Search

We present for the first time an integrated wirelessly powered Arduino processor and Bluetooth interface that are co-rotated with the cartridge to allow large-scale process integration on a centrifugal microfluidic platform. This highly modular, electronically controlled “Lab-on-a-Disc” system (eLoaD) can independently actuate up to 128 normally-closed valves by an array of microheaters during rotation for comprehensive, highly parallelized sample-to-answer automation. Additionally, we implement real-time optical (colour intensity) measurement for closed-loop control of liquid handling, sample preparation and detection.

BACKGROUND Microbial translocation has been associated with an increase in immune activation and inflammation in HIV infection despite effective highly active antiretroviral therapy. It has been shown that some probiotics have a beneficial effect by reducing intestinal permeability and, consequently, microbial translocation. OBJECTIVES To assess changes in microbial translocation and inflammation after treatment with probiotics (Saccharomyces boulardii) in HIV-1-infected patients with virologic suppression. METHODS A double-blind, randomized, placebo-controlled trial was conducted in 44 nonconsecutive HIV-1-infected patients with viral load of

Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER “wires” senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed --86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

The pathomechanism of Alzheimer's disease (AD) is multifactorial although the most popular hypotheses are centered on the effects of the misfolded, aggregated protein, amyloid beta (Abeta) and on Tau hyperphosphorylation.Double blinded clinical trials were planned to demonstrate the effect of Colostrinin (CLN) on instrumental daily activities of AD patients. The potential molecular mechanisms by which CLN mediates its effects were investigated by gene expression profiling.RNAs isolated from CLN-treated cells were analyzed by high-density oligonucleotide arrays. Network and pathway analyses were performed using the Ingenuity Pathway Analysis software.The Full Sample Analysis at week 15 showed a stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favor of CLN (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared to more advanced cases (p = 0.01). Data derived from microarray network analysis show that CLN elicits highly complex and multiphasic changes in the cells' transcriptome. Importantly, transcriptomal analysis showed that CLN alters gene expression of molecular networks implicated in Abeta precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Abeta. In addition, CLN enhanced the defense against oxidative stress and decreased expression of inflammatory chemokines and cytokines, thereby attenuating inflammatory processes that precede Alzheimer's and other neurological diseases.Together these data suggest that CLN has promising potential for clinical use in prevention and therapy of Alzheimer's and other age-associated central nervous system diseases.

Colostrinin (CLN) is a uniform mixture of low-molecular weight proline-rich polypeptides isolated from the mother's first milk, colostrum. Exposure of cells to CLN decreases intracellular levels of reactive oxygen species by regulating glutathione metabolism and modulating activities of antioxidant enzymes and mitochondrial function. It also inhibits beta amyloid-induced apoptosis and induces neurite outgrowth of pheochromocytoma cells. Administration of CLN to Alzheimer's disease patients has resulted in a stabilizing effect on cognitive function. We analyzed CLN-induced gene expression changes using high-density oligonucleotide arrays and transcriptomal network analysis. We found that CLN elicited highly complex and multiphasic changes in the gene expression profile of treated cells. CLN treatment affected a total of 58 molecular networks, 27 of which contained at least 10 differentially expressed genes. Here we present CLN-modulated gene networks as potential underlying molecular mechanisms leading to the reported effects of CLN on cellular oxidative state, chemokine and cytokine production, and cell differentiation, as well as on pathological processes like allergy, asthma, Alzheimer's, and other neurological diseases. Based on our results, we also predict possible modulatory effects of CLN on adipocytokine gene networks that play a crucial role in the pathobiology of diabetes, cardiovascular disorders, obesity, and inflammation. Taken together, CLN-altered gene expression networks presented here provide the molecular basis for previously described biological phenomena and predict potential fields of application for CLN in the prevention and treatment of diseases.

An amperometric peroxide biosensor was prepared by electrochemical deposition of horseradish peroxidase (HRP) on a Pt disc electrode modified with polyaniline (PANI) film doped with polyvinyl sulphonate (PVS). Electrochemical characterisation of the PANI-PVS film (without HRP) indicates a conducting electroactive polymer that exhibits fast reversible electrochemistry in 1 M HCl. The HRP-based sensor was stable and gave rise to reproducible steady state responses for up to two weeks, when operated as both organic phase and aqueous phase H 2 O 2 biosensors at -100 mV/Ag-AgCl and 25°C. The aqueous phase for the H 2 O 2 assay was 0·05 M phosphate buffer, pH 6·88, while acetone, acetonitrile, propan-2-ol and tetrahydrofuran (THF) organic phases were used. The analyses of the calibration curves of the biosensor showed that the system followed a Michaelis-Menten kinetics when operated either as organic- or aqueous-phase biosensors. The kinetic parameters K m ′ (apparent Michaelis-Menten constant), k cat ′ (apparent biosensor turnover rate constant), and k cat ′/ K m ′ biosensing efficiency parameter) were evaluated from the steady-state amperometric data obtained in the five solvent media. The values of the biosensor efficiency factor, k cat ′/ K m ′, show that the sensor exhibits greater efficiency for analyte detection when operated in organic-phase mode in acetonitrile medium than in aqueous buffer.

A mild and rapid protocol for cleavage of phosphate, phosphonate and phosphoramide esters. The scope and limitations of this microwave-assisted reaction is explored here.

Since temperature affects the inactivation rate of viruses in natural water systems, the aim of this study was to determine if a temperature shift could influence the structural integrity of model viruses. When crude lysates of MS-2 phage were seeded into groundwater microcosms and incubated at 27°C, complete virus inactivation took place in eight days. The temperature was then shifted to 4°C. Three days after the temperature shift, a two-log increase in virus titer (reactivation) occurred. However, when purified MS-2 lysates were added to groundwater microcosms, no reactivation was obtained. No reactivation of poliovirus took place when similar microcosm experiments were done. The sedimentation coefficients of MS-2 shifted from 80S to 58S, 48S, 37S, 32S, and 18S as inactivation proceeded in groundwater and distilled water controls. Similarly, the sedimentation coefficients of polioviruses changed from 156S to 142S, 135S, 117S, 105S, 95S, and 80 S as inactivation took place. There was no correlation between % virus inactivation and % decrease in virions with intact sedimentation coefficients, as reported earlier for poliovirus inactivated by chlorine. The results presented support our hypothesis that virus inactivation proceeds gradually, involving the rearrangement and (or) loss of capsomere components that may eventually lead to the ejection of nucleic acids. The intermediate particles generated as inactivation proceeds may be in a reversibly inactivated state, and may revert back to a fully infectious state when chemical components stabilize the virus particle.Key words: poliovirus, MS-2, groundwater, virus inactivation, virus reactivation.