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1.
Biomolecules ; 13(7)2023 06 21.
Article in English | MEDLINE | ID: mdl-37509056

ABSTRACT

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500-4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes. METHODS: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107). RESULTS: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (-3.50 vs. -2.04 mL/min/1.73 m2/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (-6.56 vs. -2.16 mL/min/1.73 m2/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11-3.16; p = 0.020). CONCLUSIONS: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD.


Subject(s)
Polycystic Kidney, Autosomal Dominant , Humans , Aged , Polycystic Kidney, Autosomal Dominant/diagnosis , Polycystic Kidney, Autosomal Dominant/genetics , TRPP Cation Channels/genetics , Mutation , Germ-Line Mutation , Biomarkers
2.
Sci Rep ; 11(1): 2280, 2021 01 26.
Article in English | MEDLINE | ID: mdl-33500464

ABSTRACT

We report the first observations of periodic oscillations of an atmospheric electric field simultaneously derived by field mills at four observation sites at a distance of 50-65 km in metropolitan Tokyo. Oscillations were detected during a snowfall event on 23-24 November, 2016. The main period of the oscillations of the atmospheric electric field at CHB was 78 min, which was similar to those at other sites. The periods of 39.0, 54.6, and 78.0 min observed at Chiba (CHB) were similar to those observed by W-band cloud radar (FALCON-I) reflectivity below a height of 5 km. High coherence of the 78-min period between the atmospheric electric field at CHB and the X-band phased array weather radar reflectivity suggest that the periodic oscillations of the atmospheric electric field during snowfall were caused by vertically convective cells in snow clouds with a radius of 60 km centered on CHB.

3.
Front Neurorobot ; 12: 22, 2018.
Article in English | MEDLINE | ID: mdl-29872389

ABSTRACT

In this paper, we propose an active perception method for recognizing object categories based on the multimodal hierarchical Dirichlet process (MHDP). The MHDP enables a robot to form object categories using multimodal information, e.g., visual, auditory, and haptic information, which can be observed by performing actions on an object. However, performing many actions on a target object requires a long time. In a real-time scenario, i.e., when the time is limited, the robot has to determine the set of actions that is most effective for recognizing a target object. We propose an active perception for MHDP method that uses the information gain (IG) maximization criterion and lazy greedy algorithm. We show that the IG maximization criterion is optimal in the sense that the criterion is equivalent to a minimization of the expected Kullback-Leibler divergence between a final recognition state and the recognition state after the next set of actions. However, a straightforward calculation of IG is practically impossible. Therefore, we derive a Monte Carlo approximation method for IG by making use of a property of the MHDP. We also show that the IG has submodular and non-decreasing properties as a set function because of the structure of the graphical model of the MHDP. Therefore, the IG maximization problem is reduced to a submodular maximization problem. This means that greedy and lazy greedy algorithms are effective and have a theoretical justification for their performance. We conducted an experiment using an upper-torso humanoid robot and a second one using synthetic data. The experimental results show that the method enables the robot to select a set of actions that allow it to recognize target objects quickly and accurately. The numerical experiment using the synthetic data shows that the proposed method can work appropriately even when the number of actions is large and a set of target objects involves objects categorized into multiple classes. The results support our theoretical outcomes.

4.
Opt Express ; 24(26): 30053-30067, 2016 Dec 26.
Article in English | MEDLINE | ID: mdl-28059390

ABSTRACT

We developed a multiple-field-of-view multiple-scattering polarization lidar (MFMSPL) to study the microphysics of optically thick clouds. Designed to measure enhanced backscattering and depolarization ratio comparable to space-borne lidar, the system consists of four sets of parallel and perpendicular channels mounted with different zenith angles. Depolarization ratios from water clouds were large as observed by MFMSPL compared to those observed by conventional lidar. Cloud top heights and depolarization ratios tended to be larger for outer MFMSPL channels than for vertically pointing channels. Co-located 95 GHz cloud radar and MFMSPL observations showed reasonable agreement at the observed cloud top height.

5.
J Biomol NMR ; 57(3): 297-304, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24146206

ABSTRACT

The production of stable isotope-labeled proteins is critical in structural analyses of large molecular weight proteins using NMR. Although prokaryotic expression systems using Escherichia coli have been widely used for this purpose, yeast strains have also been useful for the expression of functional eukaryotic proteins. Recently, we reported a cost-effective stable isotope-labeled protein expression using the hemiascomycete yeast Kluyveromyces lactis (K. lactis), which allow us to express exogenous proteins at costs comparable to prokaryotic expression systems. Here, we report the successful production of highly deuterated (>90 %) protein in the K. lactis system. We also examined the methyl-selective (1)H, (13)C-labeling of Ile, Leu, and Val residues using commonly used amino acid precursors. The efficiency of (1)H-(13)C-incorporation varied significantly based on the amino acid. Although a high level of (1)H-(13)C-incorporation was observed for the Ile δ1 position, (1)H, (13)C-labeling rates of Val and Leu methyl groups were limited due to the mitochondrial localization of enzymes involved in amino acid biosynthesis and the lack of transporters for α-ketoisovalerate in the mitochondrial membrane. In line with this notion, the co-expression with branched-chain-amino-acid aminotransferase in the cytosol significantly improved the incorporation rates of amino acid precursors. Although it would be less cost-effective, addition of (13)C-labeled valine can circumvent problems associated with precursors and achieve high level (1)H, (13)C-labeling of Val and Leu. Taken together, the K. lactis system would be a good alternative for expressing large eukaryotic proteins that need deuteration and/or the methyl-selective (1)H, (13)C-labeling for the sensitive detection of NMR resonances.


Subject(s)
Isotope Labeling , Kluyveromyces/metabolism , Nuclear Magnetic Resonance, Biomolecular , Proteins/chemistry , Carbon Isotopes/chemistry , Deuterium/chemistry , Gene Expression , Isoleucine/chemistry , Kluyveromyces/genetics , Leucine/chemistry , Maltose-Binding Proteins/chemistry , Maltose-Binding Proteins/genetics , Maltose-Binding Proteins/metabolism , Nuclear Magnetic Resonance, Biomolecular/methods , Transaminases/chemistry , Transaminases/genetics , Transaminases/metabolism , Valine/chemistry
6.
J Biol Chem ; 287(40): 33706-18, 2012 Sep 28.
Article in English | MEDLINE | ID: mdl-22869376

ABSTRACT

Ceramide transport from the endoplasmic reticulum to the Golgi apparatus is crucial in sphingolipid biosynthesis, and the process relies on the ceramide trafficking protein (CERT), which contains pleckstrin homology (PH) and StAR-related lipid transfer domains. The CERT PH domain specifically recognizes phosphatidylinositol 4-monophosphate (PtdIns(4)P), a characteristic phosphoinositide in the Golgi membrane, and is indispensable for the endoplasmic reticulum-to-Golgi transport of ceramide by CERT. In this study, we determined the three-dimensional structure of the CERT PH domain by using solution NMR techniques. The structure revealed the presence of a characteristic basic groove near the canonical PtdIns(4)P recognition site. An extensive interaction study using NMR and other biophysical techniques revealed that the basic groove coordinates the CERT PH domain for efficient PtdIns(4)P recognition and localization in the Golgi apparatus. The notion was also supported by Golgi mislocalization of the CERT mutants in living cells. The distinctive binding modes reflect the functions of PH domains, as the basic groove is conserved only in the PH domains involved with the PtdIns(4)P-dependent lipid transport activity but not in those with the signal transduction activity.


Subject(s)
Golgi Apparatus/metabolism , Protein Serine-Threonine Kinases/chemistry , Amino Acid Motifs , Amino Acid Sequence , Endoplasmic Reticulum/metabolism , Humans , Kinetics , Lipids/chemistry , Liposomes/chemistry , Magnetic Resonance Spectroscopy/methods , Models, Molecular , Molecular Conformation , Molecular Sequence Data , Mutagenesis, Site-Directed , Phosphatidylinositols/chemistry , Protein Conformation , Protein Structure, Tertiary , Sequence Homology, Amino Acid , Surface Plasmon Resonance
7.
Biotechnol Bioeng ; 109(1): 244-51, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21809333

ABSTRACT

Cell transfer printing from patterned poly(ethylene glycol)-oleyl surfaces onto biological hydrogel sheets is investigated herein, as a new cell stamping method for both cell microarray and tissue engineering. By overlaying a hydrogel sheet on the cells immobilized on the poly(ethylene glycol)-oleyl surface and successively peeling it off, the immobilized cells were transferred onto a hydrogel sheet because the adhesive interaction between the cells and the hydrogel was stronger than that between the cells and the poly(ethylene glycol)-oleyl surface. Four types of human cell could be efficiently transferred onto a rigid collagen sheet. The transfer printing ratios, for all cells, were above 80% and achieved within 90 min. A cell microarray was successfully prepared on a collagen gel sheet using the present stamping method. We have also demonstrated that the transferred pattern of endothelial cells is transformed to the patterned tube-like structure on the reconstituted basement membrane matrix. Finally, the patterns of two types of endothelial cell are shown to be easily prepared on the matrix, and the desired tube-like structures, including the orderly pattern of the two different cells, were formed spontaneously. Thus, the present poly(ethylene glycol)-oleyl coated substrates are useful for rapid and efficient cell stamping, in the preparation of multi-cellular pattern on extracellular matrices.


Subject(s)
Biocompatible Materials/chemistry , Hydrogels/chemistry , Polyethylene Glycols/chemistry , Tissue Engineering/methods , Cell Line , Cell Survival , Humans , Surface Properties
8.
Biosci Biotechnol Biochem ; 74(1): 18-23, 2010.
Article in English | MEDLINE | ID: mdl-20057148

ABSTRACT

We investigated the effects of oral intake of Lactobacillus helveticus-fermented milk whey on the intact and sodium dodecylsulfate (SDS)-exposed skin of Hos:HR-1 hairless mice. The mice were allowed to drink 10% L. helveticus-fermented milk whey in distilled water ad libitum for 5 weeks. SDS solution was topically applied to the dorsal skin at 4 weeks, leading to the development of dermatitis. The skin moisture content, transepidermal water loss, and sizes of the dermatitis areas were periodically measured. Compared with oral intake of water alone, oral intake of water containing L. helveticus-fermented milk whey for 4 weeks significantly lowered transepidermal water loss from intact skin, significantly reduced in size the areas of early SDS-induced dermatitis, and ameliorated both the SDS-induced decrease in moisture content and the increase in transepidermal water loss. These results suggest that oral intake of L. helveticus-fermented milk whey might be effective in promoting the epidermal barrier function and in preventing the onset of dermatitis.


Subject(s)
Dermatitis/prevention & control , Fermentation , Lactobacillus helveticus/metabolism , Milk/microbiology , Skin/metabolism , Sodium Dodecyl Sulfate/pharmacology , Water/metabolism , Administration, Oral , Animals , Body Weight , Dermatitis/etiology , Dermatitis/metabolism , Dermatitis/physiopathology , Drinking , Eating , Male , Mice , Skin/drug effects
9.
J Agric Food Chem ; 56(3): 854-8, 2008 Feb 13.
Article in English | MEDLINE | ID: mdl-18193838

ABSTRACT

Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) are antihypertensive tripeptides isolated from milk fermented with Lactobacillus helveticus and inhibit angiotensin-converting enzyme (ACE). We investigated whether these peptides were generated from beta-casein by digestive enzymes and whether they were resistant to enzymatic hydrolysis, using an in vitro model. VPP and IPP were not generated from beta-casein by gastrointestinal enzymes; instead, a number of longer peptides including VPP and IPP sequences were detected. The fermentation step would therefore be necessary to produce these antihypertensive tripeptides. VPP and IPP themselves were hardly digested by digestive enzymes, suggesting that orally administered VPP and IPP remain intact in the intestine, retaining their activity until adsorption. The present study also demonstrated that various functional peptide sequences in beta-casein were resistant to gastrointestinal enzymes. There may be a strong correlation between the resistance of peptides to gastrointestinal digestion and their real physiological effects after oral administration.


Subject(s)
Antihypertensive Agents/metabolism , Caseins/chemistry , Digestion , Gastrointestinal Tract/enzymology , Oligopeptides/metabolism , Amino Acid Sequence , Animals , Caco-2 Cells , Drug Stability , Fermentation , Humans , Milk/chemistry , Oligopeptides/biosynthesis , Peptide Fragments/chemistry , Peptide Fragments/metabolism
10.
J Nutr Biochem ; 18(2): 140-5, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16781862

ABSTRACT

Milk fermented with a starter containing Lactobacillus helveticus and Saccharomyces cerevisiae is drunk on a daily basis by many people in Japan and has several beneficial effects. We studied the influence of this fermented milk product on muscle damage after prolonged exercise in rats. Wistar rats were divided into four groups: rested controls, rested rats given fermented milk diet, exercised rats and exercised rats given fermented milk diet. After 3 weeks of acclimatization, both exercise groups were made to run on a treadmill at 26 m/min for 60 min. Exercise increased the serum creatine kinase level, as well as myeloperoxidase activity and the level of thiobarbituric-acid-reactive substances in the gastrocnemius muscle after 24 h. These changes were ameliorated by intake of fermented milk. An increase of CINC-1 was also ameliorated by fermented milk. Furthermore, milk diet increased the mRNA and protein levels of protective proteins such as antioxidants and chaperone proteins. These results indicate that fermented milk can ameliorate delayed-onset muscle damage after prolonged exercise, which is associated with an increased antioxidant capacity of muscles.


Subject(s)
Cultured Milk Products/physiology , Muscle, Skeletal/injuries , Physical Exertion/physiology , Animals , Antioxidants/analysis , Blotting, Western , Chemokine CXCL1 , Chemokines, CXC/analysis , Creatine Kinase/blood , Cultured Milk Products/microbiology , Diet , Lactobacillus helveticus , Male , Muscle Proteins/analysis , Muscle Proteins/genetics , Muscle, Skeletal/enzymology , Neutrophils/enzymology , Neutrophils/physiology , Peroxidase/blood , RNA, Messenger/analysis , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Saccharomyces cerevisiae , Superoxide Dismutase/analysis , Superoxide Dismutase/genetics , Superoxide Dismutase-1 , Thiobarbituric Acid Reactive Substances/analysis
11.
Biosci Biotechnol Biochem ; 66(2): 378-84, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11999412

ABSTRACT

Some of the food-derived tripeptides with angiotensin converting enzyme (ACE)-inhibitory activity have been reported to be hypotensive after being orally administered. The mechanism for the intestinal transport of these tripeptides was studied by using monolayer-cultured human intestinal Caco-2 cells which express many enterocyte-like functions including the peptide transporter (PepT1)-mediated transport system. Val-Pro-Pro, an ACE-inhibitory peptide from fermented milk, was used as a model tripeptide. A significant amount of intact Val-Pro-Pro was transported across the Caco-2 cell monolayer. This transport was hardly inhibited by a competitive substrate for PepT1. Since no intact Val-Pro-Pro was detected in the cells, Val-Pro-Pro apically taken by Caco-2 cells via PepT1 was likely to have been quickly hydrolyzed by intracellular peptidases, producing free Val and Pro. These findings suggest that PepT1-mediated transport was not involved in the transepithelial transport of intact Val-Pro-Pro. Paracellular diffusion is suggested to have been the main mechanism for the transport of intact Val-Pro-Pro across the Caco-2 cell monolayer.


Subject(s)
Epithelium/metabolism , Intestinal Mucosa/metabolism , Oligopeptides/metabolism , Biological Transport , Caco-2 Cells , Chromatography, High Pressure Liquid , Endocytosis/drug effects , Humans , Hydrolysis
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