Skeletopy of the intumescentia lumbalis and conus medullaris applied to epidural anaesthesia in Leopardus geoffroyi

Background: Leopardus geoffroyi is a Neotropical wild felid with wide distribution in the south of the South American continent. The objective was to investigate the skeletopy of the intumescentia lumbalis (IL) and conus medullaris (CM) from 11 specimens of L. geoffroyi collected dead on highways. Materials and methods: The cadavers were fixed in formaldehyde solution and dissected to allow the dorsal exposure of IL and CM. The cranial and caudal limits were marked with radiopaque pins and radiographic projections were used to determine the skeletopy. The lengths of IL and CM were measured with a pachymeter. Results: In most specimens, the IL was located at the level of L4 and L5 vertebrae, although in 4 (1 male and 3 females) individuals its cranial limit was L3 and in 3 specimens (2 male and 1 female) the caudal limit was L6. The length of IL was 35.6 ± 6.7 mm. The CM had its base predominantly at the level of the L5 vertebra, although in some specimens the base was in L4 and in others in L6. The apex of the CM can be found since the lumbosacral junction until the level of the Cd2 vertebra. The CM measured 74.4 ± 14.3 mm. Conclusions: Based on the skeletopy, it can be suggested that epidural anaesthesia procedures in L. geoffroyi are safer with the introduction of the catheter through the sacrocaudal interarcual space, as recommended by some anaesthetists for the domestic cat

SysZNF: the C2H2 zinc finger gene database

C2H2 zinc finger (C2H2-ZNF) genes are one of the largest and most complex gene super-families in metazoan genomes, with hundreds of members in the human and mouse genome. The ongoing investigation of this huge gene family requires computational support to catalog genotype phenotype comparisons of C2H2-ZNF genes between related species and finally to extend the worldwide knowledge on the evolution of C2H2-ZNF genes in general. Here, we systematically collected all the C2H2-ZNF genes in the human and mouse genome and constructed a database named SysZNF to deposit available datasets related to these genes. In the database, each C2H2-ZNF gene entry consists of physical location, gene model (including different transcript forms), Affymetrix gene expression probes, protein domain structures, homologs (and synteny between human and mouse), PubMed references as well as links to relevant public databases. The clustered organization of the C2H2-ZNF genes is highlighted. The database can be searched using text strings or sequence information. The data are also available for batch download from the web site. Moreover, the graphical gene model/protein view system, sequence retrieval system and some other tools embedded in SysZNF facilitate the research on the C2H2 type ZNF genes under an integrative view. The database can be accessed from the URL http://epgd.biosino.org/SysZNF

RA-specific expression profiles and new candidate genes

Objective: To identify rheumatoid arthritis- (RA)-specific profiles of differentially expressed genes. Methods: Synovial tissues from RA and osteoarthritis (OA) patients and from normal joints were selected according to their disease-characteristic histology. Gene expression was analyzed using DNA microarrays (GeneChip; Unigene-array) and representational difference analysis (RDA). Data were validated on larger cohorts of patients by RT-PCR. Results: Nine hundred and eighty genes were significantly regulated in RA synovial tissue as compared with non-RA. Specialized cluster analysis identified a set of 312 genes as sufficient of unequivocally discriminating RA from non-RA patterns (class discovery). Genes of highest regulation were associated with leukocyte activation (chemokines, chemokine receptors, B- and T-cell genes), endothelial and angiogenic activation, tissue destruction and remodelling [MMP-3, BMP-4, TIMPs]. Interestingly, a large set of genes was down-regulated in RA (TGF-β superfamily, apoptosis-related genes, transcription factors). Osteopontin-like genes (n=46) — up-regulated in RA — and glutathione peroxidase-3-like genes (n=85) — down-regulated in RA — yielded the highest correlation coefficients (>0.94). Megakaryocyte stimulating factor (MSF), down-regulated in a subset of RA, may hold the key to subclassification: a loss-of-function mutation in the MSF-encoding gene leads to synovial hyperplasia in camptodactyly–arthropathy–coxa vara–pericarditis syndrome, and, as in RA, also to pericardial involvement. A further candidate, vitamin-D3-up-regulated protein-1 (VDUP-1), is regulated like MSF and predisposes to premature coronary artery disease when mutated, again a feature of a subset of RA. Conclusion: RA specific gene profiles were identified and are useful to improve diagnostics of the disease. Novel gene candidates not yet in the focus of RA pathogenesis have been identified that are likely to further the understanding of RA

Methods to detect faulty splices in the superconducting magnet system of the LHC

The incident of 19 September 2008 at the LHC was caused by a faulty inter-magnet splice of about 200 nΩ resistance. Cryogenic and electrical techniques have been developed to detect other abnormal splices, either between or inside the magnets. The existing quench protection system can be used to detect internal splices with R>20 nΩ. Since this system does not cover the bus between magnets, the cryogenic system is used to measure the rate of temperature rise due to ohmic heating. Accuracy of a few mK/h, corresponding to a few Watts, has been achieved, allowing detection of excess resistance, if it is more than 40 nΩ in a cryogenic subsector (two optical cells). Follow-up electrical measurements are made in regions identified by the cryogenic system. These techniques have detected two abnormal internal magnet splices of 100 nΩ and 50 nΩ respectively. In 2009, this ad hoc system will be replaced with a permanent one to monitor all splices at the nΩ level

A Large Hadron Electron Collider at CERN

This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed to run synchronously with the LHC in the twenties and to achieve an integrated luminosity of O(100) fb$^{-1}$. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC

Robust computational reconstitution – a new method for the comparative analysis of gene expression in tissues and isolated cell fractions

BACKGROUND: Biological tissues consist of various cell types that differentially contribute to physiological and pathophysiological processes. Determining and analyzing cell type-specific gene expression under diverse conditions is therefore a central aim of biomedical research. The present study compares gene expression profiles in whole tissues and isolated cell fractions purified from these tissues in patients with rheumatoid arthritis and osteoarthritis. RESULTS: The expression profiles of the whole tissues were compared to computationally reconstituted expression profiles that combine the expression profiles of the isolated cell fractions (macrophages, fibroblasts, and non-adherent cells) according to their relative mRNA proportions in the tissue. The mRNA proportions were determined by trimmed robust regression using only the most robustly-expressed genes (1/3 to 1/2 of all measured genes), i.e. those showing the most similar expression in tissue and isolated cell fractions. The relative mRNA proportions were determined using several different chip evaluation methods, among which the MAS 5.0 signal algorithm appeared to be most robust. The computed mRNA proportions agreed well with the cell proportions determined by immunohistochemistry except for a minor number of outliers. Genes that were either regulated (i.e. differentially-expressed in tissue and isolated cell fractions) or robustly-expressed in all patients were identified using different test statistics. CONCLUSION: Robust Computational Reconstitution uses an intermediate number of robustly-expressed genes to estimate the relative mRNA proportions. This avoids both the exclusive dependence on the robust expression of individual, highly cell type-specific marker genes and the bias towards an equal distribution upon inclusion of all genes for computation

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups

DNA methylation in the promoter region of the p16 (CDKN2/MTS-1/INK4A) gene in human breast tumours

The p16 (CDKN2/MTS-1/INK4A) gene is one of several tumour-suppressor genes that have been shown to be inactivated by DNA methylation in various human cancers including breast tumours. We have used bisulphite genomic sequencing to examine the detailed sequence specificity of DNA methylation in the CpG island promoter/exon 1 region in the p16 gene in DNA from a series of human breast cancer specimens and normal human breast tissue (from reductive mammaplasty). The p16 region examined was unmethylated in the four normal human breast specimens and in four out of nine breast tumours. In the other five independent breast tumour specimens, a uniform pattern of DNA methylation was observed. Of the nine major sites of DNA methylation in the amplified region from these tumour DNAs, four were in non-CG sequences. This unusual concentration of non-CG methylation sites was not a general phenomenon present throughout the genome of these tumour cells because the methylated CpG island regions of interspersed L1 repeats had a pattern of (almost exclusively) CG methylation similar to that found in normal breast tissue DNA and in DNA from tumours with unmethylated p16 genes. These data suggest that DNA methylation of the p16 gene in some breast tumours could be the result of an active process that generates a discrete methylation pattern and, hence, could ultimately be amenable to theraputic manipulation. © 1999 Cancer Research Campaig

Integrative modeling of transcriptional regulation in response to antirheumatic therapy

<p>Abstract</p> <p>Background</p> <p>The investigation of gene regulatory networks is an important issue in molecular systems biology and significant progress has been made by combining different types of biological data. The purpose of this study was to characterize the transcriptional program induced by etanercept therapy in patients with rheumatoid arthritis (RA). Etanercept is known to reduce disease symptoms and progression in RA, but the underlying molecular mechanisms have not been fully elucidated.</p> <p>Results</p> <p>Using a DNA microarray dataset providing genome-wide expression profiles of 19 RA patients within the first week of therapy we identified significant transcriptional changes in 83 genes. Most of these genes are known to control the human body's immune response. A novel algorithm called TILAR was then applied to construct a linear network model of the genes' regulatory interactions. The inference method derives a model from the data based on the Least Angle Regression while incorporating DNA-binding site information. As a result we obtained a scale-free network that exhibits a self-regulating and highly parallel architecture, and reflects the pleiotropic immunological role of the therapeutic target TNF-alpha. Moreover, we could show that our integrative modeling strategy performs much better than algorithms using gene expression data alone.</p> <p>Conclusion</p> <p>We present TILAR, a method to deduce gene regulatory interactions from gene expression data by integrating information on transcription factor binding sites. The inferred network uncovers gene regulatory effects in response to etanercept and thus provides useful hypotheses about the drug's mechanisms of action.</p