Exosomes are secreted vesicles arising from the fusion of multivesicular bodies (MVBs) with the plasma membrane. Despite their importance in various processes, the molecular mechanisms controlling their formation and release remain unclear. Using nematodes and mammary tumor cells, we show that Ral GTPases are involved in exosome biogenesis. In Caenorhabditis elegans, RAL-1 localizes at the surface of secretory MVBs. A quantitative electron microscopy analysis of RAL-1–deficient animals revealed that RAL-1 is involved in both MVB formation and their fusion with the plasma membrane. These functions do not involve the exocyst complex, a common Ral guanosine triphosphatase (GTPase) effector. Furthermore, we show that the target membrane SNARE protein SYX-5 colocalizes with a constitutively active form of RAL-1 at the plasma membrane, and MVBs accumulate under the plasma membrane when SYX-5 is absent. In mammals, RalA and RalB are both required for the secretion of exosome-like vesicles in cultured cells. Therefore, Ral GTPases represent new regulators of MVB formation and exosome release. 相似文献
Clathrin/AP2-coated vesicles are the principal endocytic carriers originating at the plasma membrane. In the experiments reported here, we used spinning-disk confocal and lattice light-sheet microscopy to study the assembly dynamics of coated pits on the dorsal and ventral membranes of migrating U373 glioblastoma cells stably expressing AP2 tagged with enhanced green fluorescence (AP2-EGFP) and on lateral protrusions from immobile SUM159 breast carcinoma cells, gene-edited to express AP2-EGFP. On U373 cells, coated pits initiated on the dorsal membrane at the front of the lamellipodium and at the approximate boundary between the lamellipodium and lamella and continued to grow as they were swept back toward the cell body; coated pits were absent from the corresponding ventral membrane. We observed a similar dorsal/ventral asymmetry on membrane protrusions from SUM159 cells. Stationary coated pits formed and budded on the remainder of the dorsal and ventral surfaces of both types of cells. These observations support a previously proposed model that invokes net membrane deposition at the leading edge due to an imbalance between the endocytic and exocytic membrane flow at the front of a migrating cell. 相似文献
IntroductionThis open-label pilot study aimed to investigate the efficacy of canakinumab in colchicine-resistant familial Mediterranean fever (FMF) patients.MethodPatients with one or more attacks in a month in the preceding 3 months despite colchicine were eligible to enter a 30-day run-in period. Patients who had an attack during the first run-in period advanced to a second 30-day period. At the first attack, patients started to receive three canakinumab 150 mg subcutaneous injections at 4-week intervals, and were then followed for an additional 2 months. Primary efficacy outcome measure was the proportion of patients with 50 % or more reduction in attack frequency. Secondary outcome measures included time to next attack following last canakinumab dose and changes in quality of life assessed by SF-36.ResultsThirteen patients were enrolled in the run-in period and 9 advanced to the treatment period. All 9 patients achieved a 50 % or more reduction in attack frequency, and only one patient had an attack during the treatment period. C-reactive protein and serum amyloid A protein levels remained low throughout the treatment period. Significant improvement was observed in both physical and mental component scores of the Short Form-36 at Day 8. Five patients had an attack during the 2-month follow-up, occurring median 71 (range, 31 to 78) days after the last dose. Adverse events were similar to those observed in the previous canakinumab trials.ConclusionCanakinumab was effective at controlling the attack recurrence in patients with FMF resistant to colchicine. Further investigations are warranted to explore canakinumab’s potential in the treatment of patients with colchicine resistant FMF.
The effects of membrane fouling reducers (MFRs) (the cationic polyelectrolyte (CPE) and FeCI3) on membrane fouling were studied in a lab-scale jet loop submerged membrane bioreactor (JL-SMBR) system. The optimum dosages of MFRs (CPE dosage = 20 mg g−1MLSS, FeCI3 dosage = 14 mg g−1MLSS) were continuously fed to JL-SMBR system. The soluble and bound EPS concentrations as well as MLSS concentration in the mixed liquor of JL-SMBR were not changed substantially by the addition of MFRs. However, significant differences were observed in particle size and relative hydrophobicity. Filtration tests were performed by using different membrane types (polycarbonate (PC) and nitrocellulose mixed ester (ME)) and various pore sizes (0.45-0.22-0.1 μm). The steady state fluxes (Jss) of membranes increased at all membranes after MFRs addition to JL-SMBR. The filtration results showed that MFRs addition was an effective approach in terms of improvement in filtration performance for both membrane types. 相似文献
The aim of this study was to demonstrate the role of curcumin on oxidative stress, cell proliferation and apoptosis in the
rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups:
sham, I/R and I/R+ curcumin; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After
I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In
the curcumin group, 3 days before I/R, curcumin (100 mg/kg) was administered by gastric gavage. All animals were sacrificed
at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation
in all groups. Curcumin treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced
superoxide dismutase, and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological
injury including mucosal erosions and villous congestion and hemorrhage. Curcumin treatment significantly attenuated the severity
of intestinal I/R injury, with inhibiting of I/R-induced apoptosis and cell proliferation. These results suggest that curcumin
treatment has a protective effect against intestinal damage induced by intestinal I/R. This protective effect is possibly
due to its ability to inhibit I/R-induced oxidative stress, apoptosis and cell proliferation. 相似文献
The aim of this study was to evaluate the possible protective effects of caffeic acid phenethyl ester (CAPE) against cholestatic
oxidative stress and liver damage in the common bile duct ligated rats. A total of 18 male Sprague–Dawley rats were divided
into three groups: control, bile duct ligation (BDL) and BDL + received CAPE; each group contain 6 animals. The rats in CAPE
treated groups were given CAPE (10 μmol/kg) once a day intraperitoneally (i.p) for 2 weeks starting just after BDL operation.
The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated
bile ducts into lobules, inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment
of BDL with CAPE attenuated alterations in liver histology. The proliferating cell nuclear antigen and the activity of TUNEL
in the BDL were observed to be reduced with the QE treatment. The application of BDL clearly increased the tissue hydroxyproline
(HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme (superoxide dismutase (SOD), glutathione peroxidase
(GPx)) activities. CAPE treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced
of SOD, and GPx enzymes in the tissues. The data indicate that CAPE attenuates BDL-induced cholestatic liver injury, bile
duct proliferation, and fibrosis. The hepatoprotective effect of CAPE is associated with antioxidative potential. 相似文献
We aimed to show the effect of osteoporosis on sleep quality in 59 postmenopausal women. The participants’ bone-mineral density levels were measured by dual-energy X-ray absorptiometry (DEXA). According to their DEXA results, participants were divided into two groups as osteoporotics and controls. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality. Fourteen osteoporotic women (43.8%) and four controls (14.8%) were “poor” sleepers (p < 0.05). Postmeno-pausal women with osteoporosis scored greater on the “sleep latency” and “sleep duration” components of PSQI than controls. According to the findings of our study, osteoporosis is a risk factor for poor sleep quality in postmenopausal women.
Bacteroides helcogenes Benno et al. 1983 is of interest because of its isolated phylogenetic location and, although it has been found in pig feces and is known to be pathogenic for pigs, occurrence of this bacterium is rare and it does not cause significant damage in intensive animal husbandry. The genome of B. helcogenes P 36-108(T) is already the fifth completed and published type strain genome from the genus Bacteroides in the family Bacteroidaceae. The 3,998,906 bp long genome with its 3,353 protein-coding and 83 RNA genes consists of one circular chromosome and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献