NEMO Binds Ubiquitinated TANK-Binding Kinase 1 (TBK1) to Regulate Innate Immune Responses to RNA Viruses

RIG-I-like receptors (RLR) are intracellular sensors utilized by nearly all cell types for recognition of viral RNA, initiation of antiviral defense, and induction of type I interferons (IFN). TBK1 is a critical kinase implicated in RLR-dependent IFN transcription. Posttranslational modification of TBK1 by K63-linked ubiquitin is required for RLR driven signaling. However, the TBK1 ubiquitin acceptor sites and the function of ubiquitinated TBK1 in the signaling cascade are unknown. We now show that TBK1 is ubiquitinated on residues K69, K154, and K372 in response to infection with RNA virus. The K69 and K154 residues are critical for innate antiviral responses and IFN production. Ubiquitinated TBK1 recruits the downstream adaptor NEMO through ubiquitin binding domains. The assembly of the NEMO/TBK1 complex on the mitochondrial protein MAVS leads to activation of TBK1 kinase activity and phosphorylation of the transcription factor, interferon response factor 3. The combined results refine current views of RLR signaling, define the role of TBK1 polyubiquitination, and detail the mechanisms involved in signalosome assembly

Effects of different dietary energy and protein levels and sex on growth performance, carcass characteristics and meat quality of F1 Angus × Chinese Xiangxi yellow cattle

BACKGROUND: The experiment evaluated the effect of nutrition levels and sex on the growth performance, carcass characteristics and meat quality of F1 Angus × Chinese Xiangxi yellow cattle. METHODS: During the background period of 184 d,23 steers and 24 heifers were fed the same ration,then put into a 2 × 2 × 2 factorial arrangement under two levels of - dietary energy (TDN: 70/80% DM), protein (CP: 11.9/14.3% DM) and sex (S: male/female) during the finishing phase of 146 d. The treatments were - (1) high energy/low protein (HELP), (2) high energy/high protein (HEHP), (3) low energy/low protein (LELP) and (4) low energy/high protein (LEHP). Each treatment used 6 steers and 6 heifers, except for HELP- 5 steers and 6 heifers. RESULTS: Growth rate and final carcass weight were unaffected by dietary energy and protein levels or by sex. Compared with the LE diet group, the HE group had significantly lower dry matter intake (DMI, 6.76 vs. 7.48 kg DM/d), greater chest girth increments (46.1 vs. 36.8 cm), higher carcass fat (19.9 vs.16.3%) and intramuscular fat content (29.9 vs. 22.8% DM). The HE group also had improved yields of top and medium top grade commercial meat cuts (39.9 vs.36.5%). The dressing percentage was higher for the HP group than the LP group (53.4 vs. 54.9%). Steers had a greater length increment (9.0 vs. 8.3 cm), but lower carcass fat content (16.8 vs. 19.4%) than heifers. The meat quality traits (shear force value, drip loss, cooking loss and water holding capacity) were not affected by treatments or sex, averaging 3.14 kg, 2.5, 31.5 and 52.9%, respectively. The nutritive profiles (both fatty and amino acid composition) were not influenced by the energy or protein levels or by sex. CONCLUSIONS: The dietary energy and protein levels and sex significantly influenced the carcass characteristics and chemical composition of meat but not thegrowth performance, meat quality traits and nutritive profiles

Factor Structure and Measurement Invariance for the Cognitive Emotion Regulation Questionnaire (CERQ) Among Women Newly Diagnosed With Breast Cancer

BackgroundGiven that emotion regulation counts for much in breast cancer, it is important to fully understand its construct. The cognitive emotion regulation questionnaire (CERQ) is a widely applied instrument for measuring conscious cognitive coping strategies in both general and clinical samples; however, there are no data on its factor structure in women with breast cancer, not to mention evidence of measurement invariance (MI) across sociodemographic variables. Thus, the purpose of the present study was to examine the latent factor structure and MI between different sociodemographic groups for CERQ in specific patients.MethodsThe sample consisted of 1032 women newly diagnosed with breast cancer, with a mean age of 47.54 years (SD = 8.51). The latent factor structure for CERQ was tested using confirmatory factor analysis (CFA). Further, MI various sociodemographic variables was evaluated by a series of multiple-group CFA process.ResultsThe nine-factor CFA model was an adequate fit for the data collected in women with breast cancer. Also, this nine-factor structure had strong factorial invariance across age, place of residence, educational levels, and employment status.ConclusionThis study firstly examined the latent factor structure for CERQ among Chinese women with malignancy and MI across various sociodemographic variables, which deepens the understanding of the construct for CERQ as a useful tool for assessing patients’ conscious cognitive component of emotion regulation based on self-report

An optimized parameter design method of SiC/Si hybrid switch considering turn-off current spike

In order to reduce the switching loss of SiC MOSFET/Si IGBT (SiC/Si) hybrid switch, the switching mode that turn off the Si IGBT prior to the SiC MOSFET is generally adopted to achieved the zero-voltage switching operation of IGBT. The minority carrier in N-base region of the IGBT are recombined in the form of exponential attenuation due to the conductivity modulation effect. When the SiC MOSFET is turned off, if the carrier recombination process of the IGBT is not finished, it needs to bear a large collector–emitter voltage change rate, resulting in apparent current spike. This current spike will increase the current stress of the device and produce additional turn-off loss. The equivalent model of double pulse test circuit of SiC/Si hybrid switch considering parasitic parameters is established, and the turn-off transient process is given analytically. The influence of turn-off delay time, circuit parameters and working conditions on current spike are analysed quantitatively. Combined with the consideration of device stress and comprehensive turn-off loss, an optimized circuit design method of SiC/Si hybrid switch considering turn-off current peak is proposed, which provides theoretical and design guidance for high reliability and high efficiency SiC/Si-based converters

Influenza A virus-host protein interactions control viral pathogenesis

The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly transmissible respiratory pathogen and represents a continued threat to global health with considerable economic and social impact. IAV is a zoonotic virus that comprises a plethora of strains with different pathogenic profiles. The different outcomes of viral pathogenesis are dependent on the engagement between the virus and the host cellular protein interaction network. The interactions may facilitate virus hijacking of host molecular machinery to fulfill the viral life cycle or trigger host immune defense to eliminate the virus. In recent years, much effort has been made to discover the virus-host protein interactions and understand the underlying mechanisms. In this paper, we review the recent advances in our understanding of IAV-host interactions and how these interactions contribute to host defense and viral pathogenesis.Peer reviewedPhysiological Science

Discovery and Identification of Pyrazolopyramidine Analogs as Novel Potent Androgen Receptor Antagonists

Androgen receptor (AR), an important target in the current androgen derivation therapy, plays a critical role in the development and progress of prostate cancer (PCa). Nonsteroidal antiandrogens, such as enzalutamide and bicalutamide, are commonly used in clinic to treat PCa. Though they are very effective at the beginning, drug resistance problem appears after about 18 months. One of the reasons is that these antiandrogens share similar structure skeleton. Therefore, it is urgent to discover novel antiandrogens with different skeletons for resistance problem. Herein, we combined structure- and ligand-based methodologies for virtual screening chemical databases to identify potent AR antagonists. Then the cytotoxic activities of the screened hit samples were evaluated by using LNCaP prostate cancer cells. Virtual screening and biological evaluation assay results suggest that several chemicals with novel pyrazolopyrimidine skeleton can inhibit the proliferation of prostate cancer cells with similar, or even higher, bioactivities to bicalutamide. AR reporter gene assay experiments proved that Compound III showed potential antagonistic effects. In addition, molecular dynamics simulations results proved that Compound III can properly bind to AR and prevent helix 12 (H12) from closing to distort the formation of activation function 2 (AF2) site, resulting in the invalid transcription. Hence, pyrazolopyrimidine was discovered as a novel, potent and promising antiandrogen skeleton deserved to be further studied

Pre-train, Adapt and Detect: Multi-Task Adapter Tuning for Camouflaged Object Detection

Camouflaged object detection (COD), aiming to segment camouflaged objects which exhibit similar patterns with the background, is a challenging task. Most existing works are dedicated to establishing specialized modules to identify camouflaged objects with complete and fine details, while the boundary can not be well located for the lack of object-related semantics. In this paper, we propose a novel ``pre-train, adapt and detect" paradigm to detect camouflaged objects. By introducing a large pre-trained model, abundant knowledge learned from massive multi-modal data can be directly transferred to COD. A lightweight parallel adapter is inserted to adjust the features suitable for the downstream COD task. Extensive experiments on four challenging benchmark datasets demonstrate that our method outperforms existing state-of-the-art COD models by large margins. Moreover, we design a multi-task learning scheme for tuning the adapter to exploit the shareable knowledge across different semantic classes. Comprehensive experimental results showed that the generalization ability of our model can be substantially improved with multi-task adapter initialization on source tasks and multi-task adaptation on target tasks