Biology subjects

Tang, Y.

Publications and source records attributed to Tang, Y..

At least 307 records · Page 17Linked to original sources

bioRxiv2019

VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating the heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in mediating release of glutamate, contributed to the inflammatory heat. It remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in Inflammatory pain mediated by Cdk5 and the heat hyperalgesia induced by complete Freunds adjuvant (CFA) can be reversed by roscovitine, a selective inhibitor for Cdk5 through inhibition of VGLUT2 expression. Immunohistochemistry results suggest that when compared with rats in a control group, rats in an experimental group showed significant coexpression of Cdk5/VGLUT2 in small and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA. Moreover, our study revealed that the expression of VGLUT2 protein in DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection. Additionally, p25 but not p35, a activator of Cdk5, protein was significantly increased and reduced by roscovitine. The increased expressions of VGLUT2 protein was significantly reduced by roscovitine as well. Our study showed that VGLUT2/Cdk5 signaling pathway contributed to the inflammatory pain medicated by Cdk5/p25.

neuroscience↗

bioRxiv2019

PD-1 expression during acute infection is repressed through 1 a LSD1- Blimp-1 axis

During prolonged exposure to antigens, such as chronic viral infections, sustained T cell receptor (TCR) signaling can result in T cell exhaustion mediated in part by expression of Programmed cell death-1 (PD-1) encoded by the Pdcd1 gene. Here, dynamic changes in histone H3K4 modifications at the Pdcd1 locus during ex vivo and in vivo activation of CD8 T cells, suggested a potential role for the histone H3 lysine 4 demethylase LSD1 in regulating PD-1 expression. CD8 T cells lacking LSD1 expressed higher levels of Pdcd1 mRNA following ex vivo stimulation, as well as increased surface levels of PD-1 during acute but not chronic infection with lymphocytic choriomeningitis virus (LCMV). Blimp-1, a known repressor of PD-1, recruited LSD1 to the Pdcd1 gene during acute but not chronic LCMV infection. Loss of DNA methylation at Pdcd1s promoter proximal regulatory regions is highly correlated with its expression. However, following acute LCMV infection where PD-1 expression levels return to near base line, LSD1-deficient CD8 T cells failed to remethylate the Pdcd1 locus to the levels of wild-type cells. Finally, in a murine melanoma model, the frequency of PD-1 expressing tumor infiltrating LSD1-deficient CD8 T cells was greater than wild-type. Thus, LSD1 is recruited to the Pdcd1 locus by Blimp-1, downregulates PD-1 expression by facilitating the removal of activating histone marks, and is important for remethylation of the locus. Together, these data provide insight into the complex regulatory mechanisms governing T cell immunity and the regulation of a critical T cell checkpoint gene.\n\nKey PointsO_LILSD1 suppress PD-1 expression following acute infection or transient induction.\nC_LIO_LIBlimp-1 binding to the Pdcd1 locus is required to recruit LSD1.\nC_LIO_LILSD1 is required to fully remethylate the PD-1 proximal promoter region.\nC_LI

immunology↗

bioRxiv2019

Histone acetylome-wide association study of tuberculosis

Host-cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Chinese discovery cohort, which were validated in a subsequent multi-ethnic cohort, thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression in a third cohort. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulated Akt-mTOR signaling and promoted Mtb clearance in vitro. We performed histone acetylation QTL analysis on the dataset and identified candidate causal variants for immune phenotypes. Our study serves as proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.

immunology↗

bioRxiv2019

The signaling mechanism of Hcy-induced atrial fibrosis mediated by TRPC3

BackgroundHigh plasma levels of homocysteine (Hcy) are regarded as a risk factor for atrial fibrillation (AF), which is closely associated with the pathological consequence of atrial fibrosis and can lead to heart failure with a high mortality rate; Currently, there is no effective therapy for preventing atrial fibrosis, owing to a lack in fundamental understanding of the underlying mechanism. Here, we show that atrial fibrosis is mediated by the relationship between canonical transient receptor potential 3 (TRPC3) channels and sirtuin type 1 (SIRT1) under the stimulation of Hcy.\n\nMethodsThe left atrial appendage was obtained from patients with either sinus rhythm (SR) or AF, who underwent cardiothoracic surgery, and used to evaluate the relationship between the concentration of Hcy and a potential mechanism of cardiac fibrosis mediated by TRPC3 and SIRT1. We next performed transverse aortic constriction (TAC) in mouse to investigate the relationship. The mechanisms underlying atrial fibrosis involving TRPC3 and SIRT1 proteins were explored by co-immunoprecipitation (co-IP), bio-layer interferometry (BLI) and lentivirus transfection experiments. Quantitative polymerase chain reaction (qPCR) and western blotting (WB) were performed to analyse gene and protein expression, respectively.\n\nResultsThe majority of AF patients displayed atrial fibrosis, as demonstrated by Masson staining and immunohistochemistry. In the mouse model of TAC, more severe fibrosis was detected in the high-Hcy diet (HH) group, compared to NH mice; and the duration of induced AF was longer in the HH groups than in the normal diet (NH) group. Moreover, the HH group exhibited higher expression levels of TRPC3 and related fibrosis proteins, such as TGF-{beta} and Col-I, than the NH group, despite also showing a higher level of SIRT1 was observed. The activator of SIRT1 (Resveratrol, Res) attenuated the enhancement of TRPC3 and decrease in SIRT1 observed in the HH group. Further cell culture experiments confirmed that Hcy could promote the proliferation and differentiation of fibroblasts, the up-regulation of TRPC3, and the decrease in the protein level of SIRT1. Ultimately, the results of Co-IP and BLI indicated a direct interaction between TRPC3-C terminal domain (569-863) and SIRT1 proteins, in which the two proteins are antagonistic and in combination regulate the pathogenesis of atrial fibrosis.\n\nConclusionsThe higher level of atrial fibrosis were observed in the HH mouse group, compared with the NH mice group, Such results suggest that AF patients may be more susceptible to atrial fibrosis and possess a high probability of progressing to hyperhomocysteinemia. Moreover, our findings are consistent with the hypothesis that TRPC3 channel up-regulation leads to abnormal accumulation of collagen, with the down-regulation of SIRT1 as an aetiological factor of high Hcy, which in turn predisposes to atrial fibrosis and strongly enhances the possibility of AF.

molecular biology↗

bioRxiv2019

Multi-omics Integrative Analysis of Acute and Relapsing Malaria in a Non-Human Primate Model of P. vivax infection

Systems-scale analysis of multiple layers of molecular and cellular data has significant potential for providing novel insights into malaria pathology and immunity. We present here a unique longitudinal multi-omics dataset encompassing Macaca mulatta blood and bone marrow responses to infection by Plasmodium cynomolgi, a non-human primate (NHP) parasite species used to model P. vivax malaria acute and relapsing infections in humans. We analyzed relationships across multiple biological layers using a mutual information-based machine learning approach to integrate heterogeneous longitudinal datasets and constructed an atlas of multi-omics relatedness networks (MORNs). Using this technique, we were able to detect signatures that defined both acute and relapsing infections. Importantly, relapse infections could be distinguished from both acutely-infected and uninfected NHP, suggesting that the host-parasite interactions during relapses are unique compared to acute Plasmodium infections. To our knowledge, this is the first report of large-scale, longitudinal multi-omics analysis of malaria in any system. This dataset, along with the method used to analyze it, provides a unique resource for the malaria research community and demonstrates the power of longitudinal infection study designs, NHP model systems and integrative multi-omics analyses.

systems biology↗

bioRxiv2019

Structure-guided function discovery of an NRPS-like glycine betaine reductase for choline biosynthesis in fungi

Nonribosomal peptide synthetases (NRPS) and NRPS-like enzymes have diverse functions in primary and secondary metabolism. By using a structure-guided approach, we uncovered the function of an NRPS-like enzyme with unusual domain architecture, catalyzing two sequential two-electron reductions of glycine betaine to choline. Structural analysis based on homology model suggests cation-{pi} interactions as the major substrate specificity determinant, which was verified using substrate analogs and inhibitors. Bioinformatic analysis indicates this NRPS-like glycine betaine reductase is highly conserved and widespread in fungi kingdom. Genetic knockout experiments confirmed its role in choline biosynthesis and maintaining glycine betaine homeostasis in fungi. Our findings demonstrate that the oxidative choline-glycine betaine degradation pathway can operate in a fully reversible fashion and provide new insights in understanding fungal choline metabolism. The use of an NRPS-like enzyme for reductive choline formation is energetically efficient compared to known pathways. Our discovery also underscores the capabilities of structure-guided approach in assigning function of uncharacterized multidomain proteins, which can potentially aid functional discovery of new enzymes by genome mining.

biochemistry↗

bioRxiv2019

An Array of 60,000 Antibodies for Proteome-Scale Antibody Generation and Target Discovery

Antibodies are essential for elucidating the roles of genes decoded by genome sequencing. However, affordable technology for proteome-scale antibody generation does not exist. To address this, we developed the Proteome Epitope Tag Antibody Library (PETAL) and its array. PETAL consists of 62,208 mAbs against 15,199 peptides from diverse proteomes. PETAL harbors binders for a great multitude of proteins in nature due to antibody multispecificity, an intrinsic feature of an antibody. Distinctive combinations of 10,000-20,000 mAbs were found to target specific proteomes by array screening. Phenotype-specific mAb-target pairs were discovered for maize and zebrafish samples. Immunofluorescence and flow cytometry mAbs for human membrane proteins and ChIP-seq mAbs for transcription factors were identified from respective proteome-binding PETAL mAbs. Differential screening of cell surface proteomes of tumor and normal tissues discovered internalizing tumor antigens for antibody-drug conjugates. By discovering high affinity mAbs at a fraction of current time and cost, PETAL enables proteome-scale antibody generation and target discovery.

systems biology↗

bioRxiv2019

Reproducibility of functional brain alterations in major depressive disorder: evidence from a multisite resting-state functional MRI study with 1,434 individuals

Resting-state functional MRI (R-fMRI) studies have demonstrated widespread alterations in brain function in patients with major depressive disorder (MDD). However, a clear and consistent conclusion regarding a repeatable pattern of MDD-relevant alterations is still limited due to the scarcity of large-sample, multisite datasets. Here, we address this issue by including a large R-fMRI dataset with 1,434 participants (709 patients with MDD and 725 healthy controls) from five centers in China. Individual functional activity maps that represent very local to long-range connections are computed using the amplitude of low-frequency fluctuations, regional homogeneity and distance-related functional connectivity strength. The reproducibility analyses involve different statistical strategies, global signal regression, across-center consistency, clinical variables, and sample size. We observed significant hypoactivity in the orbitofrontal, sensorimotor, and visual cortices and hyperactivity in the frontoparietal cortices in MDD patients compared to the controls. These alterations are not affected by different statistical analysis strategies, global signal regression and medication status and are generally reproducible across centers. However, these between-group differences are partially influenced by the episode status and the age of disease onset in patients, and the brain-clinical variable relationship exhibits poor cross-center reproducibility. Bootstrap analyses reveal that at least 400 subjects in each group are required to replicate significant alterations (an extent threshold of P<.05 and a height threshold of P<.001) at 50% reproducibility. Together, these results highlight reproducible patterns of functional alterations in MDD and relevant influencing factors, which provides crucial guidance for future neuroimaging studies of this disorder.

neuroscience↗

bioRxiv2019

Direct synthesis of EM-visible gold nanoparticles on genetically encoded tags for single-molecule visualization in cells

Single-molecule visualization in cells with genetically encoded tags for electron microscopy (EM) has been a long-awaited but unimplemented tool for cell biologists. Here, we report an approach for directly synthesizing EM-visible gold nanoparticles (AuNPs) on cysteine-rich tags for single-molecule visualization in cells. We first uncovered an auto-nucleation suppression mechanism that allows specific synthesis of AuNPs on isolated cysteine-rich tags. We next exploited this mechanism to develop an approach for single-molecule detection of proteins in prokaryotic cells and achieved an unprecedented labeling efficiency. We then expanded it to more complicated eukaryotic cells and successfully detected the proteins targeted to various organelles, including the membranes of endoplasmic reticulum (ER) and nuclear envelope, ER lumen, nuclear pores, spindle pole bodies, and mitochondrial matrix. Thus, our implementation of genetically encoded tags for EM should allow cell biologists to address an enormous range of biological questions at single-molecule level in diverse cellular ultrastructural contexts without using antibodies.

biophysics↗

bioRxiv2019

MATRIEX Imaging: Multi-Area Two-photon Real-time In-vivo Explorer

Two-photon laser scanning microscopy, originally developed since 1990s1, has been widely applied for biomedical research in recent decades, particularly popular among neuroscientists for studying neural functions in vivo2. However, it is typically restricted to one imaging area that is orthogonal to the optical axis. Here, we demonstrate a novel multi-axis optical conjugation method that enables two-photon imaging at single-cell resolution simultaneously in multiple areas at different depths, each of which could have a view diameter of ~200 m and could be largely freely targeted within a zone up to 12-mm diameter. For example, we show simultaneous imaging of neuronal activities in the primary visual cortex (V1), the primary motor cortex (M1) and the hippocampal CA1 region of awake mice. This method can be readily implemented on a single conventional two-photon microscope to enable multi-area exploration of neuronal activities in vivo.

neuroscience↗

bioRxiv2018

A VTA GABAergic neural circuit mediates visually evoked innate defensive responses

Innate defensive responses are essential for animal survival and are conserved across species. The ventral tegmental area (VTA) plays important roles in learned appetitive and aversive behaviors, but whether it plays a role in mediating or modulating innate defensive responses is currently unknown. We report that GABAergic neurons in the mouse VTA (VTAGABA+) are preferentially activated compared to VTA dopaminergic (VTADA+) neurons when a threatening visual stimulus evokes innate defensive behavior. Functional manipulation of these neurons showed that activation of VTAGABA+ neurons is indispensable for looming-evoked defensive flight behavior and photoactivation of these neurons is sufficient for looming-evoked defensive-like flight behavior, whereas no such role can be attributed for VTADA+ neurons. Viral tracing and in vivo and in vitro electrophysiological recordings showed that VTAGABA+ neurons receive direct excitatory inputs from the superior colliculus (SC). Furthermore, we showed that glutamatergic SC-VTA projections synapse onto VTAGABA+ neurons that project to the central nucleus of the amygdala (CeA) and that the CeA is involved in mediating the defensive behavior. Our findings demonstrate that visual information about aerial threats access to the VTAGABA+ neurons mediating innate behavioral responses, suggesting a more general role for the VTA.

neuroscience↗

bioRxiv2018

Structural Basis for Stereoselective Dehydration and Hydrogen-Bonding Catalysis by the SAM-Dependent Pericyclase LepI

LepI is an S-adenosylmethionine (SAM)-dependent pericyclase that catalyzes the formation of 2-pyridone natural product leporin C. Biochemical characterization showed LepI can catalyze the stereoselective dehydration to yield a reactive (E)-quinone methide which can undergo a bifurcating intramolecular Diels-Alder (IMDA) and hetero-Diels-Alder (HDA) cyclization from an ambimodal transition state, and a [3,3]-retro-Claisen rearrangement to recycle the IMDA product into leporin C. Here we solved the X-ray crystal structures of SAM-bound LepI, and in complex with a substrate analog, the product leporin C, and a retro-Claisen reaction transition-state analog to understand the structural basis for the multitude of reactions. Structural and mutational analysis revealed how Nature evolves a classic methyltransferase active site into one that can serve as a dehydratase and a multifunctional pericyclase. Catalysis of both sets of reactions employ His133 and Arg295, two active site residues that are not found in canonical methyltransferases. An alternative role of SAM, which is not found to be in direct contact of the substrate, is also proposed.

biochemistry↗

bioRxiv2018

A new massively parallel nanoball sequencing platform for whole exome research

BackgroundWhole exome sequencing (WES) has been widely used in human genetics research. BGISEQ-500 is a recently established next-generation sequencing platform. However, the performance of BGISEQ-500 on WES is not well studied. In this study, we evaluated the performance of BGISEQ-500 on WES by side-to-side comparison with Hiseq4000, on wellcharacterized human sample NA12878.\n\nResultsBGISEQ demonstrated similarly high reproducibility as Hiseq for variation detection. Also, the SNPs from BGISEQ data is highly consistent with Hiseq results (concordance 96.5%[~]97%). Variation detection accuracy was subsequently evaluated with data from the genome in a bottle project as the benchmark. Both platforms showed similar sensitivity and precision in SNP detection. While in indel detection, BGISEQ showed slightly higher sensitivity and lower precision. The impact of sequence depth and read length on variation detection accuracy was further analyzed, and showed that variation detection sensitivity still increasing when the sequence depth is larger than 100x, and the impact of read length is minor when using 100x data.\n\nConclusionsThis study suggested that BGISEQ-500 is a qualified sequencing platform for WES.

genomics↗

bioRxiv2018

The ghr-miR164 and GhNAC100 module participates in cotton plant defence against Verticillium dahliae

Previous reports have shown that many miRNAs were identified at the early induction stage during which Verticillium dahliae localizes at the root surface. In this study, we constructed two sRNA libraries of cotton root responses to this fungus at the later induction stage when the pathogen enters the root vascular tissue. We identified 71 known miRNAs and 378 novel miRNAs from two pathogen-induced sRNAs and the control libraries. Combined with degradome and sRNA sequencing, 178 corresponding miRNA target genes were identified, in which 40 target genes from differentially expressed miRNAs were primarily associated with oxidation-reduction and stress responses. More importantly, we characterized the ghr-miR164-GhNAC100 module in the response of the plant to V dahliae infection. A GUS fusion reporter showed that ghr-miR164 directly cleaved the mRNA of GhNAC100 in the post-transcriptional process. ghr-miR164-silencing increased the resistance of the plant to this fungus, while the knockdown of GhNAC100 elevated the susceptibility of the plant, indicating that ghr-miR164-GhNAC100 modulates plant defence through the post-transcriptional regulation. Our data documented that there are numerous miRNAs at the later induction stage that participate in the plant response to V. dahliae, suggesting that miRNAs play important roles in plant resistance to vascular disease.\n\nHighlightAccording to degradome and sRNA sequencings of cotton root in responses to Verticillium dahliae at the later induction stage, many miRNAs and corresponding targets including ghr-miR164-GhNAC100 module participate plant defence.

molecular biology↗

bioRxiv2018

Targeting RyR2 with a phosphorylation site-specific nanobody Reverses Dysfunction of Failing Cardiomyocytes in Rat

Chronic PKA phosphorylation of RyR2 has been shown to increased diastolic SR Ca2+ leak and lead to cardiac dysfunction. Since the change of phosphorylation level of RyR2 is a biomarker of failing heart, we attempted to verify the hypothesis that intracellular gene delivery of a RyR2 targeting phosphorylation site-specific nanobody could preserve contractility of failing myocardium. In present study, we acquired the RyR2-specific nanobodies from a phage display library which are variable domains of camellidae heavy chain-only antibodies (VHH). One of the monoclonal nanobodies, AR185, inhibiting RyR2 phosphorylation in an in vitro assay was then chosen for further investigation. We investigated the potential of adeno-associated virus (AAV)-9-mediated cardiac expression of AR185 against post-ischemic heart failure. Adeno-associated virus gene delivery elevated the intracellular expression AR185 protein in the ischemic heart failure model of rats, and this treatment normalized the systolic and diastolic dysfunction of the failing myocardium in vivo and in vitro by reversing myocardial Ca2+ handling. Furthermore, AR185 gene transfer to failing cardiomyocytes reduced the frequency of sarcoplasmic reticulum (SR) calcium leak, thereby restoring the attenuated intracellular calcium transients and SR calcium load. Moreover, AR185 gene transfer inhibited PKA phosphorylation of RyR2 in failing cardiomyocytes. Our results provided strong pre-clinical experimental evidence of the cardiac expression of RyR2 nanobody with AAV9 vectors as a promising therapeutic strategy for ischemic heart failure.

pathology↗

bioRxiv2018

B1a cells protect against Schistosoma japonicum-induced liver inflammation and fibrosis by controlling monocyte infiltration

During Schistosoma infection, lack of B cells results in more severe granulomas, inflammation, and fibrosis in the liver, but the mechanisms underlying this pathology remain unclear. Thus, our aim was to clarify the mechanisms underpinning the immunomodulation of B cells in mice infected with Schistosoma japonicum. We found that B cell deficiency led to aggravated liver pathology, as demonstrated by increases in the size of the egg-associated granulomas, alanine transaminase levels, and collagen deposition. Compared with infected wild-type mice, infected B cell-deficient MT mice showed increased infiltration of Ly6Chi monocytes and higher levels of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 6, and interleukin 12) and chemokines ([C-C motif] ligands (CCL)2, CCL3, CCL4, and CCL5). The results of flow cytometric analysis and cell transfer experiments showed that B1a cells increased significantly in the liver following S. japonicum infection, with some of those cells deriving from the peritoneal cavity. We also found that secretion of IL-10 from hepatic B cells increased significantly in infected wild-type mice and that this IL-10 was mainly derived from B1a cells. In addition, adoptively transferring peritoneal cavity B cells purified from wild-type, but not from IL-10-deficient mice, to MT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. These reductions were accompanied by decreases in the expression levels of chemokines and inflammatory cytokines. Taken together, these data indicated that after S. japonicum infection, an increased number of hepatic B1a cells secrete IL-10, which inhibits the expression of chemokines and cytokines and suppresses the infiltration of Ly6Chi monocytes into the liver thereby alleviating liver early inflammation and late fibrosis. Understanding this immunomodulatory role of B1a cells in schistosomiasis may lead to the development of therapeutic strategies for Schistosoma-induced liver disease.\n\nAuthor summaryInfection with Schistosoma, a waterborne parasitic flatworm (trematode) commonly called a blood fluke, results in strong granulomatous inflammation caused by the deposition of eggs in the liver. A granuloma is a substantial immune cell infiltration around the eggs intermixed with liver cells that can protect the host against liver damage. However, excessive infiltration and inflammation can lead to severe liver injury and fibrosis. Here, we found that B1a cells accumulate in the liver of mice after S. japonicum-induced infection and that these B1a cells release the anti-inflammatory cytokine interleukin 10 to regulate inflammation. The B1a cell-derived interleukin 10 inhibits the expression of chemokines (which attract cells such as monocytes to sites of infection or inflammation) and thus restrains excessive infiltration of Ly6Chi monocytes (which may have proinflammatory activity) into the liver, thereby alleviating early inflammation and later fibrosis. Our study provides insight into the immunomodulation of B1a cells in schistosomiasis and offers key information for the development of therapeutic strategies in Schistosoma-induced liver disease.

immunology↗

bioRxiv2018

Tau Secretion and Propagation Is Regulated by p300/CBP via Autophagy-Lysosomal Pathway in Tauopathy

The trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. Tau secretion from neurons is the first step in tau transmission, but little is known about the cellular mechanism. Here, we report that p300/CBP, the lysine acetyltransferase that acetylates tau and regulates its homeostasis and toxicity, serves as a key regulator of tau secretion by inhibiting the autophagy-lysosomal pathway (ALP). Increased p300/CBP activity was associated with impaired function of this pathway in a tau transgenic mouse model. p300/CBP hyperactivation increased tau secretion by blocking autophagic flux. Conversely, inhibiting p300/CBP genetically or pharmacologically promoted autophagic flux, and reduced tau accumulation, tau secretion, and tau propagation in fibril-induced tau spreading models in vitro and in vivo. Our findings show that p300/CBP-induced impairment in the ALP underlies excessive unconventional secretion and pathogenic spread of tau.

neuroscience↗

bioRxiv2018

FirstSV: Fast and Accurate Approach of Structural Variations Detection for Short DNA fragments

Structural variations caused by gene fusion represent a major class of somatically acquired variations in human malignancies, and include deletions, inversions, and translocations. Short fragmented reads are the main source of data from 2nd-generation sequencing, and detecting structural variations from this type of data is different from that of 1st-generation sequencing, where the read length is much longer. Current detection methods are low in specificity and are inefficient. We developed a hybrid algorithm, FirstSV, to meet the clinical demand for fast and accurate structural variation detection. Its main features include cluster analysis, realignment, and local assembly. FirstSV was validated with simulated data, with data from real patient samples, with data from standard testing samples, and with downloaded public data sets. FirstSV outperforms public-available methods in terms of sensitivity, precision, and operational efficiency. FirstSV is freely available at https://github.com/shenjia1/FirstSV.

bioinformatics↗