Skeletal muscle uncoupling protein-3 (UCP3) is reduced in type 2 diabetes, and in the pre-diabetic condition of impaired glucose tolerance (IGT). Here we examined whether intervention programs known ...to improve insulin sensitivity are paralleled by an increase in skeletal muscle UCP3 protein levels. Skeletal muscle UCP3 protein content was measured before and after one year of an exercise intervention in muscle biopsies of eight diabetic subjects. In addition, UCP3 was measured in IGT subjects before and after 1 year of following a lifestyle-intervention program or serving as control. In the diabetic patients a significant increase of ~75% in UCP3 protein was found after 1 year of exercise training (P < 0.05). In IGT subjects UCP3 protein increased in the intervention group (P = 0.02), while UCP3 remained unaltered in the control group (P = 0.64). Both, exercise training and a lifestyle-intervention program increase UCP3 protein content in skeletal muscle of subjects with reduced glycaemic control, indicating a restoration towards normal UCP3 levels. These data support the idea that UCP3 has a role in the aetiology of type 2 diabetes mellitus.
To determine p53 and p16 status as molecular markers of bladder cancer, in histologically proven benign bladder biopsies, obtained from lesions suspect for malignancy as judged by fluorescence ...cystoscopy. Immunohistochemical (IHC) staining was performed for p53 and p16, using the antibodies DO-7 and AB-4, respectively. The tissue sections were scored in percentages of nuclear staining for p53 and p16. Of 247 biopsies, 41/49 lesions appeared suspicious on fluorescence cystoscopy, but were histopathologically benign. 2/40 (5%) were > or =20% p53 positive as compared to 7/128 (5.5%) of all histopathologically benign biopsies. 24/37 (64.9%) were p16 negative (<5% positive cells) as compared to 84/125 (67.2%) of all benign biopsies. Most biopsies had a moderate to high degree of chronic cystitis. False positive lesions of fluorescence cystoscopy did not differ from benign lesions detected by standard white light cystoscopy with regard to p53 and p16 immunoreactivity. Little evidence remains for these lesions to be pre-malignant.
In adipose tissue, the microsomal enzyme 1,2-acyl CoA:diacylglyceroltransferase-1 (DGAT1) plays an important role in triglyceride storage. Because DGAT1 is expressed in skeletal muscle as well, we ...aimed to directly test the effect of DGAT1 on muscular triglyceride storage by overexpressing DGAT1 using in vivo DNA electroporation. A pcDNA3.1-DGAT1 construct in saline was injected in the left tibialis anterior muscle of rats, followed by the application of eight transcutaneous pulses, using the contralateral leg as sham-electroporated control. Electroporation of the DGAT1 construct led to significant overexpression of the DGAT1 protein. The functionality of DGAT1 overexpression is underscored by the pronounced diet-responsive increase in intramyocellular lipid (IMCL) storage. In chow-fed rats, DGAT1-positive myocytes showed significantly higher IMCL content compared with the control leg, which was almost devoid of IMCL (1.99 ± 1.13% vs. 0.017 ± 0.014% of total area fraction; P < 0.05). High-fat feeding increased IMCL levels in both DGAT1-positive and control myocytes, resulting in very high IMCL levels in DGAT1-overexpressing myocytes (4.96 ± 1.47% vs. 0.80 ± 0.14%; P < 0.05).
Our findings indicate that DGAT1 contributes to the storage of IMCL and that in vivo DNA electroporation is a promising tool to examine the functional consequences of altered gene expression in mature skeletal muscle.
...we collected faecal samples from 17 patients diagnosed with ulcerative colitis and 17 healthy controls, and determined levels of N-nitrosodimethylamine (NDMA), a predominant carcinogenic NOC, ...using gas chromatography-mass spectrometry, as previously described.).
We discuss a synchronous direct-sequence code division multiple-access (DS-CDMA) system based on block spreading in the presence of frequency-selective fading. Note that block spreading, which is ...also known as chip interleaving, refers to a spreading of a data block sequence, which is obtained by dividing a data symbol sequence into consecutive blocks. For such a system, we develop a simple new receiver that completely removes the multiuser interference (MUI) without using any channel information. The MUI-free operation is obtained by the use of a shift-orthogonal set of code sequences on which this receiver is based. Within the framework of the MUI-free receiver, we further present a subspace deterministic blind single-user channel estimation algorithm. As a benchmark for the MUI-free receiver and the corresponding subspace deterministic blind single-user channel estimation algorithm, we consider the linear multiuser equalizer and the corresponding subspace deterministic blind multiuser channel estimation algorithm developed by Liu and Xu (1996) for a standard synchronous DS-CDMA system in the presence of frequency-selective fading. We show that the complexity of the MUI-free receiver using the corresponding subspace deterministic blind single-user channel estimation algorithm is much smaller than the complexity of the linear multiuser equalizer using the corresponding subspace deterministic blind multiuser channel estimation algorithm. We further show that the performance of the MUI-free receiver is comparable with the performance of the linear multiuser equalizer. This is for the case in which the channels are known as well as for the case in which the channels are estimated with the corresponding subspace deterministic blind channel estimation algorithm.
Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis ...and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up.
Especially in dry summers, such as 2003 in Europe, wetlands may become subject to desiccation and oxidation processes may affect sediment top layers. In this paper, we present the results of a study ...in which the development of the pore water chemistry (major ions, nitrate, ammonium, phosphate and some metals) was monitored during experimental desiccation of previously anaerobic freshwater sediments. Three sediments with different concentrations of oxidizable sulphur were compared. Sediments appeared to respond very differently to prolonged oxidation due to desiccation. It can be concluded that oxidizable sulphur pools play an important role in freshwater wetlands. Water level fluctuations may have beneficial effects in sediments of which the buffer capacity is large enough to prevent acidification as a result of oxidation of reduced sulphur compounds. Oxidation of such sediments will result in net nitrogen losses and a decrease of the phosphate availability. Desiccation of sediments with high oxidizable sulphur contents, however, might lead to reactions that resemble those observed in acid sulphate soils. Extreme acidification might occur resulting in the mobilisation of high concentrations of potentially toxic metals such as aluminium and zinc. Dissolution of oxidized iron at very low pH will also result in the release of previously adsorbed phosphate. In freshwater systems, high concentrations of reduced sulphur will especially accumulate in reductive and iron-rich sediments which are fed by sulphate-enriched groundwater and which almost never fall dry.
Functional magnetic resonance imaging (fMRI) is a tool for mapping brain function that utilizes neuronal activity-induced changes in blood oxygenation. An efficient three-dimensional fMRI method is ...presented for imaging brain activity on conventional, widely available, 1.5-T scanners, without additional hardware. This approach uses large magnetic susceptibility weighting based on the echoshifting principle combined with multiple gradient echoes per excitation. Motor stimulation, induced by self-paced finger tapping, reliably produced significant signal increase in the hand region of the contralateral primary motor cortex in every subject tested.
The accuracy of forward models for EEG partly depends on the conductivity values of the head tissues. Yet, the influence of the conductivities on the model output is still not well understood. In ...this paper, we apply a variance-based sensitivity analysis method to the most common EEG forward models (three or four layers). This method is global because it quantifies the influence of each parameter with all the parameters varying at the same time. With nonlinear models, it helps to understand the interaction between parameters, which is not possible with simple sensitivity analyses (one-at-a-time variations, derivatives, and perturbations). By analyzing the potential topographies at the electrodes, we obtained several results. For a shallow dipole, the EEG topographies are mainly sensitive to the interaction between skull and scalp conductivities. It means that the variability of the EEG topographies is driven mostly by a function of skull and scalp conductivities. Similar results are presented for skull anisotropy and a current injection as performed in electrical impedance tomography. This global sensitivity analysis gives new information about EEG forward models-it identifies the main input parameters that need model refinement-and directions on how to calibrate these models.
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