NF-κB transcription factors are involved in the cellular response to stress, and are regulated by inhibitor (IκB)proteins, which prevent NF-κB-mediated transcription by maintaining NF-κB in the cytoplasm. Proteins from other pathways are also known to regulate NF-κB negatively, notably the glucocorticoid receptor (GR) and IL-4-responsive STAT6. Both pathways were shown to inhibit NF-κB-mediated transcription, by expressing either STAT6 or GR and activating the respective pathways. Using fluorescent fusion proteins, we show that GR alters the timing of activated p65 NF-κB nuclear occupancy by increasing the export rate of p65 and is independent of whether GR is present as a dimer or monomer. Expression of STAT6 was also shown to alter p65 nuclear occupancy but appeared to affect the import rate and hence the overall maximal level of p65 translocation. Activating STAT6 with IL-4 prior to activating NF-κB significantly increased this inhibition. Investigation of IκBa showed that activated STAT6 inhibited TNFα-mediated IκBa phosphorylation and degradation, whereas GR activation did not alter IκBαkinetics. This demonstrates a clear separation of two distinct mechanisms of inhibition by STAT6 and GR upon the NF-κB pathway.
OBJECTIVE To compare body condition score (BCS) and urinalysis variables between dogs with and without calcium oxalate (CaOx) uroliths. DESIGN Case-control study. ANIMALS 46 Miniature Schnauzers, 16 Bichons Frises, and 6 Shih Tzus. PROCEDURES Medical records were reviewed for Miniature Schnauzers, Bichons Frises, and Shih Tzus that were examined between January 2001 and November 2014 for another urolithiasis study or for a urolith removal procedure. Dogs with CaOx uroliths were classified as cases. Dogs without a history of urinary tract disease and with no evidence of radiopaque uroliths on abdominal radiographs were classified as controls. Each case was matched with 1 control on the basis of age (± 2 years), sex, and breed. Body condition score and urinalysis results were compared between cases and controls, and the relationship between BCS and urine pH was analyzed. RESULTS Median BCS was significantly greater for cases than controls, although the proportion of overweight dogs did not differ significantly between the 2 groups. Urine pH was negatively associated with age, but was not associated with BCS or the presence of CaOx uroliths. Cases infrequently had acidic urine or CaOx crystalluria but frequently had hematuria and proteinuria. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with CaOx uroliths had a greater median BCS than control dogs, but the clinical importance of that finding was unclear. Acidic urine and CaOx crystalluria were uncommon and not adequate predictors of CaOx urolith status. Hematuria and proteinuria were commonly observed in dogs with CaOx urolithiasis, but they are not pathognomonic for that condition.
Grasslands are imperiled due to land conversion, fragmentation, woody encroachment, population growth, and global warming. What remains of intact grasslands are vital for the ecosystem services they provide. Wildlife species native to the North American Great Plains evolved in response to very specific and differing habitats. Without variation in vegetation structure and composition (heterogeneity) the number of species that can thrive is minimized, as are the interconnected ecosystem services. Landowners’ assistance in the maintenance of grassland ecosystems is essential because Great Plains grasslands are primarily privately managed. Thus, increasing heterogeneity on working rangelands is a partial solution to balancing the needs of wildlife with that of cattle production. This study tested a predictive model of factors influencing attitudes toward heterogeneous and landscape-scale ranch management. An online survey was sent to ranchers within prescribed-burn and grazing groups in the Great Plains. Predictors of landscape-scale management were spirituality, stewardship, social descriptive norms, consideration of future consequences, and participation in grassland activities. The lone predictor of attitudes toward heterogeneous grassland management was consideration of future consequences. Even though the survey targeted groups that were more likely to be higher in heterogeneous attitudes, a vast majority are still following the “manage to the middle” paradigm. It appears these ranchers are unaware of the benefits of a heterogeneous landscape and the compatibility of its associated management techniques with their cattle production goals. To improve the adoption of techniques that promote vegetation heterogeneity, more resources should be devoted to demonstrating how these practices benefit ranchers’ cattle business alongside the larger landscape.
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