PHOSPHORYLATION OF TAU PROTEIN IN BRAIN REGIONS OF CHRONIC RENAL FAILURE - INDUCED RATS: AMELIORATIVE EFFECT OF ERYTHROPOIETIN

Objectives: Chronic kidney disease (CKD) is a major clinical health problem as it is a systemic disorder that causes widespread organ damageand it is related to significant morbidity and mortality. Numerous studies have shown that, cognitive dysfunction increase in prevalence, due toincrease in reactive oxygen species in CKD severity. Tau proteins are proteins that stabilize microtubules. Hyperphosphorylation of tau reduces itsability to bind to microtubule causes dystabilization and production of neurofibrillary tangles (NFT) and neurodegeneration in the brain. Aberranthyperphosphorylation of tau is critical to the progression of neurodegeneration. Erythropoietin (EPO), a glycoprotein has been in clinical use formillions of anemic patients, and some studies show it has a neuroprotective role. Till now studies on the level of tau protein phosphorylation in brainregions of CKD-induced experimental animals and impact of EPO therapy are scarce. The aim of this study is to determine the impact of CKD and EPOtherapy on tau protein phosphorylation in brain regions of experimental rats.Methods: This study was performed on 48 adult male Wistar rats. Two phases were conducted to find out the difference between simultaneous andposttreatment of EPO. Phase I: 24 adult male Wistar rats were divided into 4 groups (6 animals each): Group 1: Control, Group 2: 0.75% of adeninemixed diet for 4 weeks, Group 3: 0.75% of adenine mixed diet was given for 4 weeks and simultaneous administration of EPO (100 IU/kg btw, ip)thrice weekly. Group 4: EPO alone (100 IU/Kg btw, ip) thrice per week. All the animals were sacrificed uniformly at the end of 4 weeks. In Phase II,24 animals were maintained separately for 40 days experimental period and divided into 4 groups. Groups 1, 2, and 4 animals were treated as samementioned in Phase I. Group 3: For EPO posttreatment, adenine mixed diet was given for 4 weeks for chronic renal failure (CRF) induction. After the 4week, EPO (100 IU/Kg btw.) was administered daily once for 12 days. At the end of the 40 days, all the animals were sacrificed uniformly. In both thephases after the treatment period, the brain tissue was removed and samples were homogenized. Total tau protein and phosphorylated tau proteinexpressions were analyzed by western blotting method.Results: In results, both the total tau and phosphorylated tau protein levels were significantly increased all the brain regions of CRF-induced groupswhen compared to control. In both simultaneous and posttreatment of EPO, the levels were retrieved.Conclusion: This study proves that EPO supplementation has a promising role in neuroprotection by preventing abnormal phosphorylated tauprotein accumulation. This study also proves the clinical usefulness of EPO as a supplemental therapeutic agent in neurotoxicity.Keywords: Chronic renal failure, Cognitive dysfunction, Hyperphosphorylation of tau protein, Erythropoietin.t

Asymptotic behaviour of estimators of the parameters of nearly unstable INAR(1) models

A sequence of first-order integer-valued autoregressive type (INAR(1)) processes is investigated, where the autoregressive type coefficients converge to 1. It is shown that the limiting distribution of the joint conditional least squares estimators for this coefficient and for the mean of the innovation is normal. Consequences for sequences of Galton{Watson branching processes with unobservable immigration, where the mean of the offspring distribution converges to 1 (which is the critical value), are discussed

Numerical preservation of velocity induced invariant regions for reaction-diffusion systems on evolving surfaces

We propose and analyse a finite element method with mass lumping (LESFEM) for the numerical approximation of reaction-diffusion systems (RDSs) on surfaces in R3 that evolve under a given velocity field. A fully-discrete method based on the implicit-explicit (IMEX) Euler time-discretisation is formulated and dilation rates which act as indicators of the surface evolution are introduced. Under the assumption that the mesh preserves the Delaunay regularity under evolution, we prove a sufficient condition, that depends on the dilation rates, for the existence of invariant regions (i) at the spatially discrete level with no restriction on the mesh size and (ii) at the fully-discrete level under a timestep restriction that depends on the kinetics, only. In the specific case of the linear heat equation, we prove a semi- and a fully-discrete maximum principle. For the well-known activator-depleted and Thomas reaction-diffusion models we prove the existence of a family of rectangles in the phase space that are invariant only under specific growth laws. Two numerical examples are provided to computationally demonstrate (i) the discrete maximum principle and optimal convergence for the heat equation on a linearly growing sphere and (ii) the existence of an invariant region for the LESFEM-IMEX Euler discretisation of a RDS on a logistically growing surface

Transglutaminase 6: a protein associated with central nervous system development and motor function.

Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Studies on phosphorus oxychloride and aluminium chloride complex

1. Anhydrous aluminium chloride reacts with phosphorus oxychloride to give a complex with a composition AlCl3.2 POCl3 which can be prepared in the form of a free flowing powder. 2. The phosphorus oxychloride-aluminium chloride complex in nitrobenzene dissociates into AlCl3.POCl3 and POCl3 as indicated by the cryoscopic measurements. 3. The solution of the complex in nitrobenzene has a higher specific conductivity than the corresponding electrical conductivities of individual components. Similar higher electrical conductance is observed when the two components are mixed in nitrobenzene in different proportions. 4.When a solution of anhydrous aluminium chloride in nitrobenzene is titrated conductometrically against a solution of phosphorus oxychloride in nitrobenzene, a limiting value in the conductivity is reached at point corresponding to the molecular composition, the components in the ratio of 1:2 AlCl3: POCl3 in solution. 5. The absorption maxima of the complex in nitrobenzene solution differ from the absorption maximum of the individual components

Automated segmentation of visceral and subcutaneous (deep and superficial) adipose tissues in normal and overweight men

10.1002/jmri.24655Journal of Magnetic Resonance Imaging414924-93