Search results for: Seven-transmembrane receptors

Authors: Rauza Sukma Rita, Katsuya Dezaki, Yuko Maejima, Toshihiko Yada

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Oxytocin is a nine-amino acid peptide synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Oxytocin promotes contraction of the uterus during birth and milk ejection during breast feeding. Although oxytocin receptors are found predominantly in the breasts and uterus of females, many tissues and organs express oxytocin receptors, including the pituitary, heart, kidney, thymus, vascular endothelium, adipocytes, osteoblasts, adrenal gland, pancreatic islets, and many cell lines. On the other hand, in pancreatic islets, oxytocin receptors are expressed in both α-cells and β-cells with stronger expression in α- cells. However, to our knowledge there are no reports yet about the effect of oxytocin on cytosolic calcium reaction on α and β-cell. This study aims to investigate the effect of oxytocin on α-cells and β-cells and its oscillation pattern. Islet of Langerhans from wild type mice were isolated by collagenase digestion. Isolated and dissociated single cells either α-cells or β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic concentration ([Ca2+]i) in single cells were measured by fura-2 microfluorimetry. After measurement of [Ca2+]i, α-cells were identified by subsequent immunocytochemical staining using an anti-glucagon antiserum. In β-cells, the [Ca2+]i increase in response to oxytocin was observed only under 8.3 mM glucose condition, whereas in α-cells, [Ca2+]i an increase induced by oxytocin was observed in both 2.8 mM and 8.3 mM glucose. The oscillation incidence was induced more frequently in β-cells compared to α-cells. In conclusion, the present study demonstrated that oxytocin directly interacts with both α-cells and β-cells and induces increase of [Ca2+]i and its specific patterns.

Keywords: α-cells, β-cells, cytosolic calcium concentration, oscillation, oxytocin.

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Authors: Shaila Ahmed, Raghu Prasad Rao Metpally, Sreedhara Sangadala, Boojala Vijay B Reddy

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Bone growth factors, such as Bone Morphogenic Protein-2 (BMP-2) have been approved by the FDA to replace grafting for some surgical interventions, but the high dose requirement limits its use in patients. Noggin, an extracellular protein, blocks the effect of BMP-2 by binding to BMP. Preventing the BMP-2/noggin interaction will help increase the free concentration of BMP-2 and therefore should enhance its efficacy to induce bone formation. The work presented here involves computational design of novel small molecule inhibitory agents of BMP-2/noggin interaction, based on our current understanding of BMP-2, and its known putative ligands (receptors and antagonists). A successful acquisition of such an inhibitory agent of BMP-2/noggin interaction would allow clinicians to reduce the dose required of BMP-2 protein in clinical applications to promote osteogenesis. The available crystal structures of the BMPs, its receptors, and the binding partner noggin were analyzed to identify the critical residues involved in their interaction. In presenting this study, LUDI de novo design method was utilized to perform virtual screening of a large number of compounds from a commercially available library against the binding sites of noggin to identify the lead chemical compounds that could potentially block BMP-noggin interaction with a high specificity.

Keywords: Transforming growth factor-beta, Bone morphogenic proteins, Noggin, LUDI de novo design method, CAP small molecules.

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Authors: A. Chakraborty, T. Gupta

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Several studies have shown the association between ambient particulate matter (PM) and adverse health effects and climate change, thus highlighting the need to limit the anthropogenic sources of PM. PM Exposure is commonly monitored as mass concentration of PM10 (particle aerodynamic diameter < 10μm) or PM2.5 (particle aerodynamic diameter < 2.5μm), although increasing toxicity with decreasing aerodynamic diameter has been reported due to increased surface area and enhanced chemical reactivity with other species. Additionally, the light scattering properties of PM increases with decreasing size. Hence, it is important to study the chemical characterization of finer fraction of the particulate matter and to identify their sources so that they can be controlled appropriately to a large extent at the sources before reaching to the receptors.

Keywords: PM1, PCA, source apportionment.

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Authors: V. Kabeer, N.K.Narayanan

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This paper reports a new pattern recognition approach for face recognition. The biological model of light receptors - cones and rods in human eyes and the way they are associated with pattern vision in human vision forms the basis of this approach. The functional model is simulated using CWD and WPD. The paper also discusses the experiments performed for face recognition using the features extracted from images in the AT & T face database. Artificial Neural Network and k- Nearest Neighbour classifier algorithms are employed for the recognition purpose. A feature vector is formed for each of the face images in the database and recognition accuracies are computed and compared using the classifiers. Simulation results show that the proposed method outperforms traditional way of feature extraction methods prevailing for pattern recognition in terms of recognition accuracy for face images with pose and illumination variations.

Keywords: Face recognition, Image analysis, Wavelet feature extraction, Pattern recognition, Classifier algorithms

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Authors: Milton Pavezzi Netto, Gustavo D'Almeida Scarpinella, Ricardo Siloto da Silva

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The springs located in urban areas are the outpouring of surface water, which can serve as water supply, effluent receptors and important local macro-drainage elements. With unplanned occupation, non-compliance with environmental legislation and the importance of these water bodies, it is vital to analyze the springs within urban areas, considering the Brazilian forest code. This paper submits an analysis and discussion methodology proposal of environmental compliance functions of urban springs, by means of G.I.S. - Geographic Information System analysis - and in situ analysis. The case study included two springs which exhibit a history of occupation along its length, with different degrees of impact. The proposed method is effective and easy to apply, representing a powerful tool for analyzing the environmental conditions of springs in urban areas.

Keywords: Springs, urban area, Brazilian forest code.

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Authors: M.M. Jafarpour, Ar. Foolad, M.K. Mansouri, Z. Nikbakhsh, H. Saeedizade

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Ammonia nitrogen is one of the most hazardous water pollutants, discharging into water receptors through industrial effluents. Negative environmental impacts of such chemical species in hydrosphere include accelerated eutrophication, water toxicity and harming the aquatics. Natural zeolite clinoptilolite has very high selectivity & capacity for ammonium cation sorption. It occurs in high abundances and rich mines of this zeolite exist in different parts of Iran and thus are available more cheaply and with different sizing. The aim of this study is to investigate ammonia nitrogen removal over this natural sorbent from real samples of high polluted wastewater discharging from a fertilizer producing plant. The experimental results showed that this natural sorbent without even any pre treatment system & with the same particle size available in Iranian markets has still high capability & selectivity in ammonia nitrogen removal both in batch and continuous tests.

Keywords: Ammonia nitrogen removal, Clinoptilolite, Naturalzeolite, Waste water.

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Authors: Zeyneb Kurt, Oguzhan Yavuz

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The feature of HIV genome is in a wide range because of it is highly heterogeneous. Hence, the infection ability of the virus changes related with different chemokine receptors. From this point, R5 and X4 HIV viruses use CCR5 and CXCR5 coreceptors respectively while R5X4 viruses can utilize both coreceptors. Recently, in Bioinformatics, R5X4 viruses have been studied to classify by using the coreceptors of HIV genome. The aim of this study is to develop the optimal Multilayer Perceptron (MLP) for high classification accuracy of HIV sub-type viruses. To accomplish this purpose, the unit number in hidden layer was incremented one by one, from one to a particular number. The statistical data of R5X4, R5 and X4 viruses was preprocessed by the signal processing methods. Accessible residues of these virus sequences were extracted and modeled by Auto-Regressive Model (AR) due to the dimension of residues is large and different from each other. Finally the pre-processed dataset was used to evolve MLP with various number of hidden units to determine R5X4 viruses. Furthermore, ROC analysis was used to figure out the optimal MLP structure.

Keywords: Multilayer Perceptron, Auto-Regressive Model, HIV, ROC Analysis

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Authors: Uun Yanuhar

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The purpose of research was to know the role of immunogenic protein of 49 kDa from V.alginolyticus which capable to initiate molecule expression of MHC Class II in receptor of Cromileptes altivelis. The method used was in vivo experimental research through testing of immunogenic protein 49 kDa from V.alginolyticus at Cromileptes altivelis (size of 250 - 300 grams) using 3 times booster by injecting an immunogenic protein in a intramuscular manner. Response of expressed MHC molecule was shown using immunocytochemistry method and SEM. Results indicated that adhesin V.alginolyticus 49 kDa which have immunogenic character could trigger expression of MHC class II on receptor of grouper and has been proven by staining using immunocytochemistry and SEM with labeling using antibody anti MHC (anti mouse). This visible expression based on binding between epitopes antigen and antibody anti MHC in the receptor. Using immunocytochemistry, intracellular response of MHC to in vivo induction of immunogenic adhesin from V.alginolyticus was shown.

Keywords: C.altivelis, immunogenic, MHC, V.alginolyticus.

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Authors: M. Michael Gromiha, Kiyonobu Yokota, Kazuhiko Fukui

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We have developed an energy based approach for identifying the binding sites and important residues for binding in protein-protein complexes. We found that the residues and residuepairs with charged and aromatic side chains are important for binding. These residues influence to form cation-¤Ç, electrostatic and aromatic interactions. Our observation has been verified with the experimental binding specificity of protein-protein complexes and found good agreement with experiments. The analysis on surrounding hydrophobicity reveals that the binding residues are less hydrophobic than non-binding sites, which suggests that the hydrophobic core are important for folding and stability whereas the surface seeking residues play a critical role in binding. Further, the propensity of residues in the binding sites of receptors and ligands, number of medium and long-range contacts, and influence of neighboring residues will be discussed.

Keywords: Protein-protein interactions, energy based approach;binding sites, propensity, long-range contacts, hydrophobicity

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Authors: O. Yavuz, L. Ozyilmaz

Abstract:

HIV-1 genome is highly heterogeneous. Due to this variation, features of HIV-I genome is in a wide range. For this reason, the ability to infection of the virus changes depending on different chemokine receptors. From this point of view, R5 HIV viruses use CCR5 coreceptor while X4 viruses use CXCR5 and R5X4 viruses can utilize both coreceptors. Recently, in Bioinformatics, R5X4 viruses have been studied to classify by using the experiments on HIV-1 genome. In this study, R5X4 type of HIV viruses were classified using Auto Regressive (AR) model through Artificial Neural Networks (ANNs). The statistical data of R5X4, R5 and X4 viruses was analyzed by using signal processing methods and ANNs. Accessible residues of these virus sequences were obtained and modeled by AR model since the dimension of residues is large and different from each other. Finally the pre-processed data was used to evolve various ANN structures for determining R5X4 viruses. Furthermore ROC analysis was applied to ANNs to show their real performances. The results indicate that R5X4 viruses successfully classified with high sensitivity and specificity values training and testing ROC analysis for RBF, which gives the best performance among ANN structures.

Keywords: Auto-Regressive Model, HIV, Neural Networks, ROC Analysis.

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: 177Lu, DOTATOC, adenocarcinoma, breast cancer, BALB/c mice.

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Authors: Ziba Omidi, Min-Ki Kim

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This research presents the design, fabrication and application of a flavor sensor for an integrated electronic tongue and electronic nose that can allow rapid characterization of multi-component mixtures in a solution. The odor gas and liquid are separated using hydrophobic porous membrane in micro fluidic channel. The sensor uses an array composed of microbeads in micromachined cavities localized on silicon wafer. Sensing occurs via colorimetric and fluorescence changes to receptors and indicator molecules that are attached to termination sites on the polymeric microbeads. As a result, the sensor array system enables simultaneous and near-real-time analyses using small samples and reagent volumes with the capacity to incorporate significant redundancies. One of the key parts of the system is a passive pump driven only by capillary force. The hydrophilic surface of the fluidic structure draws the sample into the sensor array without any moving mechanical parts. Since there is no moving mechanical component in the structure, the size of the fluidic structure can be compact and the fabrication becomes simple when compared to the device including active microfluidic components. These factors should make the proposed system inexpensive to mass-produce, portable and compatible with biomedical applications.

Keywords: Optical Sensor, Semiconductor manufacturing, Smell sensor, Taste sensor.

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Authors: G. V. Novikov, V. S. Sivozhelezov, S. S. Kolesnikov, K. V. Shaitan

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The study reports about the influence of binding of orthosteric ligands as well as point mutations on the conformational dynamics of β-2-adrenoreceptor. Using molecular dynamics simulation we found that there was a little fraction of active states of the receptor in its apo (ligand free) ensemble corresponded to its constitutive activity. Analysis of MD trajectories indicated that such spontaneous activation of the receptor is accompanied by the motion in intracellular part of its alpha-helices. Thus receptor’s constitutive activity directly results from its conformational dynamics. On the other hand the binding of a full agonist resulted in a significant shift of the initial equilibrium towards its active state. Finally, the binding of the inverse agonist stabilized the receptor in its inactive state. It is likely that the binding of inverse agonists might be a universal way of constitutive activity inhibition in vivo. Our results indicate that ligand binding redistribute pre-existing conformational degrees of freedom (in accordance to the Monod-Wyman-Changeux-Model) of the receptor rather than cause induced fit in it. Therefore, the ensemble of biologically relevant receptor conformations is encoded in its spatial structure, and individual conformations from that ensemble might be used by the cell in conformity with the physiological behavior.

Keywords: Seven-transmembrane receptors, constitutive activity, activation, x-ray crystallography, principal component analysis, molecular dynamics simulation.

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Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

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Authors: B. Chouhan, A. Denesyuk, J. Heino, M. S. Johnson, K. Denessiouk

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Integrins are a large family of multidomain α/β cell signaling receptors. Some integrins contain an additional inserted I domain, whose earliest expression appears to be with the chordates, since they are observed in the urochordates Ciona intestinalis (vase tunicate) and Halocynthia roretzi (sea pineapple), but not in integrins of earlier diverging species. The domain-s presence is viewed as a hallmark of integrins of higher metazoans, however in vertebrates, there are clearly three structurally-different classes: integrins without I domains, and two groups of integrins with I domains but separable by the presence or absence of an additional αC helix. For example, the αI domains in collagen-binding integrins from Osteichthyes (bony fish) and all higher vertebrates contain the specific αC helix, whereas the αI domains in non-collagen binding integrins from vertebrates and the αI domains from earlier diverging urochordate integrins, i.e. tunicates, do not. Unfortunately, within the early chordates, there is an evolutionary gap due to extinctions between the tunicates and cartilaginous fish. This, coupled with a knowledge gap due to the lack of complete genomic data from surviving species, means that the origin of collagen-binding αC-containing αI domains remains unknown. Here, we analyzed two available genomes from Callorhinchus milii (ghost shark/elephant shark; Chondrichthyes – cartilaginous fish) and Petromyzon marinus (sea lamprey; Agnathostomata), and several available Expression Sequence Tags from two Chondrichthyes species: Raja erinacea (little skate) and Squalus acanthias (dogfish shark); and Eptatretus burgeri (inshore hagfish; Agnathostomata), which evolutionary reside between the urochordates and osteichthyes. In P. marinus, we observed several fragments coding for the αC-containing αI domain, allowing us to shed more light on the evolution of the collagen-binding integrins.

Keywords: Integrin αI domain, integrin evolution, collagen binding, structure, αC helix

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Authors: Aladdin Al-Tarawneh

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The Quran, as it is the sacred book of Islam and considered the literal word of God (Allah) in Arabic, is highly translated into many languages; however, the foreignising or the literal approach excessively stains the quality and discredits the final product in the eyes of its receptors. Such an approach fails to capture the intended meaning of the Quran and to communicate it in any language. Therefore, this study is conducted to propose a different approach that seeks involving other ones according to a hybrid model. Indeed, this study challenges the binary adherence that is highly used in Translation Studies (TS) in general and in the translation of the Quran in particular. Drawing on the genuine fact that the Quran can be communicated in any language in terms of meaning, and the translation is not sacred; this paper approaches the translation of the Quran by blending different methods like domestication or foreignisation in a systematic way, avoiding the binary choice made by many translators. To reach this aim, the paper has a conceptual part that seeks to elucidate and clarify the main methods employed in TS, and criticise and modify them to propose the new hybrid approach (the hybrid model) for translating the Quran – that is, the deductive method. To support and validate the outcome of the previous part, a comparative model is employed in order to highlight the differences between the suggested translation and other widely used ones – that is, the inductive method. By applying this methodology, the paper proves that there is a deficiency of communicating the original meaning of the Quran in light of the foreignising approach. In conclusion, the paper suggests producing a Quran translation has to take into account the adoption of many techniques to express the meaning of the Quran as understood in the original, and to offer this understanding in English in the most native-like manner to serve the intended target readers.

Keywords: Quran translation, hybrid approach, domestication, foreignisation, hybrid model.

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Authors: M. Areekijseree, W. Pongsawat, M. Pumipaiboon, C. Thepsithar, S. Sengsai, T. Chuen-Im

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Morphological interaction of porcine cumulus-oocyte complexes (pCOCs) was investigated on in vitro condition using electron microscope (SEM and TEM). The totals of 1,923 oocytes were round in shape, surrounded by Zona pellucida with layer of cumulus cells ranging between 59.29-202.14 μm in size. They were classified into intact-, multi-, partial cumulus cell layer oocyte, and completely denuded oocyte, at the percentage composition of 22.80% 32.70%, 18.60%, and 25.90 % respectively. The pCOCs classified as intact- and multi cumulus cell layer oocytes were further culturing at 37°C with 5% CO2, 95% air atmosphere and high humidity for 44 h in M199 with Earle’s salts supplemented with 10% HTFCS, 2.2 mg/mL NaHCO3, 1 M Hepes, 0.25 mM pyruvate, 15 μg/mL porcine follicle-stimulating hormone, 1 μg/mL LH, 1μg/mL estradiol with ethanol, and 50 μg/mL gentamycin sulfate. On electron microscope study, cumulus cells were found to stick their processes to secrete substance from the sac-shape end into Zona pellucida of the oocyte and also communicated with the neighboring cells through their microvilli on the beginning of incubation period. It is believed that the cumulus cells communicate with the oocyte by inserting the microvilli through this gap and embedded in the oocyte cytoplasm before secreting substance, through the sac-shape end of the microvilli, to inhibit primary oocyte development at the prophase I. Morphological changes of the complexes were observed after culturing for 24-44 h. One hundred percentages of the cumulus layers were expanded and cumulus cells were peeling off from the oocyte surface. In addition, the round-shape cumulus cells transformed themselves into either an elongate shape or a columnar shape, and no communication between cumulus neighboring cells. After 44 h of incubation time, diameter of oocytes surrounded by cumulus cells was larger than 0 h incubation. The effect of hormones in culture medium is exerted by their receptors present in porcine oocyte. It is likely that all morphological changes of the complexes after hormone treatment were to allow maturation of the oocyte. This study demonstrated that the association of hormones in M199 could promote porcine follicle activation in 44 h in vitro condition. This culture system should be useful for studying the regulation of early follicular growth and development, especially because these follicles represent a large source of oocytes that could be used in vitro for cell technology.

Keywords: Cumulus cells, electron microscopy (SEM and TEM), in vitro, porcine oocyte.

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