bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Object Profiles Regression Analysis (SOPRA): A novel method for analyzing high content cell-based screens
Authors: Gurumurthy Rajendra Kumar , Pleissner Klaus-Peter , Chumduri Cindrilla , Meyer Thomas F. , Mäurer André P. 
Published: September 2021

AbstractMotivationHigh content screening (HCS) experiments generate complex data from multiple object features for each cell within a treated population. Usually these data are analyzed by using population-averaged values of the features of interest, increasing the amount of false positives and the need for intensive follow-up validation. Therefore, there is a strong need for novel approaches with reproducible hit prediction by identifying significantly altered cell populations.ResultsHere we describe SOPRA, a workflow for analyzing image-based HCS data based on regression analysis of non-averaged object features from cell populations, which can be run on hundreds of samples using different cell features. Following plate-wise normalization the values are counted within predetermined binning intervals, generating unique frequency distribution profiles (histograms) for each population, which are then normalized to control populations. Statistically significant differences are identified using a regression model approach. Significantly changed profiles can be used to generate a heatmap from which altered cell populations with similar phenotypes are identified, enabling detection of siRNAs and compounds with the same ‘on-target’ profile, reducing the number of false positive hits. A screen for cell cycle progression was used to validate the workflow, which identified statistically significant changes induced by siRNA-mediated gene perturbations and chemical inhibitors of different cell cycle stages.
A Drosophila Su(H) Model of Adams-Oliver Syndrome Reveals Notch Cofactor Titration as a Mechanism Underlying Developmental Defects
Authors: Gagliani Ellen K. , Gutzwiller Lisa M. , Kuang Yi , Odaka Yoshinobu , Hoffmeister Phillipp , Hauff Stefanie , Turkiewicz Aleksandra , Harding-Theobald Emily , Dolph Patrick J. , Borggrefe Tilman , Oswald Franz , Gebelein Brian , Kovall Rhett A. 
Published: September 2021

ABSTRACTNotch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that Drosophila with a single copy of the AOS-like Su(H) allele behave in an opposing manner as flies with a Su(H) null allele due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants decrease DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby a single RBPJ allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.
Basic reproduction numbers of three strains of mouse hepatitis viruses in mice
Authors: Nakayama Masataka , Kyuwa Shigeru 
Published: September 2021

AbstractMouse hepatitis virus (MHV) is a murine coronavirus and one of the most important pathogens in laboratory mice. Although various strains of MHV have been isolated, they are generally excreted in the feces and transmitted oronasally via aerosols and contaminated bedding. In this study, we attempted to determine the basic reproduction numbers of three strains of MHV to improve our understanding of MHV infections in mice. Five-week-old female C57BL/6J mice were inoculated intranasally with either the Y, NuU, or JHM variant strain of MHV and housed with two naive mice. After 4 weeks, the presence or absence of anti-MHV antibody in the mice was determined by the enzyme-linked immunosorbent assay. We also examined the distribution of MHV in the organs of Y, NuU, or JHM variant-infected mice. Our data suggest that the transmissibility of MHV is correlated with viral growth in the gastrointestinal tract of infected mice. To the best of our knowledge, this is the first report to address the basic reproduction numbers among pathogens in laboratory animals.
Dissection of function and recognition mechanism of M. tuberculosis ESX-1 secreted virulence factor EspC
Authors: Sharma Ruby , Kashyap Vipin K. , Kumar Manoj , Bansal Abhisheka , Saxena Ajay K. 
Published: September 2021

ABSTRACTMycobacterium tuberculosis uses the ESAT-6 system-1/type VII (ESX-1) system for secretion of virulence proteins into the host cell, however the mechanism of virulence proteins secretion, molecular components and regulation of ESX-1 system are only partly understood. In the current study, we have analyzed the biological function and recognition mechanism between ESX-1 virulence EspC and EccA1 ATPase proteins. The EspC enters into A549 human lung carcinoma cells and exhibited cytotoxicity, as observed in MTT Assay. To understand the recognition mechanism between EspC and EccA1 ATPase, the EspC and EccA1 mutants were generated based on EspC~EccA1 interactions, as observed in molecular modeling. Binding analysis shows that EspC export arm interacts specifically to the β-hairpin insertion motif of the TPR domain of EccA1 ATPase. Mutations in these epitopes lead to significant decrease/or abolish the binding between EspC and EccA1 ATPase. Our study provides insight into biological function and recognition mechanism between EspC and EccA1 ATPase, which can be used as target to prevent EspC secretion/ or in general virulence factor secretion by mycobacterial ESX-1 system.
Coat color mismatch improves survival of a keystone boreal herbivore: energetic advantages exceed lost camouflage
Authors: Kennah Joanie L. , Peers Michael J. L. , Wal Eric Vander , Majchrzak Yasmine N. , Menzies Allyson K. , Studd Emily K. , Boonstra Rudy , Humphries Murray M. , Jung Thomas S. , Kenney Alice J. , Krebs Charles J. , Boutin Stan 
Published: September 2021

AbstractClimate warming is causing asynchronies between animal phenology and environments. Mismatched traits, like coat color change mismatched with snow, can decrease survival. However, coat change does not serve a singular adaptive benefit of camouflage, and alternate coat change functions may confer advantages that supersede mismatch costs. We found that mismatch reduced rather than increased, autumn mortality risk of snowshoe hares in Yukon by 86.5 %. We suggest that the increased coat insulation and lower metabolic rates of winter acclimatized hares confer energetic advantages to white mismatched hares that reduce their mortality risk. We found that white mismatched hares forage 17-77 minutes less per day than matched brown hares between 0 and -10 °C, thus lowering their predation risk and increasing survival. We found no effect of mismatch on spring mortality risk, where mismatch occurred at warmer temperatures, suggesting a potential temperature limit where the costs of conspicuousness outweigh energetic benefits.
Purinergic receptor P2RY14 cAMP signaling regulates EGFR-driven Schwann cell precursor self-renewal and nerve tumor initiation in neurofibromatosis
Authors: Patritti-Cram Jennifer , Wu Jianqiang , Kuninaka Shinji , Coover Robert A. , Hennigan Robert F. , Rizvi Tilat A. , Chaney Katherine E. , Ravindran Ramya , Cancelas Jose A. , Spinner Robert J. , Ratner Nancy 
Published: September 2021

AbstractNeurofibromatosis type 1 (NF1) is a genetic disorder characterized by nerve tumors called neurofibromas, in which Schwann cells (SCs) lack NF1 and show deregulated RAS signaling. NF1 is also implicated in regulation of cAMP. Gene expression profiling and protein expression identified P2RY14 in SCs and SC precursors (SCPs) implicating P2RY14 as a candidate upstream regulator of cAMP in EGF-dependent SCP. We found that SCP self-renewal was reduced by genetic or pharmacological inhibition of P2RY14. In NF1 deficient SCs and malignant peripheral nerve sheath tumor (MPNST) cells, P2RY14 inhibition decreased EGFR-driven phospho-Akt and increased cAMP signaling. In a neurofibroma mouse model, genetic deletion of P2RY14 increased mouse survival, delayed neurofibroma initiation and rescued cAMP signaling. Conversely, elevation of cAMP diminished SCP number in vitro and diminished SC proliferation in neurofibroma bearing mice in vivo. These studies identify the purinergic receptor P2RY14 as a critical G-protein-coupled receptor (GPCR) in NF1 mutant SCPs and SCs and suggest roles for EGFR-GPCR crosstalk in facilitating SCP self-renewal and neurofibroma initiation via cAMP and EGFR-driven phospho-Akt.
γ-TuRCs are required for asymmetric microtubule nucleation from the somatic Golgi of Drosophila neurons
Authors: Mukherjee Amrita , Conduit Paul T. 
Published: September 2021

AbstractMicrotubules are polarised polymers nucleated by multi-protein γ-tubulin ring complexes (γ-TuRCs). Within neurons, microtubule polarity is plus-end-out in axons and mixed or minus-end-out in dendrites. Previously we showed that within the soma of Drosophila sensory neurons γ-tubulin localises asymmetrically to Golgi stacks, Golgi-derived microtubules grow asymmetrically towards the axon, and growing microtubule plus-ends are guided towards the axon and restricted from entering dendrite in a Kinesin-2-dependent manner (Mukerjee et al., 2020). Here we show that depleting γ-TuRCs perturbs the direction of microtubule growth from the Golgi stacks, consistent with a model for asymmetric microtubule nucleation involving γ-TuRCs and other nucleation-promoting factors. We also directly observe microtubule turning along microtubule bundles and show that depleting APC, proposed to link Kinesin-2 to plus ends, reduces microtubule turning and increases plus end growth into dendrites. These results support a model of asymmetric nucleation and guidance within the neuronal soma that helps establish and maintain overall microtubule polarity.
The retromer complex regulates C. elegans development and mammalian ciliogenesis
Authors: Xie Shuwei , Smith Ellie , Dierlam Carter , Mathew Danita , Davis Angelina , Williams Allana , Naslavsky Naava , Iyer Jyoti , Caplan Steve 
Published: September 2021

AbstractThe mammalian retromer is comprised of subunits VPS26, VPS29 and VPS35, and a more loosely-associated sorting nexin (SNX) heterodimer. Despite known roles for the retromer in multiple trafficking events in yeast and mammalian cells, its role in development is poorly understood, and its potential function in primary ciliogenesis remains unknown. Using CRISPR-Cas9 editing, we demonstrated that vps-26 homozygous knockout C. elegans have reduced brood sizes and impaired vulval development, as well as decreased body length which has been linked to defects in primary ciliogenesis. Since many endocytic proteins are implicated in the generation of primary cilia, we addressed whether the retromer regulates ciliogenesis in mammalian cells. We observed VPS35 localized to the primary cilium, and depletion of VPS26, VPS35 or SNX1/SNX5 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the capping protein, CP110, and was required for its removal from the mother centriole. Herein, we characterize new roles for the retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, and suggest a novel role for the retromer in CP110 removal from the mother centriole.
Synergistic effect of polybenzoxazine/ZrO2encapsulated polyurethane nanocomposite coatings for enhanced barrier properties of steel in seawater
Authors: Xavier Joseph Raj 
Published: September 2021

PurposeThe purpose of this study is to use polybenzoxazine (Pbz) functionalized ZrO2nanoparticles to synthesize polyurethane (PU)-PbZ/ZrO2nanocomposite. The results derived from the electrochemical impedance spectroscopy (EIS) and polarization studies indicated the superior anticorrosive activity of PU-Pbz/ZrO2nanocomposite coatings compared to those of plain PU coatings. The decreased corrosion current was detected on the scratch of the PU-Pbz/ZrO2nanocomposite-coated mild steel surface by scanning electrochemical microscopy (SECM) compared to other studied coatings. The superior anticorrosive and mechanical properties of the proposed nanocomposite coatings provide a new horizon in the development of high-performance anticorrosive coatings for various industries.Design/methodology/approachThe Pbz functionalized ZrO2nanoparticles were characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX) and thermogravimetric analysis (TGA) in terms of the structural, morphological and thermal properties of these coatings. A different formulation of coatings such as PU, PU-Pbz, PU-ZrO2and PU-Pbz/ZrO2were prepared and investigated for their corrosion protection performance on mild steel in natural seawater by electrochemical techniques. The surface morphological studies were done by SEM/EDX and XRD analysis.FindingsThe superior anticorrosive property of the proposed nanocomposite coatings provides a new horizon in the development of high-performance anticorrosive coatings for various industries. Addition of Pbz wrapped ZrO2nanoparticles into the PU coating resulted in the blockage of charge transfer at the metal/electrolyte interface, which reduced the dissolution of mild steel. It was revealed from the SEM/EDX analysis that the formation of the corrosion products at the metal/electrolyte interface behaved as the passive layer which reduced the dissolution of steel.Originality/valueThe inclusion of polybenzoxazine functionalized ZrO2nanoparticles to the polyurethane coating reinforces the barrier and mechanical properties of PU-Pbz/ZrO2nanocomposite, which is due to the synergistic effect of ZrO2and Pbz.
The role of buyer-seller guanxi facets and positions in social commerce: an analysis of the buyer's perspective in Taiwan
Authors: Wu Wen-Kuei , Wu Hsiao-Chung , Lai Chih-Sung 
Published: September 2021

PurposeThis study aims to explore how a buyer's perceived buyer-seller (B-S) guanxi facets (i.e. ganqing, renqing and mianzi) and guanxi positions (i.e. zi-ji-ren, shou-ren and sheng-ren) affect the seller's influence effectiveness (SIE) and purchase intention (PI) in social commerce.Design/methodology/approachThis study conducted an online survey in three cities of Taiwan and collected a total of 364 data. The structural equation modeling and cluster analysis were used to test research hypotheses.FindingsThe results indicate that (1) each guanxi facet exerts a different and positive impact on SIE, but only one guanxi facet – renqing – helps improve PI, (2) guanxi facets can be used to predict the buyer's perceived guanxi position toward the seller, (3) the effect of guanxi facets on SIE and PI varies across B-S guanxi positions and (4) the SIE positively mediates effects of guanxi facets on the PI.Originality/valueThis study demonstrates the individual effect of each guanxi facet on SIE and PI and affirms the implicit guanxi position features guanxi facets and determines the buyer's perceived SIE and PI as well. To the best of our knowledge, these findings are rarely proposed in previous research and are beneficial for understanding the guanxi mechanism in social commerce.
Peatland microhabitat heterogeneity drives phototrophic microbe distribution and photosynthetic activity
Authors: Hamard Samuel , Küttim Martin , Céréghino Regis , Jassey Vincent E. J. 
Published: September 2021

SummaryPhototrophic microbes are widespread in soils, but their contribution to soil carbon (C) uptake remains underexplored in most terrestrial systems, including C‐accreting systems such as peatlands. Here, by means of metabarcoding and ecophysiological measurements, we examined how microbial photosynthesis and its biotic (e.g., phototrophic community structure, biomass) and abiotic drivers (e.g., Sphagnum moisture, light intensity) vary across peatland microhabitats. Using a natural gradient of microhabitat conditions from pool to forest, we show that the structure of phototrophic microbial communities shifted from a dominance of eukaryotes in pools to prokaryotes in forests. We identified five groups of co‐occurring phototrophic operational taxonomic units with specific environmental preferences across the gradient. Along with such structural changes, we found that microbial C uptake was the highest in the driest and shadiest microhabitats. This study renews and improves current views on phototrophic microbes in peatlands, as the contribution of microbial photosynthesis to peatland C uptake has essentially been studied in wet microhabitats.
Risk of caesarean delivery in labour induction: a systematic review and external validation of predictive models
Authors: López‐Jiménez N , García‐Sánchez F , Hernández‐Pailos R , Rodrigo‐Álvaro V , Pascual‐Pedreño A , Moreno‐Cid M , Delgado‐Rodríguez M , Hernández‐Martínez A 
Published: September 2021

BackgroundDespite the existence of numerous published models predicting the risk of caesarean delivery in women undergoing induction of labour (IOL), validated models are scarce.ObjectivesTo systematically review and externally assess the predictive capacity of caesarean delivery risk models in women undergoing IOL.Search strategyStudies published up to 15 January 2021 were identified through PubMed, CINAHL, Scopus and ClinicalTrials.gov, without temporal or language restrictions.Selection criteriaStudies describing the derivation of new models for predicting the risk of caesarean delivery in labour induction.Data collection and analysisThree authors independently screened the articles and assessed the risk of bias (ROB) according to the prediction model risk of bias assessment tool (PROBAST). External validation was performed in a prospective cohort of 468 pregnancies undergoing IOL from February 2019 to August 2020. The predictive capacity of the models was assessed by creating areas under the receiver operating characteristic curve (AUCs), calibration plots and decision curve analysis (DCA).Main resultsFifteen studies met the eligibility criteria; 12 predictive models were validated. The quality of most of the included studies was not adequate. The AUC of the models varied from 0.520 to 0.773. The three models with the best discriminative capacity were those of Levine et al. (AUC 0.773, 95% CI 0.720–0.827), Hernández et al. (AUC 0.762, 95% CI 0.715–0.809) and Rossi et al. (AUC 0.752, 95% CI 0.707–0.797).ConclusionsPredictive capacity and methodological quality were limited; therefore, we cannot currently recommend the use of any of the models for decision making in clinical practice.Tweetable abstractPredictive models that predict the risk of cesarean section in labor inductions are currently not applicable.
Redback spider bites in children in South Australia: A 10‐year review of antivenom effectiveness
Authors: Cocks Jane , Chu Simon , Gamage Lalith , Rossaye Sasha , Schutz Jacquie , Soon Aun Woon (Cindy) 
Published: September 2021

AbstractObjectiveTo describe the South Australian paediatric redback spider bite experience and to examine the hypothesis that redback antivenom (RBAV) treatment in children is clinically effective.MethodsRetrospective chart review of all children under 18 years of age presenting to the EDs of the three major paediatric or mixed hospitals in Adelaide, South Australia, with a discharge diagnosis of redback spider envenomation between 1 January 2010 and 31 March 2020. The main outcome measures include: patient and bite demographics; presenting symptoms and signs; treatment provided; clinical effects at 2 h post RBAV administration on pain, diaphoresis, blood pressure, heart rate and systemic features; overall clinical impression of RBAV effectiveness and resolution of symptoms prior to discharge.ResultsThere were 256 patient encounters involving 235 patients. Latrodectism was described in one‐third (34%) of the cases. Sixty‐one patients received RBAV and in 57 (93%) patients the RBAV had good clinical effect. Two hours post RBAV administration, pain resolved in 71%, hypertension resolved in 62%, diaphoresis resolved in 43% and tachycardia resolved in 82%. There were no cases of urticaria or anaphylaxis and one case of serum sickness.ConclusionsThis retrospective review of redback spider envenomation in South Australian children over a 10‐year period has demonstrated clinical effectiveness of RBAV in paediatric patients across all age groups, observed in both clinician perceived results and measurable outcomes. RBAV remains an effective treatment for redback envenomation in children.
Identification of the β thalassemia allele β–50 and analysis of the hematology data of carriers in a southern Chinese population
Authors: Long Ju , Liu Enqi 
Published: September 2021

AbstractDuring a routine test, we identified a 38‐year‐old man who had a positive hematology screening result but was negative for hot spot variants of his thalassemia gene. Further analysis identified β–50 (HBB: c.‐100G>A). It was first suggested that β–50 was a β+‐thal allele, and some research groups suggested this allele was a silent β‐thal allele. To fully understand the hematological phenotype of the β–50 allele, we screened for individuals carrying β–50 in the general population and performed hematology analysis on these carriers. A real‐time PCR detection system was designed to verify samples carrying β–50. Twenty‐one thousand samples and 43 pedigree samples were screened, and 86 β–50 carriers were detected. We performed hematological analysis on 65 individuals older than 3 years who had normal serum ferritin and analyzed the data. A total of 34.62% of the β–50/βN individuals had mean cellular volume (MCV) or mean cellular hemoglobin (MCH) values slightly lower than the positive cutoff value of screening; the β–50 carriers’ Hb A2 value was slightly elevated. According to the test results, β–50 carriers have slight changes in hematology parameters, including slight decreases in MCV and MCH and slight increases in Hb A2; however, these effects do not reach the degree of traditional β+ alleles. Females with genotype β–50/β0 show a degree of decline in hematological indicators during pregnancy. Therefore, we should describe β–50 as a β++ thalassemia allele, and identification of β–50 can explain slight changes in hematological indicators in some carriers.