Liquid-liquid phase separation (LLPS) explains many intracellular activities, but its role in extracellular functions has not been studied to the same extent. Here we report how LLPS mediates the extracellular function of galectin-3, the only monomeric member of the galectin family. The mechanism through which galectin-3 agglutinates (acting as a "bridge" to aggregate glycosylated molecules) is largely unknown. Our data show that its N-terminal domain (NTD) undergoes LLPS driven by interactions between its aromatic residues (two tryptophans and 10 tyrosines). Our lipopolysaccharide (LPS) micelle model shows that the NTDs form multiple weak interactions to other galectin-3 and then aggregate LPS micelles. Aggregation is reversed when interactions between the LPS and the carbohydrate recognition domains are blocked by lactose. The proposed mechanism explains many of galectin-3's functions and suggests that the aromatic residues in the NTD are interesting drug design targets.
Background Arteriovenous access (AV) thrombosis is an important and preventable problem amongst chronic hemodialysis (HD) patients. Systolic blood pressure (SBP) fluctuation relates to higher cardiovascular mortality amongst these patients. We proposed there is a close relation between SBP changes and arteriovenous (AV) access thrombosis. We also determined other risk factors and biochemical parameters related to AV access failure. Methods 50 HD patients with thrombosis and 50 HD patients without thrombosis were included in the study. Odds ratios and 95% confidence intervals were estimated with multivariate‐adjusted logistic regression models to determine the association between potential thrombosis‐related risk factors and thrombosis risk. Results Elder adults, women, and patients with AV grafts, lower intradialytic SBP and higher SBP variations during HD sessions had higher incidence of AV access thrombosis. AV access infection and decreased blood flow (BF) velocity were associated with an increased incidence of thrombotic events, whereas the use of anti‐thrombotic agents was associated with a decreased incidence of thrombotic events. Further, anaemia, hypoalbuminemia, hyperlipidemia, and impaired mineral metabolism parameters were also found to be associated with AV access thrombosis. Conclusions Close monitoring and management of intradialytic hypotension and SBP fluctuation in every HD session are important. Some important and novel modifiable risk factors related to AV access thrombosis were identified in this study (eg, AV access infection, decreased BF and abnormal biochemical parameters, etc). Earlier surveillance and modification of these risk factors is crucial to prevent AV access failure in HD patients.
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