bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome analysis of the binucleate ciliate Tetrahymena thermophila with asynchronous nuclear cell cycles
Authors: Zhang L , Cervantes MD , Pan S , Lindsley J , Dabney A , Kapler GM 
Published: July 2022

ABSTRACTAs a prototypic ciliated protozoan, Tetrahymena thermophila harbors two functionally and physically distinct nuclei within a shared cytoplasm. During vegetative growth, the ‘cell cycles’ of the diploid germline micronucleus and polyploid somatic macronucleus are offset. Micronuclear S phase initiates just before cell division and is completed in daughter cells prior to the onset of macronuclear S phase. Whereas mitotic micronuclear division occurs mid-cell cycle, amitotic macronuclear division immediately precedes cytokinesis. Here we report the first RNA-seq analysis across the cell cycle of a binucleated organism. RNA was isolated at 30 min intervals across 1.5 vegetative cell cycles, starting with a macronuclear G1 population synchronized by centrifugal elutriation. Using MetaCycle, 3244 of the predicted 26,000+T. thermophila genes were shown to be cell cycle regulated. Proteins that are required in micro- and macronuclei exhibit a single mRNA peak that correlates with their macronuclear function, while the expression of nucleus-limited protein-coding genes, including nucleoporins and importins, peak prior to their respective nucleus-specific role. Cyclin D and cyclin A/B genes showed distinct expression patterns that predict nucleus-specific functions. Clustering of periodically expressed genes revealed seven gene expression patterns. Four clusters have known PANTHER GO biological processes that are overrepresented for G1/S and G2/M phase functions. We propose that these clusters encode known and novel factors that coordinate micro- and macronuclear-specific events such as mitosis, amitosis, DNA replication and cell division.
Multi-omics analysis of sarcospan overexpression in mdx skeletal muscle reveals compensatory remodeling of cytoskeleton-matrix interactions that promote mechanotransduction pathways
Authors: McCourt Jackie L. , Stearns-Reider Kristen M. , Mamsa Hafsa , Shu Cynthia , Afsharinia Mohammad Hossein , Gibbs Elizabeth M. , Shin Kara M. , Kurmangaliyev Yerbol Z. , Schmitt Lauren R. , Hansen Kirk C. , Crosbie Rachelle H. 
Published: July 2022

ABSTRACTBackgroundThe dystrophin-glycoprotein complex (DGC) is a critical adhesion complex of the muscle cell membrane, providing a mechanical link between the extracellular matrix (ECM) and the cortical cytoskeleton that stabilizes the sarcolemma during repeated muscle contractions. One integral component of the DGC is the transmembrane protein, sarcospan (SSPN). Overexpression of SSPN in the skeletal muscle of mdx mice (murine model of DMD) restores muscle fiber attachment to the ECM in part through an associated increase in utrophin and integrin adhesion complexes at the cell membrane, protecting the muscle from contraction-induced injury. In this study, we utilized transcriptomic and ECM protein-optimized proteomics data sets from wild-type, mdx, and mdx transgenic (mdxTG) skeletal muscle tissues to identify pathways and proteins driving the compensatory action of SSPN overexpression.MethodsThe tibialis anterior and quadriceps muscles were isolated from wild-type, mdx, and mdxTG mice and subjected to bulk RNA-Seq and global proteomics analysis using methods to enhance capture of ECM proteins. Data sets were further analyzed through the Ingenuity Pathway Analysis (QIAGEN) and integrative gene set enrichment to identify candidate networks, signaling pathways, and upstream regulators.ResultsThrough our multi-omics approach, we identified 3 classes of differentially expressed genes and proteins in mdxTG muscle, included those that were: 1) unrestored (significantly different from wild-type, but not from mdx), 2) restored (significantly different from mdx, but not from wild-type), and 3) compensatory (significantly different from both wild-type and mdx). We identified signaling pathways that may contribute to the rescue phenotype, most notably cytoskeleton and ECM organization pathways. ECM optimized-proteomics revealed an increased abundance of collagens II, V, and XI, along with β-spectrin in mdxTG samples. Using Ingenuity Pathway Analysis, we identified upstream regulators that are computationally predicted to drive compensatory changes, revealing a possible mechanism of SSPN rescue through a rewiring of cell-ECM bidirectional communication. We found that SSPN overexpression results in upregulation of key signaling molecules associated with regulation of cytoskeleton organization and mechanotransduction, including Rho, RAC, and Wnt.ConclusionsOur findings indicate that SSPN overexpression rescues dystrophin deficiency partially through mechanotransduction signaling cascades mediated through components of the ECM and the cortical cytoskeleton.
Precise control of neural activity using dynamically optimized electrical stimulation
Authors: Shah Nishal P. , Phillips A.J. , Madugula Sasi , Lotlikar Amrith , Gogliettino Alex R. , Hays Madeline , Grosberg Lauren , Brown Jeff , Dusi Aditya , Tandon Pulkit , Hottowy Pawel , Dabrowski Wladyslaw , Sher Alexander , Litke Alan M. , Mitra Subhasish , Chichilnisky E.J. 
Published: July 2022

AbstractNeural implants have the potential to restore lost sensory function by electrically evoking the complex naturalistic activity patterns of neural populations. However, it can be difficult to predict and control evoked neural responses to simultaneous multi-electrode stimulation due to nonlinearity of the responses. We present a solution to this problem and demonstrate its utility in the context of a bi-directional retinal implant for restoring vision. A dynamically optimized stimulation approach encodes incoming visual stimuli into a rapid, greedily chosen, temporally dithered and spatially multiplexed sequence of simple stimulation patterns. Stimuli are selected to optimize the reconstruction of the visual stimulus from the evoked responses. Temporal dithering exploits the slow time scales of downstream neural processing, and spatial multiplexing exploits the independence of responses generated by distant electrodes. The approach was evaluated using an experimental laboratory prototype of a retinal implant: large-scale, high-resolution multi-electrode stimulation and recording of macaque and rat retinal ganglion cellsex vivo. The dynamically optimized stimulation approach substantially enhanced performance compared to existing approaches based on static mapping between visual stimulus intensity and current amplitude. The modular framework enabled parallel extensions to naturalistic viewing conditions, incorporation of perceptual similarity measures, and efficient implementation for an implantable device. A direct closed-loop test of the approach supported its potential use in vision restoration.Impact StatementA novel method of electrical stimulation to precisely control neural activity for sensory restoration exhibits improvements in visual stimulus reconstruction, enables efficient hardware design, and extends to naturalistic conditions.
Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: July 2022

AbstractPediatric Crohn Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim of this investigation is to identify the key genes in CD and uncover their potential functions. We downloaded the next generation sequencing (NGS) dataset GSE101794 from the Gene Expression Omnibus (GEO) database. The NGS dataset GSE101794 was used to screen differentially expressed genes (DEGs) between samples from patients with CD and healthy controls. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Subsequently, a protein - protein interaction (PPI) network, modules, miRNA- hub gene regulatory network and TF - hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Receiver operating characteristic curve (ROC) analysis was applied to validate the hub genes. A total of 957 DEGs were identified, including 478 up regulated genes and 479 down regulated genes. GO and REACTOME results suggested that several Go terms and pathways are involved in response to stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system and biological oxidations. The top centrality hub genes MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 and TMEM25 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation identified key genes and signal pathways, which might help us improve our understanding of the molecular mechanisms of CD and identify some novel therapeutic targets for CD.
High conservation of the dental plaque microbiome community across populations with differing subsistence strategies and levels of market integration
Authors: Velsko Irina M. , Gallois Sandrine , Stahl Raphaela , Henry Amanda G. , Warinner Christina 
Published: July 2022

AbstractIndustrialization - including urbanization, participation in the global food chain, and consumption of heavily processed foods - is thought to drive substantial shifts in the human microbiome. While diet strongly influences stool microbiome composition, the influence of diet on the oral microbiome, and particularly dental plaque, is largely speculative. Here we investigated whether dental plaque microbial communities are distinctly different across populations with dissimilar subsistence strategies and degree of industrialized market integration. Using a metagenomic approach, we compared the dental plaque microbiomes of Baka foragers and Nzime subsistence agriculturalists in Cameroon (n = 46) with the dental plaque and calculus microbiomes of highly industrialized populations in North America and Europe. We found that differences in microbial taxonomic composition between populations were minimal, with high conservation of abundant microbial taxa and no significant differences in microbial diversity related to dietary practices. Instead, we find that the major source of variation in dental plaque microbial species composition is related to tooth location and oxygen availability, and may be influenced by toothbrushing or other dental hygiene measures. Our results support that dental plaque, in contrast to the stool microbiome, maintains an inherent stability against ecological perturbations in the oral environment.
Replication origin mapping in the malaria parasite Plasmodium falciparum
Authors: Totañes Francis Isidore Garcia , Gockel Jonas , Chapman Sarah E. , Bártfai Richárd , Boemo Michael A. , Merrick Catherine J. 
Published: July 2022

SUMMARYThe malaria parasite Plasmodium falciparum replicates via schizogony: a fundamentally unusual type of cell cycle involving asynchronous replication of multiple nuclei within the same cytoplasm. It also has one of the most A/T-biased genomes ever sequenced. Here, we present the first comprehensive study of the specification and activation of DNA replication origins during Plasmodium schizogony. Potential replication origins were found to be abundant, with ORC1-binding sites detected every ∼800 bp throughout the genome. They had no motif enrichment, but were biased towards areas of higher G/C content. Origin activation was then measured at single-molecule resolution via new DNAscent technology that measures fork movement by detecting base analogues BrdU and EdU in DNA sequenced on the Oxford nanopore platform (https://github.com/MBoemo/DNAscent). DNAscent-called origins were found to be much less dense than ORC1-binding sites, with origins activated preferentially in areas of low transcriptional activity. Consistently, replication forks moved fastest through the most lowly transcribed genes, suggesting that conflicts between transcription and origin firing inhibit efficient replication, and that P. falciparum has evolved its S-phase to minimise such conflicts.
A system-level view on the function of natural eukaryotic biomes through taxonomically resolved metabolic pathway profiling
Authors: Gutierrez Jayson , Hablützel Pascal I. 
Published: July 2022

AbstractHigh-throughput sequencing of environmental samples has dramatically improved our understanding of the molecular activities of complex microbial communities in their natural environments. For instance, by enabling taxonomic profiling and differential gene expression analysis, microbiome studies have revealed intriguing associations between community structure and ecosystem functions. However, the effectiveness of sequence data analysis to characterize the functioning of microbial ecosystems at the systems level (e.g. metabolic pathways) and at high taxonomic resolution has thus far been limited by the quality and scope of reference sequence databases. In this work, we applied state of the art bioinformatics tools to leverage publicly available genome/gene sequences for a wide array of (mostly eukaryotic) planktonic organisms to build a customized protein sequence database. Based on this, our goal is to conduct a systems-level interrogation of environmental samples, which can effectively augment the insights obtained through traditional gene-centric analysis (i.e. analysis of single gene expression profiles at the genome-wide level). To achieve this, we utilized the popular HUMAnN pipeline, which has proven effective at delineating taxon-specific metabolic pathways that may be actively contributing to the overall functioning of a microbiome. To test the efficacy of our database customization for mapping metabolic pathway activities in complex planktonic ecosystems, we reanalyzed previously published metatranscriptome datasets derived from different marine environments. Our results demonstrate that database customization can substantially improve our ability to quantitatively assess core metabolic processes across taxonomically diverse marine microbiomes, which have so far remained largely uncharacterized at the systems level. By further expanding on the taxonomic and functional complexity of our database with newly released high-quality genome assemblies and gene catalogs for marine microbes, we aim to improve our ability to map the molecular traits that drive changes in the composition and functioning of marine planktonic networks through space and time.
Interdependent progression of bidirectional sister replisomes in E. coli
Authors: Chen P.J. , McMullin A.B. , Visser B.J. , Mei Q. , Rosenberg S.M. , Bates D. 
Published: July 2022

AbstractBidirectional DNA replication complexes initiated from the same origin remain colocalized in a factory configuration for part or all of their lifetimes. However, there is little evidence that sister replisomes are functionally interdependent, and the consequence of factory replication is unknown. Here, we investigated the functional relationship between sister replisomes in E. coli, which naturally exhibits both factory and solitary configurations in the same replication cycle. Using an inducible transcription factor roadblocking system, we found that blocking one replisome caused a significant decrease in overall progression and velocity of the sister replisome. Remarkably, progression was impaired only if the block occurred while sister replisomes were still in a factory configuration – blocking one fork had no significant effect on the other replisome when sister replisomes were physically separate. Disruption of factory replication also led to increased fork stalling and requirement of fork restart mechanisms. These results suggest that physical association between sister replisomes is important for establishing an efficient and uninterrupted replication program. We discuss the implications of our findings on mechanisms of replication factory structure and function, and cellular strategies of replicating problematic DNA such as highly transcribed segments.
Presynaptic contact and activity opposingly regulate postsynaptic dendrite outgrowth
Authors: Heckman Emily L. , Doe Chris Q. 
Published: July 2022

AbstractThe organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly and robustly respond to developmental variability in presynaptic location and input strength.
ArcRegulates a Second-Guessing Cognitive Bias During Naturalistic Foraging Through Effects on Discrete Behavior Modules
Authors: Ravens Alicia , Stacher-Hörndli Cornelia N. , Emery Jared , Steinwand Susan , Shepherd Jason D. , Gregg Christopher 
Published: July 2022

ABSTRACTForaging involves innate decision heuristics that are adapted for the wild but can cause economically suboptimal cognitive biases in some contexts. The mechanisms underlying cognitive biases are poorly understood but are likely genetic. Here, we investigate foraging in fasted mice using a naturalistic paradigm and uncover an innate “second-guessing” cognitive bias that involves repeatedly investigating an empty former food patch instead of consuming available food. Second-guessing prevents mice from maximizing feeding benefits in the task. Since learning and memory are involved, we tested roles for the synaptic plasticity gene,Arc,and found thatArc−/−mice show a specific lack of second-guessing.Arc−/−males reap benefits by increasing food consumption. Unsupervised machine learning decompositions of foraging show thatArcaffects discrete, stereotyped foraging sequences that we call modules within a rich naturalistic behavioral landscape. Thus, our study reports a second- guessing cognitive bias, ethological roles forArcin naturalistic foraging, and links between genetically determined foraging modules and cognitive bias in decision making.
Toward a public sector asset optimization strategy: the case of Indonesia
Authors: Nanang Rustanto , Susilawati Connie , Skitmore Martin 
Published: July 2022

Purpose
Governments in developing countries manage their considerable state assets for public service delivery directly. In Indonesia, the Directorate of State Asset Management responsible for developing the national strategy for state asset optimization requires the determination of key elements and prioritization tools. The purpose of this paper is to show that a simple calculation using the combination of the balanced scorecard (BCS) and analytical hierarchy process (AHP) will help in the prioritization of strategy development.

Design/methodology/approach
A questionnaire survey of 131 multistakeholder respondents to identify the most important key elements and the best alternative for asset optimization was done in this study.

Findings
The respondents agree on the most important key elements, and that the best alternative for asset optimization is the efficient maintenance of assets. Competitive human resources comprise the recommended second key element, and that improvements in asset performance and value will improve public service as the second-highest alternative. This study also shows the importance of the integration of asset optimization in existing government strategic instruments supported by a comprehensive data set related to public assets and their performance.

Originality/value
This paper provides a new contribution to integrating asset optimization strategies as the core of the organization’s performance and prioritization strategies. Additional BSC perspectives are suggested, with the inclusion of AHP for prioritization. In addition, this study includes the opinions of all the stakeholders, from external users to the central management. The flexibility of the tools to adapt to the existing strategic framework will allow their application by different agencies and in different countries.
Predicting investors’ intention to invest in the stock market during COVID-19: can we use an extended theory of planned behavior?
Authors: Kumari J.S. , Senani K.G.P. , Ajward Roshan 
Published: July 2022

Purpose
This study aims to explain investors’ intention to invest in the stock market amid the COVID-19 pandemic by expanding the Theory of Planned Behavior (TPB).

Design/methodology/approach
This study adopts a quantitative approach, and a questionnaire-based survey was conducted to collect responses from existing and potential individual investors. To test the relationships between variables, structural equation modeling was used.

Findings
The findings indicated that investors’ attitude and perceived behavioral control had a significant influence on investment intentions. Further, perceived knowledge of COVID-19 improved the ability to predict the intention to invest. Moreover, psychological risk significantly moderated the association between subjective norms related to investors and their attitudes. Overall, the tested model was able to better account for the intention of investors in stock market investments.

Research limitations/implications
In this study, only the investor reactions in the context of an emerging market were evaluated, and future studies could focus on different market contexts and perform comparative studies. Financial markets could be considered as a mechanism that has a direct impact on the wealth distribution of society, and the key findings of this study could be used to promote investment in emerging markets, where participation is comparatively low.

Originality/value
The TPB was expanded by incorporating investors’ perceived knowledge of COVID-19 and psychological risk dimensions, which were then tested in an emerging market context to fill the knowledge gap identified in the contemporary behavioral finance literature.