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Insights into the pathogenesis of multiple system atrophy: focus on glial cytoplasmic inclusions

Translational Neurodegeneration 2020年第1期9卷 66-80页

作者： Seiji Kaji takakuni maki Tomoyuki Ishimoto Hodaka Yamakado Ryosuke Takahashi Department of Neurology Graduate School of MedicineKyoto University54 Shogoin-Kawahara-choSakyo-kuKyotoJapan

Multiple system atrophy(MSA)is a debilitating and fatal neurodegenerative disorder.The disease severity warrants urgent development of disease-modifying therapy,but the disease pathogenesis is still enigmatic.Neurodegeneration in MSA brains is preceded by the emergence of glial cytoplasmic inclusions(GCIs),which are insoluble α-synuclein accumulations within oligodendrocytes(OLGs).Thus,preventive strategies against GCI formation may suppress disease progression.However,although numerous studies have tried to elucidate the molecular pathogenesis of GCI formation,difficulty remains in understanding the pathological interaction between the two pivotal aspects of GCIs;asynuclein and OLGs.The difficulty originates from several enigmas:1)what triggers the initial generation and possible propagation of pathogenic α-synuclein species?2)what contributes to OLG-specific accumulation of α-synuclein,which is abundantly expressed in neurons but not in OLGs?and 3)how are OLGs and other glial cells affected and contribute to neurodegeneration?The primary pathogenesis of GCIs may involve myelin dysfunaion and dyshomeostasis of the oligodendroglial cellular environment such as autophagy and iron metabolism.We have previously reported that oligodendrocyte precursor cells are more prone to develop intracellular inclusions in the presence of extracellular fibrillary α-synuclein.This finding implies a possibility that the propagation of GCI pathology in MSA brains is mediated through the internalization of pathological α-synuclein into oligodendrocyte precursor cells.In this review,in order to discuss the pathogenesis of GCIs,we will focus on the composition of neuronal and oligodendroglial inclusions in synucleinopathies.Furthermore,we will introduce some hypotheses on how α-synuclein pathology spreads among OLGs in MSA brains,in the light of our data from the experiments with primary oligodendrocyte lineage cell culture.While various reports have focused on the mysterious source of α-synuclein in GCIs,insights into the mechanism wh

关键词： Multiple system atrophy a-synuclein Glial cytoplasmic inclusion Prion Neurodegeneration Oligodendrocyte Microglia Astrocyte Oligodendrocyte precursor cell

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Assessing mixing uniformity in microreactors via in-line spectroscopy

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Chinese Journal of Chemical Engineering 2024年第2期66卷 119-124页

作者： Shusaku Asano Shinji Kudo Taisuke maki Yosuke Muranaka Kazuhiro Mae Jun-ichiro Hayashi Institute for Materials Chemistry and Engineering Kyushu UniversityKasuga 816-8580Japan Department of Chemical Engineering Graduate School of EngineeringKyoto UniversityJapan

Mixing behavior is critical for enhancing the selectivity of fast chemical reactions in microreactors.A high Reynolds number(Re)improves the mixing rate and selectivity of the reactions,but some exceptions of increasing side product yield with the higher Re have been reported.This study investigated the mixing uniformity in microreactors with in-line UV-vis spectroscopy to clarify the relationship between reaction selectivity and chaotic mixing with the higher Re.A colorization experiment of thymolphthalein in an acidic solution was conducted with an excess acid amount to the base to indicate a non-uniformly mixed region.Non-uniformity significantly increased with Re.At the same time,the degree of mixing,which was measured by a usual decolorization experiment,showed that the mixing rate increased with Re.The in-line analysis of the Villermaux-Dushman reaction during the mixing clarified that side product yield significantly increased with Re at around 300 and then decreased at around 1100.These results suggest the compensation effect between the mixing uniformity and mixing rate on the selectivity of the mixing-sensitive reactions.Faster mixing,characterized by a larger Re,can disturb mixing uniformity and,in some cases,decrease reaction selectivity.

关键词： Microreactor Villermaux-Dushman reaction In-line analysis Mixing Mass transfer Uniformity

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日本学界中国古代逻辑思想研究的历程及其特点

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逻辑学研究 2024年第1期17卷 30-54页

作者：深川真树南京师范大学公共管理学院哲学系

19世纪西方文明的冲击,促使东亚知识分子重新审视传统学术,并在中国古代思想中发现逻辑思想。日本学界较早接受西方学术,其对中国古代逻辑思想的研究也取得丰硕成果。日本学者最初是以西方传统形式逻辑为标准,考察中国古代思想,后来逐... 详细信息

19世纪西方文明的冲击,促使东亚知识分子重新审视传统学术,并在中国古代思想中发现逻辑思想。日本学界较早接受西方学术,其对中国古代逻辑思想的研究也取得丰硕成果。日本学者最初是以西方传统形式逻辑为标准,考察中国古代思想,后来逐渐开始关注中国古代汉语的特性,从语言学的角度探究中国古代逻辑思想。这些是日本学界中国古代逻辑思想研究的独特途径。此外,日本在这个领域的研究,从以西方逻辑学为标准看待中国的逻辑思想,转向探究中国独有的逻辑思想。中国学界对中国古代逻辑思想的研究也呈现出类似的趋势。两国学界应加强交流,共同推动中国古代逻辑思想的研究。

关键词：日本中国逻辑思维汉学

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Effect of the Arrangement of a New-Type of Turbulator Inserts on Heat Pipe Exchanger Performances

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Fluid Dynamics & Materials Processing 2023年第10期19卷 2749-2759页

作者： Ibtisam A.Hasan Wafa maki Department of Electromechanical Engineering The University of TechnologyBaghdadIraq

This research tests the effect of introducing turbulators of a new type into a circular tube heat exchanger under a constant and uniform longitudinal heatﬂux condition.A 45 mm diameter copper tube with a length of 1,350 mm is utilized with a solid disk being inserted inside the tube,which consists of three sections,each one containing two slots.The slot is cut at a 45 degree angle toward the inner tube surface,which results in diverging theﬂow toward the inner hot tube surface in order to enhance the heat transfer process.Air is considered as the workingﬂuid with Prandtl number 0.71.The Reynolds number spans the interval from 6,000–13,500,which indicates that the consideredﬂow is turbulent.The heat exchanger performance is studied and analyzed in terms of average Nusselt number.The experimental results show that the Nusselt number value is directly proportional to the increase of the Reynolds number,and the number of turbulators inserts.With the use of three novel turbulators,the heat transfer was about 3.15 times higher than that in the smooth tube and the friction factor was about 1.11.

关键词： Heat pipe exchanger heat transfer inserts(NT inserts) turbulators(novel turbulators) disk(solid disk)

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Ablation for Benign Liver Tumors:Current Concepts and Limitations

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Journal of Clinical and Translational Hepatology 2023年第1期11卷 244-252页

作者： Hitoshi Maruyama maki Tobari Hiroaki Nagamatsu Tadashi Yamaguchi Shuichiro Shiina Department of Gastroenterology Juntendo UniversityTokyoJapan Center for Frontier Medical Engineering Chiba UniversityChibaJapan

Percutaneous ablation under imaging guidance is a curative treatment that can induce complete tumor necrosis with advantages of minimal invasiveness and a low risk of complications.Thermal ablation,which includes radiofrequency ablation and microwave ablation,is a representative technique that has sufficient antitumor effects in cases of hepatocellular carcinoma with≤3 lesions measuring≤3 cm and preserved liver function.The short-and long-term outcomes of patients are comparable with those achieved with surgical resection.Despite their nonmalignant nature,some benign liver tumors require treatment for symptoms caused by the presence of the tumor and/or continuous enlargement.Ablation may be the treatment of choice because it has lower burden on patients than surgical treatment.This review describes the recent concepts,progress,and limitations of ablation-based treatment for benign liver tumors.

关键词： Liver tumor Radiofrequency ablation Microwave ablation Benign

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Long-term survival of the Sister Mary Joseph nodule originating from breast cancer:A case report

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World Journal of Clinical Cases 2023年第34期11卷 8205-8211页

作者： Koji Kanayama maki Tanioka Yoshitsugu Hattori Takuya Iida Mutsumi Okazaki Department of Plastic and Reconstructive Surgery The University of TokyoTokyo 113-8655Japan Department of Medical Oncology National Cancer Center HospitalTokyo 104-0045Japan

BACKGROUND A Sister Mary Joseph nodule(SMJN)is an uncommon cutaneous metastasis found in the umbilicus,indicating an advanced malignancy.SMJNs typically originate from intra-abdominal sources,rarely from breast cancer.Diagnosis suggests a poor prognosis with a median survival of approximately 8 mo after detection.Managing patients with SMJNs is challenging,as most receive limited palliative care only.The optimal strategy for long-term survival of these patients remains unclear.CASE SUMMARY A 58-year-old female,previously diagnosed with right breast cancer 17 years ago and underwent breast-conserving surgery,adjuvant radiotherapy,and endocrine therapy,presented with a 2-cm umbilical nodule.Thirteen years previously,metastases were detected in the right supraclavicular,infraclavicular,hilar,and mediastinal lymph nodes.An umbilical nodule emerged four years before the date of presentation,confirmed as a skin metastasis of primary breast cancer upon excisional biopsy.Despite initial removal,the nodule recurred and grew,leading to her referral to our hospital.The patient underwent extensive excision of the umbilical tumor and immediate abdominal wall reconstruction.Endocrine therapy was continued postoperatively.Five years later,no local recurrence was observed,and the patient continued to work full-time,achieving over 9 years of survival following SMJN diagnosis.CONCLUSION This case study aimed to identify the optimal strategy for achieving extended survival outcomes in patients with SMJN through comprehensive treatment.We presented a case of the longest survival in a patient after undergoing a multidisciplinary treatment regimen.Our findings underscore the significance of adopting a multimodal treatment approach comprising timely and wide excision along with adjunctive therapy.This approach can control the disease,prolong survival,and improve the quality of life in patients with SMJN.

关键词： Sister Mary Joseph nodule Breast cancer Cutaneous metastasis Long-term survival Abdominal wall reconstruction Case report

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Structure and function of ALG-2,a penta-EF-hand calcium-dependent adaptor protein

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Science China(Life Sciences) 2011年第8期54卷 770-779页

作者： Masatoshi maki Hironori SUZUKI Hideki SHIBATA Department of Applied Molecular Biosciences Graduate School of Bioagricultural SciencesNagoya University Structural Biology Research Center Photon FactoryInstitute of Materials Structure ScienceHigh Energy Accelerator Research Organization

ALG-2(a gene product of PDCD6) is a 22-kD protein containing five serially repetitive EF-hand structures and belongs to the penta-EF-hand(PEF) family,including the subunits of typical calpains.ALG-2 is the most conserved protein among the PEF family members and its homologs are widely found in eukaryotes.X-ray crystal structures of various PEF proteins including ALG-2 have common features:presence of eightα-helices and dimer formation via paired EF5s that are positioned in anti-parallel orientation.ALG-2 forms a homodimer and a heterodimer with its closest paralog peflin.Like calmodulin,a well-known four-EF-hand protein,ALG-2 interacts with various proteins in a Ca2+-dependent fashion,but the binding motifs are completely different.With some exceptions,ALG-2-interacting proteins commonly contain Pro-rich regions,and ALG-2 recognizes at least two distinct Pro-containing motifs:PPYP(X) nYP(X,variable;n=4 in ALIX and PLSCR3) and PXPGF(represented by Sec31A) .A shorter alternatively spliced isoform,lacking two residues and designated ALG-2 GF122,does not bind ALIX but maintains binding capacity to Sec31A.X-ray crystal structural analyses have revealed that binding of calcium ions induces the configuration of the side chain of R125 so that it opens Pocket 1,which accepts PPYP,but Pocket 1 remains closed in the case of ALG-2 GF122.ALG-2 dimer has two ligand-binding sites,each in a monomer molecule,and appears to function as a Ca2+-dependent adaptor protein to either stabilize a preformed complex or to bridge two proteins on scaffolds in systems of the endosomal sorting complex required for transport(ESCRT) and ER-to-Golgi transport.

关键词：晶体结构分析钙蛋白酶 ALG 接头异源二聚体蛋白相互作用手型选择性剪接

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Antibodies in celiac disease:implications beyond diagnostics

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Cellular & Molecular Immunology 2011年第2期8卷 103-109页

作者： Sergio Caja Markku maki Katri Kaukinen Katri Lindfors Pediatric Research Centre University of Tampere and Tampere University HospitalTampereFinland Medical School University of Tampere and Department of Gastroenterology and Alimentary Tract SurgeryTampere University HospitalTampereFinland

Celiac disease is a multisystemic dietary,gluten-induced autoimmune disorder characterized by the presence of transglutaminase(TG)2 serum autoantibodies.Distinct autoantibodies targeting members of the TG family(TG2,TG3 and TG6)are found deposited in small-bowel mucosa and in extraintestinal tissues affected by the disease.Serum autoantibodies against other self-antigens also emerge in untreated celiac disease patients.Although villous atrophy and crypt hyperplasia in small-bowel biopsy samples are still the gold standards in diagnostics,celiac disease-specific antibodies are widely used as diagnostic aids.Gluten-induced small-bowel mucosal T-cell response is the cornerstone in the pathogenesis of the disorder,but humoral immunity may also play a central role.This review article is focused on the autoantibodies that occur in the context of celiac disease.The article summarizes the diagnostic utility of different celiac-related antibodies and discusses their roles in the pathogenesis of the disease.

关键词： antibody celiacdisease diagnostics pathogenesis

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Manipulation of polarization topology using a Fabry-Pérot fiber cavity with a higher-order mode optical nanofiber

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Photonics Research 2023年第6期11卷 1029-1037页

作者： maki MAEDA JAMEESH KELOTH SÍLE NIC CHORMAIC Okinawa Institute of Science and Technology Graduate University OnnaOkinawa 904-0495Japan

Optical nanofiber cavity research has mainly focused on the fundamental mode.Here,a Fabry-Pérot fiber cavity with an optical nanofiber supporting the higher-order modes(TE01,TM01,HEo21,and HEe21)is demonstrated.Using cavity spectroscopy,with mode imaging and analysis,we observed cavity resonances that exhibited complex,inhomogeneous states of polarization with topological features containing Stokes singularities such as C-points,Poincarévortices,and L-lines.In situ tuning of the intracavity birefringence enabled the desired profile and polarization of the cavity mode to be obtained.We believe these findings open new research possibilities for cold atom manipulation and multimode cavity quantum electrodynamics using the evanescent fields of higher-order mode optical nanofibers.

关键词： polarization fiber optical

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：ognitive changes associated with ADT： a review of the iterature

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Asian Journal of Andrology 2012年第2期14卷 232-238页

作者： Rhoda J Jamadar Mary J Winters Pauline M maki Center for Cognitive Medicine Department of Psychiatry university of Illinois at Chicago Chicago IL 60612 USA Department of Psychology University of Illinois at Chicago Chicago IL 60612 USA

The use of androgen deprivation therapy （ADT） has increased since the early 1990s after early detection efforts and greater use of the prostate-specific antigen （PSA） test. Although ADT is associated with favorable clinical outcomes, ADT has been associated with an increased risk for cardiovascular disease, increased serum cholesterol, triglycerides, insulin resistance, body mass index and fat body mass. Here we review findings from 11 clinical studies examining the effects of ADT on cognition as measured by standardized tests in cognitive domains such as verbal and spatial memory. Most of these studies have important limitations, including small sample sizes, suboptimal control groups and baseline group differences in confounding factors. Despite these limitations, the best designed studies, those comparing patients on ADT to healthy controls, generally suggest that spatial memory might be especially sensitive to the effects of ADT. Critically, to date there is only one study involving random assignment of ADT versus close clinical observation. That study revealed a decrease in verbal memory with ADT, but was limited in sample size and did not include a measure of spatial memory. A recent observational study revealed no substantial evidence of cognitive impairment with ADT, even in the domain of verbal memory. Like the randomizedstudy, however, this large observational study lacked a measure of spatial memory. Overall, the studies with the best controls suggest a potential negative impact of ADT on spatial memory, and perhaps verbal memory, and a need for continued investigation of the impact of ADT on cognition, particularly in these two cognitive domains.

关键词： androgen deprivation therapy cognition prostate cancer

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