace current animal testing. Genomic Allergen Rapid Detection (GARD™) is a state-of-the-art technology platform, the most advanced application of which is the assay for assessment of skin sensitizing chemicals, GARD™skin. The methodology is based on a dendritic cell (DC)-like cell line, thus mimicking the mechanistic events leading to initiation and modulation of downstream immunological responses. Induced transcriptional changes are measured following exposure to test chemicals, providing a detailed evaluation of cell activation. These changes are associated with the immunological decision-making role of DCs in vivo and include among other phenotypic modifications, up-regulation of co-stimulatory molecules, induction of cellular and oxidative stress pathways and xenobiotic responses, and provide a holistic readout of substance-induced DC activation. Here, results from an inter-laboratory ring trial of GARD™skin, conducted in compliance with OECD guidance documents and comprising a blinded chemical test set of 28 chemicals, are summarized. The assay was found to be transferable to naïve laboratories, with an inter-laboratory reproducibility of 92.0%. The within-laboratory reproducibility ranged between 82.1% and 88.9%, whereas the cumulative predictive accuracy across the 3 laboratories was 93.8%. It was concluded that GARD™skin is a robust and reliable method for the identification of skin sensitizing chemicals and suitable for stand-alone use or as a constituent of integrated testing. These data form the basis for the regulatory validation of GARD™skin.
Hepatocyte-Derived Exosomes Promote Liver Immune Tolerance: Possible Implications for Idiosyncratic Drug-Induced Liver Injury
Authors: Holman Natalie S , Church Rachel J , Nautiyal Manisha , Rose Kelly A , Thacker Sarah E , Otieno Monicah A , Wolf Kristina K , LeCluyse Edward , Watkins Paul B , Mosedale Merrie 
Published: May 2019

Abstract
Most idiosyncratic drug-induced liver injury appears to result from an adaptive immune attack on the liver. Recent evidence suggests that the T-cell response may be facilitated by the loss of immune tolerance. In this study, we explored the hypothesis that constitutively released hepatocyte-derived exosomes (HDE) are important for maintaining normal liver immune tolerance. Exosomes were isolated from the conditioned medium of primary human hepatocytes via polymer precipitation. Mock controls were prepared by processing fresh medium that was not hepatocyte exposed with precipitation reagent. THP-1 monocytes were then treated with HDE or an equivalent volume of mock control for 24 h, followed by a 6-h stimulation with LPS. HDE exposure resulted in a significant decrease in the LPS-induced media levels of interleukin-1β and interleukin-8. Gene expression profiling performed in THP-1 cells just prior to LPS-induced stimulation identified a significant decrease among genes associated with innate immune response. MicroRNA (miRNA) profiling was performed on the HDE to identify exosome contents that may drive immune suppression. Many of the predicted mRNA target genes for the most abundant microRNAs in HDE were among the differentially expressed genes in THP-1 cells. Taken together, our data suggest that HDE play a role in maintaining normal liver immune tolerance. Future experiments will explore the possibility that drugs causing idiosyncratic liver injury promote the loss of homeostatic HDE signaling.
Differential Sensitivity to In Vitro Inhibition of Cytochrome P450 Aromatase (CYP19) Activity Among 18 Freshwater Fishes
Authors: Doering Jon A , Villeneuve Daniel L , Fay Kellie A , Randolph Eric C , Jensen Kathleen M , Kahl Michael D , LaLone Carlie A , Ankley Gerald T 
Published: May 2019

Abstract
There is significant concern regarding potential impairment of fish reproduction associated with endocrine disrupting chemicals. Aromatase (CYP19) is a steroidogenic enzyme involved in the conversion of androgens to estrogens. Inhibition of aromatase by chemicals can result in reduced concentrations of estrogens leading to adverse reproductive effects. These effects have been extensively investigated in a small number of laboratory model fishes, such as fathead minnow (Pimephales promelas), Japanese medaka (Oryzias latipes), and zebrafish (Danio rerio). But, differences in sensitivity among species are largely unknown. Therefore, this study took a first step toward understanding potential differences in sensitivity to aromatase inhibitors among fishes. Specifically, a standard in vitro aromatase inhibition assay using subcellular fractions of whole tissue homogenates was used to evaluate the potential sensitivity of 18 phylogenetically diverse species of freshwater fish to the nonsteroidal aromatase inhibitor fadrozole. Sensitivity to fadrozole ranged by more than 52-fold among these species. Five species were further investigated for sensitivity to up to 4 additional nonsteroidal aromatase inhibitors, letrozole, imazalil, prochloraz, and propiconazole. Potencies of each of these chemicals relative to fadrozole ranged by up to 2 orders of magnitude among the 5 species. Fathead minnow, Japanese medaka, and zebrafish were among the least sensitive to all the investigated chemicals; therefore, ecological risks of aromatase inhibitors derived from these species might not be adequately protective of more sensitive native fishes. This information could guide more objective ecological risk assessments of native fishes to chemicals that inhibit aromatase.
Pharmacologically targeting a novel pathway of sodium iodide symporter trafficking to enhance radioiodine uptake
Authors: Fletcher Alice , Read Martin L. , Thornton Caitlin E.M. , Larner Dean P. , Poole Vikki L. , Brookes Katie , Nieto Hannah R. , Alshahrani Mohammed , Thompson Rebecca J. , Lavery Gareth G. , Campbell Moray J. , Boelaert Kristien , Turnell Andrew S. , Smith Vicki E. , McCabe Christopher J. 
Published: May 2019

ABSTRACTRadioiodine treatment fails ≥25% of patients with thyroid cancer and has been proposed as a potential treatment for breast cancer. Cellular iodide uptake is governed by the sodium iodide symporter (NIS), which is frequently mislocalized in thyroid and breast tumours. However, the trafficking of NIS to the plasma membrane (PM) is ill-defined. Through mass spectrometry, co-immunoprecipitation, cell surface biotinylation and proximity ligation assays we identify two proteins which control NIS subcellular trafficking: ADP-ribosylation factor 4 (ARF4) and valosin-containing protein (VCP). HiLo microscopy revealed ARF4 enhanced NIS trafficking in co-incident PM vesicles, governed by a C-terminal VXPX motif, whilst papillary thyroid cancers (PTC) demonstrate repressed ARF4 expression. In contrast, VCP, the central protein in ER-associated degradation, specifically bound NIS and decreased its PM localization. Five chemically distinct allosteric VCP inhibitors all overcame VCP-mediated repression of NIS function. In mice, two re-purposed FDA-approved VCP inhibitors significantly enhanced radioiodine uptake into thyrocytes, whilst human primary thyrocytes showed similar increases. Critically, PTC patients with high tumoural VCP expression who received radioiodine had strikingly worse disease-free survival. These studies now delineate the mechanisms of NIS trafficking, and for the first time open the therapeutic possibility of systemically enhancing radioiodine uptake in patients via FDA-approved drugs.One Sentence SummaryNovel NIS interactors ARF4 and VCP alter NIS trafficking in vitro, and FDA-approved VCP inhibitors can significantly enhance radioiodine uptake.
Inhibition of host Lactate dehydrogenase A by a small-molecule limitsMycobacterium tuberculosisgrowth and potentiates bactericidal activity of isoniazid
Authors: Krishnamoorthy Gopinath , Kaiser Peggy , Abed Ulrike Abu , Weiner January , Moura-Alves Pedro , Brinkmann Volker , Kaufmann Stefan H. E. 
Published: May 2019

ABSTRACTLactate dehydrogenase A (LDHA) mediates interconversion of pyruvate and lactate. Increased lactate turnover is shared by malignant and immune cells. Hypoxic lung granuloma inMycobacterium tuberculosis-infected animals present elevated levels ofLdhaand lactate. Such alteration in metabolic milieu could influence the outcome of interactions betweenM. tuberculosisand its infected immune cells. Given the central role of LDHA for tumorigenicity, targeting lactate metabolism is a promising approach for cancer therapy. Here, we sought to determine the importance of LDHA for Tuberculosis (TB) disease progression and its potential as a host-directed therapeutic target. To this end, we administered FX11, a small-molecule NADH-competitive LDHA inhibitor, toM. tuberculosisinfected C57BL/6J mice and Nos2−/−mice with hypoxic necrotizing lung TB lesions mimicking human pathology more closely. FX11 did not inhibitM. tuberculosisgrowth in aerobic/hypoxic liquid culture, but modestly reduced the pulmonary bacterial burden in C57BL/6J mice. Intriguingly, FX11 administration limitedM. tuberculosisreplication and onset of necrotic lesions in Nos2−/−mice. In this model, Isoniazid (INH) monotherapy has been known to exhibit biphasic killing kinetics owing to the probable selection of an INH-tolerant subpopulation. This adverse effect was corrected by adjunct FX11 treatment and augmented the INH-derived bactericidal effect againstM. tuberculosis. Our findings therefore support LDHA as a potential target for host-directed adjunctive TB therapy and encourage further investigations into the underlying mechanism.IMPORTANCETuberculosis (TB) continues to be a global health threat of critical dimension. Standard TB drug treatment is prolonged and cumbersome. Inappropriate treatment or non-compliance results in emergence of drug-resistantMycobacterium tuberculosisstrains (MDR-TB) that render current treatment options ineffective. Targeting the host immune system as adjunct therapy to augment bacterial clearance is attractive as it is also expected to be effective against MDR-TB. Here, we provide evidence that pharmaceutical blockade of host lactate dehydrogenase A (LDHA) by a small-molecule limitsM. tuberculosisgrowth and reduces pathology. Notably, LDHA inhibition potentiates the effect of Isoniazid, a first-line anti-TB drug. Hence, its implications of our findings for short-term TB treatment are profound. In sum, our findings establish murine LDHA as a potential target for host-directed TB therapy.
Origin of the bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord
Authors: Thouvenin Olivier , Keiser Ludovic , Cantaut-Belarif Yasmine , Carbo-Tano Martin , Verweij Frederik , Jurisch-Yaksi Nathalie , Bardet Pierre-Luc , Niel Guillaume Van , Gallaire François , Wyart Claire 
Published: May 2019

AbstractThe circulation of cerebrospinal fluid (CSF) plays pivotal roles for body axis formation and brain development. During embryogenesis, CSF is rich in particles and proteins and flows bidirectionally in the central canal. The origins of bidirectional flow and its impact on development are unknown. Experiments combined with modeling and simulations demonstrate that the bidirectionality of CSF flow is generated locally by caudally-polarized motile cilia confined to the ventral wall of the central canal. Such active bidirectional flow of the CSF accelerates the long-range transport of particles propagating rostrally and caudally. In addition, spontaneous muscle contractions increase local CSF flow and consequently enhance long-range transport of extracellular lipidic particles. Focal ablation of the channel connecting brain ventricles to the central canal reduces embryo length, indicating that long-range transport contributes to embryonic growth. Our study also demonstrates that at this early stage, motile cilia ensure the proper formation of the central canal.
Rewiring of transcriptional networks as a major event leading to the diversity of asexual multicellularity in fungi
Authors: Etxebeste Oier , Otamendi Ainara , Garzia Aitor , Espeso Eduardo A. , Cortese Marc S. 
Published: May 2019

AbstractComplex multicellularity (CM) is characterized by the generation of three-dimensional structures that follow a genetically controlled program. CM emerged at least five times in evolution, one of them in fungi. There are two types of CM programs in fungi, leading, respectively, to the formation of sexual or asexual spores. Asexual spores foment the spread of mycoses, as they are the main vehicle for dispersion. In spite of this key dependence, there is great morphological diversity of asexual multicellular structures in fungi. To advance the understanding of the mechanisms that control initiation and progression of asexual CM and how they can lead to such a remarkable morphological diversification, we studied 503 fungal proteomes, representing all phyla and subphyla, and most known classes. Conservation analyses of 33 regulators of asexual development suggest stepwise emergence of transcription factors. While velvet proteins constitute one of the most ancient systems, the central regulator BrlA emerged late in evolution (with the class eurotiomycetes). Some factors, such as MoConX4, seem to be species-specific. These observations suggest that the emergence and evolution of transcriptional regulators rewire transcriptional networks. This process could reach the species level, resulting in a vast diversity of morphologies.One-sentence summaryA study of the evolution of regulators that control the production of asexual spores in fungi.
Genetic Resilience of a Once Endangered Species, Tibetan Antelope (Pantholops hodgsonii)
Authors: Shi Yue , Chen Jiarui , Su Jianping , Zhang Tongzuo , Wasser Samuel K. 
Published: May 2019

AbstractPopulation reduction is generally assumed to reduce the population’s genetic diversity and hence its ability to adapt to environmental change. However, if life history traits that promote gene flow buffer populations from such impacts, conservation efforts should aim to maintain those traits in vulnerable species. Tibetan antelope (Pantholops hodgsonii) has experienced population reduction by 95% due to poaching during the 20thcentury. We hypothesize that opportunities for gene flow provided by their sex-specific migration buffered their genetic diversity from the poaching impacts. We measured the mtDNA (control region, CR) and nuDNA (microsatellites or STRs) diversity, population differentiation, along with the change in effective population size (pre-poaching era vs. post-poaching era) and tested for a genetic bottleneck. Our results showed that Tibetan antelope maintained considerable genetic diversity in both mtDNA CR and STR markers (Hd= 0.9970 and Hobs= 0.8446, respectively), despite a marked reduction in post-poaching effective population size 368.9 (95% CI of 249.3 - 660.6) compared to the pre-poaching average (4.93×103- 4.17×104). Post-poached populations also had low population structure and showed no evidence of a genetic bottleneck. Pairwise Fstvalues using CR haplotype frequencies were higher than those using STR allele frequencies, suggesting different degrees of gene flow mediated by females and males. This study suggests that the Tibetan antelope’s sex-specific migration buffered their loss of genetic diversity in the face of severe demographic decline. These findings highlight the importance of recognizing the traits likely to maintain genetic diversity and promoting conservation efforts that allow them to be exercised. For Tibetan antelope, this requires assuring that their migration routes remain unobstructed by growing human disturbances while continuing to enforce anti-poaching law enforcement efforts.
Novel functions of Kaposi’s sarcoma herpesvirus viral FLICE inhibitory protein
Authors: Herold Kevin , Ruffin Ayana , Constantine Mathew , Causey Amerria , Mitchell Ashley E. , Chmura Jennifer C. , Moorad Razia , Ehrlich Elana S. 
Published: May 2019

AbstractKSHV viral FLICE inhibitory protein (vFLIP) is a potent activator of NF-κB signaling and an inhibitor of apoptosis and autophagy. Inhibition of vFLIP function and NF-κB signaling promotes lytic reactivation. Here we provide evidence for a novel function of vFLIP in promoting NFκB signaling through inhibition of the DUB activity of the negative regulator, A20. We demonstrate interaction of vFLIP with the Itch/A20 ubiquitin editing complex. We have identified a SUMO interaction motif in vFLIP that is required for NF-κB activation. Mutation of the SIM in BAC16 resulted in increased spontaneous RTA expression and loss of spindle cell morphology. Our results suggest a role for SUMO in mediating vFLIP function and provide evidence for vFLIP modulation of the negative regulation of NF-κB signaling by A20. Our results provide further insight into the function of vFLIP and SUMO in the regulation of NF-κB signaling and the latent lytic transition.