Motoaki Fukasawa - Academia.edu (original) (raw)

Papers by Motoaki Fukasawa

Research paper thumbnail of Author Response: Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment

Research paper thumbnail of Expression of 3β-hydroxysteroid dehydrogenase (hsd3b), star and ad4bp/sf-1 during gonadal development in medaka (Oryzias latipes)

General and Comparative Endocrinology, Apr 1, 2012

Background. Human 3b-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidog... more Background. Human 3b-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings. Methods. Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo. Results. The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth. Conclusions. Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.

Research paper thumbnail of Subarachnoid hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser1412 in the dentate gyrus of the rat brain

Nitric Oxide, Dec 1, 2018

hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyru... more hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyrus of the rat brain, Nitric Oxide (2017),

Research paper thumbnail of 3P-333 Phase contrast observation of ultrastructures inside vitrified cells(The 46th Annual Meeting of the Biophysical Society of Japan)

Seibutsu Butsuri, 2008

AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and ... more AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and its applicaLioll to cdls 1inkoto Sakaia) Kbvchi inoue(ij Ken Llehtxra(Iy SLitoshi KbgztrLay Wbgaaki ftvtt(iYft enLmxLctifl"oLir[cfLah fokyo lnst of fechy colrelatlenspLutrosLvpy }intittomo NotnigraCly FyJ ntkahashtO) unLhihtho Satorey Feng Zhonqgangev Jbheo ,Nakcxmuraa) MitsatcthaK)igoC!) (1 Dq)tLitL SaLnce CTraduateSlrhootoi'MLdi[aiS"enLL lhniqsata Lbuv 2 Gcnerai LdLthcalEdueanon Cenkr Schoot of indfcme lhmmgttttT Untv 3 Central Jaboratv-jiv Research andEdecation Scho-l (g MLdi"ne nimagata Univ 4 Depf Bio SFsrem Fng Gtaduak SLhool ofS"Lnce and Fnglneenng l2imagata Ongv 5 Lab ldekcuiaF Celi Qynamxcs GnadtiatF Sfhuog ofLijl 6etLn" Hbkkaick] [ nn

Research paper thumbnail of Dopamine release by moxibustion stimulation revealed by microdialysis

Neuroscience Research, 2010

Research paper thumbnail of Manganese-enhanced magnetic resonance imaging detects activation of limbic structures in response to auditory stimuli of different frequencies

Magnetic Resonance Imaging, Dec 1, 2022

Research paper thumbnail of Immunohistochemical Localization of Mitochondrial Fatty Acid β-Oxidation Enzymes in Rat Testis

Journal of Histochemistry and Cytochemistry, Oct 29, 2009

The testis consists of two types of tissues, the interstitial tissue and the seminiferous tubule,... more The testis consists of two types of tissues, the interstitial tissue and the seminiferous tubule, which have different functions and are assumed to have different nutritional metabolism. The localization of enzymes of the mitochondrial fatty acid b-oxidation system in the testis was investigated to obtain a better understanding of nutrient metabolism in the testis. Adult rat testis tissues were subjected to immunoblot analysis for quantitation of the amounts of enzyme proteins, to DNA microarray analysis for gene expression, and to immunofluorescence and immunoelectron microscopy for localization. Quantitative analysis by immunoblot and DNA microarray revealed that enzymes occur abundantly in Leydig cells in the interstitial tissue but much less so in the seminiferous tubules. Immunohistochemistry revealed that Leydig cells in the interstitial tissue and Sertoli cells in the seminiferous tubules contain a full set of mitochondrial fatty acid b-oxidation enzymes in relatively plentiful amounts among the cells in the testis, but that this is not so in spermatogenic cells. This characteristic localization of the mitochondrial fatty acid b-oxidation system in the testis needs further elucidation in terms of a possible role for it in the nutritional metabolism of spermatogenesis.

Research paper thumbnail of Poster Presentations

Nephrology

Objectives: Peritonitis is a common complication with inflammatory status. Lipopolysaccharide (LP... more Objectives: Peritonitis is a common complication with inflammatory status. Lipopolysaccharide (LPS)-induced inflammatory status could be restored by peroxisome proliferator-activated receptor (PPAR) γ agonists and extracellularsignal-regulated kinases 1/2 (ERK1/2) inactivation. This study aimed to investigate the association or interaction between PPARγ and ERK1/ 2 in LPS-induced inflammation in peritonitis. Methods: Human peritoneal mesothelial cells (HPMCs) were maintained in DMEM supplemented with series concentrations of LPS for time series. Cellularinterleukins (ILs) were measured using enzyme-linked immunosorbent assay (ELISA) assay. Expression or activation of cyclin-dependent kinase (CDK)5, ERK1/2, PPARγ were detected using PCR and/or Western blot. Results: LPS-induced doseand time-dependent increment in cellular IL-1β, IL-6 and IL-12 contents and CDK5 expression as well as PPARγ phosphorylation, and 1 μg/ml LPS treatment for 12 h was the optimal experimental design for inflammation stimulation. Overdose LPS or excessive time induced lower inflammatory status. LPS stimulation also induced activation of ERK1/ 2 and interaction between CDK5 and p25/p35. Further experiments showed inhibition of ERK1/2 by AZD0364 prevented LPS-induced IL-1β, IL-6, IL-12, ERK1/2, CDK5 and PPARγ, and CDK5 siRNA suppressed LPS-induced IL-1β, IL-6, IL-12, CDK5 and PPARγ. Conclusions: Our results suggested that LPS-induced inflammation in HPMCs could be prevented by inhibition of ERK1/2/CDK5 axis through at least partially PPARγ. 167 LOSARTAN REDUCES EARLY ALBUMINURIA IN DIABETIC NEPHROPATHY BY REGULATING CAVEOLIN1-MEDIATED ALBUMIN TRANSCYTOSIS ACROSS GLOMERULAR ENDOTHELIAL CELLS DI ZHANG, YI ZHAO, YI GONG, YUE QIU, YUMEI WANG Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science And Technology, Wuhan, China Objectives: Diabetic nephropathy is a serious disease threatening human health. Albuminuria is the first clinical manifestation of diabetic nephropathy (DN), and it is also an independent risk factor for the progression of DN. Losartan reduces albuminuria in DN patients in various aspects, however, the precise mechanism is unknown. Caveolin 1 (Cav1), as an endocytosis dependent protein, plays an important role in albumin transcytosis across vascular endothelial cells, which may be involved in the formation of albuminuria in diabetic nephropathy. The purpose of this study is to investigate whether losartan could regulate the formation of early albuminuria in DN by regulating Cav1-mediated albumin transcytosis across glomerular endothelial cells. Methods: Human renal glomerular endothelial cells (HRGEC) were cultured in vitro to construct albumin transcytosis model. Albumin transcytosis across HRGECs was detected by microplate reader and Western blot under normal glucose and high glucose medium respectively. Then, Cav-1 protein expression was detected in above mentioned conditions, and the influence on albumin transcytosis was examined when Cav-1 was inhibited. Finally, the effect on albumin transcytosis and Cav-1 expression were evaluated when losartan was applied. Results: In high glucose medium, albumin transcytosis across HRGECs and protein expression of Cav-1 were significantly increased in time-dependent manner. Knocking down Cav-1 dramatically reduced albumin transcytosis across HRGECs in high glucose medium. And losartan significantly downregulated the protein expression of Cav-1 in HGRECs and albumin transcytosis across HRGECs in high glucose group. Conclusions: The possible mechanism of early albuminuria reduction by losartan in diabetic nephropathy could be its regulation of Cav1-mediated albumin transcytosis across glomerular endothelial cells. This new finding may provide a new target for losartan in the treatment of albuminuria in DN

Research paper thumbnail of Manganese-enhanced magnetic resonance imaging detects activation of limbic structures in response to auditory stimuli of different frequencies

Magnetic Resonance Imaging

Research paper thumbnail of OUP accepted manuscript

Microscopy, May 10, 2022

The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified i... more The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified in electron microscopy by the morphological criteria of lamellae. A 3-dimensional analyses with serial block-face scanning electron microscope (SBF-SEM), a volume-SEM proficient in obtaining large volumes of data at the whole-cell level, could be a promising technique for understanding the precise distribution and complex ultrastructure of Golgi apparatus, although optimal methods for such analyses remain unclear since the observation can be hampered with sample charging and low image contrast, and manual segmentation often requires significant manpower. The present study attempted the whole-cell observation and semi-automatic classification and segmentation of the Golgi apparatus in rat hepatocytes for the first time by SBF-SEM via ZIO staining, a classical osmium impregnation. The staining electron-densely visualized individual Golgi lamellae, and their ultrastructure could stably be observed without any noticeable charging. The simple thresholding of the serial images enabled the efficient reconstruction of the labeled Golgi apparatus, which revealed plural Golgi apparatus in one hepatocyte. The combination of the heavy metal-based histochemistry of zinc, iodine and osmium (ZIO) staining and SBF-SEM was useful in the 3-dimensional observation of the Golgi apparatus at the whole-cell level because of two technical advantages: (i) visualization of the Golgi apparatus without any heavy metal staining and efficient acquisition of the block-face images without additional conductive staining or any devices for eliminating charging; (ii) easy identification of the staining and hassle-free, semi-automatic classification and segmentation by simple thresholding of the images. This novel approach could elucidate the topographic characteristics of the Golgi apparatus in hepatocytes.

Research paper thumbnail of Whole-cell observation of ZIO-stained Golgi apparatus in rat hepatocytes with serial block-face scanning electron microscope, SBF-SEM

Microscopy

The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified i... more The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified in electron microscopy by the morphological criteria of lamellae. A 3-dimensional analyses with serial block-face scanning electron microscope (SBF-SEM), a volume-SEM proficient in obtaining large volumes of data at the whole-cell level, could be a promising technique for understanding the precise distribution and complex ultrastructure of Golgi apparatus, although optimal methods for such analyses remain unclear since the observation can be hampered with sample charging and low image contrast, and manual segmentation often requires significant manpower. The present study attempted the whole-cell observation and semi-automatic classification and segmentation of the Golgi apparatus in rat hepatocytes for the first time by SBF-SEM via ZIO staining, a classical osmium impregnation. The staining electron-densely visualized individual Golgi lamellae, and their ultrastructure could stably be ob...

Research paper thumbnail of Characterization of the nutrient‐metabolism in Sertoli cells by immunohistochemical and DNA microarray analyses

Research paper thumbnail of Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surr... more Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2,294 animals with genetic...

Research paper thumbnail of A Study on FEM Analysis of a Flexible Tactile Sensor Using Structure of Subcutaneous Tissue

The Proceedings of JSME annual Conference on Robotics and Mechatronics (Robomec), 2018

The development of a tactile sensor for robots is proceeding, whereas, there are many problems su... more The development of a tactile sensor for robots is proceeding, whereas, there are many problems such as flexibility and detection area. Human skin has softness, high sensitivity and broad receptive field. The structure of the human skin gives us effective design for tactile sensors. Thus, we focused on the structure of human subcutaneous tissue, and have developed a flexible tactile sensor based on collagen fiber and adipose tissue structure. In this study, we verified the effectiveness of the tactile sensor based on the structure of the subcutaneous tissue by using FEM analysis.

Research paper thumbnail of Subarachnoid hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser1412 in the dentate gyrus of the rat brain

Nitric Oxide, 2018

hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyru... more hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyrus of the rat brain, Nitric Oxide (2017),

Research paper thumbnail of Basic quantitative study on stress dispersion in subcutaneous tissue by the distribution of collagen fibers

The Proceedings of the Bioengineering Conference Annual Meeting of BED/JSME, 2017

Research paper thumbnail of 3P-333 Phase contrast observation of ultrastructures inside vitrified cells(The 46th Annual Meeting of the Biophysical Society of Japan)

Seibutsu Butsuri, 2008

AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and ... more AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and its applicaLioll to cdls 1inkoto Sakaia) Kbvchi inoue(ij Ken Llehtxra(Iy SLitoshi KbgztrLay Wbgaaki ftvtt(iYft enLmxLctifl"oLir[cfLah fokyo lnst of fechy colrelatlenspLutrosLvpy }intittomo NotnigraCly FyJ ntkahashtO) unLhihtho Satorey Feng Zhonqgangev Jbheo ,Nakcxmuraa) MitsatcthaK)igoC!) (1 Dq)tLitL SaLnce CTraduateSlrhootoi'MLdi[aiS"enLL lhniqsata Lbuv 2 Gcnerai LdLthcalEdueanon Cenkr Schoot of indfcme lhmmgttttT Untv 3 Central Jaboratv-jiv Research andEdecation Scho-l (g MLdi"ne nimagata Univ 4 Depf Bio SFsrem Fng Gtaduak SLhool ofS"Lnce and Fnglneenng l2imagata Ongv 5 Lab ldekcuiaF Celi Qynamxcs GnadtiatF Sfhuog ofLijl 6etLn" Hbkkaick] [ nn

Research paper thumbnail of Collagen fibers induce expansion of receptive field of Pacinian corpuscles

Advanced Robotics, 2015

Pacinian corpuscles within the skin are mechanoreceptors with a high sensitivity and a broad rece... more Pacinian corpuscles within the skin are mechanoreceptors with a high sensitivity and a broad receptive field, and they contribute to texture evaluation and contact detection. They are distributed in small numbers in the subcutaneous tissue, which is a deep layer in the skin. We propose a new skin model with texture of collagen fibers, based on observations of the thumb of a Macaca fuscata. A finite element analysis using the model reveals that collagen fibers disperse stress concentrations in the subcutaneous tissue, leading to a broad receptive field for Pacinian corpuscles while maintaining their high sensitivity.

Research paper thumbnail of Basic Study on a Soft Tactile Sensor Based on Subcutaneous Tissue with Collagen Fibers

Lecture Notes in Computer Science, 2016

Humans have a high sensitivity and a broad receptive field in tactile function and the skin perfo... more Humans have a high sensitivity and a broad receptive field in tactile function and the skin performs an important role to propagate mechanical stimulation to mechanoreceptors. Previously, a finite element analysis using a skin model with collagen fibers revealed that the collagen fibers disperse stress concentrations in subcutaneous tissue. Thus, this paper presents the development of a soft tactile sensor having a structure of the subcutaneous tissue composed of adipose tissue and the collagen fibers by using urethane resins. As a sensing element, the compression of the adipose tissue part occurred by deformation on the sensor’s surface is measured by using the water level. A response of the proposed sensor is compared with a response of a sensor having a conventional uniform structure. The results indicate that the proposed sensor has a broad receptive field maintaining a high sensitivity as compared with the uniform sensor.

Research paper thumbnail of Identification of feline immunodeficiency virus subtype-B on St. Kitts, West Indies by quantitative PCR

The Journal of Infection in Developing Countries, 2011

Introduction: Although antibodies to the feline immunodeficiency virus (FIV) have been detected b... more Introduction: Although antibodies to the feline immunodeficiency virus (FIV) have been detected by SNAP assay in cats from St. Kitts, there have been no molecular studies to further confirm the infection and determine the FIV subtypes present. Methodology: Total nucleic acids were extracted from EDTA whole blood specimens from 35 cats, followed by quantitative fluorescence resonance energy transfer (FRET) PCR under a six-channel LightCycler 2.0 Instrument with Software version 4.1. Results: Four of 11 stray cats (36 %) but none of 24 owned cats were FIV positive by real-time PCR. High-resolution melting curve analysis indicated that all four positive cats were infected with FIV subtype-B. Conclusions: This is the first molecular characterization of FIV subtypes on St. Kitts and the results confirm the high prevalence of FIV infection in stray cats on the island.

Research paper thumbnail of Author Response: Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment

Research paper thumbnail of Expression of 3β-hydroxysteroid dehydrogenase (hsd3b), star and ad4bp/sf-1 during gonadal development in medaka (Oryzias latipes)

General and Comparative Endocrinology, Apr 1, 2012

Background. Human 3b-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidog... more Background. Human 3b-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings. Methods. Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo. Results. The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth. Conclusions. Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.

Research paper thumbnail of Subarachnoid hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser1412 in the dentate gyrus of the rat brain

Nitric Oxide, Dec 1, 2018

hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyru... more hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyrus of the rat brain, Nitric Oxide (2017),

Research paper thumbnail of 3P-333 Phase contrast observation of ultrastructures inside vitrified cells(The 46th Annual Meeting of the Biophysical Society of Japan)

Seibutsu Butsuri, 2008

AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and ... more AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and its applicaLioll to cdls 1inkoto Sakaia) Kbvchi inoue(ij Ken Llehtxra(Iy SLitoshi KbgztrLay Wbgaaki ftvtt(iYft enLmxLctifl"oLir[cfLah fokyo lnst of fechy colrelatlenspLutrosLvpy }intittomo NotnigraCly FyJ ntkahashtO) unLhihtho Satorey Feng Zhonqgangev Jbheo ,Nakcxmuraa) MitsatcthaK)igoC!) (1 Dq)tLitL SaLnce CTraduateSlrhootoi'MLdi[aiS"enLL lhniqsata Lbuv 2 Gcnerai LdLthcalEdueanon Cenkr Schoot of indfcme lhmmgttttT Untv 3 Central Jaboratv-jiv Research andEdecation Scho-l (g MLdi"ne nimagata Univ 4 Depf Bio SFsrem Fng Gtaduak SLhool ofS"Lnce and Fnglneenng l2imagata Ongv 5 Lab ldekcuiaF Celi Qynamxcs GnadtiatF Sfhuog ofLijl 6etLn" Hbkkaick] [ nn

Research paper thumbnail of Dopamine release by moxibustion stimulation revealed by microdialysis

Neuroscience Research, 2010

Research paper thumbnail of Manganese-enhanced magnetic resonance imaging detects activation of limbic structures in response to auditory stimuli of different frequencies

Magnetic Resonance Imaging, Dec 1, 2022

Research paper thumbnail of Immunohistochemical Localization of Mitochondrial Fatty Acid β-Oxidation Enzymes in Rat Testis

Journal of Histochemistry and Cytochemistry, Oct 29, 2009

The testis consists of two types of tissues, the interstitial tissue and the seminiferous tubule,... more The testis consists of two types of tissues, the interstitial tissue and the seminiferous tubule, which have different functions and are assumed to have different nutritional metabolism. The localization of enzymes of the mitochondrial fatty acid b-oxidation system in the testis was investigated to obtain a better understanding of nutrient metabolism in the testis. Adult rat testis tissues were subjected to immunoblot analysis for quantitation of the amounts of enzyme proteins, to DNA microarray analysis for gene expression, and to immunofluorescence and immunoelectron microscopy for localization. Quantitative analysis by immunoblot and DNA microarray revealed that enzymes occur abundantly in Leydig cells in the interstitial tissue but much less so in the seminiferous tubules. Immunohistochemistry revealed that Leydig cells in the interstitial tissue and Sertoli cells in the seminiferous tubules contain a full set of mitochondrial fatty acid b-oxidation enzymes in relatively plentiful amounts among the cells in the testis, but that this is not so in spermatogenic cells. This characteristic localization of the mitochondrial fatty acid b-oxidation system in the testis needs further elucidation in terms of a possible role for it in the nutritional metabolism of spermatogenesis.

Research paper thumbnail of Poster Presentations

Nephrology

Objectives: Peritonitis is a common complication with inflammatory status. Lipopolysaccharide (LP... more Objectives: Peritonitis is a common complication with inflammatory status. Lipopolysaccharide (LPS)-induced inflammatory status could be restored by peroxisome proliferator-activated receptor (PPAR) γ agonists and extracellularsignal-regulated kinases 1/2 (ERK1/2) inactivation. This study aimed to investigate the association or interaction between PPARγ and ERK1/ 2 in LPS-induced inflammation in peritonitis. Methods: Human peritoneal mesothelial cells (HPMCs) were maintained in DMEM supplemented with series concentrations of LPS for time series. Cellularinterleukins (ILs) were measured using enzyme-linked immunosorbent assay (ELISA) assay. Expression or activation of cyclin-dependent kinase (CDK)5, ERK1/2, PPARγ were detected using PCR and/or Western blot. Results: LPS-induced doseand time-dependent increment in cellular IL-1β, IL-6 and IL-12 contents and CDK5 expression as well as PPARγ phosphorylation, and 1 μg/ml LPS treatment for 12 h was the optimal experimental design for inflammation stimulation. Overdose LPS or excessive time induced lower inflammatory status. LPS stimulation also induced activation of ERK1/ 2 and interaction between CDK5 and p25/p35. Further experiments showed inhibition of ERK1/2 by AZD0364 prevented LPS-induced IL-1β, IL-6, IL-12, ERK1/2, CDK5 and PPARγ, and CDK5 siRNA suppressed LPS-induced IL-1β, IL-6, IL-12, CDK5 and PPARγ. Conclusions: Our results suggested that LPS-induced inflammation in HPMCs could be prevented by inhibition of ERK1/2/CDK5 axis through at least partially PPARγ. 167 LOSARTAN REDUCES EARLY ALBUMINURIA IN DIABETIC NEPHROPATHY BY REGULATING CAVEOLIN1-MEDIATED ALBUMIN TRANSCYTOSIS ACROSS GLOMERULAR ENDOTHELIAL CELLS DI ZHANG, YI ZHAO, YI GONG, YUE QIU, YUMEI WANG Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science And Technology, Wuhan, China Objectives: Diabetic nephropathy is a serious disease threatening human health. Albuminuria is the first clinical manifestation of diabetic nephropathy (DN), and it is also an independent risk factor for the progression of DN. Losartan reduces albuminuria in DN patients in various aspects, however, the precise mechanism is unknown. Caveolin 1 (Cav1), as an endocytosis dependent protein, plays an important role in albumin transcytosis across vascular endothelial cells, which may be involved in the formation of albuminuria in diabetic nephropathy. The purpose of this study is to investigate whether losartan could regulate the formation of early albuminuria in DN by regulating Cav1-mediated albumin transcytosis across glomerular endothelial cells. Methods: Human renal glomerular endothelial cells (HRGEC) were cultured in vitro to construct albumin transcytosis model. Albumin transcytosis across HRGECs was detected by microplate reader and Western blot under normal glucose and high glucose medium respectively. Then, Cav-1 protein expression was detected in above mentioned conditions, and the influence on albumin transcytosis was examined when Cav-1 was inhibited. Finally, the effect on albumin transcytosis and Cav-1 expression were evaluated when losartan was applied. Results: In high glucose medium, albumin transcytosis across HRGECs and protein expression of Cav-1 were significantly increased in time-dependent manner. Knocking down Cav-1 dramatically reduced albumin transcytosis across HRGECs in high glucose medium. And losartan significantly downregulated the protein expression of Cav-1 in HGRECs and albumin transcytosis across HRGECs in high glucose group. Conclusions: The possible mechanism of early albuminuria reduction by losartan in diabetic nephropathy could be its regulation of Cav1-mediated albumin transcytosis across glomerular endothelial cells. This new finding may provide a new target for losartan in the treatment of albuminuria in DN

Research paper thumbnail of Manganese-enhanced magnetic resonance imaging detects activation of limbic structures in response to auditory stimuli of different frequencies

Magnetic Resonance Imaging

Research paper thumbnail of OUP accepted manuscript

Microscopy, May 10, 2022

The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified i... more The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified in electron microscopy by the morphological criteria of lamellae. A 3-dimensional analyses with serial block-face scanning electron microscope (SBF-SEM), a volume-SEM proficient in obtaining large volumes of data at the whole-cell level, could be a promising technique for understanding the precise distribution and complex ultrastructure of Golgi apparatus, although optimal methods for such analyses remain unclear since the observation can be hampered with sample charging and low image contrast, and manual segmentation often requires significant manpower. The present study attempted the whole-cell observation and semi-automatic classification and segmentation of the Golgi apparatus in rat hepatocytes for the first time by SBF-SEM via ZIO staining, a classical osmium impregnation. The staining electron-densely visualized individual Golgi lamellae, and their ultrastructure could stably be observed without any noticeable charging. The simple thresholding of the serial images enabled the efficient reconstruction of the labeled Golgi apparatus, which revealed plural Golgi apparatus in one hepatocyte. The combination of the heavy metal-based histochemistry of zinc, iodine and osmium (ZIO) staining and SBF-SEM was useful in the 3-dimensional observation of the Golgi apparatus at the whole-cell level because of two technical advantages: (i) visualization of the Golgi apparatus without any heavy metal staining and efficient acquisition of the block-face images without additional conductive staining or any devices for eliminating charging; (ii) easy identification of the staining and hassle-free, semi-automatic classification and segmentation by simple thresholding of the images. This novel approach could elucidate the topographic characteristics of the Golgi apparatus in hepatocytes.

Research paper thumbnail of Whole-cell observation of ZIO-stained Golgi apparatus in rat hepatocytes with serial block-face scanning electron microscope, SBF-SEM

Microscopy

The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified i... more The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified in electron microscopy by the morphological criteria of lamellae. A 3-dimensional analyses with serial block-face scanning electron microscope (SBF-SEM), a volume-SEM proficient in obtaining large volumes of data at the whole-cell level, could be a promising technique for understanding the precise distribution and complex ultrastructure of Golgi apparatus, although optimal methods for such analyses remain unclear since the observation can be hampered with sample charging and low image contrast, and manual segmentation often requires significant manpower. The present study attempted the whole-cell observation and semi-automatic classification and segmentation of the Golgi apparatus in rat hepatocytes for the first time by SBF-SEM via ZIO staining, a classical osmium impregnation. The staining electron-densely visualized individual Golgi lamellae, and their ultrastructure could stably be ob...

Research paper thumbnail of Characterization of the nutrient‐metabolism in Sertoli cells by immunohistochemical and DNA microarray analyses

Research paper thumbnail of Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surr... more Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2,294 animals with genetic...

Research paper thumbnail of A Study on FEM Analysis of a Flexible Tactile Sensor Using Structure of Subcutaneous Tissue

The Proceedings of JSME annual Conference on Robotics and Mechatronics (Robomec), 2018

The development of a tactile sensor for robots is proceeding, whereas, there are many problems su... more The development of a tactile sensor for robots is proceeding, whereas, there are many problems such as flexibility and detection area. Human skin has softness, high sensitivity and broad receptive field. The structure of the human skin gives us effective design for tactile sensors. Thus, we focused on the structure of human subcutaneous tissue, and have developed a flexible tactile sensor based on collagen fiber and adipose tissue structure. In this study, we verified the effectiveness of the tactile sensor based on the structure of the subcutaneous tissue by using FEM analysis.

Research paper thumbnail of Subarachnoid hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser1412 in the dentate gyrus of the rat brain

Nitric Oxide, 2018

hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyru... more hemorrhage induces neuronal nitric oxide synthase phosphorylation at Ser 1412 in the dentate gyrus of the rat brain, Nitric Oxide (2017),

Research paper thumbnail of Basic quantitative study on stress dispersion in subcutaneous tissue by the distribution of collagen fibers

The Proceedings of the Bioengineering Conference Annual Meeting of BED/JSME, 2017

Research paper thumbnail of 3P-333 Phase contrast observation of ultrastructures inside vitrified cells(The 46th Annual Meeting of the Biophysical Society of Japan)

Seibutsu Butsuri, 2008

AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and ... more AdimsM R superTesolutieu miLroscope based on transient fiuoreseencc detected IR specrroscopy and its applicaLioll to cdls 1inkoto Sakaia) Kbvchi inoue(ij Ken Llehtxra(Iy SLitoshi KbgztrLay Wbgaaki ftvtt(iYft enLmxLctifl"oLir[cfLah fokyo lnst of fechy colrelatlenspLutrosLvpy }intittomo NotnigraCly FyJ ntkahashtO) unLhihtho Satorey Feng Zhonqgangev Jbheo ,Nakcxmuraa) MitsatcthaK)igoC!) (1 Dq)tLitL SaLnce CTraduateSlrhootoi'MLdi[aiS"enLL lhniqsata Lbuv 2 Gcnerai LdLthcalEdueanon Cenkr Schoot of indfcme lhmmgttttT Untv 3 Central Jaboratv-jiv Research andEdecation Scho-l (g MLdi"ne nimagata Univ 4 Depf Bio SFsrem Fng Gtaduak SLhool ofS"Lnce and Fnglneenng l2imagata Ongv 5 Lab ldekcuiaF Celi Qynamxcs GnadtiatF Sfhuog ofLijl 6etLn" Hbkkaick] [ nn

Research paper thumbnail of Collagen fibers induce expansion of receptive field of Pacinian corpuscles

Advanced Robotics, 2015

Pacinian corpuscles within the skin are mechanoreceptors with a high sensitivity and a broad rece... more Pacinian corpuscles within the skin are mechanoreceptors with a high sensitivity and a broad receptive field, and they contribute to texture evaluation and contact detection. They are distributed in small numbers in the subcutaneous tissue, which is a deep layer in the skin. We propose a new skin model with texture of collagen fibers, based on observations of the thumb of a Macaca fuscata. A finite element analysis using the model reveals that collagen fibers disperse stress concentrations in the subcutaneous tissue, leading to a broad receptive field for Pacinian corpuscles while maintaining their high sensitivity.

Research paper thumbnail of Basic Study on a Soft Tactile Sensor Based on Subcutaneous Tissue with Collagen Fibers

Lecture Notes in Computer Science, 2016

Humans have a high sensitivity and a broad receptive field in tactile function and the skin perfo... more Humans have a high sensitivity and a broad receptive field in tactile function and the skin performs an important role to propagate mechanical stimulation to mechanoreceptors. Previously, a finite element analysis using a skin model with collagen fibers revealed that the collagen fibers disperse stress concentrations in subcutaneous tissue. Thus, this paper presents the development of a soft tactile sensor having a structure of the subcutaneous tissue composed of adipose tissue and the collagen fibers by using urethane resins. As a sensing element, the compression of the adipose tissue part occurred by deformation on the sensor’s surface is measured by using the water level. A response of the proposed sensor is compared with a response of a sensor having a conventional uniform structure. The results indicate that the proposed sensor has a broad receptive field maintaining a high sensitivity as compared with the uniform sensor.

Research paper thumbnail of Identification of feline immunodeficiency virus subtype-B on St. Kitts, West Indies by quantitative PCR

The Journal of Infection in Developing Countries, 2011

Introduction: Although antibodies to the feline immunodeficiency virus (FIV) have been detected b... more Introduction: Although antibodies to the feline immunodeficiency virus (FIV) have been detected by SNAP assay in cats from St. Kitts, there have been no molecular studies to further confirm the infection and determine the FIV subtypes present. Methodology: Total nucleic acids were extracted from EDTA whole blood specimens from 35 cats, followed by quantitative fluorescence resonance energy transfer (FRET) PCR under a six-channel LightCycler 2.0 Instrument with Software version 4.1. Results: Four of 11 stray cats (36 %) but none of 24 owned cats were FIV positive by real-time PCR. High-resolution melting curve analysis indicated that all four positive cats were infected with FIV subtype-B. Conclusions: This is the first molecular characterization of FIV subtypes on St. Kitts and the results confirm the high prevalence of FIV infection in stray cats on the island.