Pivotal Role of Toll-Like Receptors 2 and 4, Its Adaptor Molecule MyD88, and Inflammasome Complex in Experimental Tubule-Interstitial Nephritis

Tubule-interstitial nephritis (TIN) results in decreased renal function and interstitial inflammation, which ultimately leads to fibrosis. Excessive adenine intake can cause TIN because xanthine dehydrogenase (XDH) can convert this purine into an insoluble compound, which precipitates in the tubuli. Innate immune sensors, such as Toll-like receptors (TLR) and inflammasome complex, play a crucial role in the initiation of inflammation. The aim of this study was to evaluate the roles of TLR-2 and -4, Myd88 and inflammasome complex in an experimental model of TIN. Here, we show that wild-type (WT) mice fed adenine-enriched food exhibited significant renal dysfunction and enhanced cellular infiltration accompanied by collagen deposition. They also presented higher gene and protein expression of pro-inflammatory cytokines. In contrast, TLR-2, -4, MyD88, ASC and Caspase-1 KO mice showed renoprotection associated with expression of inflammatory molecules at levels comparable to controls. Furthermore, treatment of WT animals with allopurinol, an XDH inhibitor, led to reduced levels of uric acid, oxidative stress, collagen deposition and a downregulation of the NF-kB signaling pathway. We concluded that MyD88 signaling and inflammasome participate in the development of TIN. Furthermore, inhibition of XDH seems to be a promising way to therapeutically target the developing inflammatory process

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Influence of feeding time on sexual maturity and carcass composition in female broiler breeders

One thousand two hundred and ninety six Arbor Acres females and 144 males were used to study the influence of feeding time on sexual maturity and carcass composition. Treatments were: T1 = feeding at 6:30 am, T2 = 50% feeding at 6:30 am and 50% at 3:30 pm (dual), T3 = feeding at 11:00 am, T4 = feeding at 3:30 pm. Nutrition and management were as recommended to the commercial line. Variables studied were: sexual maturity at 5% production (SM), mean egg production percentage (PEP) body weight (BW), carcass composition, tibia weight (TIBW) and tibia calcium (Ca) and phosphorus (P) contents. Analysis of variance was used, and the means were compared using Student's t test. T2 females reached SM at 25.92 weeks, which was earlier (p<0.01) than the other treatments. PEP was greater (p<0.01) for T1 and T2 than for the other treatments. BW was greater in T1 and smaller in T4 (p<0.05) than in the other treatments. TIBW was greater in T3 than in T1 and T2 (p<0.05), with no effect (p>0.10) on carcass dry matter (DM), ether extract (EE), crude protein (CP) and ash (ASH). DM, EE, TIBW, Ca and P increased (p<0.05) whereas CP and ASH decreased with age. Time of feeding influenced body weight, but not carcass composition. Hens fed twice a day had earlier sexual maturity and similar egg production compared to those fed once at 6:30 am

Performance of female broiler breeders submitted to different feeding schedules

The performance of Arbor Acres broiler breeders (1,296 females; 144 roosters) was evaluated when submitted to the following treatments (T): T1 = feeding at 6:30 a.m. (control); T2 = 50% feeding at 6:30 a.m. and 50% at 3:30 p.m. (dual feeding); T3 = feeding at 11:00 a.m.; and T4 = feeding at 3:30 p.m. Treatments were randomly distributed in 48 pens. There were 27 females and 3 males in each pen and 12 repetitions per treatment. Nutrition and management were as recommended for the commercial strain. It was evaluated age at first egg (AFE), total egg production (TEP), number of days with production above 80% (DAP80), laying peak (P), female mortality (MOR), and gross profit margin (GM) per hen. Data were submitted to analysis of variance and means were compared by Student's t-Test. TEP of T1 (186.3±2.3) and T2 (186.5±1.5) were higher (p0.10) among treatments. GM per hen was better (p<0.05) in T1 and T2 hens. Control and dual treatments were more efficient than other treatments. It was concluded that it is possible to change conventional feeding management's by the dual feeding system