150 research outputs found

    A robust method for estimating gene expression states using Affymetrix microarray probe level data

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    <p>Abstract</p> <p>Background</p> <p>Microarray technology is a high-throughput method for measuring the expression levels of thousand of genes simultaneously. The observed intensities combine a non-specific binding, which is a major disadvantage with microarray data. The Affymetrix GeneChip assigned a mismatch (MM) probe with the intention of measuring non-specific binding, but various opinions exist regarding usefulness of MM measures. It should be noted that not all observed intensities are associated with expressed genes and many of those are associated with unexpressed genes, of which measured values express mere noise due to non-specific binding, cross-hybridization, or stray signals. The implicit assumption that all genes are expressed leads to poor performance of microarray data analyses. We assume two functional states of a gene - expressed or unexpressed - and propose a robust method to estimate gene expression states using an order relationship between PM and MM measures.</p> <p>Results</p> <p>An indicator 'probability of a gene being expressed' was obtained using the number of probe pairs within a probe set where the PM measure exceeds the MM measure. We examined the validity of the proposed indicator using Human Genome U95 data sets provided by Affymetrix. The usefulness of 'probability of a gene being expressed' is illustrated through an exploration of candidate genes involved in neuroblastoma prognosis. We identified the candidate genes for which expression states differed (un-expressed or expressed) when compared between two outcomes. The validity of this result was subsequently confirmed by quantitative RT-PCR.</p> <p>Conclusion</p> <p>The proposed qualitative evaluation, 'probability of a gene being expressed', is a useful indicator for improving microarray data analysis. It is useful to reduce the number of false discoveries. Expression states - expressed or unexpressed - correspond to the most fundamental gene function 'On' and 'Off', which can lead to biologically meaningful results.</p

    A Novel Animal Model of Borrelia recurrentis Louse-Borne Relapsing Fever Borreliosis Using Immunodeficient Mice

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    Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primates (i.e., not in other laboratory or domestic animals). Here, we present the first non-primate animal model of LBRF, using SCID (-B, -T cells) and SCID BEIGE (-B, -T, -NK cells) immunocompromised mice. These animals were infected with B. recurrentis A11 or A17, or with B. duttonii 1120K3 as controls. B. recurrentis caused a relatively mild but persistent infection in SCID and SCID BEIGE mice, but did not proliferate in NUDE (-T) and BALB/c (wild-type) mice. B. duttonii was infectious but not lethal in all animals. These findings demonstrate that the immune response can limit relapsing fever even in the absence of humoral defense mechanisms. To study the significance of phagocytic cells in this context, we induced systemic depletion of such cells in the experimental mice by injecting them with clodronate liposomes, which resulted in uncontrolled B. duttonii growth and a one-hundred-fold increase in B. recurrentis titers in blood. This observation highlights the role of macrophages and other phagocytes in controlling relapsing fever infection. B. recurrentis evolved from B. duttonii to become a primate-specific pathogen that has lost the ability to infect immunocompetent rodents, probably through genetic degeneration. Here, we describe a novel animal model of B. recurrentis based on B- and T-cell-deficient mice, which we believe will be very valuable in future research on LBRF. Our study also reveals the importance of B-cells and phagocytes in controlling relapsing fever infection

    Pain patterns and descriptions in patients with radicular pain: Does the pain necessarily follow a specific dermatome?

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    <p>Abstract</p> <p>Background</p> <p>It is commonly stated that nerve root pain should be expected to follow a specific dermatome and that this information is useful to make the diagnosis of radiculopathy. There is little evidence in the literature that confirms or denies this statement. The purpose of this study is to describe and discuss the diagnostic utility of the distribution of pain in patients with cervical and lumbar radicular pain.</p> <p>Methods</p> <p>Pain drawings and descriptions were assessed in consecutive patients diagnosed with cervical or lumbar nerve root pain. These findings were compared with accepted dermatome maps to determine whether they tended to follow along the involved nerve root's dermatome.</p> <p>Results</p> <p>Two hundred twenty-six nerve roots in 169 patients were assessed. Overall, pain related to cervical nerve roots was non-dermatomal in over two-thirds (69.7%) of cases. In the lumbar spine, the pain was non-dermatomal in just under two-thirds (64.1%) of cases. The majority of nerve root levels involved non-dermatomal pain patterns except C4 (60.0% dermatomal) and S1 (64.9% dermatomal). The sensitivity (SE) and specificity (SP) for dermatomal pattern of pain are low for all nerve root levels with the exception of the C4 level (Se 0.60, Sp 0.72) and S1 level (Se 0.65, Sp 0.80), although in the case of the C4 level, the number of subjects was small (n = 5).</p> <p>Conclusion</p> <p>In most cases nerve root pain should not be expected to follow along a specific dermatome, and a dermatomal distribution of pain is not a useful historical factor in the diagnosis of radicular pain. The possible exception to this is the S1 nerve root, in which the pain does commonly follow the S1 dermatome.</p

    Differential Allocation of Constitutive and Induced Chemical Defenses in Pine Tree Juveniles: A Test of the Optimal Defense Theory

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    Optimal defense theory (ODT) predicts that the within-plant quantitative allocation of defenses is not random, but driven by the potential relative contribution of particular plant tissues to overall fitness. These predictions have been poorly tested on long-lived woody plants. We explored the allocation of constitutive and methyl-jasmonate (MJ) inducible chemical defenses in six half-sib families of Pinus radiata juveniles. Specifically, we studied the quantitative allocation of resin and polyphenolics (the two major secondary chemicals in pine trees) to tissues with contrasting fitness value (stem phloem, stem xylem and needles) across three parts of the plants (basal, middle and apical upper part), using nitrogen concentration as a proxy of tissue value. Concentration of nitrogen in the phloem, xylem and needles was found to be greater higher up the plant. As predicted by the ODT, the same pattern was found for the concentration of non-volatile resin in the stem. However, in leaf tissues the concentrations of both resin and total phenolics were greater towards the base of the plant. Two weeks after MJ application, the concentrations of nitrogen in the phloem, resin in the stem and total phenolics in the needles increased by roughly 25% compared with the control plants, inducibility was similar across all plant parts, and families differed in the inducibility of resin compounds in the stem. In contrast, no significant changes were observed either for phenolics in the stems, or for resin in the needles after MJ application. Concentration of resin in the phloem was double that in the xylem and MJ-inducible, with inducibility being greater towards the base of the stem. In contrast, resin in the xylem was not MJ-inducible and increased in concentration higher up the plant. The pattern of inducibility by MJ-signaling in juvenile P. radiata is tissue, chemical-defense and plant-part specific, and is genetically variable

    The provocative lumbar facet joint

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    Low back pain is the most common pain symptom experienced by American adults and is the second most common reason for primary care physician visits. There are many structures in the lumbar spine that can serve as pain generators and often the etiology of low back pain is multifactorial. However, the facet joint has been increasingly recognized as an important cause of low back pain. Facet joint pain can be diagnosed with local anesthetic blocks of the medial branches or of the facet joints themselves. Subsequent radiofrequency lesioning of the medial branches can provide more long-term pain relief. Despite some of the pitfalls associated with facet joint blocks, they have been shown to be valid, safe, and reliable as a diagnostic tool. Medial branch denervation has shown some promise for the sustained control of lumbar facet joint-mediated pain, but at this time, there is insufficient evidence that it is a wholly efficacious treatment option. Developing a universal algorithm for evaluating facet joint-mediated pain and standard procedural techniques may facilitate the performance of larger outcome studies. This review article provides an overview of the anatomy, pathophysiology, diagnosis, and treatment of facet joint-mediated pain

    Pathogenesis, diagnosis and management of pneumorrhachis

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    Pneumorrhachis (PR), the presence of intraspinal air, is an exceptional but eminent radiographic finding, accompanied by different aetiologies and possible pathways of air entry into the spinal canal. By reviewing the literature and analysing a personal case of traumatic cervical PR after head injury, we present current data regarding the pathoanatomy, clinical and radiological presentation, diagnosis and differential diagnosis and treatment modalities of patients with PR and associated pathologies to highlight this uncommon phenomenon and outline aetiology-based guidelines for the practical management of PR. Air within the spinal canal can be divided into primary and secondary PR, descriptively classified into extra- or intradural PR and aetiologically subsumed into iatrogenic, traumatic and nontraumatic PR. Intraspinal air is usually found isolated not only in the cervical, thoracic and, less frequently, the lumbosacral regions but can also be located in the entire spinal canal. PR is almost exceptional associated with further air distributions in the body. The pathogenesis and aetiologies of PR are multifold and can be a diagnostic challenge. The diagnostic procedure should include spinal CT, the imaging tool of choice. PR has to be differentiated from free intraspinal gas collections and the coexistence of air and gas within the spinal canal has to be considered differential diagnostically. PR usually represents an asymptomatic epiphenomenon but can also be symptomatic by itself as well as by its underlying pathology. The latter, although often severe, might be concealed and has to be examined carefully to enable adequate patient treatment. The management of PR has to be individualized and frequently requires a multidisciplinary regime

    Male mating biology

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    Before sterile mass-reared mosquitoes are released in an attempt to control local populations, many facets of male mating biology need to be elucidated. Large knowledge gaps exist in how both sexes meet in space and time, the correlation of male size and mating success and in which arenas matings are successful. Previous failures in mosquito sterile insect technique (SIT) projects have been linked to poor knowledge of local mating behaviours or the selection of deleterious phenotypes during colonisation and long-term mass rearing. Careful selection of mating characteristics must be combined with intensive field trials to ensure phenotypic characters are not antagonistic to longevity, dispersal, or mating behaviours in released males. Success has been achieved, even when colonised vectors were less competitive, due in part to extensive field trials to ensure mating compatibility and effective dispersal. The study of male mating biology in other dipterans has improved the success of operational SIT programmes. Contributing factors include inter-sexual selection, pheromone based attraction, the ability to detect alterations in local mating behaviours, and the effects of long-term colonisation on mating competitiveness. Although great strides have been made in other SIT programmes, this knowledge may not be germane to anophelines, and this has led to a recent increase in research in this area
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