Deficiency of the purinergic receptor 2X7 attenuates nonalcoholic steatohepatitis induced by high-fat diet. possible role of the NLRP3 Inflammasome

Molecular mechanisms driving transition from simple steatosis to nonalcoholic steatohepatitis (NASH), a critical step in the progression of nonalcoholic fatty liver disease (NAFLD) to cirrhosis, are poorly defined. This study aimed at investigating the role of the purinergic receptor 2X7 (PR2X7), through the NLRP3 inflammasome, in the development of NASH. To this end, mice knockout for the Pr2x7 gene (Pr2x7 −/−) and coeval wild-type (WT) mice were fed a high-fat diet (HFD) or normal-fat diet for 16 weeks. NAFLD grade and stage were lower in Pr2x7 −/− than WT mice, and only 1/7 Pr2x7 −/− animals showed evidence of NASH, as compared with 4/7 WT mice. Molecular markers of inflammation, oxidative stress, and fibrosis were markedly increased in WT-HFD mice, whereas no or significantly reduced increments were detected in Pr2x7 −/− animals, which showed also decreased modulation of genes of lipid metabolism. Deletion of Pr2x7 gene was associated with blunted or abolished activation of NLRP3 inflammasome and expression of its components, which were induced in liver sinusoidal endothelial cells challenged with appropriate stimuli. These data show that Pr2x7 gene deletion protects mice from HFD-induced NASH, possibly through blunted activation of NLRP3 inflammasome, suggesting that PR2X7 and NLRP3 may represent novel therapeutic targets

Effects of THI changes on milk production and composition of three dairy cattle farms in Mugello from 2010 to 2018: a preliminary study

Submitted 2020-07-03 | Accepted 2020-09-09 | Available 2020-12-01https://doi.org/10.15414/afz.2020.23.mi-fpap.167-173Global warming is already affecting several areas and a further increase of 1.5°C is expected by 2050. Dairy cattle are particularly sensitive to high temperature. So, the aim of this study was to examine the effect of temperature-humidity index (THI) on milk traits, considering changes of climatic parameters in the different seasons from 2010 to 2018. The study was conducted in 3 farms located in a hilly-mountainous area of Tuscany, the Mugello, situated from 220 to 450 m above sea level. Data on average daily milk yield and composition were monthly collected in the 3 farms from 2010 to 2018, while climatic parameters were recorded by a climatic station located in the area of the farms. As regards the climatic parameters, no significant variations have been observed in the last decade. The THI calculated thanks to the recording of temperature and humidity of the weather station, during the warmest months, was high enough to cause heat stress. The milk quality traits declined when THI increased. In conclusion, there was not any evidence that global warming has been affecting Mugello, but, despite its altitude, high THI usually reached during spring and summer seasons are already high enough to cause heat stress and a further increase could worsen farm productivity.Keywords: climate change, milk quality, heat stress, dairy cowReferencesAmamou, H. et al. (2019). Thermotolerance indicators related to production and physiological responses to heat stress of Holstein cows. Journal of Thermal Biology, 82, 90–98. https://doi.org/10.1016/j.jtherbio.2019.03.016André, G. et al. (2011). Quantifying the effect of heat stress on daily milk yield and monitoring dynamic changes using an adaptive dynamic model. 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Global assessment of heat wave magnitudes from 1901 to 2010 and implications for the river discharge of the Alps. Science of the Total Environment, 571, 1330–1339. https://doi.org/10.1016/j.scitotenv.2016.07.008

Mutations in the met Oncogene Unveil a "Dual Switch" Mechanism Controlling Tyrosine Kinase Activity *

The met oncogene, encoding the high affinity hepatocyte growth factor receptor, is the only known gene inherited in human cancer that is invariably associated with somatic duplication of the mutant locus. Intriguingly, mutated Met requires ligand stimulation in order to unleash its transforming potential. Furthermore, individuals bearing a germ line met mutation develop cancer only late in life and with incomplete penetrance. To date, there is no molecular explanation for this unique behavior, which is unusual for a dominant oncogene. Here we investigate the molecular mechanisms underlying met oncogenic conversion by generating antibodies specific for the differently phosphorylated forms of the Met protein. Using these antibodies, we show that activation of wild-type Met is achieved through sequential phosphorylation of Tyr1235 and Tyr1234 in the activation loop and that mutagenesis of either tyrosine dramatically impairs kinase function. Surprisingly, oncogenic Met mutants never become phosphorylated on Tyr1234 despite their high enzymatic activity, and mutagenesis of Tyr1234 does not affect their biochemical or biological function. By analyzing the enzymatic properties of the mutant proteins in different conditions, we demonstrate that oncogenic mutations do not elicit constitutive kinase activation but simply overcome the requirement for the second phosphorylation step, thus reducing the threshold for activation. In the presence of activating signals, these mutations result therefore in a dynamic imbalance toward the active conformation of the kinase. This explains why mutant met provides an oncogenic predisposition but needs a second activating "hit," provided by sustained ligand stimulation or receptor overexpression, to achieve a fully transformed phenotype

A New Polysaccharide Carrier Isolated from Camelina Cake: Structural Characterization, Rheological Behavior, and Its Influence on Purple Corn Cob Extract’s Bioaccessibility

A polysaccharide fraction obtained from camelina cake (CCP), selected as a carrier to encapsulate purple corn cob extract (MCE), was investigated. A wide population of carbohydrate polymers (with a polydispersivity index of 3.26 ± 0.07 and an average molecular weight of about 139.749 × 103 ± 4.392 × 103 g/mol) with a gel-like behavior and a thixotropic feature characterized the fraction. MCE-CCP combinations (50-50 and 25-75, w/w), selected based on CCP encapsulation efficiency, were tested for their stability and MCE polyphenols' bioaccessibility during digestion (monitored using an in vitro static procedure). During the oral and gastric phases of the digestion process, CCP gradually swelled and totally released MCE polyphenols. MCE-CCP50 had the fastest release. Moreover, anthocyanins were still detectable during the duodenal phase, in both MCE-CCP ingredients. Furthermore, CCP (5 mg/mL) exerted in vitro potential hypocholesterolemic activity via bile salts binding during digestion

Application of Virtual Fencing for the management of Limousin cows at pasture

A potential use of pasture-based systems requires an efficient grazing management strategy. Thanks to the Virtual Fencing (VF) physical fences are replaced by virtual ones and, when the animals approach the boundaries, they receive a paired stimulus: an audio cue followed by a low electrical pulse if animals cross over the fences. This study aims to i) to evaluate the animal’s ability to learn, and then respond positively, to VF ii) VFs’ efficiency to manage the herd within grazing areas virtually delimitated; iii) to assess the chronic stress related to the VF, evaluating the hair cortisol concentration (HCC), during the experiment. Twenty Limousine cows were fitted with a commercial VF-GPS collars (Nofence AS, Batnfjordsør, Norway). The experiment was divided into four trials: Trial zero (T0) with inactive collars to let the animals get acquainted with them; Trial one (T1) where three of the four virtual boundaries coincided with the physical ones, while the virtual one was set across the pasture to restrict the grazing area; Trial two (T2) in which the grazing area was further extended moving forwards the virtual board; Trial three (T3) in which the virtual line was set longways to the pasture. Results show a significant decrease of stimuli delivered (i.e., sounds and electrical pulses) (p < 0.001), among trials. Moreover, a reduction (p < 0.0250) in the ratio between sounds and electrical pulses was observed between T1 and T3, with T2 being like both. Regarding the cows’ learning capacity, the events in which the sounds were followed by electrical pulses were significantly less in T3 (p < 0.001). Furthermore, in T3 the duration of the audio tones was lower than T1 and T2 (p < 0.0005). Animals were increasingly kept inside the inclusion zones during the trials, with the lowest number of escape events from the inclusion zone registered in T3 (p < 0.001). No differences were observed in the HCC before and after the VF treatment. The progressive reduction of the studied parameters between following sessions, indicates an increase in associative learning through time. VF virtual fencing has proven to be an effective tool in managing Limousin cows at pasture. However, future research is needed to evaluate the animals’ performances in terms of grazing activities and on the assessment of chronic stress conditions as well

Cinta senese burgers with omega-3 fatty acids: effect of storage and type of enrichment on quality characteristics

In Cinta Senese meat, polyunsaturated fatty acids (PUFAs) only consists in the 10-11% of total fat. Moreover the eicosapentaenoic and docosahexaenoic acids, which are two of the most important omega-3 PUFAs to human health, are not present in pork meat, but they are very abundant in fish products

Measuring Consumers’ Preferences for Traditional and Innovative Pork Products

In this research we proposed an integrated methodological approach to measure the “real” consumers’ preference towards new Traditional (TPP) and Innovative Pork Products (ITPP) from three untapped pig breeds in Spain (Porc Negre), Italy (Cinta Senese) and Slovenia (Krškopolje). We first analyse consumers’ perception towards the traditional concept in pork products. Results showed high preference heterogeneity amongst countries. After the eating experience, the expected preferences were affected significantly in particular in Italy and Slovenia. The likelihood to purchase the innovative pork products increased as well

Effects of Protein Restriction on Performances and Meat Quality of Cinta Senese Pig Reared in an Organic System

In lean genotypes, protein restriction during growing increases intramuscular fat content without affecting the overall carcass fatness. The present study aims to assess the feasibility of applying this feeding management on an obese pig, the Cinta Senese, since obese genotypes are characterized by great lipogenic potential often leading to excessively high backfat deposits. Twenty pigs of average weight 38 kg, were divided in two groups, the first group was fed a protein restricted diet (9% of crude protein), while the second one a normal diet (13.5% of crude protein). During finishing, both groups were fed the same diet (10% of crude protein). Average daily gain, protein conversion index, backfat thickness, carcass weight, and prime cuts were determined. A loin sample joint was dissected in intermuscular fat, bone, subcutaneous fat, longissimus lumborum, and psoas major. On longissimus lumborum, physical and chemical analysis was carried out. The fatty acid profile of longissimus lumborum and loin subcutaneous fat were determined. Data were analyzed by analysis of variance. Protein conversion index resulted lower in the restricted group, while backfat was slightly greater. Meat quality traits were not affected by feeding management. Slightly modifications in subcutaneous outer layer fatty acids profile were observed. The protein restriction during growing did not seem a suitable mode of feeding management for Cinta Senese pigs