Rosenowen5511

Oxytocin is involved in a broad array of social behaviours. While saliva has been used regularly to investigate the role of oxytocin in social behaviour of mammal species, so far, to our knowledge, no-one has tried to measure its homolog, mesotocin, in birds' saliva. Therefore, in this study we measured salivary mesotocin in common ravens (Corvus corax), and subsequently explored its link to three aspects of raven sociality. We trained ravens (n = 13) to voluntarily provide saliva samples and analysed salivary mesotocin with a commercial oxytocin enzyme-immunoassay kit, also suitable for mesotocin. After testing parallelism and recovery, we investigated the effect of bonding status, sex and season on mesotocin levels. We found that mesotocin was significantly more likely to be detected in samples taken during the breeding season (spring) than during the mating season (winter). In those samples in which mesotocin was detected, concentrations were also significantly higher during the breeding than during the mating season. In contrast, bonding status and sex were not found to relate to mesotocin detectability and concentrations. The seasonal differences in mesotocin correspond to behavioral patterns known to be associated with mesotocin/oxytocin, with ravens showing much more aggression during the mating season while being more tolerant of conspecifics in the breeding season. We show for the first time that saliva samples can be useful for the non-invasive determination of hormone levels in birds. However, the rate of successfully analysed samples was very low, and collection and analysis methods will benefit from further improvements.Hypochlorous acid (HOCl) is the active oxidizing principle underlying drinking water disinfection, also delivered by numerous skin disinfectants and released by standard swimming pool chemicals used on a global scale, a topic of particular relevance in the context of the ongoing COVID-19 pandemic. However, the cutaneous consequences of human exposure to HOCl remain largely unknown, posing a major public health concern. Here, for the first time, we have profiled the HOCl-induced stress response in reconstructed human epidermis and SKH-1 hairless mouse skin. In addition, we have investigated the molecular consequences of solar simulated ultraviolet (UV) radiation and HOCl combinations, a procedure mimicking co-exposure experienced for example by recreational swimmers exposed to both HOCl (pool disinfectant) and UV (solar radiation). First, gene expression elicited by acute topical HOCl exposure was profiled in organotypic human reconstructed epidermis. Next, co-exposure studies (combining topical HOCl and UV) pf UV-induced carcinogenesis. Apoptozole chemical structure If translatable to human skin these observations provide novel insights on molecular consequences of chlorination stress relevant to environmental exposure and therapeutic intervention.Incidence of hepatotoxicity following acute drug-induced proteasomal inhibition and development of chronic proteasome dysfunction in obesity and insulin resistance underscores the crucial importance of hepatic protein homeostasis albeit with an elusive molecular basis and therapeutic opportunities. Apart from lipotoxicity and endoplasmic reticulum (ER) stress, herein we report that hepatocytes are highly susceptible to proteasome-associated metabolic stress attune to altered redox homeostasis. Bortezomib-induced proteasomal inhibition caused severe hepatocellular injury independent of ER stress via proapoptotic Apoptosis Signal-regulating Kinase 1 (ASK1)- c-Jun N-terminal kinase (JNK1)- p38 signaling concomitant with inadequate peroxisome proliferator-activated receptor γ (PPARγ)- Nuclear factor erythroid 2-related factor 2 (Nrf2) -driven antioxidant response. Although inhibition of ASK1 rescued acute hepatotoxicity, hepatic depletion of PPARγ or its physiological activator pigment epithelium-derived factor (PEDF) further aggravated liver injury even under ASK1 inhibition, emphasizing that endogenous PPARγ driven antioxidant activity serves as a prerequisite for the favorable therapeutic outcome of ASK1 inhibition. Consequently, ASK1 inhibitor selonsertib and PPARγ agonist pioglitazone in pharmacological synergism ameliorated bortezomib-induced hepatotoxicity and significantly prolonged survival duration in mice. Moreover, we showed that proteasome dysfunction is associated with ASK1 activation and insufficient PPARγ/Nrf2-driven antioxidative response in a subset of human nonalcoholic steatohepatitis (NASH) patients and the preclinical NASH model. The latter remains highly responsive to the drug combination marked by revamped proteasomal activity and alleviated hallmarks of NASH such as steatosis, fibrosis, and hepatocellular death. We thus uncovered a pharmacologically amenable interdependent binodal molecular circuit underlying hepatic proteasomal dysfunction and associated oxidative injury.

A calcar collar may reduce risk of periprosthetic fracture of the femur, through collar contact. We estimated the effect of collar contact on periprosthetic fracture mechanics using a collared fully coated cementless femoral stem and then estimated the effect of initial calcar-collar separation on the likelihood of collar contact.

Three groups of six composite left femurs with increasing calcar-collar separation in each group, underwent periprosthetic fracture simulation in a materials testing machine. Fracture torque and rotational displacement were measured and torsional stiffness and rotational work prior to fracture were estimated. Calcar collar contact prior to fracture was identified using high speed camera footage.

Where calcar-collar contact occurred fracture torque was greater (47.33 [41.03 to 50.45] Nm versus 38.26 [33.70 to 43.60] Nm, p=0.05), Rotational displacement was less (16.6 [15.5 to 22.3] degrees versus 21.2 [18.9 to 28.1] degrees, p=0.07), torsional stiffness was greater (151.38 [123.04 to 160.42] rad.Nm

versus 96.86 [84.65 to 112.98] rad.Nm

, p<0.01) and rotational work was similar (5.88 [4.67, 6.90] J versus 5.31 [4.40, 6.56] J, p=0.6). Odds ratio (OR) of not achieving collar contact (95% confidence interval) increased 3.8 fold (95% CI 1.6 to 30.2, p<0.05) for each millimetre of separation in the regression model. 95% chance of collar contact was associated with a separation of 1mm or less.

Surgeons should reduce calcar-collar separation at stem implantation to a maximum of 1mm to increase the chance of calcar-collar contact during injury and reduce the risk of early post-operative femoral fracture.

Surgeons should reduce calcar-collar separation at stem implantation to a maximum of 1 mm to increase the chance of calcar-collar contact during injury and reduce the risk of early post-operative femoral fracture.