3,370 research outputs found
Altered expression of the voltage-gated calcium channel subunit α2δ-1: a comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain.
The auxiliary α2δ-1 subunit of voltage-gated calcium channels is up-regulated in dorsal root ganglion neurons following peripheral somatosensory nerve damage, in several animal models of neuropathic pain. The α2δ-1 protein has a mainly presynaptic localization, where it is associated with the calcium channels involved in neurotransmitter release. Relevant to the present study, α2δ-1 has been shown to be the therapeutic target of the gabapentinoid drugs in their alleviation of neuropathic pain. These drugs are also used in the treatment of certain epilepsies. In this study we therefore examined whether the level or distribution of α2δ-1 was altered in the hippocampus following experimental induction of epileptic seizures in rats, using both the kainic acid model of human temporal lobe epilepsy, in which status epilepticus is induced, and the tetanus toxin model in which status epilepticus is not involved. The main finding of this study is that we did not identify somatic overexpression of α2δ-1 in hippocampal neurons in either of the epilepsy models, unlike the upregulation of α2δ-1 that occurs following peripheral nerve damage to both somatosensory and motor neurons. However, we did observe local reorganisation of α2δ-1 immunostaining in the hippocampus only in the kainic acid model, where it was associated with areas of neuronal cell loss, as indicated by absence of NeuN immunostaining, dendritic loss, as identified by areas where microtubule-associated protein-2 immunostaining was missing, and reactive gliosis, determined by regions of strong OX42 staining
Flavor SU(3) symmetry and QCD factorization in and decays
Using flavor SU(3) symmetry, we perform a model-independent analysis of
charmless decays. All the relevant
topological diagrams, including the presumably subleading diagrams, such as the
QCD- and EW-penguin exchange diagrams and flavor-singlet weak annihilation
ones, are introduced. Indeed, the QCD-penguin exchange diagram turns out to be
important in understanding the data for penguin-dominated decay modes. In this
work we make efforts to bridge the (model-independent but less quantitative)
topological diagram or flavor SU(3) approach and the (quantitative but somewhat
model-dependent) QCD factorization (QCDF) approach in these decays, by
explicitly showing how to translate each flavor SU(3) amplitude into the
corresponding terms in the QCDF framework. After estimating each flavor SU(3)
amplitude numerically using QCDF, we discuss various physical consequences,
including SU(3) breaking effects and some useful SU(3) relations among decay
amplitudes of and .Comment: 47 pages, 3 figures, 28 table
Mesenchymal stem cell-based therapy for ischemic stroke
Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field
A validation of the Oswestry Spinal Risk Index
Purpose
The purpose of this study was to validate the Oswestry Spinal Risk Index (OSRI) in an external population. The OSRI predicts survival in patients with metastatic spinal cord compression (MSCC).
Methods
We analysed the data of 100 patients undergoing surgical intervention for MSCC at a tertiary spinal unit and recorded the primary tumour pathology and Karnofsky performance status to calculate the OSRI. Logistic regression models and survival plots were applied to the data in accordance with the original paper.
Results
Lower OSRI scores predicted longer survival. The OSRI score predicted survival accurately in 74% of cases (p = 0.004).
Conclusions
Our study has found that the OSRI is a significant predictor of survival at levels similar to those of the original authors and is a useful and simple tool in aiding complex decision making in patients presenting with MSC
Antibiotikaeinsatz in der Bayerischen Schweinehaltungspraxis ABYS: Antibiotikaeinsatz und Antibiotikaresistenz in ökologischen Betrieben
Between 2012 and 2014, ABYS study recorded antibiotic use, detection and resistance data for 23 organic and 35 conventional pig farms. Antibiotic contents of
farm-made fertilizers were assessed by LC/MS-MS. Phenotypic antimicrobial resistance was investigated in Escherichia (E.) coli (indicator bacteria); antimicrobial
resistance genes of the total bacterial microbiota (sul(II), tet(A), tet(B), tet(M); marker Measured in nUDD (number of animals treated multiplied by treatment days), colistin
was the most frequently used antibiotic, in organic farms followed by tylosin, doxycycline and amoxicillin. Antibiotic residues were rarely detected; however, manure contained up to 10^8 antimicrobial resistance genes per gram; concentrations were higher when the antibiotic had been used on farm. In six farms, antimicrobial resistant E. coli were tracked from the moment when pigs were placed on farm. Some isolates carried a broad variety of resistances from the
very beginning that were maintained until slaughter, despite the fact that partly no antibiotics were applied during fattening. Approaches for reducing carry-over of antimicrobial resistant bacteria will be discusse
Early (and Later) LHC Search Strategies for Broad Dimuon Resonances
Resonance searches generally focus on narrow states that would produce a
sharp peak rising over background. Early LHC running will, however, be
sensitive primarily to broad resonances. In this paper we demonstrate that
statistical methods should suffice to find broad resonances and distinguish
them from both background and contact interactions over a large range of
previously unexplored parameter space. We furthermore introduce an angular
measure we call ellipticity, which measures how forward (or backward) the muon
is in eta, and allows for discrimination between models with different parity
violation early in the LHC running. We contrast this with existing angular
observables and demonstrate that ellipticity is superior for discrimination
based on parity violation, while others are better at spin determination.Comment: 31 pages, 19 figures. References added, minor modifications made to
section
Proteolytic maturation of α 2 δ represents a checkpoint for activation and neuronal trafficking of latent calcium channels
The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ. Uncleaved α2δ does not support trafficking of CaV2.2 channel complexes into neuronal processes, and inhibits Ca2+ entry into synaptic boutons, and we can reverse this by controlled intracellular proteolytic cleavage. We propose a model whereby uncleaved α2δ subunits maintain immature calcium channels in an inhibited state. Proteolytic processing of α2δ then permits voltage-dependent activation of the channels, acting as a checkpoint allowing trafficking only of mature calcium channel complexes into neuronal processes
A double shunt technique for the prevention of ischaemia of a congenital, solitary, pelvic kidney during abdominal aortic aneurysm repair: a case report
<p>Abstract</p> <p>Introduction</p> <p>Congenital solitary pelvic kidney is a rare condition, and its association with an abdominal aortic aneurysm is even more unusual. To the best of our knowledge, only two such cases have been reported in the literature to date.</p> <p>Case presentation</p> <p>We report the case of a 59-year-old Caucasian man with a congenital solitary pelvic kidney, who was found to have an abdominal aortic aneurysm 83 mm in diameter. Abdominal computed tomography angiography clearly identified two renal arteries, one originating from the aortic bifurcation. and the other from the proximal portion of the right common iliac artery. At surgery, renal ischaemia was prevented by introduction of an axillofemoral shunt (consisting of two femoral cannulas and a vent tube of extracorporeal circulation) from the right axillary to the right femoral artery, and a second Argyle shunt from the right common iliac artery to the origin of the left renal artery. A 20 mm Dacron tube graft was then implanted. Our patient's postoperative renal function was normal.</p> <p>Conclusion</p> <p>The renal preservation double shunt technique used in this case seems to be effective during abdominal aortic aneurysm repair.</p
Systematic search for putative new domain families in Mycoplasma gallisepticum genome
<p>Abstract</p> <p>Background</p> <p>Protein domains are the fundamental units of protein structure, function and evolution. The delineation of different domains in proteins is important for classification, understanding of structure, function and evolution. The delineation of protein domains within a polypeptide chain, namely at the genome scale, can be achieved in several ways but may remain problematic in many instances. Difficulties in identifying the domain content of a given sequence arise when the query sequence has no homologues with experimentally determined structure and searching against sequence domain databases also results in insignificant matches. Identification of domains under low sequence identity conditions and lack of structural homologues acquire a crucial importance especially at the genomic scale.</p> <p>Findings</p> <p>We have developed a new method for the identification of domains in unassigned regions through indirect connections and scaled up its application to the analysis of 434 unassigned regions in 726 protein sequences of <it>Mycoplasma gallisepticum </it>genome. We could establish 71 new domain relationships and probable 63 putative new domain families through intermediate sequences in the unassigned regions, which importantly represent an overall 10% increase in PfamA domain annotation over the direct assignment in this genome.</p> <p>Conclusions</p> <p>The systematic analysis of the unassigned regions in the <it>Mycoplasma gallisepticum </it>genome has provided some insight into the possible new domain relationships and putative new domain families. Further investigation of these predicted new domains may prove beneficial in improving the existing domain prediction algorithms.</p
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