bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coming out of the ashes we rise: Culturally and linguistically diverse international nursing students during the COVID-19 pandemic
Authors: Lim Eric , Ng Linda , Zhou Huaqiong , Nair Ambili , Kalembo Fatch 
Published: May 2024

AbstractBackground and aimResearch on international students conducted during the COVID-19 pandemic has persistently highlighted the vulnerabilities and challenges that they experienced when staying in the host country to continue with their studies. The findings from such research can inevitably create a negative image of international students and their ability to respond to challenges during unprecedented times. Therefore, this paper took a different stance and reported on a qualitative study that explored culturally and linguistically diverse (CaLD) international nursing students who overcame the challenges brought about by the pandemic to continue with their studies in Australia.MethodA descriptive qualitative research design guided by the processes of constructivist grounded theory was selected to ascertain insights from participants’ experiences of studying abroad in Australia during the COVID-19 pandemic.ResultsThree themes emerged from the collected data that described the participants’ lived experiences, and they were: 1)Viewing international education as the pursuit of a better life, 2)Focusing on personal growth, and 3)Coming out of the ashes we rise.DiscussionThe findings highlight the importance of recognising the investments and sacrifices that CaLD international students and their families make in pursuit of international tertiary education. The findings also underscore the importance of acknowledging the qualities that CaLD international students have to achieve self-growth and ultimately self-efficacy as they stay in the host country during a pandemic.ConclusionFuture research should focus on identifying strategies that are useful for CaLD international nursing students to experience personal growth and ultimately self-efficacy and continue with their studies in the host country during times of uncertainty such as a pandemic.
Combinatorial Wnt signaling determines wing margin color patterns of the swallowtail butterfly ground plan
Authors: Mazo-Vargas Anyi , Liang Alan , Liang Brian , McDonald Jeanne M.C. , Martin Arnaud , Reed Robert D. 
Published: May 2024

AbstractThe intricate wing patterns of butterflies are thought to derive from a morphological ground plan that anchors homology relationships between individual color pattern elements and serves as an archetype for comparative analysis. These patterns undergo modifications that drive the diverse morphologies observed in nature. While brush-footed butterflies (Nymphalidae) have been well studied, assigning homologies with other lepidopteran families remains challenging due to substantial divergence. Here, we focus on swallowtails (Papilionidae), an early-diverging butterfly lineage known for its outstanding diversity in wing shapes and patterns but lacking a developmental framework. Through qualitative and phylogenetic analyses, CRISPR perturbation assays, andin situexpression experiments, we investigate homologies between papilionid butterflies, offering phylogenetic and molecular characterization of the Papilionidae wing ground plan. Our results highlight the roles ofWntAandWnt6in patterning papilionid signature wing elements, such as the glauca and the Submarginal spots. Notably, the nymphalids’ distinct Central Symmetry System is either reduced or absent in the family, with marginal systems expanding proximally. Our data illuminate a highly adaptable patterning system driven by Wnt signaling pathways in developing butterfly wings.
Y chromosome linked UTY modulates sex differences in valvular fibroblast methylation in response to nanoscale extracellular matrix cues
Authors: Gorashi Rayyan M. , Baddour Talia , Chittle Sarah J. , Vélez Nicole E. Félix , Wenning Michaela A. , Anseth Kristi S. , Mestroni Luisa , Peña Brisa , Guo Peng , Aguado Brian A. 
Published: May 2024

AbstractAortic valve stenosis (AVS) is a progressive disease wherein males more often develop valve calcification relative to females that develop valve fibrosis. Valvular interstitial cells (VICs) aberrantly activate to myofibroblasts during AVS, driving the fibrotic valve phenotype in females. Myofibroblasts further differentiate into osteoblast-like cells and produce calcium nanoparticles, driving valve calcification in males. We hypothesized the lysine demethylase UTY (ubiquitously transcribed tetratricopeptide repeat containing, Y-linked) decreases methylation uniquely in male VICs responding to nanoscale extracellular matrix cues to promote an osteoblast-like cell phenotype. Here, we describe a hydrogel biomaterial cell culture platform to interrogate how nanoscale cues modulate sex-specific methylation states in VICs activating to myofibroblasts and osteoblast-like cells. We found UTY modulates the osteoblast-like cell phenotype in response to nanoscale cues uniquely in male VICs. Overall, we reveal a novel role of UTY in the regulation of calcification processes in males during AVS progression.
Moesin controls cell-cell fusion and osteoclast function
Authors: Dufrancais Ophélie , Verdys Perrine , Plozza Marianna , Métais Arnaud , Juzans Marie , Sanchez Thibaut , Bergert Martin , Halper Julia , Panebianco Christopher J , Mascarau Rémi , Gence Rémi , Arnaud Gaëlle , Neji Myriam Ben , Maridonneau-Parini Isabelle , Cabec Véronique Le , Boerckel Joel D , Pavlos Nathan J , Diz-Muñoz Alba , Lagarrigue Frédéric , Blin-Wakkach Claudine , Carréno Sébastien , Poincloux Renaud , Burkhardt Janis K , Raynaud-Messina Brigitte , Vérollet Christel 
Published: May 2024

ABSTRACTCell-cell fusion is an evolutionarily conserved process that is essential for many functions, including fertilisation and the formation of placenta, muscle and osteoclasts, multinucleated cells that are unique in their ability to resorb bone. The mechanisms of osteoclast multinucleation involve dynamic interactions between the actin cytoskeleton and the plasma membrane that are still poorly characterized. Here, we found that moesin, a cytoskeletal linker protein member of the Ezrin/Radixin/Moesin (ERM) protein family, is activated during osteoclast maturation and plays an instrumental role in both osteoclast fusion and function. In mouse and human osteoclast precursors, moesin inhibition favors their ability to fuse into multinucleated osteoclasts. Accordingly, we demonstrated that moesin depletion decreases membrane-to-cortex attachment and enhances the formation of tunneling nanotubes (TNTs), F-actin-based intercellular bridges that we reveal here to trigger cell-cell fusion. Moesin also controls HIV-1- and inflammation-induced cell fusion. In addition, moesin regulates the formation of the sealing zone, the adhesive structure determining osteoclast bone resorption area, and thus controls bone degradation, via a β3-integrin/RhoA/SLK pathway. Supporting our results, moesin-deficient mice present a reduced density of trabecular bones and increased osteoclast abundance and activity. These findings provide a better understanding of the regulation of cell-cell fusion and osteoclast biology, opening new opportunities to specifically target osteoclast activity in bone disease therapy.
Recurrent extreme climatic events are driving gorgonian populations to local extinction: low adaptive potential to marine heatwaves
Authors: Ramirez-Calero Sandra , Gómez-Gras D , Barreiro A , Bensoussan N , Figuerola-Ferrando L , Jou M , López-Sanz A , López-Sendino P , Medrano A , Montero-Serra I , Pagès-Escolà M , Linares C , Ledoux JB , Garrabou J 
Published: May 2024

AbstractExtreme climatic events (ECEs), such as marine heatwaves (MHWs), are a major threat to biodiversity. Understanding the variability in ecological responses to recurrent ECEs within species and underlying drivers arise as a key issue owing to their implications for conservation and restoration. Yet, our knowledge on such ecological responses is limited since it has been mostly gathered following “single-event approaches” focused on one particular event. These approaches provide snapshots of ecological responses but fall short of capturing heterogeneity patterns that may occur among recurrent ECEs, questioning current predictions regarding biodiversity trends. Here, we adopt a “multi-event” perspective to characterize the effects of recurrent ECEs and the ecological responses inParamuricea clavata, a Mediterranean temperate coral threatened by MHWs. Through a common-garden experiment repeated three consecutive years with the same individuals from three populations, we assessed the respective roles of environmental (year effect), genetic (population effect) and phenotypic (population-by-environmentinteractions effect) components in the ecological response to recurrent heat stress. The environmental component (year) was the main driver underlying the responses ofP. clavatacolonies across experiments. To build on this result, we showed that: i) the ecological responses were not related to population (genetic isolation) and individual (multilocus heterozygosity) genetic make-up, ii) while all the individuals were characterized by a high environmental sensitivity (genotype-by-environmentinteractions) likely driven byin-situsummer thermal regime. We confront our experimental results toin situmonitoring of the same individuals conducted in 2022 following two MHWs (2018, 2022). This confirms that the targeted populations harbor limited adaptive and plastic capacities to on-going recurrent ECEs and thatP. clavatamight face unavoidable population collapses in shallow Mediterranean waters. Overall, we suggest that biodiversity forecasts based on “single event” experiments may be overly optimistic and underscore the need to consider the recurrence of ECEs in assessing threats to biodiversity.
A toolbox for genetic targeting of the claustrum
Authors: Tuberosa Joël , Boillat Madlaina , Dal Col Julien , Marconi Leonardo , Codourey Julien , Mannino Loris , Georgiou Elena , Menoud Marc , Carleton Alan , Rodriguez Ivan 
Published: May 2024

ABSTRACTThe claustrum (CLA), a subcortical nucleus in mammals, essentially composed of excitatory projection neurons and known for its extensive connections with the neocortex, has recently been associated with a variety of functions ranging from consciousness to impulse control. However, research on the CLA has been challenging due to difficulties in specifically and comprehensively targeting its neuronal populations. In various cases, this limitation has led to inconsistent findings and a lack of reliable data. In the present work, we describe the expression profile of theSmim32gene, which is almost exclusively transcribed in excitatory neurons of the CLA and the endopiriform nucleus, as well as in inhibitory neurons of the thalamic reticular nucleus. Leveraging this unique expression pattern, we developed a series of Cre- and Flippase-expressing knockin and BAC transgenic mouse lines with different expression profiles. With these novel tools in hand, we propose new standards for the interrogation of CLA function.
Cluster efficient pangenome graph construction with nf-core/pangenome
Authors: Heumos Simon , Heuer Michael F. , Hanssen Friederike , Heumos Lukas , Guarracino Andrea , Heringer Peter , Ehmele Philipp , Prins Pjotr , Garrison Erik , Nahnsen Sven 
Published: May 2024

AbstractMotivationPangenome graphs offer a comprehensive way of capturing genomic variability across multiple genomes. However, current construction methods often introduce biases, excluding complex sequences or relying on references. The PanGenome Graph Builder (PGGB) addresses these issues. To date, though, there is no state-of-the-art pipeline allowing for easy deployment, efficient and dynamic use of available resources, and scalable usage at the same time.ResultsTo overcome these limitations, we presentnf-core/pangenome, a reference-unbiased approach implemented in Nextflow following nf-core’s best practices. Leveraging biocontainers ensures portability and seamless deployment in HPC environments. Unlike PGGB, nf-core/pangenome distributes alignments across cluster nodes, enabling scalability. Demonstrating its efficiency, we constructed pangenome graphs for 1000 human chromosome 19 haplotypes and 2146E. colisequences, achieving a two to threefold speedup compared to PGGB without increasing greenhouse gas emissions.Availabilitynf-core/pangenome is released under the MIT open-source license, available on GitHub and Zenodo, with documentation accessible athttps://nf-co.re/pangenome/1.1.2/docs/usage.Contactsimon.heumos@qbic.uni-tuebingen.de,sven.nahnsen@qbic.uni-tuebingen.de
Energy-Based Systematic Modeling of Adaptive Immune Repertoire Behavior: Study on Cell Proliferation & Somatic Hypermutation process
Authors: Chen Yexing , Ni Haiwen , Ma Jin , Li Yongjie , Huang Chen , Yang Sixian , Xie Xiangfei , Lv Haitao , Li Min , Cao Peng 
Published: May 2024

AbstractMonitoring and describing the adaptive immune repertoire(IR) for disease detection and diagnosis is essential in healthcare research. Many phenomenon have been observed to generalize the static property of IR, but the mathematical description of the formation and dynamic changes of IR still lacks research. Here, we present a mathematical and physical model to interpret the cell proliferation and somatic hypermutation(SHM) process in IR, difficulties to generate different clones in IR are computed, and IR distance is calculated as the minimum effort required to transform one IR distribution to another. IR distribution and distance can be detected from samples containing 104cells. The validity of our method is confirmed by the unsupervised clustering of data from mice spleen and clinical PBMC samples including various immune stages and diseases. Our work dynamically characterize and quantify IR process, enabling a macroscopic immunoevaluation by sensitive immune fluctuation detection from minute samples.
OoCount: A Machine-Learning Based Approach to Mouse Ovarian Follicle Counting and Classification
Authors: Folts Lillian , Martinez Anthony S. , Bunce Corey , Capel Blanche , McKey Jennifer 
Published: May 2024

AbstractThe number and distribution of ovarian follicles in each growth stage provides a reliable readout of ovarian health and function. Leveraging techniques for three-dimensional (3D) imaging of ovariesin totohas the potential to uncover total, accurate ovarian follicle counts. However, because of the size and holistic nature of these images, counting oocytes is time consuming and difficult. The advent of deep-learning algorithms has allowed for the rapid development of ultra-fast, automated methods to analyze microscopy images. In recent years, these pipelines have become more user-friendly and accessible to non-specialists. We used these tools to create OoCount, a high-throughput, open-source method for automatic oocyte segmentation and classification from fluorescent 3D microscopy images of whole mouse ovaries using a deep-learning convolutional neural network (CNN) based approach. We developed a fast tissue-clearing and spinning disk confocal-based imaging protocol to obtain 3D images of whole mount perinatal and adult mouse ovaries. Fluorescently labeled oocytes from 3D images of ovaries were manually annotated in Napari to develop a machine learning training dataset. This dataset was used to retrain StarDist using a CNN within DL4MicEverywhere to automatically label all oocytes in the ovary. In a second phase, we utilize Accelerated Pixel and Object Classification, a Napari plugin, to classify labeled oocytes and sort them into growth stages. Here, we provide an end-to-end protocol for producing high-quality 3D images of the perinatal and adult mouse ovary, obtaining follicle counts and staging. We also demonstrate how to customize OoCount to fit images produced in any lab. Using OoCount, we can obtain accurate counts of oocytes in each growth stage in the perinatal and adult ovary, improving our ability to study ovarian function and fertility.Graphical AbstractSummary sentenceThis protocol introduces OoCount, a high-throughput, open-source method for automatic oocyte segmentation and classification from fluorescent 3D microscopy images of whole mouse ovaries using a machine learning-based approach.
Multiregional Representations of Intertemporal Decision Making in Human Single Neurons
Authors: Gill Jay L. , Omidbeigi Mahmoud , Ryu Jihye , Suthana Nanthia , Kao Jonathan C. , Bari Ausaf 
Published: May 2024

AbstractCharacterization of the neural basis of delay discounting provides insight into the origin of impulsive decision-making, which underlies several psychiatric diseases including substance use disorder. Here, we identify human single unit representations of decisions, and their level of difficulty, in the orbitofrontal cortex, hippocampus and amygdala that are related to preferences for immediate vs. delayed rewards. Results provide an initial account of multiregional intracranial computations related to impulsive behaviors in humans.
Inhibition of EGFR/ErbB does not protect againstC. difficiletoxin B
Authors: Siddiqi Uswah , Lunnemann Hannah M. , Childress Kevin O. , Shupe John A. , Rutherford Stacey A. , Farrow Melissa A. , Washington M. Kay , Coffey Robert J. , Lacy D. Borden , Markham Nicholas O. 
Published: May 2024

AbstractClostridioides difficileis a common cause of diarrhea and mortality, especially in immunosuppressed and hospitalized patients.C. difficileis a toxin-mediated disease, but the host cell receptors forC. difficiletoxin B (TcdB) have only recently been revealed. Emerging data suggest TcdB interacts with receptor tyrosine kinases during infection. In particular, TcdB can elicit Epidermal Growth Factor Receptor (EGFR) transactivation in human colonic epithelial cells. The mechanisms for this function are not well understood, and the involvement of other receptors in the EGFR family of Erythroblastic Leukemia Viral Oncogene Homolog (ErbB) receptors remains unclear. Furthermore, in an siRNA-knockdown screen for protective genes involved with TcdB toxin pathogenesis, we show ErbB2 and ErbB3 loss resulted in increased cell viability. We hypothesize TcdB induces the transactivation of EGFR and/or ErbB receptors as a component of its cell-killing mechanism. Here, we show in vivo intrarectal instillation of TcdB in mice leads to phosphorylation of ErbB2 and ErbB3. However, immunohistochemical staining for phosphorylated ErbB2 and ErbB3 indicated no discernible difference between control and TcdB-treated mice for epithelial phospho-ErbB2 and phospho-ErbB3. Human colon cancer cell lines (HT29, Caco-2) exposed to TcdB were not protected by pre-treatment with lapatinib, an EGFR/ErbB2 inhibitor. Similarly, lapatinib pre-treatment failed to protect normal human colonoids from TcdB-induced cell death. Neutralizing antibodies against mouse EGFR failed to protect mice from TcdB intrarectal instillation as measured by edema, inflammatory infiltration, and epithelial injury. Our findings suggest TcdB-induced colonocyte cell death does not require EGFR/ErbB receptor tyrosine kinase activation.
Exploration-exploitation trade-off is regulated by metabolic state and taste value inDrosophila
Authors: Whitehead Samuel C. , Sahai Saumya Y. , Stonemetz Jamie , Yapici Nilay 
Published: May 2024

SUMMARYSimilar to other animals, the fly,Drosophila melanogaster,changes its foraging strategy from exploration to exploitation upon encountering a nutrient-rich food source. However, the impact of metabolic state or taste/nutrient value on exploration vs. exploitation decisions in flies is poorly understood. Here, we developed a one-source foraging assay that uses automated video tracking coupled with high-resolution measurements of food ingestion to investigate the behavioral variables flies use when foraging for food with different taste/caloric values and when in different metabolic states. We found that flies alter their foraging and ingestive behaviors based on their hunger state and the concentration of the sucrose solution. Interestingly, sugar-blind flies did not transition from exploration to exploitation upon finding a high-concentration sucrose solution, suggesting that taste sensory input, as opposed to post-ingestive nutrient feedback, plays a crucial role in determining the foraging decisions of flies. Using a Generalized Linear Model (GLM), we showed that hunger state and sugar volume ingested, but not the nutrient or taste value of the food, influence flies’ radial distance to the food source, a strong indicator of exploitation. Our behavioral paradigm and theoretical framework offer a promising avenue for investigating the neural mechanisms underlying state and value-based foraging decisions in flies, setting the stage for systematically identifying the neuronal circuits that drive these behaviors.
Metabolome-wide association of carotid intima media thickness identifies FDX1 as a determinant of cholesterol metabolism and cardiovascular risk in Asian populations
Authors: Sadhu Nilanjana , Dalan Rinkoo , Jain Pritesh R , Lee Chang Jie Mick , Pakkiri Leroy Sivappiragasam , Tay Kai Yi , Mina Theresia H , Low Dorrain , Min Yilin , Ackers-Johnson Matthew , Thi Thi Tun , Kota Vishnu Goutham , Shi Yu , Liu Yan , Yu Henry , Tay Darwin , Ng Hong Kiat , Wang Xiaoyan , Wong Kari E , Lam Max , Guan Xue Li , Bertin Nicolas , Wong Eleanor , Best James , Sarangarajan Rangaprasad , Elliott Paul , Riboli Elio , Lee Jimmy , Lee Eng Sing , Ngeow Joanne , Tan Patrick , Cheung Christine , Drum Chester Lee , Foo Roger SY , Michelotti Gregory A , Yu Haojie , Sheridan Patricia A , Loh Marie , Chambers John C 
Published: May 2024

AbstractThe burden of cardiovascular disease (CVD) is rising in the Asia-Pacific region, in contrast to falling CVD mortality rates in Europe and North America. To provide new insights into the pathways influencing cardiovascular risk in Asian populations, we quantified 883 metabolites by untargeted mass spectroscopy in 8,124 Singaporean adults, and investigated their relationships to carotid intima media thickness (cIMT), a marker of atherosclerosis. We found that plasma concentrations of 3beta-hydroxy-5-cholestenoate (3BH5C), a cholesterol metabolite, associated inversely with cIMT (Beta[SE]=-0.013[0.002]). Genetic instruments support a causal relationship of 3BH5C metabolic pathways on cardiovascular risk, with a 5-6 fold higher effect size in Asians (ORGSMR[95% CI]=0.89[0.87-0.92], ORIVW[95% CI]=0.86[0.80-0.92]) compared to Europeans (ORIVW[95% CI] = 0.98[0.96-0.99]). Colocalization analyses indicate the presence of a shared causal variant between 3BH5C plasma levels and expression of ferredoxin-1 (FDX1), a protein essential for sterol and bile acid synthesis. We validatedFDX1as a key regulator of 3BH5C synthesis in hepatocytes, and macrophages, and cholesterol efflux in aortic smooth muscle cells, through knockout and overexpression models. In summary, this study makes an important contribution to our understanding of the metabolic basis for atherosclerosis in Asian populations, and identifiesFDX1as a potential therapeutic target for prevention of CVD.