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Yu, T.

Publications and source records attributed to Yu, T..

At least 127 records · Page 7Linked to original sources
bioRxiv2020

Inference of sexual selection from pairwise contests

Sexual selection, whether mediated by male-male competition, female choice, male choice, or other factors influencing reproductive outcomes, can be usefully framed as a series of pairwise contests. Experimental evolutionary biologists have long used male-choice and female-choice experiments to quantify genotype-specific mating success, a key component of fitness. Here, we consider Drosophila mate-choice experiments and apply the Bradley-Terry model, which has been explicitly designed to quantify the merits of contestants and establish a ranking based on results from pairwise contests. The Bradley-Terry model can also be used to predict the probabilities of outcomes for contests that have not yet taken place. Leave-one-out validation allows us to assess both model fit and predictive performance for unobserved contests. After applying these methods to Drosophila mate-choice experiments, we interpret the results in terms of sexual selection and discuss the implications of deviations from a well-fitting model.

evolutionary biology↗
bioRxiv2020

Untargeted Metabolomics Shows Alterations in Homocysteine, Lipids, and Fatty Acids Predicting Memory Decline in Healthy Middle-Aged Individuals

INTRODUCTIONSome aspects of memory start declining in the fifth decade which may be related to systemic metabolic changes. These changes have not been fully identified. This is the first Metabolome-Wide Association Study of the human plasma for the longitudinal change in memory in healthy adults. METHODSUltra-high resolution mass spectrometry with liquid chromatography was performed on 207 University employees plasma. RESULTSFrom 10,201 measured metabolic features, 558 differed between those experiencing change vs no change in memory (False Discovery Rate, FDR< 0.2). Differentially abundant metabolites were observed in lipid and fatty acid metabolism pathways: glycerophospholipid (p=0.0003), fatty acid (p=0.0003) and linoleate (p=0.0003) pathways. Within these pathways, higher homocysteine (OR for memory decline=1.09, FDR=0.19) and lower arachidonic acid (OR=0.97, FDR=0.19), sterol (OR=0.92, FDR=0.02), acetylcholine (OR=0.78, FDR=0.19), carnitine (OR=0.75, FDR=0.19) and linoleic acid (OR=0.74, FDR=0.19) were associated memory decline. DISCUSSIONAltered systemic lipid and fatty acid are linked with early memory decline in middle-aged individuals.

neuroscience↗
bioRxiv2019

Prognostic significances of interleukin-17-producing cells and Th17 cells in malignant cancers: a meta-analysis of the literatures

Background and purposeAs a proinflammatory factor, interleukin-17 (IL-17) can play a role in both tumor promotion and suppression. IL-17 is traditionally regarded as secreting mainly by CD4+ T helper cells (Th17 cells), while other immune subsets have been proved to produce IL-17, called IL-17+ cells. Considerable studies have drawn controversial conclusions about association between IL-17+/Th17 cells and prognosis of cancer patients. This meta-analysis was performed to systematically and quantitatively analyze prognostic values of IL-17+ cells and Th17 cells in cancer patients. MethodsA comprehensive retrieval was conducted in Pubmed (MEDLINE) and EMBASE databases. Pooled risk ratios (RRs) or hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were calculated to evaluate the prognostic values of IL-17+ cells and Th17 cells in cancer patients. ResultsA total of 42 studies with 5039 patitents were included. High IL-17+ cells was significantly associated with tumor recurrence (RR = 4.23, 95% CI [1.58, 11.35]), worse disease free survival (DFS) (HR = 1.84, 95% CI [1.22, 2.77]) and overall survival (OS) (HR = 1.39, 95% CI [1.04, 1.87]), especially in cancers of digestive system. Besides, no significant difference was observed between high IL-17+ cells and histological grade, lymph node metastasis, tumor volume, clinical stages or distant metastasis. Moreover, there was no significant difference in OS between high and low Th17 cells in cancer patients (HR = 0.93, 95% CI [0.58, 1.49]). ConclusionsThis meta-analysis suggests high IL-17+ cells could be an indicator for worse survival in patients with malignant cancers, especially with cancers of digestive system. Although high Th17 cells appears to have non-statistically significance on prognosis, more clinical studies should be implemented to investigate the underlying function of Th17 cells within tumor microenvironment. This study put forward a new insight for potential application of anti-IL-17 target therapy in cancer therapeutics.

cancer biology↗
bioRxiv2019

Genetic Deletion of TrpV1 and TrpA1 Does not Alter Avoidance of or Patterns of Brainstem Activation to Citric Acid in Mice

Exposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similarly to wildtype mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford et. al 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in wildtype (WT) and TrpA1/V1 double KO (TRPA1/V1Db1-/-) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, 30 mM citric acid, along with 100 M SC45647 and H2O. Both WT and TRPA1/V1Db1-/- show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36 respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Db1-/-animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.

neuroscience↗
bioRxiv2019

MACS: Rapid aqueous clearing system for three-dimensional mapping of intact organs

Tissue optical clearing techniques have provided important tools for large-volume imaging. Aqueous-based clearing methods are known for good fluorescence preservation and scalable size maintenance, but are limited by either long incubation time, or insufficient clearing performance, or requirements for specialized devices. Additionally, due to the use of high concentration organic solvents or detergents, few clearing methods are compatible with lipophilic dyes while maintaining high clearing performance. To address these issues, we developed a rapid, highly efficient aqueous clearing method with robust compatibility, termed m-xylylenediamine (MXDA)-based Aqueous Clearing System (MACS). MACS can render intact organs highly transparent in a fairly short time and possesses ideal compatibility with multiple probes, especially for lipophilic dyes. Using MACS, we cleared the adult mouse brains within only 2.5 days for three-dimensional (3D) imaging of the neural structures labelled by various techniques. Combining MACS with DiI labelling, we visualized the vascular structures of various organs. MACS provides a useful tool for 3D mapping of intact tissues and is expected to facilitate morphological, physiological and pathological studies of various organs.

bioengineering↗
bioRxiv2019

Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy

Instant 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale mapping of entire macro-scale organs at high spatial resolution, thereby overcoming the throughput limit of current 3D microscopy implementations. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our method yields 3D images with high, isotropic spatial resolution and rapid acquisition improved by two-orders of magnitude. We demonstrate the imaging of whole brain ([~]400 mm3), entire gastrocnemius and tibialis muscles ([~]200 mm3) of mouse at subcellular resolution (0.5-m isovoxel) and ultra-high throughput of 5[~]10 minutes per sample. Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, were also readily enabled by our method.

bioengineering↗
bioRxiv2019

Analysis the Detailed Process of Glomerular Capillary Formation Using Immunofluorescence Perform With Ultrathick Section

BackgroundGlomerular capillary formation is one of the fundamental mysteries in renal developmental biology. However, there are still debates on this issue, and its detailed formation process has not been clarified.\n\nResultsTo resolve this problem, we performed antibody staining with ultra-thick section on embryonic and postnatal mouse kidneys to detect and analyze the development of glomerular capillaries. We found that blood vessel of the fetal kidneys expanded through proliferation and sprouting. During the comma-stage and S-shaped stages, 3-4 capillaries began to bud and migrate into the glomerular cleft, forming a capillary bed in the Bowmans capsule. Then, the capillary bed expanded into mature glomerular capillary by intussusceptive angiogenesis. The afferent and efferent arterioles were formed through pruning. The distribution of VEGFA in the nephron epithelial cells but not only in podocytes, induced multiple capillaries sprouted into the glomerular cleft. And CXCR4 played an important role in the differentiation and expansion of capillary bed into glomerular capillary.\n\nConclusionsImmunofluorescence performed with ultra-thick section allowed us to investigate the development of complex structure tissues systematically and comprehensively.

developmental biology↗
bioRxiv2019

Predicting cellular position in the Drosophila embryo from Single-Cell Transcriptomics data

Single-cell RNA-seq technologies are rapidly evolving but while very informative, in standard scRNAseq experiments the spatial organization of the cells in the tissue of origin is lost. Conversely, spatial RNA-seq technologies designed to keep the localization of the cells have limited throughput and gene coverage. Mapping scRNAseq to genes with spatial information increases coverage while providing spatial location. However, methods to perform such mapping have not yet been benchmarked. To bridge the gap, we organized the DREAM Single-Cell Transcriptomics challenge focused on the spatial reconstruction of cells from the Drosophila embryo from scRNAseq data, leveraging as gold standard genes with in situ hybridization data from the Berkeley Drosophila Transcription Network Project reference atlas. The 34 participating teams used diverse algorithms for gene selection and location prediction, while being able to correctly localize rare subpopulations of cells. Selection of predictor genes was essential for this task and such genes showed a relatively high expression entropy, high spatial clustering and the presence of prominent developmental genes such as gap and pair-ruled genes and tissue defining markers.

systems biology↗
bioRxiv2019

An integrated Asian human SNV and indel benchmark combining multiple sequencing methods

Precision medicine of human requires an accurate and complete reference variant benchmark for different populations. A human standard cell line of NA12878 provides a good reference for part of the human populations, but it is still lack of a fine reference standard sample and variant benchmark for the Asians. Here, we constructed a stabilized cell line of a Chinese Han volunteer. We received about 4.16T clean data of the sample using eight sequencing strategies in different laboratories, including two BGI regular NGS platforms, three Illumina regular NGS platforms, two linked-read libraries, and PacBio CCS model. The sequencing depth and reference coverage of eight sequencing strategies have reached the saturation. We detected small variants of SNPs and Indels using the eight data sets and obtained eight variant sets by performing a series of strictly quality control. Finally, we got 3.35M SNPs and 349K indels supported by all of sequencing data, which could be considered as a high confidence standard small variant sets for the studies. Besides, we also detected 5,913 high quality SNPs located in the high homologous regions supported by both linked-reads and CCS data benefited by their long-range information, while these regions are recalcitrant to regular NGS data due to the limited mappability and read length. We compared the later SNPs against the public databases and 969 sites of them were novel SNPs, indicating these SNPs provide a vital complement for the variant database. Moreover, we also phased more than 99% heterozygous SNPs also supported by linked-reads and CCS data. This work provided an integrated Asians SNV and indel benchmark for the further basic studies and precision medicine.

genomics↗
bioRxiv2019

Multiple Myeloma DREAM Challenge Reveals Epigenetic Regulator PHF19 As Marker of Aggressive Disease

While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients do not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involve assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post challenge analysis identified a novel expression-based risk marker and histone modifier, PHF19, which featured prominently in several independent models. Lastly, we show that a simple four feature predictor composed of age, International Staging System stage (ISS), and expression of PHF19 and MMSET performs similarly to more complex models with many more gene expression features included.\n\nKey pointsO_LIMost comprehensive and unbiased assessment of prognostic biomarkers in MM resulting in a robust and parsimonious model.\nC_LIO_LIIdentification of PHF19 as the expression based biomarker most strongly associated with rapid progression in MM patients.\nC_LI

cancer biology↗
bioRxiv2019

Efficient multiplex genome editing using CRISPR-Mb3Cas12a in mice

Despite many advantages over Cas9, Cas12a has not been widely used in genome editing in mammalian cells largely due to its strict requirement of the TTTV protospacer adjacent motif (PAM) sequence. Here, we report that Mb3Cas12a (Moraxella bovoculi AAX11_00205) could edit the genome in murine zygotes independent of TTTV PAM sequences and with minimal on-target mutations and close to 100% editing efficiency when crRNAs of 23nt spacers were used.\n\nSummary statementCRISPR-Mb3Cas12a can target a broader range of sequences in murine zygotes compared to AsCas12a and LbCas12a, and has lower on-target effects than Cas9 and high overall knock-in efficiency.

genomics↗
bioRxiv2019

Epigenetics biomarkers of delirium: immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients

BackgroundThe authors previously hypothesized the role of epigenetics in pathophysiology of delirium, and tested DNA methylation (DNAm) change among pro-inflammatory cytokines along with aging in blood, glia and neuron. The authors reported that DNAm level of the TNF-alpha decreases along with aging in blood and glia, but not in neuron; however, DNAm differences between delirium cases and non-delirium controls have not been investigated directly. Therefore, in the present study, DNAm differences in blood between delirium patients and controls without delirium were examined.\n\nMethodsA case-control study with 92 subjects was conducted. Whole blood samples were collected and genome-wide DNAm was measured by the Infinium HumanMethylationEPIC BeadChip arrays. The correlation between DNAm levels in the TNF-alpha and age, network analysis, and the correlation between age and DNAm age were tested.\n\nResultsOnly delirium cases showed 3 CpGs sites in the TNF-alpha significantly correlated to age after multiple corrections. A genome-wide significant CpG site near the gene of LDLRAD4 was identified. In addition, network analysis showed several significant pathways with false discovery rate adjusted p-value < 0.05. The top pathway with GO was immune response, and the second top pathway with KEGG was cholinergic synapse. Although there was no statistically significant difference, DNAm age among non-delirium controls showed \"slower aging\" compared to delirium cases.\n\nConclusionsDNAm differences were shown both at gene and network levels between delirium cases and non-delirium controls. This finding indicates that DNAm status in blood has a potential to be used as epigenetic biomarkers for delirium.

neuroscience↗
bioRxiv2019

A Unique Mouse Model of Early-Life Exercise Enables Lasting Hippocampal Synaptic Plasticity and Memory

Aerobic exercise is a powerful modulator of learning and memory. Molecular mechanisms underlying the cognitive benefits of exercise are well documented in adult rodents. Animal models of exercise targeting specific postnatal periods of hippocampal development and plasticity are lacking. Here we characterize a model of early-life exercise (ELE) in male and female mice designed with the goal of identifying critical periods by which exercise may have a lasting impact on hippocampal memory and synaptic plasticity. Mice freely accessed a running wheel during three postnatal periods: the 4th postnatal week (juvenile ELE, P21-27), 6th postnatal week (adolescent ELE, P35-41), or 4th-6th postnatal weeks (juvenile-adolescent ELE, P21-41). All exercise groups significantly increased their running distances over time. When exposed to a weak learning stimulus, mice that had exercised during the juvenile period were able to form lasting long-term memory for a hippocampus-dependent spatial memory task. Electrophysiological experiments revealed enhanced long-term potentiation in hippocampal CA1 the juvenile-adolescent ELE group only. Furthermore, basal synaptic transmission was significantly increased in all mice that exercised during the juvenile period. Our results suggest early-life exercise can enable hippocampal memory, synaptic plasticity, and basal synaptic physiology when occurring during postnatal periods of hippocampal maturation.

neuroscience↗
bioRxiv2019

Elizabethkingia anophelis response to iron stress: physiologic, genomic, and transcriptomic analyses

Elizabethkingia anophelis bacteria encounter fluxes of iron in the midgut of mosquitoes, where they live as symbionts. They also establish bacteremia with severe clinical manifestations in humans, and live in water service lines in hospitals. In this study, we investigated the global gene expression responses of E. anophelis to iron fluxes in the midgut of female Anopheles stephensi mosquitoes fed sucrose or blood, and in iron-poor or iron-rich culture conditions. Of 3,686 transcripts revealed by RNAseq technology, 218 were upregulated while 112 were down-regulated under iron-poor conditions. Most of these differentially expressed genes (DEGs) were enriched in functional groups assigned within \"biological process,\" \"cell component\" and \"molecular function\" categories. E. anophelis possessed 4 iron/heme acquisition systems. Hemolysin gene expression was significantly repressed when cells were grown under iron-rich or high temperature (37{degrees}C) conditions. Furthermore, hemolysin gene expression was down-regulated after a blood meal, indicating that E. anophelis cells responded to excess iron and its associated physiological stress by limiting iron loading. By contrast, genes encoding respiratory chain proteins were up-regulated under iron-rich conditions, allowing these iron-containing proteins to chelate intracellular free iron. In vivo studies showed that growth of E. anophelis cells increased 3-fold in blood-fed mosquitoes over those in sucrose-fed ones. Deletion of aerobactin synthesis genes led to impaired cell growth in both iron-rich and iron-poor media. Mutants showed more susceptibility to H2O2 toxicity and less biofilm formation than did wild-type cells. Mosquitoes with E. anophelis experimentally colonized in their guts produced more eggs than did those treated with erythromycin or left unmanipulated, as controls. Results reveal that E. anophelis bacteria respond to varying iron concentration in the mosquito gut, harvest iron while fending off iron-associated stress, contribute to lysis of red blood cells, and positively influence mosquito host fecundity.

microbiology↗
bioRxiv2019

Adaptive evolution targets a piRNA precursor transcription network

In Drosophila, transposon-silencing piRNAs are derived from heterochromatic clusters and a subset of euchromatic transposon insertions, which are transcribed from internal non-canonical initiation sites and flanking canonical promoters. Rhino binds to Deadlock, which recruits TRF2 to promote non-canonical transcription of these loci. Cuff co-localizes with Rhino and Del. The role of Cuff is less well understood, but the cuff gene shows hallmarks of adaptive evolution, which frequently targets functional interactions within host defense systems. We show that Drosophila simulans cuff is a dominant negative allele when expressed in Drosophila melanogaster, where it traps Deadlock, TRF2 and the transcriptional co-repressor CtBP in stable nuclear complexes. Cuff promotes Rhino and Deadlock localization, driving non-canonical transcription. CtBP, by contrast, suppresses canonical cluster and transposon transcription, which interferes with downstream non-canonical transcription and piRNA production. Cuff, TRF2 and CtBP thus form a network that balances canonical and non-canonical piRNA precursor transcription.

genetics↗
bioRxiv2019

Batch Effect Correction of RNA-seq Data through Sample Distance Matrix Adjustment

Batch effect is a frequent challenge in deep sequencing data analysis that can lead to misleading conclusions. We present scBatch, a numerical algorithm that conducts batch effect correction on the count matrix of RNA sequencing (RNA-seq) data. Different from traditional methods, scBatch starts with establishing an ideal correction of the sample distance matrix that effectively reflect the underlying biological subgroups, without considering the actual correction of the raw count matrix itself. It then seeks an optimal linear transformation of the count matrix to approximate the established sample pattern. The benefit of such an approach is the final result is not restricted by assumptions on the mechanism of the batch effect. As a result, the method yields good clustering and gene differential expression (DE) results. We compared the new method, scBatch, with leading batch effect removal methods ComBat and mnnCorrect on simulated data, real bulk RNA-seq data, and real single-cell RNA-seq data. The comparisons demonstrated that scBatch achieved better sample clustering and DE gene detection results.

bioinformatics↗
bioRxiv2019

In Vitro Potent Activity of ε-poly-L-lysine against Candida albicans and the Underlying Mechanisms

ObjectiveThis study aimed to examine the antifungal activity of {varepsilon}-poly-L-lysine ({varepsilon}-PL) against the planktonic cells or biofilms of Candida albicans and explore the underlying mechanism.\n\nMethodsThe minimal inhibitory concentration, minimum fungal concentration, and sessile minimal inhibitory concentration were estimated. The germ tube formation and yeast-to-hypha transformation of C. albicans in different media that induced mycelial growth were recorded. The effect of different concentrations of {varepsilon}-PL on the biofilm formation process and mature biofilm of C. albicans was determined. The reactive oxygen species (ROS) and malondialdehyde (MDA) contents of C. albicans after {varepsilon}-PL treatment were measured. The changes in major virulence genes and proteins of C. albicans were detected.\n\nResults{varepsilon}-PL (512 g/mL) exerted a strong inhibitory effect on C. albicans and biofilms. It blocked the yeast-to-hypha transition and reduced the germ tube formation and germ tube length of C. albicans. The MDA and ROS contents showed an upward trend, indicating a positive correlation with the concentration. Further, {varepsilon}-PL inhibited the high expression of virulence genes in oxidative stress induced by C. albicans. The main peak in the mass spectrum of C. albicans was found to be clear.\n\nConclusions{varepsilon}-PL exerted a significant antifungal effect on the phytoplankton and biofilm of C. albicans. High concentrations of {varepsilon}-PL significantly inhibited the main mycelium of C. albicans. {varepsilon}-PL induced ROS, released cytochrome C, attacked the C. albicans cell membrane to aggravate its lipid oxidation, and inhibited the expression of C. albicans-associated virulence genes and proteins, thereby exerting a bacteriostatic effect.\n\nImportanceThe last two decades have seen a growing trend toward the failure of current antifungal drugs attributed to Candida biofilms. Under appropriate conditions, adherence and colonization of planktonic cells on host tissues and medical devices initiate multicellular organization called biofilm, which is an organized heterogeneous mixture of yeast, hyphae, and pseudohyphal forms embedded in a complex extracellular matrix. Compared with the planktonic cells, biofilms show high resistance to a wide variety of antifungal agents and tolerance to harsh environments and host immune system. Moreover, the development of antifungal drugs is costly, long-term, and difficult. Thus, researchers turned their attention to natural antibacterial peptides, hoping to find an effective antifungal substance or enhance the sensitivity of the existing antifungal drugs to C. albicans.

microbiology↗