bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating “tip fog”: Embracing uncertainty in tip measurements
Authors: Beaulieu Jeremy M. , O’Meara Brian C. 
Published: August 2024

AbstractNature is full of messy variation, which serves as the raw material for evolution. However, in comparative biology this variation is smoothed into averages. Overlooking this variation not only weakens our analyses but also risks selecting inaccurate models, generating false precision in parameter estimates, and creating artificial patterns. Furthermore, the complexity of uncertainty extends beyond traditional “measurement error,” encompassing various sources of intraspecific variance. To address this, we propose the term “tip fog” to describe the variance between the true species mean and what is recorded, without implying a specific mechanism. We show why accounting for tip fog remains critical by showing its impact on continuous comparative models and discrete comparative and diversification models. We rederive methods to estimate this variance and use simulations to assess its feasibility and importance in a comparative context. Our findings reveal that ignoring tip fog substantially affects the accuracy of rate estimates, with higher tip fog levels showing greater biases from the true rates, as well as affecting which models are chosen. The findings underscore the importance of model selection and the potential consequences of neglecting tip fog, providing insights for improving the accuracy of comparative methods in evolutionary biology.
UnigeneFinder: An automated pipeline for gene calling from transcriptome assemblies without a reference genome
Authors: Xue Bo , Prado Karine , Rhee Seung Yon , Stata Matt 
Published: August 2024

ABSTRACTFor most species in nature, transcriptome data is much more readily available than genome data. Without a reference genome, however, gene calling is cumbersome and inaccurate due to the high degree of redundancy inde novotranscriptome assemblies. To simplify and increase the accuracy ofde novotranscriptome assembly in the absence of a reference genome, we developed UnigeneFinder. Combining several clustering methods, UnigeneFinder substantially reduces the redundancy typical of raw transcriptome assemblies. This pipeline offers an effective solution to the problem of inflated transcript numbers, achieving a closer representation of the actual underlying genome. UnigeneFinder performs comparably or better, compared to existing tools, on plant species with varying genome complexities. UnigeneFinder is the only available transcriptome redundancy solution that fully automates the generation of primary transcript, coding region, and protein sequences, analogous to those available for high quality reference genomes. These features, coupled with the pipeline’s cross-platform implementation and focus on automation and an accessible user interface, make UnigeneFinder a useful tool for many downstream sequence-based analyses in non-model organisms lacking a reference genome, including differential gene expression analysis, accurate ortholog identification, functional enrichments, and evolutionary analyses. UnigeneFinder also runs efficiently both on high-performance computing (HPC) systems and personal computers, further reducing barriers to use.
Induction of Ferroptosis by an Amalgam of Extracellular Vesicles and Iron Oxide Nanoparticles Overcomes Cisplatin Resistance in Lung Cancer
Authors: Paramanantham Anjugam , Asfiya Rahmat , Manjunath Yariswamy , Xu Lei , McCully Grace , Das Siddharth , Yang Hu , Kaifi Jussuf T. , Srivastava Akhil 
Published: August 2024

AbstractExtracellular vesicles (EVs) hold potential as effective carriers for drug delivery, providing a promising approach to resolving challenges in lung cancer treatment. Traditional treatments, such as with the chemotherapy drug cisplatin, encounter resistance in standard cell death pathways like apoptosis, prompting the need to explore alternative approaches. This study investigates the potential of iron oxide nanoparticles (IONP) and EVs to induce ferroptosis—a regulated cell death mechanism—in lung cancer cells. We formulated a novel EV and IONP-based system, namely ‘ExoFeR’, and observed that ExoFeR demonstrated efficient ferroptosis induction, evidenced by downregulation of ferroptosis markers (xCT/SLC7A11 and GPX4), increased intracellular and mitochondrial ferrous iron levels, and morphological changes in mitochondria. To enhance efficacy, tumor-targeting transferrin (TF)-conjugated ExoFeR (ExoFeRTF) was developed. ExoFeRTFoutperformed ExoFeR, exhibiting higher uptake and cell death in lung cancer cells. Mechanistically, nuclear factor erythroid 2-related factor 2 (Nrf2)—a key regulator of genes involved in glutathione biosynthesis, antioxidant responses, lipid metabolism, and iron metabolism—was found downregulated in the ferroptotic cells. Inhibition of Nrf2 intracellular translocation in ExoFeRTF-treated cells was also observed, emphasizing the role of Nrf2 in modulating ferroptosis-dependent cell death. Furthermore, ExoFeR and ExoFeRTFdemonstrated the ability to sensitize chemo-resistant cancer cells, including cisplatin-resistant lung cancer patient-derived tumoroid organoids. In summary, ExoFeRTFpresents a promising and multifaceted therapeutic approach for combating lung cancer by intrinsically inducing ferroptosis and sensitizing chemo-resistant cells.
Feminization of social play behavior depends on microglia
Authors: VanRyzin Jonathan W , Marquardt Ashley E , McCarthy Margaret M 
Published: August 2024

AbstractMany sex differences in brain and behavior are established developmentally by the opposing processes of feminization and masculinization, which manifest following differential steroid hormone exposure in early life. The cellular mechanisms underlying masculinization are well-documented, a result of the fact that it is steroid-mediated and can be easily induced in newborn female rodents via exogenous steroid treatment. However, the study of feminization of particular brain regions has largely been relegated to being “not masculinization” given the absence of an identified initiating trigger. As a result, the mechanisms of this key developmental process remain elusive. Here we describe a novel role for microglia, the brain’s innate immune cell, in the feminization of the medial amygdala and a complex social behavior, juvenile play. In the developing amygdala, microglia promote proliferation of astrocytes equally in both sexes, with no apparent effect on rates of cell division, but support cell survival selectively in females through the trophic actions of Tumor Necrosis Factor α (TNFα). We demonstrate that disrupting TNFα signaling, either by depleting microglia or inhibiting the associated signaling pathways, prevents the feminization of astrocyte density and increases juvenile play levels to that seen in males. This data, combined with our previous finding that male-like patterns of astrocyte density are sculpted by developmental microglial phagocytosis, reveals that sexual differentiation of the medial amygdala involves opposing tensions between active masculinization and active feminization, both of which require microglia but are achieved via distinct processes.Significance StatementThe cellular mechanisms by which sex differences in the brain arise provide insight into the cellular basis of behavior. Most mechanistic studies have focused on the process whereby regions of the male brain are differentiated from the female in response to elevated gonadal steroid in development due to the tractability of inducing masculinization by blocking steroid action in males or providing exogenous steroids to newborn females. As such, feminization is usually defined as “not masculinized”. Here, we demonstrate the active feminization of astrocyte density in a brain region modulating complex social behavior, rough-and-tumble play in juveniles. These findings indicate that lower levels of playfulness in females is an actively regulated process as opposed to simply being a lack of masculinization.
Blocking toxin function and modulating the gut microbiota: caffeic acid phenethyl ester as a potential treatment forClostridioides difficileinfection
Authors: Guo Yan , Zhang Yong , Wang Guizhen , Liu Hongtao , Wang Jianfeng , Deng Xuming , He Liuqing , Qiu Jiazhang 
Published: August 2024

AbstractClostridioides difficileinfection (CDI) is the leading cause of hospital-acquired diarrhea that seriously threatens public health. The disruption of normal gut microbiota by the use of broad-spectrum antimicrobial agents enables C. difficile to proliferate in the colon. The emergence and prevalence of hypervirulent C. difficile strains result in increased morbidity, mortality, and high recurrence rates of CDI, thus creating a pressing need for novel therapeutics. The multi-domain toxins TcdA and TcdB are the primary determinants of CDI pathogenesis, rendering them ideal drug targets in the anti-virulence paradigm. In this study, we identified caffeic acid and its derivatives from natural compounds library as active inhibitors of TcdB via a cell-based high-throughput phenotypic screening. Further mechanistic investigations revealed that caffeic acid phenethyl ester (CAPE) could directly bind to TcdB, thus suppressing InsP6-induced autoproteolysis and inhibiting glucosyltransferase activity. CAPE treatment remarkably reduces the pathology of CDI in a murine infection model in terms of alleviated diarrhea symptoms, decreased bacterial colonization, and relieved histopathological lesions. Moreover, CAPE treatment ofC. difficile-challenged mice induces a remarkable increase in the diversity and composition of the gut microbiota (e.g.,Bacteroidesspp.) and alterations of gut metabolites (e.g., adenosine, D-proline, and melatonin), which might partially contribute to the therapeutic outcomes of CAPE against CDI. Our results reveal the potential of CAPE as a therapeutic for the management of CDI, or CAPE might serve as a lead compound for the development of antivirulence drugs targeting TcdB.
IGPR-1 is phosphorylated on the immunoreceptor tyrosine-based motif, stimulates AKT pathway and supports melanoma growth
Authors: Rahimi Nader , Potluri Sreesaisowmya , Chitalia Vipul 
Published: August 2024

ABSTRACTMelanoma is a lethal form of skin cancer that impacts one out of every five Americans and ranks as the fifth most prevalent cancer among men and women in the United States. Immunoglobulin (Ig) and Proline-rich Receptor-1 (IGPR-1, also called TMIGD2/CD28H) is closely related to immune checkpoint, CD28/PDL1 family receptors. It controls important cellular processes including, immune cell regulation, cell-cell adhesion, mechanosensing, autophagy, and angiogenesis, and its activity is associated with multiple human malignancies. However, the role and signaling mechanism of IGPR-1 in melanoma remains largely undefined. Here, we report that IGPR-1 is mutated or upregulated in nearly 13% of melanoma and its pro-tumor signaling in melanoma cells is mediated by phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM) tyrosine (Y222). IGPR-1 is phosphorylated at Y222 in human melanoma and cell culture. Phosphorylation of Y222 is context-dependent and is catalyzed by EGFR and Src kinase. Inhibition of EGFR by pharmacological and shRNA strategies inhibited phosphorylation of Y222, whereas stimulation with EGF promoted phosphorylation of Y222 in vivo and recombinant active EGFR catalyzed its phosphorylation in anin vitrokinase assay.In vivoco-immunoprecipitation andin vitroGST-pull-down assays demonstrated that phospho-Y222 facilitates the binding of IGPR-1 with the SH2 domain-containing proteins, SHC1 and SHP2. IGPR-1 stimulates multiple key signal transduction pathways relevant to tumorigenesis, including AKT, mTOR, and MAPK. Mutation of Y222 blocked IGPR-1-mediated activation of AKT and MAPK leading to inhibition of 3D-spheroid tumor growth. By investigating the immunoreceptor tyrosine-based motif signaling of IGPR-1, this study uncovers new findings that could have significant diagnostic and therapeutic implications for melanoma.
The structural basis for RNA slicing by human Argonaute2
Authors: Mohamed Abdallah A. , Wang Peter Y. , Bartel David P. , Vos Seychelle M. 
Published: August 2024

SUMMARYArgonaute (AGO) proteins associate with guide RNAs to form complexes that slice transcripts that pair to the guide. This slicing drives post-transcriptional gene-silencing pathways that are essential for many eukaryotes and the basis for new clinical therapies. Despite this importance, structural information on eukaryotic AGOs in a fully paired, slicing-competent conformation—hypothesized to be intrinsically unstable—has been lacking. Here we present the cryogenic-electron microscopy structure of a human AGO−guide complex bound to a fully paired target, revealing structural rearrangements that enable this conformation. Critically, the N domain of AGO rotates to allow the RNA full access to the central channel and forms contacts that license rapid slicing. Moreover, a conserved loop in the PIWI domain secures the RNA near the active site to enhance slicing rate and specificity. These results explain how AGO accommodates targets possessing the pairing specificity typically observed in biological and clinical slicing substrates.
Multi-Modal Large Language Model Enables Protein Function Prediction
Authors: Huo Mingjia , Guo Han , Cheng Xingyi , Singh Digvijay , Rahmani Hamidreza , Li Shen , Gerlof Philipp , Ideker Trey , Grotjahn Danielle A. , Villa Elizabeth , Song Le , Xie Pengtao 
Published: August 2024

AbstractPredicting the functions of proteins can greatly accelerate biological discovery and applications, where deep learning methods have recently shown great potential. However, these methods predominantly predict protein functions as discrete categories, which fails to capture the nuanced and complex nature of protein functions. Furthermore, existing methods require the development of separate models for each prediction task, a process that can be both resource-heavy and time-consuming. Here, we present ProteinChat, a versatile, multi-modal large language model that takes a protein’s amino acid sequence as input and generates comprehensive narratives describing its function. ProteinChat is trained using over 1,500,000 (protein, prompt, answer) triplets curated from the Swiss-Prot dataset, covering diverse functions. This novel model can universally predict a wide range of protein functions, all within a single, unified framework. Furthermore, ProteinChat supports interactive dialogues with human users, allowing for iterative refinement of predictions and deeper exploration of protein functions. Our experimental results, evaluated through both human expert assessment and automated metrics, demonstrate that ProteinChat outperforms general-purpose LLMs like GPT-4, one of the flagship LLMs, by over ten-fold. In addition, ProteinChat exceeds or matches the performance of task-specific prediction models.
Membrane microdomains are crucial forMycobacterium marinumEsxA-dependent membrane damage, escape to the cytosol and infection
Authors: Bosmani Cristina , Perret Angélique , Leuba Florence , Guého Aurélie , Hanna Nabil , Soldati Thierry 
Published: August 2024

ABSTRACTInfection by pathogenic mycobacteria such asMycobacterium tuberculosisdisrupts the membrane of the Mycobacterium-Containing Vacuole (MCV). The key effector EsxA, secreted via the ESX-1 type-VII system, is pivotal in this process, yet its membranolytic activity is not fully elucidated. Infecting the amoebaDictyostelium discoideumwithMycobacterium marinum, we demonstrate that the composition of the MCV membrane, notably its sterol-rich microdomains, significantly influences damage and rupture. Disruption of these microdomains through the knockout of organizing proteins, termed vacuolins, or through sterol depletion, markedly diminishesM. marinum-induced membrane damage and cytosolic escape, thereby increasing cellular resistance to infection. Furthermore, we establish that vacuolins and sterols are essential for thein vitropartitioning of EsxA within membranes. Extending our findings to mammalian cells, we show that the role of microdomain organizers and sterols is evolutionarily conserved; specifically, flotillin knockdown and sterol depletion enhance the resistance of murine microglial cells toM. marinuminfection. Our results underscore the critical role of host membrane microdomains in facilitating mycobacterial membranolytic activity and subsequent cytosolic access, pivotal for a successful infection.
The influence of perceived streamer characteristics and product characteristics on consumer behavior inertia in livestreaming contexts
Authors: Yuan Chunlin , Yin Yajing , Zhang Zeran , Wang Shuman , Moon Hakil 
Published: August 2024

PurposeThis study aims to develop a chain-mediated model to examine how streamer and product characteristics influence consumer behavior inertia (CBI) based on an extended cognitive-affective-conative (CAC) perspective.Design/methodology/approachThis study used an online survey concerning the livestreaming activities of 250 experienced shoppers to measure the proposed model.FindingsStreamer (product) attractiveness mediates the relationship between streamer (product) characteristics and shopping experience memory. Streamer (product) attractiveness and shopping experience memory have a chain mediating effect between the streamer (product) characteristics and CBI.Originality/valueTheoretically, the study demonstrates the critical role of attractiveness and shopping experience memory in the formation of consumer inertia and complements current explanations of consumer continuance of buying through livestreaming. From a managerial standpoint, the findings provide guidelines for enterprises carrying out livestreaming business on how to improve inertia to realize a stable profit source.
Influencer-generated content on social media: how does influencers’ self-disclosure affect followers’ purchase intentions?
Authors: Zhang Honghong 
Published: August 2024

PurposeThis study investigates the effects of two types of self-disclosure by influencers (i.e. personal self-disclosure and professional self-disclosure) on followers’ parasocial relationships with them and online engagement with their content, which eventually affect followers’ purchase intentions.Design/methodology/approachThis study collected data based on a cross-sectional survey of 823 social media users. Structural equation modeling analysis was used to test the overall structural model and the mediating roles of parasocial relationships and engagement.FindingsThis study reveals that influencers’ personal self-disclosure has a positive impact on followers’ parasocial relationships with them and online engagement with their content. Interestingly, the results indicate an inverted U-shaped relationship between influencers’ professional self-disclosure and followers’ parasocial relationships, as well as online engagement with the influencers’ content. Furthermore, followers’ parasocial relationships and engagement partially mediate the impact of influencers’ personal and professional self-disclosure on followers’ purchase intentions.Research limitations/implicationsThis study contributes to the literature by revealing the underlying mechanisms of the differential effects of influencers’ personal and professional self-disclosure on followers’ purchase intentions.Practical implicationsThe findings will assist marketers in leveraging influencer-generated content to enhance influencer marketing effectiveness.Originality/valueThis research provides a better understanding of the potential linear and nonlinear effects of influencers’ self-disclosure on followers’ parasocial relationships and engagement in social media marketing.
Navigating the innovation frontier: ambidextrous strategies, knowledge creation, and organizational agility in the pursuit of competitive excellence
Authors: Waseel Abdul Hakeem , Zhang Jianhua , Shehzad Muhammad Usman , Hussain Sarki Irshad , Kamran Muhammad Wajid 
Published: August 2024

PurposeThis study examines the link between the knowledge creation process, ambidextrous innovation, and competitive advantage. Further, this study also tested the moderating role of organizational agility on the relationship between the knowledge creation process and ambidextrous innovation.Design/methodology/approachThe empirical study’s data were collected by surveying 306 respondents employed in 140 Pakistani Small and Medium Enterprises (SMEs). The questionnaire was designed according to the study’s requirements and was based on theoretical knowledge and findings from previous research on the knowledge-creation process, ambidextrous innovation, and competitive advantage. All hypotheses were tested using a structured regression method.FindingsThe study indicates that the knowledge creation process significantly impacts a firm’s competitive advantage. Additionally, this study demonstrates that ambidextrous innovation can moderate the relationship between the knowledge-creation process and competitive advantage.Research limitations/implicationsFuture studies should examine mediating factors, such as organizational culture, leadership style, and industry characteristics, as well as moderating variables, such as environmental turbulence.Practical implicationsThis study guides SME leaders on the importance of knowledge creation and ambidextrous innovation in achieving operational success and gaining a competitive advantage.Originality/valueThis study explores how the knowledge creation process directly and indirectly, enhances organizational capacity for competitive advantage through the mediating roles of ambidextrous innovation and the moderating role of organizational agility.
Exploring factors influencing smart tourism destination visiting behaviors in a historic country: a theory of e-consumption behavior
Authors: Hasan Abdulla Al-Towfiq , Rahman Md. Masudur , Gani Mohammad Osman 
Published: August 2024

PurposeThis study aims to explore factors that influence tourists’ visiting behaviors towards smart tourism destinations (STDs) by extending the theory of planned behavior.Design/methodology/approachPartial least squares structural equation modeling (PLS-SEM) technique is used to test the proposed hypotheses by analyzing 413 usable responses that are collected through personal interviews. Moreover, data are collected using structured interviews and analyzed by SmartPLS, 3.3.3.FindingsThis study results reveal that STD visit intentions significantly influence STD visiting behaviors among international and domestic tourists in Bangladesh. Moreover, the results show that e-attitude, resource efficiency norms and perceived environmental sustainability have significant impacts on STD visit intentions.Practical implicationsThe study findings indicate that destinations’ electronic flowcharts of places, usage of low impact and biodegradable materials and history and culture presented in the forms of games and stories increase travelers’ motivation to visit STDs.Originality/valueThe study provides empirical evidence to support the importance of factors enhancing travelers’ STD visiting behaviors by integrating e-attitude, resource efficiency norms, perceived environmental sustainability and STD visit intentions.