Nurs Womens Health
April 2019
Human trafficking is a significant women's health issue in the United States. Clinicians who provide care to women are often unaware of the signs and symptoms of human trafficking and are unprepared to provide appropriate care. Nurses represent one of the few agents of change who women may encounter while they are in captivity; this places nurses at the forefront of their care.
View Article and Find Full Text PDFN-Glycosylation plays an important role in protein folding and function. Previous studies demonstrate that a phenylalanine residue introduced at the n-2 position relative to an Asn-Xxx-Thr/Ser N-glycosylation sequon increases the glycan occupancy of the sequon in insect cells. Here, we show that any aromatic residue at n-2 increases glycan occupancy in human cells and that this effect is dependent upon oligosaccharyltransferase substrate preferences rather than differences in other cellular processing events such as degradation or trafficking.
View Article and Find Full Text PDFThe accumulation of cross-β-sheet amyloid fibrils is the hallmark of amyloid diseases. Recently, we reported the discovery of amyloid disaggregase activities in extracts from mammalian cells and Caenorhabditis elegans. However, we have discovered a problem with the interpretation of our previous results as Aβ disaggregation in vitro.
View Article and Find Full Text PDFYeast heat shock protein 104 (Hsp104), the only known eukaryotic disaggregase, remodels both disordered protein aggregates and cross-β sheet amyloids. To handle this diverse clientele, DeSantis et al. report that Hsp104 hexamers use distinct mechanisms-individual subunits are able to dissolve disordered aggregates, but global subunit cooperativity is required to untangle amyloids.
View Article and Find Full Text PDFN-glycosylation can increase the rate of protein folding, enhance thermodynamic stability, and slow protein unfolding; however, the molecular basis for these effects is incompletely understood. Without clear engineering guidelines, attempts to use N-glycosylation as an approach for stabilizing proteins have resulted in unpredictable energetic consequences. Here, we review the recent development of three "enhanced aromatic sequons," which appear to facilitate stabilizing native-state interactions between Phe, Asn-GlcNAc and Thr when placed in an appropriate reverse turn context.
View Article and Find Full Text PDFThe process of amyloid-β (Aβ) fibril formation is genetically and pathologically linked to Alzheimer's disease (AD). Thus, a selective and sensitive method for quantifying Aβ fibrils in complex biological samples allows a variety of hypotheses to be tested. Herein, we report the basis for a quantitative in vitro kinetic aggregation assay that detects seeding-competent Aβ aggregates in mammalian cell culture media, in Caenorhabditis elegans lysate, and in mouse brain homogenate.
View Article and Find Full Text PDFThe formation of amyloid, a cross-beta-sheet fibrillar aggregate, is associated with a variety of aging-associated degenerative diseases. Herein, we report the existence of a mammalian amyloid disaggregase activity that is present in all tissues and cell types tested. Homogenates from mammalian tissues and cell lines are able to disaggregate amyloid fibrils composed of amyloid beta (A beta)(1-40) or the 8 kDa plasma gelsolin fragment.
View Article and Find Full Text PDFFamilial amyloidosis of Finnish type (FAF), or gelsolin amyloidosis, is a systemic amyloid disease caused by a mutation (D187N/Y) in domain 2 of human plasma gelsolin, resulting in domain 2 misfolding within the secretory pathway. When D187N/Y gelsolin passes through the Golgi, furin endoproteolysis within domain 2 occurs as a consequence of the abnormal conformations that enable furin to bind and cleave, resulting in the secretion of a 68 kDa C-terminal fragment (amino acids 173-755, C68). The C68 fragment is cleaved upon secretion from the cell by membrane type 1 matrix metalloprotease (MT1-MMP), affording the 8 and 5 kDa fragments (amino acids 173-242 and 173-225, respectively) comprising the amyloid fibrils in FAF patients.
View Article and Find Full Text PDFProtein aggregation is a common feature of late onset neurodegenerative disorders, including Alzheimer's disease. In Alzheimer's disease, misassembly of the Abeta peptide is genetically linked to proteotoxicity associated with disease etiology. A reduction in Abeta proteotoxicity is accomplished, in part, by the previously reported Abeta disaggregation and proteolysis activities-under partial control of heat shock factor 1, a transcription factor regulating proteostasis in the cytosol and negatively regulated by insulin growth factor signaling.
View Article and Find Full Text PDFThermoTRPs, a subset of the Transient Receptor Potential (TRP) family of cation channels, have been implicated in sensing temperature. TRPM8 and TRPA1 are both activated by cooling; however, it is unclear whether either ion channel is required for thermosensation in vivo. We show that mice lacking TRPM8 have severe behavioral deficits in response to cold stimuli.
View Article and Find Full Text PDFEnvironmental temperature is thought to be directly sensed by neurons through their projections in the skin. A subset of the mammalian transient receptor potential (TRP) family of ion channels has been implicated in this process. These "thermoTRPs" are activated at distinct temperature thresholds and are typically expressed in sensory neurons.
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