bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic analysis of TGFβ-mediated fibrosis in primary human Tenon’s fibroblasts
Authors: Pasvanis Zoe , Boynes Antony , Kong Roy C.K. , Chan Elsa C. , Wong Raymond C.B. , Gaskin Jennifer Fan 
Published: March 2024

AbstractGlaucoma filtration surgery (GFS) is performed to slow down disease progression in glaucoma, a leading cause of irreversible blindness worldwide. Following surgery, pathological wound healing may lead to conjunctival fibrosis and filtering failure. Myofibroblasts are the key cells responsible for postoperative conjunctival scarring. This study aims to further understand the molecular mechanisms of conjunctival fibrosis following GFS. We utilised RNA-sequencing (RNA-seq) to delineate the TGFβ1 induced changes in the transcriptome of human Tenon’s fibroblasts (HTFs). RNA sequencing was performed on HTFs after 5 days of TGFβ1 treatment. Following quality control, 3,362 differentially expressed genes were identified, of which 1,532 were upregulated and 1,820 were downregulated. We identified signaling pathways associated with the pathogenesis of conjunctival fibrosis. The DEGs (differentially expressed genes) were enriched in pathways including myofibroblast differentiation, TGFβ-signaling, collagen and extracellular matrix organization, epithelial to mesenchymal transition, and cell cycle regulation. The results of this study identified the transition from HTF to myofibroblast is characterised by the upregulation of key genes includingLDLRAD4, CDKN2B, FZD8, MYOZ1, and the downregulation ofSOD3, LTBP4andRCAN2. This unprecedented insight into the transcriptional landscape of HTFs and myofibroblast differentiation is essential to understand the pathophysiology of conjunctival scarring and develop new therapeutic agents.
Why the adventitious roots of poplar are so colorful: RNAseq and metabolomic analysis reveal flavonols, flavones, and anthocyanins accumulation in canker pathogens-induced adventitious roots in poplar
Authors: Min Li , Yuchen Fu , Jinxin Li , Wanna Shen , Li Wang , Zheng Li , Shiqi Zhang , Huixiang Liu , Xiaohua Su , Jiaping Zhao 
Published: March 2024

AbstractRecently, we observed a novel allometry on poplar stems, with copious colorful adventitious roots (ARs) induced by fungal canker pathogens. Here, we reveal chemical, physiological, and molecular mechanisms of AR coloration in a poplar-pathogen (Valsa sordida/Botrosphaeria dothidea) interaction system using our phloem girdling-inoculation system. Light-induced coloration in ARs: red/rosy under sunlight and milky white under shading. Chemical and metabolomic analyses indicated that numerous (93 in all 110) and high relative intensities/contents of flavonoids metabolites (mainly including flavonols, flavones, and anthocyanins class) accumulate in red ARs, some flavones and anthocyanins metabolites all contribute to the color of poplar ARs, and cyanidin-3-O-glucoside is the most abundant colorant. Integrated analysis of metabolomic and transcriptomic analysis suggested that sunlight exposure redirected metabolomic flux from the flavonoid biosynthesis pathway to the flavonols and flavones branch pathways, induced by the upregulation of FLS (flavonol synthase/flavanone 3-hydroxylase) and other structural genes. The anthocyanins metabolomic analysis and the downregulation of the ANS (anthocyanin synthase) gene illustrated a retard of metabolomic flux from leucoanthocyanidins to anthocyanidins; meanwhile, metabolomic results and the upregulation of gene BZ1 (Bronze 1, anthocyanin 3-O-glucosyltransferase) illustrated that sunlight triggered a rapid biosynthesis of anthocyanin metabolites in poplar ARs, which based on the substrate level of anthocyanidins. Transcriptomic and RT-qPCR analyses showed that transcriptional factor MYB113, HY5 (ELONGATED HYPOCOTYL5), and COP1 (Ring-finger protein CONSTITUTIVE PHOTOMORPHOGENIC1) genes positively regulate the expression of the flavonoid/anthocyanin biosynthesis structural genes (such as genes encoding BZ1, FLS, LAR, etc.) in both sunlight-exposed red ARs and white ARs after light exposure, suggesting sunlight induces anthocyanins biosynthesis through the interaction between “MBW” complex and COP1-HY5 module. Moreover, results also showed that 1 SPL gene (squamosa promoter-binding-like protein gene, target of miR156), one component of miR156-SPL module, downregulated in sunlight-exposed poplar ARs, implying the biosynthesis flavonoid/anthocyanin be regulated at the posttranscriptional level. Additionally, this study provides a potential AR experimental system for research on flavonoid/anthocyanin biosynthesis in tree species.
Unravelling the Transcriptomic Symphony of Sarcopenia: Key Pathways and Hub Genes Altered by Muscle Ageing and Caloric Restriction Revealed by RNA Sequencing
Authors: Altab Gulam , Merry Brian J. , Beckett Charles W. , Raina Priyanka , Lopes Inês , Goljanek-Whysall Katarzyna , de Magalhães João Pedro 
Published: March 2024

AbstractSarcopenia is a disease involving extensive loss of muscle mass and strength with age and is a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to explicate the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a proven prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. Collected data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key “hub” proteins involved in their activation.RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and the immune response; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. Hub genes implicated in both ageing and CR includedGc,Plg,Irf7,Ifit3,Usp18,Rsad2,BlmandRT1-A2, whilst those exclusively implicated in CR responses includedAlb,Apoa1,Ambp,F2,Apoh,Orm1,Mx1,Oasl2andRtp4. Hub genes involved in ageing but unaffected by CR includedFgg,Fga,FgbandSerpinc1. In conclusion, this comprehensive RNA sequencing study highlighted gene expression patterns, hub genes and signalling pathways most affected by ageing in skeletal muscle. This data may provide the initial evidence for several targets for therapeutic interventions against sarcopenia.
Physiological correlates of a simple saccadic-decision task to extended objects in superior colliculus
Authors: Caziot B. , Cooper B. , Harwood M. R. , McPeek R. M. 
Published: March 2024

AbstractOur vision is best only in the center of our gaze, and we use saccadic eye movements to direct gaze to objects and features of interest. We make more than 180,000 saccades per day, and accurate and efficient saccades are crucial for most visuo-motor tasks. Saccades are typically studied using small point stimuli, despite the fact that most real-world visual scenes are composed of extended objects. Recent studies in humans have shown that the initiation latency of saccades is strongly dependent on the size of the target (the “size-latency effect”), perhaps reflecting a tradeoff between the cost of making a saccade to a target and the expected information gain that would result. Here, we investigate the neuronal correlates of the size-latency effect in the macaque superior colliculus. We analyzed the latency variations of saccades to different size targets within a stochastic accumulator model framework. The model predicted a steeper increase in activity for smaller targets compared to larger ones. Surprisingly, the model also predicted an increase in saccade initiation threshold for larger targets. We found that the activity of intermediate-layer SC visuomotor neurons is in close agreement with the model predictions. We also found evidence that these effects may be a consequence of the visual responses of SC neurons to targets of different sizes. These results shed new light on the sources of delay within the saccadic system, a system that we heavily depend upon in the performance of most visuo-motor tasks.
Social ageing can protect against infectious disease in a group-living primate
Authors: Siracusa Erin R. , Pavez-Fox Melissa A. , Negron-Del Valle Josué E. , Phillips Daniel , Platt Michael L. , Snyder-Mackler Noah , Higham James P. , Brent Lauren J. N. , Silk Matthew J. 
Published: March 2024

AbstractThe benefits of social living are well established, but sociality also comes with costs, including infectious disease risk. This cost-benefit ratio of sociality is expected to change across individuals’ lifespans, which may drive changes in social behaviour with age. To explore this idea, we combine data from a group-living primate for which social ageing has been described with epidemiological models to show that having lower social connectedness when older can protect against the costs of a hypothetical, directly transmitted endemic pathogen. Assuming no age differences in epidemiological characteristics (susceptibility to, severity, and duration of infection), older individuals suffered lower infection costs, which was explained largely because they were less connected in their social networks than younger individuals. This benefit of ‘social ageing’ depended on epidemiological characteristics and was greatest when infection severity increased with age. When infection duration increased with age, social ageing was beneficial only when pathogen transmissibility was low. Older individuals benefited most from having a lower frequency of interactions (strength) and network embeddedness (closeness) and benefited less from having fewer social partners (degree). Our study provides a first examination of the epidemiology of social ageing, demonstrating the potential for pathogens to influence evolutionary dynamics of social ageing in natural populations.
Drumming Performance and Underlying Muscle Activities in a Professional Rock Drummer with Lower-Limb Dystonia: A Case Study
Authors: Honda Kazuaki , Sata Shizuka , Komine Mizuki , Yamaguchi Satoshi , Kim SungHyek , Kashino Makio , Fujii Shinya 
Published: March 2024

AbstractTask-specific focal dystonia (TSFD), characterized by the loss of fine motor control and coordination, affects drummers’ lower-limb movements, yet it remains relatively understudied, leaving a gap in understanding its effects on drumming performance and underlying muscle activities. This study explores lower limb dystonia’s impact on drumming performance and underlying muscle activity in a professional rock drummer. The drummer executed an eight-beat pattern on a drum kit, emphasizing kicking the bass drum on the initial beat and performing syncopation of the third beat. Dystonia symptoms primarily manifested in the initial beat, with fewer symptoms on syncopation of the third beat. Analysis revealed decreased bass-drum sound peak amplitude during the initial beat and increased (becoming more negative) synchronization error. Electromyographic (EMG) measurements of ten muscles in the affected right lower limb showed significant changes in the Biceps Femoris (BF), Tibialis Anterior (TA), Extensor Digitorum Longus (EDL), and Extensor Digitorum Brevis (EDB) muscles during symptom onset. Notably, we observed 1) earlier overactivation of the TA and EDL muscles during the leg lift-up motion or preparatory phase of pedaling, 2) reduced activation of the EDB muscle, and 3) increased activation of the BF muscle during the final pedaling movement when symptoms occurred. These findings suggest that lower-limb dystonia symptoms are characterized by a reduction in amplitude and an increase in synchronization error, potentially due to premature overactivation of the ankle dorsiflexor muscles.
BET inhibitors as a therapeutic intervention in gastrointestinal gene signature-positive castration-resistant prostate cancer
Authors: Shukla Shipra , Li Dan , Nguyen Holly , Conner Jennifer , Bayshtok Gabriella , Cho Woo Hyun , Pachai Mohini , Teri Nicholas , Campeau Eric , Attwell Sarah , Trojer Patrick , Ostrovnaya Irina , Gopalan Anuradha , Corey Eva , Chi Ping , Chen Yu 
Published: March 2024

ABSTRACTA subgroup of castration-resistant prostate cancer (CRPC) aberrantly expresses a gastrointestinal (GI) transcriptome governed by two GI-lineage-restricted transcription factors, HNF1A and HNF4G. In this study, we found that expression of GI transcriptome in CRPC correlates with adverse clinical outcomes to androgen receptor signaling inhibitor treatment and shorter overall survival. Bromo- and extra-terminal domain inhibitors (BETi) downregulated HNF1A, HNF4G, and the GI transcriptome in multiple CRPC models, including cell lines, patient-derived organoids, and patient-derived xenografts, while AR and the androgen-dependent transcriptome were largely spared. Accordingly, BETi selectively inhibited growth of GI transcriptome-positive preclinical models of prostate cancer. Mechanistically, BETi inhibited BRD4 binding at enhancers globally, including both AR and HNF4G bound enhancers while gene expression was selectively perturbed. Restoration of HNF4G expression in the presence of BETi rescued target gene expression without rescuing BRD4 binding. This suggests that inhibition of master transcription factors expression underlies the selective transcriptional effects of BETi.SIGNIFICANCEGI transcriptome expression in CRPC is regulated by the HNF1A-HNF4G-BRD4 axis and correlates with worse clinical outcomes. Accordingly, BET inhibitors significantly reduce tumor cell growth in multiple GI-transcriptome-positive preclinical models of CRPC. Our studies point that expression of GI transcriptome could serve as a predictive biomarker to BETi therapy response.
Navigated range expansion promotes migratory culling
Authors: Zhang Yi , Hu Qingjuan , Su Yingtong , Chu Pan , Wei Ting , Li Xuefei , Liu Chenli , Fu Xiongfei 
Published: March 2024

AbstractMotile organisms can expand into new territories and increase their fitness, while nonmotile viruses usually depend on host migration to spread across long distances. In general, faster host motility facilitates virus transmission. However, recent ecological studies have also shown that animal host migration can reduce viral prevalence by removing infected individuals from the migratory group. Here, we use a bacteria-bacteriophage co-propagation system to investigate how host motility affects viral spread during range expansion. We find that phage spread during chemotaxis-driven navigated range expansion decreases as bacterial migration speed increases. Theoretical and experimental analyses show that the navigated migration leads to a spatial sorting of infected and uninfected hosts in the co-propagating front of bacteria-bacteriophage, with implications for the number of cells left behind. The preferential loss of infected cells in the co-propagating front inhibits viral spread. Further increase in host migration speed leads to a phase transition that eliminates the phage completely. These results illustrate that navigated range expansion of the host can promote the migratory culling of infectious diseases in the migration group.Significance StatementHost migration is commonly believed to accelerate the spread of infectious diseases. However, recent ecological studies suggest that migration may impede this spread. In our study, we developed a synthetic host-virus co-propagation model to explore the impact of host range expansion on the interplay between host mobility and virus spatial distribution. Our experimental and theoretical analysis revealed the spatial sorting of uninfected and infected hosts in the navigated propagating front leads to faster back diffusion of infected hosts. This self-organized structure allowed the migrating host population to eradicate the infectious disease, independent of intricate host-virus dynamics.
Clinical multi-omics reveals the role of Tuomin Zhiti Decoction Intervention in Allergic Rhinitis from the perspective of biological network
Authors: Zhao Weibo , Wang Boyang , Kong Lingyao , Wang Qi , Li Shao 
Published: March 2024

AbstractBackgroundIncreasing evidence showed that seasonal allergic rhinitis (SAR), as an allergy disease, could be alleviated with traditional Chinese medicine (TCM) formula, one example being Tuomin Zhiti Decoction (TZD). However, as a complex composition of TCM herbs, the mechanism of TZD in the treatment of SAR remain unclear.PurposeUncover the mechanism of TZD for treating SAR based on computational analysis and clinical multi-omics experiments.Study designIntegrate computational analysis including network target analysis and machine learning algorithms with clinical multi-omics experiments and public omics data.MethodsBy analyzing TZD’s composition through a network-based method, we identified the biological effects of each compound, constructing a comprehensive biological network to elucidate TZD’s molecular and pathway mechanisms against AR. Single-arm clinical trials on the gut microbiome and serum transcriptomics corroborated our computational insights. Further validation through public omics data highlighted key TZD compounds, paving the way for future research.ResultsTZD was discovered to exert a regulatory effect on various modules associated with AR, as demonstrated by the constructed biological network. Insights from gut microbiome and serum transcriptomics in clinical trials, where immune-related microbiomes represented by Prevotella, as well as pathways and biological processes including antigen processing and presentation, activation and regulating immune cell surface receptor, were markedly enriched (Pvalue < 0.05), indicated that TZD played a pivotal role in modulating immune processes and the immune cells against AR. With the verification of multi-omics, it was determined that TZD potentially influences immune responses and downstream immune cells like CD4+ T cells, through both direct mechanisms involving antigen and indirect mechanisms mediated by gut microbiomes in the treatment of AR.ConclusionThrough combination of computational prediction and analysis together with clinical multi-omics, a network target based framework provided a new insight for uncovering the mechanism of TZD for treating AR.
Associations Between Air Pollution and relative Leukocyte Telomere Length Among Northern Swedish Adults: Insights from the Betula Study
Authors: Raza Wasif , Pudas Sara , Kanninen Katja M. , Flanagan Erin , Degerman Sofie , Adolfsson Rolf , Giugno Rosalba , Topinka Jan , Zeng Xiao-wen , Oudin Anna 
Published: March 2024

ABSTRACTAir pollution is increasingly discussed as a risk factor for dementia, but the biological mechanisms are not yet fully understood. Cellular integrity markers like telomere length are relevant to investigate in relation to air pollution exposure in this context, as they are associated with aging and dementia. Previous studies on air pollution and telomere length have somewhat mixed results, which may partly be due to differences in air pollution modelling, composition, and concentrations. The study aimed to investigate the relationship between source-specific air pollution exposure and telomere length in a low-level air pollution area.Data were obtained from the Betula project, a longitudinal study in Northern Sweden dedicated to studying aging, memory and dementia. A total of 519 participants who were recruited between 1988 and 1995 were included, whose relative telomere length was measured, and who were followed-up with respect to dementia for more than 20 years. To estimate annual mean air pollution concentrations, a dispersion model linked to each participant’s residential address was employed. We conducted linear regression to explore the associations between annual mean air pollution concentrations at participants’ residences and relative leukocyte telomere length.In the whole sample, there was no support for air pollution to affect telomere length, with regression slope estimates close to zero and p-values >0.10. There were tendencies for a positive association of longer telomere length and higher exposure to air pollution among individuals who were later diagnosed with dementia (N = 74), but these findings were not conclusive (p-values >0.10). The findings raise questions about susceptibility to air pollution and the state of the inflammatory response in individuals who later will develop dementia. Given the imprecise nature of these estimates, caution is advised in their interpretation however, and validation in other studies is essential.
Autoimmune antibody-induced neuronal hyperactivity triggers pathological Tau in IgLON5 disease
Authors: Askin Bilge , Gómez César Cordero , Duong Sophie Lan-Linh , Kilic Cagla , Goihl Alexander , Newman Andrew , Wagner Jessica , Thomas Valentine , Lamberty Janne , Huebschmann Sabrina , Semenova Ekaterina , Körtvelyessy Peter , Reinhold Dirk , Kornau Hans-Christian , Turko Paul , Neher Jonas J. , Schmitz Dietmar , Rost Benjamin R. , Diez Lisa , Prüss Harald , Wegmann Susanne 
Published: March 2024

AbstractAnti-IgLON5 disease is an autoimmunity/neurodegeneration overlap disorder in which autoantibodies (AABs) against the neuronal cell surface protein IgLON5 lead to profound brain dysfunction. Brains of patients show Tau pathology, neuroinflammation, and neurodegeneration in multiple brain regions. Through administering patient-derived α-IgLON5 AABs to mice and cultured neurons, we here deciphered the cellular mechanisms of Tau pathology and neurodegeneration in α-IgLON5 disease, highlighting a central role of neuronal activity modulation in the disease pathology. Pathogenic human α-IgLON5 AABs induced acute neuronal hyperactivity, which triggered Tau changes typically found early in Tau-related neurodegenerative diseases like Alzheimer’s disease (AD). α-IgLON5 AAB-induced Tau phosphorylation and somatodendritic resorting selectively occurred in key hippocampal connections, involving dentate gyrus granule cells, mossy fiber projections and commissural fiber tracts. These changes were accompanied by a Tau-specific neuroinflammatory response, involving the complement pathway, microglial MHC class II proteins, T cell receptors, and deregulation of synaptic activity and cell-cell interactions. These findings provide new insights into the origin of autoimmune-triggered α-IgLON5 disease pathology and highlight that, similar to recent reports in AD patients, neuronal hyperactivity may be a disease-overarching driver of Tau pathology.