bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cis-Regulatory Atlas in Primary Human CD4+ T Cells
Authors: Stefan Kurtis , Barski Artem 
Published: December 2022

AbstractCis-regulatory elements (CRE) are critical for coordinating gene expression programs that dictate cell-specific differentiation and homeostasis. Recently developed self-transcribing active regulatory region sequencing (STARR-Seq) has allowed for genome-wide annotation of functional CREs. Despite this, STARR-Seq assays are only employed in cell lines, in part, due to difficulties in delivering reporter constructs. Herein, we implemented and validated a STARR-Seq–based screen in human CD4+ T cells using a non-integrating lentiviral transduction system. Lenti-STARR-Seq is the first example of a genome-wide assay of CRE function in human primary cells, identifying thousands of functional enhancers and negative regulatory elements (NREs) in human CD4+ T cells. Results of the screen were validated using traditional luciferase assays. Genome-wide, we find clear differences between enhancers and NREs in nucleosome positioning, chromatin modification, eRNA production, and transcription factor binding. Our findings support the idea of silencer repurposing as enhancers in alternate cell types. Collectively, these data suggest that Lenti-STARR-Seq is a can be used for CRE screening in primary human cell types.
Convergent adaptation of true crabs (Decapoda: Brachyura) to a gradient of terrestrial environments
Authors: Wolfe Joanna M. , Ballou Lauren , Luque Javier , Watson-Zink Victoria M. , Ahyong Shane T. , Barido-Sottani Joëlle , Chan Tin-Yam , Chu Ka Hou , Crandall Keith A. , Daniels Savel R. , Felder Darryl L. , Mancke Harrison , Martin Joel W. , Ng Peter K.L. , Ortega-Hernández Javier , Theil Emma Palacios , Pentcheff N. Dean , Robles Rafael , Thoma Brent P. , Tsang Ling Ming , Wetzer Regina , Windsor Amanda M. , Bracken-Grissom Heather D. 
Published: December 2022

AbstractFor much of terrestrial biodiversity, the evolutionary pathways of adaptation from marine ancestors are poorly understood, and have usually been viewed as a binary trait. True crabs, the decapod crustacean infraorder Brachyura, comprise over 7,600 species representing a striking diversity of morphology and ecology, including repeated adaptation to non-marine habitats. Here, we reconstruct the evolutionary history of Brachyura using new and published sequences of 10 genes for 344 tips spanning 88 of 109 brachyuran families. Using 36 newly vetted fossil calibrations, we infer that brachyurans most likely diverged in the Triassic, with family-level splits in the late Cretaceous and early Paleogene. By contrast, the root age is underestimated with automated sampling of 328 fossil occurrences explicitly incorporated into the tree prior, suggesting such models are a poor fit under heterogeneous fossil preservation. We apply recently defined trait-by-environment associations to classify a gradient of transitions from marine to terrestrial lifestyles. We estimate that crabs left the marine environment at least seven and up to 17 times convergently, and returned to the sea from non-marine environments at least twice. Although the most highly terrestrial- and many freshwater-adapted crabs are concentrated in Thoracotremata, Bayesian threshold models of ancestral state reconstruction fail to identify shifts to higher terrestrial grades due to the degree of underlying change required. Lineages throughout our tree inhabit intertidal and marginal marine environments, corroborating the inference that the early stages of terrestrial adaptation have a lower threshold to evolve. Our framework and extensive new fossil and natural history datasets will enable future comparisons of non-marine adaptation at the morphological and molecular level. Crabs provide an important window into the early processes of adaptation to novel environments, and different degrees of evolutionary constraint that might help predict these pathways.
Quinazoline-quinoline bisubstrate inhibitors target eukaryotic translation initiation factor 3 inPlasmodium falciparum
Authors: Dobrescu Irina , Hammam Elie , Dziekan Jerzy M. , Claës Aurélie , Halby Ludovic , Preiser Peter , Bozdech Zbynek , Arimondo Paola B. , Scherf Artur , Nardella Flore 
Published: December 2022

AbstractMalaria drug resistance is hampering the fight against the deadliest parasitic disease affecting over 200 million people worldwide. We recently developed quinoline-quinazoline-based inhibitors (as compound70) as promising new antimalarials. Here we aimed to investigate their mechanism of action by using Thermal Proteome Profiling (TPP). The eukaryotic translation initiation factor 3 (EIF3i) subunit I was identified as the main target of the inhibitor inP. falciparum. This protein is not a known drug target in malaria parasites.P. falciparumparasite lines were generated expressing either a HA tag or an inducible knockdown of the PfEIF3i gene to further characterize the target protein. PfEIF3i was stabilized in presence of the compound70in a cellular thermal shift-western blot assay, confirming that PfEIF3i is a target of quinoline-quinazoline-based inhibitors. In addition, PfEIF3i-inducible knock-down blocks intra-erythrocytic development in the trophozoite stage indicating that it has a vital function. We show that PfEIF3i is mostly expressed in late intraerythrocytic stages and localizes in the cytoplasm. Previous mass spectrometry reports show that EIF3i is expressed in all parasite life cycle stages. Hence, quinoline-quinazoline-based inhibitors allowed to identify PfEIF3i as a valuable target for the design of new antimalarial drugs active all along the life cycle of the parasite.
The SUMO-interacting Motif in NS2 promotes adaptation of avian influenza virus to mammals
Authors: Sun Liuke , Kong Huihui , Yu Mengmeng , Zhang Zhenyu , Zhang Haili , Na Lei , Qu Yuxing , Zhang Yuan , Chen Hualan , Wang Xiaojun 
Published: December 2022

SUMMARYSpecies differences in the host factor ANP32A/B result in the restriction of avian influenza virus polymerase (vPol) in mammalian cells. Efficient replication of avian influenza viruses in mammalian cells often requires adaptive mutations, such as PB2-E627K, to enable the virus to utilize mammalian ANP32A/B. However, the molecular basis for the productive replication of avian influenza viruses without prior adaptation in mammals remain poorly understood. We show that influenza A virus protein NS2 help to overcome mammalian ANP32A/B-mediated restriction to avian vPol activity by promoting avian vRNP assembly and enhancing mammalian ANP32A/B-vRNP interactions. A conserved SUMO interaction motif (SIM) in NS2 is required for its avian polymerase-enhancing properties. We also demonstrate that disrupting SIM integrity in NS2 impairs avian influenza virus replication and pathogenicity in mammalian hosts, but not in avian hosts. Our results identify NS2 as a cofactor in the adaptation process of avian influenza viruses to mammals.
A retrospective study of knowledge management for integrated resorts (IRs) crisis preparedness
Authors: Zhang Su , Hsu Fu-Chieh , Zhang Yang 
Published: December 2022

Purpose
This study aims to propose a systematic knowledge management model to explore the causal links leading to the organizational crisis preparedness (OCP) level of integrated resorts (IRs) during the COVID-19 pandemic based on the intangible capital of organizational climate, dynamic capability, substantive capability and commitment.

Design/methodology/approach
The authors use data obtained from IRs in Macau. The Wuli–Shili–Renli (WSR) approach underpins the study. Structural equation modeling following fuzzy-set qualitative comparative analysis (fsQCA) was used for data processing.

Findings
The results showed that organizational climate has an essential role in IRs preparedness for crises and affects their dynamic capacity, substantive capacity and commitment. The fsQCA results revealed that the relationships between conditions with a higher level of dynamic and substantive capability lead to higher OCP scores.

Practical implications
Executives should develop systemic thinking regarding organization preparedness in IRs for crisis management. A comprehensive understanding of the IRs’ business environment and crises is necessary, as they will require different factor constellations to allow the organization to perform well in a crisis. Financial support for employees could ensure their assistance when dealing with such situations. Rapid response teams should be set up for daily operations and marketing implementation of each level of the IRs management systems.

Originality/value
This study contributes to the extant literature on IRs crisis management in the OCP aspect. The authors constructed a systematic composite picture of organization executives’ knowledge management through the three layers of intangible capitals in WSR. Moreover, the authors explored causal links of WSR from symmetric and asymmetric perspectives.
Invasive plants have greater growth than co‐occurring natives in live soil subjected to a drought‐rewetting treatment
Authors: Zhang Xue , Oduor Ayub M. O. , Liu Yanjie 
Published: December 2022

Abstract

Several studies have shown that invasive plant species respond more negatively to drought than native plant species, but little remains understood of how and whether drought‐rewetting events may affect growth of invasive and co‐occurring native plant species both directly and indirectly through soil microorganisms.

In a fully crossed factorial design, we grew individuals of four congeneric pairs of invasive and native plant species in 2.5 L pots that contained live or sterilized field soil under one of three drought treatments: no‐drought, drought, drought‐rewetting.

Results show that drought caused a significantly greater decline in total biomass of invasive plant species than that of native plant species regardless of the presence of live soil microorganisms. However, total biomass of the invasive plant species exhibited a greater recovery from drought following rewetting than did that of the native plant species. Moreover, recovery from drought in invasive plant species tended to be stronger in live soil than in sterilized soil, while for the native plant species, recovery from drought was stronger in sterilized soil than in live soil.

Overall, these results suggest that in ecosystems that experience cycles of drought and rewetting, invasive plant species may grow larger than co‐occurring native plant species. Moreover, soil microorganisms may facilitate greater recovery from drought in invasive plant species than in co‐occurring native plant species.

Read the free Plain Language Summary for this article on the Journal blog.
Sex‐specific differences in T‐cell immune dysregulation and aberrant response to inflammatory stimuli in offspring exposed to maternal chronic inflammation
Authors: Liu Jin , Liu Yang , Kirschen Gregory , Liu Anguo , Lei Jun , Burd Irina 
Published: December 2022

AbstractProblemsMaternal chronic inflammation (MI) can adversely affect offspring's immune development resulting in dysregulation of splenic T cells. Interleukin 1 beta (IL‐1β) contributes to mediating inflammation in the placenta to induce fetal toxicity and cause long‐term postnatal sequelae. In this study, we investigated how MI affects the T‐cell immune development from the fetal to the neonatal period and how offspring responded to postnatal IL‐1β challenge when exposed to an adverse intrauterine environment. We also extend these studies to examine the sex‐specific differences.Methods of StudyTime‐pregnant CD1 dams were administrated with four consecutive injections of mouse recombinant Interleukin‐1β (rIL‐1β) or phosphate‐buffered saline (PBS) from embryonic day (E)14 to E17. Pups were treated with rIL‐1β or PBS at postnatal day (PND)11 (pre‐weaning) or PND24 (post‐weaning). Pups’ splenic immune cells were isolated and then characterized using flow cytometry.ResultsAt PND12, no differences were observed either in Ctrl or MI offspring. At PND25, we observed elevated amount of CD8+ T cells, descending CD4+/CD8+ and Treg/Teff ratio in MI offspring. Pre‐weaning rIL‐1β administration did not affect T‐cell subpopulation in Ctrl pups while post‐weaning rIL‐1β administration increased T cells and CD8+ T cells and decreased CD4+/CD8+ and Treg/Teff ratio in Ctrl offspring. Furthermore, pre‐weaning rIL‐1β administration decreased the frequency of T cells and Treg/Teff ratio in MI pups while post‐weaning rIL‐1β administration increased Tregs and Treg/Teff in MI pups. Regarding sex‐specific changes, we observed that at PND12, MI females exhibited higher CD4+/CD8+ and Treg/Teff ratio than Ctrl females. At PND25, we observed elevated amount of CD8+ T cells, descending CD4+/CD8+ and Treg/Teff ratio in MI Females, while MI males did not show any changes in T‐cell population. Pre‐weaning rIL‐1β administration decreased T‐cell frequency in both MI males and females and decreased Treg/Teff ratio only in MI females. Post‐weaning rIL‐1β administration increased Tregs and Treg/Teff ratio, and decreased CD4+/CD8+ ratio in MI females.ConclusionsPrenatal‐inflammation‐exposed offspring exhibited dysfunctional T‐cell immunity and regulatory immune responses to postnatal challenges, showing both sex‐specific and age‐dependent differences. It could be speculated from our results that experiencing environmental challenges or adverse stimuli during the vulnerable intrauterine period, such as maternal chronic inflammation, stress, preterm birth, and chronic infections, might induce fetal immune reprogramming and potentially cause long‐term adverse immune consequences, such as a predisposition to allergic diseases, autoimmune diseases, asthma and pediatric mortality of unknown etiology.
School principals' mental health and well‐being under threat: A longitudinal analysis of workplace demands, resources, burnout, and well‐being
Authors: Marsh Herbert W. , Dicke Theresa , Riley Phil , Parker Philip D. , Guo Jiesi , Basarkod Geetanjali , Martin Andrew J. 
Published: December 2022

AbstractSchools are critical organisational settings, and school principals face extreme stress levels. However, there are few large‐scale, longitudinal studies of demands and resources that drive principals' health and well‐being. Using the Job Demands‐Resources (JD‐R) framework, we evaluated longitudinal reciprocal effects over 3 years relating to job demands, job resources (resilience), job‐related outcomes (burnout and job satisfaction), and personal outcomes (happiness and physical health) for a nationally representative sample of 3683 Australian school principals. Prior demands and resources led to small changes in subsequent outcomes, beneficial effects of resources, and adverse effects of demands, particularly for job‐related outcomes. Furthermore, we also found reverse‐reciprocal effects, prior outcomes (burnout and job satisfaction) influencing subsequent job characteristics. However, in response to substantively and theoretically important research questions, we found no support for Yerkes–Dodson Law (nonlinear effects of demands) or Nietzsche effects and inoculation effects (that which does not kill you, makes you stronger; manageable levels of demands build resilience). Relating our study to new and evolving issues in JD‐R research, we offer limitations of our research—and JD‐R theory and research more generally—and directions for further research in this essentially unstudied application of JD‐R to school principals' mental health and well‐being.
Generative models for visualizing idiosyncratic impressions
Authors: Todorov Alexander , Uddenberg Stefan , Albohn Daniel 
Published: December 2022

AbstractIn their comprehensive review of research on impressions from faces, Sutherland and Young (this issue) highlight both the remarkable progress and the many challenges facing the field. We focus on two of the challenges: the need for generative, powerful models of impressions and the idiosyncratic nature of complex impressions.
Soluble epoxide hydrolase inhibition enhances production of specialized pro‐resolving lipid mediator and promotes macrophage plasticity
Authors: Abdalla Henrique B. , Alvarez Carla , Wu Yu‐Chiao , Rojas Paola , Hammock Bruce D. , Maddipati Krishna R. , Trindade‐da‐Silva Carlos Antonio , Soares Mariana Q. S. , Clemente‐Napimoga Juliana T. , Kantarci Alpdogan , Napimoga Marcelo H. , Van Dyke Thomas E. 
Published: December 2022

Background and PurposeEpoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFA) are lipid mediators that are rapidly inactivated by soluble epoxide hydrolase (sEH). Uncontrolled and chronic inflammatory disorders fail to sufficiently activate endogenous regulatory pathways, including the production of specialized pro‐resolving mediators (SPMs). Here, we addressed the relationship between SPMs and the EET/sEH axis and explored the effects of sEH inhibition on resolving macrophage phenotype.Experimental ApproachMice were treated with a sEH inhibitor, EETs, or sEH inhibitor + EETs (combination) before ligature placement to induce experimental periodontitis. Using RT‐qPCR, gingival samples were used to examine SPM receptors and osteolytic and inflammatory biomarkers. Maxillary alveolar bone loss was quantified by micro‐CT and methylene blue staining. SPM levels were analysed by salivary metabolo‐lipidomics. Gingival macrophage phenotype plasticity was determined by RT‐qPCR and flow cytometry. Effects of sEH inhibition on macrophage polarization and SPM production were assessed with bone marrow‐derived macrophages (BMDMs).Key ResultsPharmacological inhibition of sEH suppressed bone resorption and the inflammatory cytokine storm in experimental periodontitis. Lipidomic analysis revealed that sEH inhibition augmented levels of LXA4, RvE1, RvE2, and 4‐HDoHE, concomitant with up‐regulation of LTB4R1, CMKLR1/ChemR23, and ALX/FPR2 SPM receptors. Notably, there is an impact on gingival macrophage plasticity was affected suggesting an inflammation resolving phenotype with sEH inhibition. In BMDMs, sEH inhibition reduced inflammatory macrophage activation, and resolving macrophages were triggered to produce SPMs.Conclusion and ImplicationsPharmacological sEH inhibition increased SPM synthesis associated with resolving macrophages, suggesting a potential target to control osteolytic inflammatory disorders.
Comparative validity of three simulation platforms for objective assessment of otoscopy skills
Authors: Rotimi Oloruntobi , Haymes Adam , Dodds Isobel , Bhutta Mahmood 
Published: December 2022

AbstractObjectivesTo assess the face, construct and content validity of three different platforms for otoscopy skills assessment, using a traditional otoscope with manikin, digital otoscope (Tympahealth) with manikin, and traditional otoscope with a low‐cost model ear (SimEar).DesignProspective mixed methods study.SettingTertiary hospital.ParticipantsPostgraduate trainees and expert assessors.Main Outcome MeasuresFace and Content validity based on expert assessor ranking on each model and their feedback from semi‐structured interviews. Construct validity based on Objective Structured Clinical Examination scores.ResultsEach platform differed in face, construct and content validity scores, with no one platform consistently outperforming others. Three main themes were identified during thematic analysis of expert assessor interviews: ability to assess what is seen, anatomical reality, and ease of use. The low‐cost model showed greatest potential, where modification to include a silicone ear could lead to high validity with marginal increase in cost.ConclusionSeveral modalities for assessing otoscopy skills exist, each with advantages and disadvantages. Modifications to a low‐cost model, for use with either a traditional or digital otoscope, could prove to be the best model.
Sensitivity and specificity of 3 Tesla magnetic resonance imaging and multidetector computed tomographic tenography to identify artificially induced soft tissue lesions in the equine cadaveric digital flexor tendon sheath
Authors: Aßmann Anton D. , Ohlerth Stefanie , Torgerson Paul R. , Bischofberger Andrea S. 
Published: December 2022

SummaryBackgroundA common cause of lameness in horses is tenovaginitis of the digital flexor tendon sheath (DFTS). Ultrasound and contrast tenography have become frequently used diagnostic tools for abnormalities in the DFTS, but are considered insufficiently accurate in describing specific lesions.ObjectivesTo determine the sensitivity and specificity of computed tomographic tenography (CTT) and 3 Tesla magnetic resonance imaging (MRI) to detect artificial lesions within the DFTS.Study designBlinded laboratory study.MethodsUsing an arthroscopic hook knife, lesions (10–20 mm long and 3–5 mm deep; n = 52) were created tenoscopically in the superficial digital flexor tendon (SDFT), deep digital flexor tendon (DDFT), manica flexoria (MF) and proximal scutum in 19 distal limb specimens. MRI and CTT were performed and images were reviewed. Sensitivity and specificity were calculated for each modality and compared.ResultsComputed tomographic tenography and MRI identification of SDFT and MF lesions showed similar sensitivity (75% vs. 85%, respectively; p = 1) and specificity for MF lesions (96% for both). SDFT lesions specificity was similar for CTT versus MRI (85% vs. 77%, respectively; p = 0.88). For DDFT lesions, MRI sensitivity (62%) was higher compared to CTT (38%), although not statistically significant (p = 0.58). MRI specificity (92%) was lower than CTT (96%, p = 1). Lesions in the proximal scutum were more frequently identified by MRI compared to CTT (sensitivity: 93% vs. 57%, p = 0.17; specificity: 96% vs. 100%, p = 1).Main limitationsArtificial, small lesions were assessed. An incomplete arthroscopic portal seal resulted in pressure loss and contrast leakage.ConclusionsThe sensitivity and specificity of both modalities are good to excellent for the diagnosis of most artificially created lesions. CTT performed similarly to MRI in detecting SDFT and MF lesions. MRI showed a higher sensitivity for the diagnosis of DDFT and proximal scutum lesions. The results indicate a future application of CTT for the diagnosis of DFTS pathologies, whenever suspecting MF tears.