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

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

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

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

Comparison of feeding diets diluted with sorghum-sudangrass silage or low-quality grass on nutrient intake and digestibility and growth performance of Holstein dairy heifers

This study was carried out to evaluate the nutrient intakes and growth of dairy heifers offered an alfalfa silage– corn silage diet (CON; 14.3% crude protein, 61.1% total digestible nutrients, 47.9% neutral detergent fiber) compared with diets containing 1 of 2 types of sorghumsudangrass (SS) silages: conventional or photoperiod sensitive. The objective of the study was to determine the potential to use SS to control dry matter (DM) and nutrient intakes and weight gain. Both diets were similar in nutrient composition, with approximately 13% crude protein, 60 to 61% total digestible nutrients, and 55% neutral detergent fiber. Seventy-two Holstein heifers (16–18 mo at study initiation) were blocked by initial body weight (light = 422 ± 12.8 kg; medium = 455 ± 14.8 kg; heavy = 489 ± 16.7 kg) with 3 pens assigned to each weight block (8 heifers/pen; 24 heifers/block). The 3 diets were randomly allocated to the pens within each block and offered for 12 wk. Heifers offered the CON diet had greater DM, protein, and energy intakes compared with those offered the SS silage-based diets due to the greater neutral detergent fiber concentration of the SS diets. With lower DM and nutrient intakes, average daily gain was in the recommended range (0.8– 1 kg/d for Holstein heifers) for heifers offered the SS silage-based diets (mean of 0.92 kg/d for both SS diets vs. 1.11 kg/d for CON). Sorting behaviors for heifers offered both SS diets were more aggressive against long, medium, and short particles compared with those of heifers offered the CON diet; however, heifers sorted large particles from photoperiod-sensitive silage more aggressively than those from conventional silage. Based on this study, SS silage-based diets can control the DM and energy intakes for heifers and maintain optimum growth rates, with harvesting at a shorter chop length likely helping to alleviate sorting issues

Mechanisms of TGFβ inhibition of LUNG endodermal morphogenesis: The role of TβRII, Smads, Nkx2.1 and Pten

AbstractTransforming growth factor-beta is a multifunctional growth factor with roles in normal development and disease pathogenesis. One such role is in inhibition of lung branching morphogenesis, although the precise mechanism remains unknown. In an explant model, all three TGFβ isoforms inhibited FGF10-induced morphogenesis of mesenchyme-free embryonic lung endoderm. Inhibition of budding by TGFβ was partially abrogated in endodermal explants from Smad3−/− or conditional endodermal-specific Smad4Δ/Δ embryonic lungs. Endodermal explants from conditional TGFβ receptor II knockout lungs were entirely refractive to TGFβ-induced inhibition. Inhibition of morphogenesis was associated with dedifferentiation of endodermal cells as documented by a decrease in key transcriptional factor, NKX2.1 protein, and its downstream target, surfactant protein C (SpC). TGFβ reduced the proliferation of wild-type endodermal cells within the explants as assessed by BrdU labeling. Gene expression analysis showed increased levels of mRNA for Pten, a key regulator of cell proliferation. Conditional, endodermal-specific deletion of Pten overcame TGFβ's inhibitory effect on cell proliferation, but did not restore morphogenesis. Thus, the mechanisms by which TGFβ inhibits FGF10-induced lung endodermal morphogenesis may entail both inhibition of cell proliferation, through increased Pten, as well as inhibition or interference with morphogenetic mediators such as Nkx2.1. Both of the latter are dependent on signaling through TβRII