TDP-43 stabilises the processing intermediates of mitochondrial transcripts

The 43-kDa trans-activating response region DNA-binding protein 43 (TDP-43) is a product of a causative gene for amyotrophic lateral sclerosis (ALS). Despite of accumulating evidence that mitochondrial dysfunction underlies the pathogenesis of TDP-43–related ALS, the roles of wild-type TDP-43 in mitochondria are unknown. Here, we show that the small TDP-43 population present in mitochondria binds directly to a subset of mitochondrial tRNAs and precursor RNA encoded in L-strand mtDNA. Upregulated expression of TDP-43 stabilised the processing intermediates of mitochondrial polycistronic transcripts and their products including the components of electron transport and 16S mt-rRNA, similar to the phenotype observed in cells deficient for mitochondrial RNase P. Conversely, TDP-43 deficiency reduced the population of processing intermediates and impaired mitochondrial function. We propose that TDP-43 has a novel role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts

Primary tumor-secreted lymphangiogenic factors induce pre-metastatic lymphvascular niche formation at sentinel lymph nodes in oral squamous cell carcinoma

Objectives: The objectives of this study were to evaluate the formation of lymphvascular niches in lymph nodes of patients with oral squamous cell carcinoma (OSCC), and investigate the roles of lymphangiogenic and angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D, expressed in the primary tumors. Materials and Methods: Forty-four patients with previously untreated clinically late T2 or T3 OSCC of cN0 were evaluated for primary tumors and 166 sentinel lymph nodes (SLNs). Primary tumors were immunohistochemically analyzed for expressions of VEGFs. Densities of lymphatic vessels (LVDpodoplanin) and high endothelial venules (HEVD) in the SLNs were also calculated using antibodies for each marker, podoplanin and MECA-79, respectively. Results: In 25 patients, all lymph nodes were metastasis-negative, whereas, in 19 patients, metastasis was positive for at least one lymph node (either at SLN, non-SLN, or nodal recurrence). From the analyses of 140 SLNs without metastasis, LVDpodoplanin in 50 SLNs of metastasis-positive cases was significantly higher than that in 90 SLNs of metastasis-negative cases (p = 0.0025). HEVD was not associated with lymph node metastasis. The patients with VEGF-A-High or VEGF-D-High tumors had significantly higher LVDpodoplanin than patients with their Low counterparts (p = 0.0233 and p = 0.0209, respectively). In cases with lymph node metastasis, the VEGF-D-expression score was significantly higher than in those without lymph node metastasis (p = 0.0006). Conclusions: These results suggest that lymph node lymphangiogenesis occurs before metastasis in OSCC. VEGF-A and VEGF-D play critical roles in this process. VEGF-D is a potential predictive marker of positive lymph node metastasis in cN0 patients. © 2015 Wakisaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Attempting to define sentinel node micrometastasis in oral squamous cell carcinoma

OBJECTIVE:The aim of this supplemental study of a sentinel node (SN) biopsy (SNB) trial for oral squamous cell carcinoma (OSCC) was to assess the effectiveness in identifying micrometastasis and determining whether elective neck dissection (END) is necessary. MATERIALS AND METHODS:Twenty-three patients with pathologically positive SNs were included. The sizes of the metastatic lesions in positive SNs (SMSNs) were classified and the rates of occult metastasis of non-SNs were compared. RESULTS:The patients were divided according to the SMSN:<0.2 mm (group A, n=3);0.2 mm to <2.0 mm (group B, n=7);and ≥2.0 mm (group C, n=13). The rates of occult metastasis in groups A, B, and C were 0% (0/3), 14% (1/7) and 23% (3/13), respectively. CONCLUSION:Rare cancer cell distribution to nodes other than SNs was observed in the patients with SN metastatic lesions of at least smaller than 0.2 mm in size, suggesting the possibility of defining SN micrometastasis in N0 OSCC

関西大学日本ポピュラー音楽アーカイブ・ミュージアムプロジェクト研究成果報告書

2014年度、2015年度 関西大学研究拠点形成支援経費報告

Disentangling Origins of Adhesive Bonding at Interfaces between Epoxy/Amine Adhesive and Aluminum

Joining metals by adhesive bonding is essential in widespread fields such as mobility, dentistry, and electronics. Although adhesive technology has grown since the 1920s, the roles of interfacial phenomena in adhesive bonding are still elusive, which hampers the on-demand selection of surface treatment and adhesive types. In the present study, we clarified how chemical interactions and mechanical interlocking governed adhesive bonding by evaluating adhesion properties at the interfaces between epoxy/amine adhesive and two kinds of Al adherends: a flat aluminum hydroxide (AlxOyHz) and technical Al plate with roughness. Spectroscopic and microscopical data demonstrate that the protonation of the amino groups in an amine hardener converts Al(OH)3 on the AlxOyHz surface to AlO(OH). The interfacial protonation results in an interfacial dipole layer with positive charges on the adhesive side, whose electrostatic interaction increases the interfacial fracture energy. The double cantilever beam tests for the flat AlxOyHz and technical Al substrates clarify that the mechanical interlocking originating from the surface roughness further increases the fracture energy. This study disentangles the roles of the chemical interactions and mechanical interlocking occurring at the epoxy adhesive/Al interface in the adhesion mechanism

Primary tumor-secreted lymphangiogenic factors induce pre-metastatic lymphvascular niche formation at sentinel lymph nodes in oral squamous cell carcinoma

Objectives The objectives of this study were to evaluate the formation of lymphvascular niches in lymph nodes of patients with oral squamous cell carcinoma (OSCC), and investigate the roles of lymphangiogenic and angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D, expressed in the primary tumors. Materials and Methods Forty-four patients with previously untreated clinically late T2 or T3 OSCC of cN0 were eval-uated for primary tumors and 166 sentinel lymph nodes (SLNs). Primary tumors were immu-nohistochemically analyzed for expressions of VEGFs. Densities of lymphatic vessels (LVDpodoplanin) and high endothelial venules (HEVD) in the SLNs were also calculated using antibodies for each marker, podoplanin and MECA-79, respectively. Results In 25 patients, all lymph nodes were metastasis-negative, whereas, in 19 patients, metasta-sis was positive for at least one lymph node (either at SLN, non-SLN, or nodal recurrence)