Association of serum-soluble heat shock protein 60 with carotid atherosclerosis: clinical significance determined in a follow-up study

BACKGROUND AND PURPOSE: Previous work has shown that soluble heat shock protein 60 (HSP60; sHSP60), present in circulating blood, is associated with carotid atherosclerosis. In the current evaluation, we tested the hypothesis that sHSP60 levels are associated with the progression of carotid arteriosclerosis, prospectively. METHODS: The association of sHSP60 with early atherogenesis (5-year development and progression of nonstenotic carotid plaques) was investigated as part of the population-based prospective Bruneck Study. The current study focused on the follow-up period between 1995 and 2000 and, thus, included 684 subjects. RESULTS: sHSP60 levels measured in 1995 and 2000 were highly correlated (r=0.40; P<0.001), indicating consistency over a 5-year period. Circulating HSP60 levels were significantly correlated with antilipopolysaccharide and anti-HSP60 antibodies. It was also elevated in subjects with chronic infection (top quintile group of HSP60, among subjects with and without chronic infection: 23.8% versus 17.0%; P=0.003 after adjustment for age and sex). HSP60 levels were significantly associated with early atherogenesis, both in the entire population (multivariate odds ratio, for a comparison between quintile group V versus I+II: 2.0 [1.2 to 3.5] and the subgroup free of atherosclerosis at the 1995 baseline: 3.8 [1.6 to 8.9]). The risk of early atherogenesis was additionally amplified when high-sHSP60 and chronic infection were present together. CONCLUSIONS: Our study provides the first prospective data confirming an association between high levels of sHSP60 and early carotid atherosclerosis. This possibly indicates an involvement of sHSP60 in activating proinflammatory processes associated with early vessel pathology

SDF1 Gene Variation Is Associated with Circulating SDF1 alpha Level and Endothelial Progenitor Cell Number-The Bruneck Study

BACKGROUND: Stromal cell-derived factor-1 (SDF1) and its receptor CXC chemokine receptor 4 (CXCR4) play a critical role in progenitor cell homing, mobilization and differentiation. It would be interesting to assess the predictive value of SDF-1alpha level for EPC number, and to ascertain whether there is a relationship between SDF1 gene variation, plasma SDF-1alpha level, and the number and function of circulating EPCs. We also tested whether EPC number and function was related to CXCR4 gene variation. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped a cohort of individuals who participated in the Bruneck Study for single nucleotide polymorphisms (SNPs) in the SDF1 and CXCR4 genes, and measured blood SDF1alpha level as well as EPC number and function. SDF1alpha levels were correlated with age, gender, alcohol consumption, circulating reticulocyte numbers, and concentrations of matrix metalloproteinase-9, C-reactive protein, cystatin C, fibrinogen and homocytein. In blood samples taken in 2005, EPC number was inversely associated with SDF1alpha level (p<0.001). EPC number in 2005 was also inversely associated with SDF1alpha level in 2000 (p = 0.009), suggesting a predictive value of plasma SDF1alpha level for EPC number. There was an association between the SDF1 gene rs2297630 SNP A/A genotype, increased SDF1alpha level (p = 0.002) and lower EPC number (p = 0.006). CONCLUSIONS: Our data indicate that a SDF1 gene variation (rs2297630) has an influence on SDF1alpha level and circulating EPC number, and that plasma SDF1alpha level is a predictor of EPC number

Robust Models for Optic Flow Coding in Natural Scenes Inspired by Insect Biology

The extraction of accurate self-motion information from the visual world is a difficult problem that has been solved very efficiently by biological organisms utilizing non-linear processing. Previous bio-inspired models for motion detection based on a correlation mechanism have been dogged by issues that arise from their sensitivity to undesired properties of the image, such as contrast, which vary widely between images. Here we present a model with multiple levels of non-linear dynamic adaptive components based directly on the known or suspected responses of neurons within the visual motion pathway of the fly brain. By testing the model under realistic high-dynamic range conditions we show that the addition of these elements makes the motion detection model robust across a large variety of images, velocities and accelerations. Furthermore the performance of the entire system is more than the incremental improvements offered by the individual components, indicating beneficial non-linear interactions between processing stages. The algorithms underlying the model can be implemented in either digital or analog hardware, including neuromorphic analog VLSI, but defy an analytical solution due to their dynamic non-linear operation. The successful application of this algorithm has applications in the development of miniature autonomous systems in defense and civilian roles, including robotics, miniature unmanned aerial vehicles and collision avoidance sensors

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts

A study of the centrifugal projections to the pigeon retina using two fluorescent markers

The centrifugal projection to the retina of the adult pigeon was studied by the retrograde transport of Diamidino yellow and Fast blue. On the contralateral side in the nucleus isthmo-opticus 8400–10,900 cells were stained while in the surrounding area 1500–2800 marked ectopic cells were counted. Up to 94 neurones, which are nearly all ectopic, project to the ipsilateral eye. Using double-labelling we concluded that there are no cells projecting to both eyes. This study shows that in the adult pigeon there exist more ectopic cells projecting to the retina than previously reported in horseradish peroxidase experiments

Motion sensitivity in the nucleus of the basal optic root of the pigeon

1. Single-unit responses to large-field movement (angular velocity, w = 0.25-42 degrees/s) of sine-wave gratings of different spatial wavelength (lambda = 5.2-41 degrees) and contrast have been recorded in the nucleus of the basal optic root (nBOR) of the accessory optic system (AOS) of the pigeon. 2. The steady-state response to moving sine-wave gratings increases with increasing contrast to reach a saturation level at 25%. 3. Generally the steady-state responses of the cells passed through a maximum when stimulated at various velocities. In 12 of the 15 cells tested with six different velocities and four different spatial wavelengths, the location of the response maximum on the velocity scale depended on the spatial wavelength (lambda) used. That is, in these cells the response depends on the temporal frequency (tf = w/lambda) of the stimulus and not on its velocity alone. This is in agreement with the prediction of the theory of motion detection according to the basic version of the correlation scheme. 4. The temporal frequency for maximal response of individual cells shifts to higher values when the contrast of the sine-wave gratings is reduced to 5%. 5. The steady-state response of 16 of the recorded directional selective cells (53) is modulated with the temporal frequency of the stimulus, regardless of the phase of the grating at the beginning of its movement. 6. In phasic-tonically responding cells, the phasic response peak decays to the steady-state level with a time constant that becomes shorter as the temporal frequency of the stimulus increases. 7. The basic version of the correlation scheme includes only the time constant of one low-pass filter. Therefore the phasic response is expected to decay to the steady-state level with one and the same time constant, and the position of the maximal response on the temporal frequency scale should not be influenced by a change of pattern contrast. According to the model, phase-dependent modulations of the steady-state response should occur only when the spatial wavelength of the stimulus pattern is large compared with the sampling base of the underlying detector. Consequently the results given in points 4-6 cannot be described by a basic version of the correlation scheme