bluuebunny/crossref_metadata_2025_split huggingface dataset:
MOPD I patient-derived cerebral organoids model microcephaly showing premature neurogenesis due to disrupted mitotic spindle orientation
Authors: Singh Jagjit , Daniels Noah J. , Pirozzi Filomena , Wynshaw-Boris Anthony , Lopez-Gonzalez Rodrigo , Padgett Richard A. 
Published: December 2022

AbstractMutations in the single-copy RNU4ATAC gene, which encodes U4atac snRNA of the minor spliceosome are linked to the developmental disorder microcephalic osteodysplastic primordial dwarfism type I (MOPD I). Partial loss-of-function mutations of U4atac snRNA lead to a poor prognosis, with less than three year survival. The most prominent characteristic of MOPD I is disrupted central nervous system development resulting in severe microcephaly and lissencephaly.In this study, we used self-organizing 3D cerebral organoids from patient-derived induced pluripotent stem cells (iPSCs) to investigate defective cellular events that disturb the laminar organization of the cortex and influence brain topology. We analyzed organoids from iPSCs homozygous for the partial loss-of-function U4atac snRNA 51G>A mutation and compared them to isogenic organoids obtained from iPSCs expressing wild-type U4atac snRNA, using immunostaining and 10X Genomics single-cell RNA sequencing. In our MOPD I organoids, we observed: a) reduced proliferation accompanied by premature neurogenesis depleting the neuro-progenitor pool due to an increased frequency of horizontal cell divisions in the ventricular zone; b) reduced numbers of intermediate progenitor and outer radial glial cells in the outer sub-ventricular zone; and c) defective radial neuronal migration, which is critical for cortical expansion in humans. Our findings therefore provide insight into MOPD I cellular pathogenesis and underline the value of these cerebral organoids as model systems for human neurodevelopmental disorders.
Systematic mapping of neural signals in the periphery reveals a rich and specific alphabet for immune cell communication
Authors: Berman Karen Regev , Milman Neta , Segev Meital , Stratovsky Elina , Shen-Orr Shai S. 
Published: December 2022

SummaryAccumulating evidence indicate a strong link between neural signals and the immune system. Given neural signals constitute a large family that may be leveraged for communication, we systematically explored the neuro-immune regulation network in the periphery and uncovered a broad yet lineage selective expression of neuro-receptors on immune cells. We constructed a rich social immune network map showing the neural molecular pathways supporting the regulation of the immune system at steady state. Our results emphasize neuro-receptors role in the commitment and differentiation of B and T cells along their developmental process. We identified the immune cells’ functionality in the specific tissue is extensively shaped by the communication with the microenvironment and nervous systems via a rich alphabet of neural mediators. Collectively, our findings suggest neural genes are an integral part of the immune regulatory system and provide clear testable new avenues of experimental follow up for neuroimmunologists and immunologists alike.Abstract FigureHighlights160 neural genes potentially active in immune cells in the periphery with high specificity to lineageNeuro-receptors co-expressed in immune lineages are enriched for biological functionsChanges in neuro-receptors expression influence the HCS differentiation and commitmentImmune-microenvironment neural signaling architecture reflects tissue biological role
A high-throughput machine vision-based univariate scale for pain and analgesia in mice
Authors: Sabnis Gautam S. , Hession Leinani E. , Kim Kyungin , Beierle Jacob A. , Kumar Vivek 
Published: December 2022

1AbstractTreatment of acute and chronic pain represent a widespread clinical challenge with poor therapeutic options. While rodents are an invaluable model to study pain, scoring nociceptive responses in clinically relevant paradigms and at high-throughput remains an unmet challenge. Therefore, there is a need for automated, high-throughput methods that sensitively and accurately assess pain and analgesia. Such objective and scalable technologies will enable the discovery of novel analgesics and yield mechanistic insights into the neural and genetic mechanisms of pain. Here, we adopt the open field arena to build a univariate scale for the formalin injection model of inflammatory pain by using a machine learning approach that incorporates 82 behavioral features. This tool outperforms traditional measures of licking and shaking in detection of formalin dose, and was validated using 4 diverse mouse strains. We also detected previously unreported differences in formalin induced nocifensive behaviors that were strain and sex specific. This model also reliably identifies morphine induced antinociception. This novel, sensitive, and inexpensive tool provides a method for quantifying voluntary nociceptive responses to facilitate genetic mapping and analgesic compound screening in a high throughput manner.
Sparse and stereotyped encoding implicates a core glomerulus for ant alarm behavior
Authors: Hart Taylor , Frank Dominic , Lopes Lindsey E. , Olivos-Cisneros Leonora , Lacy Kip D. , Trible Waring , Ritger Amelia , Valdés-Rodríguez Stephany , Kronauer Daniel J. C. 
Published: December 2022

AbstractAnts communicate via large arrays of pheromones and possess expanded, highly complex olfactory systems, with antennal lobes in the brain comprising ~500 glomeruli. This expansion implies that odors could activate hundreds of glomeruli, which would pose challenges for higher order processing. To study this problem, we generated the first transgenic ants, expressing the genetically encoded calcium indicator GCaMP6s in olfactory sensory neurons. Using two-photon imaging, we mapped complete glomerular responses to four ant alarm pheromones. Alarm pheromones robustly activated ≤6 glomeruli, and activity maps for the three pheromones inducing panic-alarm in our study species converged on a single glomerulus. These results demonstrate that, rather than using broadly tuned combinatorial encoding, ants employ precise, narrowly tuned, and stereotyped representation of alarm pheromone cues. The identification of a central sensory hub glomerulus for alarm behavior suggests that a simple neural architecture is sufficient to translate pheromone perception into behavioral outputs.
Electrophysiological Activity of Primary Cortical Neuron-Glia Mixed Cultures
Authors: Goshi Noah , Kim Hyehyun , Girardi Gregory , Gardner Alexander , Seker Erkin 
Published: December 2022

AbstractBackgroundWe have previously described a tri-culture of neurons, astrocytes, and microglia that accurately mimics thein vivoneuroinflammatory response (both neurotoxic and neuroprotective) to a wide range of neuroinflammatory stimuli. Electrophysiological activity is an essential measure of neuronal function, which is influenced by neuroinflammation. Microelectrode array (MEA) technology is a versatile tool to non-invasively studyin vitroneural networks by simultaneously recording electrophysiological activity from multiple sites. In this study, we used extracellular recordings to determine the effect of microglia on neural network formation and stability in primary cortical cultures and monitor the changes in neural activity in response to neuroinflammatory stimuli.MethodsPrimary neonatal rat cortical tri-cultures of neurons, astrocytes, and microglia or co-cultures of neurons and astrocytes were cultured on custom MEAs and the neural activity was monitored for 21 daysin vitroto assess culture maturation and network formation. Quantification of synaptic puncta and averaged spike waveforms were used to determine the difference in excitatory to inhibitory neuron ratio (E/I ratio) of the neurons in tri- and co-cultures. The electrophysiological response to lipopolysaccharide (LPS) treatment of both culture types were compared.ResultsThe tri- and co-culture showed minimal difference in electrophysiological markers of neural network formation and stability with the exception of a significant increase in spike frequency in the tri-culture at later timepoints (DIV 17 and 21). Additionally, there was no significant difference in the density of either post-synaptic or excitatory pre-synaptic puncta between the culture types. However, characterization of the average spike waveforms revealed that the tri-culture had an E/I ratio much closer to that found in the rat cortex. Finally, only the tri-culture displayed a significant decrease in both the number of active channels and spike frequency following LPS exposure.ConclusionsThis study demonstrates that the microglia in the tri-culture do not disrupt neural network formation and stability as quantified using extracellular recordings and may be a better representation of thein vivocortex due to the closer E/I ratio than more traditional isolated neuron and neuron-astrocyte co-cultures. Additionally, the tri-culture is better able to mimic the neuroinflammatory response to LPS, which was quantified via changes in neural electrophysiological activity.
The Role of Polyglutamine in Inter- and Intra-molecular Interactions in Med15-dependent Regulation
Authors: Cooper David G. , Fassler Jan S. 
Published: December 2022

AbstractMed15 is a general transcriptional regulator and member of the tail module of the RNA Pol II Mediator complex. TheS. cerevisiaeMed15 protein has a well-structured N-terminal KIX domain, three Activator Binding Domains (ABDs) and several naturally variable polyglutamine (poly-Q) tracts (Q1, Q2, Q3) embedded in an intrinsically disordered central region, and a C-terminal Mediator Association Domain (MAD). We investigated how the presence of ABDs and changes in length and composition of poly-Q tracts influences Med15 activity and function using phenotypic, gene expression, and transcription factor interaction assays of truncation, deletion, and synthetic alleles. We found that individual Med15 activities were influenced by the number of activator binding domains (ABDs) and adjacent polyglutamine composition. We also observed that distant glutamine tracts and Med15 phosphorylation affected the activities of the KIX domain, suggesting that intramolecular interactions may be required for KIX domain interactions with transcription factors. We conclude that robust Med15 activity required at least the Q1 tract and that the length of that tract modulates activity in a context-dependent manner. We speculate that the glutamine tract provides a degree of intramolecular flexibility that is needed for Med15 function. Finally, we found that loss of Msn2-dependent transcriptional activation in Med15 Q1 tract variants correlates well with a reduction in Msn2:Med15 interaction strength.
The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting
Authors: Vengayil Vineeth , Niphadkar Shreyas , Adhikary Swagata , Varahan Sriram , Laxman Sunil 
Published: December 2022

AbstractMany cells in high glucose repress mitochondrial respiration, as observed in the Crabtree and Warburg effects. Our understanding of biochemical constraints for mitochondrial activation is limited. Using aSaccharomyces cerevisiaescreen, we identified the conserved deubiquitinase Ubp3 (Usp10), as necessary for mitochondrial repression. Ubp3 mutants have increased mitochondrial activity despite abundant glucose, along with decreased glycolytic enzymes, and a rewired glucose metabolic network with increased trehalose production. UtilizingΔubp3cells, along with orthogonal approaches, we establish that the high glycolytic flux in glucose continuously consumes free Pi. This restricts mitochondrial access to inorganic phosphate (Pi), and prevents mitochondrial activation. Contrastingly, rewired glucose metabolism with enhanced trehalose production and reduced GAPDH (as inΔubp3cells) restores Pi. This collectively results in increased mitochondrial Pi and derepression, while restricting mitochondrial Pi transport prevents activation. We therefore suggest that glycolytic-flux dependent intracellular Pi budgeting is a key constraint for mitochondrial repression.
Order and disorder in the evolution of online knowledge community: an investigation of the chaotic behavior in social tagging systems with evidence of stack overflow
Authors: Shi Yanqing , Cao Hongye , Chen Si 
Published: December 2022

PurposeOnline question-and-answer (Q&A) communities serve as important channels for knowledge diffusion. The purpose of this study is to investigate the dynamic development process of online knowledge systems and explore the final or progressive state of system development. By measuring the nonlinear characteristics of knowledge systems from the perspective of complexity science, the authors aim to enrich the perspective and method of the research on the dynamics of knowledge systems, and to deeply understand the behavior rules of knowledge systems.Design/methodology/approachThe authors collected data from the programming-related Q&A site Stack Overflow for a ten-year period (2008–2017) and included 48,373 tags in the analyses. The number of tags is taken as the time series, the correlation dimension and the maximum Lyapunov index are used to examine the chaos of the system and the Volterra series multistep forecast method is used to predict the system state.FindingsThere are strange attractors in the system, the whole system is complex but bounded and its evolution is bound to approach a relatively stable range. Empirical analyses indicate that chaos exists in the process of knowledge sharing in this social labeling system, and the period of change over time is about one week.Originality/valueThis study contributes to revealing the evolutionary cycle of knowledge stock in online knowledge systems and further indicates how this dynamic evolution can help in the setting of platform mechanics and resource inputs.
The mediating role of social dynamics in the influence of absorptive capacity and tacit knowledge sharing on project performance
Authors: Boamah Fredrick Ahenkora , Zhang Jianhua , Shehzad Muhammad Usman , Ahmad Mubashir 
Published: December 2022

PurposeThis research aims to establish a comprehensive approach that integrates the aspects to describe how knowledge is focused, developed, reassigned, and implemented to increase project effectiveness. This study examines the interaction of social factors that influences tacit knowledge sharing, absorptive capacity, and project site performance.Design/methodology/approachThe data were collected from Chinese project-based organizations and examined using structural equation modeling (SEM) to test the model and evaluate the hypothesis.FindingsThe findings reveal that good knowledge governance and tacit knowledge sharing are essential prerequisites to boost the project’s absorptive capability. Furthermore, social dynamics favorably modify the link between absorptive capacity, tacit knowledge sharing, and project results. The findings are supportive of the proposed model in general.Originality/valueThis research addresses the critical issue of project knowledge management systems and presents a comprehensive framework that broadens the technical and interpretative bounds of current models designed to achieve project success.
Regression trees for hospitality data analysis
Authors: Tsionas Mike , Assaf A. George 
Published: December 2022

Purpose
The purpose of this note is to describe the concept of regression trees (RTs) for hospitality data analysis.

Design/methodology/approach
RT is an effective non-parametric predicting modelling approach that would free researchers from the need to force a certain functional form. The method does not require normalization or scaling of data.

Findings
The authors illustrate how RTs can be used to find a model that would result in the best prediction.

Research limitations/implications
A common challenge facing hospitality researchers is to estimate a regression model with the correct specification. RTs can help researchers identify the best explanatory model for prediction.

Originality/value
This paper describes the concept of RTs for the modelling of hospitality data.
Magnetohydrodynamic hybrid nanofluid flow over a decelerating rotating disk with Soret and Dufour effects
Authors: Vijay Neha , Sharma Kushal 
Published: December 2022

PurposeThe investigation of fluid flow over a rotating disk has been increasing due to the spread of machine technology. Because of this development, we scrutinized the Magnetohydrodynamic (MHD) flow of hybrid nanofluid caused by a decelerating rotating disk with Ohmic heating, Soret and Dufour effects. The disk's angular velocity is taken to be an inversely time-dependent linear function. Moreover, the temperature-dependent viscosity of hybrid nanofluid is incorporated in the present investigation. Methanol is considered as base fluid, while copper oxide (CuO) and magnesium oxide (MgO) are nanoparticles.Design/methodology/approachEstimated fundamental partial differential equations of flow problems are altered as a dimensionless system of ordinary differential equations using appropriate similarity transformation and solved using a numerical technique: BVP Midrich scheme in Maple software. The impression of emerging non-dimensional parameters is portrayed graphically. All outcomes are shown in the velocity, temperature and concentration profiles.FindingsThe developed flow problem involves a non-dimensional parameter (A) that reveals the deceleration of the disk. For larger values of A, the disk decelerates faster and for some fixed time, the fluid surrounding the disk revolves more rapidly than the disk itself. The radial velocity of fluid diminishes and axial velocity becomes uniform when the disk is subjected to wall suction velocity (B).Originality/valueThis analysis is significant in biomedical engineering, cancer therapeutic, manufacturing industries and nano-drug suspension in pharmaceuticals. The novelty of the current study is the hybrid nanofluid flow with Ohmic heating, Soret and Dufour effects on a decelerating rotating disk. To the best of the author's knowledge, no such consideration has been published in the literature.
Challenges and opportunities in IT transformation of public service delivery: case of India Post
Authors: Sinha Shekhar Kumar , Mukhopadhyay Sandip , Upadhyay Parijat , Dwivedi Yogesh K. , Bhattacharyya Subhajit , Paul Manas , Bhattacharyy Amrita K. 
Published: December 2022

Purpose
Legacy organizations, particularly government departments, have always remained focused on technology acquisition at a low cost. However, they must balance their quest for better financial performance with a commitment to social obligations and inclusiveness. This study aims to analyze the issues faced by a public sector department, India Post, in its digitization process.

Design/methodology/approach
This study takes a case-based approach to analyze India Post’s digitization journey through the theoretical prism of the technology, organization and environment framework.

Findings
The organization’s ability to benefit from innovative technology is constrained by its outdated structure and business processes. The other constraints include the limited technological know-how within the organization and the lack of intricate organizational process knowledge of today’s vendors.

Practical implications
This study portends important implications for policymakers and provides a base for several inquiries for future research. This study attempted to identify the facilitators and inhibitors of digitization initiatives of a legacy government organization with extensive outreach in rural economy which policymakers can consider while rolling out digitization initiatives for public sector organizations.

Originality/value
There are very few studies available as published literature which examined the digitization journey of a legacy government organization in a developing economy. To the best of the authors’ knowledge, there was no published literature available on India Post’s digital transformation process.
An integrated QFD and fuzzy TOPSIS approach for supplier evaluation and selection
Authors: Sharma Jitendra , Tripathy Bibhuti Bhusan 
Published: December 2022

PurposeSupplier evaluation and selection is an essential (multi-criteria decision-making) MCDM process that considers qualitative and quantitative factors. This research work attempts to use a MCDM technique based on merging fuzzy Technique for Order Preference by Similarity to Ideal Solution (F-TOPSIS) and Quality Function Deployment (QFD) ideas. The study attempts to find the supplier's attributes (HOWs) to accomplish its goals after determining the product's characteristics to suit the company's needs (WHATs).Design/methodology/approachThe proposed research methodology comprises the following four steps: Step 1: Determine the product purchase requirements (“WHATs”) and those pertinent to supplier evaluation (“HOWs”). In Step 2, the relative importance of the “WHAT-HOW” correlation scores is determined and also the resulting weights of “HOWs”. In Step 3, linguistic evaluations of possible suppliers in comparison to subjective criteria are given to the decision-makers. Step 4 combines the QFD and F-TOPSIS techniques to select suppliers.FindingsA fuzzy MCDM method based on fusing and integrating fuzzy information and QFD is presented to solve the drawbacks of conventional decision-making strategies used in supplier selection. Using the F-TOPSIS method, fuzzy positive ideal solution (FPIS) and fuzzy negative ideal solution (FNIS), the relative closeness coefficient values for all alternatives are computed. The suppliers are ranked by relating the closeness of coefficient values. This method permits the combination of ambiguous and subjective data expressed as fuzzy-defined integers or linguistic variables.Originality/valueQFD and TOPSIS, two widely used approaches, are combined in this article to rank and evaluate suppliers based on the traits that the suppliers choose to prioritize. This study demonstrates that the method employed could address multiple-criteria decision-making scenarios in a computationally efficient manner. The effectiveness and applicability of the method are illustrated using an example.