Biology subjects

Tang, Y.

Publications and source records attributed to Tang, Y..

22 records · Page 2Linked to original sources

bioRxiv2017

Processive movement of actin by biased polymerization: a new paradigm of axonal transport

Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/dis-assembly events (\"hotspots\") and elongating polymers along the axon-shaft (\"trails\"). Using a combination of live imaging, super-resolution microscopy, and modeling, here we explore how these axonal actin dynamics can lead to processive transport. We found abundant actin nucleation, along with a slow, anterogradely-biased flow of actin in axon-shafts. Starting with first principles of monomer/filament assembly - and incorporating imaging data - we generated a quantitative model simulating axonal hotspots and trails. Our simulations predict that the axonal actin dynamics indeed lead to an anterogradely-biased flow of the population, at rates consistent with slow transport. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin. This mechanism is distinct from polymer-sliding, and seems well suited to convey highly dynamic cytoskeletal cargoes.\n\nAcknowledgementsThis work was supported by an NIH grant to SR (R01NS075233). The authors thank Stephanie Gupton (UNC) for the Mena/Vasp constructs.

neuroscience↗

bioRxiv2017

Deficit in parietal memory network underlies auditory hallucination: a longitudinal study

Auditory hallucination is a prominent and common symptom in schizophrenia. Previous neuroimaging studies have yielded mixed results of its brain network deficits. We proposed a novel hypothesis that parietal memory network, centered at the precuneus, plays a critical role in auditory hallucination. This network is adjacent and partially overlaps with the default mode network, and has been associated with brain function of familiarity labelling in memory processing. Using a longitudinal design and a large cohort of first-episode, drug-naive schizophrenia patients, we examined this hypothesis and further investigated whether the functional connectivity patterns of the parietal memory network can serve as a neuroimaging marker for auditory hallucination and help to predict future treatment effects. Resting-state scans from 59 first-episode drug-naive schizophrenic patients (27 with and 32 without hallucination) and 53 healthy control subjects were acquired at the baseline test, and 56 of them were scanned again after two months. Functional connectivity strength within the parietal memory network and between this network and memory hubs was across the three groups at baseline and follow-up scans. Results showed that decreased functional connectivity strength within the parietal memory network was specific to the auditory hallucination group (p = 0.009, compare to the healthy subjects; p = 0.029, compare to the patients without hallucination), with the precuneus representing the largest group difference. The intra-network connectivity strength of the precuneus negatively correlated with the severity of hallucination at the baseline scan (r = -0.437, p = 0.029), and it was significantly increased after two-month medication (p = 0.039). Logistic regression analysis and crossvalidation test demonstrated that the functional connectivity strength of the precuneus and precuneus-hippocampus connectivity could differentiate patients with or without auditory hallucination with a sensitivity of 0.750 and a specificity of 0.708. Moreover, crossvalidation test showed that these imaging features at the baseline scan well predicted the extents of positive symptom improvement in the hallucination group after the two-month medication (R2 = 0.433, p = 0.022). Our results provide evidence for a critical role of the parietal memory network underlying auditory hallucination, and further propose a novel neuroimaging marker for identifying patients, accessing severity, and prognosis of treatment effect for auditory hallucination.\n\nAbbreviations

neuroscience↗

bioRxiv2017

T-bet+ CD11c+ B Cells Are Critical For Anti-Chromatin IgG Production In The Development Of Lupus

A hallmark of systemic lupus erythematosus is high titers of circulating autoantibody. A novel CD11c+ B cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c+ B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with great autoantibody production. In the present study we investigated the role of CD11c+ B cells in the pathogenesis of lupus in the cGVHD model. Here, we found the percentage and absolute number of CD11c+ B cells and titer of sera anti-chromatin IgG and IgG2a antibody were increased in cGVHD mice. CD11c+ plasma cells from cGVHD mice produced large amounts of anti-chromatin IgG2a upon stimulation. Depletion of CD11c+ B cells reduced anti-chromatin IgG and IgG2a production. T-bet expression was further shown to be upregulated in CD11c+ B cells. Knockout of T-bet in B cells alleviated cGVHD. The percentage of T-bet+ CD11c+ B cells was elevated in lupus patients and positively correlated with serum anti-chromatin levels. Our findings suggest T-bet+ CD11c+ B cells contribute to the pathogenesis of lupus and provides potential target for therapeutic intervention.

immunology↗

bioRxiv2017

Reversed graph embedding resolves complex single-cell developmental trajectories

Organizing single cells along a developmental trajectory has emerged as a powerful tool for understanding how gene regulation governs cell fate decisions. However, learning the structure of complex single-cell trajectories with two or more branches remains a challenging computational problem. We present Monocle 2, which uses reversed graph embedding to reconstruct single-cell trajectories in a fully unsupervised manner. Monocle 2 learns an explicit principal graph to describe the data, greatly improving the robustness and accuracy of its trajectories compared to other algorithms. Monocle 2 uncovered a new, alternative cell fate in what we previously reported to be a linear trajectory for differentiating myoblasts. We also reconstruct branched trajectories for two studies of blood development, and show that loss of function mutations in key lineage transcription factors diverts cells to alternative branches on the a trajectory. Monocle 2 is thus a powerful tool for analyzing cell fate decisions with single-cell genomics.

genomics↗