A Rac1-independent role for P-Rex1 in melanoblasts

No abstract available

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Four-Week Nutritional Audit of Preterm Infants Born <33 Weeks Gestation

Aim: Preterm nutritional audits have previously been conducted using assumed milk composition. We audited protein and energy intakes in the first 28 days of preterm life using both assumed milk composition and milk analysis to assess their effect on weight gain and to determine if the recommended reasonable range of intakes were met. Methods: Parenteral and enteral intakes and weight gain were recorded daily for infants (n = 63) born <33 weeks gestation, using assumed milk composition. Macronutrient composition was determined by milk analysis for a subset of infants (n = 36). Linear mixed models analysis was used to assess the influence of energy and protein intakes on weight gain. Results: (Data median (range)): Infants (n = 63) gestation and birth weight were 30 (24–32) weeks and 1400 (540–2580) g, respectively. Macronutrient milk composition was variable: protein 16.6 (13.4–27.6) g/L, fat 46.1 (35.0–62.4) g/L, lactose 68.0 (50.9–74.8) g/L, energy 3074 (2631–3761) kJ/L. Intakes based on measured composition differed from assumed. Protein intake was significantly associated with weight gain. Compared to infants with longer gestations, those born <28 weeks gestation were fed lower volumes, were more reliant on parenteral nutrition, took an additional seven days to transition to fortified feeds and median weight gain velocity took a fortnight longer to reach targets.Conclusion: Preterm milk composition is variable and routine fortification using assumed composition may result in inappropriate nutrition. Fortification regimens stratified by birth gestation may be necessary to achieve preterm nutrition and growth targets. Milk analysis is required for accurate nutritional audit

Giving and sharing in the computer-mediated economy

The paper examines how digital technology mediates the behaviour of consumers in three online systems that facilitate offline gift giving and sharing (Freecycle, Couchsurfing, and Landshare). Findings derived from a netnography and depth interviews reveal how technology is used to enact and influence the management of identity, partner selection, ritual normalisation, and negotiation of property rights. The findings have significant implications for the design and management of systems that encourage non-monetary forms of collaborative consumption

Invasion of Normal Human Fibroblasts Induced by v-Fos Is Independent of Proliferation, Immortalization, and the Tumor Suppressors p16(INK4a) and p53

Invasion is generally perceived to be a late event during the progression of human cancer, but to date there are no consistent reports of alterations specifically associated with malignant conversion. We provide evidence that the v-Fos oncogene induces changes in gene expression that render noninvasive normal human diploid fibroblasts highly invasive, without inducing changes in growth factor requirements or anchorage dependence for proliferation. Furthermore, v-Fos-stimulated invasion is independent of the pRb/p16(INK4a) and p53 tumor suppressor pathways and telomerase. We have performed microarray analysis using Affymetrix GeneChips, and the gene expression profile of v-Fos transformed cells supports its role in the regulation of invasion, independent from proliferation. We also demonstrate that invasion, but not proliferation, is dependent on the activity of the up-regulated epidermal growth factor receptor. Taken together, these results indicate that AP-1-directed invasion could precede deregulated proliferation during tumorigenesis and that sustained activation of AP-1 could be the epigenetic event required for conversion of a benign tumor into a malignant one, thereby explaining why many malignant human tumors present without an obvious premalignant hyperproliferative dysplastic lesion

Prenatal protein restriction does not affect the proliferation and differentiation of rat preadipocytes

Poor development in utero may favor the development of obesity in adulthood. Animal studies showed that embryo manipulation in vitro or nutritional insults during the embryonic and fetal stages of development may lead to obesity in adult life. We studied the in vitro proliferation and differentiation of adipocytes to investigate whether early protein restriction may program cell growth and development. In a series of experiments, 2 different low-protein diet protocols were compared. In both cases, pregnant rats were fed a diet with a high (18-20%) or low (8-9%) protein content during gestation and/or lactation. Preadipocytes were isolated from the fetuses, neonates, and weanling offspring. Moderate protein restriction, imposed during either gestation and/or lactation, did not affect the capacity of preadipose cells to divide or store fat. Because previous studies showed that early protein restriction alters the metabolism of sulfur amino acids, we also investigated the effects of methionine, taurine, and homocysteine on proliferation and differentiation of preadipocytes. The supplementation of the diet with methionine or the addition of homocysteine and taurine to the culture media did not influence the development of preadipocytes. We obtained no evidence for the direct reprogramming of the precursor or stem cells and suggest that the subsequent alteration in fat accretion may therefore reflect a change in the neuroendocrine environment