bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scalable ultra-high-throughput single-cell chromatin and RNA sequencing reveals gene regulatory dynamics linking macrophage polarization to autoimmune disease
Authors: Lobato-Moreno Sara , Yildiz Umut , Claringbould Annique , Servaas Nila H. , Vlachou Evi P. , Arnold Christian , Bauersachs Hanke Gwendolyn , Campos-Fornés Víctor , Prummel Karin D. , Noh Kyung Min , Marttinen Mikael , Zaugg Judith B. 
Published: December 2023

AbstractEnhancers and transcription factors (TFs) are crucial in regulating cellular processes, including disease-associated cell states. Current multiomic technologies to study these elements in gene regulatory mechanisms lack multiplexing capability and scalability. Here, we present SUM-seq, a cost-effective, scalableSingle-cellUltra-high-throughputMultiomic sequencing method for co-assaying chromatin accessibility and gene expression in single nuclei. SUM-seq enables profiling hundreds of samples at the million cell scale and outperforms current high-throughput single-cell methods. We applied SUM-seq to dissect the gene regulatory mechanisms governing macrophage polarization and explored their link to traits from genome-wide association studies (GWAS). Our analyses confirmed known TFs orchestrating M1 and M2 macrophage programs, unveiled key regulators, and demonstrated extensive enhancer rewiring. Integration with GWAS data further pinpointed the impact of specific TFs on a set of immune traits. Notably, inferred enhancers regulated by the STAT1/STAT2/IRF9 (ISGF3) complex were enriched for genetic variants associated with Crohn’s disease, ulcerative colitis and multiple sclerosis, and their target genes included known drug targets. This highlights the potential of SUM-seq for dissecting molecular disease mechanisms. SUM-seq offers a cost-effective, scalable solution for ultra-high-throughput single-cell multiomic sequencing, excelling in unraveling complex gene regulatory networks in cell differentiation, responses to perturbations, and disease studies.
Feeding-state dependent neuropeptidergic modulation of reciprocally interconnected inhibitory neurons biases sensorimotor decisions inDrosophila
Authors: de Tredern Eloïse , Manceau Dylan , Blanc Alexandre , Sakagiannis Panagiotis , Barre Chloe , Sus Victoria , Viscido Francesca , Hasan Md Amit , Autran Sandra , Nawrot Martin , Masson Jean-Baptiste , Jovanic Tihana 
Published: December 2023

AbstractAnimals’ feeding state changes behavioral priorities and thus influences even non-feeding related decisions. How is the feeding state information transmitted to non-feeding related circuits and what are the circuit mechanisms involved in biasing non-feeding related decisions remains an open question. By combining calcium imaging, neuronal manipulations, behavioral analysis and computational modeling, we determined that the competition between different aversive responses to mechanical cues is biased by feeding state changes. We found that this is achieved by differential modulation of two different types of reciprocally connected inhibitory neurons promoting opposing actions. This modulation results in a more frequent active type of response and less frequently a protective type of response if larvae are fed sugar compared to when they are fed a balanced diet. The information about the internal state is conveyed to the inhibitory neurons through homologues of the vertebrate neuropeptide Y known to be involved in regulating feeding behavior.
Relentless Selection: The importance of within-generation selection in heterogeneous habitats
Authors: Ehrlich Moritz A. , DeLiberto Amanda N. , Drown Melissa K. , Oleksiak Marjorie F. , Crawford Douglas L. 
Published: December 2023

AbstractNatural selection relentlessly reshapes the genetic and phenotypic composition of populations, yet often adaptations cannot emerge due to excessive migration and gene flow. Nevertheless, in heterogeneous habitats strong selection could temporarily establish significant trait divergence among environmental patches. Here, we show that inFundulus heteroclitus,a single generation of selection drives significant phenotypic divergence (5-15%) in organismal metabolic rate, cardiac metabolic rate and hypoxia tolerance. This divergence occurs among individuals of the same panmictic population residing in environmentally distinct microhabitats. Phenotypic divergence remains observable following long-term common-gardening and is supported by previous work documenting fine-scale, genetic divergence among microhabitat residents. We show that the magnitude of within-generation trait divergence is on the order of what is commonly observed among more isolated populations that have diverged over multiple generations. Although panmictic reproduction among microhabitat residents erodes trait divergence every generation, strong selection could potentially reestablish it in the next. In heterogeneous habitats, transient, fine-scale divergence could have a considerable impact on eco-evolutionary dynamics. Ignoring its contribution to overall trait variance could limit our ability to define meaningful, evolved divergence.SummaryNatural selection can lead to changes in organisms’ traits over time. Typically, these changes occur slowly over multiple generations and over large spatial scales. By studying a wild population of Atlantic killifish, we show that a single generation of natural selection can generate substantial trait variation over short distances. We observe significant differences in several physiological traits among individuals inhabiting distinct ‘microhabitats’ in a patchy salt marsh environment. These differences are unlikely due to physiological acclimation and are best explained by strong, natural selection removing those individuals not suited to a particular microhabitat. Previous studies support natural selection as the most likely explanation, having shown subtle genetic differences among microhabitat residents. Remarkably, the magnitude of trait divergence is on the order of what is typically observed among populations that have diverged over multiple generations and larger spatial scales. Our results highlight the significant contribution of natural selection to trait variation in patchy environments, even over exceptionally short time and small spatial scales.
Identification of active transposable element candidates from ROH in a de novo assembled chromosome-scale genome of a Nishikigoi, an ornamental fish derived from Common carp (Cyprinus carpio)
Authors: Hosaka Aoi 
Published: December 2023

AbstractTransposable Elements (TEs) are major components of the genome. To understand their function and evolution, it is necessary to identify active TEs from a diverse range of organisms. Here, I report the genome of the Nishikigoi, an ornamental fish derived from the Common carp, and the novel approach to detecting active TE candidates.I constructed a chromosome-scale assembly using long-read sequencing and Hi-C methods. It revealed that Nishikigoi has Robertsonian-like chromosomal translocations not seen in Common carp. I also found that Nishikigoi has a significantly different genetic background from Common carp, reflecting the intensive breeding history.Furthermore, by focusing on Runs of Homozygosity (ROH) islands in the Nishikigoi genome and analyzing structural variations with long-read sequencing, I identified several active TE candidates.This study not only revealed the unique genetic features of Nishikigoi but also demonstrated the potential for a novel approach in the search for active TEs.
All three MutL complexes are required for repeat expansion in a human stem cell model of CAG-repeat expansion mediated glutaminase deficiency
Authors: Hayward Bruce , Kumari Daman , Santra Saikat , van Karnebeek Clara D.M. , van Kuilenburg André B.P. , Usdin Karen 
Published: December 2023

AbstractThe Repeat Expansion Diseases (REDs) arise from the expansion of a disease-specific short tandem repeat (STR). Different REDs differ with respect to the repeat involved, the cells that are most expansion prone and the extent of expansion. Furthermore, whether these diseases share a common expansion mechanism is unclear. To date, expansion has only been studied in a limited number of REDs. Here we report the first studies of the expansion mechanism in induced pluripotent stem cells derived from a patient with a form of the glutaminase deficiency disorder known as Global Developmental Delay, Progressive Ataxia, And Elevated Glutamine (GDPAG; OMIM# 618412) caused by the expansion of a CAG-STR in the 5’ UTR of the glutaminase (GLS) gene. We show that alleles with as few as ∼120 repeats show detectable expansions in culture despite relatively low levels of R-loops formed at this locus. Additionally, using a CRISPR-Cas9 knockout approach we show that PMS2 and MLH3, the constituents of MutLα and MutLγ, the 2 mammalian MutL complexes known to be involved in mismatch repair (MMR), are essential for expansion. Furthermore, PMS1, a component of a less well understood MutL complex, MutLβ, is also important, if not essential, for repeat expansion in these cells. Our results provide insights into the factors important for expansion and lend weight to the idea that, despite some differences, the same mechanism is responsible for expansion in many, if not all, REDs.
Drought impact on phellem development: identification of novel gene regulators and evidence of photosynthetic activity
Authors: Barros Pedro M. , Sapeta Helena , Lucas Diogo A. , Oliveira M. Margarida 
Published: December 2023

AbstractQuercus suber(cork oak) is a sustainably exploited forest resource, producing a unique renewable raw material known as cork. With drought events imposing a negative impact on tree vitality, we need more knowledge on the genetic and environmental regulation of cork development to protect the cork sector. We focused on characterizing long-term drought-induced molecular adaptations occurring in stems, and identifying key genetic pathways regulating phellem development. One-year-old cork oak plants were grown for 6 months under well-watered, or water-deficit (WD) conditions and main stems were targeted for histological characterization and transcriptomic analysis. WD treatment impaired secondary growth, by reducing meristem activity at both vascular cambium and phellogen. We analyzed the transcriptional changes imposed by WD in phellem, inner bark, and xylem, and found a global downregulation of genes related to cell division, differentiation, and cell wall biogenesis. Phellem and inner bark showed upregulation of photosynthesis-related genes, highlighting a determinant role of stem photosynthesis in the adaptation to long-term drought. We show that developing phellem cells contain chloroplasts and their abundance increases under WD. Finally, we propose new candidate regulatory genes involved in the regulation of phellogen activity and demonstrate the involvement of phellem in drought-induced bark photosynthesis in young plants.HighlightPhellem development in cork oak is impaired in drought adaptation, by negative regulation of cell division and differentiation programs, while photosynthesis is induced to contributing to CO2recycling in the stem.
Stabilization of F-actin bySalmonellaeffector SipA resembles the structural effects of inorganic phosphate and phalloidin
Authors: Niedzialkowska Ewa , Runyan Lucas A. , Kudryashova Elena , Egelman Edward H. , Kudryashov Dmitri S. 
Published: December 2023

AbstractEntry ofSalmonellainto host enterocytes strictly relies on its pathogenicity island 1 effector SipA. We found that SipA binds to F-actin in a unique mode in a 1:2 stoichiometry with picomolar affinity. A cryo-EM reconstruction revealed that SipA’s globular core binds at the grove between actin strands, whereas the extended C-terminal arm penetrates deeply into the inter-strand space, stabilizing F-actin from within. The unusually strong binding of SipA is achieved via a combination of fast association via the core and very slow dissociation dictated by the arm. Similarly to Pi, BeF3, and phalloidin, SipA potently inhibited actin depolymerization by ADF/cofilin, which correlated with the increased filament stiffness, supporting the hypothesis that F-actin’s mechanical properties contribute to the recognition of its nucleotide state by protein partners. The remarkably strong binding to F-actin maximizes the toxin’s effects at the injection site while minimizing global influence on the cytoskeleton and preventing pathogen detection by the host cell.
MERITS: a web-based integratedMycobacterialPE/PPE protein database
Authors: He Zhijie , Wang Cong , Guo Xudong , Sun Heyun , Bi Yue , Pitt Miranda E. , Li Chen , Song Jiangning , Coin Lachlan JM , Li Fuyi 
Published: December 2023

AbstractMotivationPE/PPE proteins, highly abundant in theMycobacteriumgenome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms ofMycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins.ResultsAddressing this gap, we introduce MERITS, a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22,353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localisation, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing Features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins.Availability and implementationMERITS is freely accessible athttp://merits.unimelb-biotools.cloud.edu.au/.
Beyond the medical file: a scoping review on patients’ perspectives on guideline-oriented depression treatment in primary care
Authors: Biersack Katharina , Sattel Heribert , Schönweger Petra , Kaspar Lea , Lehnen Nadine , Gensichen Jochen , Henningsen Peter ,   the POKAL group
Published: December 2023

AbstractObjectivesDepressive disorders are common in the primary care setting. Primary care practitioners must deal with different disorders and keep up with evidence-based treatment. Clinical practice guidelines (CPG) offer accessible information about up-to-date care but are poorly implemented. Research on the implementation of CPGs has focused on the practitioners’ perspective but has neglected the patients’ perspective largely.This scoping review aimed to identify terms related to the concept of ‘patients’ perspectives on depression treatment in primary care building a comprehensive framework and to identify researched barriers and facilitators to partaking in care.MethodsWe conducted a scoping review on Medline and Psycinfo. Eligible publications contained information from the patients’ point of view on depression treatment in primary care in OECD member states. We used the PCC-framework to obtain inclusion criteria. Publications until August 2nd 2023 were considered.ResultsWe included 232 publications. Current literature focuses on behavioral and easily collected measures like satisfaction and on patient-sided barriers and facilitators to adherence. Other treatment-related behaviors are less researched. Patients often report exclusively or mainly physical symptoms in their visits which can impede diagnosis.ConclusionThis review provides a comprehensive framework for the concept. Research on the patients’ perspective on depression treatment in primary care is still inconclusive.RegistrationThis review is registered via OSF (https://osf.io/p9rnc).
Navigating the digital travel landscape: understanding the role of technology readiness in OTAs acceptance and usage for hotel bookings
Authors: Azdel Abdul Aziz , Awang Khairil Wahidin , Yusof Raja Nerina Raja , Hanafiah Mohd Hafiz 
Published: December 2023

PurposeThis paper delves into the multi-faceted factors influencing the adoption and utilisation of online travel agencies (OTAs) for reserving hotel accommodations. The study aims to expand upon the unified theory of acceptance and use of technology (UTAUT2) framework to accomplish this objective by integrating the critical dimension of technology readiness (TR).Design/methodology/approachFour hundred and fifty-three (453) inbound tourists were asked to share their feedbacks on their recent OTA booking experience. Structural equation modelling (SEM) was used to confirm the study model and test the study hypotheses.FindingsThis study found that the motivating TR attributes favourably affect the acceptance and actual use of OTAs, while the inhibitors TR reflects adverse effects on OTA’s usage. On the other hand, the OTAs usage attributes: performance expectancy, effort expectancy, social influence, facilitating condition, hedonic motivation, price value and habit are all significant determinants of consumers' behavioural intention.Originality/valueThe originality of this study lies in providing a more comprehensive explanation and prediction of consumer behaviour in relation to OTAs. Specifically, it recognises the importance of TR as a significant determinant of technology adoption and usage within the service industry realm.
The role of institutional and stakeholder interaction in integrated reporting policy development
Authors: AbuRaya Rania 
Published: December 2023

Purpose
This study aims to investigate the role of institutional and stakeholder interaction in the development of integrated reporting policy by the International Integrated Reporting Council (IIRC). It helps advance the theory of integrated reporting and offers insights into its fundamental concepts and relevant issues.

Design/methodology/approach
A flexible pattern-matching qualitative research approach is used and an analytical framework of integrated reporting historical foundations and conceptual background is developed. An IIRC case analysis is conducted by using a chronological content analysis of the International Integrated Reporting Framework and related initiatives and publications for integrated reporting policy pronouncements.

Findings
Institutional and stakeholder pressures within both the organization’s macro and micro contexts have played an effective role in transforming corporate reporting practices. In an integrated reporting context, institutional forces of normative and mimetic isomorphism seem to have more influence on organizations than coercive pressures, where stakeholder pressures with limited official power derive influence from their legitimacy while urgency is evidently implied. Findings indicate that integrated reporting policy has emerged analogously with the institutional environment and stakeholders’ expectations. The distinct nature of integrated reporting has caused a paradigm shift from silo thinking of wealth creation to integrated thinking of value creation.

Research limitations/implications
This is an exploratory study that does not consider different prominent integrated reporting models. It has important implications for policymakers in articulating the integration of financial and nonfinancial metrics for reporting overall corporate performance. It can help academics build on integrated reporting foundations for conducting future research and assist practitioners in operationalizing integrated reporting policy into practice. Moreover, it has potential prospects for international business in developing integrated reporting policies and strategies aimed at creating mutual value in specific international contexts.

Originality/value
Integrated reporting represents a new internationally developing reporting trend with distinct reporting features and foundations for value creation. The study provides considerable addition to emerging research into the growing awareness of integrated reporting policy, develops a conceptual model of institutional and stakeholder interaction and theorizes on such interplay, identifies the potential influences under which integrated reporting is likely to occur and offers key insights into integrated reporting policy. Hence, it contributes to the ongoing global challenge of promoting the reporting transition to integrated reporting and its perceived future endorsement.
The moderating effect of financial constraints on the relationship between stock price crash risk and managerial ability
Authors: Shelih Ragia , Wang Li 
Published: December 2023

Purpose
This study aims to empirically explore the influence of managerial ability on crash risk and the moderating effect of financial constraints on this interrelationship.

Design/methodology/approach
Using a sample of listed corporations in the Egyptian Stock Exchange during 2018–2021, the authors test the hypotheses by using the measures and methods well established in prior literature. The authors also conduct multiple robustness analyses to ensure the validity of the empirical results.

Findings
The findings suggest that managerial ability can effectively inhibit crash risk. In addition, the authors report that financial constraints significantly dampen this relationship. Thus, financial restrictions play a striking role in hampering the managerial ability to prevent stock crashes. Furthermore, the authors document that the moderating role of severe financing constraints is more prominent during the Covid-19 pandemic period.

Originality/value
The originality of this study stems from the following considerations. First, this study enriches relevant studies on crash risk by providing evidence from one of the emerging markets in the Middle East; thereby, contrasting with those in developed economies. Second, to the best of the authors’ knowledge, this is the first study investigating the moderating impact of financing constraints on the managerial ability and crash risk nexus. Therefore, this work adds value to the extant knowledge by scrutinizing this important issue and providing novel empirical evidence.
Exploring a comprehensive evaluation model for measuring spatial equity in the layout of city community elderly service facilities: a case study in Xi’an, China
Authors: Wang Peiyu , Zhang Qian , Li Zhimin , Wang Fang , Shi Ying 
Published: December 2023

PurposeThe study aims to devise a comprehensive evaluation model (CEM) for evaluating spatial equity in the layout of elderly service facilities (ESFs) to address the inequity in the layout of ESFs within city center communities characterized by limited land resources and a dense elderly population.Design/methodology/approachThe CEM incorporates a suite of analytical tools, including accessibility assessment, Lorenz curve and Gini coefficient evaluations and spatial autocorrelation analysis. Utilizing this model, the study scrutinized the distributional equity of three distinct categories of ESFs in the city center of Xi’an and proposed targeted optimization strategies.FindingsThe findings reveal that (1) there are disparities in ESFs’ accessibility among different categories and communities, manifesting a distinct center (high) and periphery (low) distribution pattern; (2) there exists inequality in ESFs distribution, with nearly 50% of older adults accessing only 18% of elderly services, and these inequalities are more pronounced in urban areas with lower accessibility, and (3) approximately 14.7% of communities experience a supply-demand disequilibrium, with demand surpassing supply as a predominant issue in the ongoing development of ESFs.Originality/valueThe CEM formulated in this study offers policymakers, urban planners and service providers a scientific foundation and guidance for decision-making or policy amendment by promptly assessing and pinpointing areas of spatial inequity in ESFs and identifying deficiencies in their development.