bluuebunny/crossref_metadata_2025 huggingface dataset:
Variant-specific priors in colocalisation analysis
Authors: Pullin Jeffrey M , Wallace Chris
Published: August 2024

Linking GWAS variants to their causal gene remains an ongoing challenge. A widely used method for performing this analysis is the coloc package for statistical colocalisation analysis, which can be used to link GWAS and eQTL associations. Currently, coloc assumes that all variants in a region are equally likely to be causal, despite the success of fine-mapping methods that use additional information to adjust their prior probabilities. In this paper we propose and implement an approach for specifying variant-specific prior probabilities in the coloc method. We describe and compare six source of information for specifying prior probabilities: non-coding constraint, enhancer-gene link scores, the output of the PolyFun method and three estimates of eQTL-TSS distance densities. Using simulations and analysis of ground-truth pQTL-eQTL colocalisations we show that variant-specific priors, particularly the eQTL-TSS distance density priors, can improve colocalisation performance. Furthermore, across GWAS-eQTL colocalisations variant-specific priors changed colocalisation significance in up to 13.5% of colocalisations, at some loci revealing the likely causal gene.
LEAF SHAPE OF QUINOA WILD ANCESTOR CHENOPODIUM HIRCINUM IN A GEOGRAPHIC CONTEXT
Authors: Curti Ramiro N , Rodriguez Jonatan , Ortega-Baes Pablo , Bramardi Sergio J , Jellen Eric , Jarvis David E , Maughan Peter J , Tester Mark , Bertero Daniel
Published: August 2024

Intraspecific variation in plant traits, such as leaf morphology, offers insights into local adaptation and the ecological niche breadth of species. Chenopodium hircinum, the wild ancestor of quinoa, is widely distributed across various ecoregions in Argentina. A detailed comparative analysis of leaf morphology across 23 populations covering its entire distribution was conducted to understand patterns of intraspecific variation along geographic gradients. Using 104 leaves from these populations, leaf shapes were described through shape, landmarks, and Fourier descriptors. Both univariate and multivariate analyses were employed to evaluate variations among and within populations and to link leaf shape patterns with climatic and geographical variables at the sites of origin. A significant variability in leaf shapes was found across all ecoregions, with marked integration among populations. While landmark-based and Fourier analyses differentiated populations, shape descriptors introduced complexity in identification. Leaf morphology varied widely, from rounded and toothed to sharply lobed, with prominent lobes located at the base or middle of the leaf. The key environmental factors influencing leaf shape, particularly lobulation and relative positioning, were mean annual temperature and altitude. The findings suggest that in C. hircinum, leaf shape variability goes beyond the simple lobed vs. entire dichotomy and is shaped by environmental temperatures. Leaf morphology and margin traits are primarily governed by the relative position of the lobes, which are strongly correlated with the mean temperature at the population origin. This convergence across different ecoregions highlights the need for further research to explore the functional significance of such variation.
Cellular and circuit features distinguish dentate gyrus semilunar granule cells and granule cells activated during contextual memory formation
Authors: Dovek Laura , Marrero Krista , Zagha Edward , Santhakumar Vijayalakshmi
Published: August 2024

The dentate gyrus is critical for spatial memory formation and shows task related activation of cellular ensembles considered as memory engrams. Semilunar granule cells (SGCs), a sparse dentate projection neuron subtype distinct from granule cells (GCs), were recently reported to be enriched among behaviorally activated neurons. However, the mechanisms governing SGC recruitment during memory formation and their role in engram refinement remains unresolved. By examining neurons labeled during contextual memory formation in TRAP2 mice, we empirically tested competing hypotheses for GC and SGC recruitment into memory ensembles. In support of the proposal that more excitable neurons are preferentially recruited into memory ensembles, SGCs showed greater sustained firing than GCs. Additionally, SGCs labeled during memory formation showed less adapting firing than unlabeled SGCs. Our recordings did not reveal glutamatergic connections between behaviorally labeled SGCs and GCs, providing evidence against SGCs driving local circuit feedforward excitation in ensemble recruitment. Contrary to a leading hypothesis, there was little evidence for individual SGCs or labeled neuronal ensembles supporting lateral inhibition of unlabeled neurons. Instead, pairs of GCs and SGCs within labeled neuronal cohorts received more temporally correlated spontaneous excitatory synaptic inputs than labeled-unlabeled neuronal pairs, validating a role for correlated afferent inputs in neuronal ensemble selection. These findings challenge the proposal that SGCs drive dentate GC ensemble refinement, while supporting a role for intrinsic active properties and correlated inputs in preferential SGC recruitment to contextual memory engrams.

Impact Statement

Evaluation of semilunar granule cell involvement in dentate gyrus contextual memory processing supports recruitment based on intrinsic and input characteristics while revealing limited contribution to ensemble refinement.
Grin1Y647S/+Mice: A Preclinical Model ofGRIN1-Related Neurodevelopmental Disorder
Authors: Sullivan Megan T. , Tidball Patrick , Yan Yuanye , Intson Katheron , Chen Wenjuan , Xu Yuchen , Venkatesan Sridevi , Horsfall Wendy , Georgiou John , Finnie Peter S.B. , Lambe Evelyn K. , Traynelis Stephen F. , Salahpour Ali , Yuan Hongjie , Collingridge Graham L. , Ramsey Amy J.
Published: August 2024

Objective

GRIN1-related neurodevelopmental disorder (GRIN1-NDD) is characterized by clinically significant variation in theGRIN1gene, which encodes the obligatory GluN1 subunit of N-methyl-D-aspartate receptors (NMDARs). The identified p.Tyr647Ser (Y647S) variant — carried by a 33-year-old female with seizures and intellectual disability — is located in the M3 helix in the GluN1 transmembrane domain. This study builds upon initialin vitroinvestigations of the functional impacts of theGRIN1Y647S variant and examines itsin vivoconsequences in a mouse model.

Methods

To investigatein vitrofunctional impacts of NMDARs containing GluN1-Y647S variant subunits, GluN1-Y647S was co-expressed with wildtype GluN2A or GluN2B subunits inXenopus laevisoocytes and HEK cells.Grin1Y647S/+mice were created by CRISPR-Cas9 endonuclease-mediated transgenesis and the molecular, electrophysiological, and behavioural consequences of the variant were examined.

Results

In vitro, NMDARs containing GluN1-Y647S show altered sensitivity to endogenous agonists and negative allosteric modulators, and reduced cell surface trafficking.Grin1Y647S/+mice displayed a reduction in whole brain GluN1 levels and deficiency in NMDAR-mediated synaptic transmission in the hippocampus. Behaviourally,Grin1Y647S/+mice exhibited spontaneous seizures, altered vocalizations, muscle strength, sociability, and problem-solving.

Interpretation

The Y647S variant confers a complexin vivophenotype, which reflects largely diminished properties of NMDAR function. As a result,Grin1Y647S/+mice display atypical behaviour in domains relevant to the clinical characteristics ofGRIN1-NDD and the individual carrying the variant. Ultimately, the characterization ofGrin1Y647S/+mice accomplished in the present work expands our understanding of the mechanisms underlyingGRIN1-NDD and provides a foundation for the development of novel therapeutics.
REDUCED CACNA1C EXPRESSION PRODUCES ANHEDONIC REACTIONS TO PALATABLE SUCROSE IN RATS: NO INTERACTIONS WITH JUVENILE OR ADULT STRESS
Authors: Gasalla Patricia , Thomas Kerrie , Wilkinson Lawrence , Hall Jeremy , Dwyer Dominic Michael
Published: August 2024

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Cav1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia, bipolar disorder, and major depression. Here we investigated the impact of mutations of one copy of Cacna1c on rats' hedonic responses to palatable sucrose (assessed using the analysis of consumption microstructure). In addition, we also investigated the effects of combining either juvenile or adult stress with the manipulation of Cacna1c. Across three experiments Cacna1c+/- rats displayed attenuated hedonic reactions to sucrose compared to WT littermate controls, despite the Cacna1c+/- rats retaining sensitivity to sucrose concentration in terms of the amount of consumption. Unexpectedly, juvenile stress enhanced rather than reduced hedonic reactions to sucrose, while adult stress did not have clear hedonic effects. The effects of Cacna1c manipulation did not interact with either juvenile or adult stress. The fact that Cacna1c+/- rats display a clear analogue of anhedonia - a reduction in the positive hedonic reactions normally elicited by highly palatable sucrose - a symptom observed transdiagnostically across psychiatric disorders linked to CACNA1C, suggests this model may play a valuable role in the translational investigation of anhedonia.
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

Mitochondria 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

Bacterial 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 Statement

Bacteria 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

The 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

Metastatic 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

The 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.
NeuroVar: An Open-source Tool for Gene Expression and Variation Data Visualization for Biomarkers of Neurological Diseases
Authors: Aribi Hiba Ben , Abassi Najla , Awe Olaitan I
Published: August 2024

Background: The expanding availability of large-scale genomic data and the growing interest in uncovering gene-disease associations call for efficient tools to visualize and evaluate gene expression and genetic variation data. Methodology: Data collection involved filtering biomarkers related to multiple neurological diseases from the ClinGen database. We developed a comprehensive pipeline that was implemented as an interactive Shiny application and a standalone desktop application. Results: NeuroVar is a tool for visualizing genetic variation (single nucleotide polymorphisms and insertions/deletions) and gene expression profiles of biomarkers of neurological diseases. Conclusion: The tool provides a user-friendly graphical user interface to visualize genomic data and is freely accessible on the project's GitHub repository (https://github.com/omicscodeathon/neurovar).
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

Identifying 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

Root 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

Objectives

The 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.

Methods

The 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.

Results

The 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.

Conclusion

This 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.
Sustained activity in a descending neuron is associated with flight saccades in Drosophila
Authors: Buchsbaum Elhanan , Schnell Bettina
Published: August 2024

Flies perform rapid turns termed saccades to change direction during flight. Evasive turns can be elicited by looming stimuli mimicking an approaching object such as a potential predator. Whereas projection neurons of the optic lobes responsive to looming stimuli have been well described, how this information is transmitted to the motor system to elicit a saccade, is not well understood. Here we describe activity of the descending neuron DNp03 in Drosophila, which receives direct input from looming-sensitive visual interneurons and projects to wing motor areas within the ventral nerve cord. Whole-cell patch-clamp recordings from this neuron during head-fixed flight confirm that DNp03 is responsive to looming stimuli on the side ipsilateral to its dendrites. In addition, activity of this neuron is state-dependent as looming stimuli only elicit spikes during flight and not rest. The behavior in response to the looming stimulus is variable, which allowed us to study how activity of DNp03 relates to the execution of a saccade. Our analysis revealed that sustained activity in DNp03, persisting even after the visual stimulus ended, was the strongest predictor of saccade execution, therefore reflecting the behavioral decision of the fly to respond to the stimulus.
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

Syphilis 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 Summary

In 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

Background

Cyanobacteria 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.

Results

A 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.

Conclusions

This 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.
DNA damage response defects induced by the formation of TDP-43 and mutant FUS cytoplasmic inclusions and their pharmacological rescue.
Authors: Farina Stefania , Esposito Francesca , Modafferi Stefania , Brandi Ornella , Di Salvio Michela , Della Valle Ilaria , Cicio Giada , Riccardi Adelaide , Pisati Federica , Garbelli Anna , D'ambrosi Nadia , Cozzolino Mauro , Cestra Gianluca , d'Adda di Fagagna Frabrizio , Gioia Ubaldo , Francia Sofia
Published: August 2024

Formation of cytoplasmic inclusions (CIs) of TDP-43 and FUS, along with DNA damage accumulation, is a hallmark of affected motor neurons in Amyotrophic Lateral Sclerosis (ALS). However, the impact of CIs on DNA damage response (DDR) and repair in this pathology remains unprobed. Here, we show that CIs of TDP-43 and FUSP525L, co-localizing with stress granules, lead to a dysfunctional DDR activation associated with physical DNA breakage. Inhibition of the activity of the DDR kinase ATM, but not of ATR, abolishes DDR signaling, indicating that DNA double-strand breaks (DSBs) are the primary source of DDR activation. In addition, cells with TDP-43 and FUSP525L CIs exhibit reduced DNA damage-induced RNA synthesis at DSBs. We previously showed that the two endoribonucleases DROSHA and DICER, also known to interact with TDP-43 and FUS during small RNA processing, contribute to DDR signaling at DSBs. Treatment with enoxacin, which stimulates DDR and repair by boosting the enzymatic activity of DICER, restores a proficient DDR and reduces DNA damage accumulation in cultured cells with CIs and in vivo in a murine model of ALS. In Drosophila melanogaster, Dicer-2 overexpression rescues TDP-43-mediated retinal degeneration. In summary, our results indicate that the harmful effects caused by TDP-43 and FUS proteinopathies include genotoxic stress and that the pharmacological stimulation of the DNA damage signaling and repair counteracts it.
A cup of coffee can boost your motor performance: Enhanced motor sequence learning with caffeine
Authors: Kim Hakjoo , Wright David L. , Kweon Jamie , Brown Joshua C.
Published: August 2024

Caffeine is consumed in various beverages, such as coffee, energy drinks, soda, and tea. The effects of caffeine have been shown to manifest in various ways across different studies. Some studies suggest that caffeine can enhance motor performance. Despite this, numerous motor learning studies do not control for participants' caffeine intake or do not record whether participants consumed caffeine. The purpose of this study was to compare the motor learning performance (i.e., online improvement) of individuals who consumed caffeine and those who did not before practice with a novel motor sequence task. Sixty-five right-handed healthy undergraduate students participated in this study. Individuals reported their caffeine consumption through a pre-experiment questionnaire prior to performing an eight-item serial reaction time task. The participants who consumed caffeine reported drinking one cup of coffee on average 158.8 minutes before performing the sequential task. The motor performance of individuals who consumed caffeine was compared to those who did not, with the caffeine-consuming group (n = 13) exhibiting faster response times during online learning than the non-caffeine group (n = 52). The findings of this study suggest that caffeine should be controlled for in future motor learning research.
Terminal nucleotidyltransferase Tent2 microRNA tailing regulates excitatory/inhibitory balance in the hippocampus
Authors: Wardaszka Patrycja , Kuzniewska Bozena , Guminska Natalia , Hojka-Osinska Anna , Puchalska Monika , Milek Jacek , Stawikowska Aleksandra , Krawczyk Pawel , Pauzin Francois Philippe , Wojtowicz Tomasz , Radwanska Katarzyna , Bramham Clive Raymond , Dziembowski Andrzej , Dziembowska Magdalena
Published: August 2024

One of the post-transcriptional mechanisms regulating the stability of RNA molecules involves the addition of non-templated nucleotides to their 3' ends, a process known as RNA tailing. To systematically investigate the physiological consequences of terminal nucleotidyltransferase TENT2 absence on RNA 3' end modifications in the mouse hippocampus we developed a new Tent2 knockout mouse. Electrophysiological measurements revealed increased excitability in Tent2 KO hippocampal neurons, and behavioral analyses showed decreased anxiety and improved fear extinction in these mice. At the molecular level, we observed a significant contribution of TENT2 to the monoadenylation of various classes of miRNAs, but found no effect of the enzyme's loss on the total poly(A) tail length of mRNAs, as measured by Direct Nanopore RNA sequencing. Alterations in the monoadenylation of a large population of microRNAs affected the overall mRNA abundance, particularly transcripts related synaptic transmission, which were downregulated in the hippocampus of Tent2 knockout mice. These changes explain the observed behavioral and electrophysiological alterations. Our data thus establish a link between TENT2-dependent microRNA tailing and the balance of inhibitory and excitatory neurotransmission.
Temporal Dynamics and Adaptive Mechanisms of Microbial Communities: Divergent Responses and Network Interactions
Authors: Sun Shengjie , Qiao Zhiyi , Tikhonenkov Denis V. , Gong Yingchun , Li Hua , Li Renhui , Sun Kexin , Huo Da
Published: August 2024

Microbial communities are integral to aquatic ecosystems, playing key roles in biogeochemical cycles, nutrient recycling, and ecosystem functioning. Despite their importance, the temporal dynamics of these communities, especially in response to short-term environmental changes, remain inadequately understood. This study utilizes high-throughput amplicon sequencing and Co-occurrence network analysis to elucidate how prokaryotic and eukaryotic microbial communities dynamically respond to short-term environmental fluctuations, and dynamics of networks. Our results reveal distinct temporal patterns, with eukaryotic communities showing consistent increases in diversity, while prokaryotic communities exhibited more pronounced fluctuations and directional changes. Co-occurrence network analysis further highlighted the differences in community structure between phases of homogenization and heterogenization. Specifically, we observed a shift from a more modular network during the homogenization phase to a more centralized network in the heterogenization phase, resulting in increased network fragility. Environmental factors, such as nutrient levels and climatic conditions, were found to play pivotal roles in shaping these dynamics. This study provides critical insights into the resilience and adaptability of microbial communities, emphasizing the intricate interplay between biodiversity, network structure, and ecosystem stability under varying environmental conditions.
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

Purpose

The 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/approach

Integrating 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.

Findings

The 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/implications

This 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 implications

The findings outline several important implications for MNEs seeking into expand to overseas markets.

Originality/value

This paper contributes a novel, combined perspective on marketing assets and marketing dynamic capability.
Employee’s narrative on quiet quitting – a qualitative analysis
Authors: Nimmi P.M. , Syed Femina , Manjaly Neenet Baby , Harsha G.
Published: August 2024

Purpose

Quiet quitting (QQ) has been around in academic and professional discussions for quite some time. Despite many definitions and reasons for QQ being proposed, no study has systematically undertaken exploratory research on the reasons and behavioral manifestations of employees who QQ.

Design/methodology/approach

Our study adopted an exploratory qualitative approach to understand the reasons for QQ without any prior judgment. We undertook interviews with 21 employees who have undergone QQ in their careers.

Findings

The qualitative inquiry brought out the reasons behind QQ. The three major reasons for QQ were identified by thematic analysis: personal, organizational politics and people dynamics. Further, overt and covert behaviors that employees undertake while QQ were framed with this study. Findings are discussed in the framework of existence, relatedness and growth (ERG) theory.

Research limitations/implications

The theoretical implications include understanding QQ within the purview of ERG theory and the frustrated regression model. Practically, measures to be taken by organizations to mitigate the instances are presented, along with employee suggestions on what measures need to be taken to avoid QQ behaviors of employees.

Originality/value

This study is a pioneering work on the exploratory understanding of QQ. Empirically validated theory formulation of QQ is developed here for the first time.
Heat transfer and entropy generation in viscous-joule heating MHD microchannels flow under asymmetric heating
Authors: Tahiri Antar , Ragueb Haroun , Moussaoui Mustafa , Mansouri Kacem , Guerraiche Djemaa , Guerraiche Khelifa
Published: August 2024

Purpose

This paper aims to present a numerical investigation into heat transfer and entropy generation resulting from magnetohydrodynamic laminar flow through a microchannel under asymmetric boundary conditions. Furthermore, the authors consider the effects of viscous dissipation and Joule heating.

Design/methodology/approach

The finite difference method is used to obtain the numerical solution. Simulations are conducted across a broad range of Hartmann (Ha = 0 ∼ 40) and Brinkman (Br = 0.01 ∼ 1) numbers, along with various asymmetric isothermal boundaries characterized by a heating ratio denoted as ϕ.

Findings

The findings indicate a significant increase in the Nusselt number with increasing Hartmann number, regardless of whether Br equals zero or not. In addition, it is demonstrated that temperature differences between the microchannel walls can lead to substantial distortions in fluid temperature distribution and heat transfer. The results reveal that the maximum entropy generation occurs at the highest values of Ha and η (a dimensionless parameter emerging from the formulation) obtained for ϕ = −1. Moreover, it is observed that local entropy generation rates are highest near the channel wall at the entrance region.

Originality/value

The study provides valuable insights into the complex interactions between magnetic fields, viscous dissipation and Joule heating in microchannel flows, particularly under asymmetric heating conditions. This contributes to a better understanding of heat transfer and entropy generation in advanced microfluidic systems, which is essential for optimizing their design and performance.