Search results for: genome scale metabolic model

Authors: Bernard Doherty, Andrew Jelfs, Aveek Dasgupta, Patrick Holden

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Many companies have moved to agile and hybrid agile methodologies where portions of the Software Design Life-cycle (SDLC) and Software Test Life-cycle (STLC) can be time boxed in order to enhance delivery speed, quality and to increase flexibility to changes in software requirements. Despite widespread proliferation of agile practices, implementation often fails due to lack of adequate project management support, decreased motivation or fear of increased interaction. Consequently, few organizations effectively adopt agile processes with tailoring often required to integrate agile methodology in large scale environments. This paper provides an overview of the challenges in implementing an innovative large-scale tailored realization of the agile methodology termed the Agile Factory Model (AFM), with the aim of comparing and contrasting issues of specific importance to organizations undertaking large scale agile development. The conclusions demonstrate that agile practices can be effectively translated to a globally distributed development environment.

Keywords: agile, agile factory model, globally distributed development, large-scale agile

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Authors: M. Suwaibah, S. W. Tan, I. Aiini, K. Yusoff, A. R. Omar

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Respiratory diseases are the most important infectious diseases affecting poultry worldwide. One of the avian respiratory virus of global importance causing significant economic losses is Infectious Bronchitis Virus (IBV). The virus causes a wide spectrum disease known as Infectious Bronchitis (IB), affecting not only the respiratory system but also the kidney and the reproductive system, depending on its strain. IB and Newcastle disease are two of the most prevalent diseases affecting poultry in Malaysia. However, a study on the molecular characterization of Malaysian IBV is lacking. In this study, an IBV strain IBS130 which was isolated in 2015 was fully sequenced using next-gene sequencing approach. Sequence analysis of IBS130 based on the complete genome, polyprotein 1ab and S1 genes were compared with other IBV sequences available in Genbank, National Center for Biotechnology Information (NCBI). IBV strain IBS130 is characterised as QX-like strain based on whole genome and S1 gene sequence analysis. Comparisons of the virus with other IBV strains showed that the nucleotide identity ranged from 67% to 99.2%, depending on the region analysed. The similarity in whole genome nucleotide ranging from 84.9% to 90.7% with the least similar was from Singapore strains (84.9%) and highly similar with China QX-like strains. Meanwhile, the similarity in polyprotein 1ab ranging from 85.3% to 89.9% with the least similar to Singapore strains (85.3%) and highly similar with Mass strains from USA.

Keywords: infectious bronchitis virus, phylogenetic analysis, chicken, Malaysia

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Authors: Surabhi Maiti, Prajakta Tamhankar, Prachi Uttam Mehta

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Since the accomplishment of the Human Genome Project, there has been an unparalled escalation in the sequencing of genomic data. This project has been the first major vault in the field of medical research, especially in genomics. This project won accolades by using a concept called Bigdata which was earlier, extensively used to gain value for business. Bigdata makes use of data sets which are generally in the form of files of size terabytes, petabytes, or exabytes and these data sets were traditionally used and managed using excel sheets and RDBMS. The voluminous data made the process tedious and time consuming and hence a stronger framework called Hadoop was introduced in the field of genetic sciences to make data processing faster and efficient. This paper focuses on using SPARK which is gaining momentum with the advancement of BigData technologies. Cloud Storage is an effective medium for storage of large data sets which is generated from the genetic research and the resultant sets produced from SPARK analysis.

Keywords: human genome project, Bigdata, genomic data, SPARK, cloud storage, Hadoop

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Authors: Jia Zhang, Fengmei Yao, Yanjing Tan

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The accurate estimation of crop yield is of great importance for the food security. In this study, a process-based mechanism model was modified to estimate yield of C4 crop by modifying the carbon metabolic pathway in the photosynthesis sub-module of the RS-P-YEC (Remote-Sensing-Photosynthesis-Yield estimation for Crops) model. The yield was calculated by multiplying net primary productivity (NPP) and the harvest index (HI) derived from the ratio of grain to stalk yield. The modified RS-P-YEC model was used to simulate maize yield in the Northeast China Plain during the period 2002-2011. The statistical data of maize yield from study area was used to validate the simulated results at county-level. The results showed that the Pearson correlation coefficient (R) was 0.827 (P < 0.01) between the simulated yield and the statistical data, and the root mean square error (RMSE) was 712 kg/ha with a relative error (RE) of 9.3%. From 2002-2011, the yield of maize planting zone in the Northeast China Plain was increasing with smaller coefficient of variation (CV). The spatial pattern of simulated maize yield was consistent with the actual distribution in the Northeast China Plain, with an increasing trend from the northeast to the southwest. Hence the results demonstrated that the modified process-based model coupled with remote sensing data was suitable for yield prediction of maize in the Northeast China Plain at the spatial scale.

Keywords: process-based model, C4 crop, maize yield, remote sensing, Northeast China Plain

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Authors: Borys Stegniy, Anton Gerilovych, Oleksii Solodiankin, Vitaliy Bolotin, Anton Stegniy, Denys Muzyka, Claudio Afonso

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New APMV was isolated from white fronted goose in Ukraine. This isolate was tested serologically using monoclonal antibodies in haemagglutination-inhibition tests against APMV1-9. As the results obtained isolate showed cross reactions with APMV7. Following investigations were provided for the full genome sequencing using random primers and cloning into pCRII-TOPO. Analysis of 100 transformed colonies of E.coli using traditional sequencing gave us possibilities to find only 3 regions, which could identify by BLAST. The first region with the length of 367 bp had 70 % nucleotide sequence identity to the APMV 12 isolate Wigeon/Italy/3920_1/2005 at genome position 2419-2784. Next region (344 bp) had 66 % identity to the same APMV 12 isolate at position 4760-5103. The last region (365 bp) showed 71 % identity to Newcastle disease virus strain M4 at position 12569-12928.

Keywords: APMV, Newcastle disease virus, Ukraine, full genome sequencing

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Authors: Ayca Bilginoglu, Belma Turan

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Metabolic syndrome, is associated impaired blood glucose level, insulin resistance, dyslipidemia caused by abdominal obesity. Also, it is related with cardiovascular risk accumulation and cardiomyopathy. The hypothesis of this study was to examine the effect of thiazolidinediones such as pioglitazone which is widely used insulin-sensitizing agents that improve glycemic control, on intracellular Na+ homeostasis in metabolic syndrome-induced cardiomyopathy in male rats. Male Wistar-Albino rats were randomly divided into three groups, namely control (Con, n=7), metabolic syndrome (MetS, n=7) and pioglitazone treated metabolic syndrome group (MetS+PGZ, n=7). Metabolic syndrome was induced by providing drinking water that was 32% sucrose, for 18 weeks. All of the animals were exposed to a 12 h light – 12 h dark cycle. Abdominal obesity and glucose intolerance had measured as a marker of metabolic syndrome. Intracellular Na+ ([Na+]i) is an important modulator of excitation–contraction coupling in heart. [Na+]i at rest and [Na+]i during pacing with electrical field stimulation in 0.2 Hz, 0.8 Hz, 2.0 Hz stimulation frequency were recorded in cardiomyocytes. Also, Na+ channel current (INa) density and I-V curve were measured to understand [Na+]i homeostasis. In results, high sucrose intake, as well as the normal daily diet, significantly increased body mass and blood glucose level of the rats in the metabolic syndrome group as compared with the non-treated control group. In MetS+PZG group, the blood glucose level and body inclined to decrease to the Con group. There was a decrease in INa density and there was a shift both activation and inactivation curve of INa. Pioglitazone reversed the shift to the control side. Basal [Na+]i either MetS and Con group were not significantly different, but there was a significantly increase in [Na+]i in stimulated cardiomyocytes in MetS group. Furthermore, pioglitazone had not effect on basal [Na+]i but it reversed the increase in [Na+]i in stimulated cardiomyocytes to the that of Con group. Results of the present study suggest that pioglitazone has a significant effect on the Na+ homeostasis in the metabolic syndrome induced cardiomyopathy in rats. All animal procedures and experiments were approved by the Animal Ethics Committee of Ankara University Faculty of Medicine (2015-2-37).

Keywords: insulin resistance, intracellular sodium, metabolic syndrome, sodium current

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Authors: Bilal Wajid, Erchin Serpedin

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The health industry is aiming towards personalized medicine. If the patient’s genome needs to be sequenced it is important that the entire analysis be completed quickly. This paper explores use of parallel computing to analyze very large sequences. Two cases have been considered. In the first case, the sequence is kept constant and the effect of increasing the number of MPI-based processes is evaluated in terms of execution time, speed and efficiency. In the second case the number of MPI-based processes have been kept constant whereas, the length of the sequence was increased.

Keywords: parallel computing, alignment, genome assembly, alignment

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Authors: Hazel Ann Gianelli Cu, Stephanie Co, Radcliff Cobankiat

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Objectives: TRC101/Veverimer is an orally administered, non absorbed, sodium- and counterion-free hydrochloric acid binder for the treatment of metabolic acidosis associated with chronic kidney disease. The main objective of this study is to determine the efficacy of TRC 101/ Veverimer 6g/day in increasing serum bicarbonate levels of chronic kidney disease patients with metabolic acidosis. In this meta analysis, we also aim to look at safety outcomes, adverse effects and if the level of serum bicarbonate reached metabolic alkalosis when given TRC101/Veverimer. Methodology: Pubmed, Cochrane, Google Scholar and Science direct were used to search for randomized controlled trials about TRC101/Veverimer use in Chronic kidney disease patients with metabolic acidosis. Search strategy according to the Prisma checklist was done with evaluation of biases and synthesis of results using the Cochrane Review Manager software 5.4. Results: Two randomized controlled trials involving 371 chronic kidney disease patients were included in this study. Results show there was a significant increase in the serum bicarbonate level when given TRC101/Veverimer compared to the placebo. Both studies had a significant number of participants who completed the studies until the end. P value of <0.00001 was used in both studies with a confidence interval of 95%. Conclusion: TRC101/Veverimer 6g/day was shown to effectively and safely increase serum bicarbonate or achieve normalization in chronic kidney disease patients with metabolic acidosis as compared with a placebo. This was associated with delayed progression of kidney disease with improvement of physical functioning, however longer duration of future studies is ideal in order to assess further the long advantages and consequences of TRC 101/Veverimer.

Keywords: chronic kidney disease, metabolic acidosis, Veverimer, TRC101

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Authors: Farzad Sharifi, Raziyeh Shamsi

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In this paper, we obtain the projection of inefficient units in data envelopment analysis (DEA) in the case of stochastic inputs and outputs using the multi-objective programming (MOP) structure. In some problems, the inputs might be stochastic while the outputs are deterministic, and vice versa. In such cases, we propose molti-objective DEA-R model, because in some cases (e.g., when unnecessary and irrational weights by the BCC model reduces the efficiency score), an efficient DMU is introduced as inefficient by the BCC model, whereas the DMU is considered efficient by the DEA-R model. In some other case, only the ratio of stochastic data may be available (e.g; the ratio of stochastic inputs to stochastic outputs). Thus, we provide multi objective DEA model without explicit outputs and prove that in-put oriented MOP DEA-R model in the invariable return to scale case can be replacing by MOP- DEA model without explicit outputs in the variable return to scale and vice versa. Using the interactive methods for solving the proposed model, yields a projection corresponding to the viewpoint of the DM and the analyst, which is nearer to reality and more practical. Finally, an application is provided.

Keywords: DEA, MOLP, STOCHASTIC, DEA-R

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Authors: Zahra Bahadoran, Parvin Mirmiran, Fereidoun Azizi

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Background: Higher consumption of white rice has been suggested as a risk factor for development of metabolic abnormalities. In this study we investigated the association between consumption of white rice and the 3-year occurrence of metabolic syndrome (MetS) in adults with and without abdominal obesity. Methods: This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study on 1476 adults, aged 19-70 years. Dietary intakes were measured, using a 168-food items validated semi-quantitative food frequency questionnaire at baseline. Biochemical and anthropometric measurements were evaluated at both baseline (2006-2008) and after 3-year follow-up (2009-2011). MetS and its components were defined according to the diagnostic criteria proposed by NCEP ATP III, and the new cutoff points of waist circumference for Iranian adults. Multiple logistic regression models were used to estimate the occurrence of the MetS in each quartile of white rice consumption. Results: The mean age of participants was 37.8±12.3 y, and mean BMI was 26.0±4.5 kg/m2 at baseline. The prevalence of MetS in subjects with abdominal obesity was significantly higher (40.9 vs. 16.2%, P<0.01). There was no significant difference in white rice consumption between the two groups. Mean daily intake of white rice was 93±59, 209±58, 262±60 and 432±224 g/d, in the first to fourth quartiles of white rice, respectively. Stratified analysis by categories of waist circumference showed that higher consumption of white rice was more strongly related to the risk of metabolic syndrome in participants who had abdominal obesity (OR: 2.34, 95% CI:1.14-4.41 vs. OR:0.99, 95% CI:0.60-1.65) Conclusion: We demonstrated that higher consumption of white rice may be a risk for development of metabolic syndrome in adults with abdominal obesity.

Keywords: white rice, abdominal obesity, metabolic syndrome, food science, triglycerides

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Authors: A. Almohammedi, A. J. Hudson, N. M. Storey

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Following ischaemia/reperfusion injury, as in a myocardial infraction, cardiac myocytes undergo oxidative stress which leads to several potential outcomes including; necrotic or apoptotic cell death or dysregulated calcium homeostasis or disruption of the electron transport chain. Several studies have shown that nitric oxide donors protect cardiomyocytes against ischemia and reperfusion. However until present, the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes is not fully understood and has not been investigated before using Raman spectroscopy. For these reasons, the aim of this study was to develop a novel technique, pre-resonance Raman spectroscopy, to investigate the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes exposed to metabolic inhibition and re-energisation. The results demonstrated the first time that Raman microspectroscopy technique has the capability to monitor the metabolic inhibition of cardiomyocytes and to monitor the effectiveness of cardioprotection by nitric oxide donor prior to metabolic inhibition of cardiomyocytes. Metabolic inhibition and reenergisation were used in this study to mimic the low and high oxygen levels experienced by cells during ischaemic and reperfusion treatments. A laser wavelength of 488 nm used in this study has been found to provide the most sensitive means of observe the cellular mechanisms of myoglobin during nitric oxide donor preconditioning, metabolic inhibition and re-energisation and did not cause any damage to the cells. The data also highlight the considerably different cellular responses to metabolic inhibition to ischaemia. Moreover, the data has been shown the relationship between the release of myoglobin and chemical ischemia where that the release of myoglobin from the cell only occurred if a cell did not recover contractility.

Keywords: ex vivo biospectroscopy, Raman spectroscopy, biophotonics, cardiomyocytes, ischaemia / reperfusion injury, cardioprotection, nitric oxide donor

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Authors: Amany Ragab, Nashwa Khairat Abousamra, Omayma Saleh, Asmaa Higazy

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Insulin resistance syndrome has been shown to be associated with many coagulation and fibrinolytic proteins and these associations suggest that some coagulation and fibrinolytic proteins have a role in atherothrombotic disorders. This study was conducted to determine the levels of some of the haemostatic parameters in subjects having metabolic syndrome and to correlate these values with the anthropometric and metabolic variables associated with this syndrome. The study included 46 obese non diabetic subjects of whom 28 subjects(group1) fulfilled the ATP III criteria of the metabolic syndrome and 18 subjects (group2) did not have metabolic syndrome as well as 14 lean subjects (group 3) of matched age and sex as a control group. Clinical and laboratory evaluation of the study groups stressed on anthropometric measurements (weight, height, body mass index, waist circumference, and sagittal abdominal diameter), blood pressure, and laboratory measurements of fasting plasma glucose, fasting insulin, serum lipids, tissue plasminogen activator (t-PA), antithrombin III activity (ATIII), protein C and von Willebrand factor (vWf) antigen. There was significant increase in the concentrations of t-PA and vWf antigens in subjects having metabolic syndrome (group 1) in comparison to the other groups while there were non-significant changes in the levels of protein C antigen and AT III activity. Both t-PA and vWf showed significant correlation with HOMA-IR as a measure of insulin sensitivity. The t-PA showed also significant correlation with most of the variables of metabolic syndrome including waist circumference, BMI, systolic blood pressure, fasting plasma glucose, fasting insulin, and HDL cholesterol. On the other hand, vWf showed significant correlations with fasting plasma glucose, fasting insulin and sagital abdominal diameter, with non-significant correlations with the other variables. Haemostatic and fibrinolytic parameters should be included in the features and characterization of the insulin resistance syndrome. t-PA and vWf antigens concentrations were increased in subjects with metabolic syndrome and correlated with the HOMA-IR measure of insulin sensitivity. Taking into consideration that both t-PA and vWf are mainly released from vascular endothelium, these findings could be an indicator of endothelial dysfunction in that group of subjects.

Keywords: insulin resistance, obesity, metabolic syndrome, coagulation

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Authors: Karina C. Azzolin, Luis E. Kosteski, Alisson S. Milani, Raquel C. Zydeck

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This work aims to represent Numerically tests experimentally developed in reduced scale walls with horizontal and inclined cuts by using the Lattice Discrete Element Method (LDEM) implemented On de Abaqus/explicit environment. The cuts were performed with depths of 20%, 30%, and 50% On the walls subjected to centered and eccentric loading. The parameters used to evaluate the numerical model are its strength, the failure mode, and the in-plane and out-of-plane displacements.

Keywords: structural masonry, wall chases, small scale, numerical model, lattice discrete element method

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Authors: Mi Kyeong Yu, Seon Jeong Lee, So Young Kim, Bora Choi, Young Mi Lee, Su-Jung Cho, Je Tae Woo, Myung-Sook Choi

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A high-fat diet (HFD) induces excessive fat accumulation in white adipose tissue (WAT), which increases metabolic disorders such as obesity, dyslipidemia and type 2 diabetes. Many plants are known to have effects that improve metabolic disorders. Therefore, the aim of this present study is to investigate the effect of nepodin-enrich plant extract on dyslipidemia, hyperglycemia in high fat diet-induced C57BL/6J mice. Male C57BL/6J mice were randomly divided into two groups, and fed HFD (20% fat, w/w) or HFD supplemented with nepodin-enrich plant extract (NPE 0.005%, w/w) for 16 weeks. Body weight and food intake were measured every week. And we also analysed metabolic rates (respiratory quotient), blood glucose level, and plasma high-density lipoprotein (HDL)-cholesterol, free fatty acid, apolipoprotein (apo) A-1 and apo B levels. Food intakes and body weights were not different between NPE group and HFD group, while plasma apo B, free fatty acid levels, and blood glucose concentration were significantly decreased in NPE group than in HFD group. Furthermore, plasma apo A and HDL-cholesterol levels in NPE group were remarkably increased than in HFD group. Metabolic rates (respiratory quotient) were significantly increased in NPE group than in HFD group. These results indicate that NPE can alleviate dyslipidemia, hyperglycemia. Further studies are required to identify the effects of NPE on metabolic disorders.

Keywords: dyslipidemia, hyperglycemia, metabolic disorders, nepodin enrich plant extract

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Authors: Hala M. Abdelkarem, Abeer H. Gafeer

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The metabolic syndrome (Mts) is a constellation of risk factors. The main objective of this study is to compare the ameliorating effect of metformin, lipitor, orilstate, lipoic acid and carnitin on insulin, lipid profile, leptin, adenonectin levels in metabolic syndrom (high fructose fed rats HF). Seventy male albino rats were divided into seven groups. G1: normal control. G2: G7 rats fed HF for 8wks. After four wk HF feeding, G3, G4, G5, G6, and G7 were orally administered (200 mg/kg daily) metformin, lipitor, orilstate, lipoic acid and carnitin respectively. All drugs were adminiseterd once daily. After 8 weeks of feeding, a significant increase in blood glucose level was observed in HF fed rats compared to normal rats, but this increase was significantly decreased after administration of metformin and lipitor. The raised of serum insulin level in HF fed rats was significantly decreased after administration of lipoic, carnitin, metformin. Significant higher concentrations of triglycerides (TG), total cholesterol & low density lipoprotein cholesterol (LDL- C) were observed in HF fed rats and these increases were significantly lowered after the administration of all the previous drugs. There was a significant decrease in serum high density lipoprotein cholesterol (HDL-C) in HF group administration of all drugs alleviates this reduction. The increased of serum leptin level in HF group was decreased significantly in met and orilstate groups. Whereas the reduction of serum adiponectin level in HF fed rats was increased in Lipitor, carnitin, orilstate groups. These data suggested that benefial effect of metformin, lipitor, orilstate, lipoic acid carnitin in reducing risk for people with decreased insulin sensitivity, increased oxidative stress and hyperlipidemia such as those with the metabolic syndrome or type 2 diabetes.

Keywords: metabolic syndrome, diabetes, proinflammation, antioxidants

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Authors: Aamir Mubashar, Ibrahim Fiaz

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This research presents a three-dimensional finite element modelling strategy to simulate damage in a quasi-static three-point bending analysis of woven twill 2/2 type carbon fibre reinforced plastic (CFRP) composite on a micro-meso level using cohesive zone modelling technique. A meso scale finite element model comprised of a number of plies was developed in the commercial finite element code Abaqus/explicit. The interfaces between the plies were explicitly modelled using cohesive zone elements to allow for debonding by crack initiation and propagation. Load-deflection response of the CRFP within the quasi-static range was obtained and compared with the data existing in the literature. This provided validation of the model at the global scale. The outputs resulting from the global model were then used to develop a simulation model capturing the micro-meso scale material features. The sub-model consisted of a refined mesh representative volume element (RVE) modelled in texgen software, which was later embedded with cohesive elements in the finite element software environment. The results obtained from the developed strategy were successful in predicting the overall load-deflection response and the damage in global and sub-model at the flexure limit of the specimen. Detailed analysis of the effects of the micro-scale features was carried out.

Keywords: woven composites, multi-scale modelling, cohesive zone, finite element model

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Authors: Quyen Vu Dang Ha, Oanh Truong Thi, Thuoc Tran Linh, Kent Carpenter, Thinh Doan Vu, Binh Dang Thuy

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Enzyme restriction site associated DNA (EzRAD) has recently emerged as a promising genomic approach for exploring fish genetic diversity on a genome-wide scale. This is a simplified method for genomic genotyping in non-model organisms and applied for SNPs discovery in the population genetics of freshwater and marine fish in the South of Vietnam. The observations of regional-scale differentiation of commercial freshwater fish (smallscale croakers Boesemania microlepis) and marine fish (emperor Lethrinus lentjan) are clarified. Samples were collected along Hau River and coastal area in the south and center Vietnam. 52 DNA samples from Tra Vinh, An Giang Province for Boesemania microlepis and 34 DNA samples of Lethrinus lentjan from Phu Quoc, Nha Trang, Da Nang Province were used to prepare EzRAD libraries from genomic DNA digested with MboI and Sau3AI. A pooled sample of regional EzRAD libraries was sequenced using the HiSeq 2500 Illumina platform. For Boesemania microlepis, the small scale population different from upstream to downstream of Hau river were detected, An Giang population exhibited less genetic diversity (SNPs per individual from 14 to 926), in comparison to Tra Vinh population (from 11 to 2172). For Lethrinus lentjan, the result showed the minor difference between populations in the Northern and the Southern Mekong River. The numbers of contigs and SNPs vary from 1315 to 2455 and from 7122 to 8594, respectively (P ≤ 0.01). The current preliminary study reveals regional scale population disconnection probably reflecting environmental changing. Additional sampling and EzRad libraries need to be implemented for resource management in the Mekong Delta.

Keywords: Boesemania microlepis, EzRAD, Lethrinus lentjan, SNPs

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Authors: Aishik Deb, Rituparna Sinha

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We have developed an algorithm to detect the abnormal segment/"structural variation in the genome across a number of samples. We have worked on simulated as well as real data from the BAM Files and have designed a segmentation algorithm where abnormal segments are detected. This algorithm aims to improve the accuracy and performance of the existing CNV-CH algorithm. The next-generation sequencing (NGS) approach is very fast and can generate large sequences in a reasonable time. So the huge volume of sequence information gives rise to the need for Big Data and parallel approaches of segmentation. Therefore, we have designed a map-reduce approach for the existing CNV-CH algorithm where a large amount of sequence data can be segmented and structural variations in the human genome can be detected. We have compared the efficiency of the traditional and map-reduce algorithms with respect to precision, sensitivity, and F-Score. The advantages of using our algorithm are that it is fast and has better accuracy. This algorithm can be applied to detect structural variations within a genome, which in turn can be used to detect various genetic disorders such as cancer, etc. The defects may be caused by new mutations or changes to the DNA and generally result in abnormally high or low base coverage and quantification values.

Keywords: cancer detection, convex hull segmentation, map reduce, next generation sequencing

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Authors: Juan Huang, Nanqu Huang, Jingshan Shi, Yu Qiu

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Objectives: There are pathophysiological connections between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), and research on drugs with hypoglycemic and beta-amyloid (Aβ)-clearing effects have great therapeutic potential for AD. Dendrobium nobile Lindl. Alkaloids (DNLA) as one of the active compounds of Dendrobium nobile Lindl. In this study, we attempted to verify the hypoglycemic effect and investigate the effects of DNLA on the amyloid precursor protein (APP) metabolic pathway of the hippocampus in db/db mice. Methods: 4-weeks-old male C57BL/KsJ mice were the control group. And the same age and sexuality db/db mice were: model, DNLA-L (20 mg/kg), DNLA-M (40 mg/kg), and DNLA-H (80 mg/kg). After, mice were treated with different concentrations of DNLA for 17 weeks. The fasting blood glucose (FBG) was detected by glucose oxidase assay every week from the 4th to last week. The protein expression of β-amyloid 1-42 (Aβ1-42), β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and APP were examined by Western blotting. Results: The concentration of FBG and the protein expression of Aβ1-42, BACE1, and APP were increased in the hippocampus of the model group. Moreover, DNLA not only significantly decreased the concentration of FBG but also reduced the protein expressions of Aβ1-42, BACE1 and APP in the hippocampus of db/db mice in a dose-dependent manner. Conclusions: DNLA can decrease the protein expressions of Aβ1-42 in the hippocampus of db/db mice, and the mechanism may be involved in the APP metabolic pathway.

Keywords: Alzheimer's disease, type 2 diabetes mellitus, β-site amyloid precursor protein-cleaving enzyme 1, traditional Chinese medicines, beta-amyloid

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Authors: Li-Hsueh Chen

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Efficient operation is more and more important for managers of hotels. Unlike the manufacturing industry, hotels cannot store their products. In addition, many hotels provide room service, and food and beverage service simultaneously. When efficiencies of hotels are evaluated, the internal structure should be considered. Hence, based on the operational characteristics of hotels, this study proposes a DEA model to simultaneously assess the efficiencies among the room production division, food and beverage production division, room service division and food and beverage service division. However, not only the enhancement of efficiency but also the adjustment of scale can improve the performance. In terms of the adjustment of scale, scale elasticity or returns to scale can help to managers to make decisions concerning expansion or contraction. In order to construct a reasonable approach to measure the efficiencies and scale elasticities of hotels, this study builds an alternative variable-returns-to-scale-based two-stage network DEA model with the combination of parallel and series structures to explore the scale elasticities of the whole system, room production division, food and beverage production division, room service division and food and beverage service division based on the data of international tourist hotel industry in Taiwan. The results may provide valuable information on operational performance and scale for managers and decision makers.

Keywords: efficiency, scale elasticity, network data envelopment analysis, international tourist hotel

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Authors: Jun Ren, Zhen-Hua Ming, He-Feng Huang, Jian-Zhong Sheng

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Adverse intrauterine stimulus during critical or sensitive periods in early life, may lead to health risk not only in later life span, but also further generations. Intrauterine hyperglycaemia, as a major feature of gestational diabetes mellitus (GDM), is a typical adverse environment for both F1 fetus and F1 gamete cells development. However, there is scare information of phenotypic difference of metabolic memory between somatic cells and germ cells exposed by intrauterine hyperglycaemia. The direct transmission effect of intrauterine hyperglycaemia per se has not been assessed either. In this study, we built a GDM mice model and selected male GDM offspring without pre-diabetic phenotype as our founders, to exclude postnatal diabetic influence on gametes, thereby investigate the direct transmission effect of intrauterine hyperglycaemia exposure on F2 offspring, and we further compared the metabolic difference of affected F1-GDM male offspring and F2 offspring. A GDM mouse model of intrauterine hyperglycemia was established by intraperitoneal injection of streptozotocin after pregnancy. Pups of GDM mother were fostered by normal control mothers. All the mice were fed with standard food. Male GDM offspring without metabolic dysfunction phenotype were crossed with normal female mice to obtain F2 offspring. Body weight, glucose tolerance test, insulin tolerance test and homeostasis model of insulin resistance (HOMA-IR) index were measured in both generations at 8 week of age. Some of F1-GDM male mice showed impaired glucose tolerance (p < 0.001), none of F1-GDM male mice showed impaired insulin sensitivity. Body weight of F1-GDM mice showed no significance with control mice. Some of F2-GDM offspring exhibited impaired glucose tolerance (p < 0.001), all the F2-GDM offspring exhibited higher HOMA-IR index (p < 0.01 of normal glucose tolerance individuals vs. control, p < 0.05 of glucose intolerance individuals vs. control). All the F2-GDM offspring exhibited higher ITT curve than control (p < 0.001 of normal glucose tolerance individuals, p < 0.05 of glucose intolerance individuals, vs. control). F2-GDM offspring had higher body weight than control mice (p < 0.001 of normal glucose tolerance individuals, p < 0.001 of glucose intolerance individuals, vs. control). While glucose intolerance is the only phenotype that F1-GDM male mice may exhibit, F2 male generation of healthy F1-GDM father showed insulin resistance, increased body weight and/or impaired glucose tolerance. These findings imply that intrauterine hyperglycaemia exposure affects germ cells and somatic cells differently, thus F1 and F2 offspring demonstrated distinct metabolic dysfunction phenotypes. And intrauterine hyperglycaemia exposure per se has a strong influence on F2 generation, independent of postnatal metabolic dysfunction exposure.

Keywords: inheritance, insulin resistance, intrauterine hyperglycaemia, offspring

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

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Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system can facilitate targeted genome editing in organisms. Dual or single guide RNA (gRNA) can program the Cas9 nuclease to cut target DNA in particular areas; thus, introducing concise mutations either via error-prone non-homologous end-joining repairing or via incorporating foreign DNAs by homologous recombination between donor DNA and target area. In spite of high demand of such promising technology, developing a well-organized procedure in order for reliable mining of potential target sites for gRNAs in large genomic data is still challenging. Hence, we aimed to perform high-throughput detection of target sites by specific PAMs for not only common Streptococcus pyogenes (SpCas9) but also for Neisseria meningitides (NmCas9) CRISPR-Cas systems. Previous research confirmed the successful application of such RNA-guided Cas9 orthologs for effective gene targeting and subsequently genome manipulation. However, Cas9 orthologs need their particular PAM sequence for DNA cleavage activity. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of the target site for the two orthogonals of Cas9 protein, we created a reliable procedure to explore possible gRNA sequences. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. Finally, a complete list of all potential gRNAs along with their locations, strands, and PAMs sequence orientation can be provided for both SpCas9 as well as another potential Cas9 ortholog (NmCas9). The artificial design of potential gRNAs in a genome of interest can accelerate functional genomic studies. Consequently, the application of such novel genome editing tool (CRISPR/Cas technology) will enhance by presenting increased versatility and efficiency.

Keywords: CRISPR/Cas9 genome editing, gRNA mining, SpCas9, NmCas9

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Authors: Dino Carpentras, Alejandro Dinkelberg, Michael Quayle

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Opinion dynamics models use an agent-based modeling approach to model people’s opinions. Model's properties are usually explored by testing the two 'degrees of freedom': the interaction rule and the network topology. The latter defines the connection, and thus the possible interaction, among agents. The interaction rule, instead, determines how agents select each other and update their own opinion. Here we show the existence of the third degree of freedom. This can be used for turning one model into each other or to change the model’s output up to 100% of its initial value. Opinion dynamics models represent the evolution of real-world opinions parsimoniously. Thus, it is fundamental to know how real-world opinion (e.g., supporting a candidate) could be turned into a number. Specifically, we want to know if, by choosing a different opinion-to-number transformation, the model’s dynamics would be preserved. This transformation is typically not addressed in opinion dynamics literature. However, it has already been studied in psychometrics, a branch of psychology. In this field, real-world opinions are converted into numbers using abstract objects called 'scales.' These scales can be converted one into the other, in the same way as we convert meters to feet. Thus, in our work, we analyze how this scale transformation may affect opinion dynamics models. We perform our analysis both using mathematical modeling and validating it via agent-based simulations. To distinguish between scale transformation and measurement error, we first analyze the case of perfect scales (i.e., no error or noise). Here we show that a scale transformation may change the model’s dynamics up to a qualitative level. Meaning that a researcher may reach a totally different conclusion, even using the same dataset just by slightly changing the way data are pre-processed. Indeed, we quantify that this effect may alter the model’s output by 100%. By using two models from the standard literature, we show that a scale transformation can transform one model into the other. This transformation is exact, and it holds for every result. Lastly, we also test the case of using real-world data (i.e., finite precision). We perform this test using a 7-points Likert scale, showing how even a small scale change may result in different predictions or a number of opinion clusters. Because of this, we think that scale transformation should be considered as a third-degree of freedom for opinion dynamics. Indeed, its properties have a strong impact both on theoretical models and for their application to real-world data.

Keywords: degrees of freedom, empirical validation, opinion scale, opinion dynamics

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Authors: Ghulam Muhammad Ali

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Unveiling of genes involved in drought and root architecture using transcriptomic analyses remained fragmented for further improvement of wheat through genome editing. The purpose of this research endeavor was to unveil the variations in different genes implicated in drought tolerance and root architecture in wheat through RNA-seq data analysis. In this study seedlings of 8 days old, 6 cultivars of wheat namely, Batis, Blue Silver, Local White, UZ888, Chakwal 50 and Synthetic wheat S22 were subjected to transcriptomic analysis for root and shoot genes. Total of 12 RNA samples was sequenced by Illumina. Using updated wheat transcripts from Ensembl and IWGC references with 54,175 gene models, we found that 49,621 out of 54,175 (91.5%) genes are expressed at an RPKM of 0.1 or more (in at least 1 sample). The number of genes expressed was higher in Local White than Batis. Differentially expressed genes (DEG) were higher in Chakwal 50. Expression-based clustering indicated conserved function of DRO1and RPK1 between Arabidopsis and wheat. Dendrogram showed that Local White is sister to Chakwal 50 while Batis is closely related to Blue Silver. This study flaunts transcriptomic sequence variations in different cultivars that showed mutations in genes associated with drought that may directly contribute to drought tolerance. DRO1 and RPK1 genes were fetched/isolated for genome editing. These genes are being edited in wheat through CRISPR-Cas9 for yield enhancement.

Keywords: transcriptomic, wheat, genome editing, drought, CRISPR-Cas9, yield enhancement

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Authors: Jamal Choudhry, Roland Larsson, Andreas Almqvist

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A multi-scale flash temperature model has been developed and validated against existing work. The core strength of the proposed model is that it can be adapted to predict flash contact temperatures occurring in various types of sliding systems. In this paper, it is used to investigate how different surface roughness parameters affect the flash temperatures. The results show that for decreasing Hurst exponents as well as increasing values of the high-frequency cut-off, the maximum flash temperature increases. It was also shown that the effect of surface roughness does not influence the average interface temperature. The model predictions were validated against data from an experiment conducted in a pin-on-disc machine. This also showed the importance of including a wear model when simulating flash temperature development in a sliding system.

Keywords: multiscale, pin-on-disc, finite element method, flash temperature, surface roughness

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

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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: Vinod Kumar Gupta, Narendrakumar M. Chaudhari, Suchismitha Iskepalli, Chitra Dutta

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Background-The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference draft genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. Results-The analysis reveals the exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from the human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. The pan-genome for Prevotella remains “open”. Distribution of various functional COG categories differs appreciably among the habitat-specific genes, within Prevotella pan-genome and between the GIT-derived Bacteroides and Prevotella. The skin and GIT isolates of Prevotella are enriched in singletons involved in Signal transduction mechanisms, while the UGT and oral isolates show higher representation of the Defense mechanisms category. No niche-specific variations could be observed in the distribution of KEGG pathways. Conclusion-Prevotella may have developed distinct genetic strategies for adaptation to different anatomical habitats through selective, niche-specific acquisition and elimination of suitable gene-families. In addition, individual microorganisms tend to develop their own distinctive adaptive stratagems through large repertoires of singletons. Such in situ, habitat-driven refurbishment of the genetic makeup can impart substantial intra-lineage genome diversity within the microbes without perturbing their general taxonomic heritage.

Keywords: body niche adaptation, human microbiome, pangenome, Prevotella

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Authors: Yunfeng Shan, Xiaoliang Wang, Youjun Zhou

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Whole-genome data from two lungfish species, along with other species, present a valuable opportunity to re-investigate the longstanding debate regarding the evolutionary relationships among tetrapods, lungfishes, and coelacanths. However, the use of bootstrap support has become outdated for large-scale phylogenomic data. Without robust phylogenetic support, the phylogenetic trees become meaningless. Therefore, it is necessary to re-evaluate the phylogenies of tetrapods, lungfishes, and coelacanths using novel measures of phylogenetic support specifically designed for phylogenomic data, as the previous phylogenies were based on 100% bootstrap support. Our findings consistently provide strong evidence favoring lungfish as the closest living relative of tetrapods. This conclusion is based on high internode certainty, relative gene support, and high gene concordance factor. The evidence stems from five previous datasets derived from lungfish transcriptomes. These results yield fresh insights into the three hypotheses regarding the phylogenies of tetrapods, lungfishes, and coelacanths. Importantly, these hypotheses are not mere conjectures but are substantiated by a significant number of genes. Analyzing real biological data further demonstrates that the inclusion of additional taxa leads to more diverse tree topologies. Consequently, gene trees and species trees may not be identical even when whole-genome sequencing data is utilized. However, it is worth noting that many gene trees can accurately reflect the species tree if an appropriate number of taxa, typically ranging from six to ten, are sampled. Therefore, it is crucial to carefully select the number of taxa and an appropriate outgroup, such as slow-evolving species, while excluding fast-evolving taxa as outgroups to mitigate the adverse effects of long-branch attraction and achieve an accurate reconstruction of the species tree. This is particularly important as more whole-genome sequencing data becomes available.

Keywords: novel measures of phylogenetic support for phylogenomic data, gene concordance factor confidence, relative gene support, internode certainty, origin of tetrapods

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Authors: Ahmet Karakuş, Akif Can Kilic, Emre Alptekin

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A growing number of studies have been conducted to determine how well-being may be predicted using well-designed models. It is necessary to investigate the backgrounds of features in order to construct a viable Subjective Well-Being (SWB) model. We have picked the suitable variables from the literature on SWB that are acceptable for real-world data instructions. The goal of this work is to evaluate the model by feeding it with SWB characteristics and then categorizing the stress levels using machine learning methods to see how well it performs on a real dataset. Despite the fact that it is a multiclass classification issue, we have achieved significant metric scores, which may be taken into account for a specific task.

Keywords: machine learning, multiclassification problem, subjective well-being, perceived stress scale

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Authors: Adel M. Zakri, Mohammed A. Al-Saleh, Judith. K. Brown, Ali M. Idris

Abstract:

Betasatellites are small circular single stranded DNA molecules found associated with begomoviruses on field symptomatic plants. Their genome size is about half that of the helper begomovirus, ranging between 1.3 and 1.4 kb. The helper begomoviruses are usually members of the family Geminiviridae. Okra leaves showing vein thickening were collected from okra plants growing in Jazan, Saudi Arabia. Total DNA was extracted from leaves and used as a template to amplify circular DNA using rolling circle amplification (RCA) technology. Products were digested with PstI to linearize the helper viral genome(s), and associated DNA satellite(s), yielding a 2.8kbp and 1.4kbp fragment, respectively. The linearized fragments were cloned into the pGEM-5Zf (+) vector and subjected to DNA sequencing. The 2.8 kb fragment was identified as Cotton leaf curl Gezira virus genome, at 2780bp, an isolate closely related to strains reported previously from Saudi Arabia. A clone obtained from the 1.4 kb fragments he 1.4kb was blasted to GeneBank database found to be a betasatellite. The genome of betasatellite was 1357-bp in size. It was found to be a recombinant containing one fragment (877-bp) that shared 91% nt identity with Cotton leaf curl Gezira betasatellite [KM279620], and a smaller fragment [133--bp) that shared 86% nt identity with Tomato leaf curl Sudan virus [JX483708]. This satellite is thus a recombinant between a malvaceous-infecting satellite and a solanaceous-infecting begomovirus.

Keywords: begomovirus, betasatellites, cotton leaf curl Gezira virus, okra plants

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