The ER and Golgi membrane system plays major roles in cell signaling and regulation of the biosynthesis/transport of proteins and lipids in response to environmental cues such as amino acid and cholesterol levels. Rab1 is the founding member of the Rab small GTPase family, which is known to mediate dynamic membrane trafficking between ER and Golgi. Growing evidence indicate that Rab1 proteins have important functions beyond their classical vesicular transport functions, including nutrient sensing and signaling, cell migration, and presentation of cell surface receptors. Moreover, deregulation of RAB1 expression has been linked to a myriad of human diseases such as cancer, cardiomyopathy and Parkinson’s disease. Further investigating these new physiological and pathological functions of Rab1 should provide new opportunities for better understanding of the disease processes and may lead to more effective therapeutic interventions.
The occurrence of antibiotics including chloramphenciol (CAP), oxytetracycline (OTC) and tetracycline (TC) was studied in municipal sewage, river water and sediment. Temporal and spatial variations of antibiotic concentrations in municipal sewage, river water and sediment were evaluated. In municipal sewage, CAP, OTC and TC concentrations were in the range of 5.8-47.4, 0.16-5.7 and 0.7-65.2 microg L(-1), respectively, and showed a temporal variation with high antibiotic concentrations appearing in the cold season. Untreated municipal sewage can seriously influence both river water and sediment. Generally, high antibiotic concentrations in river water appeared in winter owing to the low flow condition as well as the high antibiotic concentration in the sewage. However, high CAP and OTC concentrations in sediment were observed in summer most likely because runoff in high flow season can carry wastes from some origins (e.g. livestock farms in the countryside) into the river. The partitioning of antibiotics in river water and sediment suggests a lower sorption of TCs to the sediment compared to previous studies, which is believed to be caused by the high Ca2+ and Mg2+ concentrations, ionic strength and pH of the river water in the carbonate area.
On the basis of the industrialized graphene nanosheets (GNs) product, we synthesized monomer casting nylon-6 (MC PA6)/GN-3-aminopropyl-terminated poly(dimethylsiloxane) (APDMS) nanocomposite in situ through the anchoring effect of APDMS onto the GN surface. APDMS/PA6 molecules were confirmed to intercalate into the GN layers by the formation of strong interfacial interactions. The intercalation ratio and the average layer thickness of the grafted GN sample decreased in the presence of APDMS. Moreover, for MC PA6/GN-APDMS nanocomposite, GN-APDMS was uniformly distributed in the matrix and no phase separation was observed. The size of spherical APDMS particles was obviously reduced compared with that of MC PA6/APDMS composite, revealing a strong interaction between APDMS and GN and the enhancement of compatibility in the composite system. Compared with neat MC PA6, the addition of GN-APDMS resulted in 12% increase in the tensile strength and 37% increase in the impact strength; meanwhile, increase in both the storage modulus (E') and the glass transition temperature (T) indicated synergistic reinforcing and toughening effect of GN-APDMS on MC PA6. Furthermore, over 81 and 48% reduction in the friction coefficient and the specific wear rate, respectively, was achieved for the nanocomposite, and the worn surface displayed flat and smooth features with a uniform depth distribution, a low annealing effect, and a reduced friction heat, further confirming the synergistic friction-reducing effect of GN-APDMS on MC PA6.
Despite recent interests in developing lysine‐targeting covalent inhibitors, no general approach is available to create such compounds. We report herein a general approach to develop cell‐active covalent inhibitors of protein kinases by targeting the conserved catalytic lysine residue using key SuFEx and salicylaldehyde‐based imine chemistries. We validated the strategy by successfully developing (irreversible and reversible) covalent inhibitors against BCR‐ABL kinase. Our lead compounds showed high levels of selectivity in biochemical assays, exhibited nanomolar potency against endogenous ABL kinase in cellular assays, and were active against most drug‐resistant ABL mutations. Among them, the salicylaldehyde‐containing A5 is the first‐ever reversible covalent ABL inhibitor that possessed time‐dependent ABL inhibition with prolonged residence time and few cellular off‐targets in K562 cells. Bioinformatics further suggested the generality of our strategy against the human kinome.
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