A geometric path from zero Lyapunov exponents to rotation cocycles

We consider cocycles of isometries on spaces of nonpositive curvature $H$. We show that the supremum of the drift over all invariant ergodic probability measures equals the infimum of the displacements of continuous sections under the cocycle dynamics. In particular, if a cocycle has uniform sublinear drift, then there are almost invariant sections, that is, sections that move arbitrarily little under the cocycle dynamics. If, in addition, $H$ is a symmetric space, then we show that almost invariant sections can be made invariant by perturbing the cocycle.Comment: To appear in Ergodic Theory and Dynamical Systems. The title was reverted to a previous one. Some modifications were made according to the referee's suggestions. We also included an alternative proof of Theorem

The significance of the time interval between antecedent pregnancy and diagnosis of high-risk gestational trophoblastic tumours

It is thought that the time interval between the antecedent pregnancy and diagnosis of gestational trophoblastic tumours (GTTs) may influence the outcome of these patients. In this study, we investigate the significance of this time interval. Multivariate analysis was used to investigate if the time interval was of prognostic significance from our cohort of 241 high-risk patients with GTT. Subsequent cutpoint analysis was used to determine an optimal cutpoint for the interval covariate. The outcome of these patients was plotted according to the Kaplan–Meier method. The time interval was of prognostic significance on multivariate analysis. A period of greater than 2.8 years after pregnancy was found to be of most significance. The 5-year overall survival was 62.0% (95% CI: 47–76%) for greater than 2.8 years vs 94% (95% CI: 91–97%) for less than 2.8 years (P<0.001). Multivariate analysis showed the presence of liver metastasis and the number of metastasis was also of prognostic importance. The interval between antecedent pregnancy and diagnosis in high-risk GTT is of prognostic significance. This gives some insight into the pathogenesis of the disease

The effect of different skin-ankle brace application pressures on quiet single-limb balance and electromyographic activation onset of lower limb muscles

<p>Abstract</p> <p>Background</p> <p>Several studies have been carried out in order to investigate the effect of ankle bracing on ankle joint function and performance. However, no study so far has examined the role of skin-brace interface pressure in neuromuscular control. The aim of this study was to investigate the effect of different skin-ankle brace interface pressures on quiet single limb balance and the electromyographic (EMG) activation sequence of four lower limb muscles.</p> <p>Methods</p> <p>Thirty three male physical education students who volunteered to take part in the study were measured under three ankle brace conditions: i) without brace, ii) with brace and 30 kPa application pressure and iii) with brace and 60 kPa application pressure. Single limb balance (anteroposterior and mediolateral parameter) was assessed on the dominant lower limb, with open and closed eyes, on a force platform, simultaneously with the EMG recording of four lower lower limb muscles' (gastrocnemius, peroneus longus, rectus femoris and biceps femoris) activation onset.</p> <p>Results</p> <p>The results showed that overall balance (total stability parameter) was not significantly affected in any of the three ankle brace conditions. However, the anteroposterior centre of pressure excursion and centre of pressure excursion velocity were significantly increased with the application of ankle brace, both with 30 and 60 kPa application pressures. Furthermore, it was found that single limb balance was significantly worse with closed eyes compared to open eyes. EMG measurements showed that the sequence of lower limb activation onset was not affected in any of the three ankle brace application conditions. The results of this study showed that the application of an ankle brace with two different skin-brace interface pressures had no effect on overall single limb balance and the sequence of lower limb muscle activation.</p> <p>Conclusion</p> <p>These findings suggest that peripheral joint receptors are either not adequately stimulated by the brace application and therefore are not able to alter the balance control strategy of the CNS, or that they play a less important role in the control of single limb balance. Further research is needed in this area with more dynamic and functional measurements, before the safe use of ankle bracing can be widely recommended.</p

Thymidine phosphorylase expression in normal, hyperplastic and neoplastic prostates: correlation with tumour associated macrophages, infiltrating lymphocytes, and angiogenesis

Thymidine phosphorylase is an angiogenic factor primarily expressed by cancer cells, stromal cells and tumour-associated macrophages in many human malignancies. These different types of thymidine phosphorylase-expressing cells, however, may have a distinct place in the angiogenic process, and this question was addressed in the present study. A series of 20 normal/hyperplastic prostate glands and 60 prostate carcinomas was investigated by immunohistochemistry, using specific antibodies for thymidine phosphorylase (P-GF.44C), tumour-associated macrophages (CD68), endothelium (CD31) and prostate specific antigen (ER-PR8). Thymidine phosphorylase expression by normal and hyperplastic epithelial or stromal cells occurred almost exclusively in the context of an intense lymphocytic infiltrate. High thymidine phosphorylase cancer cells and thymidine phosphorylase stromal cells expression was associated with high angiogenesis in prostate carcinomas, and this significant association was extended to include both tumour-associated macrophages and tumour-infiltrating lymphocytes. Thymidine phosphorylase expression and tumour-infiltrating lymphocytes were related inversely with prostate specific antigen reactivity. In conclusion, thymidine phosphorylase is a major angiogenic factor in prostate carcinomas and its up-regulation is likely to occur in the context of a host immune response

An Allograft Glioma Model Reveals the Dependence of Aquaporin-4 Expression on the Brain Microenvironment

Aquaporin-4 (AQP4), the main water channel of the brain, is highly expressed in animal glioma and human glioblastoma in situ. In contrast, most cultivated glioma cell lines don’t express AQP4, and primary cell cultures of human glioblastoma lose it during the first passages. Accordingly, in C6 cells and RG2 cells, two glioma cell lines of the rat, and in SMA mouse glioma cell lines, we found no AQP4 expression. We confirmed an AQP4 loss in primary human glioblastoma cell cultures after a few passages. RG-2 glioma cells if grafted into the brain developed AQP4 expression. This led us consider the possibility of AQP4 expression depends on brain microenvironment. In previous studies, we observed that the typical morphological conformation of AQP4 as orthogonal arrays of particles (OAP) depended on the extracellular matrix component agrin. In this study, we showed for the first time implanted AQP4 negative glioma cells in animal brain or flank to express AQP4 specifically in the intracerebral gliomas but neither in the extracranial nor in the flank gliomas. AQP4 expression in intracerebral gliomas went along with an OAP loss, compared to normal brain tissue. AQP4 staining in vivo normally is polarized in the astrocytic endfoot membranes at the glia limitans superficialis and perivascularis, but in C6 and RG2 tumors the AQP4 staining is redistributed over the whole glioma cell as in human glioblastoma. In contrast, primary rat or mouse astrocytes in culture did not lose their ability to express AQP4, and they were able to form few OAPs

Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs.</p> <p>Methods</p> <p>We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue.</p> <p>Conclusions</p> <p>Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.</p

Uneven spread of cis- and trans-editing aminoacyl-tRNA synthetase domains within translational compartments of P. falciparum

Accuracy of aminoacylation is dependent on maintaining fidelity during attachment of amino acids to cognate tRNAs. Cis- and trans-editing protein factors impose quality control during protein translation, and 8 of 36 Plasmodium falciparum aminoacyl-tRNA synthetase (aaRS) assemblies contain canonical putative editing modules. Based on expression and localization profiles of these 8 aaRSs, we propose an asymmetric distribution between the parasite cytoplasm and its apicoplast of putative editing-domain containing aaRSs. We also show that the single copy alanyl- and threonyl-tRNA synthetases are dually targeted to parasite cytoplasm and apicoplast. This bipolar presence of two unique synthetases presents opportunity for inhibitor targeting their aminoacylation and editing activities in twin parasite compartments. We used this approach to identify specific inhibitors against the alanyl- and threonyl-tRNA synthetases. Further development of such inhibitors may lead to anti-parasitics which simultaneously block protein translation in two key parasite organelles, a strategy of wider applicability for pathogen control

Frequent loss of heterozygosity and altered expression of the candidate tumor suppressor gene 'FAT' in human astrocytic tumors

Background: We had earlier used the comparison of RAPD (Random Amplification of Polymorphic DNA) DNA fingerprinting profiles of tumor and corresponding normal DNA to identify genetic alterations in primary human glial tumors. This has the advantage that DNA fingerprinting identifies the genetic alterations in a manner not biased for locus. Methods: In this study we used RAPD-PCR to identify novel genomic alterations in the astrocytic tumors of WHO grade II (Low Grade Diffuse Astrocytoma) and WHO Grade IV (Glioblastoma Multiforme). Loss of heterozygosity (LOH) of the altered region was studied by microsatellite and Single Nucleotide Polymorphism (SNP) markers. Expression study of the gene identified at the altered locus was done by semi-quantitative reverse-transcriptase-PCR (RT-PCR). Results: Bands consistently altered in the RAPD profile of tumor DNA in a significant proportion of tumors were identified. One such 500 bp band, that was absent in the RAPD profile of 33% (4/12) of the grade II astrocytic tumors, was selected for further study. Its sequence corresponded with a region of FAT, a putative tumor suppressor gene initially identified in Drosophila. Fifty percent of a set of 40 tumors, both grade II and IV, were shown to have Loss of Heterozygosity (LOH) at this locus by microsatellite (intragenic) and by SNP markers. Semi-quantitative RT-PCR showed low FAT mRNA levels in a major subset of tumors. Conclusion: These results point to a role of the FAT in astrocytic tumorigenesis and demonstrate the use of RAPD analysis in identifying specific alterations in astrocytic tumors