Pathologies caused by mutations in extracellular matrix proteins are generally considered to result from the synthesis of extracellular matrices that are defective. Mutations in type X collagen cause metaphyseal chondrodysplasia type Schmid (MCDS), a disorder characterised by dwarfism and an expanded growth plate hypertrophic zone. We generated a knock-in mouse model of an MCDS–causing mutation (COL10A1 p.Asn617Lys) to investigate pathogenic mechanisms linking genotype and phenotype. Mice expressing the collagen X mutation had shortened limbs and an expanded hypertrophic zone. Chondrocytes in the hypertrophic zone exhibited endoplasmic reticulum (ER) stress and a robust unfolded protein response (UPR) due to intracellular retention of mutant protein. Hypertrophic chondrocyte differentiation and osteoclast recruitment were significantly reduced indicating that the hypertrophic zone was expanded due to a decreased rate of VEGF–mediated vascular invasion of the growth plate. To test directly the role of ER stress and UPR in generating the MCDS phenotype, we produced transgenic mouse lines that used the collagen X promoter to drive expression of an ER stress–inducing protein (the cog mutant of thyroglobulin) in hypertrophic chondrocytes. The hypertrophic chondrocytes in this mouse exhibited ER stress with a characteristic UPR response. In addition, the hypertrophic zone was expanded, gene expression patterns were disrupted, osteoclast recruitment to the vascular invasion front was reduced, and long bone growth decreased. Our data demonstrate that triggering ER stress per se in hypertrophic chondrocytes is sufficient to induce the essential features of the cartilage pathology associated with MCDS and confirm that ER stress is a central pathogenic factor in the disease mechanism. These findings support the contention that ER stress may play a direct role in the pathogenesis of many connective tissue disorders associated with the expression of mutant extracellular matrix proteins.

We report the results of a long-term, multi-site field trial of a situated awareness device for families called the "Whereabouts Clock". The Clock displayed family members' current location as one of four privacy-preserving, deliberately coarse-grained categories (HOME, WORK, SCHOOL or ELSEWHERE). In use, the Clock supported not only family co-ordination but also more emotive aspects of family life such as reassurance, connectedness, identity and social touch. This emphasized aspects of family life frequently neglected in Ubicomp, such as the ways in which families' awareness of each others' activities contributes to a sense of a family's identity. We draw further on the results to differentiate between location as a technical aspect of awareness systems and what we characterize as "location-in-interaction". Location-in-interaction is revealed as an emotional, accountable and even moral part of family life.

Pregnancy is associated with profound changes in renal hemodynamics and electrolyte handling. Relaxin, a hormone secreted by the corpus luteum, has been shown to induce pregnancy-like increases in renal blood flow and glomerular filtration rate (GFR) and alter osmoregulation in nonpregnant female and male rats. However, its effects on renal electrolyte handling are unknown. Accordingly, the influence of short (2 h)- and long-term (7 day) infusion of relaxin on renal function was determined in the male rat. Short term infusion of recombinant human relaxin (rhRLX) at 4 microg.h(-1).100 g body wt(-1) induced a significant increase in effective renal blood flow (ERBF) within 45 min, which peaked at 2 h of infusion (vehicle, n = 6, 2.1 +/- 0.4 vs. rhRLX, n = 7, 8.1 +/- 1.1 ml.min(-1).100 g body wt(-1), P < 0.01). GFR and urinary excretion of electrolytes were unaffected. After a 7-day infusion of rhRLX at 4 microg/h, ERBF (1.4 +/- 0.2 vs. 2.5 +/- 0.4 ml.min(-1).100 g body wt(-1), P < 0.05), urine flow rate (3.1 +/- 0.3 vs. 4.3 +/- 0.4 microl.min(-1).100 g body wt(-1), P < 0.05) and urinary sodium excretion (0.8 +/- 0.1 vs. 1.2 +/- 0.1 micromol.min(-1).100 g body wt(-1), P < 0.05) were significantly higher; plasma osmolality and sodium concentrations were lower in rhRLX-treated rats. These data show that long-term relaxin infusion induces a natriuresis and diuresis in the male rat. The mechanisms involved are unclear, but they do not involve changes in plasma aldosterone or atrial natriuretic peptide concentrations.

We present an investigation into how hand usage is affected by different body postures (Sitting at a table, Lying down and Standing) when interacting with smartphones. We theorize a list of factors (smartphone support, body support and muscle usage) and explore their influence the tilt and rotation of the smartphone. From this we draw a list of hypotheses that we investigate in a quantitative study. We varied the body postures and grips (Symmetric bimanual, Asymmetric bimanual finger, Asymmetric bimanual thumb and Single-handed) studying the effects through a dual pointing task. Our results showed that the body posture Lying down had the most movement, followed by Sitting at a table and finally Standing. We additionally generate reports of motions performed using different grips. Our work extends previous research conducted with multiple grips in a sitting position by including other body postures, it is anticipated that UI designers will use our results to inform the development of mobile user interfaces.