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1.
Sci Rep ; 11(1): 7491, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820918

RESUMO

Despite the intensive study of the viral spread of fake news in political echo chambers (ECs) on social networking services (SNSs), little is known regarding the underlying structure of the daily information spread in these ECs. Moreover, the effect of SNSs on opinion polarisation is still unclear in terms of pluralistic information access or selective exposure to opinions in an SNS. In this study, we confirmed the steady, highly independent nature of left- and right-leaning ECs, both of which are composed of approximately 250,000 users, from a year-long reply/retweet network of 42 million Japanese Twitter users. We found that both communities have similarly efficient information spreading networks with densely connected and core-periphery structures. Core nodes resonate in the early stages of information cascades, and unilaterally transmit information to peripheral nodes. Each EC has resonant core users who amplify and steadily spread information to a quarter of a million users. In addition, we confirmed the existence of extremely aggressive users of ECs who co-reply/retweet each other. The connection between these users and top influencers suggests that the extreme opinions of the former group affect the entire community through the top influencers.

2.
J Neuroendocrinol ; 33(3): e12961, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33675127

RESUMO

Under severe calorie restriction (CR), the ghrelin-growth hormone axis in mice is involved in the maintenance of plasma glucose levels. Ghrelin, a stomach-derived acylated peptide, is up-regulated by the sympathetic nerve in the negative energy status. Central corticotrophin-releasing factor receptor (CRF-R) signalling stimulates the sympathetic tone. The present study aimed to examine the effect of central CRF-R signalling on the maintenance of plasma glucose concentrations in severe calorie-restricted mice with the involvement of ghrelin. Intracerebroventricular injections of urocorin-1 and urocorin-2, which are natural ligands for CRF-R1 and CRF-R2, elevated plasma ghrelin concentrations and ghrelin elevation with an i.c.v. injection of urocorin-1 was cancelled by atenolol (ß1 adrenergic receptor antagonist) administration. We then established a mice model of 60% CR and found that the administration of [d-Lys3]-GHRP-6 (a ghrelin receptor antagonist) in mice under 60% CR reduced the plasma glucose concentration more compared to the vehicle mice. Similarly, the atenolol injection in mice under 60% CR significantly reduced the plasma glucose concentration, which was rescued by the co-administration of ghrelin. An i.c.v. injection of the alpha helical CRH, a non-selective corticotrophin-releasing factor receptor antagonist, in mice under 60% CR significantly reduced the plasma glucose concentration, although the co-administration of α-helical CRH with ghrelin maintained plasma glucose levels. These results suggest that central CRF-R signalling is involved in the maintenance of plasma glucose levels in mice under severe CR via the sympathetic-ghrelin pathway.

4.
Curr Opin Endocrinol Diabetes Obes ; 28(2): 238-242, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394720

RESUMO

PURPOSE OF REVIEW: Ghrelin was discovered in 1999; extensive research and clinical studies on ghrelin have been published in the last 20 years. Physiological research on ghrelin ranges from its appetite-stimulating effects to its association with energy homeostasis. The physiological effects of ghrelin in the gastrointestinal tract and its relevance in the pathological conditions of the gastrointestinal tract have gradually become clearer. The purpose of the review is to provide current information on ghrelin cell biology and physiology, particularly in the gastrointestinal tract. RECENT FINDINGS: Ghrelin-producing cells in the stomach are characterized as X/A-like cells, but immunohistochemical analyses have revealed co-expression of several secreted proteins and hormones in ghrelin-producing cells such as nesfatin-1, somatostatin, and pancreastatin. Furthermore, the local physiological roles and/or mechanisms of ghrelin in gastrointestinal functions such as gastric motility and inflammation are discussed. SUMMARY: Ghrelin is a brain-gut hormone with a wide range of physiological actions; hence, it is important to understand its effects on the physiological functions of the gastrointestinal tract to elucidate the biological significance of ghrelin.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33121756

RESUMO

Highly dispersed graphene nanosheets (GNS) are directly integrated into polyurethane sponge for the very first time. Individual GNS with an average thickness of 5 nm were uniformly encapsulated in polyurethane sponge (PUF). Highly durable, flexible, hydrophilic GNS/PUF demonstrated excellent organic dye absorption properties. For a detailed study, we selected typical water-soluble organic dyes such as methylene blue (MB), ethidium bromide (EtBr), eosin Y (EY). The adsorption behavior follows the Langmuir isotherm model indicating strong monolayer chemisorption. Adsorption capacity (µmol/g) of GNS while using in GNS/PUF is 586.8 (MB), 843.1 (EtBr), and 813.3 (EY). Thermodynamic study on the adsorption with three organic dyes using GNS/PUF revealed that the process was spontaneous and exothermic in nature. Additionally, the rate of adsorption is higher and follow the pseudo-second-order kinetic model. The detailed pH-dependent study showed that cationic dyes' adsorption increases with an increase in pH, and anionic dyes follow the opposite trend. The overall results show that the new adsorbent has highly suitable for practical application.

6.
Sci Rep ; 10(1): 10126, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576884

RESUMO

High-performance/low-cost platinum (Pt)-based electrocatalysts have been established by top-coating both sides of a titanium plate with Pt nanoparticles. The average diameter of the Pt nanoparticles used in this study is approximately 100 nm. Three types of Pt top-coated Pt/Ti electrocatalysts, each having different top-coated Pt layer thicknesses, are prepared. Type I is a monolayered Pt top-coated type, in which the thickness of the top-coated Pt layer is approximately 100 nm; Type II is a few-layered type with a top-coated Pt layer thickness of approximately 200 nm, and Type III is a multilayered type with a top-coated Pt layer thickness of approximately 750 nm. The mass loading of Pt is 0.0215 mg cm-2 for Type I, 0.043 mg cm-2 for Type II, and 0.161 mg cm-2 for Type III. The electrocatalytic activities of each type of Pt/Ti electrocatalyst are evaluated through the electrolysis of acidic water and tap water. Type I gives the highest electrocatalytic efficiencies, which are comparable or even better than the electrocatalytic efficiencies of the state-of-the-art commercially available Pt/C electrode and other metal-/carbon-based HER catalysts. For example, in the case of the electrolysis of acidic water at an overpotential of 0.15 V, Type I shows a Tafel slope of 29 mV dec-1 and a current density of 27.5 mA cm-2. Even in the case of the electrolysis of tap water, Type I gives an HER Faradaic efficiency of 92%. A model of water (H2O), hydronium ions (H3O+), and hydroxyl ions (OH-) properly adsorbing on the Pt (111) facet is proposed to explain the electrocatalytic mechanism. New insights into the distinguishing properties of the resultant electrolyzed hydrogen water (EHW), namely, the healthy beneficial effects of EHW, are also described, and a new concept of storing and carrying reductive hydrogen (H*) by free Pt nanoparticles is proposed.

7.
Heliyon ; 6(6): e04160, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32577559

RESUMO

For research domains such as life sciences, which pursue fundamental scientific understanding and applications intended for immediate use, academic entrepreneurship has played a pivotal role in commercialization. This paper presents an evaluation method of researchers related to user-inspired fundamental research, using global databases of startup finances and academic research papers of "startup readiness." Case studies of startups related to biopharmaceutical research topics suggest that the biopharmaceutical field has rich opportunities stemming from scientific research, commercialization, and entrepreneurship. This evaluation method sorts specific industry segments by which financing activities are active, and by which related growing research topics attract increased academic attention. We constructed networks of author citation and co-authorship from paper citation networks related to research topics in industry segments in the biopharmaceutical domain. Results obtained across all research topics we surveyed demonstrated that authors in the top 10% of degree centrality ranking in both networks are far more likely to be startup participants than other authors. Our computational approach might provide convenient, dynamic, global, and real-time understanding of the "startup readiness" of researchers working with research topics for which academic attention is emerging in actively financed biopharmaceutical fields.

8.
Sci Rep ; 10(1): 8456, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439939

RESUMO

Conventionally, the importance of nodes in a network has been debated from the viewpoint of the amount of information received by the nodes and its neighbors. While node evaluation based on the adjacency relationship mainly uses local proximity information, the community structure that characterizes the network has hardly been considered. In this study, we propose a new node index that contributes to the understanding of the inter-community structure of a network by combining the measures of link distribution and community relevance. The visualization of node rankings and rank correlations with respect to the attack tolerance of networks demonstrated that the proposed index shows the highest performance in comparison with five previously proposed indexes, suggesting a new way to detect latent mediators in heterogeneous networks.

9.
J Hazard Mater ; 386: 121979, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31891821

RESUMO

Prussian blue (PB), an adsorbent for the selective elimination of radioactive cesium from water, is highly versatile due to its unique crystal structure. However, PB crystals quickly decompose in an alkaline solution, generating hazardous cyanide contamination. In this research, the alkaline susceptibility of PB was remedied by incorporating copper sulfate as a protector. A stability assessment was conducted at several environmental conditions, such as high pH and temperatures from 10 °C to 50 °C, in seawater, artificial seawater, and river water. The crystalline and chemical stability of PB in the new class of composite was extremely high, even at a pH value of 11.2, as confirmed using XRD and total cyanide analysis. A comprehensive mechanism study revealed that, at high pH, the copper ions that cover the PB react with hydroxide ions to form copper hydroxide and shielding inner crystals. To decontaminate radioactive cesium, the first step was to immobilize nano PB on a cellulose nanofiber, followed by copper sulfate stabilization. Then, a spongiform adsorbent was made using polyurethane as the precursor. The new stabilized PB showed promising adsorption efficiency. Thus, this research will open a new range of applications for all existing and emerging PB-based adsorbents.

10.
Gen Comp Endocrinol ; 285: 113294, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585115

RESUMO

Motilin and ghrelin were identified in the pheasant by molecular cloning, and the actions of both peptides on the contractility of gastrointestinal (GI) strips were examined in vitro. Molecular cloning indicated that the deduced amino acid sequences of the pheasant motilin and ghrelin were a 22-amino acid peptide, FVPFFTQSDIQKMQEKERIKGQ, and a 26-amino acid peptide, GSSFLSPAYKNIQQQKDTRKPTGRLH, respectively. In in vitro studies using pheasant GI strips, chicken motilin caused contraction of the proventriculus and small intestine, whereas the crop and colon were insensitive. Human motilin, but not erythromycin, caused contraction of small intestine. Chicken motilin-induced contractions in the proventriculus and ileum were not inhibited by a mammalian motilin receptor antagonist, GM109. Neither atropine (a cholinergic receptor antagonist) nor tetrodotoxin (a neuron blocker) inhibited the responses of chicken motilin in the ileum but both drugs decreased the responses to motilin in the proventriculus, suggesting that the contractile mechanisms of motilin in the proventriculus was neurogenic, different from that of the small intestine (myogenic). On the other hand, chicken and quail ghrelin did not cause contraction in any regions of pheasant GI tract. Since interaction of ghrelin and motilin has been reported in the house musk shrew, interaction of two peptides was examined. The chicken motilin-induced contractions were not modified by ghrelin, and ghrelin also did not cause any contraction under the presence of motilin, suggesting the absence of interaction in both peptides. In conclusion, both the motilin system and ghrelin system are present in the pheasant. Regulation of GI motility by motilin might be common in avian species. However, absence of ghrelin actions in any GI regions suggests the avian species-related difference in regulation of GI contractility by ghrelin.


Assuntos
Aves/metabolismo , Trato Gastrointestinal/fisiologia , Grelina/farmacologia , Motilina/farmacologia , Contração Muscular/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Atropina/farmacologia , Sequência de Bases , Galinhas , Clonagem Molecular , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Trato Gastrointestinal/efeitos dos fármacos , Grelina/química , Grelina/genética , Humanos , Masculino , Motilina/química , Motilina/genética , Proventrículo/efeitos dos fármacos , Codorniz , Ratos , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo , Tetrodotoxina/farmacologia
11.
J Smooth Muscle Res ; 56(0): 69-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33473062

RESUMO

Gastric contractions show two specific patterns in many species, migrating motor contractions (MMC) and postprandial contractions (PPCs), that occur in the fasted and fed states, respectively. In this study, we examined the role of somatostatin (SST) in gastric motility both in vivo and in vitro using the Asian house shrew (Suncus murinus). We performed in vivo recordings of gastric motility and in vitro organ bath experiments using S. murinus, which was recently established as a small laboratory animal for use in tests of gastrointestinal motility. SST (1.65 µg kg-1 min-1) was intravenously administered during phase II of MMC and PPCs. Next, the effect of SST on motilin-induced gastric contractions at phase I of MMC was measured. Cyclosomatostatin (CSST), an SST receptor antagonist, was administered at the peak of phase III of MMC. In addition, the effect of SST (10-11-10-9 M) on motilin-induced gastric contractions was evaluated using an organ bath experiment in vitro. In conscious, free-moving S. murinus, the administration of SST decreased the occurrence of the spontaneous phase II of MMC and PPCs. Pretreatment with SST and octreotide suppressed the induction of motilin-induced gastric contractions both in vivo and in vitro. Administration of CSST before the peak of spontaneous phase III contractions had no effect on gastric contractions. Endogenous SST is not involved in the regulation of gastric MMC and PPCs, but exogenous SST suppresses spontaneous gastric contractions. Thus, SST would be good for treating abnormal gastrointestinal motility disorders.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31594654

RESUMO

Alteration in the gastrointestinal (GI) motility and transit comprises an important component of the functional gastrointestinal disorders (FGID). Available animal GI motility and transit models are to study symptoms (delayed gastric emptying, constipation, diarrhea) rather than biological markers to develop an effective treatment that targets the underlying mechanism of altered GI motility in patients. Animal data generated from commonly used methods in human like scintigraphy, breath test and wireless motility capsule may directly translate to the clinic. However, species differences in the control mechanism or pharmacological responses of GI motility may compromise the predictive and translational value of the preclinical data to human. In this review we aim to provide a summary on animal models used to mimic GI motility alteration in FGID, and the impact of the species differences in the physiological and pharmacological responses on the translation of animal GI motility and transit data to human.


Assuntos
Gastroenteropatias/diagnóstico , Motilidade Gastrointestinal/fisiologia , Trânsito Gastrointestinal/fisiologia , Animais , Feminino , Humanos , Masculino , Resultado do Tratamento
13.
Cell Biol Int ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31293061

RESUMO

Motilin, a 22-amino-acid peptide produced in the upper small intestine, induces strong gastric contraction in fasted state. In many rodents, motilin and its cognate receptors exist as pseudogenes, which has delayed motilin research in the past decades. Recently, the house musk shrew (Suncus murinus) was developed as a useful model for studying motilin and gastrointestinal motility. However, due to a lack of motilin-producing cell lines and difficulties in culturing small intestinal cells, the regulatory mechanisms of motilin secretion and its messenger RNA (mRNA) transcription have remained largely unclear. In this study, we generated small intestinal organoids from S. murinus for the first time. Using methods similar to mouse organoid generation, we found crypt-like budding structures 3 days after isolating intestinal tissues. The organoids grew gradually with time. In addition, the generated organoids were able to be passaged and maintained for 6 months or longer. Motilin messenger RNA (mRNA) and immunopositive cells were observed in both S. murinus intestinal organoids and primary tissues. This is the first report of intestinal organoids in S. murinus, and our results suggest that S. murinus intestinal organoids could be useful for analyzing motilin secretion and transcription.

14.
Mol Cell Endocrinol ; 496: 110518, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344393

RESUMO

Neuromedin U (NMU) shows circadian expression in the rat pars tuberalis (PT), and is known to be suppressed by melatonin. Here we examined the involvement of adenosine in the regulation of Nmu expression. We found that the rat PT expressed adenosine receptor A2b and that an adenosine receptor agonist, NECA, stimulated Nmu expression in brain slice cultures. In vitro promoter assays revealed that NECA stimulated Nmu promoter activity via a cAMP response element (CRE) in the presence of adenosine receptor A2b. NECA also increased the levels of phosphorylated CRE-binding protein. These findings suggest that adenosine stimulates Nmu expression by activating the cAMP signaling pathway through adenosine receptor A2b in the rat PT. This is the first report to demonstrate that Nmu expression in the PT is regulated by adenosine, which acts as an intravital central metabolic signal, in addition to melatonin, which acts as an external photoperiodic environmental signal.


Assuntos
Adenosina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Neuropeptídeos/biossíntese , Hipófise/metabolismo , RNA Mensageiro/biossíntese , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Animais , AMP Cíclico/metabolismo , Masculino , Hipófise/citologia , Ratos , Ratos Endogâmicos F344 , Receptor A2B de Adenosina/metabolismo
15.
Dev Comp Immunol ; 100: 103427, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31278953

RESUMO

The intestinal epithelial monolayer forms a mucosal barrier between the gut microbes and the host tissue. The mucosal barrier is composed of mucins and antimicrobial peptides and proteins (AMPs). Several animal studies have reported that Paneth cells, which occupy the base of intestinal crypts, play an important role in the intestinal innate immunity by producing AMPs, such as lysozyme, Reg3 lectins, α-defensins, and group IIA secretory phospholipase A2 (GIIA sPLA2). The house musk shrew (Suncus murinus) has only a few intestinal commensal bacteria and is reported to lack Paneth cells in the intestine. Although the expression of lysozyme was reported in the suncus intestine, the expression of other AMPs has not yet been reported. Therefore, the current study was focused on GIIA sPLA2 expression in Suncus murinus. GIIA sPLA2 mRNA was found to be most abundant in the spleen and also highly expressed in the intestine. Cells expressing GIIA sPLA2 mRNA were distributed not only in the crypt, but also in the villi. In addition, intragastric injection of lipopolysaccharide increased GIIA sPLA2 expression in the small intestine of suncus. These results suggest that suncus may host unique AMP-secreting cells in the intestine.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Fosfolipases A2 do Grupo II/metabolismo , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Musaranhos/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/imunologia , Clonagem Molecular , Feminino , Fosfolipases A2 do Grupo II/genética , Fosfolipases A2 do Grupo II/imunologia , Mucosa Intestinal/metabolismo , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Masculino , RNA Mensageiro/isolamento & purificação , RNA Mensageiro/metabolismo , Musaranhos/genética , Musaranhos/metabolismo , Baço/imunologia , Baço/metabolismo
16.
Can J Physiol Pharmacol ; 97(10): 909-915, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31100203

RESUMO

Molecular hydrogen (H2) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of H2 was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (•OH). However, after chronic administration of H2 in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of H2. It suggests indirect signaling of H2 and gastrointestinal tract is involved. Indirect effects of H2 could be tested by giving H2 water only before nerve injury, as preconditioning. For example, preconditioning of H2 for certain a period (∼7 days) in Parkinson's disease model mice shows significant neuroprotection. As the mechanism of indirect effect, H2 in drinking water induces ghrelin production and release from the stomach via ß1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood-brain barrier, activates its receptor, growth-hormone secretagogue receptor. H2-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of H2 and raise intriguing preventive and therapeutic options using H2.


Assuntos
Grelina/metabolismo , Hidrogênio/administração & dosagem , Doenças Neurodegenerativas/terapia , Neuroproteção/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/terapia , Animais , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Ingestão de Líquidos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Grelina/sangue , Humanos , Doenças Neurodegenerativas/sangue , Estresse Oxidativo/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/sangue , Receptores de Grelina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Água/química
17.
Cell Tissue Res ; 376(3): 401-412, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30680460

RESUMO

Lysozyme is one of the most prominent antimicrobial peptides and has been identified from many mammalian species. However, this enzyme has not been studied in the order Insectivora, which includes the most primitive placental mammals. Here, we done the lysozyme cDNA from Suncus murinus (referred to as suncus, its laboratory name) and compare the predicted amino acid sequence to those from other mammalian species. Quantitative PCR analysis revealed a relatively higher expression of this gene in the spleen and gastrointestinal tract of suncus. The lysozyme-immunopositive (ip) cells were found mainly in the red pulp of the spleen and in the mucosa of the whole small intestine, including the follicle-associated epithelium and subepithelial dome of Peyer's patches. The lysozyme-ip cells in the small intestine were mostly distributed in the intestinal crypt, although lysozyme-expressing cells were found not only in the crypt but also in the villi. On the other hand, only a few lysozyme-ip cells were found in the villi and some granules showing intense fluorescence were located toward the lumen. As reported for other mammals, Ki67-ip cells were localized in the crypt and did not co-localize with the lysozyme-ip cells. Moreover, fasting induced a decrease in the mRNA levels of lysozyme in the intestine of suncus. In conclusion, we firstly identified the lysozyme mRNA sequence, clarified expression profile of lysozyme transcripts in suncus and found a unique distribution of lysozyme-producing cells in the suncus intestine.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Muramidase/química , Musaranhos/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/metabolismo , Mucosa Intestinal/enzimologia , Muramidase/genética , Muramidase/isolamento & purificação , Muramidase/metabolismo , Nódulos Linfáticos Agregados/enzimologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Baço/metabolismo , Distribuição Tecidual , Transcriptoma
18.
Gen Comp Endocrinol ; 274: 106-112, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30677392

RESUMO

Motilin (MLN), a 22-amino-acid peptide hormone, is generally present in the mucosa of the upper gastrointestinal (GI) tract, mainly the duodenum of mammals, and it regulates GI motility, especially that related to interdigestive migrating contraction. However, MLN and its receptor are absent in mice and rats, and MLN does not cause any mechanical responses in the rat and mouse GI tracts. The guinea-pig is also a rodent, but expression of the MLN gene in the guinea-pig has been reported. In the present study, two guinea-pig MLNs, FIPIFTYSELRRTQEREQNKGL found in the Ensemble Genome Database (gpMLN-1) and FVPIFTYSELRRTQEREQNKRL reported by Xu et al. (2001) (gpMLN-2), were synthesized, and their biological activities were evaluated in the rabbit duodenum and guinea-pig GI tract in vitro. Both gpMLNs showed contractile activity in longitudinal muscle strips of the rabbit duodenum. The EC50 values of gpMLN-1 and gpMLN-2 were slightly higher than that of human MLN (hMLN), but the maximum contractions were as same as that of hMLN. Treatment with GM109 and hMLN-induced receptor desensitization decreased the contractile activity of both gpMLNs, indicating that the two gpMLN candidates are able to activate the MLN receptor (MLN-R) of the rabbit duodenum. In guinea-pig GI preparations, hMLN and gpMLNs did not show any mechanical responses in circular muscle strips from the gastric antrum or in longitudinal strips of the duodenum, ileum and colon although acetylcholine and 1,1-dimethyl-4-phenylpiperazinium (DMPP) caused definite mechanical responses. The DMPP-induced neural responses in the gastric circular muscle and ileal longitudinal muscles were not modified by gpMLN-1. Even in the gastric and ileal strips with intact mucosa, no mechanical responses were seen with either of the gpMLNs. Furthermore, RT-PCR using various primer sets failed to amplify the gpMLN-2 mRNA. In conclusion, gpMLNs including one that was already reported and the other that was newly found in a database were effective to the rabbit MLN-R, whereas they did not cause any contractions or modification of neural responses in the guinea-pig GI tract, indicating that the MLN system is vestigial and not functional in regulation of GI motility in the guinea-pig as well as in other rodents such as rats and mice.


Assuntos
Motilidade Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/fisiologia , Motilina/farmacologia , Acetilcolina/farmacologia , Animais , Duodeno/efeitos dos fármacos , Duodeno/fisiologia , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Cobaias , Humanos , Técnicas In Vitro , Masculino , Motilina/genética , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Coelhos , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo
19.
Sci Rep ; 8(1): 9176, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907775

RESUMO

Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by ß-oxidation of long-chain fatty acids provided from the circulation.


Assuntos
Ácidos Graxos/metabolismo , Grelina/metabolismo , Processamento de Proteína Pós-Traducional , Acilação , Aciltransferases/antagonistas & inibidores , Aciltransferases/metabolismo , Animais , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Masculino , Camundongos , Oxirredução , RNA Mensageiro/metabolismo
20.
PLoS One ; 13(5): e0197260, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29782521

RESUMO

Several network features and information retrieval methods have been proposed to elucidate the structure of citation networks and to detect important nodes. However, it is difficult to retrieve information related to trends in an academic field and to detect cutting-edge areas from the citation network. In this paper, we propose a novel framework that detects the trend as the growth direction of a citation network using network representation learning(NRL). We presume that the linear growth of citation network in latent space obtained by NRL is the result of the iterative edge additional process of a citation network. On APS datasets and papers of some domains of the Web of Science, we confirm the existence of trends by observing that an academic field grows in a specific direction linearly in latent space. Next, we calculate each node's degree of trend-following as an indicator called the intrinsic publication year (IPY). As a result, there is a correlation between the indicator and the number of future citations. Furthermore, a word frequently used in the abstracts of cutting-edge papers (high-IPY paper) is likely to be used often in future publications. These results confirm the validity of the detected trend for predicting citation network growth.


Assuntos
Modelos Teóricos , Publicações , Pesquisa/tendências , Comunicação Acadêmica , Aprendizagem , Publicações/tendências , Comunicação Acadêmica/tendências , Terminologia como Assunto
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