5 research outputs found
Caspase‐8 variant G regulates rheumatoid arthritis fibroblast‐like synoviocyte aggressive behavior
Objective:
Fibroblast-like synoviocytes (FLS) play a pivotal role in rheumatoid arthritis (RA) by contributing to synovial inflammation and progressive joint damage. An imprinted epigenetic state is associated with the FLS aggressive phenotype. We identified CASP8 (encoding for caspase-8) as a differentially marked gene and evaluated its pathogenic role in RA FLSs.
Methods:
RA FLS lines were obtained from synovial tissues at arthroplasty and used at passage 5-8. Caspase-8 was silenced using small interfering RNA, and its effect was determined in cell adhesion, migration and invasion assays. Quantitative reverse transcription PCR and western blot were used to assess gene and protein expression, respectively. A caspase-8 selective inhibitor was used determine the role of enzymatic activity on FLS migration and invasion. Caspase-8 isoform transcripts and epigenetic marks in FLSs were analyzed in FLS public databases. Crystal structures of caspase-8B and G were determined.
Results:
Caspase-8 deficiency in RA FLSs reduced cell adhesion, migration, and invasion independent of its catalytic activity. Epigenetic and transcriptomic analyses of RA FLSs revealed that a specific caspase-8 isoform, variant G, is the dominant isoform expressed (~80% of total caspase-8) and induced by PDGF. The crystal structures of caspase-8 variant G and B were identical except for a unique unstructured 59 amino acid N-terminal domain in variant G. Selective knockdown of caspase-8G was solely responsible for the effects of caspase-8 on calpain activity and cell invasion in FLS.
Conclusion:
Blocking caspase-8 variant G could decrease cell invasion in diseases like RA without the potential deleterious effects of nonspecific caspase-8 inhibition
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Recognize basic emotional statesin speech by machine learning techniques using mel-frequency cepstral coefficient features
Speech Emotion Recognition (SER) has been widely used in many fields, such as smart home assistants commonly found in the market. Smart home assistants that could detect the user’s emotion would improve the communication between a user and the assistant enabling the assistant to offer more productive feedback. Thus, the aim of this work is to analyze emotional states in speech and propose a suitable algorithm considering performance verses complexity for deployment in smart home devices. The four emotional speech sets were selected from the Berlin Emotional Database (EMO-DB) as experimental data, 26 MFCC features were extracted from each type of emotional speech to identify the emotions of happiness, anger, sadness and neutrality. Then, speaker-independent experiments for our Speech emotion Recognition (SER) were conducted by using the Back Propagation Neural Network (BPNN), Extreme Learning Machine (ELM), Probabilistic Neural Network (PNN) and Support Vector Machine (SVM). Synthesizing the recognition accuracy and processing time, this work shows that the performance of SVM was the best among the four methods as a good candidate to be deployed for SER in smart home devices. SVM achieved an overall accuracy of 92.4% while offering low computational requirements when training and testing. We conclude that the MFCC features and the SVM classification models used in speaker-independent experiments are highly effective in the automatic prediction of emotion
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Caspase-8 Variant G Regulates Rheumatoid Arthritis Fibroblast-Like Synoviocyte Aggressive Behavior.
ObjectiveFibroblast-like synoviocytes (FLS) play a pivotal role in rheumatoid arthritis (RA) by contributing to synovial inflammation and progressive joint damage. An imprinted epigenetic state is associated with the FLS aggressive phenotype. We identified CASP8 (encoding for caspase-8) as a differentially marked gene and evaluated its pathogenic role in RA FLSs.MethodsRA FLS lines were obtained from synovial tissues at arthroplasty and used at passage 5-8. Caspase-8 was silenced using small interfering RNA, and its effect was determined in cell adhesion, migration and invasion assays. Quantitative reverse transcription PCR and western blot were used to assess gene and protein expression, respectively. A caspase-8 selective inhibitor was used determine the role of enzymatic activity on FLS migration and invasion. Caspase-8 isoform transcripts and epigenetic marks in FLSs were analyzed in FLS public databases. Crystal structures of caspase-8B and G were determined.ResultsCaspase-8 deficiency in RA FLSs reduced cell adhesion, migration, and invasion independent of its catalytic activity. Epigenetic and transcriptomic analyses of RA FLSs revealed that a specific caspase-8 isoform, variant G, is the dominant isoform expressed (~80% of total caspase-8) and induced by PDGF. The crystal structures of caspase-8 variant G and B were identical except for a unique unstructured 59 amino acid N-terminal domain in variant G. Selective knockdown of caspase-8G was solely responsible for the effects of caspase-8 on calpain activity and cell invasion in FLS.ConclusionBlocking caspase-8 variant G could decrease cell invasion in diseases like RA without the potential deleterious effects of nonspecific caspase-8 inhibition