Echocardiographic changes in the development of the athlete's heart in 9 to 20-year-old male subjects

The purpose of this cross-sectional investigation was to estimate the age at which specific traits of the “athlete's heart”first appear and how they evolve from the beginning of regular physical training until young adulthood in healthy active males. Male athletes (n=389) and non-athletes (n=55) aged between 9 and 20 years were examined by two-dimensionally guided M-mode and Doppler echocardiography. Intragroup differences were examined by t-tests for independent samples between age groups of two years each. Morphologic variables were related to body size by using ratio indices in which the power terms of numerator and denominator were matched. Relative left ventricular muscle mass (LVMM) was significantly larger in the athletic males at age of 11–12, and this significant difference was maintained with advancing age. Most of this increase of LVMM could be attributed to the increase in wall thickness that became significantly manifest first in the 13- to 14-year-old athletic subjects but was demonstrable in all the other groups. A significantly larger left ventricular internal diameter was only found in the age-group of 15–16. Fractional shortening percentage (FS%) did not show any change, while resting heart rate was decreased in our athletic groups

Arterial Tortuosity Syndrome: a vitamin C compartmentation disease?

Arterial tortuosity syndrome (ATS, MIM #208050) is a rare autosomal recessive connective tissue disorder characterized by tortuosity and elongation of the large and medium-sized arteries and a propensity towards aneurysm formation and vascular dissection. ATS is caused by mutations in SLC2A10 encoding the facilitative glucose transporter 10 (GLUT10), whose role in the ATS pathogenesis remains still controversial. We recently showed that GLUT10 deficiency causes the dysregulation of several genes/proteins involved in TGFβ signaling, extracellular matrix architecture and pathways that control oxidative stress response. GLUT10 should be located intracellularly; however, neither the exact localization, i.e., nuclear membrane, mitochondria, or endoplasmic reticulum (ER), nor the transported substances, i.e., glucose or dehydroascorbic acid (DAA), have been demonstrated. Here, we demonstrate that GLUT10 facilitates DAA uptake into the endomembranes and, in particular, into ER. GLUT10 produced by in vitro translation and incorporated into proteoliposomes efficiently transports DAA. Silencing of GLUT10 in hTERT immortalized human fibroblasts compromised DAA transport activity through the endomembranes. Similarly, in plasma membrane-permeabilized ATS fibroblasts a huge decrease in DAA transport was observed and the stable re-expression of GLUT10 restored the impaired DAA transport activity. Immunocytochemistry of human control fibroblasts showed a perinuclear abundance of GLUT10. Immunoblotting of subcellular fractions from human control fibroblasts revealed that GLUT10 was principally present in the microsomal fraction, containing ER-derived vesicles, as showed by the presence of the specific ER marker proteins GRP78 and GRP94, and by the almost complete absence of mitochondrial and cytoplasmic markers, VDAC1, cyclophilin D, and GAPDH, respectively. Transient expression of V5-tagged GLUT10 in ATS patients’ fibroblasts and co-localization experiments with the specific ER marker PDI definitely confirmed the ER localization of GLUT10. Overall, the present findings demonstrate that GLUT10 facilitates DAA uptake into the ER lumen and likely to the nucleoplasm through the nuclear envelope, which is a subdomain of the ER. Our findings support both “antioxidant-” and “enzyme cofactor-” models of a vitamin C-related pathology. Indeed, AA acts as an antioxidant/electron acceptor protecting against oxidative stress-induced cellular damage by scavenging free radicals also during the process of oxidative protein folding. Furthermore, AA is an essential cofactor for α-ketoglutarate-dependent dioxygenases, such as prolyl and lysyl hydroxylases inside the ER and for ten-eleven translocation demethylases and the Jumonji protein family present in the nucleus. Thus, shortage of AA in the lumenal compartments of the secretory pathway and in the nucleoplasm can depress the production of extracellular matrix proteins at both post-translational and epigenetic levels

The architectures of translation : a magic carpet-ride through space and time (or, the awkward story of how we dis/placed Krisztina Tóth’s short fiction from Hungarian to English)

This interdisciplinary paper unfolds an account of a collaborative translation project, which draws on Ellen Eve Frank’s concept of “literary architecture” to propose a process of “architectural translation”. Our proposal is illustrated by a detailed account of our experiences translating the short fiction of contemporary Hungarian writer, Krisztina Tóth (b. 1967) into English. Staged as a journey through space, time and text, our enquiry frames the process in Barbara Godard’s terms as one of dis/placement, finding resonances with Rosi Braidotti’s nomadic subject and practices of feminist mimesis. Situating Tóth’s fiction in a European feminist literary heritage, we deploy a range of concepts drawn from translation, architecture, literary criticism and feminist philosophy to synthesise a translation strategy which engages the spatial, not only as a metaphor but a methodology for our project. In this account, we propose an architectural methodology as a tool for radical translators, and offer the process of translation as a way of thinking about internal and external spaces in postcolonial contexts

Intraluminal calcium of the liver endoplasmic reticulum stimulates the glucuronidation of p-nitrophenol.

The relationship between the intraluminal Ca2+ content of endoplasmic reticulum and the rate of the glucuronidation of p-nitrophenol was investigated in isolated rat hepatocytes. Different agents which decrease the Ca2+ level in the endoplasmic reticulum [calcium ionophores (A23187, ionomycin) or Ca(2+)-ATPase inhibitors(thapsigargin,2,5-di-(t-butyl)-1,4-benzohydroquinone+ ++)] inhibited the conjugation of p-nitrophenol. Depletion of intracellular Ca2+ stores by preincubation of hepatocytes in the absence of free Ca2+ (in the presence of excess EGTA) also decreased the rate of glucuronidation; Ca2+ re-admission to EGTA-treated hepatocytes restored glucuronidation. In intact liver microsomes the p-nitrophenol UDP-glucuronosyl-transferase activity was not modified by varying the external free Ca2+ concentrations within a cytosol-like range. Emptying of the Ca2+ from the lumen of microsomal vesicles by A23187, after MgATP-stimulated Ca2+ sequestration, decreased the glucuronidation of p-nitrophenol. A similar effect was observed in filipin-permeabilized hepatocytes. In native and in detergent-treated microsomes, Ca2+ (1-10 mM) increased the p-nitrophenol UDP-glucuronosyltransferase activity. It is suggested that the physiological concentration of Ca2+ in the lumen of the endoplasmic reticulum is necessary for the optimal activity of p-nitrophenol UDP-glucuronosyltransferase; the depletion of Ca2+ decreases the activity of the enzyme