bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eukfinder: a pipeline to retrieve microbial eukaryote genomes from metagenomic sequencing data
Authors: Zhao Dandan , Salas-Leiva Dayana E. , Williams Shelby K. , Dunn Katherine A. , Roger Andrew J. 
Published: December 2023

ABSTRACTWhole-genome shotgun (WGS) metagenomic sequencing of microbial communities allows us to discover the functions, physiologies, and evolutionary histories of microbial prokaryote and eukaryote members of diverse ecosystems. Despite their importance, metagenomic studies of microbial eukaryotes lag behind those of prokaryotes, due to the difficulty in identifying and assembling high-quality eukaryotic genomes from WGS data. To address this problem, we have developed Eukfinder, a bioinformatics pipeline that recovers and assembles nuclear and mitochondrial genomes of eukaryotic microbes from WGS metagenomics data. As part of its workflow, it utilizes two specialized databases to classify reads based on taxonomy which can be customized to the dataset or environment of interest. We applied Eukfinder to human gut microbiome WGS metagenomic sequencing data to recover genomes from the protistan parasiteBlastocystissp., a highly prevalent colonizer of the gastrointestinal tract of humans and animals. We tested Eukfinder using both a series of simulated gut microbiome datasets, which included varying numbers ofBlastocystisreads combined with bacterial reads and by using real metagenomic gut samples containingBlastocystis.We compared the results of Eukfinder with other published workflows. With sufficient reads, Eukfinder efficiently assembles high-quality near-complete nuclear and mitochondrial genomes from diverseBlastocystissubtypes from metagenomic data without the aid of a reference genome. Furthermore, with sufficient depth of sequence sampling, Eukfinder outperforms similar tools used to recover eukaryotic genomes from metagenomic data. Eukfinder will be a useful tool for reference-independent and cultivation-free study of eukaryotic microbial genomes from environmental metagenomic sequencing samples.IMPORTANCERapid advancements in next-generation sequencing technologies have made whole-genome shotgun (WGS) metagenomic sequencing an efficient method forde novoreconstruction of microbial genomes from samples taken from different environments. So far, thousands of new prokaryotic genomes have been characterized from strains or species that were unknown to science. However, the relatively large size and complexity of protistan genomes has, until recently, precluded the use of the WGS metagenomic approach to sample microbial eukaryotic diversity. The bioinformatics pipeline we developed, Eukfinder, can recover eukaryotic microbial genomes from environmental WGS metagenomic samples. By retrieving high-quality protistan genomes from diverse metagenomic samples, we can increase numbers of reference genomes available to aid future metagenomic investigations into the functions, physiologies, and evolutionary histories of eukaryotic microbes in the gut microbiome and a variety of other ecosystems.
Novel inhibitors of TTLL12’s oncogenic potential that overcome suppression of ligation of nitrotyrosine to the C-terminus of detyrosinated α-tubulin
Authors: Deshpande Amit , Brants Jan , Wasylyk Christine , van Hooij Onno , Verhaegh Gerald W , Maas Peter , Schalken Jack A , Wasylyk Bohdan 
Published: December 2023

AbstractTubulin tyrosine ligase 12 (TTLL) is a promising target for therapeutic intervention since it has been implicated in tumour progression, the innate immune response to viral infection, ciliogenesis and abnormal cell division. It is the most mysterious of a fourteen-member TTL/TTLL family, since, although it is the topmost conserved in evolution, it does not have predicted enzymatic activities. TTLL12 seems to act as a pseudo-enzyme that modulates various processes indirectly. Given the need to target its functions, we initially set out to identify a property of TTLL12 that could be used to develop a reliable high-throughput screening assay. We discovered that TTLL12 suppresses the cell toxicity of nitrotyrosine (3-nitrotyrosine) and its ligation to the C-terminus of detyrosinated α-tubulin (abbreviated to ligated-nitrotyrosine). Nitrotyrosine is produced by oxidative stress and is associated with cancer progression. Ligation of nitrotyrosine has been postulated to be a check-point induced by excessive cell stress. We found that the cytotoxicities of nitrotyrosine and tubulin poisons are independent of one another, suggesting that drugs that increase nitrotyrosination could be complementary to current tubulin-directed therapeutics. TTLL12 suppression of nitrotyrosination of α-tubulin was used to develop a robust cell-based ELISA assay that detects increased nitrotyrosination in cells that overexpress TTLL12 We adapted it to a high throughput format and used it to screen a 10,000 molecule World Biological Diversity SETTMcollection of low-molecular weight molecules. Two molecules were identified that robustly activate nitrotyrosine ligation at 1 μM concentration. This is the pioneer screen for molecules that modulate nitrotyrosination of α-tubulin. The molecules from the screen will be useful for the study of TTLL12, as well as leads for the development of drugs to treat cancer and other pathologies that involve nitrotyrosination.
Structural insights into rice KAI2 receptor provide functional implications for perception and signal transduction
Authors: Guercio Angelica M. , Gilio Amelia K. , Pawlak Jacob , Shabek Nitzan 
Published: December 2023

AbstractKAI2 proteins, classified as plant α/β hydrolase receptors, are capable of perceiving smoke-derived butenolide signals and endogenous, yet unidentified KAI2-ligands (KLs). While the number of functional KAI2 receptors varies among land plant species, rice possesses only one KAI2 gene. Rice, a significant crop and representative of grasses, relies on KAI2-mediated Arbuscular mycorrhiza (AM) symbioses to flourish in traditionally arid and nutrient-poor environments. This study presents the first crystal structure of an active rice KAI2 hydrolase receptor. Our structural and biochemical analyses uncover grass-unique pocket residues influencing ligand sensitivity and hydrolytic activity. Through structure-guided analysis, we identify a specific residue whose mutation enables the increase or decrease of ligand perception, catalytic activity, and signal transduction. Furthermore, we investigate rice KAI2-mediated signaling by examining its ability to form a complex with its binding partner, the F-box protein DWARF3 (D3) ubiquitin ligase, demonstrating the significant role of hydrophobic interactions in the KAI2-D3 interface. This study provides new insights into the diverse and pivotal roles of the KAI2 signaling pathway in the plant kingdom, particularly in grasses.
A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system
Authors: Moreno-Campos Rodrigo , Singleton Eileen W. , Uribe Rosa A. 
Published: December 2023

AbstractThe vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential GI functions such as gut motility and water balance, the ENS serves as a pivotal bidirectional link in the gut-brain axis. During early development, the ENS is primarily derived from enteric neural crest cells (ENCCs). Disruptions to ENCC development, as seen in conditions like Hirschsprung disease (HSCR), lead to absence of ENS in the GI, particularly in the colon. In this study, using zebrafish, we devised anin vivoF0 CRISPR-based screen employing a robust, rapid pipeline integrating single-cell RNA sequencing, CRISPR reverse genetics, and high-content imaging. Our findings unveil various genes, including those encoding for opioid receptors, as possible regulators of ENS establishment. In addition, we present evidence that suggests opioid receptor involvement in neurochemical coding of the larval ENS. In summary, our work presents a novel, efficient CRISPR screen targeting ENS development, facilitating the discovery of previously unknown genes, and increasing knowledge of nervous system construction.
Obesity modifies cell fate plasticity ofPdgfrα-expressing adipocyte progenitors to promote an aberrant mammary microenvironment
Authors: Kwende Sharon A. , Nuthalapati Prashant , Sunder Singh Jacqulene P. , Maity Subhajit , Ning Dun , Shryock Douglas G. , Xuan Zhenyu , Joshi Purna A. 
Published: December 2023

AbstractExcess fat gain culminating in obesity is a mounting global pandemic associated with a myriad of diseases including a higher risk of developing multiple cancers such as breast cancer. The underlying biological basis for obesity-linked breast cancer is attributed to alterations in adipose tissue-derived endocrine, metabolic and inflammatory factors. However, the precise cell types responsible for generating a cancer-susceptible mammary gland in obesity are not well understood. Using diet-induced obesity in conjunction with genetic reporter mouse models, we reveal elevated mammary adipocyte progenitors (MAPs) expressing Platelet-Derived Growth Factor Receptor alpha (PDGFRα) in the mammary tissue microenvironment during obesity. Single-cell RNA sequencing analysis demonstrate intensified obesity-driven trajectories of MAPs to immune and epithelial progenitor cells. Further, lineage tracing indicates an invasive cellular state of MAPs that confers greater access of MAP descendants into the mammary epithelium concomitant with their transition into immune and epithelial cell fates. MAPs in obesity exhibit heightened activation of cancer-associated and inflammatory pathways whereEgfris identified as a common target upregulated in MAPs. Mechanistic studies on purified MAPs with a major obesity diet component and EGFR stimulation corroborate dynamic EGFR-mediated MAP responses. Our findings uncover MAPs as key contributors to forging an aberrant mammary gland in obesity, providing insight into the potential utility of targeting this cell lineage for eradicating cancer risk related to augmented adiposity.
Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape
Authors: Cook Ashley L , Sur Surojit , Dobbyn Laura , Watson Evangeline , Cohen Joshua D , Ptak Blair , Lee Bum Seok , Paul Suman , Hsiue Emily , Popoli Maria , Vogelstein Bert , Papadopoulos Nickolas , Bettegowda Chetan , Gabrielson Kathy , Zhou Shibin , Kinzler Kenneth W , Wyhs Nicolas 
Published: December 2023

SummaryDespite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on the tumor cell surface. As an intrinsic cellular pathway, nonsense-mediated decay (NMD) conceals neoantigens through the destruction of the RNA products from genes harboring truncating mutations. We developed and conducted a high throughput screen, based on the ratiometric analysis of transcripts, to identify critical mediators of NMD. This screen implicated disruption of kinase SMG1’s phosphorylation of UPF1 as a potential disruptor of NMD. This led us to design a novel SMG1 inhibitor, KVS0001, that elevates the expression of transcripts and proteins resulting from truncating mutationsin vivoandin vitro. Most importantly, KVS0001 concomitantly increased the presentation of immune-targetable HLA class I-associated peptides from NMD-downregulated proteins on the surface of cancer cells. KVS0001 provides new opportunities for studying NMD and the diseases in which NMD plays a role, including cancer and inherited diseases.One Sentence SummaryDisruption of the nonsense-mediated decay pathway with a newly developed SMG1 inhibitor within-vivoactivity increases the expression of T-cell targetable cancer neoantigens resulting from truncating mutations.
Single tissue proteomics inCaenorhabditis elegansreveals proteins resident in intestinal lysosome-related organelles
Authors: Tan Chieh-Hsiang , Wang Ting-Yu , Park Heenam , Lomenick Brett , Chou Tsui-Fen , Sternberg Paul W. 
Published: December 2023

AbstractThe nematode intestine is the primary site for nutrient uptake and storage as well as the synthesis of biomolecules; lysosome-related organelles known as gut granules are important for many of these functions. Aspects of intestine biology are not well understood, including the export of the nutrients it imports and the molecules it synthesizes, as well as the complete functions and protein content of the gut granules. Here, we report a mass spectrometry-based proteomic analysis of the intestine of theCaenorhabditis elegansand of its gut granules. Overall, we identified approximately 5,000 proteins each in the intestine and the gonad and showed that most of these proteins can be detected in samples extracted from a single worm, suggesting the feasibility of individual-level genetic analysis using proteomes. Comparing proteomes and published transcriptomes of the intestine and the gonad, we identified proteins that appear to be synthesized in the intestine and then transferred to the gonad. To identify gut granule proteins, we compared the proteome of individual intestines deficient in gut granules to the wild-type. The identified gut granule proteome includes proteins known to be exclusively localized to the granules and additional putative novel gut granule proteins. We selected two of these putative gut granule proteins for validation via immunohistochemistry, and our successful confirmation of both suggests that our strategy was effective in identifying the gut granule proteome. Our results demonstrate the practicability of single tissue mass-spectrometry- based proteomic analysis in small organisms and in its utility for making discoveries.Significance statementWe show that tissue-specific proteomic analysis is achievable and can be done efficiently at an individual level in a small nematode, with resolution sufficient for genetic analysis on a single animal basis. With data collected from single animals, we produced high-quality sets of proteins that described the proteomes of the gonad and the intestine. Comparison of these proteomes with the organs’ transcriptomes improved our understanding of interorgan protein transport. We applied single-tissue proteomic to describe the proteome of the gut granules in the nematode intestine, a specialized lysosome-related organelle with important functions but which is not well characterized, identifying proteins not previously known to be associated with LROs and verifying two by subcellular localization.
A conceptual framework for the ICU of the future evaluated by the MIMIC-III digital archive
Authors: Markopoulos Dimitrios , Tsolakidis Anastasios , Triantafyllou Ioannis , Giannakopoulos Georgios A. , Skourlas Christos 
Published: December 2023

Purpose
This study aims to analyze a conspicuous corpus of literature related to the field of technology-based intensive care research and to develop an architecture model of the future smart intensive care unit (ICU).

Design/methodology/approach
Papers related to the topics of electronic health record (EHR), big data, data flow and clinical decision support in ICUs were investigated. These concepts have been analyzed in combination with secondary use of data, prediction models, data standardization and interoperability challenges. Based on the findings, an architecture model evaluated using MIMIC III is proposed.

Findings
Research identified issues regarding implementation of systems, data sources, interoperability, management of big data and free text produced in ICUs and lack of accuracy of prediction models. ICU should be treated as part of a greater system, able to intercommunicate with other entities.

Research limitations/implications
The research examines the current needs of ICUs in interoperability and data management. As environment changes dynamically, continuous assessment and evaluation of the model with other ICU databases is required.

Originality/value
The proposed model improves ICUs interoperability in national health system, ICU staff intercommunication, remote access and decision support. Its modular approach ensures that ICUs can have their own particularities and specialisms while ICU functions provide ongoing expertise and training to upgrade its staff.
Exploring the influence of content marketing strategies on the expansion of the fashion second-hand market: a theoretical prediction study
Authors: wei Lingwen , Hong Yan , Zeng Xianyi 
Published: December 2023

PurposeThe purpose of this research is to conduct a theoretical prediction study exploring the effectiveness of different content marketing strategies in expanding the second-hand market for fashion brands, comparing the costs and risks involved in these strategies in practice.Design/methodology/approachFirst, the expert interview method is employed to extract the content marketing strategies of the fashion second-hand market. Then, a descriptive space that is able to identify various fashion brand images is established. Then, experts' perceptions of the relationships between content marketing strategies and fashion brand image dimensions are obtained through a subjective evaluation procedure. Data of semantic evaluation were quantified and analyzed using the fuzzy logic method.FindingsWhen fashion brands expand to the second-hand market, they not only need to focus on improving the individual differentiation of products but also give priority to the quality of products and services and the overall customer experience. Exploring the “social impact strategy” will become an important direction for the development of fashion brands in the future.Originality/valueThe research methodology employed herein exhibits a noteworthy degree of novelty. This study introduces a pioneering theoretical prediction approach utilizing fuzzy logic, marking the inaugural exploration of this emerging and captivating dimension within the context of the study. Simultaneously, the study provides comparative results among content marketing strategies for expanding the fashion second-hand market, offering guidance for market expansion.
Real versus virtual celebrity endorsement: presentation of online product information and consumer attitudes toward digital products
Authors: Li Baoku , Nan Yafeng 
Published: December 2023

PurposeThis paper aims to reveal the influence of the presentation of online product information (POPI) on consumer attitudes in the context of online buying digital products.Design/methodology/approachTwo main experimental designs are used to collect data. The ANOVA, t-test and Bootstrap methods are applied to check hypotheses.FindingsFindings of Study 1 indicate that if the POPI is combined with different types of celebrity endorsement (CE) (real vs virtual), the self-brand connection will be changed and further influence consumer attitudes toward digital products. Study 2 verifies the diverse moderating effects of the type of virtual CE. The CRP (central-route presentation) online product information with SVCE (super-realistic-digital virtual CE) can decrease consumer attitudes, while the PRP (peripheral-route presentation) online product information with AVCE (anthropomorphic virtual CE) can enhance consumer attitudes.Practical implicationsE-commerce enterprises should optimize the current layout of POPI by considering diverse matchings between POPI and CE to increase consumer attitudes. Moreover, marketers could make various schemes of POPI considering (virtual) CE and self-brand connection.Originality/valueFindings contribute to understanding the relationship between POPI and consumer attitudes considering the mediation of self-brand connection and the mediations of virtual/real CE. Additionally, this study bridges the gap between research on virtual CE and business practices.
A VUCA-ready workforce: exploring employee competencies and learning and development implications
Authors: Shet Sateesh V. 
Published: December 2023

PurposeThe author aims to develop an employee competency framework for a volatility, uncertainty, complexity and ambiguity (VUCA) environment and propose learning and development (L&D) interventions for organisations and employees to develop competencies for thriving in a VUCA environment.Design/methodology/approachThe framework synthesis method was used to determine employee competencies that are essential in a VUCA world.FindingsThe author identified 10 competencies that are essential for employee development in a VUCA world. The author categorised these employee competencies as cognitive (cognitive flexibility, agility mindset and personal ambidexterity), cross-cultural (cross-cultural intelligence and cross-cultural collaboration), analytical (creativity and complex problem solving) and personal effectiveness competencies (personal resilience, continuous learning and adaptive mindset).Practical implicationsThe proposed competencies could be used for the personal development of employees and organisations. The VUCA competency framework developed in this study includes behavioural dimensions for each competency, which could be used in self-assessment, recruitment and selection and talent and performance management. Furthermore, the author proposes L&D interventions required for developing these competencies. Overall, this study contributes to human resources (HR) development in the VUCA era by proposing the development of specific individual competencies as necessary conditions for survival and growth.Originality/valueVUCA competencies empower employees to not only survive but also thrive in an unpredictable and rapidly changing world. By incorporating these competencies in L&D interventions, organisations can help employees develop the necessary competencies to thrive in a VUCA environment, thus contributing to their personal and organisational success.
Lung and blood perioperative metalloproteinases in patients undergoing oncologic lung surgery: Prognostic implications
Authors: Alonso Angel , de la Gala Francisco , Vara Elena , Hortal Javier , Piñeiro Patricia , Reyes Almudena , Simón Carlos , Garutti Ignacio 
Published: December 2023

AbstractBackgroundMetalloproteinases (MMPs) have been reported to be related to oncologic outcomes. The main goal of the study was to study the relationship between these proteins and the long‐term prognosis of patients undergoing oncologic lung resection surgery.MethodsThis was a substudy of the phase IV randomized control trial (NCT 02168751). We analyzed MMP‐2, ‐3, ‐7, and ‐9 in blood samples and bronchoalveolar lavage (LBA) and the relationship between MMPs and long postoperative outcomes (survival and disease‐free time of oncologic recurrence).ResultsSurvival was longer in patients who had lower MMP‐2 levels than those with higher MMP‐2 in blood samples taken 6 h after surgery (6.8 vs. 5.22 years; p = 0.012) and MMP‐3 (6.82 vs. 5.35 years; p = 0.03). In contrast, survival was longer when MMP‐3 levels were higher in LBA from oncologic lung patients than those with lower MMP‐3 (7.96 vs. 6.02 years; p = 0.005). Recurrence‐free time was longer in patients who had lower MMP‐3 levels in blood samples versus higher (5.97 vs. 4.23 years; p = 0.034) as well as lower MMP‐7 (5.96 vs. 4.5 years; p = 0.041) or lower MMP‐9 in LBA samples (6.21 vs. 4.18 years; p = 0.012).ConclusionMMPs were monitored during the perioperative period of oncologic lung resection surgery. These biomarkers were associated with mortality and recurrence‐free time. The role of the different MMPs analyzed during the study do not have the same prognostic implications after this kind of surgery.