A negative reciprocal regulatory axis between cyclin D1 and HNF4α modulates cell cycle progression and metabolism in the liver.

Hepatocyte nuclear factor 4α (HNF4α) is a master regulator of liver function and a tumor suppressor in hepatocellular carcinoma (HCC). In this study, we explore the reciprocal negative regulation of HNF4α and cyclin D1, a key cell cycle protein in the liver. Transcriptomic analysis of cultured hepatocyte and HCC cells found that cyclin D1 knockdown induced the expression of a large network of HNF4α-regulated genes. Chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated that cyclin D1 inhibits the binding of HNF4α to thousands of targets in the liver, thereby diminishing the expression of associated genes that regulate diverse metabolic activities. Conversely, acute HNF4α deletion in the liver induces cyclin D1 and hepatocyte cell cycle progression; concurrent cyclin D1 ablation blocked this proliferation, suggesting that HNF4α maintains proliferative quiescence in the liver, at least, in part, via repression of cyclin D1. Acute cyclin D1 deletion in the regenerating liver markedly inhibited hepatocyte proliferation after partial hepatectomy, confirming its pivotal role in cell cycle progression in this in vivo model, and enhanced the expression of HNF4α target proteins. Hepatocyte cyclin D1 gene ablation caused markedly increased postprandial liver glycogen levels (in a HNF4α-dependent fashion), indicating that the cyclin D1-HNF4α axis regulates glucose metabolism in response to feeding. In AML12 hepatocytes, cyclin D1 depletion led to increased glucose uptake, which was negated if HNF4α was depleted simultaneously, and markedly elevated glycogen synthesis. To summarize, mutual repression by cyclin D1 and HNF4α coordinately controls the cell cycle machinery and metabolism in the liver.

Use of Beauveria bassiana to control northern fowl mites (Ornithonyssus sylviarum) on roosters in an agricultural research facility.

Treatment of Northern fowl mite (Ornithonyssus sylviarum) infestation on poultry in research facilities can be challenging. The mite has a rapid reproductive cycle (egg to adult in 5 to 7 d), and chemical treatments can be toxic to birds, personnel, and the environment. In addition, antimite treatment may interfere with experimental research designs. The current study evaluated the efficacy of topical application of an entomopathogenic fungus, Beauveria bassiana, in the treatment of a naturally occurring infestation of Northern fowl mites in pen-housed roosters (n = 14; age, 18 mo). Two groups of 7 roosters each were used in 2 experiments: Beauveria (30 mL, 2.9 × 10(10) spores per bird) compared with water (30 mL, control), and Beauveria compared with the common topical organophosphate agent tetrachlorvinphos-dichlorvos (30 mL). We also assessed a higher dose of Beauveria (300 mL, 2.9 × 10(11) spores per bird) in the 7 birds that were not exposed to tetrachlorvinphos-dichlorvos. Beauveria reduced mite levels relative to the control group but did not outperform tetrachlorvinphos-dichlorvos when used at an equal volume and frequency. Increasing the volume and frequency of Beauveria application improved outcomes such that visual inspection failed to detect any mites. The results presented here suggest that, when applied in sufficient doses, Beauveria effectively reduces mites on poultry and can be an important part of an integrated pest management program. Additional research is needed to document the most effective dose, frequency, and location of B. bassiana application to control Northern fowl mites in poultry.