50 research outputs found

    CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology

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    Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca2+ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca2+/calmodulin-dependent protein kinase Iα (CaMKIα). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIα is a widely expressed protein kinase, suggesting that Ca2+ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types

    Assessment of a self-assembling peptide gel, SPG-178, in providing a clear operative field for trabeculectomy surgery for glaucoma in an animal model

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    The presence of blood during ophthalmic surgery is problematic, as it can obstruct a surgeon’s view of the operative field. This is particularly true when performing trabeculectomy surgery to enhance ocular fluid outflow and reduce intraocular pressure as a treatment for glaucoma, one of the most common vision loss conditions worldwide. In this study, we investigated the performance of a transparent, self-assembling peptide gel (SPG-178) and its ability to maintain visibility during trabeculectomy surgery. Unlike the hyaluronic acid gel commonly used in ophthalmic surgery, SPG-178 did not permit the ingress of blood into the gel itself. Rather, it forced blood to flow peripherally to the gel. Moreover, if bleeding occurred under the SPG-178 gel, perfusion with saline was able to effectively flush the blood away along the interface between the SPG-178 and the ocular tissue (in this case scleral) to clear the surgical field of view. In experimental trabeculectomy surgeries with mitomycin C used as an adjuvant, there were no differences in the postoperative recovery of intraocular pressure or bleb morphology with or without the use of SPG-178. SPG-178, therefore, when used in a gel formulation, represents a new material for use in intraocular surgery to ensure a clear operative field with likely beneficial treatment outcomes

    Towards the Realization of Higher Connectivity in MgB2 Conductors: In-situ or Sintered Ex-situ?

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    The two most common types of MgB2 conductor fabrication technique - in-situ and ex-situ - show increasing conflicts concerning the connectivity, an effective current-carrying cross-sectional area. An in-situ reaction yields a strong intergrain coupling with a low packing factor, while an ex-situ process using pre-reacted MgB2 yields tightly packed grains, however, their coupling is much weaker. We studied the normal-state resistivity and microstructure of ex-situ MgB2 bulks synthesized with varied heating conditions under ambient pressure. The samples heated at moderately high temperatures of ~900{\deg}C for a long period showed an increased packing factor, a larger intergrain contact area and a significantly decreased resistivity, all of which indicate the solid-state self-sintering of MgB2. Consequently the connectivity of the sintered ex-situ samples exceeded the typical connectivity range 5-15% of the in-situ samples. Our results show self-sintering develops the superior connectivity potential of ex-situ MgB2, though its intergrain coupling is not yet fulfilled, to provide a strong possibility of twice or even much higher connectivity in optimally sintered ex-situ MgB2 than in in-situ MgB2.Comment: 17 pages, 5 figure
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