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Decreased mitochondrial translation confers 3,3′-Diindolylmethane resistance to Schizosaccharomyces pombe
No full text3,3′-Diindolylmethane (DIM), a compound derived from natural fruits and vegetables, is widely recognized for its anti-cancer activity. However, its action mechanisms remain ambiguous. In this study, to study the molecular mechanism of 3,3′-Diindolylmethane, we identified a novel mutation in the gene of mitochondrial translation elongation factor EF-Ts (tsf1+), a key factor in mitochondrial protein translation, that conferred DIM resistance to Schizosaccharomyces pombe. The tsf1Δ also conferred DIM resistance. Decreased mitochondrial translation was found to be responsible for conferring DIM resistance to Schizosaccharomyces pombe, as the cells gained DIM resistance after treatment with chloramphenicol, a specific mitochondrial translation inhibitor. Notably, tsf1Δ conferred DIM resistance in the absence of either autophagy-related protein, Atg7, or nuclear envelope protein, Lem2, two proteins that have been reported to be required for cell survival in the presence of DIM. Overall, this study revealed novel biological functions of DIM and highlighted its potential as an anti-cancer agent
Downscaling Urban Resilience Assessment: A Spatiotemporal Analysis of Urban Blocks using the Fuzzy Delphi Method and K-means Clustering
No full textThe spatiotemporal assessment of urban resilience is crucial for planning and policy-making toward addressing climate change and other societal challenges. However, our comprehension of urban resilience at smaller scales is limited. This study not only advances urban resilience research by developing an efficient measurement approach but also contributes to practice by evaluating resilience at the city block level, thereby informing targeted interventions. Our study aimed to downscale the unit of analysis for urban resilience assessment by focusing on the social, economic, housing and infrastructural, and environmental dimensions of blocks in the southern districts of Tehran between 2006 and 2016. The Fuzzy Delphi Method was utilized to determine the indicators for urban resilience assessment. The Analytic Hierarchy Process technique was employed to weigh these indicators. Subsequently, the PROMETHEE technique was applied to evaluate the resilience of urban blocks. Finally, the K-Means algorithm was utilized to cluster the urban blocks. The results indicate that from 2006 to 2016, the southern districts of Tehran saw a marked reduction in overall resilience. This decline affected 48 % of the urban blocks, encompassing 60 % of the area and 62 % of the population. The results of applying the K-means algorithm for urban block clustering did not align with the boundaries of the southern districts of Tehran. This finding highlights that assessing resilience on smaller scales could lead to more accurate conclusions
Periodontal tissue regeneration with cementogenesis after application of brain-derived neurotrophic factor in 3-wall inflamed intra-bony defect
No full textObjective
The purpose of this study is to investigate regenerative process by immunohistochemical analysis and evaluate periodontal tissue regeneration following a topical application of BDNF to inflamed 3-wall intra-bony defects.
Background
Brain-derived neurotrophic factor (BDNF) plays a role in the survival and differentiation of central and peripheral neurons. BDNF can regulate the functions of non-neural cells, osteoblasts, periodontal ligament cells, endothelial cells, as well as neural cells. Our previous study showed that a topical application of BDNF enhances periodontal tissue regeneration in experimental periodontal defects of dog and that BDNF stimulates the expression of bone (cementum)-related proteins and proliferation of human periodontal ligament cells.
Methods
Six weeks after extraction of mandibular first and third premolars, 3-wall intra-bony defects were created in mandibular second and fourth premolars of beagle dogs. Impression material was placed in all of the artificial defects to induce inflammation. Two weeks after the first operation, BDNF (25 and 50 μg/mL) immersed into atelocollagen sponge was applied to the defects. As a control, only atelocollagen sponge immersed in saline was applied. Two and four weeks after the BDNF application, morphometric analysis was performed. Localizations of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA)-positive cells were evaluated by immunohistochemical analysis.
Results
Two weeks after application of BDNF, periodontal tissue was partially regenerated. Immunohistochemical analyses revealed that cells on the denuded root surface were positive with OPN and PCNA. PCNA-positive cells were also detected in the soft connective tissue of regenerating periodontal tissue. Four weeks after application of BDNF, the periodontal defects were regenerated with cementum, periodontal ligament, and alveolar bone. Along the root surface, abundant OPN-positive cells were observed. Morphometric analyses revealed that percentage of new cementum length and percentage of new bone area of experimental groups were higher than control group and dose-dependently increased.
Conclusion
These findings suggest that BDNF could induce cementum regeneration in early regenerative phase by stimulating proliferation of periodontal ligament cells and differentiation into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration in inflamed 3-wall intra-bony defects
Nesprin1 Deficiency Is Associated with Poor Prognosis of Renal Cell Carcinoma and Resistance to Sunitinib Treatment
No full textIntroduction:
Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC).
Methods:
In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and gene set enrichment analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC.
Results:
Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells; however, it did not influence the proliferation of cells. RNA sequencing and gene set enrichment analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival.
Conclusions:
The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment
Weak Kondo Coupling Antiferromagnet CePd3Sn2 with Quasi-One-Dimensional Ce Chains
No full textCePd3Sn2 with Ce-chains along the orthorhombic b axis has been reported to order antiferromagnetically at TN ∼ 0.6 K. Above TN, the specific heat C(T) exhibits a long tail whose origin remains elusive. Here we report on the physical properties of single-crystalline samples inferred from electrical resistivity ρ(T), magnetization M(B), and C(T). The measurements reveal rather weak anisotropic properties characterized by the lowest ρ(T) and the highest saturation M(B) along the b axis. The ρ(T) data along the three principal directions exhibit no clear signature of Kondo scattering and decrease with negative curvatures on cooling from 2 K to TN = 0.67 K. The magnetic susceptibility and inelastic neutron scattering data are reproduced by the crystal electric field (CEF) model for the Ce3+ ion with two excited CEF doublets at rather low energies 27 and 191 K, respectively, above the ground state doublet. The isothermal M(B) curves at 0.3 K show metamagnetic transitions at B || b = 1.8 T and B || c = 1.5 T and upward increases before saturation for the three directions. The antiferromagnetic order is destroyed by the application of magnetic field in an anisotropic way at around B || b = 3 T, B || c = 4 T, and B || a = 5 T. The obtained results are discussed by comparing with those reported for quasi-one-dimensional Ce compounds.This work was financially supported by JST FOREST No. JPMJFR2233, the Mazda Foundation No. 21KK-191, and JSPS KAKEHI Nos. JP21K03473, JP22K03529, JP22KJ2336, and JP23H04870. D.T.A. would like to thank the Royal Society of London for International Exchange funding between the UK and Japan, Newton Advanced Fellowship funding between UK and China, and EPSRC UK for the funding (Grant No. EP/W00562X/1)
Detection of seco-macrotetrolides caused by regiospecific hydrolysis in Indonesian Streptomyces strains isolated at the karst area in Sulawesi Island
No full textAmong a total of 30 endophytic Streptomyces strains collected at the karst area in Sulawesi Island, Indonesia, four strains showed antimicrobial activity together with distinct purple-colored spot(s) on TLC after anisaldehyde staining and baking. Four endophytic strains AA004, AA010, AA034, and AA035 accumulated ionophore macrotetrolides (cyclic tetraesters) including nonactin, monactin, dinactin, trinactin, and tetranactin. Occasionally, strains AA034 and AA035 accumulated considerable amount of seco-macrotetrolides (ring-opened, linear macrotetrolides) including seco-dinactin, seco-monactin, and seco-trinactin, together with macrotetrolides as above mentioned. Time-course increase of seco-macrotetrolides indicates the subsequent hydrolysis of macrotetrolides. Seco-macrotetrolides in strain AA034 were separated from macrotetrolides and other metabolites through Sephadex LH20 and silica gel chromatographies, although seco-macrotetrolides contain inseparable five analogs. We here investigated the hydrolyzed positions in seco-macrotetrolides. ESI-CID-MS/MS analysis of seco-dinactin (m/z 805 as [M+Na]+) and its derivatives, methyl ester (m/z 819 as [M+Na]+) and O-acetyl methyl ester (m/z 861 as [M+Na]+), revealed that seco-dinactin obtained in strains AA034/AA035 is a single regioisomer with a cleavage at an ester bond between the alcohol of (−)-homononactate and the carboxylate of (+)-nonactate, suggesting the regioselective hydrolysis on the occurrence of seco-dinactin. Further ESI-CID-MS/MS analysis revealed that seco-monactin (m/z 791 as [M+Na]+) is also single regioisomer with the ester-bond cleavage between the alcohol of (−)-homononactate and the carboxylate of (+)-nonactate. In the case of seco-trinactin (m/z 819 as [M+Na]+), additional regioisomer with the ester-bond cleavage between the alcohol of (−)-homononactate and the carboxylate of (+)-homononactate was detected, together with the regioisomer with the ester-bond cleavage between the alcohol of (−)-homononactate and the carboxylate of (+)-nonactate. A mixture of seco-macrotetrolides exhibited no antimicrobial activity, indicating the importance of macrocyclic structure for antimicrobial activity.This work was supported by Grants-in-Aid for Scientific Research (B) (No. 22H02274 to K.A.), and Fund for the Promotion of Joint International Research (Fostering Joint International Research (B) (No. 19KK0149 to K.A.) from Japan Society for the Promotion of Science (JSPS). Kenji Arakawa was supported by the JSPS Program for Fostering Globally Talented Researchers (No. JPMXS05S2900002). Alimuddin Ali was supported by the Ministry of Education and Culture, Indonesia, through DIPA Universitas Negeri Makassar (No. 570/UN36/HK/2022). Sisun Choi and Eung-Soo Kim were supported by the National Research Foundation in Korea (No. NRF-2021R1A2C2012203). Rukman Muslimin received a Scholarship for Research Students (Special Selection) from Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), and Novice Lecture Fund DIKTI (Indonesia) 2022 and 2023 (Nos. 003/E5/PG.02.00/2022 and 185/E5/PG.02.00.PL/2023). This work was partly supported by a JSPS A3 Foresight Program (to S.C., E.-S.K., and K.A.)
Language practice and beliefs of domestic and L2 English international students in an English-taught program in Japanese higher education
No full textThis study compared domestic and international students regarding their self-evaluated English proficiency, language performance in English-medium instruction (EMI) classrooms, and their language beliefs. They were enrolled in an English-taught program (ETP) in a Japanese university. EMI courses and programs have strategically increased to attract overseas students and improve domestic students’ English proficiency. Despite extensive EMI research, few studies have focused on EMI experiences of both domestic and international students. Thus, the study analyzed online survey responses from 84 domestic and 24 international students, mostly from Asia. Noticeably, domestic students rated their English proficiency lower than their L2 English international group. Also, the former group found it significantly difficult in performing language tasks, compared to the latter group. Critically, L2 English international students preferred first language (L1) English-speaking instructors and expect non-L1 English lecturers to use native English, whereas Japanese students showed appreciation of lecturers using their L1 in EMI context
Controlling the Magnetic Responsiveness of Cellulose Nanofiber Particles Embedded with Iron Oxide Nanoparticles
No full text2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofiber (TOCN) particles, an innovative biobased material derived from wood biomass, have garnered significant interest, particularly in the biomedical field, for their distinctive properties as biocompatible particle adsorbents. However, their microscopic size complicates their separation in liquid media, thereby impeding their application in various domains. In this study, superparamagnetic magnetite nanoparticles (NPs), specifically iron oxide Fe3O4 NPs with an average size of 15 nm, were used to enhance the collection efficiency of TOCN-Fe3O4 composite particles synthesized through spray drying. These composite particles exhibited a remarkable ζ-potential (approximately −50 mV), indicating their high stability in water, as well as impressive magnetization properties (up to 47 emu/g), and rapid magnetic responsiveness within 60 s in water (3 wt % Fe3O4 to TOCN, 1 T magnet). Furthermore, the influence of Fe3O4 NP concentrations on the measurement of the speed of magnetic separation was quantitatively discussed. Additionally, the binding affinity of the synthesized particles for proteins was assessed on a streptavidin–biotin binding system, offering crucial insights into their binding capabilities with specific proteins and underscoring their significant potential as functionalized biomedical materials
就職活動を通してのキャリアレジリエンスの形成
No full textThe purpose of this study was to confirm whether career resilience changes through job hunting, and to clarify how the state of career resilience before job-hunting affects cognitive changes, behavior, and thoughts during job-hunting activities following rejection, and how these affect the state of career resilience after job-hunting. Online surveys were conducted before and after job-hunting activities. Data on 93 students who completed both surveys and experienced rejection during job-hunting were analyzed. A paired t-test was conducted on the scores before and after job-hunting, and a significant difference was found only in optimism about the future, with the score after job-hunting being higher. Path analysis also suggested that changing one’s perspective and clarifying one’s goal are particularly effective activities during job-hunting to improve one’s career resilience. It was also confirmed that the higher the degree of ability to cope with problems and changes, optimism about the future, and interest in novelty before job-hunting, the more likely the person was to change one’s perspective and clarify one’s goal. These results suggest that career resilience is not enhanced simply by experiencing job-hunting, but rather that career resilience may be developed by overcoming the experience of being rejected by changing perspective and clarifying goals during job hunting activities