bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilevel Plasticity and Altered Glycosylation Drive Aggressiveness in Hypoxic and Glucose-Deprived Bladder Cancer Cells
Authors: Peixoto Andreia , Ferreira Dylan , Miranda Andreia , Relvas-Santos Marta , Freitas Rui , Veth Tim S. , Brandão Andreia , Ferreira Eduardo , Paulo Paula , Cardoso Marta , Gaiteiro Cristiana , Cotton Sofia , Soares Janine , Lima Luís , Teixeira Filipe , Ferreira Rita , Palmeira Carlos , Heck Albert J. R. , Oliveira Maria José , Silva André M. N. , Santos Lúcio Lara , Ferreira José Alexandre 
Published: October 2023

AbstractBladder tumours with aggressive characteristics often present with microenvironmental niches marked by low oxygen levels (hypoxia) and limited glucose supply due to inadequate vascularization. The molecular mechanisms facilitating cellular adaptation to these stimuli remain largely elusive. Employing a multi-omics approach, we discovered that hypoxic and glucose- deprived cancer cells enter a quiescent state supported by mitophagy, fatty acidβ-oxidation, and amino acid catabolism, concurrently enhancing their invasive capabilities. Reoxygenation and glucose restoration efficiently reversed cell quiescence without affecting cellular viability, highlighting significant molecular plasticity in adapting to microenvironmental challenges. Furthermore, cancer cells exhibited substantial perturbation of proteinO-glycosylation, leading to simplified glycophenotypes with shorter glycosidic chains. Exploiting glycoengineered cell models, we established that immature glycosylation contributes to reduced cell proliferation and increased invasion. Our findings collectively indicate that hypoxia and glucose deprivation trigger cancer aggressiveness, reflecting an adaptive escape mechanism underpinned by altered metabolism and protein glycosylation, providing grounds for clinical intervention.
Protein Phosphatase PP1 Regulation of Pol II Phosphorylation is Linked to Transcription Termination and Allelic Exclusion of VSG Genes and TERRA in Trypanosomes
Authors: Kieft Rudo , Zhang Yang , Yan Haidong , Schmitz Robert J. , Sabatini Robert 
Published: October 2023

ABSTRACTThe genomes ofLeishmaniaand trypanosomes are organized into polycistronic transcription units flanked by a modified DNA base J involved in promoting RNA polymerase II (Pol II) termination. We recently characterized aLeishmaniacomplex containing a J-binding protein, PP1 protein phosphatase 1, and PP1 regulatory protein (PNUTS) that controls transcription termination potentially via dephosphorylation of Pol II by PP1. WhileT. bruceicontains eight PP1 isoforms, none purified with the PNUTS complex, suggesting a unique PP1-independent mechanism of termination. We now demonstrate that the PP1-binding motif of TbPNUTS is required for function in terminationin vivoand that TbPP1-1 modulates Pol II termination inT. bruceiinvolving dephosphorylation of the C-terminal domain of the large subunit of Pol II. PP1-1 knock-down results in increased cellular levels of phosphorylated large subunit of Pol II accompanied by readthrough transcription and pervasive transcription of the entire genome by Pol II, including Pol I transcribed loci that are typically silent, such as telomeric VSG expression sites involved in antigenic variation and production of TERRA RNA. These results provide important insights into the mechanism underlying Pol II transcription termination in primitive eukaryotes that rely on polycistronic transcription and maintain allelic exclusion of VSG genes.
Identification and full-genome assembly of novel Colorado potato beetle iflavirus and solinvi-like virus with SISPA Sequencing
Authors: Antonets Maria , Bodnev Sergei , Rotskaya Ulyana , Kosman Elena , Tregubchak Tatyana , Bauer Tatyana , Azaev Mamedyar , Kryukov Vadim , Antonets Denis 
Published: October 2023

AbstractThe Colorado potato beetle is one of the most devastating potato pests widespread in the world. However, its viral pathogens remain highly unexplored. Here using SISPA high-throughput sequencing of Colorado potato beetle (CPB) samples derived from prepupal larvae that died from an unknown infection, we have identified two previously unknown viruses and assembled their full-length genomic sequences. The subsequent genetic and phylogenetic analysis of the obtained sequences demonstrated that the isolated viruses, namedLeptinotarsa iflavirus 1andLeptinotarsa solinvi-like virus 1, are the novel representatives ofIflaviridaeandSolinviviridaeviral families, respectively. To the best of our knowledge, these are the first sequencing-confirmed insect viruses derived directly from CPB samples. And we also propose thatLeptinotarsa iflavirus 1may be associated with lethal disease in CPB.
In Vitro Safety Signals for Potential Clinical Development of the Anti-Inflammatory Pregnane X Receptor Agonist FKK6
Authors: Dvořák Zdeněk , Vyhlídalová Barbora , Pečinková Petra , Li Hao , Anzenbacher Pavel , Špičáková Alena , Anzenbacherová Eva , Chow Vimanda , Liu Jiabao , Krause Henry , Wilson Derek , Berés Tibor , Tarkowski Petr , Chen Dajun , Mani Sridhar 
Published: October 2023

ABSTRACTBackground and purposeBased on the mimicry of microbial metabolites, functionalized indoles were demonstrated as the ligands and agonists of the pregnane X receptor (PXR). The lead indole, FKK6, displayed PXR-dependent protective effects in DSS-induced colitis in mice andin vitrocytokine-treated intestinal organoid cultures. Here, we performed the initialin vitropharmacological profiling of FKK6.Experimental approachA complex series of cell-free and cell-based assays were employed. The organic synthesis, and advanced analytical chemistry methods were used.Key resultsFKK6-PXR interactions were characterized by hydrogen-deuterium exchange mass spectrometry. Screening FKK6 against potential cellular off-targets revealed high PXR selectivity. FKK6 has poor aqueous solubility but was highly soluble in simulated gastric and intestinal fluids. FKK6 was bound to plasma proteins and chemically stable in plasma. The partition coefficient of FKK6 was 2.70, and FKK6 moderately partitioned into red blood cells. In Caco2 cells, FKK6 displayed high permeability (A-B: 22.8 × 10-6cm.s-1) and no active efflux. These data are indicative of essentially completein vivoabsorption of FKK6. FKK6 was rapidly metabolized by cytochromes P450, notably by CYP3A4 in human liver microsomes. Two oxidized FKK6 derivatives, including N6-oxide and C19-phenol, were detected, and these metabolites had 5-7 × lower potency as PXR agonists than FKK6. This implies that despite high intestinal absorption, FKK6 is rapidly eliminated by the liver, and its PXR effects are predicted to be predominantly in the intestines.Conclusion and implicationsThe PXR ligand and agonist FKK6 has a suitable pharmacological profile supporting its potential preclinical development.BULLET POINT SUMMARYWhat is already known:Microbial metabolite mimic FKK6 is a hPXR agonist with anti-inflammatory properties in mice and human.Thein vitroPXR binding, absorption, and metabolism have not been completely characterized.What this study adds:PXR selectivity with unique binding mode, high intestinal cell permeability, rapid and complex microsomal metabolism.Initial testing for predicted metabolites shows reduced potency as PXR agonists.Clinical significance:PXR effects of FKK6 are predicted to be predominantly in the intestines.FKK6 has a suitable pharmacological profile supporting its potential preclinical development.
A spatial-temporal map of glutamatergic neurogenesis in embryonic cerebellar nuclei uncovers a high degree of cellular heterogeneity
Authors: Casoni Filippo , Croci Laura , Marroni Francesca , Demenego Giulia , Cremona Ottavio , Codazzi Franca , Consalez G. Giacomo 
Published: October 2023

ABSTRACTThe nuclei are the main output structures of the cerebellum. Each and every cerebellar cortical computation reaches several areas of the brain by means of CN processing and integration. Nevertheless our knowledge of these structures is still limited compared to the cerebellar cortex. Here, we present a genetic inducible fate mapping study characterizing rhombic lip-derived glutamatergic neurons of the nuclei, the most conspicuous family of long-range cerebellar efferent neurons. Glutamatergic neurons mainly occupy dorsal and lateral territories of the lateral and interposed nuclei, as well as the entire medial nucleus. They are born starting from about embryonic day 9.5, with a peak between 10.5 and 12.5, and invade the nuclei with a lateral to medial progression. While some markers label a heterogeneous population of neurons sharing a common location (Brn2), others appear to be lineage specific (Tbr1, Lmx1a, Meis2). A comparative analysis of Tbr1 and Lmx1a distributions reveals an incomplete overlap in their expression domains, in keeping with the existence of separate efferent subpopulations. Finally, some tagged glutamatergic progenitors are not labeled by any of the markers used in this study, disclosing further complexity. Taken together, our results obtained in late embryonic nuclei shed light on the heterogeneity of the excitatory neuron pool, underlying the diversity in connectivity and functions of this largely unexplored cerebellar territory. Our findings lay the groundwork for focused functional analyses of individual subpopulations of nuclear neurons.
EdTech applications and their adoption in Indian education sector–a bibliometric analysis and systematic literature review
Authors: Aaradhi Vaibhav , Chakraborty Debarun 
Published: October 2023

PurposeThis research intends to analyse the trend in educational technology (EdTech) over the last 20 years using systematic scientific mapping and bibliometric analysis and how it relates to the Indian context. Considering the anticipated growth in this field over the previous three years post-pandemic, an existing literature analysis is required. This study aims to map the existing intellectual structure in EdTech applications to extend the knowledge base further in this field. This study also intends to research how the Indian education sector compares in terms of the research output for the EdTech sector, considering the increased government focus on online learning as per the education policy in 2020. The study's findings will pave the way for sustainable research that will be extended in the future.Design/methodology/approachBibliometric analysis is conducted on the manuscripts extracted from Web of Science databases for the last 20 years (from 2003 to 2023). This study uses a descriptive research approach for bibliometric analysis as, by nature, this is an exploratory investigation, and no physical or existing experiment can be performed on the quantification, characteristic or productivity of EdTech applications. VoS Viewer and R software are extensively considered for a detailed bibliometric analysis.FindingsE-learning, blended learning and distance education emerged as the most frequently used keywords. The results reveal that technology adoption, higher education, technology and modelling are the most researched topics in this field.Research limitations/implicationsThis research is limited to the last 20 years' database obtained from the Web of Science database and limited to educational, management and operation databases only.Practical implicationsThe paper intends to analyse the global scenario of EdTech research and ensures that the paper will effectively connect with researchers, educators, policymakers and practitioners from different parts of the world. The results derived from the bibliometric analysis, cluster analysis and identification of key authors, journals and countries can contribute towards the improved contribution in this area.Originality/valueThe paper discusses the research in EdTech over the last two decades and effectively tries to bridge the gap in global research. Integrating systematic scientific mapping and bibliometric analysis is an innovative way to assess the growth and impact of EdTech. Considering the post-pandemic scenario and the government's emphasis on online learning, these are consistent with current developments.
Institutional investors' information needs in the context of the sustainable finance disclosure regulation (EU/2019/2088): the implications for companies' sustainability reporting
Authors: Gebhardt Maria , Schneider Anne , Seefloth Marcel , Zülch Henning 
Published: October 2023

PurposeThe paper aims to provide companies with a better understanding of the needs of institutional investors to improve the disclosure of sustainability information by companies. The study investigates the changed information needs of institutional investors resulting from the Sustainable Finance Disclosure Regulation (SFDR).Design/methodology/approachThis study uses an internet-based survey instrument amongst institutional investors to gain insights into their needs regarding sustainability information. The authors received 155 responses in total and use descriptive statistics and t-tests to analyse the survey data.FindingsThe results demonstrate that the implementation of the SFDR challenges institutional investors, as it affects their decision process. Additionally, the findings still indicate a lack of available corporate sustainability information, making it even more challenging for institutional investors to make appropriate investment decisions. Respondents suggest that information on climate-related risks is more important than the European Union (EU) Taxonomy metrics for meeting the SFDR requirements.Research limitations/implicationsThe findings are mainly restricted to the opinion of European investors. However, the evidence contributes to the existing literature by investigating institutional investors' information needs in the new regulatory landscape.Practical implicationsAs the study provides insights into institutional investors' needs, reporting companies recognise the relevance of transparently providing sustainability information to be further considered in the investment process of institutional investors despite the regulation. The findings can help regulators develop uniform and global sustainability reporting standards.Originality/valueThis paper is the first to provide evidence on sustainability information requested on the institutional investors' side. The survey gathers primary data from professional investment members unavailable in databases or reports.
The encroachment strategy under eco-innovation collaboration with delayed realized efficiency information
Authors: Li Yating , Chen Ting , Zhang Xinxin , Yuan Jiahang 
Published: October 2023

PurposeEco-innovation products, which means achieving more efficient and responsible use of resources and reducing the detrimental impact on the environment, can win a competitive advantage for the enterprises. But it is not easy to implement due to the high cost of eco-innovative technologies development, the uncertainty of market needs and return risk of investment. Many enterprises seek collaborations from their upstream suppliers to jointly carry out eco-innovation, such as Apple, IBM and Nike. A unique feature of collaboration is that efforts by one party enhance the marginal value of the other party's efforts. However, the collaboration will make the partner know the eco-innovation technology and prompt the partner to encroach the market to sell competitive products by herself. Motivated by this observation, this paper considers the optimal collaboration strategy on eco-innovation between upstream and downstream supply chain member and the optimal encroachment strategy of upstream supplier in a supply chain.Design/methodology/approachThis paper models a supply chain wherein a supplier provides products or materials for her manufacturer and cooperates with her manufacturer in eco-innovation. Also, the supplier could encroach on the market to sell similar products by herself. Then this paper uses game theory and mathematical modeling to do relative analysis.FindingsThe analysis reveals several interesting insights. First, eco-innovation collaboration makes supplier encroachment no longer only rely on the encroachment cost. The delayed realized eco-innovation efficiency information also plays a vital role. Second, different from previous research, the authors find the manufacturer's preference for supplier encroachment depends on the uncertainty of eco-innovation efficiency and potential market demand. Third, both partial and full encroachment strategies of the supplier can effectively improve the eco-innovation level.Originality/valueThe paper is the first to take the interplay between collaboration and encroachment into account in a supply chain. The results caution enterprises and policymakers to take vertical collaboration and delayed realized information into account in the competitive supply chain before making any operational decisions. Furthermore, the authors propose that governmental intervention aimed at stimulating supplier encroachment in appropriate circumstances can contribute to the improved environmental performance of products.
Alberta's Suicide Prevention Training Programs: A Retrospective Comparison with Rothman's Developmental Research Model
Authors: Ramsay R. F. , Cooke M. A. , Lang W. A. 
Published: October 2023

ABSTRACT: Developmental research is used to transform existing knowledge into applied programs. A social research and development (R&D) method, developed by Rothman for the human service professions, is compared with the method used to develop the Suicide Prevention Training Programs in Alberta, Canada. A retrospective review compares the development of these programs, which have since been implemented both nationally and internationally, with Rothman's model; discusses social R&D as a transformation methodology; and draws conclusions about the probable success of using developmental research methods in the human services.The review finds that the Alberta method closely paralleled the phases of Rothman's model. Results show that the transformation of knowledge about suicide into widely disseminated suicide prevention training programs can be attributed to the application of social R&D principles. The study concludes that the use of developmental research methods to establish human service programs should increase the probability of their success.
The dual role of GoPGF reveals that the pigment glands are synthetic sites of gossypol in aerial parts of cotton
Authors: Zhang Zhen‐Nan , Long Lu , Zhao Xiao‐Tong , Shang Shen‐Zhai , Xu Fu‐Chun , Zhao Jing‐Ruo , Hu Gai‐Yuan , Mi Ling‐Yu , Song Chun‐Peng , Gao Wei 
Published: October 2023

Summary
Gossypol and the related terpenoids are stored in the pigment gland to protect cotton plants from biotic stresses, but little is known about the synthetic sites of these metabolites.
Here, we showed that GoPGF, a key gene regulating gland formation, was expressed in gland cells and roots. The chromatin immunoprecipitation sequencing (ChIP‐seq) analysis demonstrated that GoPGF targets GhJUB1 to regulate gland morphogenesis.
RNA‐sequencing (RNA‐seq) showed high accumulation of gossypol biosynthetic genes in gland cells. Moreover, integrated analysis of the ChIP‐seq and RNA‐seq data revealed that GoPGF binds to the promoter of several gossypol biosynthetic genes. The cotton callus overexpressing GoPGF had dramatically increased the gossypol levels, indicating that GoPGF can directly activate the biosynthesis of gossypol. In addition, the gopgf mutant analysis revealed the existence of both GoPGF‐dependent and ‐independent regulation of gossypol production in cotton roots.
Our study revealed that the pigment glands are synthetic sites of gossypol in aerial parts of cotton and that GoPGF plays a dual role in regulating gland morphogenesis and gossypol biosynthesis. The study provides new insights for exploring the complex relationship between glands and the metabolites they store in cotton and other plant species.
LTP2 hypomorphs show genotype‐by‐environment interaction in early seedling traits in Arabidopsis thaliana
Authors: Alexandre Cristina M. , Bubb Kerry L. , Schultz Karla M. , Lempe Janne , Cuperus Josh T. , Queitsch Christine 
Published: October 2023

Summary
Isogenic individuals can display seemingly stochastic phenotypic differences, limiting the accuracy of genotype‐to‐phenotype predictions. The extent of this phenotypic variation depends in part on genetic background, raising questions about the genes involved in controlling stochastic phenotypic variation.
Focusing on early seedling traits in Arabidopsis thaliana, we found that hypomorphs of the cuticle‐related gene LIPID TRANSFER PROTEIN 2 (LTP2) greatly increased variation in seedling phenotypes, including hypocotyl length, gravitropism and cuticle permeability. Many ltp2 hypocotyls were significantly shorter than wild‐type hypocotyls while others resembled the wild‐type.
Differences in epidermal properties and gene expression between ltp2 seedlings with long and short hypocotyls suggest a loss of cuticle integrity as the primary determinant of the observed phenotypic variation. We identified environmental conditions that reveal or mask the increased variation in ltp2 hypomorphs and found that increased expression of its closest paralog LTP1 is necessary for ltp2 phenotypes.
Our results illustrate how decreased expression of a single gene can generate starkly increased phenotypic variation in isogenic individuals in response to an environmental challenge.
Inductive and divisional posets
Authors: Pagaria Roberto , Pismataro Maddalena , Tran Tan Nhat , Vecchi Lorenzo 
Published: October 2023

AbstractWe call a poset factorable if its characteristic polynomial has all positive integer roots. Inspired by inductive and divisional freeness of a central hyperplane arrangement, we introduce and study the notion of inductive posets and their superclass of divisional posets. It then motivates us to define the so‐called inductive and divisional abelian (Lie group) arrangements, whose posets of layers serve as the main examples of our posets. Our first main result is that every divisional poset is factorable. Our second main result shows that the class of inductive posets contains strictly supersolvable posets, the notion recently introduced due to Bibby and Delucchi (2022). This result can be regarded as an extension of a classical result due to Jambu and Terao (Adv. in Math. 52 (1984) 248–258), which asserts that every supersolvable hyperplane arrangement is inductively free. Our third main result is an application to toric arrangements, which states that the toric arrangement defined by an arbitrary ideal of a root system of type , or with respect to the root lattice is inductive.
Sharp Bounds and Precise Values for the Ni-Chromatic Number of Graphs
Authors: Yu Yangfan , Sun Yuefang 
Published: October 2023

Let [Formula: see text] be a connected undirected graph. A vertex coloring [Formula: see text] of [Formula: see text] is an [Formula: see text]-vertex coloring if for each vertex [Formula: see text] in [Formula: see text], the number of different colors assigned to [Formula: see text] is at most [Formula: see text]. The [Formula: see text]-chromatic number of [Formula: see text], denoted by [Formula: see text], is the maximum number of colors which are used in an [Formula: see text]-vertex coloring of [Formula: see text]. In this paper, we provide sharp bounds for [Formula: see text] of a graph [Formula: see text] in terms of its vertex cover number, maximum degree and diameter, respectively. We also determine precise values for [Formula: see text] in some cases.