13,265 research outputs found

    Understanding the ECG part 1: anatomy and physiology

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    This first article in a series on 12-lead ECG interpretation explores the importance of the ECG as a diagnostic tool, discusses the anatomy and physiology underpinning cardiac electrical activity, and introduces the basic waveforms seen on the ECG

    Recently identified forms of epidermolysis bullosa

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    Epidermolysis bullosa (EB) comprises a collection of clinically diverse inherited blistering diseases that affect the skin and, in some subtypes, mucous membranes and other organs. Currently classified into four main subtypes (EB simplex, junctional EB, dystrophic EB, and Kindler syndrome, mainly based on the level of skin cleavage), the spectrum of EB extends to more than 30 clinical subtypes with pathogenic mutations in at least 18 distinct genes. This review focuses on three recent additions to variants of EB: all are autosomal recessive, and result from mutations in either DST-e (coding for epidermal dystonin, also known as the 230 kDa bullous pemphigoid antigen, BP230), EXPH5 (coding for exophilin-5, also known as Slac2-b), or ITGA3 (coding for the integrin alpha-3 subunit). Each of these new forms of EB is reviewed with respect to the initial gene discovery, clinical features, the current mutation database, and skin pathology. Awareness of these recently described forms of EB is helpful in the clinical evaluation of patients with EB and in defining genotype-phenotype correlation for inherited blistering skin diseases

    Micromechanical tuning elements in a 620-GHz monolithic integrated circuit

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    While monolithic integrated-circuit technology promises a practical means for realizing reliable reproducible planar millimeter and submillimeter-wave circuits, conventional planar circuits do not allow for critical post-fabrication optimization of performance. A 620-GHz quasi-optical monolithic detector circuit is used here to demonstrate the performance of two integrated micromechanical planar tuning elements. This is the first reported demonstration of integrated micromechanical tuning at submillimeter wavelengths. The tuning elements, called sliding planar backshorts (SPBs), are used to adjust the electrical length of planar transmission-line tuning stubs to vary the power delivered between a substrate-lens coupled planar antenna and a thin-film bismuth detector over a range of nearly 15 dB. The circuit performance agrees with theoretical calculations and microwave measurements of a -0.06-dB reflection coefficient made for a scale model of the integrated tuners. The demonstrated tuning range for the SPB tuners indicates that they can be valuable for characterizing components in developmental circuits and for optimizing the in-use performance of various millimeter and submillimeter-wave integrated circuits

    Epac and the high affinity rolipram binding conformer of PDE4 modulate neurite outgrowth and myelination using an in vitro spinal cord injury model

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    <b>Background and Purpose</b><p></p> cAMP and pharmacological inhibition of PDE4, which degrades it, are promising therapeutic targets for the treatment of spinal cord injury (SCI). Using our previously described in vitro SCI model, we studied the mechanisms by which cAMP modulators promote neurite outgrowth and myelination using enantiomers of the PDE4-specific inhibitor rolipram and other modulators of downstream signalling effectors.<p></p> <b>Experimental Approach</b><p></p> Rat mixed neural cell myelinating cultures were cut with a scalpel and treated with enantiomers of the PDE4-specific inhibitor rolipram, Epac agonists and PKA antagonists. Neurite outgrowth, density and myelination were assessed by immunocytochemistry and cytokine levels analysed by qPCR.<p></p> <b>Key Results</b><p></p> Inhibition of the high-affinity rolipram-binding state (HARBS), rather than the low-affinity rolipram binding state (LARBS) PDE4 conformer promoted neurite outgrowth and myelination. These effects were mediated through the activation of Epac and not through PKA. Expression of the chemokine CXCL10, known to inhibit myelination, was markedly elevated in astrocytes after Rho inhibition and this was blocked by inhibition of Rho kinase or PDE4.<p></p> <b>Conclusions and Implications</b><p></p> PDE4 inhibitors targeted at the HARBS conformer or Epac agonists may provide promising novel targets for the treatment of SCI. Our study demonstrates the differential mechanisms of action of these compounds, as well as the benefit of a combined pharmacological approach and highlighting potential promising targets for the treatment of SCI. These findings need to be confirmed in vivo

    Rcf1 and Rcf2, Members of the Hypoxia-induced Gene 1 Protein Family, Are Critical Components of the Mitochondrial Cytochrome bc1-cytochrome Oxidase Supercomplex

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    We report that Rcf1 (formerly Aim31), a member of the conserved hypoxia-induced gene 1 (Hig1) protein family, represents a novel component of the yeast cytochrome bc1-cytochrome c oxidase (COX) supercomplex. Rcf1 (respiratory supercomplex factor 1) partitions with the COX complex, and evidence that it may act as a bridge to the cytochrome bc1 complex is presented. Rcf1 interacts with the Cox3 subunit and can do so prior to their assembly into the COX complex. A close proximity of Rcf1 and members of the ADP/ATP carrier (AAC) family was also established. Rcf1 displays overlapping function with another Hig1-related protein, Rcf2 (formerly Aim38), and their joint presence is required for optimal COX enzyme activity and the correct assembly of the cytochrome bc1-COX supercomplex. Rcf1 and Rcf2 can independently associate with the cytochrome bc1-COX supercomplex, indicating that at least two forms of this supercomplex exist within mitochondria. We provide evidence that the association with the cytochrome bc1-COX supercomplex and regulation of the COX complex are a conserved feature of Hig1 family members. Based on our findings, we propose a model where the Hig1 proteins regulate the COX enzyme activity through Cox3 and associated Cox12 protein, in a manner that may be influenced by the neighboring AAC proteins
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