Rat Parathyroid Gland, with Special Reference to Its Blood Vascular Bed, Pericapillary Space and Intercellular Space

The blood vascular bed, perivascular space and intercellular space of the rat parathyroid gland were studied using scanning electron microscopy of vascular casts, freeze-cracked tissue samples, and NaOH-digested tissue blocks. The findings were supplemented by transmission light and electron microscopy of iron colloid-treated or enzyme-digested tissue sections. The rat parathyroid gland contained a rich network of capillaries. These capillaries were surrounded by marked pericapillary spaces which were demarcated by basal lamina of both capillaries and parenchymal cells. The pericapillary spaces contained numerous collagen fibrils, and issued many crista-like projections which ran deep into the sheets of parenchymal cells. The intercellular spaces of parenchymal cells contained neither basal lamina nor collagen fibrils. The surfaces of the parenchymal cells showed strong negative charging, and maintained the intercellular spaces. The luminal surfaces of the capillary endothelium also showed strong negative charging, and maintained the capillary lumen.</p

Interfacial Element for Finite Element Modal Analysis of Bolted Joints

Multi-material structures are going to be a main scheme to construct automobiles. For the construction of multi-material structures, techniques to join dissimilar materials are required. The major joining techniques are classified into welding, adhesion and mechanical fastening such as bolted joints and riveting. Especially, bolted joints enable joining of metallic materials (steel and aluminium alloy, etc.) and non-metallic materials (CFRP, etc.) with high joint strength. However, the total stiffness of structures with bolted joints is relatively low because interfaces in bolted joints just contact each other, and its interfacial stiffness is lower than elastic modulus of base materials. Moreover, interfacial stiffness of bolted joints depends on clamping force of bolt and nut. This study has proposed an interfacial element for finite element modal analysis of bolted joints. The interfacial element simulates interfacial stiffness of bolted joints. Contact of interfaces is assumed to be the Hertzian contact of elastic asperities whose peak heights obey the Gaussian distribution. Based on this assumption, the stiffness of the interfacial element is derived from the compressive stress and the surface texture of the interfaces. By using the finite element model with the interfacial element, the modal analysis computes the natural frequency and the vibration mode. Finite element simulations and hammering tests have been conducted with several bolted joints. In general, the natural frequency of the bolted joints in the hammering tests increases with the increase in the clamping force, but it is lower than the calculation results in which the stiffness reduction of the jointed interfaces is ignored. The calculation results by using the proposed interfacial element agree with the hammering tests. Therefore, the proposed interfacial element contributes to improvement of modal analysis of bolted joints by mathematically modelling stiffness reduction of jointed interfaces based on tribology

<総説>前シナプス・アクティブゾーンにおける蛋白質間相互作用

脳内には数千億を超える神経細胞が複雑な神経回路網を形成している。神経回路網が適切に形成・維持されることで学習や記憶などの正常な脳機能が営まれる。一方で,その破綻は自閉症や統合失調症などの精神神経疾患を引き起こす。神経回路網における情報伝達の要はシナプスと呼ばれる神経細胞間の接着部位であり,このシナプスの形成・維持・破綻のメカニズムを明らかにすることで,複雑な神経回路網の動作原理を分子レベルで解明できると考えられる。本稿では,特に前シナプスからの神経伝達物質放出に関わる構造体・アクティブゾーンの分子構造基盤に関する最近の研究を紹介したい。journal articl

Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1

The cytomatrix at the active zone (CAZ) has been implicated in defining the site of Ca2+-dependent exocytosis of neurotransmitter. We have identified here a novel CAZ protein of ∼120 kD from rat brain and named it CAST (CAZ-associated structural protein). CAST had no transmembrane segment, but had four coiled-coil domains and a putative COOH-terminal consensus motif for binding to PDZ domains. CAST was localized at the CAZ of conventional synapses of mouse brain. CAST bound directly RIM1 and indirectly Munc13-1, presumably through RIM1, forming a ternary complex. RIM1 and Munc13-1 are CAZ proteins implicated in Ca2+-dependent exocytosis of neurotansmitters. Bassoon, another CAZ protein, was also associated with this ternary complex. These results suggest that a network of protein–protein interactions among the CAZ proteins exists at the CAZ. At the early stages of synapse formation, CAST was expressed and partly colocalized with bassoon in the axon shaft and the growth cone. The vesicles immunoisolated by antibassoon antibody–coupled beads contained not only bassoon but also CAST and RIM1. These results suggest that these CAZ proteins are at least partly transported on the same vesicles during synapse formation

Genetic and clinical landscape of Chinese frontotemporal dementia: dominance of TBK1 and OPTN mutations

Background: Our study aims to evaluate the genetic and phenotypic spectrum of Frontotemporal dementia (FTD) gene variant carriers in Chinese populations, investigate mutation frequencies, and assess the functional properties of TBK1 and OPTN variants. Methods: Clinically diagnosed FTD patients underwent genetic analysis through exome sequencing, repeat-primed polymerase chain reaction, and Sanger sequencing. TBK1 and OPTN variants were biologically characterized in vitro using immunofuorescence, immunoprecipitation, and immunoblotting analysis. The frequencies of genes implicated in FTD in China were analyzed through a literature review and meta-analysis. Results: Of the 261 Chinese FTD patients, 61 (23.4%) carried potential causative variants in FTD-related genes, including MAPT (n=17), TBK1 (n=7), OPTN (n=6), GRN (n=6), ANXA11 (n=4), CHMP2B (n=3), C9orf72 GGGGCC repeats (n=2), CYLD (n=2), PRNP (n=2), SQSTM1 (n=2), TARDBP (n=2), VCP (n=1), CCNF (n=1), CHCHD10 (n=1), SIGMAR1 (n=1), CHCHD2 (n=1), FUS (n=1), TMEM106B (n=1), and UBQLN2 (n=1). 29 variants can be considered novel, including the MAPT p.D54N, p.E342K, p.R221P, p.T263I, TBK1 p.E696G, p.I37T, p.E232Q, p.S398F, p.T78A, p.Q150P, p.W259fs, OPTN p.R144G, p.F475V, GRN p.V473fs, p.C307fs, p.R101fs, CHMP2B p.K6N, p.R186Q, ANXA11 p.Q155*, CYLD p.T157I, SQSTM1 p.S403A, UBQLN2 p.P509H, CCNF p.S160N, CHCHD10 p.A8T, SIGMAR1 p.S117L, CHCHD2 p.P53fs, FUS p.S235G & p.S236G, and TMEM106B p.L144V variants. Patients with TBK1 and OPTN variants presented with heterogeneous clinical phenotypes. Functional analysis demonstrated that TBK1 I37T and E232Q mutants showed decreased autophosphorylation, and the OPTN phosphorylation was reduced by the TBK1 I37T mutant. The OPTN-TBK1 complex formation was enhanced by the TBK1 E696G mutant, while OPTN R144G and F475V mutants exhibited reduced recruitment to autophagosomes compared to the wild-type. The overall frequency of TBK1 and OPTN in Chinese FTD patients was 2.0% and 0.3%, respectively. Conclusions: Our study demonstrates the extensive genetic and phenotypic heterogeneity of Chinese FTD patients.TBK1 mutations are the second most frequent cause of clinical FTD after MAPT in the Chinese

A Comparison of Magnifying Chromoendoscopy Versus Narrow Band Imaging in the Diagnosis of Depth of Invasion for Early Colorectal Cancers

Although chromoendoscopy and narrow band imaging (NBI) are widely used in diagnosing the invasion depth of colorectal cancers, comparative studies of these modalities are lacking. This meta-analysis compared the performance of these two modalities in colorectal cancer diagnosis. MEDLINE, EMBASE, and Cochrane Library were searched for relevant original articles published up to December 20th, 2010. Major criteria for article inclusion were: (i) magnifying chromoendoscopy or NBI was used as a diagnostic modality and pit pattern or vascular pattern was used as a diagnostic classification; (ii) sensitivity and specificity were reported; (iii) absolute numbers of true-positive, false-positive, true-negative, and false-negative cases, or their equivalent, were provided; and (iv) pathology of biopsy, endoscopy, or surgical treatment was used as the reference standard. Sensitivity and specificity were pooled using a random effects model. Regression analysis was performed to compare the discriminatory power between chromoendoscopy and NBI by including a dummy variable. We made the assumption that a positive regression coefficient implied a better discriminatory power for NBI, and vice versa. Of 1846 screened articles, 16 fulfilled all inclusion criteria. Pooled sensitivity for chromoendoscopy and NBI was 0.85 (95% CI: 0.82-0.87) and 0.80 (0.76-0.85), respectively, and specificity was 0.98 (0.97-0.99) and 0.98 (0.97-0.99), respectively. The regression coefficient for chromoendoscopy versus NBI was -0.02 (95%CI: -1.18-1.71). These results indicate that chromoendoscopy and NBI may have similar power for the diagnostic assessment of colonic neoplasms. However, other factors such as convenience, time, and cost still must be taken into account in making the final diagnostic choice