bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient self-organization of blastoids solely from mouse ESCs is facilitated by transient reactivation of 2C gene network
Authors: Jana Debabrata , Singh Priya , Sailasree Purnima , Kumar Nithyapriya , Vishnu Vijay V , Kale Hanuman T , Lakshmi Jyothi , Kumari Asha , Sowpati Divya Tej , Shekar P Chandra 
Published: April 2023

SummaryHuman pluripotent stem cells (hPSCs) can self-organize into a blastocyst-like structure (blastoid) by virtue of their full developmental potential. The pluripotent mouse embryonic stem cells (mESC) are considered to lack this potential and hence can form blastoids only when combined with trophoblast stem cells. We performed a small molecule and cytokine screen to demonstrate that mESC have full potential to efficiently self-organize themselves into E-blastoids (ESC-blastoids). The morphology, cell lineages and the transcriptome of these blastoids resemble the mouse blastocyst. The E-blastoids undergo implantation andin uterodevelopment in mice. The transient reactivation of the 2C-gene network by retinoid signaling is essential for E-blastoid generation. GSK3β activity is critical for retinoid signaling and consequent 2C gene network activation. Collectively, the mESC possess full developmental potential to generate blastoids similar to hPSCs and other mammals. The plasticity of PSCs to self-organize into blastoids is not exclusive to humans or larger mammals; rather, it could be a general feature shared by most mammals, including rodents.
PGSbuilder: An end-to-end platform for human genome association analysis and polygenic risk score predictions
Authors: Lee Ko-Han , Lee Yi-Lun , Hsieh Tsung-Ting , Chang Yu-Chuan , Wang Su-Shia , Fann Geng-Zhi , Lin Wei-Che , Chang Hung-Ching , Chen Ting-Fu , Li Peng-Husan , Kuo Ya-Ling , Chen Pei-Lung , Juan Hsueh-Fen , Tsai Huai-Kuang , Chen Chien-Yu , Huang Jia-Hsin 
Published: April 2023

AbstractUnderstanding the genetic basis of human complex diseases is increasingly important in the development of precision medicine. Over the last decade, genome-wide association studies (GWAS) have become a key technique for detecting associations between common diseases and single nucleotide polymorphisms (SNPs) present in a cohort of individuals. Alternatively, the polygenic risk score (PRS), which often applies results from GWAS summary statistics, is calculated for the estimation of genetic propensity to a trait at the individual level. Despite many GWAS and PRS tools being available to analyze a large volume of genotype data, most clinicians and medical researchers are often not familiar with the bioinformatics tools and lack access to a high-performance computing cluster resource. To fill this gap, we provide a publicly available web server, PGSbuilder, for the GWAS and PRS analysis of human genomes with variant annotations. The user-friendly and intuitive PGSbuilder web server is developed to facilitate the discovery of the genetic variants associated with complex traits and diseases for medical professionals with limited computational skills. For GWAS analysis, PGSbuilder provides the most renowned analysis tool PLINK 2.0 package. For PRS, PGSbuilder provides six different PRS methods including Clumping and Thresholding, Lassosum, LDPred2, GenEpi, PRS-CS, and PRSice2. Furthermore, PGSbuilder provides an intuitive user interface to examine the annotated functional effects of variants from known biomedical databases and relevant literature using advanced natural language processing approaches. In conclusion, PGSbuilder offers a reliable platform to aid researchers in advancing the public perception of genomic risk and precision medicine for human disease genetics. PGSbuilder is freely accessible athttp://pgsb.tw23.org.
Association between the skin microbiome and MHC class II diversity in an amphibian
Authors: Cortazar-Chinarro M , Richter-Boix A , Rodin-Mörch P , Halvarsson P , Logue JB , Laurila A , Höglund J 
Published: April 2023

AbstractIt has become clear that the microbiome plays an important role in determining host health, diseases, and phenotypic variation. There is increasing evidence that the microbiome influences host fitness and its adaptation to the environment is changing our thinking on host-microbe interactions. However, it remains unclear how a host genotype shapes its microbiome. Here, we explored how genetic background and evolutionary history influence associated microbiome in amphibian populations. We studied how skin bacterial diversity is associated with the Major Histocompatibility Complex (MHC) class II exon 2 diversity in 12 moor frog populations belonging to two geographical clusters that show signatures of past and ongoing differential selection patterns. We found that bacterial alpha-diversity remained similar between the two clusters, while MHC haplotype-supertypes and genetic diversity differed between the clusters. Bacterial alpha-diversity was positively correlated with expected MHC heterozygosity and negatively with MHC nucleotide diversity. We also found that bacterial community composition differed significantly between the two geographic clusters and between specific MHC supertypes. These findings further suggest that population historical demographic events influence hologenomic variation and provide new insights into how immunogenetic host variability and microbial diversity may jointly influence host fitness with consequences for disease susceptibility and population persistence.
Plant recognition byTrichoderma harzianumelicits upregulation of a novel secondary metabolite cluster required for colonization
Authors: Schalamun Miriam , Li Guofen , Hinterdobler Wolfgang , Großkinsky Dominik K. , Compant Stéphane , Dreux-Zigha Assia , Gerke Jennifer , Cox Russell , Schmoll Monika 
Published: April 2023

AbstractTrichoderma harzianumis a filamentous ascomycete frequently applied as biocontrol agent in agriculture. While mycoparasitism and antagonism ofTrichodermaspp. against fungal pathogens are well known, early fungal responses to the presence of a plant await broader investigation. Analyzing early stages of plant-fungus communication we show thatT. harzianumB97 chemotropically responds to a plant extract and that both plant and fungus alter secondary metabolite secretion upon recognition. We developed a strategy for omics-analysis simulating conditions of early plant recognition eliciting a chemotropic response in the fungus and found 102 genes to be differentially regulated, including nitrate and nitrite reductases. Additionally, the previously uncharacterizedPlantCommunicationAssociated (PCA) gene cluster was strongly induced upon recognition of the plant, comprises a palindromic DNA motif and was essential for plant colonization. The PCA-cluster is only present in the Harzianum clade ofTrichodermaand closely related to a homologous cluster inMetarhiziumspp. Horizontal gene transfer (HGT) was detected for PCA-cluster genes by plants, while the cluster inT. harzianumis likely under balancing or positive selection.Hence, the PCA-cluster mediates early fungus-plant chemical communication and may be responsible for the high potential ofT. harzianumand closely related species for biocontrol applications.Plain language summaryInteractions of plants with fungi – beneficial or pathogenic – are crucial for the ecological function of both partners. Yet, the chemical “language” they use and how or when they use it is still insufficiently known. We describe discovery of a novel gene cluster, which is strongly induced upon plant recognition and essential for plant-fungal interkingdom interaction in the biocontrol-agentTrichoderma harzianum.
G-quadruplexe as a structural modulator of Intron Retention upon viral infection
Authors: Lejault Pauline , Terrier Michel-Pierre , Vannutelli Anaïs , Bolduc François , Brand Carolin , Perreault Martin Bisaillon Jean Pierre 
Published: April 2023

AbstractAmongst the wide array of alternative splicing events (ASE), the intrinsic mechanisms of intron retention have remained elusive. This particular type of ASE has long been characterized as an artifact, but recent studies have shown its implication in numerous diseases. It has also been revealed that numerous viruses choose to disrupt alternative splicing to escape cellular immune response and further their proliferation. The main focus of this study was to investigate the G-quadruplex role in Alternative Splicing Events (ASEs) that occur following Flavivirus infections. After having demonstrated that G-quadruplexes structures are mainly formed in Intron Retained Transcripts by RNA-seq, our attention turned toward the ULK3 gene, coding for a serine/threonine kinase regulating autophagy, an essential mechanism in the cellular response to stress and even pathogen infections. In this study, we revealed the presence of a G-quadruplex in the first intron of the ULK3 gene near the 3 ’ splice site. Furthermore, we assayed the formation and stability of this G-quadruplex in vitro and showed that its formation affects IR, as demonstrated by comparisons between wild-type and mutant transfected mini-genes. Finally, we identified the specific RNA-binding protein signature for this G-quadruplex, thereby uncovering the novel role of G-quadruplexes in Alternative Splicing.
Carcinoma-associated fibroblast-like tumor cells remodel the Ewing sarcoma tumor microenvironment
Authors: Wrenn Emma D. , Apfelbaum April A. , Rudzinski Erin R. , Deng Xuemei , Jiang Wei , Sud Sudha , Van Noord Raelene A. , Newman Erika A. , Garcia Nicolas M. , Hoglund Virginia J. , Bhise Shruti S. , Kanaan Sami B. , Waltner Olivia G. , Furlan Scott N. , Lawlor Elizabeth R. 
Published: April 2023

ABSTRACTTumor heterogeneity is a major driver of cancer progression. In epithelial-derived malignancies, carcinoma-associated fibroblasts (CAFs) contribute to tumor heterogeneity by depositing extracellular matrix (ECM) proteins that dynamically remodel the tumor microenvironment (TME). Ewing sarcomas (EwS) are histologically monomorphous, mesenchyme-derived tumors that are devoid of CAFs. Here we identify a previously uncharacterized subpopulation of transcriptionally distinct EwS tumor cells that deposit pro-tumorigenic ECM. Single cell analyses revealed that these CAF-like cells differ from bulk EwS cells by their upregulation of a matrisome-rich gene signature that is normally repressed by EWS::FLI1, the oncogenic fusion transcription factor that underlies EwS pathogenesis. Further, our studies showed that ECM-depositing tumor cells express the cell surface marker CD73, allowing for their isolation ex vivo and detection in situ. Spatial profiling of tumor xenografts and patient biopsies demonstrated that CD73+EwS cells and tumor cell-derived ECM are prevalent along tumor borders and invasive fronts. Importantly, despite loss of EWS::FLI1-mediated gene repression, CD73+EwS cells retain expression of EWS::FLI1 and the fusion-activated gene signature, as well as tumorigenic and proliferative capacities. Thus, EwS tumor cells can be reprogrammed to adopt CAF-like properties and these transcriptionally and phenotypically distinct cell subpopulations contribute to tumor heterogeneity by remodeling the TME.
Enhanced nonenzymatic RNA copying within-situactivation of short oligonucleotides
Authors: Ding Dian , Zhang Stephanie J. , Szostak Jack 
Published: April 2023

ABSTRACTThe nonenzymatic copying of RNA is thought to have been necessary for the transition between prebiotic chemistry and ribozyme-catalyzed RNA replication in the RNA World. We have previously shown that a potentially prebiotic nucleotide activation pathway based on phospho-Passerini chemistry can lead to the efficient synthesis of 2-aminoimidazole activated mononucleotides when carried out under freeze-thaw cycling conditions. Such activated nucleotides react with each other to form 5′-5′ 2-aminoimidazolium bridged dinucleotides, enabling template-directed primer extension to occur within the same reaction mixture. However, mononucleotides linked to oligonucleotides by a 5′-5′ 2-aminoimidazolium bridge are superior substrates for nonenzymatic primer extension, due to their higher intrinsic reactivity and their higher template affinity. Here we show that eutectic phase phospho-Passerini chemistry efficiently activates short oligonucleotides and promotes the formation of monomer-bridged-oligonucleotide species during freeze-thaw cycles. We then demonstrate thatin-situgenerated monomer-bridged-oligonucleotides lead to efficient nonenzymatic template copying in the same reaction mixture. Our findings pave the way for future research into the activation of complex mixtures of mono- and oligonucleotides for the enhanced copying and potentially the replication of arbitrary RNA sequences.
Cryo-EM structures of tau filaments from SH-SY5Y cells seeded with brain extracts from cases of Alzheimer’s disease and corticobasal degeneration
Authors: Tarutani Airi , Lövestam Sofia , Zhang Xianjun , Kotecha Abhay , Robinson Andrew C. , Mann David M.A. , Saito Yuko , Murayama Shigeo , Tomita Taisuke , Goedert Michel , Scheres Sjors H.W. , Hasegawa Masato 
Published: April 2023

AbstractThe formation of amyloid filaments through templated seeding is believed to underlie the propagation of pathology in most human neurodegenerative diseases. A widely used model system to study this process is to seed amyloid filament formation in cultured cells using human brain extracts. Here, we report the electron cryo-microscopy (cryo-EM) structures of tau filaments from undifferentiated seeded SH-SY5Y cells, that transiently expressed N-terminally HA-tagged 1N3R or 1N4R human tau, using brain extracts from individuals with AD or CBD. Although the resulting filament structures differed from those of the brain seeds, some degree of structural templating was observed. Studying templated seeding in cultured cells, and determining the structures of the resulting filaments, can thus provide insights into the cellular aspects underlying neurodegenerative diseases.
Corporate governance and bank performance: evidence from banking sector of Pakistan
Authors: Athar Muhammad , Chughtai Sumayya , Rashid Abdul 
Published: April 2023

Purpose
The aim of this study is to understand how board structure, size of audit committee (AC), gender diversity and ownership structure influence banks’ performance in Pakistan. This study also aims to examine how various dimensions of governance differently affect the different measures of bank performance.

Design/methodology/approach
This study used panel estimation techniques to quantify the impact of various elements of corporate governance on bank performance by taking annual data of 19 Pakistani banks for the period 2013–2020. The corporate governance is measured by board size, CEO duality, AC size, ownership structure and gender diversity. To get the robust results, this study measures bank performance by considering different indicators, namely, return on assets, earning per share, technical efficiency (TE) and total factor productivity. The empirical investigation is based on several well-known and well-accepted governance theories such as the agency theory, the stewardship theory, the tokenism/critical mass theory and the information asymmetry theory.

Findings
The findings of the study reveal that the size of board and ACs both significantly improve profitability and productivity, whereas they decrease TE. Further, the findings suggest that most of the indicators of gender diversity significantly deteriorate the performance of banks. However, ownership structure significantly improves banks’ earnings per share and TE. This study further illustrates that CEO’s duality does not have any significant impact on bank performance. This finding holds true for all the performance measures considered for this study.

Practical implications
The findings are of great importance to various stakeholders, especially to policymakers to know about the factors influencing different measures of performance. Specifically, based on these findings, they can devise the result-oriented strategies to enhance the financial and real performance of banks. The findings also suggest that both investors and owners should take into consideration the governance indicators while evaluating banks’ performance by using accounting, market-based, efficiency and productivity measures.

Originality/value
This research adds to the vast body of existing knowledge about the effectiveness of corporate governance by investigating how the different dimensions of corporate governance and gender diversity influence bank performance in a developing country, namely, Pakistan. Further, this study elaborates the domestic rules/regulations, governance theories and governance framework and practices and tries to link the empirical findings with them for better understanding the role of governance in determining the performance of the banking sector of Pakistan.
A multi-fidelity surrogate model based on extreme support vector regression: fusing different fidelity data for engineering design
Authors: Shi Mao-Lin , Lv Liye , Xu Lizhang 
Published: April 2023

PurposeExtreme support vector regression (ESVR) has been widely used in the design, analysis and optimization of engineering systems of its fast training speed and good computational ability. However, the ESVR model is only able to utilize one-fidelity information of engineering system. To solve this issue, this paper extends extreme support vector regression (ESVR) to a multi-fidelity surrogate (MFS) model which can make use of a few expensive but higher-fidelity (HF) samples and a lot of inaccurate but cheap low-fidelity (LF) samples, named ESVR-MFS.Design/methodology/approachIn the ESVR-MFS model, a kernel matrix is designed to evaluate the relationship between the HF and LF samples. The root mean square error of HF samples is used as the training error metric, and the optimal hyper-parameters of the kernel matrix are obtained through a heuristic algorithm.FindingsA number of numerical problems and three engineering problems are used to compare the ESVR-MFS model with the single-fidelity ESVR model and two benchmark MFS models. The results show that the ESVR-MFS model exhibits competitive performance in both numerical cases and practical cases tested in this work.Practical implicationsThe proposed approach exhibits great capability for practical multi-fidelity engineering design problems.Originality/valueA MFS model is proposed based on ESVR, which can make full use of the advantages of both HF data and LF data to achieve optimal results at same or lower cost.
Strategies for managing the political risk of investing in infrastructure projects, in developing countries
Authors: Jiang Weiling , Martek Igor 
Published: April 2023

PurposePolitical risk has been identified as a major impediment to the success of foreign invested projects, in developing countries. Infrastructure projects are especially sensitive to host-country political climates. Governance in emerging economies can be unstable, which adversely impacts infrastructure projects, given their high capital-intensity, long operational periods and high asset specificity. While the detrimental impact of political risk is well documented, the mitigation of such impacts on infrastructure projects remains largely unexamined. This study, therefore, addresses this by exploring the available identified political risk management (PRM) strategies based on resilience theory and evaluating their effectiveness.Design/methodology/approachA mixed-method approach was employed to identify PRM strategies. Firstly, a comprehensive literature review identified 40 potential PRM strategies. However, the applicability of those 40 strategies was uncertain due to the scarcity of PRM studies. Thus, expert interviews, drawing on the insights of Chinese infrastructure industry professionals with experience in FII, were applied to review the identified strategies. This process reduced the pool of applicable strategies to 34. Subsequently, 356 questionnaires were sent out to investors from China, Australia and Singapore, with 218 valid responses returned. Based on the data collected from the surveys, statistical analysis was used to evaluate and classify applicable PRM strategies.FindingsResults reveal the most effective top five strategies for offsetting the detrimental effects of political risk on foreign infrastructure investment to be: (1) selection of suitable markets and projects; (2) maintaining good relationship with government; (3) purchasing political insurance; (4) utilizing capable contractors from both host country and home country; and (5) adopting an appropriate entry mode. The 34 strategies were further consolidated into four meta-strategies through factor analysis, resulting in the formulation of a strategy selection matrix.Originality/valueThe findings of this study offer a rational means by which infrastructure investment practitioners considering projects in developing countries, may arrive at an optimal political risk mitigation strategy. The findings also offer government of host countries directives to improving the political environment in order to attract foreign investment flows into local infrastructure projects.
Determinants of climate-smart agricultural practices in smallholder plots: evidence from Wadla district, northeast Ethiopia
Authors: Belay Alebachew Destaw , Kebede Wuletaw Mekuria , Golla Sisay Yehuala 
Published: April 2023

Purpose
This study aims to examine determinants of farmers’ use of climate-smart agricultural practices, specifically improved crop varieties, intercropping, improved livestock breeds and rainwater harvesting in Wadla district, northeast Ethiopia.

Design/methodology/approach
A cross-sectional household survey was used. A structured interview schedule for respondent households and checklists for key informants and focus group discussants were used. This study used both descriptive statistics and a multivariate probit econometric model to analyze the collected data. The model was used to compute factors influencing the use of climate-smart agricultural practices in the study area.

Findings
The results revealed that households adopted selected practices. The likelihood of farmers’ decisions to use improved crop varieties, intercropping, improved livestock breeds and rainwater harvesting was 85%, 52%, 69% and 59%, respectively. The joint probability of using these climate-smart agricultural practices was 23.7%. The model results confirmed that sex, level of education, livestock holding, access to credit, farm distance, market distance and training were significant factors that affected the use of climate-smart agricultural practices in the study area.

Originality/value
The present study used the most selected locally practiced interventions for climate-smart agriculture.