bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cohesin forms fountains at active enhancers inC. elegans
Authors: Isiaka Bolaji N. , Semple Jennifer I. , Haemmerli Anja , Thapliyal Saurabh , Stojanovski Klement , Das Moushumi , Gilbert Nick , Glauser Dominique A. , Towbin Benjamin , Jost Daniel , Meister Peter 
Published: July 2023

AbstractTranscriptional enhancers must find their target genes both efficiently and specifically. Chromatin conformation capture revealed the critical function of three-dimensional chromosome segmentation by topologically associated domains (TADs) to limit the search space of enhancers for promoters in mammals. In nematodes, although more than 30’000 sequences with characteristic enhancer chromatin features have been identified, the autosomal genome is not segmented by TADs, raising the question of the mechanism directing enhancer-promoter specificity. Using high-resolution HiC, we show that enhancer loci correlate with 3D hairpin-like structures extending 10-50 kb from the enhancers, hereafter designated as fountains. Fountains are specific to active enhancers, accumulate the major somatic cohesin and disappear when the latter is cleavedin vivo. Fountains accumulate topological constraints and are enriched for topoisomerases and the negatively-supercoiled DNA binder psoralen. Short-term topoisomerase depletion leads to small-scale structural changes at the fountain tip. Functionally, fountain disappearance correlates with enhancer-proximal gene activation, suggesting fountains play a similar role as TADs and direct enhancer-promoter interactions, in particular for genes expressed in neurons. We directly observe this cell-type specific upregulation for theskn-1/Nrfgene in a pair of head neurons. Phenotypically, cohesin cleavage has a major impact on nematode movement and foraging attitudes, demonstrating that changes in neuronal gene expression impact nervous system function, reminiscent of pathologies caused by cohesin mutations in humans. Together, this study highlights a clear link between 3D genome organization at enhancers by cohesin, transcriptional gene regulation and animal behavior.
Two successive oligomeric Munc13 assemblies scaffold vesicle docking and SNARE assembly to support neurotransmitter release
Authors: Bera Manindra , Grushin Kirill , Sundaram R Venkat Kalyana , Shahanoor Ziasmin , Chatterjee Atrouli , Radhakrishnan Abhijith , Lee Seong , Padmanarayana Murugesh , Coleman Jeff , Pincet Frédéric , Rothman James E , Dittman Jeremy S 
Published: July 2023

AbstractThe critical presynaptic protein Munc13 serves numerous roles in the process of docking and priming synaptic vesicles. Here we investigate the functional significance of two distinct oligomers of the Munc13 core domain (Munc13C) comprising C1-C2B-MUN-C2C. Oligomer interface point mutations that specifically destabilized either the trimer or lateral hexamer assemblies of Munc13C disrupted vesicle docking, trans-SNARE formation, and Ca2+-triggered vesicle fusion in vitro and impaired neurotransmitter secretion and motor nervous system function in vivo. We suggest that a progression of oligomeric Munc13 complexes couples vesicle docking and assembly of a precise number of SNARE molecules to support rapid and high-fidelity vesicle priming.
Kin-recognition shapes collective behaviors in the cannibalistic nematodePristionchus pacificus
Authors: Hiramatsu Fumie , Lightfoot James W. 
Published: July 2023

AbstractKin-recognition is observed across diverse species forming an important behavioral adaptation influencing organismal interactions. In most species, proximate level mechanisms are poorly characterized, but in the nematodePristionchus pacificusmolecular components regulating its kin-recognition system have been identified which determine its predatory behaviors. This ability prevents the killing of kin however, its impact on other interactions including collective behaviors is unknown. Utilizing pairwise aggregation assays between distinct strains ofP. pacificus, we observed aggregation between kin but not distantly related con-specifics. In these assays, only one strain aggregates with solitary behavior induced in the rival. Abolishing predation throughPpa-nhr-40mutations results in rival strains successfully aggregating together. Additionally, interactions betweenP. pacificuspopulations andCaenorhabditis elegansare dominated byP. pacificuswhich also disruptsC. elegansaggregation dynamics. Thus, aggregating strains ofP. pacificuspreferentially group with kin, revealing competition and nepotism as previously unknown components influencing collective behaviors in nematodes.
Genome-wide expression QTL mapping reveals the highly dynamic regulatory landscape of a major wheat pathogen
Authors: Abraham Leen Nanchira , Croll Daniel 
Published: July 2023

AbstractBackgroundIn agricultural ecosystems, outbreaks of diseases are frequent and pose a significant threat to food security. A successful pathogen undergoes a complex and well-timed sequence of regulatory changes to avoid detection by the host immune system, hence well-tuned gene regulation is essential for survival. However, the extent to which the regulatory polymorphisms in a pathogen population provide an adaptive advantage is poorly understood.ResultsWe usedZymoseptoria tritici, one of the most important pathogens of wheat, to generate a genome-wide map of regulatory polymorphism governing gene expression. We investigated genome-wide transcription levels of 146 strains grown under nutrient starvation and performed expression quantitative trait loci (eQTL) mapping. We identifiedcis-eQTLs for 65.3% of all genes and the majority of all eQTL loci are within 2kb upstream and downstream of the transcription start site (TSS). We also show that polymorphism in different gene elements contributes disproportionally to gene expression variation. Investigating regulatory polymorphism in gene categories, we found an enrichment of regulatory variants for genes predicted to be important for fungal pathogenesis but with comparatively low effect size, suggesting a separate layer of gene regulation involving epigenetics. We also show that previously reported trait-associated SNPs in pathogen populations are frequentlycis-regulatory variants of neighboring genes with implications for the trait architecture.ConclusionsOverall, our study provides extensive evidence that single populations segregate large-scale regulatory variation and are likely to fuel rapid adaptation to resistant hosts and environmental change.
Leaf susceptibility of Macaronesian laurel forest species toPhytophthora ramorum
Authors: Moralejo Eduardo , García-Muñoz José A. , Denman Sandra , Giménez-Romero Àlex 
Published: July 2023

AbstractPhytophthora ramorum(Pr) is an invasive oomycete in Europe and North America and the causal agent of sudden oak death (SOD), which occurs along the coastal fog belt of California and southwestern Oregon, and it also causes sudden larch death in the UK. The Macaronesian laurel forest (MLF), a relict subtropical evergreen forest of the North Atlantic islands, shares climatic and some taxonomic affinities with those areas affected by SOD. To assess the disease risk, we tested the foliage susceptibility of MLF species and their capacity to sustainPrsporulation and compared the climatic suitability with other areas where the pathogen is established. Detached leaves of 15 species were inoculated with zoospores and mycelium (through wounding) with fivePrisolates belonging to the EU1 and NA1 clonal lineages. MLF species showed diverse responses toPr, ranging from extensive necroses onViburnum tinusto asymptomatic sporulation onPicconia excelsa. Eleven species developed necrotic lesions to different degrees through zoospore inoculation while this increased to 13 species through wound treatment. Overall, small necrotic lesions (i.e. tolerance) were predominant, butPrwas rather aggressive toV. tinus,Arbutus canariensisandIlex canariensis. Although the mean sporangial production was generally low (25-201 sporangia) in all species, the number of sporangia per leaf in five MLF species was similar to those reported forUmbellularia californica, a key host driving the SOD epidemics in California. Climatic suitability indexes in MLF areas were similar to those where SOD is found in California. Our results indicate a moderate to high risk ofPrestablishment if the pathogen is introduced in the MLF.
A 3D microtumour system that faithfully represents ovarian cancer minimal residual disease
Authors: Yang Xingyun , Artibani Mara , Jin Yongcheng , Aggarwal Aneesh , Zhang Yujia , Muñoz-Galvan Sandra , Mikhailova Ellina , Rai Lena , Mukherjee Nobina , Kumar Ravinash Krishna , Albukhari Ashwag , Zhou Linna , Ahmed Ahmed Ashour , Bayley Hagan 
Published: July 2023

AbstractBackgroundBulk cancer and minimal residual disease (MRD) are characterised by different molecular drivers and therefore necessitate different therapeutic strategies. However, there are currently no 3D models that can faithfully recapitulate MRDex vivofor therapy development.MethodsA microfluidic technique was implemented to construct 3D microtumours, in which tumour cells, either by themselves or with fibroblasts, were encapsulated in viscous hydrogels. The 3D microtumours were analysed for their response to first-line chemotherapeutics and characterised through RNA-Seq, by comparing them to both 2D cultures and clinical samples.ResultsOur microfluidic platform guarantees the fabrication of 3D microtumours of tailorable size and cell content, which recreate key features of tumours such as hypoxia, characteristic organization of the cytoskeleton and a dose-response to chemotherapeutics close to the physiological range. The 3D microtumours were also used to examine non-genetic heterogeneity in ovarian cancer and could fully reflect the recently described “Oxford Classic” five molecular signatures.The gene expression profile of 3D microtumours following chemotherapy treatment closely resembled that of MRD in ovarian cancer patients, showing the upregulation of genes involved in fatty acid metabolism. We demonstrate that these 3D microtumours are ideal for drug development by showing how they support the identification of a promising inhibitor of fatty acid oxidation, perhexiline, which specifically targets chemotherapy-resistant MRD ovarian cancer cells and not bulk cancer cells.ConclusionWe have obtained the first 3D model of ovarian cancer MRD by using microtumours generated through microfluidics. This system is ideal for high-throughput drug screening and, given its versatility, it can be readily extended to additional types of cancer, as well as accommodate multiple cell types to generate complex tumour microenvironments.
Low vision practice and service provision among Optometrists in Ghana: a nationwide survey
Authors: Akuffo Kwadwo Owusu , Duah Junior Isaiah Osei , Acquah Eldrick Adu , Mensa Elna Abadua , Amoah Andoh Albert Kwadjo , Kumah David Ben , Boateng Bridget Senya , Boateng Josephine Ampomah , Osei-Poku Kofi , Eisenbarth Werner 
Published: July 2023

AbstractAimTo characterize practice patterns of low vision services among Optometrists in Ghana.MethodsThe nationwide cross-sectional survey identified entities through the Ghana Optometrists Association (GOA) registry and utilized a semi-structured questionnaire to consolidate survey information that comprises practitioners’ demographics, available services, diagnostic equipment, barriers to service provision and utilization, and interventions.Results300 Optometrists were identified, with 213 surveyed (71% response rate). About fifty percent (52.6%) were in private practice, and more than two-thirds (77%) did not provide low vision services. Most (≥ 70%) established lack of assistive devices, and basic eye care examination kits as the main barriers to low vision service provision. Similarly, practitioners reported unawareness of the presence of low vision centres (76.1%), and high cost of low vision aids (75.1%) as the prime perceived barriers for patients to utilize low vision services. Continuous professional development and public education (89-90%) were suggestive interventions to improve the uptake of low vision services. After statistical adjustment, private facility type (Adjusted odds ratio [AOR] = 0.35, p = 0.010) and lack of basic eye examination kits (AOR = 0.32, p = 0.002) were significantly associated with reduced odds of low vision service provision. Conversely, 15-19 years of work experience (AOR = 8.49, p = 0.022) were significantly associated with increased odds of low vision service provision.ConclusionOverall, the results indicate inadequate low vision coverage and service delivery. Government policies must be directed towards equipping practitioners with equipment and subsidize patient cost of treatment to optimize low vision care.What is already known on this topic?Fewer past studies have reported poor low vision service delivery in selected regions and hospitals in Ghana. However, this evidence is an under-representation of the coverage of low vision service delivery in the country and warrants a more robust design to obtain comprehensive estimates.What this study addsThe current study extends the existing literature by providing extensive evidence on the practice pattern of low vision services, barriers, and interventions in Ghana.How this study might affect research, practice, or policy?The unmet needs of low vision service delivery for residual vision necessitate institutionalizing pragmatic strategies to augment low vision service delivery, uptake, and delivery in the region.Synopsis/PrecisThis paper highlights the scope of low vision practice in Ghana. The findings show an unmet low vision coverage, significantly influenced by practice settings, years of work experience, and rudimentary eye examination equipment.
Population suppression by release of insects carrying a dominant sterile homing gene drive targetingdoublesexinDrosophila
Authors: Chen Weizhe , Guo Jialiang , Liu Yiran , Champer Jackson 
Published: July 2023

AbstractGene drive alleles, which bias their own inheritance and increase in frequency, show great promise for blocking disease transmission or directly suppressing pest populations. The most common engineered drive system is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after CRISPR cleavage. One successful homing drive example targets a female-specific exon indoublesexinAnophelesmosquitos, suppressing the population by inducing recessive sterility in female drive homozygotes. We found that inDrosophila melanogaster, a 3-gRNA drive disrupting thedoublesexfemale exon resulted in a masculine phenotype and dominant female sterility. Resistance alleles formed by end-joining repair were also dominant sterile. This was likely caused by expression of male-specific transcripts in females with drive and resistance alleles, disrupting sex development. Based on this construct, we proposed a new pest suppression system called “Release of Insects carrying a Dominant-sterile Drive” (RIDD). This entails continuously releasing drive heterozygous males, with drive and resistance alleles causing sterility in females. The drive remains at high frequency longer than currently used dominant female-lethal alleles (RIDL) due to drive conversion in males, and drive alleles also cause sterility based on resistance, both substantial advantages. With weekly releases of drive males into a cage population with overlapping generations, our RIDD system targetingdsxreached 100% prevalence within 27 weeks, progressively reducing egg production and eventually causing total population collapse. RIDD combines the merits of homing gene drive and RIDL. It is powerful but self-limiting, unlike unconfined standard homing drives, allowing for targeted population suppression.
Safeguarding the unknown: performance measurement, academic agency and the meaning of research quality in practice
Authors: Bedford David S. , Granlund Markus , Lukka Kari 
Published: July 2023

PurposeThe authors examine how performance measurement systems (PMSs) and academic agency influence the meaning of research quality in practice. The worries are that the notion of research quality is becoming too simplistically and narrowly determined by research quality's measurable proxies and that academics, especially manager-academics, do not sufficiently realise this risk. Whilst prior literature has covered the effects of performance measurement in the university sector broadly and how PMSs are mobilised locally, there is only little understanding of whether and how PMSs affect the meaning of research quality in practice.Design/methodology/approachThe study is designed as a comparative case study of two university faculties in Finland. The role of conceptual analysis plays a notable role in the study, too.FindingsThe authors find that manager-academics of the two examined faculties have rather similar conceptual understandings of research quality. However, there were differences in the degree of slippage between the “espoused-meaning” of research quality and “meaning-in-practice” of research quality. The authors traced these differences to how the local PMS and manager-academics’ agency relate to one another within the context of increasing global and national performance pressures. The authors developed a tentative framework for the various “styles of agency”. This suggests how the relationship between the local PMS and manager-academics’ exerted agency shapes the “degrees of freedom” of the meaning of research quality in practice.Originality/valueGiven that research quality lies at the heart of academic work, the authors' paper indicates that exploring the three matters – performance measurement, the agency of manager-academics and the meaning of research quality in practice – in combination is crucial for the sustainability of the academe. The authors contribute to the literature by detailing the way in which local PMS and manager-academics' agency have material impacts on what research quality means in practice. The authors conclude by highlighting the pressing need for manager-academics to exercise the agency in efforts to safeguard a broad and pluralistic understanding of research quality in practice.
Crowdfunding in times of crisis – the interplay of uncertainty and backers' well-being in small business rescue campaigns
Authors: Efrat Kalanit , Gilboa Shaked , Wald Andreas 
Published: July 2023

PurposeThe economic crisis triggered by the COVID-19 pandemic seriously jeopardized small businesses. To survive, many small businesses turned to their networks by launching crowdfunding “rescue” campaigns, which were very successful in eliciting both funding and community support. This study aims to explain this success from the backers' perspective by addressing support intentions in uncertain times. The authors examine backers' paradoxical behavior by investigating the influence of ambiguity aversion (individual uncertainty), business-level uncertainty and environmental uncertainty on backers' intentions to support small businesses and the interaction of uncertainty with backers' well-being.Design/methodology/approachSurvey data from 230 backers of small business rescue campaigns were analyzed using structural equation modeling.FindingsThe findings indicate that ambiguity aversion negatively dominates backers' support intentions. However, under the mediating effect of well-being, business-level and environmental uncertainties positively impact backers' intentions, whereas ambiguity aversion becomes non-significant.Originality/valueUncertainties are supposed to have a negative influence on individual well-being. By contrast, this study shows that backers' well-being is influenced by the context of the crowdfunding campaign. Uncertain conditions can provide value in addition to the benefits gained by backers from supporting crowdfunding campaigns.
Post hoc security and privacy concerns in mobile apps: the moderating roles of mobile apps’ features and providers
Authors: Nikkhah Hamid Reza , Grover Varun , Sabherwal Rajiv 
Published: July 2023

Purpose
This study aims to argue that user’s continued use behavior is contingent upon two perceptions (i.e. the app and the provider). This study examines the moderating effects of user’s perceptions of apps and providers on the effects of security and privacy concerns and investigate whether assurance mechanisms decrease such concerns.

Design/methodology/approach
This study conducts a scenario-based survey with 694 mobile cloud computing (MCC) app users to understand their perceptions and behaviors.

Findings
This study finds that while perceived value of data transfer to the cloud moderates the effects of security and privacy concerns on continued use behavior, trust only moderates the effect of privacy concerns. This study also finds that perceived effectiveness of security and privacy intervention impacts privacy concerns but does not decrease security concerns.

Originality/value
Prior mobile app studies mainly focused on mobile apps and did not investigate the perceptions of app providers along with app features in the same study. Furthermore, International Organization for Standardization 27018 certification and privacy policy notification are the interventions that exhibit data assurance mechanisms. However, it is unknown whether these interventions are able to decrease users’ security and privacy concerns after using MCC apps.
Influence of wheel profile wear coupled with friction coefficient on the dynamic response of subway vehicles
Authors: Li Hongxiao , Li Li 
Published: July 2023

PurposeThe purpose of this study is to match appropriate friction coefficients for subway operational vehicles, considering the dynamic variations of wheel profile wear.Design/methodology/approachThis study combines experimental testing and numerical simulation to investigate the influence of wheel profile wear coupled with the friction coefficient on the vehicle dynamic response.FindingsFor the test route in this paper, it is recommended to control the friction coefficient on straight sections between 0.25 and 0.3, and on curved sections between 0.2 and 0.3. This satisfies the required adhesion coefficient for normal train traction and braking, while also ensuring the straight running performance and curve negotiation performance of the vehicle.Practical implicationsReasonable friction coefficient ranges are proposed for straight and curved track lines to improve the operational safety and economy of the vehicles. Moreover, this study can provide a theoretical basis and reference direction for developing anti-wear measures for rail vehicles operating on fixed routes.Originality/valueConsidering the wear characteristics of operating vehicles and the dynamic changes in the wear profile, this paper explores the adaptability of different degrees of wheel wear profiles to different friction coefficients. Based on the response characteristics of vehicle dynamics, reasonable lubrication recommendations are proposed for this operating vehicle.