bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular localization of GPCR kinases differentially modulate biased signaling at CXCR3
Authors: Gardner Julia , Eiger Dylan Scott , Hicks Chloe , Choi Issac , Pham Uyen , Rajagopal Sudarshan 
Published: July 2022

ABSTRACTSome G protein-coupled receptors (GPCRs) demonstrate biased signaling, where ligands of the same receptor differentially activate specific downstream signaling pathways over others. Ligand-specific receptor phosphorylation by GPCR kinases (GRKs) is one mechanism underlying this phenomenon. Recent evidence demonstrates that GPCRs traffic to and signal from subcellular compartments beyond the plasma membrane, a paradigm termed location bias. Here, we show that GRKs translocate to endosomes following stimulation of the chemokine receptor CXCR3 and other GPCRs. The GRK recruitment patterns at the plasma membrane and endosome are distinct and depend on the identity of the ligand used to activate the receptor. Using cells deficient of GRKs, we demonstrate that biased ligands have unique signaling profiles upon rescue of location-specific GRK isoforms. Our work highlights a role of the GRKs in location-biased GPCR signaling and demonstrates the complex interactions between ligand, GRK isoform and cellular location that contribute to biased signaling.
Context-dependent differences in the functional responses of Lactobacillaceae strains to fermentable sugars
Authors: Suissa Ronit , Oved Rela , Maan Harsh , Gilhar Omri , Meijler Michael , Koren Omry , Kolodkin-Gal Ilana 
Published: July 2022

AbstractLactobacillaceae are Gram-positive rods, facultative anaerobes, and belong to the lactic acid bacteria (LAB) that frequently serve as probiotics. We systematically compared five LAB strains for the effects of different carbohydrates on their free-living and biofilm lifestyles. We found that fermentable sugars triggered a heterogeneous response in LAB strains, frequently manifested specifically in altered carrying capacity during planktonic growth and colony development. The fermentation capacities of the strains were compatible and could not account for heterogeneity in their differential carrying capacity in liquid and on a solid medium. Among tested LAB strains, L. paracasei, and L. rhamanosus GG survived self-imposed acid stress while L. acidophilus was extremely sensitive to its own glucose utilization acidic products. The addition of a buffering system during growth on a solid medium significantly improved the survival of most tested probiotic strains during fermentation. We suggest that the optimal performance of the beneficial microbiota members belonging to lactobacilli is heterogeneous and varies as a function of the growth model and the dependency on a buffering system.
Activating and repressing gene expression between chromosomes during stochastic fate specification
Authors: Urban Elizabeth A. , Chernoff Chaim , Layng Kayla Viets , Han Jeong , Anderson Caitlin , Konzman Daniel , Johnston Robert J. 
Published: July 2022

AbstractDNA elements act across long genomic distances to regulate gene expression in processes including enhancer-promoter interactions and imprinting. During the gene-regulatory phenomenon of transvection in Drosophila, DNA elements on one allele of a gene act between chromosomes to increase or decrease expression of another allele of the gene. Despite the discovery of transvection over 60 years ago, little is known about its biological role. Furthermore, how different cis regulatory DNA elements contribute to the activation or repression of transvection at distinct times during development is unclear. Here, we studied the stochastic expression of spineless (ss) in developing photoreceptors in the fly eye to understand gene activation and repression between chromosomes. We identified a biological role for transvection in regulating expression of naturally occurring ss alleles. We characterized CRISPR-engineered deletions of sequences across the ss locus and identified DNA elements required for activating and repressing transvection. We found that different enhancers participated in transvection at different times during development to promote gene expression and specify cell fates. Bringing a silencer element on a heterologous chromosome into proximity with the ss locus “reconstituted” the gene, leading to repression. Our studies show that transvection regulates gene expression via distinct DNA elements at specific timepoints in development, with implications for genome organization and architecture.
HP1-driven phase separation recapitulates the thermodynamics and kinetics of heterochromatin condensate formation
Authors: Tortora Maxime M.C. , Brennan Lucy D. , Karpen Gary , Jost Daniel 
Published: July 2022

ABSTRACTThe spatial segregation of pericentromeric heterochromatin (PCH) into distinct, membrane-less nuclear compartments involves the binding of Heterochromatin Protein 1 (HP1) to H3K9me2/3-rich genomic regions. While HP1 exhibits liquid-liquid phase separation propertiesin vitro, its mechanistic impact on the structure and dynamics of PCH condensate formationin vivoremains largely unresolved. Here, using biophysical modeling, we systematically investigate the mutual coupling between self-interacting HP1-like molecules and the chromatin polymer. We reveal that the specific affinity of HP1 for H3K9me2/3 loci facilitates coacervationin nucleo, and promotes the formation of stable PCH condensates at HP1 levels far below the concentration required to observe phase separation in purified protein assaysin vitro. These heterotypic HP1-chromatin interactions give rise to a strong dependence of the nucleoplasmic HP1 density on HP1-H3K9me2/3 stoichiometry, consistent with the thermodynamics of multicomponent phase separation. The dynamical crosstalk between HP1 and the viscoelastic chromatin scaffold also leads to anomalously-slow equilibration kinetics, which strongly depend on the genomic distribution of H3K9me2/3 domains, and result in the coexistence of multiple long-lived, microphase-separated PCH compartments. The morphology of these complex coacervates is further found to be governed by the dynamic establishment of the underlying H3K9me2/3 landscape, which may drive their increasingly abnormal, aspherical shapes during cell development. These findings compare favorably to 4D microscopy measurements of HP1 condensates that we perform in liveDrosophilaembryos, and suggest a general quantitative model of PCH formation based on the interplay between HP1-based phase separation and chromatin polymer mechanics.SIGNIFICANCE STATEMENTThe compartmentalization of pericentromeric heterochromatin (PCH), the highly-repetitive part of the genome, into membrane-less organelles enriched in HP1 proteins, is critical to both genetic stability and cell fate determination. While HP1 can self-organize into liquid-like condensatesin vitro, the roles of HP1 and the polymer chromatin in forming 3D PCH domainsin vivoare still unclear. Using molecular simulations, we show that key kinetic and thermodynamic features of PCH condensates are consistent with a phase-separation mode of organization driven by the genomic distribution of methylated domains and HP1 self-attraction and affinity for heterochromatin. Our predictions are corroborated by live-microscopy performed during early fly embryogenesis, suggesting that a strong crosstalk between HP1-based phase separation and chromosome mechanics drive PCH condensate formation.
Non-isolated neural tube defects with comorbid malformations are responsive to population-level folic acid supplementation in Northern China
Authors: Che Xiaoyu , Liu Jufen , Galea Gabriel L. , Zhang Yali , Greene Nicholas D. E. , Zhang Le , Jin Lei , Wang Linlin , Ren Aiguo , Li Zhiwen 
Published: July 2022

AbstractBackgroundComorbid congenital malformation of multiple organs may indicate shared genetic/teratogenic causality. Folic acid supplementation reduces population-level prevalance of isolated neural tube defects (NTDs), but whether complex cases involving independent malformtions are also repsonsive is unknown. We aimed to describe the epidemiology of NTDs with comorbid malformations in a Chinese population and assess the impact of folic acid supplementation.MethodsData from five counties in northern China were obtained between 2002 to 2021 through a population-based birth defects surveillance system. All live births, stillbirths, and terminations because of NTDs at any gestational age were recorded. NTDs were classified as spina bifida, anaecephaly or encephalocele. Isolated NTDs included spina bifida cases with presumed secondary malformations (hydrocephalus, hip dislocation, talipes). Non-isolated NTDs were those with independent concomittant malformations.ResultsA total of 296,306 births and 2,031 cases of NTDs were recorded in 2002-2021. 4.8 % of NTDs (97/2031) had comorbid defects, which primarily affected the abdominal wall (25/97), musculoskeletal system (24/97), central nervous system (22/97), and face (15/97). The relative risk of cleft lip or/and palate, limb reduction defects, hip dislocation, gastroschisis, omphalocele, hydrocephalus and urogenital system defects was significantly greater in infants with NTDs than the general population. Population-level folic acid supplementation significantly reduced the prevalence of both isolated and non-isolated NTDs.ConclusionEpidemiologically, non-isolated NTDs follow similar trends as isolated cases and are responsive to primary prevention by folic acid supplementation. Various clinically-important congenital malformations are over-represented in individuals with NTDs, suggesting common etiology.
Is anybody ‘Learning’ from Deaths? Sequential content and reflexive thematic analysis of national statutory reporting within the NHS in England 2017-2020
Authors: Brummell Z , Braun D , Hussein Z , Moonesinghe SR , Vindrola-Padros C 
Published: July 2022

AbstractIntroductionThe imperative to learn when a patient dies due to problems in care is absolute. In 2017, the Learning from Deaths (LfDs) framework, a countrywide patient safety programme, was launched in the National Health Service (NHS) in England. NHS Secondary Care Trusts (NSCTs) are legally required to publish quantitative and qualitative information relating to deaths due to problems in care within their organisation, including any learning derived from these deaths.MethodAll LfDs report from 2017 – 2020 were reviewed and evaluated, quantitatively and qualitatively using sequential content and reflexive thematic analysis, through a critical realist lens.ResultsThe majority of NSCTs have identified learning, actions and, to a lesser degree, assessed the impact of these actions. The most frequent learning relates to missed/delayed/uncoordinated care and communication/cultural issues. System issues and lack of resources feature infrequently. There is significant variation amongst NSCTs as to what ‘learning’ in this context actually means and a lack of oversight combining patient safety initiatives.DiscussionEngagement of NSCTs with the LfDs programme varies significantly. Learning as a result of the LfDs programme is occurring. The significance or value of this learning in preventing future patient deaths remains unclear. Consensus about what constitutes effective learning with regards to patient safety needs to be defined and agreed upon.
Comparative analysis of retracted pre-print and peer-reviewed articles on COVID-19
Authors: Sra Manraj Singh , Arora Mehak , Mazumder Archisman , Goyal Ritik Mahaveer , Parameswaran Giridara G , Meena Jitendra Kumar 
Published: July 2022

AbstractIntroductionDue to the accelerated pace and quantum of scientific publication during the COVID-19 pandemic, a large number of articles on COVID-19 have been retracted. Pre-prints though not peer-reviewed offer the advantage of rapid dissemination of new findings. In this study, we aim to systematically compare the article characteristics, time to retraction, social media attention, citations, and reasons for retraction between retracted pre-print and peer-reviewed articles on COVID-19.MethodsWe utilized the Retraction Watch database to identify retracted articles on COVID-19 published from 1stJanuary 2020 to 10thMarch 2022. The articles were reviewed and metadata such as article characteristics (type, category), time to retraction, reasons for retraction, and Altmetric Attention Score (AAS) and citation count were collected.ResultsWe identified 40 retracted pre-prints and 143 retracted peer-reviewed articles. The median (IQR) retraction time for pre-print and peer-reviewed articles was 29 (10-81.5) days and 139 (63-202) days (p = 0.0001). Pre-prints and peer-reviewed article had median (IQR) AAS of 26.5 (4-1155) and 8 (1-38.5), respectively (p = 0.0082). The median (IQR) citation count for pre-prints and peer-reviewed articles was 3 (0-14) and 3 (0-17), respectively (p = 0.5633). The AAS and citation counts were correlated for both pre-prints (r = 0.5200, p = 0.0006) and peer-reviewed articles(r = 0.5909, p = 0.0001). The commonest reason for retraction for pre-prints and peer-reviewed articles concerns about data and results.ConclusionThe increased adoption of pre-prints results in faster identification of erroneous articles compared to the traditional peer-review process.
Early-life inflammatory markers and subsequent episodes of depression and psychotic experiences in the ALSPAC birth cohort
Authors: Edmondson-Stait A. J. , Shen X. , Adams M. J. , Barbu M. C. , Jones H. J. , Miron V. E. , Allardyce J. , Boardman J. P. , Lawrie S. M. , McIntosh A. M. , Khandaker G. M. , Kwong A. S. F. , Whalley H. C. 
Published: July 2022

AbstractBackgroundInflammation is implicated in depression and psychosis, including association of childhood inflammatory markers on the subsequent risk of developing symptoms. However, it is unknown whether early-life inflammatory markers are associated with the number of depressive and psychotic symptoms from childhood to adulthood.MethodsUsing the prospective Avon Longitudinal Study of Children and Parents birth cohort (N=up-to 6,401), we have examined longitudinal associations of early-life inflammation [exposures: interleukin-6 (IL-6), C-reactive protein (CRP) levels at age 9y; IL-6 and CRP DNA-methylation (DNAm) scores at birth and age 7y; and IL-6 and CRP polygenic risk scores (PRSs)] with the number of depressive episodes and psychotic experiences (PEs) between ages 10-28 years. Psychiatric outcomes were assessed using the Short Mood and Feelings Questionnaire and Psychotic Like Symptoms Questionnaires, respectively. Exposure-outcome associations were tested using negative binomial models, which were adjusted for metabolic and sociodemographic factors.ResultsSerum IL-6 levels at age 9y were associated with the total number of depressive episodes between 10-28y (n=4,262; β=0.086; 95%CI:0.036-0.137; pFDR=0.009). CRP DNAm score at birth was associated with total number of PEs, size but this association did not survive correction for multiple testing (n=822; β=0.204; 95%CI:0.024-0.388; puncorrected=0.027; pFDR=0.252). Other immune measures were not associated with depression or PEs.ConclusionsEarly-life inflammatory markers are associated with the burden of depressive episodes and of PEs subsequently from childhood to adulthood. These findings support a potential role of early-life inflammation in the aetiology of depression and psychosis and highlight inflammation as a potential target for treatment and prevention.
Tejas functions as a core component of nuage assembly and precursor processing inDrosophilapiRNA biogenesis
Authors: Lin Yuxuan , Suyama Ritsuko , Kawaguchi Shinichi , Iki Taichiro , Kai Toshie 
Published: July 2022

SUMMARYPiwi-interacting RNAs (piRNAs), a class of 23- to 29-nt gonad-specific small RNAs, function to combat transposons in gonads. piRNAs are thought to be processed and amplified in membrane-less granules called nuage in germline cells. InDrosophila, two PIWI family proteins, several Tudor-domain containing (Tdrd) proteins and RNA helicases are assembled at perinuclear region of germline cells, forming nuage to process into piRNAs. Among those, Tejas (Tej), a fly homolog of mouse Tdrd5, has been known as a robust nuage component required for piRNA biogenesis in germline cells, yet its molecular functions remained elusive. To understand its molecular basis on nuage assembly and functions for piRNA biogenesis, we investigated subcellular localization of fluorescent-tagged nuage proteins including Tej and monitored the behavior of piRNA precursors. Tej functions as a core component for assembly of Vasa and Spindle-E to nuage granules through distinct motifs, respectively. The loss of Tej function resulted in malformation of nuage and accumulation of piRNA precursorsen routein processing, perturbing further piRNA biogenesis in germline cells. Our study also revealed that the low complexity region of Tej regulates the mobility of nuage by phase separation. Collectively, we propose that Tej plays a pivotal role in processing of piRNA precursors by assembling RNA helicases, Vasa and Spindle-E, to nuage, by controlling the dynamics of nuage components.
Traditional communities and dietary habits: understanding the dynamics of food and climate change in the western Himalayan region
Authors: Das Suraj , Mishra Anindya Jayanta 
Published: July 2022

PurposeThe present exploratory study aimed (1) to explore the traditional dietary habits of local communities, (2) to analyze the shift in traditional eating practices and (3) to examine the changes observed in socio-cultural beliefs system due to climate change.Design/methodology/approachA cross-sectional study was conducted with purposive sampling of 210 households in the select ten villages of the western Himalayan region. Open-ended interview questionnaires and a close-ended survey on a 5-point Likert scale are used. Statistical Package for the Social Sciences (SPSS) version 24 is used for the exploratory factor analysis. Further, Atlas-ti version 8 is also employed for thematic analysis.FindingsThe exploratory and thematic analysis illustrated that socio-ecological beliefs are crucial in food choices, but cultural beliefs are also changing due to climate change. Thus, the shift in socio-cultural beliefs can significantly affect the nutritional security of the indigenous societies during climate-induced emergencies in the mountain regions.Practical implicationsTherefore, the findings of the study are significant for a comprehensive understanding of the traditional dietary practice of the indigenous community for an evidence-based inclusive food security and climate change adaptation policy.Originality/valueThe inclusion of cultural practices is evident for ensuring the nutritional security. But, the magnitude of the climate-induced impacts on customary societies is not yet fully understood. Thus, the current study was conducted.
MNEs’ corporate governance disclosure: a strategic response to corrupt environments
Authors: Juliao-Rossi Jorge , Losada-Otalora Mauricio , Católico-Segura Diego Fernando 
Published: July 2022

Purpose
This study aims to examine how corruption influences the voluntary disclosure of corporate governance (CG)-related information by developed country multinationals (DC-MNEs) and emerging market multinationals (EM-MNEs) investing in six Latin American countries.

Design/methodology/approach
The study uses information from 300 MNEs included in the 2018 ranking of the 500 Largest Latin American companies (America Economía, 2018). Each MNE’s final annual report for the financial year ending 2018 was examined and coded to obtain the corporate governance disclosure index. Fractional probit regression was applied to test the hypotheses of the research.

Findings
DC-MNEs disclose more CG-related information in corrupt environments than EM-MNEs. This differentiated behavior occurs because DC-MNEs face higher legitimacy pressures in corrupt environments than EM-MNEs and because EM-MNEs are more experienced than DC-MNEs in dealing with such corrupt environments.

Practical implications
While both EM-MNEs and DC-MNEs need to continue investing in corrupt countries to grow, they need to disclose CG-related information as a strategic tool to manage the legitimacy issues triggered by corruption in the markets they operate.

Originality/value
Despite corruption being pervasive in emerging markets, its implications for firms’ strategic behaviors are still under-researched. This paper extends the scope of corporate governance and international business fields by studying how MNEs respond to relevant dimensions of the macro environment. This research shows that voluntary disclosure of CG-related information is a strategic response of the MNEs to gain legitimacy in corrupt environments.
A framework for continuation of digitalization in construction: a PLS-SEM approach
Authors: Bajpai Avirag , Misra Subhas C. 
Published: July 2022

PurposeIndian construction firms are falling behind in the use of digital technology in the workplace, and this study aims to give a framework and assess the role of enablers in the implementation and continuing digitalization of the Indian construction sector.Design/methodology/approachAn exploratory qualitative research technique is used in this article, and multiple detailed interviews and surveys are done with professionals from the industry and academia. To conclude the significance and relevance of the different constructs and indicators, the partial least square-structural equation modeling (PLS-SEM) approach is used.FindingsBarriers are essential enablers for effective implementation, while success factors are important drivers for the successful continuance of digitalization in the construction sector. However, stakeholders' perceived benefit has a substantial role in both implementation and continuance.Research limitations/implicationsIn this research paper, the scope of this investigation for a generalized exploratory study is restricted to construction firms within India. Further, a rigorous longitudinal study may also be performed to examine the subjectivity of the responses in order to ensure digital continuation. This study identifies limited manifest indicators. Additional indications, however, may be included based on the other company's resources, structure and geographic location.Practical implicationsThe study's findings have two implications. In the beginning, it gives a direction to the construction sector by highlighting the framework in which implementation and continuance both should have to be executed, and this is the critical area for the successful continuance of digitalization in construction. Second, the research shows that the digitalization process is similar to the adoption of innovation, in which the deployment and persistent use of the new technology are important for facilitating the transformation.Originality/valueIn two respects, the study is distinctive. To begin, this is one of the limited efforts to comprehend digitalization from the Indian perspective. Second, the study reveals that the PLS-SEM approach can be effectively used in the developing subject of the construction digitalization concept.