Insulin resistance, induced either by obesity or genetic manipulation and steatosis do not cause mitochondrial dysfunction in mouse liver. Also, mitochondrial dysfunction is not a prerequisite for liver steatosis. However, severe insulin deficiency and high blood glucose levels lead to an enhanced performance and better coupling of the RC. This may represent an adaptation to fuel overload and the high energy-requirement of an unsuppressed gluconeogenesis.

words)Operators of highly automated driving systems may exhibit behaviour characteristic for overtrust issues due to an insufficient awareness of automation fallibility. Consequently, situation awareness in critical situations is reduced and safe driving performance following emergency takeovers is impeded. A driving simulator study was used to assess the impact of dynamically communicating system uncertainties on monitoring, trust, workload, takeovers, and physiological responses. The uncertainty information was conveyed visually using a stylised heart beat combined with a numerical display and users were engaged in a visual search task.Multilevel analysis results suggest that uncertainty communication helps operators calibrate their trust and gain situation awareness prior to critical situations, resulting in safer takeovers.Additionally, eye tracking data indicate that operators can adjust their gaze behaviour in correspondence with the level of uncertainty. However, conveying uncertainties using a visual display significantly increases operator workload and impedes users in the execution of nondriving related tasks. Keywords: vehicle ergonomics; attitudes and behaviour; attention and vigilance; humancomputer-interaction; information displaysPractitioner summary (50 words): This paper illustrates how the communication of system uncertainty information helps operators calibrate their trust in automation and, consequently, gain situation awareness. Multilevel analysis results of a driving simulator study affirm the benefits for trust calibration and highlight that operators adjust their behaviour according to multiple uncertainty levels.

Autosomal dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulo-in terstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life. This disorder was described to have an age of onset between the age of 20-30 years or even later. Mutations in the Uromodulin (UMOD) gene were published in patients with familial juvenile hyperuricemic nephropathy (FJHN) and MCKD2. Clinical data and blood samples of 16 affected individuals from 11 different kindreds were collected. Mutational analysis of the UMOD gene was performed by exon polymerase chain reaction (PCR) and direct sequencing. We found the heterozygous C744G (Cys248Trp) mutation, which was originally published by our group, in an additional four kindreds from Europe and Turkey. Age of onset ranged from 3 years to 39 years. The phenotype showed a variety of symptoms such as urinary concentration defect, vesicoureteral reflux, urinary tract infections, hyperuricemia, hypertension, proteinuria, and renal hypoplasia. Haplotype analysis showed cosegragation with the phenotype in all eight affected individuals indicating that the C744G mutation may be due to a founder effect. Moreover, we describe a novel T229G (Cys77Gly) mutation in two affecteds of one kindred. Three of the affected individuals were younger than 10 years at the onset of MCKD2/FJHN. Symptoms include recurrent urinary tract infections compatible with the published phenotype of the Umod knockout mouse model. This emphasizes that MCKD2 is not just a disease of the young adult but is also relevant for children.

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Ocular surface disorders, such as pterygium, cicatricial pemphigoid and external disruptions, can cause severe inflammation, scarring, fornix shortening as well as ankyloblepharon. Current treatments do not resolve these conditions sufficiently. The aim of this study was to evaluate clinical applicability and suitability of plastic compressed collagen to serve as a substrate for the expansion of human conjunctival epithelial cells in order to develop an epithelialized conjunctival substitute for fornix reconstruction. Human conjunctival epithelial cells were expanded on plastic compressed collagen gels. Epithelial cell characteristics were evaluated by haematoxylin and eosin staining, electron microscopy and cytokeratin expression. The expression of putative epithelial progenitor cell markers p63α, ABCG2 and CK15 was assessed by immunostaining. The proliferative capacity and clonal growth of the cells was evaluated before (P0) and after expansion (P1) on the plastic compressed collagen gels by colony forming efficiency assay. The potential clinical applicability of this gel substitutes was evaluated by assessment of their biomechanical properties as well as their surgical handling. Human conjunctival epithelial cells cultured on plastic and plastic compressed collagen gels formed a confluent cell layer and expressed CK19. The cells showed expression of the putative epithelial progenitor cell markers p63α, ABCG2 and CK15 and sustained colony forming ability. The compressed collagen gels showed a high ultimate tensile strength and elasticity and the surgical handling of gels was comparable to amniotic membrane. An epithelialized conjunctival tissue construct on the basis of compressed collagen might therefore be a promising alternative bioartificial tissue substitute for conjunctival reconstruction.

Aim: To determine the distribution of major basement membrane constituents, particularly nidogen 1 and 2, in young and aging mouse retinae. Methods: The specificity of antibodies against basement membrane proteins was ascertained by immunoblotting with proteins extracted from mouse retinae. The same antibodies were used in indirect immunofluorescence microscopy to localize basement membrane proteins in paraffin sections of retinae from 1-, 12- and 18-month-old C57BL/6 mice. Results: At a young age, laminin, perlecan and collagen IV were most abundant in Bruch’s membrane. Later, the proteins were clearly detected in capillary basement membranes and the inner limiting membrane. In both of these basement membranes, a massive increase in protein amount was seen upon aging, whereas in Bruch’s membrane the staining intensity was less drastically changed. Both nidogen 1 and 2 were present in vascular basement membranes and Bruch’s membrane throughout the age periods studied. In the inner limiting membrane, the nidogens were more strongly expressed at higher ages, with an earlier and more extensive deposition of nidogen 1. Conclusions: All major basement membrane constituents are present in the mouse retina, but the onset of deposition differs among the different proteins and between the various retinal basement membranes. In general, basement membrane protein deposition increases with age.

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Safe manual driving performance following takeovers in conditionally automated driving systems is impeded by a lack in situation awareness, partly due to an inappropriate trust in the system's capabilities. Previous work has indicated that the communication of system uncertainties can aid the trust calibration process. However, it has yet to be investigated how the information is best conveyed to the human operator. The study outlined in this publication presents an interface layout to visualise function-specific uncertainty information in an augmented reality display and explores the suitability of 11 visual variables. 46 participants completed a sorting task and indicated their preference for each of these variables. The results demonstrate that particularly colour-based and animation-based variables, above all hue, convey a clear order in terms of urgency and are well-received by participants. The presented findings have implications for all augmented reality displays that are intended to show content varying in urgency.