Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns.

In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2-63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient\u27s tumour, must be carefully interpreted

The PLASMONX Project for advanced beam physics experiments

The Project PLASMONX is well progressing into its design phase and has entered as well its second phase of procurements for main components. The project foresees the installation at LNF of a Ti:Sa laser system (peak power > 170 TW), synchronized to the high brightness electron beam produced by the SPARC photo-injector. The advancement of the procurement of such a laser system is reported, as well as the construction plans of a new building at LNF to host a dedicated laboratory for high intensity photon beam experiments (High Intensity Laser Laboratory). Several experiments are foreseen using this complex facility, mainly in the high gradient plasma acceleration field and in the field of mono- chromatic ultra-fast X-ray pulse generation via Thomson back-scattering. Detailed numerical simulations have been carried out to study the generation of tightly focused electron bunches to collide with laser pulses in the Thomson source: results on the emitted spectra of X-rays are presented

Genetic correlations between diabetes and glaucoma: an analysis of continuous and dichotomous phenotypes

Purpose: A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits.Design: Cross-sectional study.Methods: We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure (IOP), central corneal thickness (CCT), corneal hysteresis (CH), corneal resistance factor (CRF), cup-disc ratio (CDR), and primary open-angle glaucoma (POAG)). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT and selected diabetes-related traits based on individual level phenotype data in two Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines (SOLAR).Results: Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a non-significant negative correlation between T2D and POAG (rg=-0.14; p=0.16). Using SOLAR, the genetic correlations between measured IOP, CCT, FBS, fasting insulin and hemoglobin A1c, were null. In contrast, genetic correlations between IOP and POAG (rg ≥0.45; p≤3.0E-04) and between CDR and POAG were high (rg =0.57; p=2.8E-10). However, genetic correlations between corneal properties (CCT, CRF and CH) and POAG were low (rg range: -0.18 - 0.11) and non-significant (p≥0.07).Conclusion: These analyses suggest there is limited genetic correlation between diabetes- and glaucoma-related traits

Measurements of sideward flow around the balance energy

Sideward flow values have been determined with the INDRA multidetector for Ar+Ni, Ni+Ni and Xe+Sn systems studied at GANIL in the 30 to 100 A.MeV incident energy range. The balance energies found for Ar+Ni and Ni+Ni systems are in agreement with previous experimental results and theoretical calculations. Negative sideward flow values have been measured. The possible origins of such negative values are discussed. They could result from a more important contribution of evaporated particles with respect to the contribution of promptly emitted particles at mid-rapidity. But effects induced by the methods used to reconstruct the reaction plane cannot be totally excluded. Complete tests of these methods are presented and the origins of the ``auto-correlation'' effect have been traced back. For heavy fragments, the observed negative flow values seem to be mainly due to the reaction plane reconstruction methods. For light charged particles, these negative values could result from the dynamics of the collisions and from the reaction plane reconstruction methods as well. These effects have to be taken into account when comparisons with theoretical calculations are done.Comment: 27 pages, 15 figure

Evidence for multiple alleles effecting muscling and fatness at the Ovine GDF8 locus

<p>Abstract</p> <p>Background</p> <p>The current investigation surveyed genetic polymorphism at the ovine <it>GDF8 </it>locus and determined its contribution to variation in muscling and fatness in sheep.</p> <p>Results</p> <p>Re-sequencing 2988 bp from a panel of 15 sires revealed a total of six SNP, none of which were located within exons of the gene. One of the identified SNP, <it>g+6723G>A</it>, is known to increase muscularity within the Belgian Texel. A genetic survey of 326 animals revealed that the mutation is near fixation within Australian Texels and present in additional breeds including White Suffolk, Poll Dorset and Lincoln. Using a resource population comprising 15 sires and 1191 half-sib progeny with genotypic data, the effect of this and other SNP was tested against a set of 50 traits describing growth, muscling, fatness, yield, meat and eating quality. The loss of function allele (<it>g+6723A</it>) showed significant effects on slaughter measurements of muscling and fatness. No effect was detected on objectively assessed meat quality however evidence was found for an association between <it>g+6723G>A</it>, decreased intramuscular fat and reduced eating quality. Haplotype analysis using flanking microsatellites was performed to search for evidence of currently unidentified mutations which might affect production traits. Four haplotypes were identified that do not carry <it>g+6723A </it>but which showed significant associations with muscling and fatness.</p> <p>Conclusion</p> <p>The finding that <it>g+6723G>A </it>is present within Australian sheep facilitated an independent evaluation into its phenotypic consequence. Testing was conducted using a separate genetic background and animals raised in different environments to the Belgian Texel in which it was first identified. The observation that the direction and size of effects for <it>g+6723A </it>is approximately consistent represented a robust validation of the effects of the mutation. Based on observed allele frequencies within breeds, selection for <it>g+6723A </it>will have the largest impact within the White Suffolk. <it>GDF8 </it>may harbour additional mutations which serve to influence economically important traits in sheep.</p

Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity.

The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress

Enhancing gold recovery from electronic waste via lixiviant metabolic engineering in Chromobacterium violaceum

10.1038/srep02236Scientific Reports3

Obesity management and continuing medical education in primary care: results of a Swiss survey

ABSTRACT: BACKGROUND: The worldwide increase in obesity is becoming a major health concern. General practitioners (GPs) play a central role in managing obesity. We aimed to examine Swiss GPs self-reported practice in diagnosis and treatment of obesity with a special focus on the performance of waist measurement.. METHODS: A structured self-reported questionnaire was mailed to 323 GPs recruited from four urban physician networks in Switzerland. Measures included professional experience, type of practice, obesity-related continuing medical education (CME) and practice in dealing with obesity such as waist measurement. We assessed the association between the performance of waist measurement and obesity-related CME by multivariate ordered logistic regression controlling for GP characteristics as potential confounders. RESULTS: A total of 187 GPs responded to the questionnaire. More than half of the GPs felt confident in managing obesity. The majority of the GPs (73%) spent less than 4 days in the last 5 years on obesity-related CME. More than half of GPs gave advice to reduce energy intakes (64%), intakes of high caloric and alcoholic drinks (56%) and to increase the physical activity (78%). Half of the GPs seldom performed waist measurement and documentation. The frequency of obesity-related CME was independently associated with the performance of waist measurement when controlled for GPs' characteristics by multivariate ordered logistic regression. CONCLUSIONS: The majority of GPs followed guideline recommendations promoting physical activity and dietary counselling. We observed a gap between the increasing evidence for waist circumference assessment as an important measure in obesity management and actual clinical practice. Our data indicated that specific obesity-related CME might help to reduce this gap