Search results for: Metabolic pathways

Authors: Baharak Khoshkholgh-Sima, Soroush Sardari, Jalal Izadi Mobarakeh, Ramezan Ali Khavari-Nejad

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There is an urgent need to develop novel Mycobacterium tuberculosis (Mtb) drugs that are active against drug resistant bacteria but, more importantly, kill persistent bacteria. Our study structured based on integrated analysis of metabolic pathways, small molecule screening and similarity Search in PubChem Database. Metabolic analysis approaches based on Unified weighted used for potent target selection. Our results suggest that pantothenate synthetase (panC) and and 3-methyl-2-oxobutanoate hydroxymethyl transferase (panB) as a appropriate drug targets. In our study, we used pantothenate synthetase because of existence inhibitors. We have reported the discovery of new antitubercular compounds through ligand based approaches using computational tools.

Keywords: In Silico, Ligand-based Virtual Screening, Metabolic Pathways, Mycobacterium tuberculosis

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Authors: Valentina L. Kouznetsova, Jonathan W. Wang, Igor F. Tsigelny

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Metabolomics has become a rising field of research for various diseases, particularly cancer. Increases or decreases in metabolite concentrations in the human body are indicative of various cancers. Further elucidation of metabolic pathways and their significance in cancer research may greatly spur medicinal discovery. We analyzed the metabolomics profiles of lung cancer. Thirty-three metabolites were selected as significant. These metabolites are involved in 37 metabolic pathways delivered by MetaboAnalyst software. The top pathways are glyoxylate and dicarboxylate pathway (its hubs are formic acid and glyoxylic acid) along with Citrate cycle pathway followed by Taurine and hypotaurine pathway (the hubs in the latter are taurine and sulfoacetaldehyde) and Glycine, serine, and threonine pathway (the hubs are glycine and L-serine). We studied interactions of the metabolites with the proteins involved in cancer-related signaling networks, and developed an approach to metabolomics biomarker use in cancer diagnostics. Our analysis showed that a significant part of lung-cancer-related metabolites interacts with main cancer-related signaling pathways present in this network: PI3K–mTOR–AKT pathway, RAS–RAF–ERK1/2 pathway, and NFKB pathway. These results can be employed for use of metabolomics profiles in elucidation of the related cancer proteins signaling networks.

Keywords: Cancer, metabolites, metabolic pathway, signaling pathway.

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Authors: Shohei Maruyama, Yasuo Matsuyama, Sachiyo Aburatani

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Development of a method to estimate gene functions is an important task in bioinformatics. One of the approaches for the annotation is the identification of the metabolic pathway that genes are involved in. Since gene expression data reflect various intracellular phenomena, those data are considered to be related with genes’ functions. However, it has been difficult to estimate the gene function with high accuracy. It is considered that the low accuracy of the estimation is caused by the difficulty of accurately measuring a gene expression. Even though they are measured under the same condition, the gene expressions will vary usually. In this study, we proposed a feature extraction method focusing on the variability of gene expressions to estimate the genes' metabolic pathway accurately. First, we estimated the distribution of each gene expression from replicate data. Next, we calculated the similarity between all gene pairs by KL divergence, which is a method for calculating the similarity between distributions. Finally, we utilized the similarity vectors as feature vectors and trained the multiclass SVM for identifying the genes' metabolic pathway. To evaluate our developed method, we applied the method to budding yeast and trained the multiclass SVM for identifying the seven metabolic pathways. As a result, the accuracy that calculated by our developed method was higher than the one that calculated from the raw gene expression data. Thus, our developed method combined with KL divergence is useful for identifying the genes' metabolic pathway.

Keywords: Metabolic pathways, gene expression data, microarray, Kullback–Leibler divergence, KL divergence, support vector machines, SVM, machine learning.

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Authors: Fabian Horn, Reinhard Guthke

Abstract:

In molecular biology, microarray technology is widely and successfully utilized to efficiently measure gene activity. If working with less studied organisms, methods to design custom-made microarray probes are available. One design criterion is to select probes with minimal melting temperature variances thus ensuring similar hybridization properties. If the microarray application focuses on the investigation of metabolic pathways, it is not necessary to cover the whole genome. It is more efficient to cover each metabolic pathway with a limited number of genes. Firstly, an approach is presented which minimizes the overall melting temperature variance of selected probes for all genes of interest. Secondly, the approach is extended to include the additional constraints of covering all pathways with a limited number of genes while minimizing the overall variance. The new optimization problem is solved by a bottom-up programming approach which reduces the complexity to make it computationally feasible. The new method is exemplary applied for the selection of microarray probes in order to cover all fungal secondary metabolite gene clusters for Aspergillus terreus.

Keywords: bottom-up approach, gene clusters, melting temperature, metabolic pathway, microarray probe design, probe selection

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Authors: Feng-Sheng Wang, Wu-Hsiung Wu, Kai-Cheng Hsu

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The optimization of biological systems, which is a branch of metabolic engineering, has generated a lot of industrial and academic interest for a long time. In the last decade, metabolic engineering approaches based on mathematical optimizations have been used extensively for the analysis and manipulation of metabolic networks. In practical optimization of metabolic reaction networks, designers have to manage the nature of uncertainty resulting from qualitative characters of metabolic reactions, e.g., the possibility of enzyme effects. A deterministic approach does not give an adequate representation for metabolic reaction networks with uncertain characters. Fuzzy optimization formulations can be applied to cope with this problem. A fuzzy multi-objective optimization problem can be introduced for finding the optimal engineering interventions on metabolic network systems considering the resilience phenomenon and cell viability constraints. The accuracy of optimization results depends heavily on the development of essential kinetic models of metabolic networks. Kinetic models can quantitatively capture the experimentally observed regulation data of metabolic systems and are often used to find the optimal manipulation of external inputs. To address the issues of optimizing the regulatory structure of metabolic networks, it is necessary to consider qualitative effects, e.g., the resilience phenomena and cell viability constraints. Combining the qualitative and quantitative descriptions for metabolic networks makes it possible to design a viable strain and accurately predict the maximum possible flux rates of desired products. Considering the resilience phenomena in metabolic networks can improve the predictions of gene intervention and maximum synthesis rates in metabolic engineering. Two case studies will present in the conference to illustrate the phenomena.

Keywords: Fuzzy multi-objective optimization problem, kinetic model, metabolic engineering.

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Authors: Mona Heydari, Ehsan Motamedian, Seyed Abbas Shojaosadati

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Prediction of perturbations after genetic manipulation (especially gene knockout) is one of the important challenges in systems biology. In this paper, a new algorithm is introduced that integrates microarray data into the metabolic model. The algorithm was used to study the change in the cell phenotype after knockout of Gss gene in Escherichia coli BW25113. Algorithm implementation indicated that gene deletion resulted in more activation of the metabolic network. Growth yield was more and less regulating gene were identified for mutant in comparison with the wild-type strain.

Keywords: Metabolic network, gene knockout, flux balance analysis, microarray data, integration.

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Authors: Y. Hong, H. Y. Hu, A. Sakoda, M. Sagehashi

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In this study, inhibition of Microcystis aeruginosa by antialgal alleochemical gramine, was studied by analyzing algal metabolic activity (represented by esterase and total dehydrogenase activities) and cell ultrastructure (showing morphological and ultrastructure alterations using transmission electron microscopy and DNA ladder analysis). After gramine exposure, esterase and total dehydrogenase activities were increased firstly but decreased later. In contrast with the controls, the cells exposed to gramine showed apparent ultrastructure alterations with thylakoids in breakage, phycobilins in decrease, lipid and cyanophycin granules abundant firstly but dissolved afterwards, DNA in fragementation. The occurrence of increase of metabolic activity and specific granules reflected that the resistance of cellular response to gramine was initiated. DNA fragementation associated with the increase of metabolic activity and specific granules hinted that gramine caused M. aeruginosa cells to initiate some morphotype of programmed cell death.

Keywords: Allelochemical, gramine, metabolic activity, Microcystis aeruginosa, ultrastructure.

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Authors: Orkide Donma, Mustafa M. Donma

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Basal metabolic rate is questioned as a risk factor for weight gain. The relations between basal metabolic rate and body composition have not been cleared yet. The impact of fat mass on basal metabolic rate is also uncertain. Within this context, indices based upon total body mass as well as total body fat mass are available. In this study, the aim is to investigate the potential clinical utility of these indices in the adult population. 287 individuals, aged from 18 to 79 years, were included into the scope of the study. Based upon body mass index values, 10 underweight, 88 normal, 88 overweight, 81 obese, and 20 morbid obese individuals participated. Anthropometric measurements including height (m), and weight (kg) were performed. Body mass index, diagnostic obesity notation model assessment index I, diagnostic obesity notation model assessment index II, basal metabolic rate-to-weight ratio were calculated. Total body fat mass (kg), fat percent (%), basal metabolic rate, metabolic age, visceral adiposity, fat mass of upper as well as lower extremities and trunk, obesity degree were measured by TANITA body composition monitor using bioelectrical impedance analysis technology. Statistical evaluations were performed by statistical package (SPSS) for Windows Version 16.0. Scatterplots of individual measurements for the parameters concerning correlations were drawn. Linear regression lines were displayed. The statistical significance degree was accepted as p < 0.05. The strong correlations between body mass index and diagnostic obesity notation model assessment index I as well as diagnostic obesity notation model assessment index II were obtained (p < 0.001). A much stronger correlation was detected between basal metabolic rate and diagnostic obesity notation model assessment index I in comparison with that calculated for basal metabolic rate and body mass index (p < 0.001). Upon consideration of the associations between basal metabolic rate-to-weight ratio and these three indices, the best association was observed between basal metabolic rate-to-weight and diagnostic obesity notation model assessment index II. In a similar manner, this index was highly correlated with fat percent (p < 0.001). Being independent of the indices, a strong correlation was found between fat percent and basal metabolic rate-to-weight ratio (p < 0.001). Visceral adiposity was much strongly correlated with metabolic age when compared to that with chronological age (p < 0.001). In conclusion, all three indices were associated with metabolic age, but not with chronological age. Diagnostic obesity notation model assessment index II values were highly correlated with body mass index values throughout all ranges starting with underweight going towards morbid obesity. This index is the best in terms of its association with basal metabolic rate-to-weight ratio, which can be interpreted as basal metabolic rate unit.

Keywords: Basal metabolic rate, body mass index, children, diagnostic obesity notation model assessment index, obesity.

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Authors: Eleftheria Tzamali, Panayiota Poirazi, Ioannis G. Tollis, Martin Reczko

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Stable bacterial polymorphism on a single limiting resource may appear if between the evolved strains metabolic interactions take place that allow the exchange of essential nutrients [8]. Towards an attempt to predict the possible outcome of longrunning evolution experiments, a network based on the metabolic capabilities of homogeneous populations of every single gene knockout strain (nodes) of the bacterium E. coli is reconstructed. Potential metabolic interactions (edges) are allowed only between strains of different metabolic capabilities. Bacterial communities are determined by finding cliques in this network. Growth of the emerged hypothetical bacterial communities is simulated by extending the metabolic flux balance analysis model of Varma et al [2] to embody heterogeneous cell population growth in a mutual environment. Results from aerobic growth on 10 different carbon sources are presented. The upper bounds of the diversity that can emerge from single-cloned populations of E. coli such as the number of strains that appears to metabolically differ from most strains (highly connected nodes), the maximum clique size as well as the number of all the possible communities are determined. Certain single gene deletions are identified to consistently participate in our hypothetical bacterial communities under most environmental conditions implying a pattern of growth-condition- invariant strains with similar metabolic effects. Moreover, evaluation of all the hypothetical bacterial communities under growth on pyruvate reveals heterogeneous populations that can exhibit superior growth performance when compared to the performance of the homogeneous wild-type population.

Keywords: Bacterial polymorphism, clique identification, dynamic FBA, evolution, metabolic interactions.

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Authors: Vladyslav Povoroznyuk, Larysa Martynyuk, Iryna Syzonenko, Liliya Martynyuk

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Osteoporosis is one of the important problems in postmenopausal women due to an increased risk of sudden and unexpected fractures. This study is aimed to determine the connection between bone mineral density (BMD) and trabecular bone score (TBS) in Ukrainian women suffering from metabolic syndrome. Participating in the study, 566 menopausal women aged 50-79 year-old were examined and divided into two groups: Group A included 336 women with no obesity (BMI ≤ 29.9 kg/m²), and Group B – 230 women with metabolic syndrome (diagnosis according to IDF criteria, 2005). Dual-energy X-ray absorptiometry was used for measuring of lumbar spine (L1-L4), femoral neck, total body and forearm BMD and bone quality indexes (last according to Med-Imaps installation). Data were analyzed using Statistical Package 6.0. A significant increase of lumbar spine (L1-L4), femoral neck, total body and ultradistal radius BMD was found in women with metabolic syndrome compared to those without obesity (p < 0.001) both in their totality and in groups of 50-59 years, 60-69 years, and 70-79 years. TBS was significantly higher in non-obese women compared to metabolic syndrome patients of 50-59 years and in the general sample (p < 0.05). Analysis showed significant positive correlation between body mass index (BMI) and BMD at all levels. Significant negative correlation between BMI and TBS (L1-L4) was established. Despite the fact that BMD indexes were significantly higher in women with metabolic syndrome, the frequency of vertebral and non-vertebral fractures did not differ significantly in the groups of patients.

Keywords: Bone mineral density, trabecular bone score, metabolic syndrome, fracture.

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Authors: Surajit Debnath, Soma Addya

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Human genome is not only the evolutionary summation of all advantageous events, but also houses lesions of deleterious foot prints. A single gene mutation sometimes may express multiple consequences in numerous tissues and a linear relationship of the genotype and the phenotype may often be obscure. ß Thalassemia minor, a transfusion independent mild anaemia, coupled with environment among other factors may articulate into phenotypic pleotropy with Hypocholesterolemia, Vitamin D deficiency, Tissue hypoxia, Hyper-parathyroidism and Psychological alterations. Occurrence of Pancreatic insufficiency, resultant steatorrhoea, Vitamin-D (25-OH) deficiency (13.86 ngm/ml) with Hypocholesterolemia (85mg/dl) in a 30 years old male ß Thal-minor patient (Hemoglobin 11mg/dl with Fetal Hemoglobin 2.10%, Hb A2 4.60% and Hb Adult 84.80% and altered Hemogram) with increased Para thyroid hormone (62 pg/ml) & moderate Serum Ca+2 (9.5mg/ml) indicate towards a cascade of phenotypic pleotropy where the ß Thalassemia mutation ,be it in the 5’ cap site of the mRNA , differential splicing etc in heterozygous state is effecting several metabolic pathways. Compensatory extramedulary hematopoiesis may not coped up well with the stressful life style of the young individual and increased erythropoietic stress with high demand for cholesterol for RBC membrane synthesis may have resulted in Hypocholesterolemia.Oxidative stress and tissue hypoxia may have caused the pancreatic insufficiency, leading to Vitamin D deficiency. This may in turn have caused the secondary hyperparathyroidism to sustain serum Calcium level. Irritability and stress intolerance of the patient was a cumulative effect of the vicious cycle of metabolic compromises. From these findings we propose that the metabolic deficiencies in the ß Thalassemia mutations may be considered as the phenotypic display of the pleotropy to explain the genetic epidemiology. According to the recommendations from the NIH Workshop on Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model, study design of observations should be informed by gene-environment hypotheses and results of a study (genetic diseases) should be published to inform future hypotheses. Variety of approaches is needed to capture data on all possible aspects, each of which is likely to contribute to the etiology of disease. Speakers also agreed that there is a need for development of new statistical methods and measurement tools to appraise information that may be missed out by conventional method where large sample size is needed to segregate considerable effect. A meta analytic cohort study in future may bring about significant insight on to the title comment.

Keywords: Genetic disease, Genetic epidemiology, Heterozygous, Phenotype, Pleotropy, ß Thalassemia minor, Metabolic compromises.

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Authors: Yi Chao Huang, Yu Ling Liao, Chiu Shuang Lin

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A data cutting and sorting method (DCSM) is proposed to optimize the performance of data mining. DCSM reduces the calculation time by getting rid of redundant data during the data mining process. In addition, DCSM minimizes the computational units by splitting the database and by sorting data with support counts. In the process of searching for the relationship between metabolic syndrome and lifestyles with the health examination database of an electronics manufacturing company, DCSM demonstrates higher search efficiency than the traditional Apriori algorithm in tests with different support counts.

Keywords: Data mining, Data cutting and sorting method, Apriori algorithm, Metabolic syndrome

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Authors: P. Pasomboon, P. Chumnanpuen, T. E-kobon

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Hyaluronic acid (HA) consists of linear heteropolysaccharides repeat of D-glucuronic acid and N-acetyl-D-glucosamine. HA has various useful properties to maintain skin elasticity and moisture, reduce inflammation, and lubricate the movement of various body parts without causing immunogenic allergy. HA can be found in several animal tissues as well as in the capsule component of some bacteria including Pasteurella multocida. This study aimed to modify a genome-scale metabolic model of Escherichia coli using computational simulation and flux analysis methods to predict HA productivity under different carbon sources and nitrogen supplement by the addition of two enzymes (GLMU2 and HYAD) from P. multocida to improve the HA production under the specified amount of carbon sources and nitrogen supplements. Result revealed that threonine and aspartate supplement raised the HA production by 12.186%. Our analyses proposed the genome-scale metabolic model is useful for improving the HA production and narrows the number of conditions to be tested further.

Keywords: Pasteurella multocida, Escherichia coli, hyaluronic acid, genome-scale metabolic model, bioinformatics.

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Authors: Vladyslav Povoroznyuk, Larysa Martynyuk, Iryna Syzonenko, Liliya Martynyuk

Abstract:

Medical, social, and economic relevance of osteoporosis is caused by reducing quality of life, increasing disability and mortality of the patients as a result of fractures due to the low-energy trauma. This study is aimed to examine the associations of metabolic syndrome components, bone mineral density (BMD) and trabecular bone score (TBS) in menopausal women with non-vertebral fractures. 1161 menopausal women aged 50-79 year-old were examined and divided into three groups: A included 419 women with increased body weight (BMI - 25.0-29.9 kg/m²), B – 442 females with obesity (BMI >29.9 kg/m²)i and C – 300 women with metabolic syndrome (diagnosis according to IDF criteria, 2005). BMD of lumbar spine (L1-L4), femoral neck, total body and forearm was investigated with usage of dual-energy X-ray absorptiometry. The bone quality indexes were measured according to Med-Imaps installation. All analyses were performed using Statistical Package 6.0. BMD of lumbar spine (L1-L4), femoral neck, total body, and ultradistal radius was significant higher in women with obesity and metabolic syndrome compared to the pre-obese ones (p<0.001). TBS was significantly higher in women with increased body weight compared to obese and metabolic syndrome patients. Analysis showed significant positive correlation between waist circumference, triglycerides level and BMD of lumbar spine and femur. Significant negative association between serum HDL level and BMD of investigated sites was established. The TBS (L1-L4) indexes positively correlated with HDL (high-density lipoprotein) level. Despite the fact that BMD indexes were better in women with metabolic syndrome, the frequency of non-vertebral fractures was significantly higher in this group of patients.

Keywords: Bone mineral density, trabecular bone score, metabolic syndrome, fracture.

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Authors: M. Marjaneh, M. Y. Narazah, H. Shahrul

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Array-based gene expression analysis is a powerful tool to profile expression of genes and to generate information on therapeutic effects of new anti-cancer compounds. Anti-apoptotic effect of thymoquinone was studied in MCF7 breast cancer cell line using gene expression profiling with cDNA microarray. The purity and yield of RNA samples were determined using RNeasyPlus Mini kit. The Agilent RNA 6000 NanoLabChip kit evaluated the quantity of the RNA samples. AffinityScript RT oligo-dT promoter primer was used to generate cDNA strands. T7 RNA polymerase was used to convert cDNA to cRNA. The cRNA samples and human universal reference RNA were labelled with Cy-3-CTP and Cy-5-CTP, respectively. Feature Extraction and GeneSpring softwares analysed the data. The single experiment analysis revealed involvement of 64 pathways with up-regulated genes and 78 pathways with downregulated genes. The MAPK and p38-MAPK pathways were inhibited due to the up-regulation of PTPRR gene. The inhibition of p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of p38-MAPK caused up-regulation of TP53 and down-regulation of Bcl2 genes indicating involvement of intrinsic apoptotic pathway. Down-regulation of CARD16 gene as an adaptor molecule regulated CASP1 and suggested necrosis-like programmed cell death and involvement of caspase in apoptosis. Furthermore, down-regulation of GPCR, EGF-EGFR signalling pathways suggested reduction of ER. Involvement of AhR pathway which control cytochrome P450 and glucuronidation pathways showed metabolism of Thymoquinone. The findings showed differential expression of several genes in apoptosis pathways with thymoquinone treatment in estrogen receptor-positive breast cancer cells.

Keywords: CARD16, CASP10, cDNA microarray, PTPRR, Thymoquinone.

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Authors: A. T. Nakysh, A. S. Idrisov, S. A. Baidurin

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This work presents the results of a study the incidence of metabolic syndrome (MetS) in women with impaired reproductive function (IRF) according to the data of Astana, Kazakhstan. The anthropometric, biochemical and instrumental studies were conducted among 515 women, of which 53 patients with MetS according to IDF criteria, 2006, were selected. The frequency of occurrence of the IRF, due to MetS is 10.3% of cases according to the data of Astana. In women of childbearing age with IRF and the MetS, blood pressure (BP), indicators of carbohydrate and lipid metabolism were significantly higher and the level of high density lipoprotein (HDL) significantly lower compared to the same in women with the IRF without MetS. The hyperandrogenism, the hyperestrogenemia, the hyperprolactinemia and the hypoprogesteronemia were found in the patients with MetS and IRF, indicating the impact of MetS on the development of the polycystic ovary syndrome in 28% of cases and hyperplastic processes of the myometrium in 20% of cases.

Keywords: Dyslipidemia, insulin resistance, metabolic syndrome, reproductive disorders, obesity.

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Authors: Orkide Donma, Mustafa M. Donma

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Chronologic age (CA) of individuals is closely related to obesity and generally affects the magnitude of obesity parameters. On the other hand, close association between basal metabolic rate (BMR) and metabolic age (MA) is also a matter of concern. It is suggested that MA higher than CA is the indicator of the need to improve the metabolic rate. In this study, the aim was to assess some commonly used obesity parameters, such as obesity degree, visceral adiposity, BMR, BMR-to-weight ratio, in several groups with varying differences between MA and CA values. The study comprises adults, whose ages vary between 18 and 79 years. Four groups were constituted. Group 1, 2, 3 and 4 were composed of 55, 33, 76 and 47 adults, respectively. The individuals exhibiting -1, 0 and +1 for their MA-CA values were involved in Group 1, which was considered as the control group. Those, whose MA-CA values varying between -5 and -10 participated in Group 2. Those, whose MAs above their real ages were divided into two groups [Group 3 (MA-CA; from +5 to + 10) and Group 4 (MA-CA; from +11 to + 12)]. Body mass index (BMI) values were calculated. TANITA body composition monitor using bioelectrical impedance analysis technology was used to obtain values for obesity degree, visceral adiposity, BMR and BMR-to-weight ratio. The compiled data were evaluated statistically using a statistical package program; SPSS. Mean ± SD values were determined. Correlation analyses were performed. The statistical significance degree was accepted as p < 0.05. The increase in BMR was positively correlated with obesity degree. MAs and CAs of the groups were 39.9 ± 16.8 vs 39.9 ± 16.7 years for Group 1, 45.0 ± 15.3 vs 51.4 ± 15.7 years for Group 2, 47.2 ± 12.7 vs 40.0 ± 12.7 years for Group 3, and 53.6 ± 14.8 vs 42 ± 14.8 years for Group 4. BMI values of the groups were 24.3 ± 3.6 kg/m², 23.2 ± 1.7 kg/m², 30.3 ± 3.8 kg/m², and 40.1 ± 5.1 kg/m² for Group 1, 2, 3 and 4, respectively. Values obtained for BMR were 1599 ± 328 kcal in Group 1, 1463 ± 198 kcal in Group 2, 1652 ± 350 kcal in Group 3, and 1890 ± 360 kcal in Group 4. A correlation was observed between BMR and MA-CA values in Group 1. No correlation was detected in other groups. On the other hand, statistically significant correlations between MA-CA values and obesity degree, BMI as well as BMR/weight were found in Group 3 and in Group 4. It was concluded that upon consideration of these findings in terms of MA-CA values, BMR-to-weight ratio was found to be much more useful indicator of the severe increase in obesity development than BMR. Also, the lack of associations between MA and BMR as well as BMR-to-weight ratio emphasize the importance of consideration of MA-CA values rather than MA.

Keywords: Basal metabolic rate, chronologic age, metabolic age, obesity degree.

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Authors: M. Sasajima, T. Yamaguchi, M. Watanabe, Y. Koike

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This paper discusses the propagation of sound waves in air, specifically in narrow rectangular pathways of an occluded-ear simulator for acoustic measurements. In narrow pathways, both the speed of sound and the phase of the sound waves are affected by the damping of the air viscosity. Herein, we propose a new finite-element method (FEM) that considers the effects of the air viscosity. The method was developed as an extension of existing FEMs for porous, sound-absorbing materials. The results of a numerical calculation for a three-dimensional ear-simulator model using the proposed FEM were validated by comparing with theoretical lumped-parameter modeling analysis and standard values.

Keywords: Ear simulator, FEM, simulation, viscosity.

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Authors: Sh. Khoshemehry, M. J. Pourvaghar, M. E. Bahram

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In modern life, daily physical activity is relatively reduced, which is why the incidence of some diseases associated with overweight and obesity, such as hypertension, diabetes and other chronic illnesses, even in young people are observed. Obesity and overweight is one of the most common metabolic disorders in industrialized countries and in developing countries. One consequence of pathological obesity is cardiovascular disease and metabolic syndrome. In the past, it was believed that adipose tissue was ineffective and served only for storing triglycerides. In this review article, it was tried to refer to the esteemed scientific sources about physical activity and responses of leptin.

Keywords: Disease, leptin, obesity, physical activity.

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Authors: M. Sasajima, M. Watanabe, T. Yamaguchi, Y. Kurosawa, Y. Koike

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Sound pathways in the enclosures of small earphones are very narrow. In such narrow pathways, the speed of sound propagation and the phase of sound waves change because of the air viscosity. We have developed a new finite element method that includes the effects of damping due to air viscosity for modeling the sound pathway. This method is developed as an extension of the existing finite element method for porous sound-absorbing materials. The numerical calculation results using the proposed finite element method are validated against the existing calculation methods.

Keywords: Simulation, FEM, air viscosity, damping.

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Authors: Thusitha Mabotuwana, Christopher S. Hall

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Radiologists routinely make follow-up imaging recommendations, usually based on established clinical practice guidelines, such as the Fleischner Society guidelines for managing lung nodules. In order to ensure optimal care, it is important to make guideline-compliant recommendations, and also for patients to follow-up on these imaging recommendations in a timely manner. However, determining such compliance rates after a specific finding has been observed usually requires many time-consuming manual steps. To address some of these limitations with current approaches, in this paper we discuss a methodology to automatically detect finding-specific follow-up recommendations from radiology reports and create a visualization for relevant subsequent exams showing the modality transitions. Nearly 5% of patients who had a lung related follow-up recommendation continued to have at least eight subsequent outpatient CT exams during a seven year period following the recommendation. Radiologist and section chiefs can use the proposed tool to better understand how a specific patient population is being managed, identify possible deviations from established guideline recommendations and have a patient-specific graphical representation of the imaging pathways for an abstract view of the overall treatment path thus far.

Keywords: Follow-up recommendations, care pathways, imaging pathway visualization, follow-up tracking.

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Authors: Ines Hamdi, Mohamed Ben Ahmed

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The understanding of the system level of biological behavior and phenomenon variously needs some elements such as gene sequence, protein structure, gene functions and metabolic pathways. Challenging problems are representing, learning and reasoning about these biochemical reactions, gene and protein structure, genotype and relation between the phenotype, and expression system on those interactions. The goal of our work is to understand the behaviors of the interactions networks and to model their evolution in time and in space. We propose in this study an ontological meta-model for the knowledge representation of the genetic regulatory networks. Ontology in artificial intelligence means the fundamental categories and relations that provide a framework for knowledge models. Domain ontology's are now commonly used to enable heterogeneous information resources, such as knowledge-based systems, to communicate with each other. The interest of our model is to represent the spatial, temporal and spatio-temporal knowledge. We validated our propositions in the genetic regulatory network of the Aarbidosis thaliana flower

Keywords: Ontological model, spatio-temporal modeling, Genetic Regulatory Networks (GRNs), knowledge representation.

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Authors: M. Sasajima, T. Yamaguchi, Y. Hu, Y. Koike

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In this paper, we discuss the propagation of sound in the narrow pathways of an occluded-ear simulator typically used for the measurement of insert-type earphones. The simulator has a standardized frequency response conforming to the international standard (IEC60318-4). In narrow pathways, the speed and phase of sound waves are modified by viscous air damping. In our previous paper, we proposed a new finite element method (FEM) to consider the effects of air viscosity in this type of audio equipment. In this study, we will compare the results from the ear simulator FEM model, and those from a three dimensional human ear canal FEM model made from computed tomography images, with the measured frequency response data from the ear canals of 18 people.

Keywords: Ear simulator, FEM, viscosity, human ear canal.

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Authors: Maryam Saeidi, Ehsan Motamedian, Seyed Abbas Shojaosadati

Abstract:

Zymomonas mobilis is known as an example of the uncoupled growth phenomenon. This microorganism also has a unique metabolism that degrades glucose by the Entner–Doudoroff (ED) pathway. In this paper, a genome-scale metabolic model including 434 genes, 757 reactions and 691 metabolites was reconstructed to simulate uncoupled growth and study its effect on flux distribution in the central metabolism. The model properly predicted that ATPase was activated in experimental growth yields of Z. mobilis. Flux distribution obtained from model indicates that the major carbon flux passed through ED pathway that resulted in the production of ethanol. Small amounts of carbon source were entered into pentose phosphate pathway and TCA cycle to produce biomass precursors. Predicted flux distribution was in good agreement with experimental data. The model results also indicated that Z. mobilis metabolism is able to produce biomass with maximum growth yield of 123.7 g (mol glucose)-1 if ATP synthase is coupled with growth and produces 82 mmol ATP gDCW-1h-1. Coupling the growth and energy reduced ethanol secretion and changed the flux distribution to produce biomass precursors.

Keywords: Genome-scale metabolic model, Zymomonas mobilis, uncoupled growth, flux distribution, ATP dissipation.

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Authors: Balgabay Sadepovich Maikanov, Laura Tyulegenovna Auteleyeva, Seidenova Simbat Polatbekovna

Abstract:

In this article reduced nutritional value of the rabbits’ meat at 1, 1 dimethylhydrazine experimental toxicosis is shown. The assay was performed on liquid chromatograph SHIMADZU LC-20 Prominence (Japan) with fluorometric and spectrophotometric detector. This research has revealed that samples of rabbit meat of the experimental group had significant differences from the control group:in amino acids concentration from 1.2% to 9.1%; vitamin concentration from 11.2% to 60.5%, macro – minerals concentration from 17.4% to 78.1% and saturated fatty acids concentration from 17,1% to 34.5%, respectively. The decrease in the chemical composition of rabbits’ meat at 1,1 dimethylhydrazine toxicosis may be due to changes in the internal processes associated with impaired metabolic homeostasis of animals.

Keywords: 1, 1-dimethylhydrazine, metabolic homeostasis, nutritional value, rabbit meat.

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Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Childhood obesity is an important clinical problem, because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21) and fetuin A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21 and fetuin A in childhood obesity, to point out possible differences between the obesity groups and to investigate possible associations among these three hepatokines in obese and morbid obese children. A total of 132 children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean±SD values of ages. Body mass index values of the obese and morbid obese groups were 25.0±3.5 kg/m2 and 29.8±5.7 kg/m2, respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants and the Ethics Committee of the institution approved the study protocol. Blood samples were obtained after an overnight fasting. Routine biochemical tests including glucose- and lipid-related parameters were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study were performed by SPSS for Windows. Statistical difference was accepted significant when p < 0.05. Statistically significant differences were found for insulin, triglyceride, high density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbid obese group. Higher adropin and fetuin A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbid obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin A (r = 0.373, p = 0.001). In conclusion, increased levels observed in adropin, FGF-21 and fetuin A have shown that these hepatokines possess increasing potential going from the obese to morbid obese state. Out of the correlations found with IR index, the most affected hepatokine was fetuin A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

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Authors: Michael Netzer, Michael Seger, Mahesh Visvanathan, Bernhard Pfeifer, Gerald H. Lushington, Christian Baumgartner

Abstract:

Lung cancer accounts for the most cancer related deaths for men as well as for women. The identification of cancer associated genes and the related pathways are essential to provide an important possibility in the prevention of many types of cancer. In this work two filter approaches, namely the information gain and the biomarker identifier (BMI) are used for the identification of different types of small-cell and non-small-cell lung cancer. A new method to determine the BMI thresholds is proposed to prioritize genes (i.e., primary, secondary and tertiary) using a k-means clustering approach. Sets of key genes were identified that can be found in several pathways. It turned out that the modified BMI is well suited for microarray data and therefore BMI is proposed as a powerful tool for the search for new and so far undiscovered genes related to cancer.

Keywords: lung cancer, micro arrays, data mining, feature selection.

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Authors: Elif Gencturk, Ekin Yurdakul, Ahmet Y. Celik, Senol Mutlu, Kutlu O. Ulgen

Abstract:

Yeast cells are generally used as a model system of eukaryotes due to their complex genetic structure, rapid growth ability in optimum conditions, easy replication and well-defined genetic system properties. Thus, yeast cells increased the knowledge of the principal pathways in humans. During fermentation, carbohydrates (hexoses and pentoses) degrade into some toxic by-products such as 5-hydroxymethylfurfural (5-HMF or HMF) and furfural. HMF influences the ethanol yield, and ethanol productivity; it interferes with microbial growth and is considered as a potent inhibitor of bioethanol production. In this study, yeast single cell behavior under HMF application was monitored by using a continuous flow single phase microfluidic platform. Microfluidic device in operation is fabricated by hot embossing and thermo-compression techniques from cyclo-olefin polymer (COP). COP is biocompatible, transparent and rigid material and it is suitable for observing fluorescence of cells considering its low auto-fluorescence characteristic. The response of yeast cells was recorded through Red Fluorescent Protein (RFP) tagged Nop56 gene product, which is an essential evolutionary-conserved nucleolar protein, and also a member of the box C/D snoRNP complexes. With the application of HMF, yeast cell proliferation continued but HMF slowed down the cell growth, and after HMF treatment the cell proliferation stopped. By the addition of fresh nutrient medium, the yeast cells recovered after 6 hours of HMF exposure. Thus, HMF application suppresses normal functioning of cell cycle but it does not cause cells to die. The monitoring of Nop56 expression phases of the individual cells shed light on the protein and ribosome synthesis cycles along with their link to growth. Further computational study revealed that the mechanisms underlying the inhibitory or inductive effects of HMF on growth are enriched in functional categories of protein degradation, protein processing, DNA repair and multidrug resistance. The present microfluidic device can successfully be used for studying the effects of inhibitory agents on growth by single cell tracking, thus capturing cell to cell variations. By metabolic engineering techniques, engineered strains can be developed, and the metabolic network of the microorganism can thus be manipulated such that chemical overproduction of target metabolite is achieved along with the maximum growth/biomass yield.  

Keywords: COP, HMF, ribosome biogenesis, thermoplastic microbioreactor, yeast.

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Authors: Nicole Pearcy, Jonathan J. Crofts, Nadia Chuzhanova

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In this paper, we employ a directed hypergraph model to investigate the extent to which environmental variability influences the set of available biochemical reactions within a living cell. Such an approach avoids the limitations of the usual complex network formalism by allowing for the multilateral relationships (i.e. connections involving more than two nodes) that naturally occur within many biological processes. More specifically, we extend the concept of network reciprocity to complex hyper-networks, thus enabling us to characterise a network in terms of the existence of mutual hyper-connections, which may be considered a proxy for metabolic network complexity. To demonstrate these ideas, we study 115 metabolic hyper-networks of bacteria, each of which can be classified into one of 6 increasingly varied habitats. In particular, we found that reciprocity increases significantly with increased environmental variability, supporting the view that organism adaptability leads to increased complexities in the resultant biochemical networks.

Keywords: Complexity, hypergraphs, reciprocity, metabolism.

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Authors: Nikhil, Ari Visa, Chin-Chao Chen, Chiu-Yue Lin, Jaakko A. Puhakka, Olli Yli-Harja

Abstract:

A predictive clustering hybrid regression (pCHR) approach was developed and evaluated using dataset from H2- producing sucrose-based bioreactor operated for 15 months. The aim was to model and predict the H2-production rate using information available about envirome and metabolome of the bioprocess. Selforganizing maps (SOM) and Sammon map were used to visualize the dataset and to identify main metabolic patterns and clusters in bioprocess data. Three metabolic clusters: acetate coupled with other metabolites, butyrate only, and transition phases were detected. The developed pCHR model combines principles of k-means clustering, kNN classification and regression techniques. The model performed well in modeling and predicting the H2-production rate with mean square error values of 0.0014 and 0.0032, respectively.

Keywords: Biohydrogen, bioprocess modeling, clusteringhybrid regression.

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