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Signals from fibronectin-binding integrins promote neural crest cell motility during development in part through protein-tyrosine kinase (PTK) activation. Neuroblastoma (NB) is a neural crest malignancy with high metastatic potential. We find that a4 and a5 integrins are present in late-stage NB tumors and cell lines derived thereof. To determine the signaling connections promoting either a4b1-or a5b1-initiated NB cell motility, pharmacological, dominant negative and short-hairpin RNA (shRNA) inhibitory approaches were undertaken. shRNA knockdown revealed that a5b1-stimulated NB motility is dependent upon focal adhesion kinase (FAK) PTK, Src PTK and p130Cas adapter protein expression. Cell reconstitution showed that FAK catalytic activity is required for a5b1-stimulated Src activation in part through direct FAK phosphorylation of Src at Tyr-418. Alternatively, a4b1-stimulated NB cell motility is dependent upon Src and p130Cas but FAK is not essential. Catalytically inactive receptor protein-tyrosine phosphatasea overexpression inhibited a4b1-stimulated NB motility and Src activation consistent with a4-regulated Src activity occurring through Src Tyr-529 dephosphorylation. In a4 shRNA-expressing NB cells, a4b1-stimulated Src activation and NB cell motility were rescued by wild type but not cytoplasmic domain-truncated a4 re-expression. These studies, supported by results using reconstituted fibroblasts, reveal that a4b1-mediated Src activation is mechanistically distinct from FAK-mediated Src activation during a5b1-mediated NB migration and support the evaluation of inhibitors to a4, Src and FAK in the control of NB tumor progression.

Purpose The aim of this study was to investigate the relationship between obesity and cognitive impairment in the Chinese elderly. Patients and methods Patients aged 60 years or above were enrolled from the Department of Geriatrics of The First Affiliated Hospital of Chongqing Medical University from March 2013 to May 2017. Mini-Mental State Examination scale was used to assess the cognitive function. Body mass index (BMI) and waist–hip ratio were used to classify obesity. Student’s t -test, Mann–Whitney U -test, or chi-squared test was used to compare the data between participants with normal cognition and participants with cognitive impairment as appropriate. Univariate logistic regression models and multivariate logistic regression models were performed to explore the relationship between BMI or abdominal obesity and cognitive impairment. Results A total of 1,100 patients including 568 men and 532 women aged 60–98 years (median age 79 years) were enrolled. After adjusting for age, gender, smoking, drinking, education level, hypercholesterolemia, hypertension, and diabetes, overweight was significantly associated with a decreased risk of cognitive impairment (OR=0.458, 95% CI=0.298–0.703, P <0.001). After adjustment for age, education level, hypercholesterolemia, hypertension, and diabetes, abdominal obesity remained significantly associated with an increased risk of cognitive impairment (OR=1.532, 95% CI=1.037–2.263, P =0.032). Conclusion Overweight is associated with a decreased risk of cognitive impairment in the Chinese elderly, while abdominal obesity is associated with an increased risk of cognitive impairment independent of conventional sociodemographic, lifestyle, and health-related comorbid factors.

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The analysis suggested that telephone follow-up interventions following a more intensive targeted approach could have a positive impact on glycaemic control for Type 2 diabetes.

PVDF/OH-BNNS nanocomposites show improved dielectric, thermal and mechanical properties through cooperation with surface hydroxylated BNNSs.

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The low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional receptor that undergoes constitutive endocytosis and recycling. To identify LRP-1 in lipid rafts, we biotin-labeled cells using a membrane-impermeable reagent and prepared Triton X-100 fractions. Raft-associated proteins were identified in streptavidin affinity-precipitates of the Triton X-100-insoluble fraction. PDGF beta-receptor was identified exclusively in lipid rafts, whereas transferrin receptor was excluded. LRP-1 distributed partially into rafts in murine embryonic fibroblasts (MEFs) and HT 1080 cells, but not in smooth muscle cells and CHO cells. LRP-1 partitioning into rafts was not altered by ligands, including alpha2-macroglobulin, platelet-derived growth factor-BB, and receptor-associated protein (RAP). To examine LRP-1 trafficking between membrane microdomains, we developed a novel method based on biotinylation and detergent fractionation. Association of LRP-1 with rafts was transient; by 15 min, nearly all of the LRP-1 that was initially raft-associated exited this compartment. LRP-1 in the Triton X-100-soluble fraction, which excludes lipid rafts, demonstrated complex kinetics, with phases reflecting import from rafts, endocytosis, and recycling. Potassium depletion blocked LRP-1 endocytosis but did not inhibit trafficking of LRP-1 from rafts into detergent-soluble microdomains. Our data support a model in which LRP-1 transiently associates with rafts but does not form a stable pool. Fluid movement of LRP-1 between microdomains may facilitate its function in promoting the endocytosis of other plasma membrane proteins, such as the urokinase receptor, which localizes in lipid rafts.