Testing a causal role for liver macrophage production of IL-6 during aging remains a challenge, yet interventions that have targeted macrophages and/or IL-6 have demonstrated promise in treating age-related diseases. These studies have demonstrated an age-related, deleterious reprogramming of macrophage function, which worsens pathology. Therefore, hepatic macrophage accrual is indeed a cause for concern, and therapies that attenuate the aged phenotype of macrophages will likely prove useful in promoting healthy aging.Activation of mitogen-activated protein kinases (MAPKs) is a key factor in the pathogenesis of cancer, although the specific role of mitogen-activated protein kinase kinase (MEK1) is not well understood. Villin promoter-driven Cre expression was used to excise a floxed stop cassette from a phosphomimetically constitutively activated MEK1 (caMEK1) expression construct in the intestine of C57BL/6 mice. Zygosity status of caMEK1 afforded assessment of the dose dependence of the effect. The expected mendelian distribution of genotypes and sex was observed in 443 progenies. Between 21 and 63 days of life, caMEK1 had no effect on body weight in male mice, but reduced body weight in female mice homozygous for caMEK1. At 10 wk of age, the ileum of caMEK1-expressing mice was characterized by the finding of dysplasia and profound changes in overall architecture. Paneth cells were nearly absent in caMEK1 homozygotes. Targeted proteomic profiling via reverse phase protein array analyses with confirmatory Western blottingociated with enhanced markers of proliferation, diminished apoptosis, alterations in cell-fate determination, cell-cell interactions, and tight junctions. This novel model provides new insights into intestinal homeostasis and carcinogenesis.(Pro)renin receptor (PRR), a 350-amino acid receptor initially thought of as a receptor for the binding of renin and prorenin, is multifunctional. In addition to its role in the renin-angiotensin system (RAS), PRR transduces several intracellular signaling molecules and is a component of the vacuolar H+-ATPase that participates in autophagy. PRR is found in the kidney and particularly in great abundance in the cortical collecting duct. In the kidney, PRR participates in water and salt balance, acid-base balance, and autophagy and plays a role in development and progression of hypertension, diabetic retinopathy, and kidney fibrosis. This review highlights the role of PRR in the development and function of the kidney, namely, the macula densa, podocyte, proximal and distal convoluted tubule, and the principal cells of the collecting duct, and focuses on PRR function in body fluid volume homeostasis, blood pressure regulation, and acid-base balance. This review also explores new advances in the molecular mechanism involving PRR in normal renal health and pathophysiological states.India enacted a new child sexual abuse law in 2012 and made important changes to the rape law in 2013 to expand the definition of rape and sexual assault, introduce several reforms and improve gender sensitivity in rape trials. However, the child sexual abuse law with its definition of who is a child has increased the age of consent for sex from 16 years to 18 years, echoed by similar changes in the rape law. This paper revisits the debates on the age of consent in India in the late nineteenth century. It reviews them in the light of the new legislative changes, adjudication of cases of sexual assault, and examines the implications of the new laws on adolescents and their sexuality. We contend that the changes in the law have resulted in several challenges for adolescents exploring their sexuality on the one hand, and for courts to adjudicate on love, romance, and elopement, on the other. Further, in conjunction with raising the age of consent, other changes such as mandatory reporting of sexual activity among adolescents, especially by hospitals, have increased family control on adolescents' sexuality and strengthened regressive social norms linked to marriages. One of the most troubling developments is the resulting barriers to adolescents' access to reproductive and sexual health care.  https://www.selleckchem.com/products/bms-927711.html  This paper explores how laws devised to address harm and extend protection to children play into dominant social norms and are in the service of protectionist and patriarchal control on young people and their sexuality.Gastric motility is coordinated by underlying bioelectrical "slow wave" activity. Slow wave dysrhythmias are associated with motility disorders, including gastroparesis, offering an underexplored potential therapeutic target. Although ablation is widely used to treat cardiac arrhythmias, this approach has not yet been trialed for gastric electrical abnormalities. We hypothesized that ablation can create localized conduction blocks and modulate slow wave activation. Radiofrequency ablation was performed on the porcine serosa in vivo, encompassing a range of parameters (55-85°C, adjacent points forming a line, 5-10 s/point). High-resolution electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to define baseline and acute postablation activation patterns. Tissue damage was evaluated by hematoxylin and eosin and c-Kit stains. Results demonstrated that RF ablation successfully induced complete conduction block and a full thickness lesion in the muscle layer at energy doses of 65-75°C for 5-10 s/point. Gastric ablation may hold therapeutic potential for gastric electrical abnormalities in the future.NEW & NOTEWORTHY This study presents gastric ablation as a new method for modulating slow wave activation and propagation in vivo, by creating localized electrical conduction blocks in the stomach, validated by high-resolution electrical mapping and histological tissue analysis. The results define the effective energy dose range for creating conduction blocks, while maintaining the mucosal and submucosal integrity, and demonstrate the electrophysiological effects of ablation. In future, gastric ablation can now be translated toward disrupting dysrhythmic slow wave activation.Criminalization of social groups can create new norms for intergroup relations. An example for this is the 2018 amendment to the Hungarian Fundamental Law, which openly criminalizes homeless people. In our research, we investigated whether criminalization of homelessness can become a source of justifying violence against homeless people in the Hungarian context. We assumed that right-wing authoritarianism and social dominance orientation would positively predict support for violence against the homeless, and the acceptance of a criminalizing law can serve as a justification for this. Our hypotheses were tested using a convenience (N = 196) and a representative sample of the population of Budapest (N = 674). We found that both RWA and SDO predicted support for violence, and this connection was mediated by the new law. We also found that justification was influenced by educational level, as the association between SDO and violence increased with higher levels of education.