Mechanisms of MEOX1 and MEOX2 Regulation of the Cyclin Dependent Kinase Inhibitors p21CIP1/WAF1 and p16INK4a in Vascular Endothelial Cells

Senescence, the state of permanent cell cycle arrest, has been associated with endothelial cell dysfunction and atherosclerosis. The cyclin dependent kinase inhibitors p21CIP1/WAF1 and p16INK4a govern the G1/S cell cycle checkpoint and are essential for determining whether a cell enters into an arrested state. The homeodomain transcription factor MEOX2 is an important regulator of vascular cell proliferation and is a direct transcriptional activator of both p21CIP1/WAF1 and p16INK4a. MEOX1 and MEOX2 have been shown to be partially functionally redundant during development, suggesting that they regulate similar target genes in vivo. We compared the ability of MEOX1 and MEOX2 to activate p21CIP1/WAF1 and p16INK4a expression and induce endothelial cell cycle arrest. Our results demonstrate for the first time that MEOX1 regulates the MEOX2 target genes p21CIP1/WAF1 and p16INK4a. In addition, increased expression of either of the MEOX homeodomain transcription factors leads to cell cycle arrest and endothelial cell senescence. Furthermore, we show that the mechanism of transcriptional activation of these cyclin dependent kinase inhibitor genes by MEOX1 and MEOX2 is distinct. MEOX1 and MEOX2 activate p16INK4a in a DNA binding dependent manner, whereas they induce p21CIP1/WAF1 in a DNA binding independent manner

Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem?

Recent studies in various rodent models of pathologic ventricular hypertrophy report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3 inactivates thyroid hormone (T3) and is mainly expressed in tissues during development. The stimulation of D3 activity in ventricular hypertrophy and subsequent heart failure is associated with severe impairment of cardiac T3 signaling. Hypoxia-induced signaling appears to drive D3 expression in the hypertrophic cardiomyocyte, but other signaling cascades implicated in hypertrophy are also capable of stimulating transcription of the DIO3 gene. Many cardiac genes are transcriptionally regulated by T3 and impairment of T3 signaling will not only reduce energy turnover, but also lead to changes in gene expression that contribute to contractile dysfunction in pathologic remodeling. Whether stimulation of D3 activity and the ensuing local T3-deficiency is an adaptive response of the stressed heart or part of the pathologic signaling network leading to heart failure, remains to be established

Disruption at the PTCHD1 Locus on Xp22.11 in Autism Spectrum Disorder and Intellectual Disability

Autism is a common neurodevelopmental disorder with a complex mode of inheritance. It is one of the most highly heritable of the complex disorders, however, the underlying genetic factors remain largely unknown. Here, we report mutations in the X-chromosome PTCHD1 (patched-related) gene, in seven families with autism spectrum disorder (ASD) and in three families with intellectual disability (ID). A 167 Kb microdeletion spanning exon 1 was found in two brothers, one with ASD the other with learning disability and ASD features, and a 90 Kb microdeletion spanning the entire gene was found in three males with ID in a second family. In 900 ASD and 208 ID male probands we identified seven different missense changes in eight probands, all male and inherited from unaffected mothers, and not found in controls. Two of the ASD individuals with missense changes also carried a de novo deletion at another ASD-susceptibility locus (DPYD and DPP6), suggesting complex genetic contributions. In additional males with ASD, we identified deletions in the 5’ flanking region of PTCHD1 disrupting a complex non-coding RNA and potential regulatory elements; equivalent changes were not found in male control individuals (p=1.2 ×10-5). Systematic screening at PTCHD1 and 5’-flanking regions, suggests involvement of this locus in ~1% of ASD and ID individuals

Wear Behaviour of Nanostructured Polymer-Based Safety Films on Soda-Lime Glass

The wear behaviour of bare and polymer-coated soda-lime glass specimens sliding against 440C stainless steel counterfaces was investigated with the aid of a pin-on-disk apparatus. The selected polymeric coatings were commercially supplied safety films, which are nowadays extensively applied on glass in the automotive and construction industry. One of their main failures is the degradation of their properties due to wear. In this work, the frictional behaviour of these coatings on glass were evaluated and compared to those of bare soda-lime glass. Correlations have been also made between the worn surfaces and weight loss in order to investigate the effect of wear conditions (speed, load) on the wear behaviour of these tribosystems. In addition, during the dry wear of soda-lime glass sliding against stainless steel counterfaces, the dominant wear mechanisms were found to be localized adhesion and abrasion, whereas, in the case of the multilayered polymeric coatings localized adhesion, deformation and tearing were observed

Systemic Candidiasis with Multiple Abscesses After Transurethral Resection of the Prostate Gland

SUMMARY. The rare case is presented of a patient who developed multiple abscesses from Candida albicans after transurethral resection of the prostate gland for benign prostatic hyperplasia. The abscesses developed in the urogenital system, the anorectal region and the lungs, and also subcutaneously. They were treated both surgically and with medication. Solitary abscess as a manifestation of candidiasis is well documented, but to the best of the authors’ knowledge this is the first report of multiple, synchronous abscesses in different systems in a patient with systemic candidiasis. Pneumon 2009, 22(4):331-336

Social Media Network Analysis of Academic Urologists’ Interaction Within Twitter Microblogging Environment

ObjectiveTo characterize academic urology Twitter presence and interaction by subspecialty designation.MethodsUsing Twitter application programming interface of available data, 94000 specific tweets were extracted for the analysis through the Twitter Developer Program. Academic urologists were defined based on American Urological Association (AUA) residency program registration of 143 residency programs, with a total of 2377 faculty. Two of 3-factor verification (name, location, specialty) of faculty Twitter account was used. Additional faculty information including sex, program location, and subspecialty were manually recorded. All elements of microblogging were captured through Anaconda Navigator. Analyzed tweets were further evaluated using natural language processing for sentiment association, mentions, and quote tweeted and retweeted. Network analysis based on interactions of academic urologist within specialty for given topic were analyzed using D3 in JavaScript. Analysis was performed in Python and R.ResultsWe identified 143 residency programs with a total of 2377 faculty (1975 men and 402 women). Among all faculty, 945 (39.7%) had registered Twitter accounts, with the majority being men (759 [80.40%] versus 185 [19.60%]). Although there were more male academic urologists across programs, women within academic urology were more likely to have a registered Twitter account overall (46% versus 38.5%) compared with men. When assessing registered accounts by sex, there was a peak for male faculty in 2014 (10.05% of all accounts registered) and peak for female faculty in 2015 (2.65%). There was no notable change in faculty account registration during COVID-19 (2019–2020). In 2022, oncology represented the highest total number of registered Twitter users (225), with the highest number of total tweets (24622), followers (138541), and tweets per user per day (0.32). However, andrology (50%) and reconstruction (51.3%) were 2 of the highest proportionally represented subspecialties within academic urology. Within the context of conversation surrounding a specified topic (#aua21), female pelvic medicine and reconstructive surgery (FPMRS) and endourology demonstrated the total highest number of intersubspecialty conversations.ConclusionsThere is a steady increase in Twitter representation among academic urologists, largely unaffected by COVID-19. While urologic oncology represents the largest group, andrology and reconstructive urology represent the highest proportion of their respective subspecialties. Interaction analysis highlights the variant interaction among subspecialties based on topic, with strong direct ties between endourology, FPMRS, and oncology