Intriguing Interpretation of Dyads in Common-Practice Tonal Music

The study offers a systematic exploration of situations in which dyads in common-practice tonal music change their meaning, when repeated or as pivots. The most common such situation is thirds that serve as either the upper or the lower pair of consonant triad members, most often with the tonic as one of the options. Sometimes, however, an implied harmony turns out to be dissonant. Occasionally, dyads other than thirds are also subject to reinterpretation. In exceptional circumstances, dyads do not imply complete harmonies

Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.

Mice deficient in the transcription factor Runx3 develop a multitude of immune system defects, including early onset colitis. This paper demonstrates that Runx3 is expressed in colonic mononuclear phagocytes (MNP), including resident macrophages (RM) and dendritic cell subsets (cDC2). Runx3 deletion in MNP causes early onset colitis due to their impaired maturation. Mechanistically, the resulting MNP subset imbalance leads to up-regulation of pro-inflammatory genes as occurs in IL10R-deficient RM. In addition, RM and cDC2 display a marked decrease in expression of anti-inflammatory/TGF β-regulated genes and β-catenin signaling associated genes, respectively. MNP transcriptome and ChIP-seq data analysis suggest that a significant fraction of genes affected by Runx3 loss are direct Runx3 targets. Collectively, Runx3 imposes intestinal immune tolerance by regulating maturation of colonic anti-inflammatory MNP, befitting the identification of RUNX3 as a genome-wide associated risk gene for various immune-related diseases in humans, including gastrointestinal tract diseases such as Crohn's disease and celiac

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)

Contains fulltext : 218165.pdf (Publisher’s version ) (Closed access)Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of Israeli IRD patients. To date, we recruited 2,420 families including 3,413 individuals with IRDs. On the basis of our estimation, these patients represent approximately 40% of Israeli IRD patients. To the best of our knowledge, this is, by far, the largest reported IRD cohort, and one of the first studies addressing the genetic analysis of IRD patients on a nationwide scale. The most common inheritance pattern in our cohort is autosomal recessive (60% of families). The most common retinal phenotype is retinitis pigmentosa (43%), followed by Stargardt disease and cone/cone-rod dystrophy. We identified the cause of disease in 56% of the families. Overall, 605 distinct mutations were identified, of which 12% represent prevalent founder mutations. The most frequently mutated genes were ABCA4, USH2A, FAM161A, CNGA3, and EYS. The results of this study have important implications for molecular diagnosis, genetic screening, and counseling, as well as for the development of new therapeutic strategies for retinal diseases

Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and is considered to be the outcome of chronic liver inflammation. Currently, the main treatment for HCC is surgical resection. However, survival rates are suboptimal partially because of tumor recurrence in the remaining liver. Our aim was to understand the molecular mechanisms linking liver regeneration under chronic inflammation to hepatic tumorigenesis. Mdr2-KO mice, a model of inflammation-associated cancer, underwent partial hepatectomy (PHx), which led to enhanced hepatocarcinogenesis. Moreover, liver regeneration in these mice was severely attenuated. We demonstrate the activation of the DNA damage-response machinery and increased genomic instability during early liver inflammatory stages resulting in hepatocyte apoptosis, cell-cycle arrest, and senescence and suggest their involvement in tumor growth acceleration subsequent to PHx. We propose that under the regenerative proliferative stress induced by liver resection, the genomic unstable hepatocytes generated during chronic inflammation escape senescence and apoptosis and reenter the cell cycle, triggering the enhanced tumorigenesis. Thus, we clarify the immediate and long-term contributions of the DNA damage response to HCC development and recurrence

Group hunting within the Carnivora: physiological, cognitive and environmental influences on strategy and cooperation

Cooperative hunting is believed to have important implications for the evolution of sociality and advanced cognitive abilities. Variation in the level of hunt organisation amongst species and how their cognitive, behavioural and athletic adaptations may contribute to observed patterns of cooperative hunting behaviour, however, are poorly understood. We, therefore, reviewed the literature for evidence of different levels of hunt organisation and cooperation in carnivorans and examined their social and physical adaptations for hunting. Descriptions of group hunting were scarce for many species and often of insufficient detail for us to be able to classify the level of hunt organisation involved. However, despite this, reports of behaviour fitting the description of collaboration, the most advanced level of hunt organisation, were found in over half the carnivorans reported to hunt cooperatively. There was no evidence that this behaviour would require advanced cognitive abilities. However, there was some evidence that both social mechanisms reducing aggression between group members and information transfer amongst individuals may aid cooperative hunting. In general, the cooperative strategies used seemed to depend partly on the species' locomotor abilities and habitat. There was some evidence that individuals take on consistent roles during cooperative hunts in some species, but it was not clear if this reflects individuals' physical differences, social factors or life experiences. Better understanding of the social, cognitive and physical mechanisms underlying cooperative hunting, and indeed establishing to what degree it exists in the first instance, will require more data for multiple individuals and species over many hunts.</p