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Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus,(More)
The nonciliated cells lining the ductuli efferentes presented three distinct cytoplasmic regions. The apical region contained, in addition to cisternae of endoplasmic reticulum and mitochondria, two distinct membranous elements. The tubulovesicular system consisted of dilated tubules connected to the apical plasma membrane and subjacent distended vesicular(More)
Three different mammalian sialidases have been described as follows: lysosomal (Neu1, gene NEU1), cytoplasmic (Neu2, gene NEU2), and plasma membrane (Neu3, gene NEU3). Because of mutations in the NEU1 gene, the inherited deficiency of Neu1 in humans causes the severe multisystemic neurodegenerative disorder sialidosis. Galactosialidosis, a clinically(More)
Neurotrophin binding to the p75 neurotrophin receptor (p75(NTR)) activates neuronal apoptosis following adult central nervous system injury, but the underlying cellular mechanisms remain poorly defined. In this study, we show that the proform of nerve growth factor (proNGF) induces death of retinal ganglion cells in adult rodents via a p75(NTR)-dependent(More)
The endocytic activity of the low cuboidal cells lining the rete testis was analyzed by electron microscopy following injection of various tracers into the lumen of these anastomotic channels. At 1 and 5 minutes after injection, cationic ferritin (CF) and concanavalin A-ferritin (Con A) were seen bound to the apical plasma membrane and to the membrane of(More)
BACKGROUND Lysosomal carboxypeptidase, cathepsin A (protective protein, CathA), is a component of the lysosomal multienzyme complex along with beta-galactosidase (GAL) and sialidase Neu1, where it activates Neu1 and protects GAL and Neu1 against the rapid proteolytic degradation. On the cell surface, CathA, Neu1, and the enzymatically inactive splice(More)
Sulfated glycoprotein-2 (SGP-2) is one of the major proteins secreted by rat Sertoli cells and epididymal cells in culture. The disulfide-linked dimeric protein secreted by Sertoli cells and found in seminiferous tubule fluid is composed of monomers of Mr 47 000 and 34 000 whereas the epididymal protein exhibits monomers of Mr 40 000 and 29 000. When both(More)
Testis brain RNA-binding protein (TB-RBP) suppresses translation in vitro and attaches mRNAs to microtubules by binding to conserved elements in the 3' untranslated regions (UTRs) of specific testis and brain mRNAs. Purification of TB-RBP from testicular and brain cytoplasmic extracts has revealed that mouse TB-RBP is 99% identical to the human protein(More)
It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated(More)