The Actin‐Binding Protein Cofilin and Its Interaction With Cortactin Are Required for Podosome Patterning in Osteoclasts and Bone Resorption In Vivo and In Vitro

The adhesion of osteoclasts (OCs) to bone and bone resorption require the assembly of specific F‐actin adhesion structures, the podosomes, and their dense packing into a sealing zone. The OC‐specific formation of the sealing zone requires the interaction of microtubule (MT) + ends with podosomes. Here, we deleted cofilin, a cortactin (CTTN)‐ and actin‐binding protein highly expressed in OCs, to determine if it acts downstream of the MT‐CTTN axis to regulate actin polymerization in podosomes. Conditional deletion of cofilin in OCs in mice, driven by the cathepsin K promoter (Ctsk‐Cre), impaired bone resorption in vivo, increasing bone density. In vitro, OCs were not able to organize podosomes into peripheral belts. The MT network was disorganized, MT stability was decreased, and cell migration impaired. Active cofilin stabilizes MTs and allows podosome belt formation, whereas MT disruption deactivates cofilin via phosphorylation. Cofilin interacts with CTTN in podosomes and phosphorylation of either protein disrupts this interaction, which is critical for belt stabilization and for the maintenance of MT dynamic instability. Accordingly, active cofilin was required to rescue the OC cytoskeletal phenotype in vitro. These findings suggest that the patterning of podosomes into a sealing zone involves the dynamic interaction between cofilin, CTTN, and the MTs + ends. This interaction is critical for the functional organization of OCs and for bone resorption. © 2016 American Society for Bone and Mineral Research.     

The DE loop of the domain III of the envelope protein appears to be associated with West Nile virus neutralization

The envelope (E) protein of WNV plays an important role in the virus neutralization. Using a mAb 5E8, a neutralizing epitope on the domain III of the E of the New York strain of WN virus was characterized. Results from neutralization-escape mutants and site-directed mutagenesis revealed that the 5E8 epitope is a highly conformation dependent epitope consisting of at least residues E330, E332 and E367 on the domain III. Besides known critical neutralizing epitopes E330 and E332, our results indicate that residue E367, a component of DE loop on the domain III, appeared to be associated with neutralization but little with neuroinvasion of the virus, as reported previously (Beasley et al., 2002).     

Serum cholesterol in idiopathic and lupus-related protein-losing enteropathy

Abstract The characteristics of protein-losing enteropathy were evaluated in patients with systemic lupus erythematosus. Among the patients with systemic lupus erythematosus (n=380) in a tertiary hospital, we reviewed the records of seven patients with generalized edema, hypoalbuminemia without proteinuria and positive results on 99mTc-labelled human serum albumin scintigrams. Patient characteristics and laboratory findings were compared between these seven patients and patients with lupus enteritis (n=15) or idiopathic protein-losing enteropathy (n=11). Compared with the lupus enteritis patients, the erythrocyte sedimentation rate and serum total cholesterol levels were significantly increased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Compared with idiopathic protein-losing enteropathy patients, the level of serum total cholesterol was significantly increased, but the level of serum albumin was decreased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Among patients with systemic lupus erythematosus-related protein-losing enteropathy, four patients had high serum total cholesterol levels (>or=248 mg/dL) and achieved complete remission after receiving high doses of steroid treatment. However, three patients who had low serum total cholesterol levels (相似文献   

Modulation of thymidine incorporation by κ-opioid ligands in rat spinal cord-dorsal root ganglion co-cultures

β-Endorphin, met-enkephalin and several μ-selective opioid agonists were shown to decrease thymidine incorporation into DNA in various neural cell cultures. We now report that the κ-selective opioid agonists U50488, U69593 and MR2034 modulate [³H]thymidine incorporation into DNA in rat spinal cord-dorsal root ganglion co-cultures. U50488 at 10 μM increased by 60% thymidine incorporation in 6-day-old cultures. The thymidine incorporation induced by U50488 was blocked by the κ-selective antagonist nor-binaltorphimine, as well as by pertussis toxin and LiCl U50488 treatment stimulated phosphatidylinositol turnover by three-fold compared with untreated controls. These findings suggest that κ-opioid agonists modulate DNA synthesis in spinal cord-dorsal root ganglion co-cultures through a mechanism which involves pertussis toxin-sensitive GTP-binding proteins, as well as activation of phosphatidylinositol turnover.     

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.     

Dubin-Johnson综合征1例

Dubin-Johnson综合征是一种先天性非溶血性黄疸,在临床中较罕见,需与其他原因所导致的黄疸相鉴别.本文报告了我院1例Dubin- Johnson综合征的诊治情况,有助于加深对该病的认识.     

Functional characterization of the Sporothrix schenckii Ktr4 and Ktr5, mannosyltransferases involved in the N-linked glycosylation pathway

Sporothrix schenckii is one of the causative agents of the deep-seated mycosis sporotrichosis, a fungal infection with worldwide distribution. Fungus-specific molecules and biosynthetic pathways are potential targets for the development of new antifungal drugs. The MNT1/KRE2 gene family is a group of genes that encode fungus-specific Golgi-resident mannosyltransferases that participate in the synthesis of O-linked and N-linked glycans. While this family is composed of five and nine members in Candida albicans and Saccharomyces cerevisiae, respectively, the S. schenckii genome contains only three putative members. MNT1 has been previously characterized as an enzyme that participates in the synthesis of both N-linked and O-linked glycans. Here, we aimed to establish the functional role of the two remaining family members, KTR4 and KTR5, in the protein glycosylation pathways by using heterologous complementation in C. albicans mutants lacking genes of the MNT1/KRE2 family. The two S. schenckii genes restored defects in the elaboration of N-linked glycans, but no complementation of mutants that synthesize truncated O-linked glycans was observed. Therefore, our results suggest that MNT1 is the sole member with a role in O-linked glycan elaboration, whereas the three family members have redundant activity in the S. schenckii N-linked glycan synthesis.     

Effect of diode-pumped solid state laser on polymerization shrinkage and color change in composite resins

A diode-pumped solid state (DPSS) laser emitting at 473 nm was used to test its influence on the degree of polymerization of composite resins. Eight composite resins were chosen and light cured with three different light-curing systems [a quartz–tungsten–halogen (QTH) lamp-based unit, a light-emitting diode (LED) unit, and a DPSS laser]. Polymerization shrinkage and color change in specimens were measured. According to the statistical analysis, each light-curing system produced a significantly different value of maximum polymerization shrinkage. In most specimens, the DPSS laser induced the least polymerization shrinkage. After being immersed in distilled water for 10 days, specimens light-cured by the DPSS laser had undergone less color change than those cured by the other units. In conclusion, the DPSS laser induced better or similar polymerization in terms of polymerization shrinkage and color change in composite resins compared with those of the QTH lamp-based and LED units.