Large defects in the upper two thirds of the face, skull, and skull base pose challenging reconstructive problems. There are a number of applicable reconstructive techniques, all with various advantages and disadvantages, available to otolaryngologists-head and neck surgeons. One method, originally described in the late 1800s, was evaluated by us. Applications of the technique included reconstruction of large defects of the forehead, dura, and anterior skull base, closure of orbital defects, and soft-tissue augmentation of the face. Advantages of this reconstructive technique are the flap's proximity to the defects and its simplicity of execution.
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http://dx.doi.org/10.1001/archotol.1986.03780010062011 | DOI Listing |
Eur J Hum Genet
January 2025
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Polycomb group (PcG) and Trithorax group (TrxG) complexes represent two major components of the epigenetic machinery. This study aimed to delineate phenotypic similarities and differences across developmental conditions arising from rare variants in PcG and TrxG genes, using data-driven approaches. 462 patients with a PcG or TrxG-associated condition were identified in the DECIPHER dataset.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, Bonn, Germany.
Mitochondria have to import a large number of precursor proteins from the cytosol. Chaperones keep these proteins in a largely unfolded state and guide them to the mitochondrial import sites. Premature folding, mitochondrial stress and import defects can cause clogging of import sites and accumulation of non-imported precursors, representing a critical burden for cellular proteostasis.
View Article and Find Full Text PDFNewly synthesized proteins destined for the secretory pathway are folded and assembled in the endoplasmic reticulum (ER) and then transported to the Golgi apparatus via COPII vesicles, which are normally 60-90 nm. COPII vesicles must accordingly be enlarged to accommodate proteins larger than 90 nm, such as long-chain collagen. Key molecules involved in this enlargement are Tango1 and Tango1-like (Tali), which are transmembrane proteins in the ER encoded by the MIA3 and MIA2 genes, respectively.
View Article and Find Full Text PDFAutophagy
January 2025
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
The synthesis of membrane and secreted proteins is safeguarded by an endoplasmic reticulum-associated ribosome quality control (ER-RQC) that promotes the disposal of defective translation products by the proteasome or via a lysosome-dependent pathway involving the degradation of portions of the ER by macroautophagy (reticulophagy). The UFMylation of RPL26 on ER-stalled ribosomes is essential for activating the ER-RQC and reticulophagy. Here, we report that the viral deubiquitinase (vDUB) encoded in the N-terminal domain of the Epstein-Barr virus (EBV) large tegument protein BPLF1 hinders the UFMylation of RPL26 on ribosomes that stall at the ER, promotes the stabilization of ER-RQC substrates, and inhibits reticulophagy.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multiomic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in and mutants, where lysosomes accumulate cholesterol.
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