bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial Dysfunction alters Early Endosome Distribution and Cargo Trafficking via ROS-Mediated Microtubule Reorganization
Authors: Vishwakarma Anjali , Chihki Lilia , Todkar Kiran , Ouellet Mathieu , Germain Marc 
Published: August 2024

AbstractMitochondria are essential for bioenergetic functions and various cellular processes, including differentiation and immunity, their dysfunction leading to several pathologies. While these pathologies have traditionally been associated with ATP deficits, mitochondrial dysfunction also leads to reactive oxygen species (ROS) generation, inflammation, and alterations the function of other organelles. While the negative impact of mitochondrial dysfunction on lysosomal activity has been established, the relationship between mitochondria and the rest of the endocytic compartment remains poorly understood. Here, we show that inhibiting mitochondrial activity through genetic and chemical approaches causes early endosome (EE) perinuclear aggregation and impairs cargo delivery to lysosomes. This impairment is due to altered microtubule architecture and centrosome dynamics, mediated by ROS. Antioxidants can rescue these EE defects, underlying the pivotal role of mitochondria in maintaining cellular activities through ROS regulation of microtubule networks. Our findings highlight the significance of mitochondria beyond ATP production, emphasizing their critical involvement in endocytic trafficking and cellular homeostasis. These insights emphasize mitochondria’s critical involvement in cellular activities and suggest novel targets for therapies to mitigate the effects of mitochondrial dysfunction.
Swashing motility: A novel propulsion-independent mechanism for surface migration inSalmonellaandE. coli
Authors: Panich Justin , Dudebout Eric M. , Wadhwa Navish , Blair David F. 
Published: August 2024

AbstractBacterial motility over surfaces is crucial for colonization, biofilm formation, and pathogenicity. Surface motility inEscherichia coliandSalmonella entericais traditionally believed to rely on flagellar propulsion. Here, we report a novel mode of motility, termed “swashing,” where these bacteria migrate on agar surfaces without functional flagella. Mutants lacking flagellar filaments and motility proteins exhibit rapid surface migration comparable to wild-type strains. Unlike previously described sliding motility, swashing is inhibited by surfactants and requires fermentable sugars. We propose that the fermentation of sugars at the colony edge produces osmolytes, creating local osmotic gradients that draw water from the agar, forming a fluid bulge that propels the colony forward. Our findings challenge the established view that flagellar propulsion is required for surface motility inE. coliandSalmonella, and highlight the role of a fermentation in facilitating bacterial spreading. This discovery expands our understanding of bacterial motility, offering new insights into bacterial adaptive strategies in diverse environments.Significance StatementBacteria move on surfaces using a variety of mechanisms, with important implications for their growth and survival in both the clinical setting (such as on the surface of medical devices) and in the wild. Surface motility in the medically important model speciesS. entericaandE. colihas been extensively studied and is thought to require flagellar propulsion. Here, we show surface expansion in these species even in the absence of propulsion by the flagella. Instead, movement is tied to fermentation and surface tension: As cells ferment sugars, they create local osmolarity gradients, which generate a wave of fluid on which the cells “swash.”
Context-specific inhibition of mitochondrial ribosomes by phenicol and oxazolidinone antibiotics
Authors: Bibel Brianna , Raskar Tushar , Couvillion Mary , Lee Muhoon , Kleinman Jordan I. , Takeuchi-Tomita Nono , Churchman L. Stirling , Fraser James S. , Fujimori Danica Galonić 
Published: August 2024

ABSTRACTThe antibiotics chloramphenicol (CHL) and oxazolidinones including linezolid (LZD) are known to inhibit mitochondrial translation. This can result in serious, potentially deadly, side effects when used therapeutically. Although the mechanism by which CHL and LZD inhibit bacterial ribosomes has been elucidated in detail, their mechanism of action against mitochondrial ribosomes has yet to be explored. CHL and oxazolidinones bind to the ribosomal peptidyl transfer center (PTC) of the bacterial ribosome and prevent incorporation of incoming amino acids under specific sequence contexts, causing ribosomes to stall only at certain sequences. Through mitoribosome profiling, we show that inhibition of mitochondrial ribosomes is similarly context-specific – CHL and LZD lead to mitoribosome stalling primarily when there is an alanine, serine, or threonine in the penultimate position of the nascent peptide chain. We further validate context-specific stalling through in vitro translation assays. A high resolution cryo-EM structure of LZD bound to the PTC of the human mitoribosome shows extensive similarity to the mode of bacterial inhibition and also suggests potential avenues for altering selectivity. Our findings could help inform the rational development of future, less mitotoxic, antibiotics, which are critically needed in the current era of increasing antimicrobial resistance.
Deciphering Pre-existing and Induced 3D Genome Architecture Changes involved in Constricted Melanoma Migration
Authors: Playter Christopher , Golloshi Rosela , Garretson Joshua H. , Gonzalez Alvaro Rodriguez , Olajide Taiwo Habeeb , Saad Ahmed , Benson Samuel John , McCord Rachel Patton 
Published: August 2024

SummaryMetastatic cancer cells traverse constricted spaces that exert forces on their nucleus and the genomic contents within. Cancerous tumors are highly heterogeneous and not all cells within them can achieve such a feat. Here, we investigated what initial genome architecture characteristics favor the constricted migratory ability of cancer cells and which arise only after passage through multiple constrictions. We identified a cell surface protein (ITGB4) whose expression correlates with increased initial constricted migration ability in human melanoma A375 cells. Sorting out this subpopulation allowed us to identify cellular and nuclear features that pre-exist and favor migration, as well as alterations that only appear after cells have passed through constrictions. We identified specific genomic regions that experienced altered genome spatial compartment profiles only after constricted migration. Our study reveals 3D genome structure contributions to both selection and induction mechanisms of cell fate change during cancer metastasis.
Parallel mechanisms signal a hierarchy of sequence structure violations in the auditory cortex
Authors: Jamali Sara , Bagur Sophie , Brémont Enora , Van Kerkoerle Timo , Dehaene Stanislas , Bathellier Brice 
Published: August 2024

AbstractThe brain predicts regularities in sensory inputs at multiple complexity levels, with neuronal mechanisms that remain elusive. Here, we monitored auditory cortex activity during the local-global paradigm, a protocol nesting different regularity levels in sound sequences. We observed that mice encode local predictions based on stimulus occurrence and stimulus transition probabilities, because auditory responses are boosted upon prediction violation. This boosting was due to both short-term adaptation and an adaptation-independent surprise mechanism resisting anesthesia. In parallel, and only in wakefulness, VIP interneurons responded to the omission of the locally expected sound repeat at sequence ending, thus providing a chunking signal potentially useful for establishing global sequence structure. When this global structure was violated, by either shortening the sequence or ending it with a locally expected but globally unexpected sound transition, activity slightly increased in VIP and PV neurons respectively. Hence, distinct cellular mechanisms predict different regularity levels in sound sequences.
Evaluating Methods for the Prediction of Cell Type-Specific Enhancers in the Mammalian Cortex
Authors: Johansen Nelson J. , Kempynck Niklas , Zemke Nathan R. , Somasundaram Saroja , Winter Seppe De , Hooper Marcus , Dwivedi Deepanjali , Lohia Ruchi , Wehbe Fabien , Li Bocheng , Abaffyová Darina , Armand Ethan J. , Man Julie De , Eksi Eren Can , Hecker Nikolai , Hulselmans Gert , Konstantakos Vasilis , Mauduit David , Mich John K. , Partel Gabriele , Daigle Tanya L. , Levi Boaz P. , Zhang Kai , Tanaka Yoshiaki , Gillis Jesse , Ting Jonathan T. , Ben-Simon Yoav , Miller Jeremy , Ecker Joseph R. , Ren Bing , Aerts Stein , Lein Ed S. , Tasic Bosiljka , Bakken Trygve E. 
Published: August 2024

SummaryIdentifying cell type-specific enhancers in the brain is critical to building genetic tools for investigating the mammalian brain. Computational methods for functional enhancer prediction have been proposed and validated in the fruit fly and not yet the mammalian brain. We organized the ‘Brain Initiative Cell Census Network (BICCN) Challenge: Predicting Functional Cell Type-Specific Enhancers from Cross-Species Multi-Omics’ to assess machine learning and feature-based methods designed to nominate enhancer DNA sequences to target cell types in the mouse cortex. Methods were evaluated based onin vivovalidation data from hundreds of cortical cell type-specific enhancers that were previously packaged into individual AAV vectors and retro-orbitally injected into mice. We find that open chromatin was a key predictor of functional enhancers, and sequence models improved prediction of non-functional enhancers that can be deprioritized as opposed to pursued forin vivotesting. Sequence models also identified cell type-specific transcription factor codes that can guide designs of in silico enhancers. This community challenge establishes a benchmark for enhancer prioritization algorithms and reveals computational approaches and molecular information that are crucial for the identification of functional enhancers for mammalian cortical cell types. The results of this challenge bring us closer to understanding the complex gene regulatory landscape of the mammalian brain and help us design more efficient genetic tools and potential gene therapies for human neurological diseases.
Unveiling the potato cultivars with microbiome interactive traits for sustainable agricultural production
Authors: Zhao Tianci , Vink Stefanie N. , Jia Xiu , Erban Alexander , Schaarschmidt Stephanie , Kopka Joachim , Zuther Ellen , Treder Krzysztof , Michałowska Dorota , Guyoneaud Rémy , Elzenga J. Theo M. , Attard Eléonore , Salles Joana Falcão 
Published: August 2024

ABSTRACTRoot traits significantly shape rhizosphere microbiomes, yet their impact on microbes is often overlooked in plant breeding programs. Here, we propose that selecting modern cultivars based on microbiome interactive traits (MITs), such as root biomass and exudate patterns, can enhance agricultural sustainability by interacting effectively with soil microbiomes, which in turn, promotes plant growth and resistance to stress, thereby reducing reliance on synthetic crop protectants. Through a stepwise selection process, we chose 51 potato cultivars based on their plant growth matrices with distinct root exudate patterns. In a greenhouse experiment, we verified their capacity to interact with the soil microbiome. These were further clustered into functional groups based on their MITs and leaf metabolites and further characterised by their rhizosphere microbiome (bacterial and fungal communities). Our results indicate a positive correlation between microbial community diversity and root biomass. A potential influence of leaf metabolites on the composition of rhizosphere bacteria was observed, supporting the plant holobiont framework. We highlight the significance of incorporating positive effects on microbiomes into the breeding targets to advance the objectives of sustainable agriculture. Finally, a set of 11 potato cultivars was selected to verify whether those with microbiome-interactive traits could contribute to sustainable agricultural production under field conditions.
Hybrid Genome Sequence ofCryptococcus neoformansof Indian origin and Comparative Genome Analysis
Authors: Sathiyamoorthy Jananishree , Ramakrishnan Jayapradha 
Published: August 2024

AbstractObjectivesThe Indian isolate ofCryptococcus neoformansunderwent complete genome sequencing to elucidate its genomic architecture and functional characteristics. Furthermore, this study aimed to comprehensively characterize the virulence factors (virulome), antibiotic resistance genes (resistome), and the pan-genome ofC. neoformansspp. through a comparative genomic analysis, providing insights into the genetic diversity and evolutionary relationships among strains.MethodsThe genomic data of a clinical strain ofC. neoformanswas assembled and annotated by MaSuRCA5 and Braker tool. Along with this, the assembled genomic data of the 11 strains were retrieved from NCBI datasets. The comparative virulome, resistome, phylogeny and of the 12C. neoformansgenomes were analyzed using DFVF, AFRbase, BLAST, CLUSTAL Omega, MEGAX, and Orthovenn3, respectively.ResultsThe sequenced isolate was identified as a member of theCryptococcus neoformansvar.grubiisubspecies. Notably, virulence-related genes comprise approximately 4.8% of the total genome. A comparative genomic analysis of 12 study genomes revealed variations in virulence patterns, including differences in melanization, immune evasion, blood-brain barrier evasion, transcriptional regulation, and oxidative stress response. The phylogenetic study using MLST and orthologous clusters categorized the subspeciesgrubiiandneoformansin different clades. Pan-genome analysis showed that 73.6% of orthologous gene clusters and 77.72% of orthologous proteins were conserved across all 12 study genomes, indicating a shared core genome. Furthermore, the evolutionary relatedness study of the pan-genome revealed gene expansion and contraction events among the study strains.ConclusionThis pioneering study presents the first comprehensive genomic and comparative genomic analysis ofCryptococcussp., incorporating data on virulence genes, antibiotic resistance, and pan-genome dynamics. Key findings reveal that strains Cn, H99, and JEC21 harbor crucial virulence genes associated with infection severity. While all study strains possess genes promoting antifungal resistance (AFR), most lack specific single nucleotide polymorphisms defining AFR. Consistent with pan-genome analysis, our results show significant gene expansion and contraction events in these strains. This study underscores the importance of bioinformatic tools for efficient whole-genome analysis and large-scale comparative genomics research.
High-quality transcriptome profile ofTreponema pallidumsubsp.pallidum: confirmation of transcriptional landscape
Authors: Grillová Linda , Carrami Eli M , Roberts-Sengier William , Thomson Nicholas R. 
Published: August 2024

AbstractSyphilis remains a critical global health challenge due to its potential for severe complications and the increase in its incidence rate over recent years. Until recently, the infectious agent of syphilis,Treponema pallidumsubsp.pallidum(TPA), could not be culturedin vitro. Advances in co-culture techniques have finally allowed for effective long-term cultivation of TPA, providing a platform to study its biology. Limited transcriptional data from TPA have been reported so far and many genes in treponemal genomes are annotated based onin silicoprediction of putative coding sequences without functional validation. To inform future syphilis vaccine development, experimental validation ofin silicopredicted genes coupled with functional annotation is necessary. In this study, strand-specific RNA-sequencing was used to reconstruct a high-quality transcriptome profile of TPA, confirming the active transcription of genes previously annotated as hypothetical, paving the way for more accurate identification of vaccine target candidates. Our transcriptomic data also revealed, for the first time, the organization of genes into transcription units, an abundance of anti-sense RNAs, and transcripts from intergenic regions, providing crucial insights for future functional genomics studies of TPA.Author SummaryIn our study, we explored the genetic activity of the bacteria responsible for syphilis,Treponema pallidumsubsp.pallidum(TPA). Although syphilis has been a known disease for centuries, the bacterium causing it has remained difficult to study because it couldn’t be easily grown in the lab. Recently, new techniques have allowed us to cultivate TPA successfully, enabling deeper investigation into its genetics. By employing directional RNA sequencing, we have mapped out which genes are actively transcribed, including those previously labeled as hypothetical. Our study has also revealed new insights into the gene organization and uncovered the presence of antisense RNA, which may regulate gene expression. These findings offer critical information that could inform future research and vaccine development efforts for syphilis.
Population genomics of a thermophilic cyanobacterium revealed divergence at subspecies level and possible adaptation genes
Authors: Chang Hsin-Ying , Yen Hsi-Ching , Chu Hsiu-An , Kuo Chih-Horng 
Published: August 2024

AbstractBackgroundCyanobacteria are diverse phototrophic microbes with ecological importance and potential for biotechnology applications. One species of thermophilic cyanobacteria,Thermosynechococcus taiwanensis, has been studied for biomass pyrolysis, estrogen degradation, and the production of bioethanol, monosaccharide, and phycocyanin. To better understand the diversity and evolution of this species, we sampled across different regions in Taiwan for strain isolation and genomic analysis.ResultsA total of 27 novel strains were isolated from nine of the 12 hot springs sampled and subjected to whole genome sequencing. Including strains studied previously, our genomic analyses encompassed 32 strains from 11 hot springs. Genome sizes among these strains ranged from 2.64 to 2.70 Mb, with an average of 2.66 Mb. Annotation revealed between 2,465 and 2,576 protein-coding genes per genome, averaging 2,537 genes. Core-genome phylogeny, gene flow estimates, and overall gene content divergence consistently supported the within-species divergence into two major populations. While isolation by distance partially explained the within-population divergence, the factors driving divergence between populations remain unclear. Nevertheless, this species likely has a closed pan-genome comprising approximately 3,030 genes, with our sampling providing sufficient coverage of its genomic diversity. To investigate the divergence and potential adaptations, we identified genomic regions with significantly lower nucleotide diversity, indicating loci that may have undergone selective sweeps within each population. We identified 149 and 289 genes within these regions in populations A and B, respectively. Only 16 genes were common to both populations, suggesting that selective sweeps primarily targeted different genes in the two populations. Key genes related to functions such as carbon fixation, photosynthesis, motility, and ion transport were highlighted.ConclusionsThis work provides a population genomics perspective on a hot spring cyanobacterial species in Taiwan. Beyond advancing our understanding of microbial genomics and evolution, the strains collected and genome sequences generated in this work provide valuable materials for future development and utilization of biological resources.
Unlocking digital innovation: a moderated-mediation approach exploring the knowledge creation processes, IT-enabled capabilities and absorptive capacity in software SMEs
Authors: Sherani  , Zhang Jianhua , Shehzad Muhammad Usman , Ali Sher , Cao Ziao 
Published: August 2024

Purpose This study aims to determine whether knowledge creation processes (KCPs) – knowledge exchange and knowledge integration affect digital innovation (DI), including information technology (IT)-enabled capabilities (ITECs) as a mediator and absorptive capacity (AC) as a moderator.Design/methodology/approach With a survey data set of 390 employees from Pakistani software small- and medium-sized enterprises (SMEs), the current study employed Structural Equation Modeling (SEM) using Smart Partial Least Squares to estimate the structural relationships in the conceptual model.Findings The results confirm that KCPs – knowledge exchange and knowledge integration positively enhance software SME's DI; ITECs play a partial mediating role in the linkage between KCPs and DI; AC positively moderates the relationship between knowledge integration and ITECs, and ITECs and DI, while AC doesn’t moderate the relationship between knowledge exchange and ITECs. The AC positively moderates the mediating role of ITECs amongst KCPs (knowledge exchange and knowledge integration) and DI, respectively.Originality/value This research uniquely integrates the knowledge-based view and dynamic capability theory to present a comprehensive framework that explains the interdependencies between knowledge process, ITECs and AC in driving DI. This approach advances the understanding of how software SMEs can strengthen internal knowledge and IT resources to achieve superior innovation outcomes.
The impact of marketing assets of foreign subsidiaries on marketing dynamic capabilities of multinational enterprises (MNEs): the mediating effect of customer orientation
Authors: Li Hui , Xu Lei , Zhang Junwei , Duan Yingwen 
Published: August 2024

PurposeThe purpose of this paper is to explore mechanisms of the overseas marketing assets needed for marketing dynamic capability in Chinese multinational enterprises (MNEs) settings. Marketing assets of foreign subsidiaries contribute to the dynamic capability of MNEs, which are crucial for their sustained competitiveness. This kind of mechanism attracts much attention in academia and industry. However, there are few studies on how dynamic capabilities are developed in MNEs considering the organizational structure of geographically dispersed assets in multiple locations. This paper aims to examine the effect of knowledge-based and relational-based marketing assets on dynamic marketing capabilities and the mediating effect of customer orientation on Chinese MNEs.Design/methodology/approachIntegrating the dynamic capability approach and the international marketing literature, this study examines the impact of two types of marketing assets of foreign subsidiaries, focusing on knowledge-based and relationship-based marketing assets, on the dynamic marketing capabilities of Chinese MNEs. A large-scale empirical study of Chinese MNEs operating in overseas markets was performed, and the questionnaires were distributed and collected.FindingsThe results suggest a positive impact of knowledge-based and relationship-based marketing assets on marketing dynamic capability. We find that customer orientation has a positive mediating effect on the relationship between marketing assets and marketing dynamic capability. We also find that the competitive strength of the overseas market negatively moderates this relationship.Research limitations/implicationsThis study aims to contribute to the existing literature with a more fine-grained understanding of marketing assets and marketing dynamic capability, then provides theoretical guidance and management suggestions for the formulation and implementation of internationalization strategies of Chinese MNEs.Practical implicationsThe findings outline several important implications for MNEs seeking into expand to overseas markets.Originality/valueThis paper contributes a novel, combined perspective on marketing assets and marketing dynamic capability.