bluuebunny/crossref_metadata_2025 huggingface dataset:
SLC25A46 is in contact with lysosomes and plays a role in mitochondrial cholesterol homeostasis
Authors: Schuettpelz Jana , Watt Kathleen , Antonicka Hana , Janer Alexandre , Larsson Ola , Shoubridge Eric A.
Published: April 2024

Mitochondrial morphology reflects the dynamic equilibrium between fusion and fission events, controlled by cellular signaling. A cytoprotective response known as stress-induced mitochondrial hyperfusion (SIMH) is triggered by nutrient starvation and we show that the outer mitochondrial membrane protein SLC25A46 is required for this response. To unravel the cellular mechanisms involved, we conducted transcriptomic analysis on control human fibroblasts and SLC25A46 knock-out cells. Our analysis revealed a remarkable divergence in the transcriptional profile of proteins associated with lysosomal function and cholesterol binding and synthesis. Further investigations using live-cell imaging validated the presence of SLC25A46 at the majority of mitochondria-lysosome contact sites. Since mitochondria-lysosome contacts are linked to cholesterol transport, we investigated the involvement of SLC25A46 in cholesterol trafficking. The SLC25A46 knock-out cell line exhibited a decrease in mitochondrial cholesterol content and distinct alterations were observed in the pattern of cholesterol trafficking compared to control. Cholesterol supplementation in the SLC25A46 knock-out cell line rescued the mitochondrial fragmentation phenotype and restored the SIMH response, suggesting a role for SLC25A46 in maintaining mitochondrial cholesterol homeostasis.

Summary blurb

The mitochondrial outer membrane protein SLC25A46 is required for SIMH triggered by nutrient starvation, localizes to lysosome contact sites and is involved in mitochondrial cholesterol homeostasis
Dynamic co-evolution of transposable elements and the piRNA pathway in African cichlid fishes
Authors: Almeida Miguel Vasconcelos , Blumer Moritz , Yuan Chengwei Ulrika , Sierra Pío , Price Jonathan L. , Quah Fu Xiang , Friman Aleksandr , Dallaire Alexandra , Vernaz Grégoire , Putman Audrey L. K. , Smith Alan M. , Joyce Domino A. , Butter Falk , Haase Astrid D. , Durbin Richard , Santos M. Emília , Miska Eric A.
Published: April 2024

East African cichlid fishes have diversified in an explosive fashion, but the (epi)genetic basis of the phenotypic diversity of these fishes remains largely unknown. Although transposable elements (TEs) have been associated with phenotypic variation in cichlids, little is known about their transcriptional activity and epigenetic silencing. Here, we describe dynamic patterns of TE expression in African cichlid gonads and during early development. Orthology inference revealed an expansion ofpiwil1genes in Lake Malawi cichlids, likely driven by PiggyBac TEs. The expandedpiwil1copies have signatures of positive selection and retain amino acid residues essential for catalytic activity. Furthermore, the gonads of African cichlids express a Piwi-interacting RNA (piRNA) pathway that target TEs. We define the genomic sites of piRNA production in African cichlids and find divergence in closely related species, in line with fast evolution of piRNA-producing loci. Our findings suggest dynamic co-evolution of TEs and host silencing pathways in the African cichlid radiations. We propose that this co-evolution has contributed to cichlid genomic diversity.
A versatile information retrieval framework for evaluating profile strength and similarity
Authors: Kalinin Alexandr A. , Arevalo John , Serrano Erik , Vulliard Loan , Tsang Hillary , Bornholdt Michael , Sivagurunathan Suganya , Rajwa Bartek , Carpenter Anne E. , Way Gregory P. , Singh Shantanu
Published: April 2024

In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging to evaluate the phenotypic activity of a sample and the phenotypic consistency among samples, due to profiles’ high dimensionality, heterogeneous nature, and non-linear properties. Existing methods leave researchers uncertain where to draw boundaries between meaningful biological response and technical noise. Here, we developed a statistical framework that uses the well-established mean average precision (mAP) as a single, data-driven metric to bridge this gap. We validated the mAP framework against established metrics through simulations and real-world data applications, revealing its ability to capture subtle and meaningful biological differences in cell state. Specifically, we used mAP to assess both phenotypic activity for a given perturbation (or a sample) as well as consistency within groups of perturbations (or samples) across diverse high-dimensional datasets. We evaluated the framework on different profile types (image, protein, and mRNA profiles), perturbation types (CRISPR gene editing, gene overexpression, and small molecules), and profile resolutions (single-cell and bulk). Our open-source software allows this framework to be applied to identify interesting biological phenomena and promising therapeutics from

large-scale profiling data.
Group Heteroscedasticity - A Silent Saboteur of Power and False Discovery in RNA-Seq Differential Expression
Authors: Chatterjee Suvo , Fadikar Arindam , Hanumesh Vrushab , Meshram Siddhant Sunil , Zoh Roger S , Ma Siyuan , Arunkumar Ganesan , Mallick Himel
Published: April 2024

Despite the availability of several high-profile, state-of-the-art methods, analyzing bulk RNA-Seq data continues to face significant challenges. Evidence from recent studies has highlighted that popular differential expression (DE) tools, such as edgeR and DESeq2, are susceptible to an alarmingly high false discovery rate (FDR). These studies suggest that the FDR inflation observed in these models could be attributed to issues such as violations of parametric assumptions or an inability to effectively handle outliers in the data. Here, we argue that group heteroscedasticity can also contribute to this elevated FDR, a phenomenon largely overlooked by the research community. We introduce a novel statistical model, Robseq, designed for effective per-feature modeling in differential analysis, particularly when the assumption of group homoscedasticity is unmet. Robseq utilizes well-established statistical machinery from the robust statistics literature, including M-estimators to robustly estimate gene expression level changes and Huber-Cameron variance estimators to calculate robust standard errors in heteroscedastic settings. Additionally, it incorporates a degrees of freedom adjustment for the Welch t-statistic, based on Bell-McCaffrey’s recommendation, for inferential purposes, effectively addressing the problem of FDR inflation in RNA-Seq differential expression. Through detailed simulations and comprehensive benchmarking, we show that Robseq successfully maintains the false discovery and type-I error rates at nominal levels while retaining high statistical power compared to well-known DE methods. Analysis of population-level RNA-Seq data further demonstrates that Robseq is capable of identifying biologically significant signals and pathways implicated in complex human diseases that otherwise cannot be revealed by published methods. The implementation of Robseq is publicly available as an R package athttps://github.com/schatterjee30/Robseq.
Dysregulation in Spatiotemporal Expression ofHMX1Coordinated by Multifaceted Enhancers Drives an Auricular Disorder
Authors: Xu Xiaopeng , Chen Qi , Huang Qingpei , Cox Timothy C. , Zhu Hao , Hu Jintian , Han Xi , Meng Ziqiu , Wang Bingqing , Liao Zhiying , Xu Wenxin , Xiao Baichuan , Lang Ruirui , Liu Jiqiang , Li Qiang , Zhang Qingguo , Antonarakis Stylianos E. , Zhang Jiao , Fan Xiaoying , Liu Huisheng , Zhang Yong-Biao
Published: April 2024

Enhancers, through the combinatorial action of transcription factors (TFs), dictate both the spatial specificity and the levels of gene expression, and their aberrations can result in diseases. The association betweenHMX1and its downstream enhancer with ear deformities has been previously documented. However, the pathogenic variations and molecular mechanisms underlying the bilateral constricted ear (BCE) malformations remain unclear. This study identifies a copy number variation (CNV) encompassing three enhancers that induces BCE. These enhancers, collectively termed the positional identity hierarchical enhancer cluster (PI-HEC), co-regulate spatiotemporal expression of theHMX1gene in a coordinated and synergistic mode, each displaying unique activity-location-structure characteristics. A thorough exploration of this regulatory locus reveals that specific motif clusters within the PI-HEC variably modulate its activity and specificity, with the high mobility group (HMG) box combined with Coordinator and homeodomain (HD)-TFs notably influencing them respectively. Our findings based on various types of mouse models, reveal that both aberrantHmx1expression in the fibroblasts of the basal pinna, originating from neural crest cells, and ectopic expression in the distal pinna structures contribute to the abnormal development of the outer ear, including the cartilage, muscle, and epidermis tissues. This study deepens our understanding of mammalian ear morphogenesis and sheds light on the complexity of gene expression regulation by enhancers and specific sequence motifs.
Perceptual Resolution of Ambiguity: Can Tuned, Divisive Normalization Account for both Interocular Similarity Grouping and Difference Enhancement
Authors: Peiso Jaelyn R. , Palmer Stephanie E. , Shevell Steven K.
Published: April 2024

Our visual system usually provides a unique and functional representation of the external world. At times, however, the visual system has more than one compelling interpretation of the same retinal stimulus; in this case, neural populations compete for perceptual dominance to resolve ambiguity. Spatial and temporal context can guide perceptual experience. Recent evidence shows that ambiguous retinal stimuli are sometimes resolved by enhancing either similarity or differences among multiple percepts. Divisive normalization is a canonical neural computation that enables context-dependent sensory processing by attenuating a neuron’s response by other neurons. Experiments here show that divisive normalization can account for perceptual representations of either similarity enhancement (so-called grouping) or difference enhancement, offering a unified framework for opposite perceptual outcomes.
A specific and portable gene expression program underlies antigen archiving by lymphatic endothelial cells
Authors: Sheridan Ryan M. , Doan Thu A. , Lucas Cormac , Forward Tadg S. , Uecker-Martin Aspen , Morrison Thomas E. , Hesselberth Jay R. , Tamburini Beth A. Jirón
Published: April 2024

Antigens from protein subunit vaccination traffic from the tissue to the draining lymph node, either passively via the lymph or carried by dendritic cells at the local injection site. Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens, and archived antigen can be released during subsequent inflammatory stimulus to improve immune responses. Here, we answer questions about how LECs achieve durable antigen archiving and whether there are transcriptional signatures associated with LECs containing high levels of antigen. We used single cell sequencing in dissociated LN tissue to quantify antigen levels in LEC and dendritic cell populations at multiple timepoints after immunization, and used machine learning to define a unique transcriptional program within archiving LECs that can predict LEC archiving capacity in independent data sets. Finally, we validated this modeling, showing we could predict antigen archiving from a transcriptional dataset of CHIKV infected mice and demonstratedin vivothe accuracy of our prediction. Collectively, our findings establish a unique transcriptional program in LECs that promotes antigen archiving that can be translated to other systems.
SPLICER: A Highly Efficient Base Editing Toolbox That EnablesIn VivoTherapeutic Exon Skipping
Authors: Miskalis Angelo , Shirguppe Shraddha , Winter Jackson , Elias Gianna , Swami Devyani , Nambiar Ananthan , Stilger Michelle , Woods Wendy S. , Gosstola Nicholas , Gapinske Michael , Zeballos Alejandra , Moore Hayden , Maslov Sergei , Gaj Thomas , Perez-Pinera Pablo
Published: April 2024

Exon skipping technologies enable exclusion of targeted exons from mature mRNA transcripts, which has broad applications in molecular biology, medicine, and biotechnology. Existing exon skipping techniques include antisense oligonucleotides, targetable nucleases, and base editors, which, while effective for specific applications at some target exons, remain hindered by shortcomings, including transient effects for oligonucleotides, genotoxicity for nucleases and inconsistent exon skipping for base editors. To overcome these limitations, we created SPLICER, a toolbox of next-generation base editors consisting of near-PAMless Cas9 nickase variants fused to adenosine or cytosine deaminases for the simultaneous editing of splice acceptor (SA) and splice donor (SD) sequences. Synchronized SA and SD editing with SPLICER improves exon skipping, reduces aberrant outcomes, including cryptic splicing and intron retention, and enables skipping of exons refractory to single splice-site editing. To demonstrate the therapeutic potential of SPLICER, we targetedAPPexon 17, which encodes the amino acid residues that are cleaved to form the Aβ plaques in Alzheimer’s disease. SPLICER reduced the formation of Aβ42 peptidesin vitroand enabled efficient exon skipping in a mouse model of Alzheimer’s disease. Overall, SPLICER is a widely applicable and efficient toolbox for exon skipping with broad therapeutic applications.
Single molecule tracking reveals nanodomains in biomolecular condensates
Authors: Gao Guoming , Sumrall Emily R. , Walter Nils G.
Published: April 2024

Protein-rich biomolecular condensates formed by phase separation1play a crucial role in cellular RNA regulation by the selective recruitment and processing of RNA molecules2. The functional impact of condensates on RNA biology relies on the residence time of individual RNA molecules within a condensate3, which is governed by intra-condensate diffusion4– the slower or more confined the diffusion, the longer the residence time. However, the spatiotemporal organization of RNA and protein diffusion within a single condensate remains largely unknown due to the challenge of accurately profiling intra-condensate diffusion behaviors down to the single-molecule level. Here we introduced a general condensate-tethering approach that allows single molecule tracking (SMT) of fluorescently labeled proteins and RNAs within non-wetted spherical 3D condensates without the interference of condensate motions. We found that a significant fraction of RNA and protein molecules are locally confined, rather than freely diffusive, within a model condensate formed by full-length, tag-free, RNA-binding protein Fused-in-Sarcoma (FUS), known for its critical roles in RNA biology under both physiological and pathological conditions5. Dynamic Point Accumulation for Imaging in Nanoscale Topography (PAINT)6reconstruction further revealed that RNA and proteins are confined to distinct slow-moving nanometer-scale regions, termed nanodomains, within a single condensate. Remarkably, nanodomains affect the diffusion but not the density of the confined biomolecules, supporting local percolation1,7rather than a secondary phase separation within the condensate as their origin. Beyond their regulatory roles on RNA residence time, nanodomains engender both elevated local connectivity and altered chemical environment, a prerequisite for pathological liquid-to-solid transition of FUS during aging. In summary, our study uncovers a patterned spatial organization of both protein and RNA molecules within a single condensate, revealing distinct diffusion dynamics that affect molecular retention time and interactions underlying cellular function and pathology.
Probiotic treatment causes sex-specific neuroprotection after traumatic brain injury in mice
Authors: Holcomb Morgan , Marshall Austin , Flinn Hannah , Lozano Mariana , Soriano Sirena , Gomez-Pinilla Fernando , Treangen Todd J. , Villapol Sonia
Published: April 2024

Background

Recent studies have shed light on the potential role of gut dysbiosis in shaping traumatic brain injury (TBI) outcomes. Changes in the levels and types ofLactobacillusbacteria present might impact the immune system disturbances, neuroinflammatory responses, anxiety and depressive-like behaviors, and compromised neuroprotection mechanisms triggered by TBI.

Objective

This study aimed to investigate the effects of a daily pan-probiotic (PP) mixture in drinking water containing strains ofLactobacillus plantarum, L. reuteri, L. helveticus, L. fermentum, L. rhamnosus, L. gasseri,andL. casei, administered for either two or seven weeks before inducing TBI on both male and female mice.

Methods

Mice were subjected to controlled cortical impact (CCI) injury. Short-chain fatty acids (SCFAs) analysis was performed for metabolite measurements. The taxonomic profiles of murine fecal samples were evaluated using 16S rRNA V1-V3 sequencing analysis. Histological analyses were used to assess neuroinflammation and gut changes post-TBI, while behavioral tests were conducted to evaluate sensorimotor and cognitive functions.

Results

Our findings suggest that PP administration modulates the diversity and composition of the microbiome and increases the levels of SCFAs in a sex-dependent manner. We also observed a reduction of lesion volume, cell death, and microglial and macrophage activation after PP treatment following TBI in male mice. Furthermore, PP-treated mice show motor function improvements and decreases in anxiety and depressive-like behaviors.

Conclusion

Our findings suggest that PP administration can mitigate neuroinflammation and ameliorate motor and anxiety and depressive-like behavior deficits following TBI. These results underscore the potential of probiotic interventions as a viable therapeutic strategy to address TBI-induced impairments, emphasizing the need for gender-specific treatment approaches.
Transfer Learning Of Gene Expression Using Reactome
Authors: Belgadi Siham , Zhang David Yu , Gopinath Ashwin
Published: April 2024

Abstract

In clinical research, translating findings from model organisms to human applications remains challenging due to biological differences between species as well as limitations of orthologous, and homologous, gene comparisons, which is fraugt with information loss as well as many-to-many mapping. To address these issues, we introduce a novel Universal Gene Embedding (UGE) model that leverages transformer-based few-shot learning for species-agnostic transfer learning with heterogeneous domain adaptation. The UGE model, trained on a dataset of gene expression from ten organs across rats and mice, establishes a unified biological latent space that effectively represents genes from any organ or species. By focusing on reactomes—comprehensive profiles of gene expression responses to drugs—the UGE model enables functional gene mapping across species based on the similarities of these profiles. Our contributions include a gene reactome vector prediction module, a robust framework for mapping drug-induced gene expression patterns across species, strategies for optimizing experimental design, and enhanced gene mapping precision. These advancements provide a new tool for genetic research and a new paradigm for cross-species insights, potentially revolutionizing our understanding of gene function, drug responses, and the translation of findings from model organisms to human clinical applications.
mTORC1-dependent SOCE activity regulates synaptic gene expression and muscle response to denervation
Authors: Prola Alexandre , Dupont Olivier , Rajendran Jayasimman , Chabry Florent , Koenig Stéphane , Frieden Maud , Castets Perrine
Published: April 2024

Neuromuscular junction (NMJ) instability is central in muscle dysfunction occurring in neuromuscular disorders and aging. NMJ maintenance requires regionalized regulation of synaptic genes, previously associated with Ca2+-dependent pathways. However, what sustains Ca2+micro-domains in myofibers and allows a rapid response to denervation is not known. Here, we identify that Store-Operated Calcium Entry (SOCE) plays a critical role in synaptic gene regulation. SOCE components show differential enrichment in sub- and non-synaptic muscle regions. Especially, STIM1 accumulation at rough endoplasmic reticulum associates with functional SOCE at the endplate. Denervation increases SOCE in non- and sub-synaptic regions, together with reticulum remodeling.Stim1knockdown hampers denervation-induced synaptic gene up-regulation, while STIM1 overexpression increases synaptic gene expression in innervated muscle. Finally, mTORC1 activation mimics the effect of denervation on SOCE capacity, STIM1 localization and reticulum remodeling. Together, our results reveal a decisive role of SOCE in sensing innervation and regulating muscle response to denervation. They further suggest that SOCE perturbation may contribute to neuromuscular integrity loss in pathological conditions associated with mTORC1 dysregulation.
Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis
Authors: Nasuuna Esther M , Nanyenya Nicholus , Kibirige Davis , Izudi Jonathan , Chikwari Chido Dziva , Kalyesubula Robert , Castelnuovo Barbara , Tomlinson Laurie A , Weiss Helen A
Published: April 2024

Background

Globally, the prevalence of chronic kidney disease (CKD) is increasing among young people living with HIV (YPLHIV), with inconsistent estimates. Aggregated data on the prevalence of CKD are needed in sub-Saharan Africa (SSA) to inform strategies for early diagnosis and management. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of CKD among YPLHIV in SSA.

Methods

We searched Medline/PubMed, EMBASE, African Index Medicus, and African Journals Online for articles reporting the prevalence of CKD among YPLHIV in SSA using predefined search strategies up to 15thJanuary 2024. The reference lists of identified articles were checked for additional eligible studies. The eligibility criteria were studies among YPHLIV aged 10-24 years reporting CKD prevalence defined by either glomerular filtration rate (GFR), albumin-to-creatinine ratio (ACR) or proteinuria. We used a narrative synthesis to report differences between the included studies. The DerSimonian-Liard random effects model was used to pool the CKD prevalence, and heterogeneity was assessed using the Cochrane Q-test and I-squared values. We assessed the risk of bias in each article using the Joanna Briggs Institute checklist and publication bias in a funnel plot and Egger’s test.

Results

Of 802 retrieved articles, 16 fulfilled the eligibility criteria and were included in the meta-analysis. Of these, 13 (86.7%) were cross-sectional studies that used estimated GFR to diagnose CKD. Only two studies followed the standard definition of CKD. The pooled CKD prevalence was 12.1% (95% CI 6.5-19.2%), ranging from 0.8% to 53.1% according to the definition used, with a high degree of heterogeneity (I2=97.5%, p<0.001). The included studies were of moderate quality, with no evidence of publication bias. Sensitivity analysis showed that the findings were robust to the methodological and analytic approach.

Conclusion

CKD prevalence among YPLHIV is moderately high and highly heterogeneous across SSA. The standard definition of CKD should be used to enable estimation of CKD prevalence in different studies and settings. HIV programs enrolling YPLHIV should routinely screen for CKD to ensure early diagnosis and management.

PROSPERO registration number

CRD42022347588.
Recurrent issues with deep neural network models of visual recognition
Authors: Maniquet Tim , Op de Beeck Hans , Costantino Andrea Ivan
Published: April 2024

Object recognition requires flexible and robust information processing, especially in view of the challenges posed by naturalistic visual settings. The ventral stream in visual cortex is provided with this robustness by its recurrent connectivity. Recurrent deep neural networks (DNNs) have recently emerged as promising models of the ventral stream, surpassing feedforward DNNs in the ability to account for brain representations. In this study, we asked whether recurrent DNNs could also better account for human behaviour during visual recognition. We assembled a stimulus set that included manipulations that are often associated with recurrent processing in the literature, like occlusion, partial viewing, clutter, and spatial phase scrambling. We obtained a benchmark dataset from human participants performing a categorisation task on this stimulus set. By applying a wide range of model architectures to the same task, we uncovered a nuanced relationship between recurrence, model size, and performance. While recurrent models reach higher performance than their feedforward counterpart, we could not dissociate this improvement from that obtained by increasing model size. We found consistency between humans and models patterns of difficulty across the visual manipulations, but this was not modulated in an obvious way by the specific type of recurrence or size added to the model. Finally, depth/size rather than recurrence makes model confusion patterns more human-like. Contrary to previous assumptions, our findings challenge the notion that recurrent models are better models of human recognition behaviour than feedforward models, and emphasise the complexity of incorporating recurrence into computational models.
Co-transcriptional splicing facilitates transcription of gigantic genes
Authors: Fingerhut Jaclyn M. , Lannes Romain , Whitfield Troy W. , Thiru Prathapan , Yamashita Yukiko M.
Published: April 2024

Although introns are typically tens to thousands of nucleotides, there are notable exceptions. In flies as well as humans, a small number of genes contain introns that are more than 1000 times larger than typical introns, exceeding hundreds of kilobases (kb) to megabases (Mb). It remains unknown why gigantic introns exist and how cells overcome the challenges associated with their transcription and RNA processing. TheDrosophilaY chromosome contains some of the largest genes identified to date: multiple genes exceed 4Mb, with introns accounting for over 99% of the gene span. Here we demonstrate that co-transcriptional splicing of these gigantic Y-linked genes is important to ensure successful transcription: perturbation of splicing led to the attenuation of transcription, leading to a failure to produce mature mRNA. Cytologically, defective splicing of the Y-linked gigantic genes resulted in disorganization of transcripts within the nucleus suggestive of entanglement of transcripts, likely resulting from unspliced long RNAs. We propose that co-transcriptional splicing maintains the length of nascent transcripts of gigantic genes under a critical threshold, preventing their entanglement and ensuring proper gene expression. Our study reveals a novel biological significance of co-transcriptional splicing.
Cardiovascular and vasomotor pulsations in the brain and periphery during awake and NREM sleep in a multimodal fMRI study
Authors: Tuunanen Johanna , Helakari Heta , Huotari Niko , Väyrynen Tommi , Järvelä Matti , Kananen Janne , Kivipää Annastiina , Raitamaa Lauri , Ebrahimi Seyed-Mohsen , Kallio Mika , Piispala Johanna , Kiviniemi Vesa , Korhonen Vesa
Published: April 2024

The glymphatic brain clearance mechanism convects brain cerebrospinal fluid driven by physiological pulsations such as cardiovascular and very low-frequency (VLF < 0.1 Hz) vasomotor waves. Presently, ultrafast functional magnetic resonance imaging (fMRI) facilitates the measurement of these signals from both venous and arterial compartments. In this study, we compared the interaction of these two pulsations in awake and sleep using fMRI and peripheral fingertip photoplethysmography in both arterial and venous signals in ten subjects (5 female). Sleep increased the power of brain cardiovascular pulsations, decreased peripheral pulsation and desynchronized them. Vasomotor waves, however, increase in both power and synchronicity in brain and peripheral signals during sleep. Peculiarly, vasomotor lag reversed in sleep within the default mode network vs. peripheral signal. Finally, sleep synchronized cerebral arterial vasomotion measured with cardiovascular hemodynamic envelope (CHe) vs. venous blood oxygenation level dependent (BOLD) signals in parasagittal brain tissue. These changes in power and pulsation synchrony may reflect differential changes in vascular control between the periphery and brain vasculature, while the increased synchrony of arterial and venous compartments may reflect increased convection of neurofluids in parasagittal areas in sleep.

Statement of Significance

This study shows that while sleep attenuated the cardiovascular synchrony and powers of pulsatility between the periphery and brain, it also increased brain tissue synchrony of venous and arterial vasomotor waves, specifically in the parasagittal regions. The study also shows that vasomotor waves increased in the human brain and the periphery during NREM sleep. Thus, sleep induces a whole-body vasomotor synchronization where the initiation of peripheral vasomotor waves is preceded within the default mode network area. Based on these results, we suggest that the synchronization of vasomotor waves may be a significant contributor to the enhancement of glymphatic fluid exchange in the human brain during sleep.
Spinal Cord Elongation Enables Proportional Regulation of the Zebrafish Posterior Body
Authors: Saunders Dillan , Camacho Carlos , Steventon Benjamin
Published: April 2024

Early embryos display a remarkable ability to regulate the patterning of tissues in response to changes in tissue size. However, it is not clear whether this ability continues into post-gastrulation stages upon cell commitment to distinct germ layers. Here, we performed targeted removal of neural fated cells in the zebrafish tailbud using multi-photon ablation. This led to a proportional reduction in the length of both the spinal cord and paraxial mesoderm in the tail, revealing a capacity to regulate tissue morphogenesis across multiple tissues to build a well-proportioned posterior body. Following analysis of cell proliferation, gene expression, signalling and cell movements, we found no evidence of cell fate switching from mesoderm to neural fate to compensate for neural progenitor loss. Furthermore, we found that tail paraxial mesoderm length is not reduced upon direct removal of an equivalent number of mesoderm progenitors, ruling out the hypothesis that neuromesodermal competent cells enable proportional regulation. Instead, reduction in the numbers of cells across the spinal cord reduces both spinal cord and paraxial mesoderm length. We conclude that spinal cord elongation is a driver of paraxial mesoderm elongation in the zebrafish posterior body and that this can explain proportional regulation of both tissues upon neural progenitor reduction.
The cytokine receptor Fn14 is a molecular brake on neuronal activity that mediates circadian functionin vivo
Authors: Ferro Austin , Arshad Anosha , Boyd Leah , Stanley Tess , Berisha Adrian , Vrudhula Uma , Gomez Adrian M. , Borniger Jeremy C. , Cheadle Lucas
Published: April 2024

To survive, organisms must adapt to a staggering diversity of environmental signals, ranging from sensory information to pathogenic infection, across the lifespan. At the same time, organisms intrinsically generate biological oscillations, such as circadian rhythms, without input from the environment. While the nervous system is well-suited to integrate extrinsic and intrinsic cues, how the brain balances these influences to shape biological function system-wide is not well understood at the molecular level. Here, we demonstrate that the cytokine receptor Fn14, previously identified as a mediator of sensory experience-dependent synaptic refinement during brain development, regulates neuronal activity and function in adult mice in a time-of-day-dependent manner. We show that a subset of excitatory pyramidal (PYR) neurons in the CA1 subregion of the hippocampus increase Fn14 expression when neuronal activity is heightened. Once expressed, Fn14 constrains the activity of these same PYR neurons, suggesting that Fn14 operates as a molecular brake on neuronal activity. Strikingly, differences in PYR neuron activity between mice lacking or expressing Fn14 were most robust at daily transitions between light and dark, and genetic ablation of Fn14 caused aberrations in circadian rhythms, sleep-wake states, and sensory-cued and spatial memory. At the cellular level, microglia contacted fewer, but larger, excitatory synapses in CA1 in the absence of Fn14, suggesting that these brain-resident immune cells may dampen neuronal activity by modifying synaptic inputs onto PYR neurons. Finally, mice lacking Fn14 exhibited heightened susceptibility to chemically induced seizures, implicating Fn14 in disorders characterized by hyperexcitation, such as epilepsy. Altogether, these findings reveal that cytokine receptors that mediates inflammation in the periphery, such as Fn14, can also play major roles in healthy neurological function in the adult brain downstream of both extrinsic and intrinsic cues.

Highlights

Neuronal activity inducesFn14expression in pyramidal neurons of the hippocampus

Fn14 constrains neuronal activity near daily transitions between light and dark

Loss of Fn14 lengthens the endogenous circadian period and disrupts sleep-wake states and memory

Microglia contact excitatory synapses in an Fn14-dependent manner
Nonlinear (3, 4, 1) multiplet of
N=4
,
d=1
supersymmetry as a semidynamical spin multiplet
Authors: Ivanov Evgeny , Sidorov Stepan
Published: April 2024

We consider a new type of N=4, d=1 semidynamical multiplet based on the nonlinear version of the mirror multiplet (3,4,1), with the triplet of bosonic physical fields parametrizing a three-dimensional sphere S3 of the radius R. The limit R→∞ amounts to the contraction S3→R3 and leads to the linear mirror multiplet (3,4,1). Spin degrees of freedom described by a Wess-Zumino action specify a two-dimensional surface embedded in the sphere S3. A pair of the examples considered correspond to the round and squashed “fuzzy” 2-spheres. We couple the squashed 2-sphere model to the dynamical mirror multiplet (2,4,2). A notable feature of this coupling is the dependence of the squashing parameter on the bosonic fields z, z¯ of the chiral multiplet.

Published by the American Physical Society
2024
Krylov complexity of modular Hamiltonian evolution
Authors: Caputa Pawel , Magan Javier M. , Patramanis Dimitrios , Tonni Erik
Published: April 2024

We investigate the complexity of states and operators evolved with the modular Hamiltonian by using the Krylov basis. In the first part, we formulate the problem for states and analyze different examples, including quantum mechanics, two-dimensional conformal field theories and random modular Hamiltonians, focusing on relations with the entanglement spectrum. We find that the modular Lanczos spectrum provides a different approach to quantum entanglement, opening new avenues in many-body systems and holography. In the second part, we focus on the modular evolution of operators and states excited by local operators in two-dimensional conformal field theories. We find that, at late modular time, the spread complexity is universally governed by the modular Lyapunov exponent λLmod=2π and is proportional to the local temperature of the modular Hamiltonian. Our analysis provides explicit examples where entanglement entropy is indeed not enough; however the entanglement spectrum is, and encodes the same information as complexity.

Published by the American Physical Society
2024
Near-wall streamwise turbulence intensity as
Reτ→∞
Authors: Hwang Yongyun
Published: April 2024

In this study, asymptotic scaling of near-wall streamwise turbulence intensity u′u′¯/uτ2 (uτ is the friction velocity) is theoretically explored. The three scalings previously proposed are first reviewed with their derivation and physical justification: (1) u′u′¯/uτ2∼lnReτ (Reτ is the friction velocity); (2) u′u′¯/uτ2∼1/U∞+ (U∞+ is the inner-scaled freestream velocity in boundary layer); (3) u′u′¯/uτ2∼Reτ−1/4. A new analysis is subsequently developed based on velocity spectrum, and two possible scenarios are identified based on the asymptotic behavior of the outer-scaling part of the near-wall velocity spectrum. In the former case, the outer-scaling part of the spectrum is assumed to reach a nonzero constant as Reτ→∞, and it results in the scaling of u′u′¯/uτ2∼lnReτ, both physically and theoretically consistent with the classical attached eddy model. In the latter case, a sufficiently rapid decay of the outer-scaling part of the spectrum with Re is assumed due to the effect of viscosity, such that u′u′¯/uτ2<∞ for all Reτ. The following analysis yields u′u′¯/uτ2∼1/lnReτ, asymptotically consistent with the scaling of

u

′

u

′

¯

/

u

τ

2

∼

1

/

U

∞

+

. The scalings are further verified with the existing simulation and experimental data and those from a quasilinear approximation [Holford ], the spectra of which all appear to favor u′u′¯/uτ2∼1/lnReτ, although new datasets for Reτ≳O(104) would be necessary to conclude this issue.

Published by the American Physical Society
2024
Almost Ricci–Yamabe soliton on contact metric manifolds
Authors: Khatri Mohan , Singh Jay Prakash
Published: April 2024

Purpose

This paper aims to study almost Ricci–Yamabe soliton in the context of certain contact metric manifolds.

Design/methodology/approach

The paper is designed as follows: In Section 3, a complete contact metric manifold with the Reeb vector field ξ as an eigenvector of the Ricci operator admitting almost Ricci–Yamabe soliton is considered. In Section 4, a complete K-contact manifold admits gradient Ricci–Yamabe soliton is studied. Then in Section 5, gradient almost Ricci–Yamabe soliton in non-Sasakian (k, μ)-contact metric manifold is assumed. Moreover, the obtained result is verified by constructing an example.

Findings

We prove that if the metric g admits an almost (α, β)-Ricci–Yamabe soliton with α ≠ 0 and potential vector field collinear with the Reeb vector field ξ on a complete contact metric manifold with the Reeb vector field ξ as an eigenvector of the Ricci operator, then the manifold is compact Einstein Sasakian and the potential vector field is a constant multiple of the Reeb vector field ξ. For the case of complete K-contact, we found that it is isometric to unit sphere S2n+1 and in the case of (k, μ)-contact metric manifold, it is flat in three-dimension and locally isometric to En+1 × Sn(4) in higher dimension.

Originality/value

All results are novel and generalizations of previously obtained results.
OpenMP-based parallel MLPG solver for analysis of heat conduction
Authors: Singh Abhishek Kumar , Singh Krishna Mohan
Published: April 2024

Purpose

In the present work, we focus on developing an in-house parallel meshless local Petrov-Galerkin (MLPG) code for the analysis of heat conduction in two-dimensional and three-dimensional regular as well as complex geometries.

Design/methodology/approach

The parallel MLPG code has been implemented using open multi-processing (OpenMP) application programming interface (API) on the shared memory multicore CPU architecture. Numerical simulations have been performed to find the critical regions of the serial code, and an OpenMP-based parallel MLPG code is developed, considering the critical regions of the sequential code.

Findings

Based on performance parameters such as speed-up and parallel efficiency, the credibility of the parallelization procedure has been established. Maximum speed-up and parallel efficiency are 10.94 and 0.92 for regular three-dimensional geometry (343,000 nodes). Results demonstrate the suitability of parallelization for larger nodes as parallel efficiency and speed-up are more for the larger nodes.

Originality/value

Few attempts have been made in parallel implementation of the MLPG method for solving large-scale industrial problems. Although the literature suggests that message-passing interface (MPI) based parallel MLPG codes have been developed, the OpenMP model has rarely been touched. This work is an attempt at the development of OpenMP-based parallel MLPG code for the very first time.
Hybrid algorithm for global optimization based on periodic selection scheme in engineering computation
Authors: Zhou Ting , Wei Yingjie , Niu Jian , Jie Yuxin
Published: April 2024

Purpose

Metaheuristic algorithms based on biology, evolutionary theory and physical principles, have been widely developed for complex global optimization. This paper aims to present a new hybrid optimization algorithm that combines the characteristics of biogeography-based optimization (BBO), invasive weed optimization (IWO) and genetic algorithms (GAs).

Design/methodology/approach

The significant difference between the new algorithm and original optimizers is a periodic selection scheme for offspring. The selection criterion is a function of cyclic discharge and the fitness of populations. It differs from traditional optimization methods where the elite always gains advantages. With this method, fitter populations may still be rejected, while poorer ones might be likely retained. The selection scheme is applied to help escape from local optima and maintain solution diversity.

Findings

The efficiency of the proposed method is tested on 13 high-dimensional, nonlinear benchmark functions and a homogenous slope stability problem. The results of the benchmark function show that the new method performs well in terms of accuracy and solution diversity. The algorithm converges with a magnitude of 10-4, compared to 102 in BBO and 10-2 in IWO. In the slope stability problem, the safety factor acquired by the analogy of slope erosion (ASE) is closer to the recommended value.

Originality/value

This paper introduces a periodic selection strategy and constructs a hybrid optimizer, which enhances the global exploration capacity of metaheuristic algorithms.
The effects of environmental factors on user’s personal traits related to mobile payment adoption: a case study of Indonesia
Authors: Lisana Lisana , Handarkho Yonathan Dri
Published: April 2024

Purpose

This study aims to investigate the influence of environmental factors on individual personality traits associated with mobile paymens (MP) adoption using the technological personal environment (TPE) theory as a framework for the proposed theoretical model.

Design/methodology/approach

A total of 736 feedback from respondents was used to validate the proposed model using structural equation modeling. The model comprises Trust and Self-efficacy to explain MP adoption from a personal trait perspective. Meanwhile, environmental aspects are represented by social influence, vendor regulations and network externalities.

Findings

The result indicates that self-efficacy has the most significant direct effect on user intention to use MP, followed in decreasing order of significance by social influence, trust, vendor regulations and network externalities. Furthermore, social influence is the most contributing aspect from the environmental area that influences user intention directly and indirectly through trust and self-efficacy as mediators. Meanwhile, the moderating effect analysis also found that gender moderates the effect of user self-efficacy on MP adoption.

Originality/value

This study fills the gap by comparing trust and self-efficacy and exploring how those factors are developed and affected by the environmental aspect of MP usage. It was discovered that self-efficacy was the most influential construct influencing the adoption of MP. Social influence was identified as the primary environmental factor that directly impacts user intention regarding MP usage. Furthermore, gender was shown as a moderator, as males place a higher value on self-efficacy as a factor affecting their intention to embrace MP in comparison to females.
The sleepless sentinel: factors that predict burnout and sleep quality in cybersecurity professionals
Authors: Reeves Andrew , Pattinson Malcolm , Butavicius Marcus
Published: April 2024

Purpose

The purpose of this study is to investigate the extent to which a sample of the Australian cybersecurity industry is impacted by burnout.

Design/methodology/approach

Based on the review of the literature, this research investigates the following three hypotheses. Gender will significantly predict burnout scores. Those who identify as women will score higher on average than those who identify as men (because of being in a male-dominated industry). Self-reported burnout will differ across job roles. In addition, the authors expect these relationships to hold across the three dimensions of burnout, namely, emotional exhaustion, depersonalisation and professional efficacy. Sleep quality will be associated with burnout.

Findings

Gender and job role were significant predictors of emotional exhaustion, but not depersonalisation or professional efficacy. The interaction between gender and job role was also significant. Senior managers experienced poorer quality sleep, and poorer sleep quality was associated with greater reported emotional exhaustion at work. For emotional exhaustion, female respondents who worked in security consultant roles tended to score higher than their male counterparts.

Practical implications

Left unaddressed, the high level of workplace burnout may add to the well-being and retention problems developing within the cybersecurity community. These results indicate that organisations should look to measure the well-being of their own cyber workforce and implement meaningful changes if they wish to keep their cyber talent and enable them to thrive at work.

Originality/value

This research paper is an extension of a previous paper by the same authors which is titled “Is Your CISO Burnt Out Yet”. This paper examined the demographic differences in workplace burnout among cybersecurity professionals.
Hospitality marketing research: bridging the practical gap
Authors: Bilgihan Anil , Hanks Lydia , Line Nathan Discepoli , Mody Makarand Amrish
Published: April 2024

Purpose

This study aims to identify the causes of the academia-industry divide in hospitality marketing research in the form of the “Research Devaluation Map” and offers ideas for discussion points and suggestions for change.

Design/methodology/approach

The conceptualization of the Research Devaluation Map was developed at an invitational thought-leadership conference. The authors were asked to produce a forward looking, critical reflection of hospitality marketing scholarship. The authors generated a preliminary idea and developed a methodology for its implementation. They then proposed a framework that explicated the divide between hospitality marketing research and industry practice and a list of discussion points regarding possible solutions.

Findings

The issues currently challenging the hospitality research field are found to include the choice of research topics (the “what”), the methods used in research (the “how”) and the systemic factors that shape the academic culture (the “systemic”). These three factors lead to a mutual devaluation of the academic–industry relationship in hospitality marketing, causing a schism between research and industry practice.

Research limitations/implications

The Research Devaluation Map serves as a springboard for future research studies, providing a framework for naming and operationalizing the antecedents and results of the divide between hospitality marketing research and practice.

Originality/value

This paper takes a holistic look at the gaps in current hospitality marketing research and puts forth a framework to explain the roots of these issues. While certain of these issues are known to both researchers and practitioners, the originality of this paper lies in the creation of the Research Devaluation Map that identifies the causes and results of the disconnect between research and practice.