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1.
Sci Rep ; 13(1): 14036, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37666858

RESUMO

Early diagnosis and treatment of depression are desirable but currently difficult due to a lack of established biomarkers. Although biomarkers for depression based on electroencephalogram (EEG) data have long been explored, most existing methods are thought to capture cognitive decline caused by depression and are unsuccessful in detecting signs of depression. Here we report that some brainwave activities involving phase resetting reflect the depressed mood at the time, which can be easily monitored by measuring the resting EEG with eyes closed for 1 min with a few electrodes. We instructed 10 participants (nine healthy and one diagnosed with depression, aged 18-34) to record their EEG for 14-26 days. We found that indicators of depressed mood were correlated with the occurrence frequency of EEG phase resetting. For most participants, the correlation coefficients swung systematically between large positive and large negative values with respect to EEG frequency; however, the frequencies at which they were maximum or minimum differed among participants. Although this study is in the pilot phase and needs further experimentation, the results are expected to lead to innovative biomarkers for early detection of depression and may contribute to a better understanding and treatment of depression.


Assuntos
Ondas Encefálicas , Disfunção Cognitiva , Humanos , Projetos Piloto , Eletroencefalografia , Eletrodos
2.
Nutrients ; 15(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37049398

RESUMO

Postmenopausal women (PMW) may experience endothelial dysfunction associated with arginine (ARG) deficiency relative to asymmetric dimethylarginine (ADMA) caused by oxidative stress. Endothelial dysfunction contributes to increased blood pressure (BP) responsiveness to sympathoexcitation induced by the cold pressor test (CPT). We investigated the effects of citrulline alone (CIT) and combined with the antioxidant glutathione (CIT+GSH) on vascular function. Forty-four healthy PMW were randomized to CIT (6 g), CIT+GSH (2 g + 200 mg: Setria®) or placebo (PL) for 4 weeks. Brachial artery flow-mediated dilation (FMD), aortic stiffness (pulse wave velocity, PWV), brachial and aortic BP reactivity to CPT, and serum fasting blood glucose (FBG), ARG, and ARG/ADMA ratio were measured. Baseline FBG was higher in CIT+GSH vs. PL. FMD increased after CIT+GSH vs. PL (p < 0.05). CIT and CIT+GSH increased ARG/ADMA (p < 0.05), but did not affect aortic PWV. CIT+GSH attenuated the brachial and aortic systolic BP and mean arterial pressure (MAP) responses to CPT vs. PL and CIT (p < 0.05). The improvements in FMD were related to baseline FMD (r = -0.39, p < 0.05) and aortic MAP response to CPT (r = -0.33, p < 0.05). This study showed that CIT+GSH improved FMD and attenuated systolic BP and MAP reactivity in PMW. Although CIT increased ARG/ADMA, it did not improve FMD in healthy PMW.


Assuntos
Citrulina , Doenças Vasculares , Humanos , Feminino , Pressão Sanguínea , Citrulina/farmacologia , Análise de Onda de Pulso , Pós-Menopausa , Glutationa , Suplementos Nutricionais , Arginina , Endotélio Vascular
3.
Neural Netw ; 154: 109-121, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35872516

RESUMO

Model-based reinforcement learning enables an agent to learn in variable environments and tasks by optimizing its actions based on the predicted states and outcomes. This mechanism has also been considered in the brain. However, exactly how the brain selects an appropriate model for confronting environments has remained unclear. Here, we investigated the model selection algorithm in the human brain during a reinforcement learning task. One primary theory of model selection in the brain is based on sensory prediction errors. Here, we compared this theory with an alternative possibility of internal model selection with reward prediction errors. To compare these two theories, we devised a switching experiment from a first-order Markov decision process to a second-order Markov decision process that provides either reward- or sensory prediction error regarding environmental change. We tested two representative computational models driven by different prediction errors. One is the sensory prediction-error-driven Bayesian algorithm, which has been discussed as a representative internal model selection algorithm in the animal reinforcement learning task. The other is the reward-prediction-error-driven policy gradient algorithm. We compared the simulation results of these two computational models with human reinforcement learning behaviors. The model fitting result supports that the policy gradient algorithm is preferable to the Bayesian algorithm. This suggests that the human brain employs the reward prediction error to select an appropriate internal model in the reinforcement learning task.


Assuntos
Tomada de Decisões , Reforço Psicológico , Animais , Teorema de Bayes , Humanos , Aprendizagem , Recompensa
4.
Heliyon ; 7(3): e06532, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33842702

RESUMO

In our previous study, we found that the vasodilation of retinal arterioles induced by acetylcholine and BMS-191011, a large-conductance Ca2+-activated K+ (BKCa) channel opener, were diminished in diabetic rats. Currently, few agents ameliorate the impaired vasodilator responses of retinal blood vessels. Our recent finding that the intravenous infusion of L-citrulline dilated retinal arterioles, suggests that L-citrulline could be a potential therapeutic agent for circulatory disorders of the retina. In this study, we determined the effect of an oral L-citrulline treatment on impaired acetylcholine- and BMS-191011-induced vasodilation in the retinal arterioles of diabetic rats. To induce diabetes, rats were administered an intravenous dose of streptozotocin (65 mg/kg) and a 5% D-glucose solution as drinking water. The L-citrulline (2 g/kg/day) and L-arginine (2 g/kg/day) treatments commenced either 15 days before or just after the streptozotocin injection and continued throughout the experimental period. A 29-day treatment with L-citrulline, but not L-arginine, significantly ameliorated the impaired acetylcholine- and BMS-191011-induced retinal vasodilation in diabetic rats without affecting their plasma glucose levels. The 2-week L-citrulline treatment tended to ameliorate the dysfunction of the acetylcholine-induced retinal vasodilation in diabetic rats. In conclusion, these results showed that the retinal blood vessel dysfunction induced by diabetes mellitus could be prevented by the long-term administration of L-citrulline and suggest that the latter could play a potentially prophylactic role in diabetic retinopathy.

5.
Biotechnol Biofuels ; 14(1): 7, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407783

RESUMO

BACKGROUND: It is desirable to improve the anaerobic digestion processes of recalcitrant materials, such as cellulose. Enhancement of methane (CH4) production from organic molecules was previously accomplished through coupling a bioelectrochemical system (BES); however, scaling-up BES-based production is difficult. Here, we developed a two-stage process consisting of a BES using low-cost and low-reactive carbon sheets as the cathode and anode, and a fixed film reactor (FFR) containing conductive material, i.e., carbon fiber textiles (CFTs) (:BES → FFR). By controlling the cathodic current at 2.7 µA/cm2 without abiotic H2 production, the three-electrode BES system was operated to mimic a microbial electrolysis cell. RESULTS: The thermophilic BES (inlet pH: 6.1) and FFR (inlet pH: 7.5) were operated using hydraulic retention times (HRTs) of 2.5 and 4.2 days, respectively, corresponding to a cellulose load of 3555.6 mg-carbon (C)/(L day). The BES → FFR process achieved a higher CH4 yield (37.5%) with 52.8 vol% CH4 in the product gas compared to the non-bioelectrochemical system (NBES) → FFR process, which showed a CH4 yield of 22.1% with 46.8 vol% CH4. The CH4 production rate (67.5 mM/day) obtained with the BER → FFR process was much higher than that obtained using electrochemical methanogenesis (0.27 mM/day). Application of the electrochemical system or CFTs improved the yields of CH4 with the NBES → FFR or BES → non-fixed film reactor process, respectively. Meta 16S rRNA sequencing revealed that putative cellulolytic bacteria (identified as Clostridium species) were present in the BES and NBES, and followed (BES→ and NBES→) FFR. Notably, H2-consuming methanogens, Methanobacterium sp. and Methanosarcina sp., showed increased relative abundances in the suspended fraction and attached fraction of (BES→) FFR, respectively, compared to that of (NBES→) FFR, although these methanogens were observed at trace levels in the BES and NBES. CONCLUSIONS: These results indicate that bioelectrochemical preprocessing at a low current effectively induces interspecies H2 transfer in the FFR with conductive material. Sufficient electrochemical preprocessing was observed using a relatively short HRT. This type of two-stage process, BES → FFR, is useful for stabilization and improvement of the biogas (CH4) production from cellulosic material, and our results imply that the two-stage system developed here may be useful with other recalcitrant materials.

6.
Exerc Sport Sci Rev ; 48(3): 133-139, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568925

RESUMO

Age-associated reduction in endothelial nitric oxide (NO) synthesis contributes to the development of cardiovascular diseases and sarcopenia. L-Citrulline is a precursor of NO with the ability to improve vascular function and muscle protein synthesis. We hypothesize that vascular and muscular benefits associated with oral L-citrulline supplementation might be augmented by concomitant supplementation with exercise training in older adults.


Assuntos
Envelhecimento/fisiologia , Citrulina/administração & dosagem , Suplementos Nutricionais , Exercício Físico/fisiologia , Condicionamento Físico Humano/fisiologia , Arginina/sangue , Disponibilidade Biológica , Índice de Massa Corporal , Endotélio Vascular/fisiologia , Endotélio Vascular/fisiopatologia , Humanos , Proteínas Musculares/biossíntese , Força Muscular , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Óxido Nítrico/biossíntese , Consumo de Oxigênio
7.
Cells ; 9(5)2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32438637

RESUMO

From cells to organisms, every living system is three-dimensional (3D), but the performance of fluorescence microscopy has been largely limited when attempting to obtain an overview of systems' dynamic processes in three dimensions. Recently, advanced light-sheet illumination technologies, allowing drastic improvement in spatial discrimination, volumetric imaging times, and phototoxicity/photobleaching, have been making live imaging to collect precise and reliable 3D information increasingly feasible. In particular, lattice light-sheet microscopy (LLSM), using an ultrathin light-sheet, enables whole-cell 3D live imaging of cellular processes, including mitosis, at unprecedented spatiotemporal resolution for extended periods of time. This technology produces immense and complex data, including a significant amount of information, raising new challenges for big image data analysis and new possibilities for data utilization. Once the data are digitally archived in a computer, the data can be reused for various purposes by anyone at any time. Such an information science approach has the potential to revolutionize the use of bioimage data, and provides an alternative method for cell biology research in a data-driven manner. In this article, we introduce examples of analyzing digital mitotic spindles and discuss future perspectives in cell biology.


Assuntos
Simulação por Computador , Coleta de Dados , Mitose , Fuso Acromático/metabolismo , Animais , Embrião não Mamífero/anatomia & histologia , Células HeLa , Humanos , Imageamento Tridimensional , Proteínas Associadas aos Microtúbulos/metabolismo , Peixe-Zebra/embriologia
8.
J Biophotonics ; 13(8): e202000071, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32388908

RESUMO

This study aims to develop a novel cross-sectional imaging of fluorescence in over-1000 nm near-infrared (OTN-NIR), which allows in vivo deep imaging, using computed tomography (CT) system. Cylindrical specimens of composite of OTN-NIR fluorophore, NaGdF4 co-doped with Yb3+ and Ho3+ (ex: 980 nm, em: 1150 nm), were embedded in cubic agar (10.5-12 mm) or in the peritoneal cavity of mice and placed on a rotatable stage. When the fluorescence from inside of the samples was serially captured from multiple angles, the images were disrupted by the reflection and refraction of emitted light on the sample-air interface. Immersing the sample into water filled in a rectangular bath suppressed the disruption at the interface and successfully reconstructed the position and concentration of OTN-NIR fluorophores on the cross-sectional images using a CT technique. This is promising as a novel three-dimensional imaging technique for OTN-NIR fluorescent image projections of small animals captured from multiple angles.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Animais , Camundongos , Microscopia de Fluorescência , Tomografia Computadorizada por Raios X
9.
Front Neurosci ; 13: 35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814924

RESUMO

In the human visual system, different attributes of an object are processed separately and are thought to be then temporarily bound by attention into an integrated representation to produce a specific response. However, if such representations existed in the brain for arbitrary multi-attribute objects, a combinatorial explosion problem would be unavoidable. Here, we show that attention may bind features of different attributes only in pairs and that bound feature pairs, rather than integrated object representations, are associated with responses for unfamiliar objects. We found that in a mapping task from three-attribute stimuli to responses, presenting three attributes in pairs (two attributes in each window) did not significantly complicate feature integration and response selection when the stimuli were not very familiar. We also found that repeated presentation of the same triple conjunctions significantly improved performance on the stimulus-response task when the correct responses were determined by the combination of three attributes, but this familiarity effect was not observed when the response could be determined by two attributes. These findings indicate that integration of three or more attributes is a distinct process from that of two, requiring long-term learning or some serial process. This suggests that integrated object representations are not formed or are formed only for a limited number of very familiar objects, which resolves the computational difficulty of the binding problem.

10.
Eur J Appl Physiol ; 119(5): 1075-1084, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30847640

RESUMO

PURPOSE: Oral L-citrulline (Cit) increases plasma L-arginine (Arg) concentration and the production of nitric oxide (NO). NO dilates blood vessels and potentially improves sports performance. The combination of oral Arg and Cit (Arg + Cit) immediately and synergistically increases plasma Arg and nitrite/nitrate (NOx) concentrations more than either Cit or Arg alone. This prompted us to assess the effects of oral Arg + Cit on 10-min cycling performance in a double-blind, randomized, placebo-controlled crossover trial. METHODS: Twenty-four male soccer players ingested either Cit + Arg or placebo (both 1.2 g/day each) for 6 days. On day 7, they ingested Cit + Arg 1 h before performing a 10-min full-power pedaling test on a bicycle ergometer. Plasma NOx and amino acid levels were measured before and after the test, as well as the participants' subjective perception of physical exertion. RESULTS: Power output was significantly greater with Cit + Arg than in the placebo group (242 ± 24 vs. 231 ± 21 W; p < 0.05). Plasma concentrations of post-exercise NOx (p < 0.05), Cit (p < 0.01) and Arg (p < 0.01) were significantly higher in the Cit + Arg than in the placebo group, whereas exercise upregulated plasma NOx concentrations in both groups (p < 0.05). Cit + Arg also gave improved post-exercise subjective perception of "leg muscle soreness" and "ease of pedaling" (both p < 0.05). CONCLUSION: Seven days of oral Citrulline (1.2 g/d) and Arginine (1.2 g/d) ingestion improved 10-min cycling performance and the perception of physical exertion in male collegiate soccer players.


Assuntos
Arginina/farmacologia , Citrulina/farmacologia , Tolerância ao Exercício/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Arginina/administração & dosagem , Citrulina/administração & dosagem , Combinação de Medicamentos , Humanos , Masculino , Futebol/fisiologia
11.
Nucleic Acids Res ; 47(D1): D859-D866, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30371824

RESUMO

Understanding anatomical structures and biological functions based on gene expression is critical in a systemic approach to address the complexity of the mammalian brain, where >25 000 genes are expressed in a precise manner. Co-expressed genes are thought to regulate cell type- or region-specific brain functions. Thus, well-designed data acquisition and visualization systems for profiling combinatorial gene expression in relation to anatomical structures are crucial. To this purpose, using our techniques of microtomy-based gene expression measurements and WebGL-based visualization programs, we mapped spatial expression densities of genome-wide transcripts to the 3D coordinates of mouse brains at four post-natal stages, and built a database, ViBrism DB (http://vibrism.neuroinf.jp/). With the DB platform, users can access a total of 172 022 expression maps of transcripts, including coding, non-coding and lncRNAs in the whole context of 3D magnetic resonance (MR) images. Co-expression of transcripts is represented in the image space and in topological network graphs. In situ hybridization images and anatomical area maps are browsable in the same space of 3D expression maps using a new browser-based 2D/3D viewer, BAH viewer. Created images are shareable using URLs, including scene-setting parameters. The DB has multiple links and is expandable by community activity.


Assuntos
Encéfalo/diagnóstico por imagem , Bases de Dados Genéticas , Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Animais , Encéfalo/anatomia & histologia , Imageamento Tridimensional/classificação , Camundongos , Software
12.
Biotechnol Biofuels ; 11: 173, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29977334

RESUMO

BACKGROUND: Bioelectrochemical systems (BESs) are an innovative technology developed to influence conventional anaerobic digestion. We examined the feasibility of applying a BES to dark hydrogen fermentation and its effects on a two-stage fermentation process comprising hydrogen and methane production. The BES used low-cost, low-reactivity carbon sheets as the cathode and anode, and the cathodic potential was controlled at - 1.0 V (vs. Ag/AgCl) with a potentiostat. The operation used 10 g/L glucose as the major carbon source. RESULTS: The electric current density was low throughout (0.30-0.88 A/m2 per electrode corresponding to 0.5-1.5 mM/day of hydrogen production) and water electrolysis was prevented. At a hydraulic retention time of 2 days with a substrate pH of 6.5, the BES decreased gas production (hydrogen and carbon dioxide contents: 52.1 and 47.1%, respectively), compared to the non-bioelectrochemical system (NBES), although they had similar gas compositions. In addition, a methane fermenter (MF) was applied after the BES, which increased gas production (methane and carbon dioxide contents: 85.1 and 14.9%, respectively) compared to the case when the MF was applied after the NBES. Meta 16S rRNA sequencing revealed that the BES accelerated the growth of Ruminococcus sp. and Veillonellaceae sp. and decreased Clostridium sp. and Thermoanaerobacterium sp., resulting in increased propionate and ethanol generation and decreased butyrate generation; however, unknowingly, acetate generation was increased in the BES. CONCLUSIONS: The altered redox potential in the BES likely transformed the structure of the microbial consortium and metabolic pattern to increase methane production and decrease carbon dioxide production in the two-stage process. This study showed the utility of the BES to act on the microbial consortium, resulting in improved gas production from carbohydrate compounds.

13.
J Int Soc Sports Nutr ; 15(1): 30, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29945625

RESUMO

BACKGROUND: Supplementation of combined glutathione (GSH) with L-citrulline in response to a single bout of resistance exercise has been shown to increase plasma nitric oxide metabolites, nitrite and nitrate and cyclic guanosine monophosphate (cGMP), which may play a role in muscle protein synthesis. As a result, in response to resistance training (RT) these responses may establish a role for GSH + L-citrulline to increase muscle mass. This study attempted to determine the effects of an 8-week RT program in conjunction with GSH (Setria®) + L-citrulline, L-citrulline-malate, or placebo supplementation on lean mass and its association with muscle strength. The secondary purpose was to assess the safety of such supplementation protocol by assessing clinical chemistry markers. METHODS: In a randomized, double-blind, placebo-controlled design, 75 resistance-trained males were randomly assigned to ingest GSH + L-citrulline (GSH + CIT), L-citrulline-malate, or cellulose placebo daily while also participating in 8 weeks of RT. The full dose of each supplement was delivered in capsules that were identical in weight, size, shape, and color. Participants completed testing sessions for body composition and muscle strength before and after 4 and 8 weeks of RT and supplementation. Venous blood samples were obtained before and after 8 weeks. RESULTS: Leg press was increased with RT but was not significantly different between groups (p > 0.05); however, bench press strength was not increased with RT (p > 0.05). There were no significant changes in total body mass, fat mass, or total body water during 8 weeks of RT and supplementation. Lean mass increased in both GSH + CIT when compared to PLC; however, the increase was significant only after 4 weeks. Lean mass and strength were positively correlated (p < 0.05) in GSH + CIT, but not CIT-malate or PLC. Neither RT nor supplementation had any significant effects on blood clinical chemistry variables (p > 0.05). CONCLUSION: Compared to PLC, supplementation of GSH + CIT during resistance training increased lean mass after 4 weeks of RT and was positively associated with muscle strength. However, after 8 weeks of RT there were no significant differences in any of the measured variables.


Assuntos
Citrulina/farmacologia , Suplementos Nutricionais , Glutationa/farmacologia , Força Muscular/efeitos dos fármacos , Treinamento Resistido , Adulto , Biomarcadores/sangue , Composição Corporal , Citrulina/análogos & derivados , Dieta , Método Duplo-Cego , Humanos , Malatos , Masculino , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto Jovem
14.
World J Gastroenterol ; 23(36): 6650-6664, 2017 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-29085210

RESUMO

AIM: To determine whether oral glutathione (GSH) administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa. METHODS: Rats were divided into eight groups. One group was fed ad libitum, another was fed ad libitum and received oral GSH, and six groups were administrated saline (SA) or GSH orally during fasting. Mucosal height, apoptosis, and cell proliferation in the jejunum were histologically evaluated. iNOS protein expression (by immunohistochemistry), nitrite levels (by high performance liquid chromatography, as a measure of NO production), 8-hydroxydeoxyguanosine formation (by ELISA, indicating ROS levels), glutathione/oxidized glutathione (GSH/GSSG) ratio (by enzymatic colorimetric detection), and γ-glutamyl transpeptidase (Ggt1) mRNA levels in the jejunum (by semi-quantitative RT-PCR) were also estimated. RESULTS: Oral GSH administration was demonstrated to drastically reduce fasting-induced intestinal atrophy in the jejunum. In particular, jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals [527.2 ± 6.9 for 50 mg/kg GSH, 567.6 ± 5.4 for 500 mg/kg GSH vs 483.1 ± 4.9 (µm), P < 0.01 at 72 h]. This effect was consistent with decreasing changes in GSH-treated animals compared to SA-treated animals for iNOS protein staining [0.337 ± 0.016 for 50 mg/kg GSH, 0.317 ± 0.017 for 500 mg/kg GSH vs 0.430 ± 0.023 (area of staining part/area of tissue), P < 0.01 at 72 h] and NO [2.99 ± 0.29 for 50 mg/kg GSH, 2.88 ± 0.19 for 500 mg/kg GSH vs 5.34 ± 0.35 (nmol/g tissue), P < 0.01 at 72 h] and ROS [3.92 ± 0.46 for 50 mg/kg GSH, 4.58 ± 0.29 for 500 mg/kg GSH vs 6.42 ± 0.52 (8-OHdG pg/µg DNA), P < 0.01, P < 0.05 at 72 h, respectively] levels as apoptosis mediators in the jejunum. Furthermore, oral GSH administration attenuated cell proliferation decreases in the fasting jejunum [182.5 ± 1.9 for 500 mg/kg GSH vs 155.8 ± 3.4 (5-BrdU positive cells/10 crypts), P < 0.01 at 72 h]. Notably, both GSH concentration and Ggt1 mRNA expression in the jejunum were also attenuated in rats following oral administration of GSH during fasting as compared with fasting alone [0.45 ± 0.12 vs 0.97 ± 0.06 (nmol/mg tissue), P < 0.01; 1.01 ± 0.11 vs 2.79 ± 0.39 (Ggt1 mRNA/Gapdh mRNA), P < 0.01 for 500 mg/kg GSH at 48 h, respectively]. CONCLUSION: Oral GSH administration during fasting enhances jejunal regenerative potential to minimize intestinal mucosal atrophy by diminishing fasting-mediated ROS generation and enterocyte apoptosis and enhancing cell proliferation.


Assuntos
Antioxidantes/farmacologia , Enterócitos/fisiologia , Glutationa/farmacologia , Mucosa Intestinal/patologia , Jejuno/patologia , Regeneração/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Atrofia/tratamento farmacológico , Atrofia/etiologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Enterócitos/efeitos dos fármacos , Jejum/efeitos adversos , Glutationa/uso terapêutico , Humanos , Mucosa Intestinal/efeitos dos fármacos , Jejuno/citologia , Jejuno/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
15.
Nat Commun ; 8: 16011, 2017 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-28685774

RESUMO

Fox odour 2,4,5-trimethyl thiazoline (TMT) is known to activate multiple glomeruli in the mouse olfactory bulb (OB) and elicits strong fear responses. In this study, we screened TMT-reactive odourant receptors and identified Olfr1019 with high ligand reactivity and selectivity, whose glomeruli are located in the posterodorsal OB. In the channelrhodopsin knock-in mice for Olfr1019, TMT-responsive olfactory-cortical regions were activated by photostimulation, leading to the induction of immobility, but not aversive behaviour. Distribution of photoactivation signals was overlapped with that of TMT-induced signals, but restricted to the narrower regions. In the knockout mice, immobility responses were reduced, but not entirely abolished likely due to the compensatory function of other TMT-responsive glomeruli. Our results demonstrate that the activation of a single glomerular species in the posterodorsal OB is sufficient to elicit immobility responses and that TMT-induced fear may be separated into at least two different components of immobility and aversion.


Assuntos
Medo/efeitos dos fármacos , Reação de Congelamento Cataléptica/efeitos dos fármacos , Bulbo Olfatório/efeitos dos fármacos , Percepção Olfatória/fisiologia , Receptores Odorantes/genética , Olfato/fisiologia , Tiazóis/farmacologia , Animais , Agentes Aversivos/isolamento & purificação , Agentes Aversivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Medo/psicologia , Fezes/química , Raposas , Reação de Congelamento Cataléptica/fisiologia , Expressão Gênica , Técnicas de Introdução de Genes , Masculino , Camundongos , Odorantes/análise , Bulbo Olfatório/fisiologia , Estimulação Luminosa , Receptores Odorantes/metabolismo , Técnicas Estereotáxicas , Tiazóis/isolamento & purificação
16.
J Pharmacol Sci ; 133(3): 146-155, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28325558

RESUMO

l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO) production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF) observed in cortical spreading depression (CSD) contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD. Moreover, l-citrulline attenuated propagation velocity of CSD induced by KCl. The effect of l-citrulline on CBF change was prevented by l-NAME, an inhibitor of NO synthase, but not by indomethacin, an inhibitor of cyclooxygenase. On the other hand, attenuation effect of l-citrulline on CSD propagation velocity was prevented not only by l-NAME but also by indomethacin. In addition, propagation velocity of CSD was attenuated by intravenous injection of NOR3, a NO donor, which was diminished by ODQ, an inhibitor of soluble guanylyl cyclase. These results suggest that NO/cyclic GMP- and prostanoids-mediated pathway differently contribute to the effect of l-citrulline on the maintenance of CBF.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Citrulina/farmacologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Óxido Nítrico/fisiologia , Prostaglandinas/fisiologia , Animais , GMP Cíclico/fisiologia , Masculino , Ratos Sprague-Dawley
17.
Biosci Biotechnol Biochem ; 81(2): 372-375, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27667025

RESUMO

We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.


Assuntos
Arginina/sangue , Arginina/farmacologia , Citrulina/administração & dosagem , Citrulina/farmacologia , Suplementos Nutricionais , Administração Oral , Adulto , Arginina/administração & dosagem , Interações Medicamentosas , Humanos , Masculino , Adulto Jovem
18.
Bioresour Technol ; 216: 830-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27318161

RESUMO

Rice straw was mechanically milled using a process consuming 1.9MJ/kg-biomass, and 10g/L of unmilled or milled rice straw was used as the carbon source for methane fermentation in a digester containing carbon fiber textile as the supporting material. Milling increased methane production from 226 to 419mL/L/day at an organic loading rate of 2180mg-dichromate chemical oxygen demand/L/day, corresponding to 260mLCH4/gVS. Storage of the fermentation effluent at room temperature decreased the weight of the milled rice straw residue from 3.81 to 1.00g/L. The supernatant of the effluent was subjected to nanofiltration. The black concentrates deposited on the nanofiltration membranes contained 53.0-57.9% lignin. Solution nuclear magnetic resonance showed that lignin aromatic components such as p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) were retained primarily, and major lignin interunit structures such as the ß-O-4-H/G unit were absent. This combinational process will aid the complete utilization of rice straw.


Assuntos
Biomassa , Lignina , Metano/química , Oryza/química , Análise da Demanda Biológica de Oxigênio , Fermentação , Lignina/isolamento & purificação , Lignina/metabolismo , Oryza/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-26900386

RESUMO

BACKGROUND: Many human studies report that nitric oxide (NO) improves sport performance. This is because NO is a potential modulator of blood flow, muscle energy metabolism, and mitochondrial respiration during exercise. L-Citrulline is an amino acid present in the body and is a potent endogenous precursor of L-arginine, which is a substrate for NO synthase. Here, we investigated the effect of oral L-citrulline supplementation on cycling time trial performance in humans. METHODS: A double-blind randomized placebo-controlled 2-way crossover study was employed. Twenty-two trained males consumed 2.4 g/day of L-citrulline or placebo orally for 7 days. On Day 8 they took 2.4 g of L-citrulline or placebo 1 h before a 4-km cycling time trial. Time taken to complete the 4 km cycle, along with power output/VO2 ratio (PO/VO2), plasma nitrite and nitrate (NOx) and amino acid levels, and visual analog scale (VAS) scores, was evaluated. RESULTS: L-Citrulline supplementation significantly increased plasma L-arginine levels and reduced completion time by 1.5 % (p < 0.05) compared with placebo. Moreover, L-citrulline significantly improved subjective feelings of muscle fatigue and concentration immediately after exercise. CONCLUSIONS: Oral L-citrulline supplementation reduced the time take to complete a cycle ergometer exercise trial. TRIAL REGISTRATION: Current Controlled Trials UMIN000014278.


Assuntos
Povo Asiático , Ciclismo , Citrulina/administração & dosagem , Suplementos Nutricionais , Tolerância ao Exercício/efeitos dos fármacos , Óxido Nítrico Sintase/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/administração & dosagem , Administração Oral , Adulto , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Citrulina/sangue , Citrulina/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/sangue , Substâncias para Melhoria do Desempenho/farmacologia , Fenômenos Fisiológicos da Nutrição Esportiva , Resultado do Tratamento
20.
J Biomed Opt ; 20(10): 101206, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26527322

RESUMO

Mitotic apparatus, which comprises hundreds of microtubules, plays an essential role in cell division, ensuring the correct segregation of chromosomes into each daughter cell. To gain insight into its regulatory mechanisms, it is essential to detect and analyze the behavior of individual microtubule filaments. However, the discrimination of discrete microtubule filaments within the mitotic apparatus is beyond the capabilities of conventional light microscopic technologies. Recently, we detected three-dimensional (3-D) microtubule growth dynamics within the cellular cytoplasmic space using lattice light-sheet microscopy in conjunction with microtubule growth marker protein end-binding 1, a microtubule plus-end-tracking protein, which was fused to green fluorescent protein (EB1-GFP). This technique enables high-resolution 3-D imaging at subsecond intervals. We adapted mathematical computing and geometric representation techniques to analyze spatial variations in microtubule growth dynamics within the mitotic spindle apparatus. Our analytical approach enabled the different dynamic properties of individual microtubules to be determined, including the direction and speed of their growth, and their growth duration within a 3-D spatial map. Our analysis framework provides an important step toward a more comprehensive understanding of the mechanisms driving cellular machinery at the whole-cell level.


Assuntos
Rastreamento de Células/métodos , Proteínas de Fluorescência Verde/farmacocinética , Imageamento Tridimensional/métodos , Proteínas Associadas aos Microtúbulos/farmacocinética , Microtúbulos/fisiologia , Fuso Acromático/fisiologia , Crescimento Celular , Corantes Fluorescentes/farmacocinética , Genes Reporter/genética , Proteínas de Fluorescência Verde/genética , Células HeLa , Humanos , Microscopia de Fluorescência/métodos , Proteínas Associadas aos Microtúbulos/genética , Microtúbulos/ultraestrutura , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacocinética , Fuso Acromático/ultraestrutura
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