Collectively, our findings provide evidence that ODC1 gene hypermethylation could be a starting point for the onset of genome-wide epigenetic aberrations in urothelial carcinogenesis. Furthermore, LINE-1 induction enabled by ODC1 interference provides a new experimental model to study mechanisms and consequences of LINE-1 activation in the etiology and progression of UC as well as presumably other cancers.From the camel's toes to the horse's hooves, the diversity in foot morphology among mammals is striking. One distinguishing feature is the presence of fat pads, which may play a role in reducing foot pressures, or may be related to habitat specialization. The camelid family provides a useful paradigm to explore this as within this phylogenetically constrained group we see prominent (camels) and greatly reduced (alpacas) fat pads. We found similar scaling of vertical ground reaction force with body mass, but camels had larger foot contact areas, which increased with velocity, unlike alpacas, meaning camels had relatively lower foot pressures. Further, variation between specific regions under the foot was greater in alpacas than camels. Together, these results provide strong evidence for the role of fat pads in reducing relative peak locomotor foot pressures, suggesting that the fat pad role in habitat specialization remains difficult to disentangle.It has been suggested that periodontitis is associated with metabolic abnormalities including non-alcoholic fatty liver disease (NAFLD). The fatty liver index (FLI) is a non-invasive surrogate marker and predictor of NAFLD. We aimed to determine whether FLI itself would be associated with periodontitis through a secondary analysis of previously reported nationally representative probability sample data of the Korean population. FLI was calculated from a previously developed algorithm which combines measures of body mass index (BMI), waist circumference, triglyceride, and gamma-glutamyl transferase (GGT). Periodontitis was diagnosed based on the Community Periodontal Index (CPI) developed by the World Health Organization. Of 4,272 participants, 26.1% were diagnosed with periodontitis. Higher FLI was associated with a higher prevalence of periodontitis (Odds ratio (OR) highest vs. lowest quartile of FLI,1.63; 95% confidence interval (CI), 1.23-2.16; P = 0.001 for trend) adjusting for confounding factors. In the highest FLI quartile, prevalence of periodontitis was higher in individuals with diabetes (OR highest vs. lowest quartile of FLI, 2.89; 95% CI, 1.01-8.27 for diabetic subgroup; OR highest vs. lowest quartile of FLI, 1.45; 95% CI, 1.07-1.96 for non-diabetic subgroup). In summary, FLI was associated with prevalent periodontitis.Protein oligomerization is a fundamental process to build complex functional modules. Domains that facilitate the oligomerization process are diverse and widespread in nature across all kingdoms of life. One such domain is the Phox and Bem1 (PB1) domain, which is functionally well-studied in the animal kingdom. However, beyond animals, neither the origin nor the evolutionary patterns of PB1-containing proteins are understood. While PB1 domain proteins have been found in other kingdoms including plants, it is unclear how these relate to animal PB1 proteins. To address this question, we utilized large transcriptome datasets along with the proteomes of a broad range of species. We discovered eight PB1 domain-containing protein families in plants, along with four each in Protozoa and Fungi and three families in Chromista. Studying the deep evolutionary history of PB1 domains throughout eukaryotes revealed the presence of at least two, but likely three, ancestral PB1 copies in the Last Eukaryotic Common Ancestor (LECA). These three ancestral copies gave rise to multiple orthologues later in evolution. Analyzing the sequence and secondary structure properties of plant PB1 domains from all the eight families showed their common ubiquitin β-grasp fold, despite poor sequence identity. Tertiary structural models of these plant PB1 families, combined with Random Forest based classification, indicated family-specific differences attributed to the length of PB1 domain and the proportion of β-sheets. Thus, this study not only identifies novel PB1 families, but also provides an evolutionary basis to understand their diverse functional interactions.The blood-brain barrier (BBB) serves to protect and regulate the CNS microenvironment. The development of an in-vitro mimic of the BBB requires recapitulating the correct phenotype of the in-vivo BBB, particularly for drug permeation studies. However the majority of widely used BBB models demonstrate low transendothelial electrical resistance (TEER) and poor BBB phenotype. The application of shear stress is known to enhance tight junction formation and hence improve the barrier function. We utilised a high TEER primary porcine brain microvascular endothelial cell (PBMEC) culture to assess the impact of shear stress on barrier formation using the Kirkstall QuasiVivo 600 (QV600) multi-chamber perfusion system. The application of shear stress resulted in a reorientation and enhancement of tight junction formation on both coverslip and permeable inserts, in addition to enhancing and maintaining TEER for longer, when compared to static conditions. Furthermore, the functional consequences of this was demonstrated with the reduction in flux of mitoxantrone across PBMEC monolayers. The QV600 perfusion system may service as a viable tool to enhance and maintain the high TEER PBMEC system for use in in-vitro BBB models.Gastrointestinal colonization has been considered as the primary source of candidaemia; however, few established mouse models are available that mimic this infection route. We therefore developed a reproducible mouse model of invasive candidiasis initiated by fungal translocation and compared the virulence of six major pathogenic Candida species. The mice were fed a low-protein diet and then inoculated intragastrically with Candida cells. Oral antibiotics and cyclophosphamide were then administered to facilitate colonization and subsequent dissemination of Candida cells. Mice infected with Candida albicans and Candida tropicalis exhibited higher mortality than mice infected with the other four species. Among the less virulent species, stool titres of Candida glabrata and Candida parapsilosis were higher than those of Candida krusei and Candida guilliermondii. The fungal burdens of C. parapsilosis and C. krusei in the livers and kidneys were significantly greater than those of C. guilliermondii.  https://www.selleckchem.com/  Histopathologically, C.