PASE: a novel method for functional prediction of amino acid substitutions based on physicochemical properties.

Background: Non-synonymous single-nucleotide polymorphisms (nsSNPs) within the coding regions of genes causing amino acid substitutions (AASs) may have a large impact on protein function. The possibilities to identify nsSNPs across genomes have increased notably with the advent of next-generation sequencing technologies. Thus, there is a strong need for efficient bioinformatics tools to predict the functional effect of AASs.

Genetic dissection of growth traits in a Chinese indigenous × commercial broiler chicken cross.

Background: In China, consumers often prefer indigenous broiler chickens over commercial breeds, as they have characteristic meat qualities requested within traditional culinary customs. However, the growth-rate of these indigenous breeds is slower than that of the commercial broilers, which means they have not yet reached their full economic value. Therefore, combining the valuable meat quality of the native chickens with the efficiency of the commercial broilers is of interest.

A novel generalized ridge regression method for quantitative genetics.

As the molecular marker density grows, there is a strong need in both genome-wide association studies and genomic selection to fit models with a large number of parameters. Here we present a computationally efficient generalized ridge regression (RR) algorithm for situations in which the number of parameters largely exceeds the number of observations. The computationally demanding parts of the method depend mainly on the number of observations and not the number of parameters.

Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment.

Background: : Recent population studies have suggested that children with multiple exposures to anesthesia and surgery at an early age are at an increased risk of cognitive impairment. The authors therefore have established an animal model with single versus multiple exposures of anesthetic(s) in young versus adult mice, aiming to distinguish the role of different types of anesthesia in cognitive impairment.

Methods: : Six- and 60-day-old mice were exposed to various anesthesia regimens.

Endothelial acyl-CoA synthetase 1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.

Objective: Saturated fatty acids, such as palmitic and stearic acid, cause detrimental effects in endothelial cells and have been suggested to contribute to macrophage accumulation in adipose tissue and the vascular wall, in states of obesity and insulin resistance. Long-chain fatty acids are believed to require conversion into acyl-CoA derivatives to exert most of their detrimental effects, a reaction catalyzed by acyl-CoA synthetases (ACSLs). The objective of this study was to investigate the role of ACSL1, an ACSL isoform previously shown to mediate inflammatory effects in myeloid cells, in regulating endothelial cell responses to a saturated fatty acid-rich environment in vitro and in vivo.

Repetitive step training with preparatory signals improves stability limits in patients with Parkinson's disease.

Objective: To examine the effects of repetitive volitional and compensatory step training with preparatory signals on the limits of stability, postural and gait skills, and spatiotemporal gait characteristics in patients with Parkinson's disease with no falls during the previous 12 months.

Design: Randomized clinical trial with assessor blinded to group assignment.

Subjects: Twenty-eight patients with Parkinson's disease with no falls during the previous 12 months.

Prevalence of circulating CD4+CD28null T cells is associated with early atherosclerotic damage in patients with end-stage renal disease undergoing hemodialysis.

CD4(+) T-cell subsets lacking surface CD28 in peripheral blood have been suggested to predispose people to atherosclerosis. To determine if CD4(+)CD28(null) T cells are involved in the immunopathological process of atherosclerotic damage in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD), we characterized peripheral-blood CD4(+)CD28(null) T cells from HD patients and investigated the association between these cells and early atherosclerotic damage. Four color flow cytometric analyses showed that HD patients had significantly higher percentages of CD4(+)CD28(null) T cells in circulating blood than healthy subjects (HS).

Inheritance beyond plain heritability: variance-controlling genes in Arabidopsis thaliana.

The phenotypic effect of a gene is normally described by the mean-difference between alternative genotypes. A gene may, however, also influence the phenotype by causing a difference in variance between genotypes. Here, we reanalyze a publicly available Arabidopsis thaliana dataset [1] and show that genetic variance heterogeneity appears to be as common as normal additive effects on a genomewide scale.

Tracheal extubation of deeply anesthetized pediatric patients: a comparison of sevoflurane and sevoflurane in combination with low-dose remifentanil.

Purpose: We aimed to observe the emergence characteristics of children tracheally extubated in deep anesthesia with sevoflurane or sevoflurane in combination with low-dose remifentanil.

Methods: We randomly allocated 50 pediatric patients undergoing elective electronic cochlear implantation to groups either receiving sevoflurane (Group S, n = 25), or sevoflurane plus low-dose remifentanil (Group SR, n = 25), during extubation from anesthesia. In Group S, subjects were tracheally extubated while breathing 1.

Propofol-remifentanil intravenous anesthesia and spontaneous ventilation for airway foreign body removal in children with preoperative respiratory impairment.

Purpose: To investigate the efficacy and safety of propofol-remifentanil total intravenous anesthesia (TIVA) and spontaneous ventilation for foreign body (FB) removal in pediatric patients with preoperative respiratory impairment.

Methods: We carried out a prospective observational clinical study of FB removal using a rigid bronchoscope under propofol-remifentanil TIVA and spontaneous ventilation in 65 pediatric patients who presented with preoperative respiratory impairment. Heart rate, blood pressure, pulse oxygen saturation (SpO(2)), respiratory rate, endtidal CO(2) (ETCO(2))(ETCO2), induction time, and remifentanil rate were recorded.

RNA interference-mediated silencing of BACE and APP attenuates the isoflurane-induced caspase activation.

Background: β-Amyloid protein (Aβ) has been shown to potentiate the caspase-3 activation induced by the commonly used inhalation anesthetic isoflurane. However, it is unknown whether reduction in Aβ levels can attenuate the isoflurane-induced caspase-3 activation. We therefore set out to determine the effects of RNA interference-mediated silencing of amyloid precursor protein (APP) and β-site APP-cleaving enzyme (BACE) on the levels of Aβ and the isoflurane-induced caspase-3 activation.

How to deal with genotype uncertainty in variance component quantitative trait loci analyses.

Dealing with genotype uncertainty is an ongoing issue in genetic analyses of complex traits. Here we consider genotype uncertainty in quantitative trait loci (QTL) analyses for large crosses in variance component models, where the genetic information is included in identity-by-descent (IBD) matrices. An IBD matrix is one realization from a distribution of potential IBD matrices given available marker information.

Hierarchical likelihood opens a new way of estimating genetic values using genome-wide dense marker maps.

Background: Genome-wide dense markers have been used to detect genes and estimate relative genetic values. Among many methods, Bayesian techniques have been widely used and shown to be powerful in genome-wide breeding value estimation and association studies. However, computation is known to be intensive under the Bayesian framework, and specifying a prior distribution for each parameter is always required for Bayesian computation.

qtl.outbred: Interfacing outbred line cross data with the R/qtl mapping software.

Background: qtl.outbred is an extendible interface in the statistical environment, R, for combining quantitative trait loci (QTL) mapping tools. It is built as an umbrella package that enables outbred genotype probabilities to be calculated and/or imported into the software package R/qtl.

Vertebrate paralogous MEF2 genes: origin, conservation, and evolution.

Background: The myocyte enhancer factor 2 (MEF2) gene family is broadly expressed during the development and maintenance of muscle cells. Although a great deal has been elucidated concerning MEF2 transcription factors' regulation of specific gene expression in diverse programs and adaptive responses, little is known about the origin and evolution of the four members of the MEF2 gene family in vertebrates.

Methodology/principal Findings: By phylogenetic analyses, we investigated the origin, conservation, and evolution of the four MEF2 genes.

Substitution pattern of the CArG element in human and mouse genomes.

cis-Elements CArG bound by serum response factor (SRF) are presently being intensively studied, but little is known about the substitution pattern of functional CArG elements. Here, we have performed the first evolutionary analysis of CArGome in the human and mouse genome through bioinformatic methods and statistical tests. We calculated the substitution rate at each site of the functional CArG elements.

The action of thrombin in intracerebral hemorrhage induced brain damage is mediated via PKCα/PKCδ signaling.

The present study investigates the role of protein kinase C alpha/delta (PKCα/PKCδ) in brain injury induced by intracerebral hemorrhage (ICH) by utilizing a rat model that received intracerebral injections of autologous blood and thrombin (TM). The activation and expression of PKC and PKCδ were analyzed by Western blot and immunohistochemistry. A PKC inhibitor, dihydrochloride (H7), was administrated intraperitoneally after injury to evaluate the effect of inhibition of PKC on ICH and TM induced brain damage.

Post-treatment of Bax-inhibiting peptide reduces neuronal death and behavioral deficits following global cerebral ischemia.

Cerebral ischemia is a major cause of adult disability and death worldwide. Evidence suggests that Bax-dependent initiation and activation of intrinsic apoptotic pathways contribute to ischemic brain injury. We investigated the Bax-inhibiting peptide VPALR, designed from the rat Ku70-Bax inhibiting domain, on the apoptotic neuronal cell death and behavioral deficits following global cerebral ischemia.

Characteristics of the CArG-SRF binding context in mammalian genomes.

Serum response factor (SRF), a member of the MADS family, binds a 10-bp cis element known as the CArG box. However, despite our extensive knowledge of SRF and the CArG box, limited information is available on the CArG-SRF binding context or how CArG flanking sequences are defined. We used statistical tests and computer simulation to find characteristics of the CArG-SRF binding context.

Anesthetic management for an infant undergoing endoscopic resection of a large subglottic papiloma.

Background: An infant with a large subglottic papilloma that caused severe respiratory distress needed anesthesia during resection of the papilloma.

Aims: We planned an approach to the airway management this infant that we thought would be successful.

Methods: We used three main tactics in managing the airway - inhaled sevoflurane, intravenous fentanyl and the patient's resumed spontaneous breathing.

Improving resolution by the second-order correlation of light fields.

As important analysis tools, microscopes with high spatial resolution are indispensable for scientific research and clinical diagnosis. We report a proof-of-principle experimental demonstration of a two-arm microscope scheme and show that, by measuring the second-order correlation of light fields, more details of an object can be obtained through recording more information about the initial illumination field. The effects arising from the transverse coherence length and the axial correlation depth of the illumination field are also discussed.

The correlations of the function and positional distribution of the cis-elements CArG around the TSS in the genes of Mus musculus.

While many studies of cis-elements CArG bound by serum response factor (SRF) are in progress, little is known about the positional distribution of the functional CArG elements around the transcription start site (TSS) of genes that they influence. We use a validated CArG data set to calculate the distance distribution of functional CArG elements around the TSS. Distances between adjacent CArGs were also analyzed.

Radial artery calcification in end-stage renal disease patients is associated with deposition of osteopontin and diminished expression of alpha-smooth muscle actin.

Aim: Vascular access is the lifeline of haemodialysis patients and radial-cephalic fistula is the preferred type of access. We investigated vascular calcification in uraemia radial arteries and compared it with clinical parameters.

Methods: Artery specimens from 30 end-stage renal disease patients were collected, examined calcification by von Kossa and Alizarin red staining.