Artificial neural network model with the parameter tuning assisted by a differential evolution technique: the study of the hold up of the slurry flow in a pipeline

This paper describes a robust hybrid artificial neural network (ANN) methodology which can offer a superior performance for the important process engineering problems. The method incorporates a hybrid artificial neural network and differential evolution technique (ANN-DE) for the efficient tuning of ANN meta parameters. The algorithm has been applied for the prediction of the hold up of the solid liquid slurry flow. A comparison with selected correlations in the literature showed that the developed ANN correlation noticeably improved the prediction of hold up over a wide range of operating conditions, physical properties, and pipe diameters

Genotyping-by-sequencing and multilocation evaluation of two interspecific backcross populations identify QTLs for yield-related traits in pigeonpea

This study has identified single-nucleotide polymorphism (SNP) markers associated with nine yield-related traits in pigeonpea by using two backcross populations (BP) developed through interspecific crosses and evaluating them at two locations and 3 years. In both the populations, markers have shown strong segregation distortion; therefore, a quantitative trait locus (QTL) mapping mixed model was used. A total of 86 QTLs explaining 12–21% phenotypic variation were detected in BP-1. On the other hand, 107 QTLs explaining 11–29% phenotypic variation were detected in BP-2. Although most QTLs were environment and trait specific, few stable and consistent QTLs were also detected. Interestingly, 11 QTLs in BP-2 were associated with more than one trait. Among these QTLs, eight QTLs associated with days to 50% flowering and days to 75% maturity were located on CcLG07. One SNP “S7_14185076” marker in BP-2 population has been found associated with four traits, namely days to 50% flowering, days to 75% maturity, primary branches per plant and secondary branches per plant with positive additive effect. Hence, the present study has not only identified QTLs for yield-related traits, but also discovered novel alleles from wild species, which can be used for improvement of traits through genomics-assisted breeding

Genotyping-by-sequencing of three mapping populations for identification of candidate genomic regions for resistance to sterility mosaic disease in pigeonpea

Sterility mosaic disease (SMD) is one of the serious production constraints that may lead to complete yield loss in pigeonpea. Three mapping populations including two recombinant inbred lines and one F2, were used for phenotyping for SMD resistance at two locations in three different years. Genotyping-by-sequencing approach was used for simultaneous identification and genotyping of SNPs on above mentioned populations. In total, 212,464, 89,699 and 64,798 SNPs were identified in ICPL 20096 × ICPL 332 (PRIL_B), ICPL 20097 × ICP 8863 (PRIL_C) and ICP 8863 × ICPL 87119 (F2) respectively. By using high-quality SNPs, genetic maps were developed for PRIL_B (1,101 SNPs; 921.21 cM), PRIL_C (484 SNPs; 798.25 cM) and F2 (996 SNPs; 1,597.30 cM) populations. The average inter marker distance on these maps varied from 0.84 cM to 1.65 cM, which was lowest in all genetic mapping studies in pigeonpea. Composite interval mapping based QTL analysis identified a total of 10 QTLs including three major QTLs across the three populations. The phenotypic variance of the identified QTLs ranged from 3.6 to 34.3%. One candidate genomic region identified on CcLG11 seems to be promising QTL for molecular breeding in developing superior lines with enhanced resistance to SMD

Indel-seq: a fast-forward genetics approach for identification of trait-associated putative candidate genomic regions and its application in pigeonpea (Cajanus cajan)

Identification of candidate genomic regions associated with target traits using conventional mapping methods is challenging and time-consuming. In recent years, a number of single nucleotide polymorphism (SNP)-based mapping approaches have been developed and used for identification of candidate/putative genomic regions. However, in the majority of these studies, insertion–deletion (Indel) were largely ignored. For efficient use of Indels in mapping target traits, we propose Indel-seq approach, which is a combination of whole-genome resequencing (WGRS) and bulked segregant analysis (BSA) and relies on the Indel frequencies in extreme bulks. Deployment of Indel-seq approach for identification of candidate genomic regions associated with fusarium wilt (FW) and sterility mosaic disease (SMD) resistance in pigeonpea has identified 16 Indels affecting 26 putative candidate genes. Of these 26 affected putative candidate genes, 24 genes showed effect in the upstream/downstream of the genic region and two genes showed effect in the genes. Validation of these 16 candidate Indels in other FW- and SMD-resistant and FW- and SMD-susceptible genotypes revealed a significant association of five Indels (three for FW and two for SMD resistance). Comparative analysis of Indel-seq with other genetic mapping approaches highlighted the importance of the approach in identification of significant genomic regions associated with target traits. Therefore, the Indel-seq approach can be used for quick and precise identification of candidate genomic regions for any target traits in any crop species

Construction of genotyping-by-sequencing based high-density genetic maps and QTL mapping for fusarium wilt resistance in pigeonpea

Fusarium wilt (FW) is one of the most important biotic stresses causing yield losses in pigeonpea. Genetic improvement of pigeonpea through genomics-assisted breeding (GAB) is an economically feasible option for the development of high yielding FW resistant genotypes. In this context, two recombinant inbred lines (RILs) (ICPB 2049 × ICPL 99050 designated as PRIL_A and ICPL 20096 × ICPL 332 designated as PRIL_B) and one F2 (ICPL 85063 × ICPL 87119) populations were used for the development of high density genetic maps. Genotyping-by-sequencing (GBS) approach was used to identify and genotype SNPs in three mapping populations. As a result, three high density genetic maps with 964, 1101 and 557 SNPs with an average marker distance of 1.16, 0.84 and 2.60 cM were developed in PRIL_A, PRIL_B and F2, respectively. Based on the multi-location and multi-year phenotypic data of FW resistance a total of 14 quantitative trait loci (QTLs) including six major QTLs explaining >10% phenotypic variance explained (PVE) were identified. Comparative analysis across the populations has revealed three important QTLs (qFW11.1, qFW11.2 and qFW11.3) with upto 56.45% PVE for FW resistance. This is the first report of QTL mapping for FW resistance in pigeonpea and identified genomic region could be utilized in GAB

Next-generation sequencing for identification of candidate genes for Fusarium wilt and sterility mosaic disease in pigeonpea (Cajanus cajan)

To map resistance genes for Fusarium wilt (FW) and sterility mosaic disease (SMD) in pigeonpea, sequencing-based bulked segregant analysis (Seq-BSA) was used. Resistant (R) and susceptible (S) bulks from the extreme recombinant inbred lines of ICPL 20096 × ICPL 332 were sequenced. Subsequently, SNP index was calculated between R- and S-bulks with the help of draft genome sequence and reference-guided assembly of ICPL 20096 (resistant parent). Seq-BSA has provided seven candidate SNPs for FW and SMD resistance in pigeonpea. In parallel, four additional genotypes were re-sequenced and their combined analysis with R- and S-bulks has provided a total of 8362 nonsynonymous (ns) SNPs. Of 8362 nsSNPs, 60 were found within the 2-Mb flanking regions of seven candidate SNPs identified through Seq-BSA. Haplotype analysis narrowed down to eight nsSNPs in seven genes. These eight nsSNPs were further validated by re-sequencing 11 genotypes that are resistant and susceptible to FW and SMD. This analysis revealed association of four candidate nsSNPs in four genes with FW resistance and four candidate nsSNPs in three genes with SMD resistance. Further, In silico protein analysis and expression profiling identified two most promising candidate genes namely C.cajan_01839 for SMD resistance and C.cajan_03203 for FW resistance. Identified candidate genomic regions/SNPs will be useful for genomics-assisted breeding in pigeonpea

Dysregulated Nephrin in Diabetic Nephropathy of Type 2 Diabetes: A Cross Sectional Study

Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy.Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005).These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets

Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions

BACKGROUND: Metastasis-associated protein 1 (MTA1), a master dual co-regulatory protein is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation and chromatin remodeling. Emerging literature establishes MTA1 to be a valid DNA-damage responsive protein with a significant role in maintaining the optimum DNA-repair activity in mammalian cells exposed to genotoxic stress. This DNA-damage responsive function of MTA1 was reported to be a P53-dependent and independent function. Here, we investigate the influence of P53 on gene regulation function of Mta1 to identify novel gene targets and functions of Mta1. METHODS: Gene expression analysis was performed on five different mouse embryonic fibroblasts (MEFs) samples (i) the Mta1 wild type, (ii) Mta1 knock out (iii) Mta1 knock out in which Mta1 was reintroduced (iv) P53 knock out (v) P53 knock out in which Mta1 was over expressed using Affymetrix Mouse Exon 1.0 ST arrays. Further Hierarchical Clustering, Gene Ontology analysis with GO terms satisfying corrected p-value<0.1, and the Ingenuity Pathway Analysis were performed. Finally, RT-qPCR was carried out on selective candidate genes. SIGNIFICANCE/CONCLUSION: This study represents a complete genome wide screen for possible target genes of a coregulator, Mta1. The comparative gene profiling of Mta1 wild type, Mta1 knockout and Mta1 re-expression in the Mta1 knockout conditions define "bona fide" Mta1 target genes. Further extensive analyses of the data highlights the influence of P53 on Mta1 gene regulation. In the presence of P53 majority of the genes regulated by Mta1 are related to inflammatory and anti-microbial responses whereas in the absence of P53 the predominant target genes are involved in cancer signaling. Thus, the presented data emphasizes the known functions of Mta1 and serves as a rich resource which could help us identify novel Mta1 functions

Rationale and study design of the prospective, longitudinal, observational cohort study “rISk strAtification in end-stage renal disease” (ISAR) study

Background: The ISAR study is a prospective, longitudinal, observational cohort study to improve the cardiovascular risk stratification in endstage renal disease (ESRD). The major goal is to characterize the cardiovascular phenotype of the study subjects, namely alterations in micro-and macrocirculation and to determine autonomic function. Methods/design: We intend to recruit 500 prevalent dialysis patients in 17 centers in Munich and the surrounding area. Baseline examinations include: (1) biochemistry, (2) 24-h Holter Electrocardiography (ECG) recordings, (3) 24-h ambulatory blood pressure measurement (ABPM), (4) 24 h pulse wave analysis (PWA) and pulse wave velocity (PWV), (5) retinal vessel analysis (RVA) and (6) neurocognitive testing. After 24 months biochemistry and determination of single PWA, single PWV and neurocognitive testing are repeated. Patients will be followed up to 6 years for (1) hospitalizations, (2) cardiovascular and (3) non-cardiovascular events and (4) cardiovascular and (5) all-cause mortality. Discussion/conclusion: We aim to create a complex dataset to answer questions about the insufficiently understood pathophysiology leading to excessively high cardiovascular and non-cardiovascular mortality in dialysis patients. Finally we hope to improve cardiovascular risk stratification in comparison to the use of classical and non-classical (dialysis-associated) risk factors and other models of risk stratification in ESRD patients by building a multivariable Cox-Regression model using a combination of the parameters measured in the study

Cardiac lymphatics in health and disease

The lymphatic vasculature, which accompanies the blood vasculature in most organs, is indispensable in the maintenance of tissue fluid homeostasis, immune cell trafficking, and nutritional lipid uptake and transport, as well as in reverse cholesterol transport. In this Review, we discuss the physiological role of the lymphatic system in the heart in the maintenance of cardiac health and describe alterations in lymphatic structure and function that occur in cardiovascular pathology, including atherosclerosis and myocardial infarction. We also briefly discuss the role that immune cells might have in the regulation of lymphatic growth (lymphangiogenesis) and function. Finally, we provide examples of how the cardiac lymphatics can be targeted therapeutically to restore lymphatic drainage in the heart to limit myocardial oedema and chronic inflammation.Peer reviewe