24 research outputs found

    Network and synaptic mechanisms underlying high frequency oscillations in the rat and cat olfactory bulb under ketamine-xylazine anesthesia

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    Wake-related ketamine-dependent high frequency oscillations (HFO) can be recorded in local field potentials (LFP) from cortical and subcortical regions in rodents. The mechanisms underlying their generation and occurrence in higher mammals are unclear. Unfortunately, anesthetic doses of pure ketamine attenuate HFO, which has precluded their investigation under anesthesia. Here, we show ketamine-xylazine (KX) anesthesia is associated with a prominent 80–130 Hz rhythm in the olfactory bulb (OB) of rats, whereas 30–65 Hz gamma power is diminished. Simultaneous LFP and thermocouple recordings revealed the 80–130 Hz rhythm was dependent on nasal respiration. This rhythm persisted despite surgical excision of the piriform cortex. Silicon probes spanning the dorsoventral aspect of the OB revealed this rhythm was strongest in ventral areas and associated with microcurrent sources about the mitral layer. Pharmacological microinfusion studies revealed dependency on excitatory-inhibitory synaptic activity, but not gap junctions. Finally, a similar rhythm occurred in the OB of KX-anesthetized cats, which shared key features with our rodent studies. We conclude that the activity we report here is driven by nasal airflow, local excitatory-inhibitory interactions, and conserved in higher mammals. Additionally, KX anesthesia is a convenient model to investigate further the mechanisms underlying wake-related ketamine-dependent HFO

    Increased oxidative stress in asthma - relation to inflammatory blood and lung biomarkers and airway remodeling indices

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    Airway inflammation in asthma is related to increased reactive oxygen species generation, potentially leading to tissue injury and subsequent airway remodeling. We evaluated oxidative stress in peripheral blood from asthmatic subjects (n = 74) and matched controls (n = 65), using recently developed real-time monitoring of the protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay. We also investigated the relation of the systemic oxidative stress response in asthma to disease severity, lung function, airway remodeling indices (lung computed tomography and histology), and blood and bronchoalveolar lavage fluid (BAL) inflammatory biomarkers. We documented enhanced systemic oxidative stress in asthma, reflected by 35% faster and 58% higher cumulative fluorescent product generation in the CBA assay (p < 0.001 for both). The dynamics of HP generation correlated inversely with lung function but not with asthma severity or histological measures of airway remodeling. HP generation was associated positively with inflammatory indices in the blood (e.g., C-reactive protein) and BAL (e.g., interleukin [IL]-6, IL-12p70, and neutrophil count). Bronchial obstruction, thicker airway walls, increased BAL IL-6, and citrullinated histone 3 in systemic circulation independently determined increased HP formation. In conclusion, a real-time CBA assay showed increased systemic HP generation in asthma. In addition, it was associated with inflammatory biomarkers, suggesting that proper disease control can also lead to a decrease in oxidative stress

    Hydrodynamics and Mass Transfer Analysis in BioFlow® Bioreactor Systems

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    Biotechnological processes involving the presence of microorganisms are realized by using various types of stirred tanks or laboratory-scale dual-impeller commercial bioreactor. Hydrodynamics and mass transfer rate are crucial parameters describing the functionality and efficiency of bioreactors. Both parameters strictly depend on mixing applied during bioprocesses conducted in bioreactors. Establishing optimum hydrodynamics conditions for the realized process with microorganisms maximizes the yield of desired products. Therefore, our main objective was to analyze and define the main operational hydrodynamic parameters (including flow field, power consumption, mixing time, and mixing energy) and mass transfer process (in this case, gas–liquid transfer) of two different commercial bioreactors (BioFlo® 115 and BioFlo® 415). The obtained results are allowed using mathematical relationships to describe the analyzed processes that can be used to predict the mixing process and mass transfer ratio in BioFlo® bioreactors. The proposed correlations may be applied for the design of a scaled-up or scaled-down bioreactors

    Common Atlas Format and 3D Brain Atlas Reconstructor: Infrastructure for Constructing 3D Brain Atlases

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    One of the challenges of modern neuroscience is integrating voluminous data of diferent modalities derived from a variety of specimens. This task requires a common spatial framework that can be provided by brain atlases. The first atlases were limited to two-dimentional presentation of structural data. Recently, attempts at creating 3D atlases have been made to offer navigation within non-standard anatomical planes and improve capability of localization of different types of data within the brain volume. The 3D atlases available so far have been created using frameworks which make it difficult for other researchers to replicate the results. To facilitate reproducible research and data sharing in the field we propose an SVG-based Common Atlas Format (CAF) to store 2D atlas delineations or other compatible data and 3D Brain Atlas Reconstructor (3dBAR), software dedicated to automated reconstruction of three-dimensional brain structures from 2D atlas data. The basic functionality is provided by (1) a set of parsers which translate various atlases from a number of formats into the CAF, and (2) a module generating 3D models from CAF datasets. The whole reconstruction process is reproducible and can easily be configured, tracked and reviewed, which facilitates fixing errors. Manual corrections can be made when automatic reconstruction is not sufficient. The software was designed to simplify interoperability with other neuroinformatics tools by using open file formats. The content can easily be exchanged at any stage of data processing. The framework allows for the addition of new public or proprietary content

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Corrosion process assessment using a novel type of coupon installation

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    The main aim of this experimental study is to test the novel type of coupon installation. This set-up was used to carry out the corrosion process under aggressive conditions. Moreover, the effect of corrosion inhibitors on the scale-forming tendency was evaluated. The corrosive conditions were defined by using the Langelier Saturation Index (this index is an approximate indicator of the degree of saturation of CaCO3 in water) and the Ryznar stability index (this index is allowed to determine if the liquid sample is aggressive or not). Additionally, the inductively coupled plasma optical emission spectroscopy analysis was used to obtain the iron and calcium ions concentrations in the liquid samples from the tested coupon installation. The corrosion process for the established conditions was also described using the corrosion rate of the tested coupons. The obtained investigation contributes significantly by developing the novel coupon installation and demonstrating the procedure for testing the corrosion process with the application of coupons. This setup and method might be successfully applied for accelerated laboratory tests

    Classification of Daily Body Weight Gains in Beef Calves Using Decision Trees, Artificial Neural Networks, and Logistic Regression

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    The aim of the present study was to compare the predictive performance of decision trees, artificial neural networks, and logistic regression used for the classification of daily body weight gains in beef calves. A total of 680 pure-breed Simmental and 373 Limousin cows from the largest farm in the West Pomeranian Province, whose calves were fattened between 2014 and 2016, were included in the study. Pre-weaning daily body weight gains were divided into two categories: A—equal to or lower than the weighted mean for each breed and sex and B—higher than the mean. Models were developed separately for each breed. Sensitivity, specificity, accuracy, and area under the curve on a test set for the best model (random forest) were 0.83, 0.67, 0.76, and 0.82 and 0.68, 0.86, 0.78, and 0.81 for the Limousin and Simmental breeds, respectively. The most important predictors were daily weight gains of the dam when she was a calf, daily weight gains of the first calf, sex of the third calf, milk yield at first lactation, birth weight of the third calf, dam birth weight, dam hip height, and second calving season. The selected machine learning models can be used quite effectively for the classification of calves based on their daily weight gains
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