BPTF Is Essential for T Cell Homeostasis and Function

Bromodomain PHD Finger Transcription Factor (BPTF), a ubiquitously expressed ATP-dependent chromatin-remodeling factor, is critical for epigenetically regulating DNA accessibility and gene expression. While BPTF is important for the development of thymocytes, its function in mature T cells remains largely unknown. By specifically deleting BPTF from late DN3/DN4 stage of developing T cells, we found that BPTF was critical for the homeostasis of T cells via a cell intrinsic manner. In addition, BPTF was essential for the maintenance and function of Treg cells. Treg cell-specific BPTF deletion led to reduced Foxp3 expression, increased lymphocyte infiltration in the non-lymphoid organs and a systemic autoimmune syndrome. These findings therefore reveal a vital role for BPTF in T and Treg cell function and immune homeostasis

Elevated Oxidative Stress and Inflammation in Hypothalamic Paraventricular Nucleus Are Associated With Sympathetic Excitation and Hypertension in Rats Exposed to Chronic Intermittent Hypoxia

Obstructive sleep apnea (OSA), characterized by recurrent collapse of the upper airway during sleep leading to chronic intermittent hypoxia (CIH), is an independent risk factor for hypertension. Sympathetic excitation has been shown to play a major role in the pathogenesis of OSA-associated hypertension. Accumulating evidence indicates that oxidative stress and inflammation in the hypothalamic paraventricular nucleus (PVN), a critical cardiovascular and autonomic center, mediate sympathetic excitation in many cardiovascular diseases. Here we tested the hypothesis that CIH elevates oxidative stress and inflammation in the PVN, which might be associated with sympathetic excitation and increased blood pressure in a rat model of CIH that mimics the oxygen profile in patients with OSA. Sprague-Dawley rats were pretreated with intracerebroventricular (ICV) infusion of vehicle or superoxide scavenger tempol, and then exposed to control or CIH for 7 days. Compared with control+vehicle rats, CIH+vehicle rats exhibited increased blood pressure, and increased sympathetic drive as indicated by the blood pressure response to ganglionic blockade and plasma norepinephrine levels. Pretreatment with ICV tempol prevented CIH-induced increases in blood pressure and sympathetic drive. Molecular studies revealed that expression of NAD(P)H oxidase subunits, production of reactive oxygen species, expression of proinflammatory cytokines and neuronal excitation in the PVN were elevated in CIH+vehicle rats, compared with control+vehicle rats, but were normalized or reduced in CIH rat pretreated with ICV tempol. Notably, CIH+vehicle rats also had increased systemic oxidative stress and inflammation, which were not altered by ICV tempol. The results suggest that CIH induces elevated oxidative stress and inflammation in the PVN, which lead to PVN neuronal excitation and are associated with sympathetic excitation and increased blood pressure. Central oxidative stress and inflammation may be novel targets for the prevention and treatment of hypertension in patients with OSA

Automating Cobb Angle Measurement for Adolescent Idiopathic Scoliosis using Instance Segmentation

Scoliosis is a three-dimensional deformity of the spine, most often diagnosed in childhood. It affects 2-3% of the population, which is approximately seven million people in North America. Currently, the reference standard for assessing scoliosis is based on the manual assignment of Cobb angles at the site of the curvature center. This manual process is time consuming and unreliable as it is affected by inter- and intra-observer variance. To overcome these inaccuracies, machine learning (ML) methods can be used to automate the Cobb angle measurement process. This paper proposes to address the Cobb angle measurement task using YOLACT, an instance segmentation model. The proposed method first segments the vertebrae in an X-Ray image using YOLACT, then it tracks the important landmarks using the minimum bounding box approach. Lastly, the extracted landmarks are used to calculate the corresponding Cobb angles. The model achieved a Symmetric Mean Absolute Percentage Error (SMAPE) score of 10.76%, demonstrating the reliability of this process in both vertebra localization and Cobb angle measurement

Comparative proteomics study on liver mitochondria of primary biliary cirrhosis mouse model

BACKGROUND: Primary biliary cirrhosis (PBC) is a liver specific chronic disease with unclear pathogenesis, especially for the early stage molecular events. The mitochondrion is a multi-functional organelle associated with various diseases including PBC. The purpose of this study was to discover the alterations in the mitochondria proteome using an early stage PBC mouse model for revealing the possible pathogenesis mechanisms in the early stages of PBC. METHODS: Mouse model of early stage of PBC was constructed by consecutive administration of poly I:C. Mitochondria of mouse models and controls were purified and comparative proteomics was performed by iTRAQ technology. Then, differentially expressed proteins were validated by western blotting. RESULTS: In total 354 proteins that satisfied the criteria for comparative proteomics study were identified. Of them, nine proteins were downregulated and 20 were up-regulated in liver mitochondria of PBC mouse model. Most differentially expressed proteins are associated with oxidation-reduction and lipid metabolism, and some are involved in the biosynthesis of steroid hormone and primary bile acid. Interestingly, four proteins (HCDH, CPT I, DECR, ECHDC2) involved in the fatty acid beta-oxidation were all upregulated. CONCLUSIONS: iTRAQ is a powerful tool for comparative proteomics study of PBC mouse model and differentially expressed proteins in mitochondria proteome of PBC mouse model provide insights for the pathogenesis mechanism at early stage of PBC

Visual Relationship Detection with Relative Location Mining

Visual relationship detection, as a challenging task used to find and distinguish the interactions between object pairs in one image, has received much attention recently. In this work, we propose a novel visual relationship detection framework by deeply mining and utilizing relative location of object-pair in every stage of the procedure. In both the stages, relative location information of each object-pair is abstracted and encoded as auxiliary feature to improve the distinguishing capability of object-pairs proposing and predicate recognition, respectively; Moreover, one Gated Graph Neural Network(GGNN) is introduced to mine and measure the relevance of predicates using relative location. With the location-based GGNN, those non-exclusive predicates with similar spatial position can be clustered firstly and then be smoothed with close classification scores, thus the accuracy of top $n$ recall can be increased further. Experiments on two widely used datasets VRD and VG show that, with the deeply mining and exploiting of relative location information, our proposed model significantly outperforms the current state-of-the-art.Comment: Accepted to ACM MM 201

Impacts of Surface Depletion on the Plasmonic Properties of Doped Semiconductor Nanocrystals

Degenerately doped semiconductor nanocrystals (NCs) exhibit a localized surface plasmon resonance (LSPR) in the infrared range of the electromagnetic spectrum. Unlike metals, semiconductor NCs offer tunable LSPR characteristics enabled by doping, or via electrochemical or photochemical charging. Tuning plasmonic properties through carrier density modulation suggests potential applications in smart optoelectronics, catalysis, and sensing. Here, we elucidate fundamental aspects of LSPR modulation through dynamic carrier density tuning in Sn-doped Indium Oxide NCs. Monodisperse Sn-doped Indium Oxide NCs with various doping level and sizes were synthesized and assembled in uniform films. NC films were then charged in an in situ electrochemical cell and the LSPR modulation spectra were monitored. Based on spectral shifts and intensity modulation of the LSPR, combined with optical modeling, it was found that often-neglected semiconductor properties, specifically band structure modification due to doping and surface states, strongly affect LSPR modulation. Fermi level pinning by surface defect states creates a surface depletion layer that alters the LSPR properties; it determines the extent of LSPR frequency modulation, diminishes the expected near field enhancement, and strongly reduces sensitivity of the LSPR to the surroundings

Enzyme-linked immunosorbent assay of changes in serum levels of growth hormone (cGH) in common carps (Cyprinus carpio)

The aim of the present study was to purify the common native carp growth hormone (ncGH), produce monoclonal antibodies (mAbs) to common native carp growth hormone (ncGH), and further enhance the sensitivity of enzyme-linked immunosorbent assays (ELISA) for ncGH. Additionally, we investigated changes in serum ncGH levels in carps raised in different environmental conditions. The recombinant grass carp (Ctenopharyngodon idella) growth hormone was purified and used as antigen to immunize the rabbit. The natural ncGH was isolated from the pituitaries of common carp. SDS-PAGE and Western blot utilizing the polyclonal anti-rgcGH antibody confirmed the purification of ncGH from pituitaries. Purified ncGH was then used as an immunogen in the B lymphocyte hybridoma technique. A total of 14 hybridoma cell lines (FMU-cGH 1-14) were established that were able to stably secrete mAbs against ncGH. Among them, eight clones (FMU-cGH1-6, 12 and 13) were successfully used for Western blot while nine clones (FMU-cGH 1-7, 9 and 10) were used in fluorescent staining and immunohistochemistry. Epitope mapping by competitive ELISA demonstrated that these mAbs recognized five different epitopes. A sensitive sandwich ELISA for detection of ncGH was developed using FMU-cGH12 as the coating mAb and FMU-cGH6 as the enzyme labeled mAb. This detection system was found to be highly stable and sensitive, with detection levels of 70 pg/mL. Additionally, we found that serum ncGH levels in restricted food group and in the net cage group increased 6.9-and 5.8-fold, respectively, when compared to controls, demonstrating differences in the GH stress response in common carp under different living conditions.The aim of the present study was to purify the common native carp growth hormone (ncGH), produce monoclonal antibodies (mAbs) to common native carp growth hormone (ncGH), and further enhance the sensitivity of enzyme-linked immunosorbent assays (ELISA) for ncGH. Additionally, we investigated changes in serum ncGH levels in carps raised in different environmental conditions. The recombinant grass carp (Ctenopharyngodon idella) growth hormone was purified and used as antigen to immunize the rabbit. The natural ncGH was isolated from the pituitaries of common carp. SDS-PAGE and Western blot utilizing the polyclonal anti-rgcGH antibody confirmed the purification of ncGH from pituitaries. Purified ncGH was then used as an immunogen in the B lymphocyte hybridoma technique. A total of 14 hybridoma cell lines (FMU-cGH 1-14) were established that were able to stably secrete mAbs against ncGH. Among them, eight clones (FMU-cGH1-6, 12 and 13) were successfully used for Western blot while nine clones (FMU-cGH 1-7, 9 and 10) were used in fluorescent staining and immunohistochemistry. Epitope mapping by competitive ELISA demonstrated that these mAbs recognized five different epitopes. A sensitive sandwich ELISA for detection of ncGH was developed using FMU-cGH12 as the coating mAb and FMU-cGH6 as the enzyme labeled mAb. This detection system was found to be highly stable and sensitive, with detection levels of 70 pg/mL. Additionally, we found that serum ncGH levels in restricted food group and in the net cage group increased 6.9-and 5.8-fold, respectively, when compared to controls, demonstrating differences in the GH stress response in common carp under different living conditions

Fatty acid metabolites of Dendrobium nobile were positively correlated with representative endophytic fungi at altitude

IntroductionAltitude, as a comprehensive ecological factor, regulates the growth and development of plants and microbial distribution. Dendrobium nobile (D. nobile) planted in habitats at different elevations in Chishui city, also shows metabolic differences and endophytes diversity. What is the triangular relationship between altitude, endophytes, and metabolites?MethodsIn this study, the diversity and species of endophytic fungi were tested by ITS sequencing and metabolic differences in plants were tested by UPLC–ESI–MS/MS. Elevation regulated the colonization of plant endophytic fungal species and fatty acid metabolites in D. nobile.ResultsThe results indicate that and high altitude was better for the accumulation of fatty acid metabolites. Therefore, the high-altitude characteristic endophytic floras were screened, and the correlation with fatty acid metabolites of plants was built. The colonization of T. rubrigenum, P. Incertae sedis unclassified, Phoma. cf. nebulosa JZG 2008 and Basidiomycota unclassified showed a significantly positive correlation with fatty acid metabolites, especially 18-carbon-chain fatty acids, such as (6Z,9Z,12Z)-octadeca-6,9,12-trienoic acid, 3,7,11,15-tetramethyl-12-oxohexadeca-2,4-dienoic acid and Octadec-9-en-12-ynoic acid. What is more fascinating is these fatty acids are the essential substrates of plant hormones.DiscussionConsequently, it was speculated that the D. nobile- colonizing endophytic fungi stimulated or upregulated the synthesis of fatty acid metabolites and even some plant hormones, thus affecting the metabolism and development of D. nobile