Alternative splicing can increase the diversity of gene functions by generating multiple isoforms with different sequences and functions. However, the extent to which splicing events have functional ...consequences remains unclear and predicting the impact of splicing events on protein activity is limited to gene-specific analysis. To accelerate the identification of functionally relevant alternative splicing events we created SAPFIR, a predictor of protein features associated with alternative splicing events. This webserver tool uses InterProScan to predict protein features such as functional domains, motifs and sites in the human and mouse genomes and link them to alternative splicing events. Alternative protein features are displayed as functions of the transcripts and splice sites. SAPFIR could be used to analyze proteins generated from a single gene or a group of genes and can directly identify alternative protein features in large sequence data sets. The accuracy and utility of SAPFIR was validated by its ability to rediscover previously validated alternative protein domains. In addition, our de novo analysis of public datasets using SAPFIR indicated that only a small portion of alternative protein domains was conserved between human and mouse, and that in human, genes involved in nervous system process, regulation of DNA-templated transcription and aging are more likely to produce isoforms missing functional domains due to alternative splicing. Overall SAPFIR represents a new tool for the rapid identification of functional alternative splicing events and enables the identification of cellular functions affected by a defined splicing program. SAPFIR is freely available at https://bioinfo-scottgroup.med.usherbrooke.ca/sapfir/, a website implemented in Python, with all major browsers supported. The source code is available at https://github.com/DelongZHOU/SAPFIR.
The antioxidative activities of a lotus seed epicarp extract in different concentrations (6.25, 12.5, 25, 50 and 100μg.mL−1) in pork homogenates representative of Chinese Cantonese Sausage were ...evaluated using three methods: thiobarbituric acid-reactive substances (TBARS) values, peroxide values (POVs) and acid values (AVs). Also the cytotoxic and anti-obesity effects of the lotus seed epicarp extracts were evaluated using an in vitro 3T3-L1 preadipocyte cell model. Results showed that the lotus seed epicarp extracts were non-toxic and effective in inhibiting preadipocyte differentiation. Supplementation of pork homogenate with lotus seed epicarp extracts was effective in retarding lipid oxidation. Moreover, the antioxidative and preadipocyte differentiation inhibition effects of the lotus seed epicarp extracts were dose-dependent. Thus, the lotus seed epicarp extract might be a good candidate as an antioxidant and anti-obesity natural additive in Chinese Cantonese Sausage.
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•We used a model in which toxicity was induced by Aβ in SH-SY5Y cells.•Salvia miltiorrhiza extract has been shown to be neuroprotective in this model.•It protected cells through ...inhibiting ROS and the mitochondrial apoptotic pathway.
The neurotoxicity of β-amyloid protein (Aβ) contributes significantly to the pathogenesis of Alzheimer’s disease (AD), and hence the attractive therapeutic strategies focusing on the modulation of Aβ-induced neurotoxicity are warranted. The present study aims to investigate the neuroprotection and underlying mechanisms by which Salvia miltiorrhiza Bunge (Lamiaceae) extract (SME) protects against Aβ25–35-induced apoptosis in SH-SY5Y cells. 2h Pre-treatment of SH-SY5Y cells with SME (0.01, 0.1 or 0.2mg raw herb/ml) concentration-dependently attenuated Aβ25–35-induced cell death, as evidenced by the increase in cell viability and decrease in neuronal apoptosis. In addition, SME suppressed the increased intracellular reactive oxygen species levels, decreased the protein expression of cleaved caspase-3, cytosolic cytochrome c, and Bax/Bcl-2 ratio. These findings taken together suggest that SME provides substantial neuroprotection against Aβ25–35-induced neurotoxicity in SH-SY5Y cells, at least in part, via inhibiting oxidative stress and attenuating the mitochondria-dependent apoptotic pathway. The approach used in this study may also be useful for the screening of therapeutic agents for AD and other related neurodegenerative disease.
The CAS-PEAL Large-Scale Chinese Face Database and Baseline Evaluations Wen Gao, Wen Gao; Bo Cao, Bo Cao; Shiguang Shan, Shiguang Shan ...
IEEE transactions on systems, man and cybernetics. Part A, Systems and humans,
2008-Jan., 2008-01-00, 20080101, Volume:
38, Issue:
1
Journal Article
In this paper, we describe the acquisition and contents of a large-scale Chinese face database: the CAS-PEAL face database. The goals of creating the CAS-PEAL face database include the following: 1) ...providing the worldwide researchers of face recognition with different sources of variations, particularly pose, expression, accessories, and lighting (PEAL), and exhaustive ground-truth information in one uniform database; 2) advancing the state-of-the-art face recognition technologies aiming at practical applications by using off-the-shelf imaging equipment and by designing normal face variations in the database; and 3) providing a large-scale face database of Mongolian. Currently, the CAS-PEAL face database contains 99 594 images of 1040 individuals (595 males and 445 females). A total of nine cameras are mounted horizontally on an arc arm to simultaneously capture images across different poses. Each subject is asked to look straight ahead, up, and down to obtain 27 images in three shots. Five facial expressions, six accessories, and 15 lighting changes are also included in the database. A selected subset of the database (CAS-PEAL-R1, containing 30 863 images of the 1040 subjects) is available to other researchers now. We discuss the evaluation protocol based on the CAS-PEAL-R1 database and present the performance of four algorithms as a baseline to do the following: 1) elementarily assess the difficulty of the database for face recognition algorithms; 2) preference evaluation results for researchers using the database; and 3) identify the strengths and weaknesses of the commonly used algorithms.
Abstract
RBFOX2 controls the splicing of a large number of transcripts implicated in cell differentiation and development. Parsing RNA-binding protein datasets, we uncover that RBFOX2 can interact ...with hnRNPC, hnRNPM and SRSF1 to regulate splicing of a broad range of splicing events using different sequence motifs and binding modes. Using immunoprecipitation, specific RBP knockdown, RNA-seq and splice-sensitive PCR, we show that RBFOX2 can target splice sites using three binding configurations: single, multiple or secondary modes. In the single binding mode RBFOX2 is recruited to its target splice sites through a single canonical binding motif, while in the multiple binding mode RBFOX2 binding sites include the adjacent binding of at least one other RNA binding protein partner. Finally, in the secondary binding mode RBFOX2 likely does not bind the RNA directly but is recruited to splice sites lacking its canonical binding motif through the binding of one of its protein partners. These dynamic modes bind distinct sets of transcripts at different positions and distances relative to alternative splice sites explaining the heterogeneity of RBFOX2 targets and splicing outcomes.
Industrial robots have great potential to machine large parts. However, the vibration or chattering induced by their inherent weak stiffness can easily damage or break the tool. Therefore, this paper ...introduced a novel tool wear monitoring method for robotic milling. Firstly, a multi-domain features extraction method was proposed to obtain local features. Then, a novel deep learning model with two parallel a parallel bidirectional long short-term memory networks (BiLSTM) (Vibration branch and Cutting Force branch) was introduced to fuse the multi-domain features and learn the time dependence patterns. The proposed method was verified on both based on robot milling Al7050-T7451 workpiece dataset and the 2010 prognostics health management (PHM) dataset. The experiment results showed that the proposed method acquired an excellent predication accuracy and strong adaptability to the change of cutting parameters. The results show that the average root mean square error (RMSE) for wear recognition based on the robot milling dataset is 10.61, with an average mean absolute error (MAE) of 9.104. The average RMSE for wear recognition based on the computerized numerical control (CNC) milling dataset is 7.83, with an average MAE of 6.62.
Stretchable electronic sensing devices are defining the path toward wearable electronics. High-performance flexible strain sensors attached on clothing or human skin are required for potential ...applications in the entertainment,health monitoring, and medical care sectors. In this work,conducting copper electrodes were fabricated onpolydimethylsiloxane as sensitive stretchable microsensors by integrating laser direct writing and transfer printing approaches. The copper electrode was reduced from copper salt using laser writing rather than the general approach of printing with pre-synthesized copper or copper oxide nanoparticles. An electrical resistivity of 96 l X cm was achieved on 40-lm-thick Cu electrodes on flexible substrates. The motion sensing functionality successfully demonstrated a high sensitivity and mechanical robustness.This in situ fabrication method leads to a path toward electronic devices on flexible substrates.
Dilated cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), an inherited degenerative disease of the cardiac and skeletal muscle caused by absence of the protein ...dystrophin. We showed one hallmark of DMD cardiomyopathy is the dysregulation of cardiac gap junction channel protein connexin-43 (Cx43). Proper Cx43 localization and function at the cardiac intercalated disc (ID) is regulated by post-translational phosphorylation of Cx43-carboxy-terminus residues S325/S328/S330 (pS-Cx43). Concurrently, Cx43 traffics along microtubules (MTs) for targeted delivery to the ID. In DMD hearts, absence of dystrophin results in a hyperdensified and disorganized MT cytoskeleton, yet the link with pS-Cx43 remains unaddressed. To gain insight into the relationship between MTs and pS-Cx43, DMD mice (mdx) and pS-Cx43-deficient (mdxS3A) mice were treated with an inhibitor of MT polymerization, colchicine (Colch). Colch treatment protected mdx, not mdxS3A mice, against Cx43 remodeling, improved MT directionality, and enhanced pS-Cx43/tubulin interaction. Likewise, severe arrhythmias were prevented in isoproterenol-stressed mdx, not mdxS3A mice. Furthermore, MT directionality was improved in pS-Cx43-mimicking mdx (mdxS3E). Mdxutr
and mdxutr
S3A mice, lacking one copy of dystrophin homolog utrophin, displayed enhanced cardiac fibrosis and reduced lifespan compared with mdxutr
S3E; and Colch treatment corrected cardiac fibrosis in mdxutr
but not mdxutr
S3A. Collectively, the data suggest that improved MT directionality reduces Cx43 remodeling and that pS-Cx43 is necessary and sufficient to regulate MT organization, which plays crucial role in correcting cardiac dysfunction in DMD mice. Thus, identification of novel organizational mechanisms acting on pS-Cx43-MT will help develop novel cardioprotective therapies for DMD cardiomyopathy.
We found that colchicine administration to Cx43-phospho-deficient dystrophic mice fails to protect against Cx43 remodeling. Conversely, Cx43-phospho-mimic dystrophic mice display a normalized MT network. We envision a bidirectional regulation whereby correction of the dystrophic MTs leads to correction of Cx43 remodeling, which in turn leads to further correction of the MTs. Our findings suggest a link between phospho-Cx43 and MTs that provides strong foundations for novel therapeutics in DMD cardiomyopathy.
Serine‐rich splicing factor 3 (SRSF3) was recently reported as being necessary to preserve RNA stability via an mTOR mechanism in a cardiac mouse model in adulthood. Here, we demonstrate the link ...between Srsf3 and mitochondrial integrity in an embryonic cardiomyocyte‐specific Srsf3 conditional knockout (cKO) mouse model. Fifteen‐day‐old Srsf3 cKO mice showed dramatically reduced (below 50%) survival and reduced the left ventricular systolic performance, and histological analysis of these hearts revealed a significant increase in cardiomyocyte size, confirming the severe remodeling induced by Srsf3 deletion. RNA‐seq analysis of the hearts of 5‐day‐old Srsf3 cKO mice revealed early changes in expression levels and alternative splicing of several transcripts related to mitochondrial integrity and oxidative phosphorylation. Likewise, the levels of several protein complexes of the electron transport chain decreased, and mitochondrial complex I‐driven respiration of permeabilized cardiac muscle fibers from the left ventricle was impaired. Furthermore, transmission electron microscopy analysis showed disordered mitochondrial length and cristae structure. Together with its indispensable role in the physiological maintenance of mouse hearts, these results highlight the previously unrecognized function of Srsf3 in regulating the mitochondrial integrity.
An output-feedback based partial integrated guidance and control (IGC) law for missile interceptor is proposed with the smooth finite time convergence property. Firstly, a novel outputfeedback based ...smooth sliding mode control is proposed for a class of nonlinear systems in the presence of immeasurable state and disturbance. The finite time convergence property of this control scheme is proved based on the Lyapunov stability and homogeneous principle. Then, the proposed control method is applied to the design of partial IGC law. A kind of scaling methods is also developed to reach the rapid convergence of the system. An important dominance of this control scheme is the smooth characteristic,which may result in chattering free convergence. The simulation results indicate the high precision and smooth elevator deflection of the proposed output feedback base partial IGC law.
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