68 research outputs found

    Superior olivary complex organization and cytoarchitecture may be correlated with function and catarrhine primate phylogeny

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    In the mammalian auditory system, the medial nucleus of the trapezoid body and the lateral superior olive (MNTB-LSO system) contribute to binaural intensity processing and lateralization. Localization precision varies with the sound frequencies. As recency of common ancestry with human beings increases, primates have improved low-frequency sensitivity and reduced sensitivity to higher frequencies. The medial part of the MNTB is devoted to higher frequency processing. Thus, its high-frequency-dependent function is nearly lost in humans and its role in binaural processing as part of the contralateral pathway to the LSO remains questionable. Here, Nissl-stained sections of the superior olivary complex of man (Homo sapiens), bonobo (Pan paniscus), chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), gibbon (Hylobates lar), and macaque (Macaca fascicularis) were compared to reveal differences and coincidences. From chimpanzees to humans, the size of the LSO decreased, and the MNTB as a compact nucleus nearly disappears. From chimpanzees to humans, the LSO/MNTB ratio increases dramatically too, whereas the LSO/MSO ratio remains 1.1; a finding that probably corresponds to the phylogenetic proximity between the species

    Heat shock proteins in chronic kidney disease

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    Heat shock proteins (HSP) form a heterogenous, evolutionarily conserved group of molecules with high sequence homology. They mainly act as intracellular chaperones, protecting the protein structure and folding under stress conditions. The extracellular HSP, released in the course of damage or necrosis, play a pivotal role in the innate and adaptive immune responses. They also take part in many pathological processes. The aim of this review is to update the recent developments in the field of HSP in chronic kidney disease (CKD), in regard to three different aspects. The first is the assessment of the role of HSP, either positive or deleterious, in the pathogenesis of CKD and the possibilities to influence its progression. The second is the impact of dialysis, being a potentially modifiable stressor, on HSP and the attempt to assess the value of these proteins as the biocompatibility markers. The last area is that of kidney transplantation and the potential role of HSP in the induction of the immune tolerance in kidney recipients

    Association of 25-hydroxyvitamin D deficiency with NT-pro BNP levels in patients with acute myocardial infarction: a cross-sectional analysis

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    <p>Abstract</p> <p>Background</p> <p>Nutritional vitamin D deficiency is an emerging risk factor for acute myocardial infarction (AMI) and heart failure. The association of 25-hydroxyvitamin D levels with N-terminal pro B-type natriuretic peptide (NT-proBNP), a robust prognostic marker for post-AMI mortality and heart failure, is unknown and could illuminate a potential pathway for adverse outcomes among post-AMI patients with 25-hydroxyvitamin D deficiency.</p> <p>Methods</p> <p>In a cross-sectional analysis, we studied 238 AMI patients from 21 U.S. centers to test the association of nutritional vitamin D (25-hydroxyvitamin D [25(OH)D]) deficiency with NT-proBNP levels. Levels of 25(OH)D levels were categorized as normal (≥30 ng/mL), insufficient (>20 - <30 ng/mL), deficient (>10 - ≤20 ng/mL), or severely deficient (≤10 ng/mL).</p> <p>Results</p> <p>Low 25(OH)D levels were found in 95.7% of AMI patients. No significant trends for higher mean baseline log NT-proBNP levels in severely deficient (6.9 ± 1.3 pg/mL), deficient (6.9 ± 1.2 pg/mL), and insufficient (6.9 ± 0.9 pg/ml) groups were observed as compared with patients having normal (6.1 ± 1.7 pg/mL) levels, <it>P </it>= 0.17. Findings were similar in the subset of patients who had follow-up NT-proBNP levels drawn at one month. In multivariate regression modeling, after adjusting for multiple covariates, 25(OH)D was not associated with NT-proBNP.</p> <p>Conclusions</p> <p>Potential associations between nutritional vitamin D deficiency and prognosis in the setting of AMI are unlikely to be mediated through NT-proBNP pathways. Future studies should examine other mechanisms, such as inflammation and vascular calcification, by which 25(OH)D deficiency could mediate adverse outcomes post-AMI.</p

    Validation of biomarkers to predict response to immunotherapy in cancer: Volume I — pre-analytical and analytical validation

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    Teaching Business Models: Approaches and Success Criteria: Introduction to special issue

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    Teaching business models (BM) and business model innovation (BMI) in universities and business schools has become a common practice. Academia has acknowledged that despite the very normative nature of the concept, business model thinking unites and synergistically binds the very fundamental decisions about a business, i.e., how to create, deliver and capture value

    Aligned Schwann cells within 3D tissue-like gels provide guidance to regenerating neurites

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    There is a clinical demand to shorten the delay of reinnervation and improve functional recovery after peripheral nerve injury. A peripheral nerve repair device with the ability to direct and promote cellular growth across a lesion would be a promising alternative to nerve autograft repair, which is the current gold standard treatment. The growth of axons across a lesion is most effective when supported by columns of aligned Schwann cells, as found in an autograft. Here we report a technique to generate aligned Schwann cells within a stable and robust 3D collagen matrix, providing a cellular biomaterial that confers alignment on regenerating neurons. Collagen gels containing F7 Schwann cells were tethered for 24 h to permit cellular self-alignment and then plastic compressed by the rapid removal of the interstitial fluid from fully hydrated gels. This process generates stable tissue-like gels with cells situated within a dense, strong, three-dimensional matrix. Cell alignment was monitored before and after plastic compression using CellTracker dye and confocal image analysis. Dissociated dorsal root ganglia (DRG) cells were cultured on the surface of the material for 3 days and neurite growth was quantified using immunostaining and confocal microscopy. Chains of aligned Schwann cells were formed within the collagen matrix and persisted following plastic compression. This robust, aligned cellular biomaterial promotes and guides neuronal growth in a manner that mimics a nerve autograft. The next stage of this work is to integrate this cellular material into a repair device. Plastic compressed gels containing aligned Schwann cells have been rolled into columns which can then be packed together. In vitro testing of this engineered endoneurium, within a silicone outer tube, demonstrates the potential of such a device to function as an implantable conduit for peripheral nerve repair

    Cerebral expression of the alpha2-subunit of soluble guanylyl cyclase is linked to cerebral maturation and sensory pathway refinement during postnatal development

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    Soluble guanylyl cylase (sGC) has been identified for being a receptor for the gaseous transmitters nitric oxide and carbon monoxide. Currently four subunits alpha1, alpha2, beta1, and beta2 have been characterized. Heterodimers of alpha and beta-subunits as well as homodimers of the beta2-subunit are known to constitute functional sGC which use GTP to form cGMP a potent signal molecule in a multitude of second messenger cascades. Since NO-cGMP signaling plays a pivotal role in neuronal development we analyzed the maturational expression pattern of the newly characterized alpha2-subunit of sGC within the brain of Wistar rats by means of RNase protection assay and immunohistochemistry. alpha2-subunit mRNA as well as immunoreactive alpha2-protein increased during postnatal cerebral development. Topographical analysis revealed a selective high expression of the alpha2-subunit in the choroid plexus and within developing sensory systems involving the olfactory and somatosensory system of the forebrain as well as parts of the auditory and visual system within the hindbrain. In cultured cortical neurons the alpha2-subunit was localized to the cell membrane, especially along neuronal processes. During the first 11 days of postnatal development several cerebral regions showed a distinct expression of the alpha2-subunit which was not paralleled by the alpha1/beta1-subunits especially within the developing thalamo-cortical circuitries of the somatosensory system. However, at later developmental stages all three subunits became more homogenously distributed among most cerebral regions, indicating that functional alpha1/beta1 and alpha2/beta1 heterodimers of sGC could be formed. Our findings indicate that the alpha2-subunit is an essential developmentally regulated constituent of cerebral sensory systems during maturation. In addition the alpha2-subunit may serve other functions than forming a functional heterodimer of sGC during the early phases of sensory pathway refinement
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