bluuebunny/crossref_metadata_2025 huggingface dataset:
External validation and further exploration of fall prediction models based on questionnaires and daily-life trunk accelerometry
Authors: Zhang Yuge , Weijer Roel H.A. , van Schooten Kimberley S. , Bruijn Sjoerd M. , Pijnappels Mirjam
Published: September 2022

Background

Ambulatory measurements of trunk accelerations can provide valuable insight into the amount and quality of daily life activities. Such information has been used to create models that aim to identify individuals at high risk of falls. However, external validation of such prediction models is lacking, yet crucial for clinical implementation. We externally validated three previously described fall prediction models (van Schooten et al., 2015a).

Methods

Complete questionnaires and one week of trunk acceleration data were obtained in 263 community-dwelling people (mean age 71.8 years, 68.1% female). To validate models, we first used the coefficients and optimal cut-offs from original cohort, then recalibrated the original models, as well as optimized parameters based on our new cohort.

Results

Among all participants, 39.9% experienced falls during 6-month follow-up. All models showed poor precision (0.20-0.49), poor sensitivity (0.32-0.58), and good specificity (0.45-0.89). Calibration of the original models had limited effect on model performance. Using coefficients and cut-offs optimized on the external cohort also had limited benefit. Last, the odds ratios in our cohort were different from those in the original cohort and indicated that gait characteristics, except for index of harmonicity ML, were not statistically significantly associated with falls.

Conclusions

Prediction of fall risk in our cohort was not as effective as in the original cohort. Recalibration as well as optimized model parameters resulted in limited increase in accuracy. Fall prediction models are highly specific to the cohort studied. This highlights the need for large representative cohorts, preferably with an external validation cohort.
Antagonistic H3K79me-H3K9ac crosstalk determines elongation at housekeeping genes to promote pluripotency
Authors: Wille Coral K. , Zhang Xiaoya , Haws Spencer A. , Denu John M. , Sridharan Rupa
Published: September 2022

Pluripotent embryonic stem cells (ESCs) have a transcriptionally permissive chromatin environment enriched for gene activation-associated histone modifications as compared to somatic cells. A striking exception is DOT1L-mediated H3K79 methylation that is considered a positive regulator of transcription. Here we find that ESCs maintain low H3K79 methylation to facilitate RNA polymerase II (RNAPII) elongation for greater nascent transcription. Inhibiting DOT1L during the reprogramming of somatic to induced pluripotent stem cells (iPSCs) enables ESC-like RNAPII and transcriptional status. Mechanistically, DOT1L inhibition causes a local gain of histone acetylation at genes that lose the most H3K79me, which unexpectedly are ubiquitously expressed genes that perform essential functions in every cell, rather than lineage specifying genes. Maintenance of this elevated histone acetylation is required for the enhanced conversion to iPSCs upon DOT1L inhibition. Remarkably, increasing global DOT1L or site-specific tethering of DOT1L is sufficient to decrease H3K9ac in ESCs. We discover a high H3ac-low H3K79me epigenetic mechanism that promotes transcription elongation at ubiquitously expressed genes to enforce pluripotent cell identity.
The Effect of P2X7 Antagonism on Subcortical Spread of Optogenetically-Triggered Cortical Spreading Depression and Neuroinflammation
Authors: Uzay Burak , Donmez-Demir Buket , Ozcan Sinem Yilmaz , Kocak Emine Eren , Yemisci Muge , Ozdemir Yasemin Gursoy , Dalkara Turgay , Karatas Hulya
Published: September 2022

Migraine is a neurological disorder characterized by episodes of severe headache. Cortical spreading depression (CSD), the electrophysiological equivalent of migraine aura, results in opening of pannexin-1 megachannels that release ATP and triggers parenchymal neuroinflammatory signaling cascade in the cortex. Migraine symptoms suggesting subcortical dysfunction bring subcortical spread of CSD under the light. Here, we investigated the role of purinergic P2X7 receptors on the subcortical spread of CSD and its consequent neuroinflammation using a potent and selective P2X7 antagonist, JNJ-47965567. P2X7 antagonism had no effect on the CSD threshold and characteristics but increased the latency to hypothalamic voltage deflection following CSD showing that ATP acts as a mediator in the subcortical spread. P2X7 antagonism also prevented hypothalamic neuronal activation following CSD, revealed by bilateral decrease in hypothalamic c-fos positive neuron count. P2X7 antagonism further stopped the CSD-induced neuroinflammation revealed by decreased nuclear translocation of NF-kappa B-p65 in astrocytes and decreased HMGB1 release. Following CSD we observed an increase in neuronal cytoplasmic P2X7R signal in cortex and subcortical structures (thalamus, hypothalamus, striatum, hippocampus) concordant with the neuroinflammation which is also prevented by P2X7R antagonism. In conclusion, our data suggest that P2X7R plays an imperative role in CSD-induced neuroinflammation, subcortical spread of CSD and CSD-induced hypothalamic neuronal activation hence can be a potential target in migraine treatment.
Optical Biopsy using a neural network to predict functional state from photos of wounds
Authors: Teague Joe , Socia Damien , An Gary , Badylak Stephen , Johnson Scott , Jiang Peng , Vodovotz Yoram , Cockrell R. Chase
Published: September 2022

Background

The clinical characterization of the functional status of active wounds remains a considerable challenge that at present, requires excision of a tissue biopsy. In this pilot study, we use a convolutional Siamese neural network architecture to predict the functional state of a wound using digital photographs of wounds in a canine model of volumetric muscle loss (VML).

Materials and Methods

Images of volumetric muscle loss injuries and tissue biopsies were obtained in a canine model of VML. Gene expression profiles for each image were obtained using RNAseq. These profiles were then converted to functional profiles using a manual review of validated gene ontology databases. A Siamese neural network was trained to regress functional profile expression values as a function of the data contained in an extracted image segment showing the surface of a small tissue biopsy. Network performance was assessed in a test set of images using Mean Absolute Percentage Error (MAPE).

Results

The network was able to predict the functional expression of a range of functions based with a MAPE ranging from ∼5% to ∼50%, with functions that are most closely associated with the early-state of wound healing to be those best-predicted.

Conclusions

These initial results suggest promise for further research regarding this novel use of ML regression on medical images. The regression of functional profiles, as opposed to specific genes, both addresses the challenge of genetic redundancy and gives a deeper insight into the mechanistic configuration of a region of tissue in wounds. As this preliminary study focuses on the first 14 days of wound healing, future work will focus on extending the training data to include longer time periods which would result in additional functions, such as tissue remodeling, having a larger presence in the training data.
Shared and unique responses in the microbiome of allopatric lizards reared in a standardized environment
Authors: Assis Braulio A. , Bell Terrence H. , Engler Heather I. , King William L.
Published: September 2022

The gut microbiome can influence host fitness and, consequently, the ecology and evolution of natural populations. Microbiome composition can be driven by environmental exposure but also by the host’s genetic background and phenotype. To contrast environmental and genetic effects on the microbiome we leverage preserved specimens of eastern fence lizards from allopatric lineages east and west of the Mississippi River but reared in standardized conditions. Bacterial composition was indistinguishable between lineages but responded significantly to host age – a proxy for environmental exposure. This was accompanied by a continuous decrease in bacterial diversity in both lineages, partially driven by decreasing evenness seen only in western lizards. These findings indicate that longer exposure to a homogeneous habitat may have a depreciating effect on microbiome diversity in eastern fence lizards, a response shared by both lineages. We highlight the importance of such effects when extrapolating patterns from laboratory experiments to the natural world.
TRPM5+microvillous tuft cells regulate neuroepithelial intrinsic olfactory stem cell proliferation
Authors: Ualiyeva Saltanat , Lemire Evan , Wong Caitlin , Boyd Amelia , Avilés Evelyn C. , Minichetti Dante G. , Perniss Alexander , Maxfield Alice , Roditi Rachel , Matsumoto Ichiro , Barrett Nora A. , Buchheit Kathleen M. , Laidlaw Tanya M. , Boyce Joshua A. , Bankova Lora G. , Haber Adam L
Published: September 2022

The olfactory neuroepithelium serves as a sensory organ for odors and is part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. A subset of these, microvillous cells (MVCs), are strategically positioned at the apical surface but their specific functions are still enigmatic and their relationship to the rest of the solitary chemosensory cell family is unclear. Here, we establish that the larger family of MVCs comprises tuft cells and ionocytes in both mice and humans. Olfactory TRPM5+tuft-MVCs share a core transcriptional profile with the chemosensory tuft family, prominently including the machinery for lipid mediator generation. Integrating analysis of the respiratory and olfactory epithelium, we define the unique receptor expression of TRPM5+tuft-MVC compared to the Gɑ-gustducin+respiratory tuft cells and characterize a new population of glandular DCLK1+tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we employed an integrated single-cell transcriptional and protein analysis. We defined a remodeling olfactory epithelial switch pathway with induction ofChil4and a distinct pathway of proliferation of the quiescent olfactory horizontal basal stem cell (HBC), both triggered in the absence of significant olfactory apoptosis. While theChil4pathway was dependent on STAT6 signaling and innate lymphocytes, neither were required for HBC proliferation. HBC proliferation was dependent on tuft-MVCs, establishing these specialized epithelial cells as both sensors for allergens and regulators of olfactory stem cell responses. Together our data provide high resolution characterization of the nasal tuft cell heterogeneity and uncover a novel mechanism by which TRPM5+tuft cells direct the olfactory mucosal response to allergens.

One Sentence Summary

We identify the enigmatic TRPM5+olfactory microvillous cells as tuft cells, and show their functional role as regulators of olfactory stem cell proliferation in response to environmental signals.
Probing Action Potential Generation and Timing under Multiplexed Basal Dendritic Computations Using Two-photon 3D Holographic Uncaging
Authors: Xiao Shulan , Yadav Saumitra , Jayant Krishna
Published: September 2022

Basal dendrites of layer 5 cortical pyramidal neurons exhibit Na+ and NMDAR spikes, and are uniquely poised to influence somatic output. Nevertheless, due to technical limitations, how multibranch basal dendritic integration shapes action-potential output remains poorly mapped. Here, we combine 3D two-photon holographic transmitter-uncaging, whole-cell dynamic-clamp, and biophysical modeling, to reveal how synchronously activated synapses (distributed and clustered) across multiple basal dendritic branches impacts action-potential generation – under quiescent and in vivo like conditions. While dendritic Na+ spikes promote milli-second precision, distributed inputs and NMDAR spikes modulate firing rates via axo-somatic persistent sodium channel amplification. Action-potential precision, noise-enhanced responsiveness, and improved temporal resolution, were observed under high conductance states, revealing multiplexed dendritic control of somatic output amidst noisy membrane-voltage fluctuations and backpropagating spikes. Our results unveil a critical multibranch integration framework in which a delicate interplay between distributed synapses, clustered synapses, and axo-somatic subthreshold conductance’s, dictates somatic spike precision and gain.
BordetellaSpp. Utilize T3SS To Promote Secretion of IL1RA Leading to Long-Term Persistent Infections
Authors: Williams Tyler L. , Roan Connor , First Nicholas , Johnson Sarah , Gestal Monica C.
Published: September 2022

A common feature of pathogens is their ability to suppress host immune responses. Understanding the molecular mechanisms and the common pathways that bacteria utilize to block host immune signaling cascade might provide novel avenues for vaccine and therapeutic development. Preventable infectious diseases remain one of the major causes of morbidity and mortality worldwide and the current rise in antibiotic resistance is increasing this burden.Bordetellaspp. are respiratory pathogens that cause the long-term illness known as whooping cough.Bordetellainfections cause over 150,000 deaths each year, despite a vaccine being available. In our studies, we used the mouse pathogenB. bronchisepticato investigate the pneumonic stage of disease, which very well mimics the fatal disease caused byB. pertussis. In our previous work we discovered aB. bronchisepticamutant, RB50ΔbtrS, that clears rapidly from the lungs of mice and generates protective immunity that lasts for at least 15 months post-challenge. Combining the mouse immunological tools and both bacteria, the wildtype RB50 and mutant RB50ΔbtrS, which persists for up to 56 days and clears in 14-21 days, respectively, we investigated the mechanisms by which the wildtypeB. bronchisepticablocks host immune response to cause long term lung infection. Previous research indicated eosinophils as critical for rapid clearance of the mutant bacteria from the lungs.In vitroassays with eosinophils demonstrated that the RB50ΔbtrSmutant strain promotes the secretion of pro-inflammatory signals. In contrast, infection of eosinophils with RB50 promoted the secretion of anti-inflammatory signals such as IL1RA. Interestingly, IL1RA was also increased in the lungs of mice infected with the wildtype but not with the mutant RB50 strain. Infection with RB50ΔbscN, which lacks a functional type 3 secretion system (T3SS), was sufficient to prevent IL1RA induction suggesting that the bacterial effector responsible for IL1RA upregulation is a substrate of the T3SS. Supplementation with IL1RA after infection with RB50 or RB50ΔbtrSresulted in increased lung bacterial burden for both bacterial strains. However, more rapid clearance of RB50 was observed after infection of mice in which IL1RA was knocked out. Furthermore, anti-IL1RA antibody treatment promoted rapid clearance of not only RB50 but also the human pathogensB. pertussisandB. parapertussis. This suggests that IL1RA may be a promising therapeutic target to treat severe cases of whooping cough.

Overall, this work demonstrates thatBordetellaspp. induces IL1RA expression to promote persistence using the T3SS. Since other bacteria have also been shown to target IL1RA, this may be a conserved bacterial mechanism to promote host-immune suppression.
Allelic variations and gene cluster modularity act as non-linear bottlenecks for cholera emergence
Authors: López-Pérez Mario , Balasubramanian Deepak , Crist Cole , Grant Trudy-Ann , Haro-Moreno Jose M. , Zaragoza-Solas Asier , Almagro-Moreno Salvador
Published: September 2022

Cholera, an acute secretory diarrhea, is caused by strains from a phylogenetically confined group within theVibrio choleraespecies, the pandemic cholera group (PCG). To date, the molecular and evolutionary factors that enable the isolated emergence of toxigenicV. choleraefrom environmental populations remain mostly enigmatic. Comprehensive analyses of over 1,100V. choleraegenomes, including novel environmental isolates from this study, reveal that the species consists of four major clades and several minor ones. PCG belongs to a large clade located within a lineage shared with environmental strains, the pandemic cholera lineage. This hierarchical classification provided us with a framework to unravel the eco-evolutionary dynamics of the genetic determinants associated with the emergence of toxigenicV. cholerae. Our analyses indicate that this phenomenon is largely dependent on the acquisition of unique modular gene clusters and allelic variations that confer a competitive advantage during intestinal colonization. We determined that certain PCG-associated alleles are essential for successful colonization whereas others provide a non-linear competitive advantage, acting as a critical bottleneck that elucidates the isolated emergence of PCG. For instance, toxigenic strains encoding non-PCG alleles of a)tcpFor b) a sextuple allelic exchange mutant for genestcpA,toxT,VC0176,VC1791,rfbTandompU, lose their ability to colonize the intestine. Interestingly, these alleles do not play a role in the colonization of model environmental reservoirs. Our study uncovers the evolutionary roots of toxigenicV. choleraeand offers a tractable approach for investigating the emergence of pathogenic clones within an environmental population.

SIGNIFICANCE

The underlying factors that lead to specific strains within a species to emerge as human pathogens remain mostly enigmatic. Toxigenic clones of the cholera agent,Vibrio cholerae, are encompassed within one phylogenomic clade, the pandemic cholera group (PCG). Here, we investigate the molecular and evolutionary factors that explain the confined nature of this group. Our analyses determined that the emergence of PCG is largely dependent on the acquisition of unique modular gene clusters and allelic variations that confer a competitive advantage during intestinal colonization. These allelic variations act as a critical bottleneck that elucidates the isolated emergence of PCG and provides a tractable blueprint for the study of the emergence of pathogenic clones within an environmental population.
Seasonal models reveal niche changes during invasion in Capsella bursa-pastoris
Authors: Brown Maya K. Wilson , Josephs Emily B.
Published: September 2022

Researchers often use ecological niche models to predict where species might establish and persist under future or novel climate conditions. However, these predictive methods assume species have stable niches across time and space. Furthermore, ignoring the time of occurrence data can obscure important information about species reproduction and ultimately fitness. In this study, we generate full-year and monthly ecological niche models for Capsella bursa-pastoris to see if we can detect changes in the seasonal niche of the species after long-distance dispersal. We find full-year ecological niche models have low transferability across continents and there are continental differences in the climate conditions that influence the distribution of C. bursa-pastoris. Monthly models have greater predictive accuracy than full-year models in cooler seasons, but the inability of any model to predict summer occurrence in North America suggests a change in the seasonal niche from the native range to the non-native range. These results highlight the utility of ecological niche models at finer temporal scales in predicting species distributions and unmasking subtle patterns of evolution.
Thalamocortical boutons cluster by ON/OFF responses in mouse primary visual cortex
Authors: Tring Elaine , Ringach Dario L.
Published: September 2022

In higher mammals, the thalamic afferents to primary visual cortex cluster according to their responses to increases (ON) or decreases (OFF) in luminance. This feature of thalamocortical wiring is thought to create columnar, ON/OFF domains in V1. We have recently shown that mice also have ON/OFF cortical domains, but the organization of their thalamic afferents remains unknown. Here we measured the visual responses of thalamocortical boutons using two-photon imaging and found they also cluster in space according to ON/OFF responses. Moreover, fluctuations in the relative density of ON/OFF boutons mirrors fluctuations in the relative density of ON/OFF receptive field positions on the visual field. These findings indicate that there is a segregation of ON/OFF signals already present in the thalamic input, a result that may reflect the spatial organization of retinal ganglion cell mosaics themselves.

New and Noteworthy

Neurons in primary visual cortex cluster into ON and OFF domains, which have shown to be linked to the organization of receptive fields and cortical maps. Here we show that in the mouse, such clustering is already present in the thalamic input, suggesting that the cortical architecture is shaped by the periphery.
Cross-species predictive modeling reveals conserved drought responses between maize and sorghum
Authors: Pardo Jeremy , Wai Ching Man , Harman Max , Nguyen Annie , Kremling Karl A. , Romay Cinta , Lepak Nicholas , Bauerle Taryn L. , Buckler Edward S. , Thompson Addie M. , VanBuren Robert
Published: September 2022

Drought tolerance is a highly complex trait controlled by numerous interconnected pathways with substantial variation within and across plant species. This complexity makes it difficult to distill individual genetic loci underlying tolerance, and to identify core or conserved drought responsive pathways. Here, we collected drought physiology and gene expression datasets across diverse genotypes of the C4 cereals sorghum and maize and searched for signatures defining water deficit responses. Differential gene expression identified few overlapping drought associated genes across sorghum genotypes, but using a predictive modeling approach, we found a shared core drought response across development, genotype, and stress severity. Our model had similar robustness when applied to datasets in maize, reflecting a conserved drought response between sorghum and maize. The top predictors are enriched in functions associated with various abiotic stress responsive pathways as well as core cellular functions. These conserved drought response genes were less likely to contain deleterious mutations than other gene sets, suggesting that core drought responsive genes are under evolutionary and functional constraints. Our findings support a broad evolutionary conservation of drought responses in C4 grasses regardless of innate stress tolerance, which could have important implications for developing climate resilient cereals.

Significance Statement

Drought is a complex and variable stress that is difficult to quantify and link to underlying mechanisms both within and across species. Here, we developed a predictive model to classify drought stress responses in sorghum and identify important features that are responsive to water deficit. Our model has high predictive accuracy across development, genotype, and stress severity, and the top features are enriched in genes related to classical stress responses and have functional and evolutionary conservation. We applied this sorghum trained model to maize, and observed similar predictive accuracy of drought responses, supporting transfer learning across plant species. Our findings suggest there are deeply conserved drought responses across C4 grasses that are unrelated to tolerance.
Resolution of structural variation in diverse mouse genomes reveals chromatin remodeling due to transposable elements
Authors: Ferraj Ardian , Audano Peter A. , Balachandran Parithi , Czechanski Anne , Flores Jacob I. , Radecki Alexander A. , Mosur Varun , Gordon David S. , Walawalkar Isha A. , Eichler Evan E. , Reinholdt Laura G. , Beck Christine R.
Published: September 2022

Diverse inbred mouse strains are among the foremost models for biomedical research, yet genome characterization of many strains has been fundamentally lacking in comparison to human genomics research. In particular, the discovery and cataloging of structural variants is incomplete, limiting the discovery of potentially causative alleles for phenotypic variation across individuals. Here, we utilized long-read sequencing to resolve genome-wide structural variants (SVs, variants ≥ 50 bp) in 20 genetically distinct inbred mice. We report 413,758 site-specific SVs that affect 13% (356 Mbp) of the current mouse reference assembly, including 510 previously unannotated variants which alter coding sequences. We find that 39% of SVs are attributed to transposable element (TE) variation accounting for 75% of bases altered by SV. We then utilized this callset to investigate the impact of TE heterogeneity on mouse embryonic stem cells (mESCs), and find multiple TE classes that influence chromatin accessibility across loci. We also identify strain-specific transcription start sites originating in polymorphic TEs that modify gene expression. Our work provides the first long-read based analysis of mouse SVs and illustrates that previously unresolved TEs underlie epigenetic and transcriptome differences in mESCs.
Impact of phylogeny on structural contact inference from protein sequence data
Authors: Dietler Nicola , Lupo Umberto , Bitbol Anne-Florence
Published: September 2022

Local and global inference methods have been developed to infer structural contacts from multiple sequence alignments of homologous proteins. They rely on correlations in amino-acid usage at contacting sites. Because homologous proteins share a common ancestry, their sequences also feature phylogenetic correlations, which can impair contact inference. We investigate this effect by generating controlled synthetic data from a minimal model where the importance of contacts and of phylogeny can be tuned. We demonstrate that global inference methods, specifically Potts models, are more resilient to phylogenetic correlations than local methods, based on covariance or mutual information. This holds whether or not phylogenetic corrections are used, and may explain the success of global methods. We analyse the roles of selection strength and of phylogenetic relatedness. We show that sites that mutate early in the phylogeny yield false positive contacts. We consider natural data and realistic synthetic data, and our findings generalise to these cases. Our results highlight the impact of phylogeny on contact prediction from protein sequences and illustrate the interplay between the rich structure of biological data and inference.
A tissue-specific ubiquitin switch coordinates brain, craniofacial, and skin development
Authors: Asmar Anthony J. , Yazejian Rita M. , Wu Youmei , Collins Jason C. , Hsin Jenny , Cho Jean , Doyle Andrew D. , Cinthala Samhitha , Simon Marleen , van Jaarsveld Richard H. , Beck David B. , Kerosuo Laura , Werner Achim
Published: September 2022

The molecular mechanisms that coordinate patterning of the embryonic ectoderm into spatially distinct lineages to form the nervous system, epidermis, and craniofacial structures are unclear. Here, biochemical disease-variant profiling reveals a posttranslational pathway that drives early ectodermal differentiation in the vertebrate head. The anteriorly expressed ubiquitin ligase CRL3-KLHL4 restricts signaling of the ubiquitous cytoskeletal regulator CDC42. The major substrate of CRL3-KLHL4 is the canonical CDC42 effector kinase PAK1 that monoubiquitylation switches into a CDC42 inhibitor. Loss of CRL3-KLHL4 or a disease-associated KLHL4 variant reduce PAK1 ubiquitylation causing overactivation of CDC42 signaling and defective ectodermal patterning and neurulation. Thus, tissue-specific, ubiquitin-dependent restriction of CDC42 signaling is essential for face, brain, and skin formation, demonstrating how cell-fate and morphometric changes are coordinated for faithful organ development.
Dopamine projections to the basolateral amygdala drive the encoding of identity-specific reward memories
Authors: Sias Ana C. , Jafar Yousif , Goodpaster Caitlin M. , Ramírez-Armenta Kathia , Wrenn Tyler M. , Griffin Nicholas K. , Patel Keshav , Lamparelli Alexander C. , Sharpe Melissa J. , Wassum Kate M.
Published: September 2022

To make adaptive decisions, we build an internal model of the associative relationships in an environment and use it to make predictions and inferences about specific available outcomes. Detailed, identity-specific cue-reward memories are a core feature of such cognitive maps. Here we used fiber photometry, cell-type and pathway-specific optogenetic manipulation, Pavlovian cue-reward conditioning, and decision-making tests in male and female rats, to reveal that ventral tegmental area dopamine (VTADA) projections to the basolateral amygdala (BLA) drive the encoding of identity-specific cue-reward memories. Dopamine is released in the BLA during cue-reward pairing and VTADA→BLA activity is necessary and sufficient to link the identifying features of a reward to a predictive cue, but does not assign general incentive properties to the cue or mediate reinforcement. These data reveal a dopaminergic pathway for the learning that supports adaptive decision making and help explain how VTADAneurons achieve their emerging multifaceted role in learning.
Integrated Model of the Vertebrate Augmin Complex
Authors: Travis Sophie M , Mahon Brian P , Huang Wei , Ma Meisheng , Rale Michael J , Kraus Jodi S , Taylor Derek J , Zhang Rui , Petry Sabine
Published: September 2022

Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which exponentially amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but understanding how augmin promotes branching has been hindered by a lack of structural information about the complex. Here, we report an integrated model of vertebrate augmin, combining cryo-electron microscopy, advanced protein structural prediction, and the visualization of fused bulky tags via negative stain electron microscopy. This strategy allowed us to identify the location and orientation of each subunit within the structure. Evolutionary analysis of augmin’s structure reveals that it is highly conserved across diverse eukaryotes, and that augmin contains a previously-unidentified microtubule binding site. Moreover, we identify homology with the kinetochore-localized NDC80 complex. This new model of the augmin complex provides insight towards the mechanism and evolution of branching microtubule nucleation.
The genetic architecture of adaptation to leaf and root bacterial microbiota inArabidopsis thaliana
Authors: Roux Fabrice , Frachon Léa , Bartoli Claudia
Published: September 2022

Understanding the role of host genome in modulating microbiota variation is a need to shed light into the holobiont theory and overcome the current limits on the description of host-microbiota interactions at the genomic and molecular levels. However, the host genetic architecture structuring microbiota is only partly described in plants. In addition, most association genetic studies on microbiota are often carried out outside the native habitats where the host evolve and the identification of signatures of local adaptation on the candidate genes has been overlooked. To fill these gaps and dissect the genetic architecture driving adaptive plant-microbiota interactions, we adopted a Genome-Environmental-Association (GEA) analysis on 141 whole-genome sequenced natural populations ofArabidopsis thalianacharacterizedin situfor their leaf and root bacterial communities and a large range of environmental descriptors (i.e. climate, soil and plant communities). Across 194 microbiota traits, a much higher fraction of among-population variance was explained by the host genetics than by ecology, with the plant neighborhood as the main ecological driver of microbiota variation. Importantly, the relative importance of host genetics and ecology expressed a phylogenetic signal at the family and genus level. In addition, the polygenic architecture of adaptation to bacterial communities was highly flexible between plant compartments and seasons. Relatedly, signatures of local adaptation were stronger on QTLs of the root microbiota in spring. Finally, we provide evidence that plant immunity, in particular theFLS2gene, is a major source of adaptive genetic variation structuring bacterial assemblages inA. thaliana.
Emergence and Persistent Dominance of Omicron BA.2.3.7 Variant in Community Outbreaks in Taiwan
Authors: Shao Pei-Lan , Tu Hsiao-Chen , Gong Yu-Nong , Shu Hung-Yu , Kirby Ralph , Hsu Li-Yun , Yeo Hui-Yee , Kuo Han-Yueh , Huang Yi-Chia , Lin Yung-Feng , Weng Hui-Ying , Wu Yueh-Lin , Chen Chien-Chih , Chen Tzen-Wen , Lee Kuo-Ming , Huang Chung-Guei , Shih Shin-Ru , Chen Wei J , Wu Chen-Chi , Yu Chong-Jen , Tsai Shih-Feng
Published: September 2022

Since April 2022, waves of Omicron cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we have analyzed 2405 PCR-positive swab samples from 2339 individuals and identified the Omicron BA.2.3.7 variant as a major lineage within the recent community outbreak in Taiwan.
Overview of maternal morbidity in Morocco Marrakech-Safi region
Authors: Hababa Hanane , Assarag Bouchra
Published: September 2022

Objectives

The measurement of less severe maternal morbidity represents many challenges for women during pregnancy and postpartum, and for the organization of health services. This article aims to test the tools for measuring maternal morbidity less severe proposed by the WHO and describe the state of play of this morbidity at the level of the prefecture of Marrakech. The second phase is to study the feasibility and acceptability of integrating these tools into the Pregnancy and Childbirth Surveillance Program.

Methods

The analysis focused on the maternal morbidities declared and diagnosed in the test, and related the feasibility and acceptability as well as the relevance of the tools tested.

Results

Most of the women who participated in the study (55.95% antenatal and 52.17% postpartum care) were not in good health (A medical or obstetric condition is diagnosed). Of these women, 35.79% had direct (obstetric) complications and 33.85% indirect (medical) complications. In terms of feasibility, the results suggest that the implementation of the tools presents challenges in terms of time, resources and coordination. Regarding the acceptability of the WMOs, the women surveyed perceive it as a useful information tool that promotes communication with health professionals and makes it possible to assess their state of health and ensure their holistic care.

Conclusion

Considering these results, the approach supports the relevance of implementing the MM measure in antenatal and postpartum care to improve the quality of care for women, to promote communication and continuity of care. However, constraints of time, resources and coordination must be taken into account for its implementation at primary health care.
Bmi1 suppresses protein synthesis and promotes proteostasis in hematopoietic stem cells
Authors: Burgess Rebecca J. , Zhao Zhiyu , Nakada Daisuke , Morrison Sean J.
Published: September 2022

The polycomb complex component Bmi1 promotes the maintenance of stem cells in multiple postnatal tissues, partly by negatively regulating the expression of p16Ink4a and p19Arf, tumor suppressors associated with cellular senescence. However, deficiency for p16Ink4a and p19Arf only partially rescues the function of Bmi1-deficient stem cells. We conditionally deleted Bmi1 from adult hematopoietic cells and found that this slowly depleted hematopoietic stem cells (HSCs). Rather than inducing senescence, Bmi1 deficiency increased HSC division. The increased cell division was caused partly by increased Aristaless-related homeobox (ARX) transcription factor expression, which also increased ribosomal RNA expression. However, ARX deficiency did not rescue HSC depletion. Bmi1 deficiency also increased protein synthesis, protein aggregation, and protein ubiquitylation independent of its effects on cell division and p16Ink4a, p19Arf, and ARX expression. Bmi1 thus promotes HSC quiescence by negatively regulating ARX expression and promotes proteostasis by suppressing protein synthesis. This highlights a new connection between the regulation of stem cell maintenance and proteostasis.
Modelling services continuance intention: evidence from apps stores
Authors: Ng Sze Ling , Rezaei Sajad , Valaei Naser , Iranmanesh Mohammad
Published: September 2022

Purpose

The objective of this study is to examine the drivers of retail apps satisfaction and continuance intention. An integrative theoretical framework was developed based on the IS success model, E-S-QUAL and expectancy and disconfirmation model to explain retail apps users’ satisfaction and continuance intention.

Design/methodology/approach

A total of 359 useable data were collected from the targeted Malaysian respondents who had experience in using retail apps services. Data were analysed using the partial least squares technique.

Findings

The results indicate that system quality and e-service quality positively influence retail apps usage satisfaction and have positive direct and indirect effects through satisfaction on continuance intention. The price level has a negative effect on retail apps usage satisfaction. Even though price level has no direct effect on continuance intention to use retail apps, it has an indirect effect on continuance intention through satisfaction.

Originality/value

Although the success of a marketing channel mainly depends on its continuance usage rather than first-time usage, few studies have paid attention to retail apps services. This study contributes to the advancement of knowledge on retail apps by explaining the roles of system quality, e-service quality and price level on retail apps satisfaction and continuance intention. Interestingly, the findings of multi-group analysis imply that female Gen Y app users are more satisfied than males while such differences do not impact their continuance intention to use the retail apps. The findings also suggested that frequency of using apps has no relevance to retail apps user satisfaction, but highly relevant to their continuance intention to use retail Apps services.
A multigroup SEM analysis of the antecedents and moderating influence of culture on workplace deviance behavior
Authors: Narayanan Kanimozhi , Moon Chanki
Published: September 2022

Purpose

Antecedents and outcomes of workplace deviance have been studied over the past few decades but there is still a lack of research from an organizational climate, witness and cultural point of view. Theoretical considerations for the present research are based on the social cognitive theory perspective where the authors expect employees's involvement in workplace destructive deviance would depend on their organizational climate perception, witness behavior and cultural orientation.

Design/methodology/approach

A total of 987 participants from India (N = 404) and USA (N = 583) completed an online questionnaire, and multi-group structural equation modeling analysis was conducted to test the hypothesized model.

Findings

Across cultural groups, higher collectivism is associated with lower engagement in workplace deviance. Furthermore, employees' higher intervening witness behavior is associated with lower destructive deviant behaviors when employees showed higher endorsement of collectivism in India (not USA). However, employees' higher self-serving witness behavior is associated with higher destructive deviant behaviors. Interestingly, employees with higher endorsement of individualism associated with organizational climate are more likely to engage in destructive deviance.

Originality/value

The main originality of this study is to further increase the understanding of the relationship between organizational climate, witness behavior (self-serving and intervening behavior) and workplace deviance (organizational and interpersonal destructive deviance) considering the role of employees' cultural orientation (individualism vs collectivism).
Unveiling the tourist’s social media cycle: use of social media during travel decision-making
Authors: Gulati Shruti
Published: September 2022

Purpose

This study aims to explore when and for what purpose is social media used by tourists in their decision-making; and to further interpret the nature of such usage.

Design/methodology/approach

An online questionnaire was administered to 530 Indians who qualified as recent tourists and social media users. Partial least square structural equation modeling (PLS-SEM) is used to analyse hypothesised relationships; the results helped us to unveil the tourist social media cycle which is a conceptual model of the results obtained.

Findings

PLS-SEM results indicate that social media is predominantly used in the pre-travel stage for evaluation purposes, during travel stage for purchase purposes and post-travel stage for post-purchase behaviour. Also, it is noted that social media use by a tourist is an ongoing process, and thus, a conceptual model in the form of tourist social media cycle is unveiled.

Practical implications

This study reveals the unique behaviour of Indian tourists with respect to using social media for travel decision-making, which establishes a different perspective of understanding and further strategizing social media’s use in tourism for a developing nation. Also, the tourist social media cycle stresses on the importance of social media as a digital repository where continuously the user-generated content is used by self (existing) or “others” (potential tourists).

Originality/value

To the best of the author’s knowledge, this is the first study that addresses the population and knowledge gap of understanding social media–based tourist behaviour providing a perspective of a developing nation, specifically India. Further, it unveils the nature of social media use by tourist in the form of a first ever tourist social media cycle.
A new sorting algorithm-based merging weighted fraction Monte Carlo method for solving the population balance equation for particle coagulation dynamics
Authors: Wang Fei , Chan Tat Leung
Published: September 2022

Purpose

The purpose of this study is to present a newly proposed and developed sorting algorithm-based merging weighted fraction Monte Carlo (SAMWFMC) method for solving the population balance equation for the weighted fraction coagulation process in aerosol dynamics with high computational accuracy and efficiency.

Design/methodology/approach

In the new SAMWFMC method, the jump Markov process is constructed as the weighted fraction Monte Carlo (WFMC) method (Jiang and Chan, 2021) with a fraction function. Both adjustable and constant fraction functions are used to validate the computational accuracy and efficiency. A new merging scheme is also proposed to ensure a constant-number and constant-volume scheme.

Findings

The new SAMWFMC method is fully validated by comparing with existing analytical solutions for six benchmark test cases. The numerical results obtained from the SAMWFMC method with both adjustable and constant fraction functions show excellent agreement with the analytical solutions and low stochastic errors. Compared with the WFMC method (Jiang and Chan, 2021), the SAMWFMC method can significantly reduce the stochastic error in the total particle number concentration without increasing the stochastic errors in high-order moments of the particle size distribution at only slightly higher computational cost.

Originality/value

The WFMC method (Jiang and Chan, 2021) has a stringent restriction on the fraction functions, making few fraction functions applicable to the WFMC method except for several specifically selected adjustable fraction functions, while the stochastic error in the total particle number concentration is considerably large. The newly developed SAMWFMC method shows significant improvement and advantage in dealing with weighted fraction coagulation process in aerosol dynamics and provides an excellent potential to deal with various fraction functions with higher computational accuracy and efficiency.
How to invest in total quality management practices for enhanced operational performance: findings from PLS-SEM and fsQCA
Authors: Acquah Innocent Senyo Kwasi , Quaicoe Judith , Arhin Michael
Published: September 2022

Purpose

Consumer expectations of quality have grown in recent years, forcing organisations, both service and manufacturing, to adopt total quality management (TQM) principles to satisfy customer demands efficiently. However, previous studies on the performance impacts of total quality management practices have mainly focused on the financial performance of firms in the manufacturing sector. This study focusses on the research questions: (1) What is the effect of TQM practices on operational performance? and (2) How do TQM practices combine to influence the operational performance of healthcare facilities?

Design/methodology/approach

Using a sample of 154 health facilities (i.e. private hospitals, pharmacies, maternity clinics, and diagnostic centres), the authors applied symmetric (PLS-SEM) and asymmetric (fsQCA) data analysis approaches to examine how TQM practices influence the operational performance of health facilities in the Ashanti Region of Ghana.

Findings

The PLS-SEM results revealed that five out of the seven TQM practices investigated influenced operational performance. However, the fsQCA results identify five different complex combinations of TQM practices that lead to operational performance.

Research limitations/implications

Longitudinal studies can be conducted in the future to assess changes in the variables over time. A control variable, such as firm size, should be considered to assess the level of implementation of TQM practices based on firm size. A different performance measure, for instance, sustainability indicators or the balance score card, could be used to examine performance.

Practical implications

A proper and coordinated integration of the TQM practices is required for firms to be able to achieve operational performance. TQM practices vary in their sufficiency for operational outcomes; therefore, management needs to carefully consider their implementation as part of the organisation's strategy.

Originality/value

This research, by focussing on TQM practices from both symmetrical and asymmetrical perspectives, contributes to the understanding of the literature on TQM, thereby providing actionable insight on how to invest in the various TQM practices for improved operational performance.