21 research outputs found
Functional and genetic analysis in type 2 diabetes of Liver X receptor alleles – a cohort study
<p>Abstract</p> <p>Background</p> <p>Liver X receptor alpha <it>(LXRA</it>) and beta (<it>LXRB</it>) regulate glucose and lipid homeostasis in model systems but their importance in human physiology is poorly understood. This project aimed to determine whether common genetic variations in <it>LXRA </it>and <it>LXRB </it>associate with type 2 diabetes (T2D) and quantitative measures of glucose homeostasis, and, if so, reveal the underlying mechanisms.</p> <p>Methods</p> <p>Eight common single nucleotide polymorphisms in <it>LXRA </it>and <it>LXRB </it>were analyzed for association with T2D in one French cohort (N = 988 cases and 941 controls), and for association with quantitative measures reflecting glucose homeostasis in two non-diabetic population-based samples comprising N = 697 and N = 1344 adults. Investigated quantitative phenotypes included fasting plasma glucose, serum insulin, and HOMA<sub>IR </sub>as measure of overall insulin resistance. An oral glucose tolerance test was performed in N = 1344 of adults. The two alleles of the proximal <it>LXRB </it>promoter, differing only at the SNP rs17373080, were cloned into reporter vectors and transiently transfected, whereupon allele-specific luciferase activity was measured. rs17373080 overlapped, according to <it>in silico </it>analysis, with a binding site for Nuclear factor 1 (NF1). Promoter alleles were tested for interaction with NF1 using direct DNA binding and transactivation assays.</p> <p>Results</p> <p>Genotypes at two <it>LXRB </it>promoter SNPs, rs35463555 and rs17373080, associated nominally with T2D (P values 0.047 and 0.026). No <it>LXRA </it>or <it>LXRB </it>SNP associated with quantitative measures reflecting glucose homeostasis. The rs17373080 C allele displayed higher basal transcription activity (P value < 0.05). The DNA-mobility shift assay indicated that oligonucleotides corresponding to either rs17373080 allele bound NF1 transcription factors in whole cell extracts to the same extent. Different NF1 family members showed different capacity to transactivate the <it>LXRB </it>gene promoter, but there was no difference between promoter alleles in NF1 induced transactivation activity.</p> <p>Conclusion</p> <p>Variations in the <it>LXRB </it>gene promoter may be part of the aetiology of T2D. However, the association between <it>LXRB </it>rs35463555 and rs17373080, and T2D are preliminary and needs to be investigated in additional larger cohorts. Common genetic variation in <it>LXRA </it>is unlikely to affect the risk of developing T2D or quantitative phenotypes related to glucose homeostasis.</p
Investigation of confined acoustic phonons of tin nanoparticles during melting
Both confined acoustic and optic phonons were detected in tin
nanoparticles embedded in a \chem{SiO}
x thin film, using
inelastic light scattering, for different values of the particle
size. The eigenfrequencies of the acoustic modes are in agreement
with theoretical calculations for the free vibrations of an
elastic sphere. By increasing the temperature, clear effects of
particle melting on the optical and acoustic modes were observed,
together with the detection of a coupling with a strong central
peak. The observation of melting, and surface melting, through
direct investigation of the nanoparticle acoustic vibrational
eigenmodes represents a novel and relevant feature of this work
Raman, optical-absorption, and transmission electron microscopy study of size effects in germanium quantum dots
Quantum confinement effects in Ge nanocrystals in the size range 26-130 Angstrom have been investigated both on the electronic joint density of states and Raman spectra. The high degree of crystallinity of the particles as well as the minimized interaction with the matrix allow detection of shift and broadening of the TO Raman peak, which can be compared with theoretical expectations based on phonon confinement. The evolution of Raman and absorption spectra and their dependence on the nanocrystal dimensions can be related
Phase transitions in gallium nanodroplets detected by dielectric spectroscopy
Both theoretical and experimental works give evidence
that gallium exhibits solid phases labelled β, γ,
δ, ϵ besides the stable α phase strongly
dependent both on the size and the confinement conditions. An
experimental technique was used based on capacitance and
conductance measurements vs. temperature in the audiofrequency
range. This technique is particularly sensitive to the conditions
of the investigated particle surface that plays a fundamental role
in the melting and more generally in the phase transition
processes. In particular the strict relation between the
derivative of the capacitance with respect to the temperature,
, and the entropy of the system is considered. In gallium
nanoparticles 20 nm in radius, only the δ phase is shown to
occur. Further the transition to liquid phase was detected. The
melting process was found to start about 65Â K below the full
melting temperature value. In the case of particles 10Â nm in
radius, where different metastable phases may occur, the
capacitance vs. temperature curve was found to display abrupt
changes of the slope. The singularities are associated to a well
defined transition temperature
No Association of PTPN1 Polymorphisms With Macronutrient Intake and Measures of Adiposity
The protein tyrosine phosphatase nonreceptor type1 (PTPN1) gene encodes for the protein tyrosine phosphatase 1B, which suppresses the signaling pathway of leptin. Variations of the PTPN1 gene may lead to changes in leptin sensitivity and thereby influence eating behavior and measures of obesity. This study investigated the association between single-nucleotide polymorphisms (SNPs) of the PTPN1 gene and eating behavior and different measures of obesity, including visceral fat. We used data from a population-based, cross-sectional study of 382 Dutch white men aged 40-80 years. Self-reported macronutrient intake was collected with a food frequency questionnaire. Anthropometrical measurements included BMI, waist and hip circumference, total lean and fat mass measured with dual-energy X-ray absorptiometry, and visceral and subcutaneous fat measured with ultrasound. Associations were studied using linear regression analysis. There were no statistically significant associations of SNPs in the PTPN1 gene with dietary phenotypes or measures of obesity