Biology subjects

Yu, H.

Publications and source records attributed to Yu, H..

At least 217 records · Page 12Linked to original sources

bioRxiv2024

Distractor-response binding influences visual search

Intertrial priming effects in visual search and action control suggest the involvement of binding and retrieval processes. However, the role of distractor-response binding (DRB) in visual search has been largely overlooked, and the specific processing stage within the functional architecture of attentional guidance where the DRB occurs remains unclear. To address these gaps, we implemented two search tasks, where participants responded based on a separate feature from the one defining the target. We kept the target dimension consistent across trials while varying the color and shape of the distractor. Moreover, we either repeated or randomized the target position in different sessions. Our results revealed a pronounced response priming, a difference between trials where the response changed vs. repeated: they were stronger when distractor features or the target position were repeated than they varied. Furthermore, the distractor feature priming, a difference between the distractor features repetition and switch, was contingent on the target position, suggesting that DRB likely operates at late stages of target identification and response selection. These insights affirm the presence of DRB during visual search and support the framework of binding and retrieval in action control as a basis for observed intertrial priming effects related to distractor features. Public significance statementThis study investigated inter-trial effects within visual search tasks and uncovered significant evidence for the role of distractor-response binding. This phenomenon involves linking a response in a given trial to the perceptual features (e.g. color and shape) of non-target items. Crucially, the study revealed that this distractor-response binding effect depends on whether the target location is repeated nearly repeated, suggesting that the retrieval of a previous response occurs at the later stages of target identification or response selection, even though non-target features likely are identified at an earlier stage.

neuroscience↗

bioRxiv2024

CTAT-LR-fusion: accurate fusion transcript identification from long and short read isoform sequencing at bulk or single cell resolution

Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential in cancer clinical diagnostics, prognostics, and for guiding therapeutic development. Most currently available methods for fusion transcript detection are compatible with Illumina RNA-seq involving highly accurate short read sequences. Recent advances in long read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single cell samples. Here we developed a new computational tool CTAT-LR-fusion to detect fusion transcripts from long read RNA-seq with or without companion short reads, with applications to bulk or single cell transcriptomes. We demonstrate that CTAT-LR-fusion exceeds fusion detection accuracy of alternative methods as benchmarked with simulated and real long read RNA-seq. Using short and long read RNA-seq, we further apply CTAT-LR-fusion to bulk transcriptomes of nine tumor cell lines, and to tumor single cells derived from a melanoma sample and three metastatic high grade serous ovarian carcinoma samples. In both bulk and in single cell RNA-seq, long isoform reads yielded higher sensitivity for fusion detection than short reads with notable exceptions. By combining short and long reads in CTAT-LR-fusion, we are able to further maximize detection of fusion splicing isoforms and fusion-expressing tumor cells. CTAT-LR-fusion is available at https://github.com/TrinityCTAT/CTAT-LR-fusion/wiki.

cancer biology↗

bioRxiv2024

Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease

Pompe disease (PD) is a progressive myopathy caused by the aberrant accumulation of glycogen in skeletal and cardiac muscle resulting from the deficiency of the enzyme acid alpha-glucosidase (GAA). Administration of recombinant human GAA as enzyme replacement therapy (ERT) works well in alleviating the cardiac manifestations of PD but loses sustained benefit in ameliorating the skeletal muscle pathology. The limited efficacy of ERT in skeletal muscle is partially attributable to its inability to curb the accumulation of new glycogen produced by the muscle enzyme glycogen synthase 1 (GYS1). Substrate reduction therapies aimed at knocking down GYS1 expression represent a promising avenue to improve Pompe myopathy. However, finding specific inhibitors for GYS1 is challenging given the presence of the highly homologous GYS2 in the liver. Antisense oligonucleotides (ASOs) are chemically modified oligomers that hybridize to their complementary target RNA to induce their degradation with exquisite specificity. In the present study, we show that ASO-mediated Gys1 knockdown in the Gaa-/- mouse model of PD led to a robust reduction in glycogen accumulation in skeletal and cardiac muscle. In addition, combining Gys1 ASO with ERT further reduced glycogen content in muscle, eliminated autophagic buildup and lysosomal dysfunction, and improved motor function in Gaa-/- mice. Our results provide a strong foundation for further validation of the use of Gys1 ASO, alone or in combination with ERT, as a therapy for PD. We propose that early administration of Gys1 ASO in combination with ERT may be the key to preventative treatment options in PD.

molecular biology↗

bioRxiv2024

Nodulation Trio in Medicago truncatula: Unveiling the Overlapping Roles of MtLYK2, MtLYK3, and MtLYK2bis

The perception of rhizobial nodulation factors (NF) by plant NF receptors is crucial for mediating legume nodulation. In Medicago truncatula nodulation, a proposed two-receptor model designates MtLYK3 as an entry receptor, while other LYK proteins, with unidentified functions, may serve as signaling receptors. Here, we generated the single, double, and triple mutants for M. truncatula MtLYK2, MtLYK3, and MtLYK2bis using CRISPR/Cas technology and examined their roles in nodulation. Our findings suggest that all three LYKs possess redundant functions in Medicago nodulation, with their distinct contributions attributed to varying transcription patterns.Our findings also suggest that a one-receptor model with multiple specificities that mediates both signaling and entry responses is more suitable in M. truncatula.

plant biology↗

bioRxiv2024

Fingerprint localisation for fine-scale wildlife tracking using automated radio telemetry

1: Automated radio telemetry systems are among the most widely applicable method for tracking wildlife at fine spatiotemporal scales. These systems are increasingly applying large networks of simple receivers to detect radio signal strength (RSS) from radio tagged individuals. Analytical methods to derive position estimates using RSS localisation, however, are relatively underdeveloped in the field of wildlife tracking. Here, we apply approaches from indoor positioning systems to develop a new method, radio fingerprinting, for localizing radio tagged animals in structurally complex, outdoor environments. This method characterizes the RSS patterns at known locations to generate a radio map of the study area, which is then used to predict the location of new RSS patterns. 2: We conducted field tests to evaluate the localisation accuracy of radio fingerprinting relative to multilateration, a commonly used method for RSS localisation. To do so, we established an experimental receiver network covering multiple habitat types and compared the localisation accuracy of radio fingerprinting to multilateration. Additionally, we evaluated how a variety of features characteristic of typical tracking datasets affected the accuracy of both methods. 3: While both methods had a similar median error ([~]30 m), the fingerprint localisation method offered several advantages over multilateration. Multilateration localisation estimates were highly affected by missed detections from the nearest receiver to the test point, which occurred in 30% of cases. In these cases, the median error was 97 m, over a 3-fold increase. Distance to the nearest receiver also biased multilateration estimates with error increasing as the distance increased. Additionally, errors from multilateration estimates were higher in more densely vegetated areas. In contrast, fingerprinting position estimates were largely robust to each of these scenarios. 4: Automated radio telemetry enables the fine-scale, continuous tracking of range-resident animals. We present radio fingerprinting as a localisation method in outdoor environments where standard localisation methods may be inadequate. This approach can be applied to any automated radio telemetry hardware and to any study system where a radio map can be generated.

animal behavior and cognition↗

bioRxiv2024

RNA Splicing Junction Landscape Reveals Abundant Tumor-Specific Transcripts in Human Cancer

RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate neoepitopes that bind to MHC class I molecules for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy. In briefThis study thoroughly analyzed RNA splicing junctions in 34,775 samples and identified 29,051 tumor-specific transcripts (TSTs), which may serve as novel cancer driver genes, neoantigens, and circulating biomarkers. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/579246v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@7e1db2org.highwire.dtl.DTLVardef@1cfbe81org.highwire.dtl.DTLVardef@1e427e1org.highwire.dtl.DTLVardef@1f655f5_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

The Xanthomonas fragariae effector XopK suppresses stomatal immunity by perturbing abscisic acid signaling in strawberry

Xanthomonas fragariae (Xaf) usually causes angular leaf spot (ALS) in strawberry all over the world. Recently, we isolated a new strain of Xaf called Xaf YL19. This strain causes not only typical ALS symptoms, but also dry cavity rot in the crown tissues of strawberries. This was the first time a Xaf strain had both of these effects in strawberries. Pathogen effectors play a crucial role in plant colonization and infection. Understanding how effector proteins escape from plant surveillance is important for plant breeding and resistance deployment. In this study, thirty-three putative effectors were predicted in Xaf YL19, and a virulent secreted effector called XopK was identified. XopK has a robust capacity for suppressing plant cell death and transcript response to infection host. Transgenic strawberries expressing XopK exhibit more susceptibility to Xaf YL19, and this was associated with weakened stomatal immunity. Additionally abscisic acid (ABA) accumulation and signaling were mainly suppressed in the presence of XopK. XopK also inhibited ABA- and methyl jasmonate (MeJA)-induced stomatal closure, and ABA- but not MeJA-induced reactive oxygen species (ROS) production. Moreover, endogenous ABA is critical for Xaf-induced ROS burst and stomatal closure. These results suggested that Xaf YL19 uses XopK to suppress JA, especially ABA signaling, for disrupting stomatal closure, and allowing its colonization for disease development. Taken together, our results provide a novel virulent mechanism by Xaf and an available strategy for resistant breeding in strawberries.

pathology↗

bioRxiv2024

The Origin and Evolution of Orphan Genes: A Case Study in Tea Plant Family

Orphan genes and transcription factor genes (TFs) are pervasive across genomes, play pivotal roles as regulators in a myriad of biological processes. Despite their ubiquity, the evolutionary trajectories and functional divergence of these genes remain largely unexplored. Theaceae family, encompassing the economically and culturally significant tea plant, presents a unique opportunity to study these dynamics. Here, we decoded a nearly complete, chromosome-scale reference genome of Stewartia gemmata spanning 2.95 Gb. This study is enhanced by integrating the genome of S. gemmata, an early-diverging species within Theaceae, crucial for phylogenomic analyses and understanding the functional dynamics of orphan genes in this family. Our analysis confirmed the absence of a recent specific whole-genome duplication (WGD) event, with tandem duplications emerging as the predominant mechanism for gene duplication at ancestral nodes within Theaceae. By conducting an extensive comparative genomics analysis across 13 Theaceae and comparing these with a wide array of eukaryotic and prokaryotic proteins, we identified 37,618 orphan genes and 25,884 TFs in Theaceae. Interestingly, some orphan genes appear to have ancient origins in tea plant ancestors, suggesting relatively early origins with frequent gains and losses, conversely, many others seem more specific and recent. Notably, the orphan genes are characterized by shorter lengths, fewer exons and functional domains than TFs, implying relatively simpler functional roles. These orphan genes demonstrate diverse cellular localization and functions as predicted by GO/KEGG analysis, and are implicated in environmental response and flavor formation in tea plants. This study not only sheds light on the distinct evolutionary histories and functional divergences between orphan genes and TFs in Theaceae, but also contributes to our understanding of the genetic complexity and adaptability of this economically and culturally valuable plant family. Short summary: The nearly complete genome of an early-diverging species Stewartia gemmata and phylogenomic studies provide insights into new gene evolution in Theaceae.

bioinformatics↗

bioRxiv2024

Neurotrophic factor Neuritin modulates T cell electrical and metabolic state for the balance of tolerance and immunity

The adaptive T cell response is accompanied by continuous rewiring of the T cells electric and metabolic state. Ion channels and nutrient transporters integrate bioelectric and biochemical signals from the environment, setting cellular electric and metabolic states. Divergent electric and metabolic states contribute to T cell immunity or tolerance. Here, we report that neuritin (Nrn1) contributes to tolerance development by modulating regulatory and effector T cell function. Nrn1 expression in regulatory T cells promotes its expansion and suppression function, while expression in the T effector cell dampens its inflammatory response. Nrn1 deficiency causes dysregulation of ion channel and nutrient transporter expression in Treg and effector T cells, resulting in divergent metabolic outcomes and impacting autoimmune disease progression and recovery. These findings identify a novel immune function of the neurotrophic factor Nrn1 in regulating the T cell metabolic state in a cell context-dependent manner and modulating the outcome of an immune response.

immunology↗

bioRxiv2024

Age-related RPE Changes in Wildtype C57BL/6J Mice Between 2 and 32 Months

PurposeThis study provides a systematic evaluation of age-related changes in RPE cell structure and function using a morphometric approach. We aim to better capture nuanced predictive changes in cell heterogeneity that reflect loss of RPE integrity during normal aging. Using C57BL6/J mice ranging from P60-P730, we sought to evaluate how regional changes in RPE shape reflect incremental losses in RPE cell function with advancing age. We hypothesize that tracking global morphological changes in RPE is predictive of functional defects over time. MethodsWe tested three groups of C57BL/6J mice (young: P60-180; Middle-aged: P365-729; aged: 730+) for function and structural defects using electroretinograms, immunofluorescence, and phagocytosis assays. ResultsThe largest changes in RPE morphology were evident between the young and aged groups, while the middle-aged group exhibited smaller but notable region-specific differences. We observed a 1.9-fold increase in cytoplasmic alpha-catenin expression specifically in the central-medial region of the eye between the young and aged group. There was an 8-fold increase in subretinal, IBA-1-positive immune cell recruitment and a significant decrease in visual function in aged mice compared to young mice. Functional defects in the RPE corroborated by changes in RPE phagocytotic capacity. ConclusionsThe marked increase of cytoplasmic alpha-catenin expression and subretinal immune cell deposition, and decreased visual output coincide with regional changes in RPE cell morphometrics when stratified by age. These cumulative changes in the RPE morphology showed predictive regional patterns of stress associated with loss of RPE integrity.

cell biology↗

bioRxiv2024

C1QA is an invariant biomarker for tissue macrophages

Macrophages play a pivotal role in immune responses, particularly in the context of combating microbial threats within tissues. The identification of reliable biomarkers associated with macrophage function is essential for understanding their diverse roles in host defense. This study investigates the potential of C1QA as an invariant biomarker for tissue macrophages, focusing on its correlation with the anti-microbial pathway. C1QA, a component of the complement system, has been previously implicated in various immune functions. Our research delves into the specific association of C1QA with tissue-resident macrophages and its implications in the context of anti-microbial responses. Through comprehensive systems biology and Boolean analysis of gene expression, we aim to establish C1QA as a consistent and reliable marker for identifying tissue macrophages. Furthermore, we explore the functional significance of C1QA in the anti-microbial pathway. This research seeks to provide valuable insights into the molecular mechanisms underlying the anti-microbial functions of tissue macrophages, with C1QA emerging as a potential key player in this intricate regulatory network. Understanding the relationship between C1QA, tissue macrophages, and the anti-microbial pathway could pave the way for the development of targeted therapeutic strategies aimed at enhancing the hosts ability to combat infections. Ultimately, our findings contribute to the expanding knowledge of macrophage biology and may have implications for the diagnosis and treatment of infectious diseases. One Sentence SummaryC1QA is a fundamental biomarker of tissue macrophages

systems biology↗

bioRxiv2024

Computation-aided Design of Rod-Shaped Janus Base Nanopieces for Improved Tissue Penetration and Therapeutics Delivery

Despite the development of various drug delivery technologies, there remains a significant need for vehicles that can improve targeting and biodistribution in "hard-to-penetrate" tissues. Some solid tumors, for example, are particularly challenging to penetrate due to their dense extracellular matrix (ECM). In this study, we have formulated a new family of rod-shaped delivery vehicles named Janus base nanopieces (Rod JBNps), which are more slender than conventional spherical nanoparticles, such as lipid nanoparticles (LNPs). These JBNp nanorods are formed by bundles of DNA-inspired Janus base nanotubes (JBNts) with intercalated delivery cargoes. To develop this novel family of delivery vehicles, we employed a computation-aided design (CAD) methodology that includes molecular dynamics and response surface methodology. This approach precisely and efficiently guides experimental designs. Using an ovarian cancer model, we demonstrated that JBNps markedly improve penetration into the dense ECM of solid tumors, leading to better treatment outcomes compared to FDA-approved spherical LNP delivery. This study not only successfully developed a rod-shaped delivery vehicle for improved tissue penetration but also established a CAD methodology to effectively guide material design.

bioengineering↗

bioRxiv2024

Engineered minimal type I CRISPR-Cas system for transcriptional activation and base editing in human cells

Type I CRISPR-Cas systems are widespread and have exhibited remarkable versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems and significantly smaller than SpCas9, can be developed into programmable tools for use in human cells. For transcriptional activation, the efficiency of the tool based on the engineered I-F2 system can match or surpass that of dCas9. Besides, narrow editing windows limit the application of base editors. Although the R-loop formed by Cascade is much wider than that by Cas9 or Cas12, the potential of base editing with Cascade has not yet been explored. We successfully created a base editor with the I-F2 Cascade, which induces a considerably wide editing window ([~]30 nt) with a bimodal distribution. The wide editing window can expand the range of targetable sites and can be useful for disrupting functional sequences and genetic screening. The editing efficiency can achieve 50% in human cells. This research underscores the application potential of compact type I systems in eukaryotes and developed a new base editor with an extraordinary wide editing window.

molecular biology↗

bioRxiv2024

SnapFISH-IMPUTE: an imputation method for multiplexed DNA FISH data

Chromatin spatial organization plays a crucial role in gene regulation. Recently developed and prospering multiplexed DNA FISH technologies enable direct visualization of chromatin conformation in nucleus. However, incomplete data caused by limited detection efficiency can substantially complicate and impair downstream analysis. Here, we present SnapFISH-IMPUTE that imputes missing values in multiplexed DNA FISH data. Analysis on multiple published datasets shows that the proposed method preserves the distribution of pairwise distances between imaging loci, and the imputed chromatin conformations are indistinguishable from the observed conformations. Additionally, imputation greatly improves downstream analyses such as identifying enhancer-promoter loops and clustering cells into distinct cell types. SnapFISH-IMPUTE is freely available at https://github.com/hyuyu104/SnapFISH-IMPUTE.

bioinformatics↗

bioRxiv2024

Broadly conserved FlgV controls flagellar assembly and Borrelia burgdorferi dissemination in mice

Flagella propel pathogens through their environments yet are expensive to synthesize and are immunogenic. Thus, complex hierarchical regulatory networks control flagellar gene expression. Spirochetes are highly motile bacteria, but peculiarly in the Lyme spirochete Borrelia burgdorferi, the archetypal flagellar regulator {sigma}28 is absent. We rediscovered gene bb0268 in B. burgdorferi as flgV, a broadly-conserved gene in the flagellar superoperon alongside {sigma}28 in many Spirochaetes, Firmicutes and other phyla, with distant homologs in Epsilonproteobacteria. We found that B. burgdorferi FlgV is localized within flagellar motors. B. burgdorferi lacking flgV construct fewer and shorter flagellar filaments and are defective in cell division and motility. During the enzootic cycle, B. burgdorferi lacking flgV survive and replicate in Ixodes ticks but are attenuated for dissemination and infection in mice. Our work defines infection timepoints when spirochete motility is most crucial and implicates FlgV as a broadly distributed structural flagellar component that modulates flagellar assembly.

microbiology↗

bioRxiv2024

Polaris Neurosense: A General-Purpose Non-invasive Neurotechnology Research Platform

This article describes our initial work toward a general-purpose platform for non-invasive neurotechnology research. This platform consists of a multi-modal wireless recording device, an associated software API, and full integration into BCI2000 software. The device is placed on the forehead and features two electroencephalographic (EEG) sensors, an inertial movement sensor (IMU), a photoplethysmogram (PPG) sensor, a microphone, and vibration-based feedback. Herein, we demonstrate different technical characteristics of our platform and its use in the context of sleep monitoring/modulation, simultaneous and synchronized recordings from different hardware, and evoked potentials. With further development and widespread dissemination, our platform could become an important tool for research into new non-invasive neurotechnology protocols in humans.

bioengineering↗

bioRxiv2024

ThermoFinder: A sequence-based thermophilic proteins prediction framework

MotivationThermophilic proteins are important for academic research and industrial processes, and various computational methods have been developed to identify and screen them. However, their performance has been limited due to the lack of high-quality labeled data and efficient models for representing protein. Here, we proposed a novel sequence-based thermophilic proteins prediction framework, called ThermoFinder. ResultsIn this study, we demonstrated that ThermoFinder outperforms previous state-of-the-art tools on two benchmark datasets, and feature ablation experiments confirmed the effectiveness of our approach. Additionally, ThermoFinder exhibited exceptional performance and consistency across two newly constructed datasets, one of these was specifically constructed for the regression-based prediction of temperature optimum values directly derived from protein sequences. The feature importance analysis, using shapley additive explanations, further validated the advantages of ThermoFinder. We believe that ThermoFinder will be a valuable and comprehensive framework for predicting thermophilic proteins.

bioinformatics↗

bioRxiv2023

Site Effects in Multisite Fetal Brain MRI: Morphological Insights into Early Brain Development

BackgroundMultisite MRI studies have become prevalent given their advantage in revealing reliable biological or clinical findings. Adult and adolescent multisite studies have demonstrated inevitable site-related non-biological effects that introduce bias. However, the site effect on fetal brain MRI remains unknown. PurposeTo identify crucial acquisition factors affecting fetal brain structural measurements and developmental patterns, while assessing the effectiveness of existing harmonization methods in mitigating site effects. Materials and MethodsBetween May 2017 and March 2022, T2-weighted fast spin-echo sequences in-utero MRI were performed in healthy fetuses from prospectively recruited pregnant volunteers on four different scanners at four sites. A generalized additive model (GAM) was used to quantitatively assess site effects, including field strength (FS), manufacture (M), in-plane resolution (R), and slice thickness (ST), on subcortical volume and cortical morphological measurements, including cortical thickness, curvature, and sulcal depth. Growth models were selected to elucidate developmental trajectories of these morphological measurements. Welchs test was performed to evaluate the influence of site effects on developmental trajectories. ComBat-GAM harmonization method was applied to mitigate site-related biases. ResultsThe final analytic sample consisted of 340 MRI scans from 218 fetuses (mean gestational age, 30.1 weeks {+/-} 4.4 [range, 21.7-40 weeks]). GAM results showed that low FS and low spatial resolution led to overestimations in selected brain regions of subcortical volumes and cortical morphological measurements, and cortical measurements were more susceptible to site effects than subcortical volumes. Only the peak cortical thickness in developmental trajectories was significantly influenced by the effects of FS and R. Notably, ComBat-GAM harmonization effectively removed site effects while preserving developmental patterns. ConclusionOur findings pinpointed the key acquisition factors in in-utero fetal brain MRI and underscored the necessity of data harmonization when pooling multisite data for fetal brain morphology investigations.

bioengineering↗