A Commentary on Perceived Need from Indian Perspective

The current Indian health –care scenario is overwhelmed not only with burden of diseases but also with quality of care and expenditures.  The structure of this paper is interwoven around a storyline about a patient and narrations of the active actors involved in the journey of illness including patient himself. The narrations are followed by a commentary as an attempt to decipher the deeper meaning of narration from the population perspectives. The essential aim of this exercise is to establish the necessity of generalist care from a qualitative view-point in Indian context

Modeling and additive manufacturing of biomimetic heterogeneous Scaffold

In this paper, a feature-based bio-CAD modeling of three-dimensional tissue scaffolds by considering spatial distribution of biologically active materials is presented for biomanufacturing and tissue engineering applications. Proposed model is based on uniform distribution of bio-active particles in different regions of scaffold, which is constrained by geometrical and biological features. The proposed method was integrated with a recently developed method of multi-material additive manufacturing of hydrogel structures, for bio-additive manufacturing of the heterogeneous scaffolds. 3D bioprinted heterogeneous scaffolds were provided as an example for physical implementation of developed algorithm to validate the model

Autologous Hematopoietic Stem Cells Are a Preferred Source to Generate Dendritic Cells for Immunotherapy in Multiple Myeloma Patients

In multiple myeloma (MM), dendritic cells (DCs), and their precursors are prone to malignant cell-mediated regulation of function leading to low efficacy of DC vaccine. DCs taken directly from MM patient's body or derived from monocytes are fewer in numbers and are also dysfunctional. Here, we investigated the functionality of Hematopoietic stem cell-derived DCs (SC-DCs) from MM patients. Mature-MM-SC-DCs showed all essential functions like antigen uptake, allogenic T cells simulation and migration comparable to those derived from healthy donor (HD) samples. A comparison of Mo-DCs and SC-DCs obtained from the same MM patients' samples revealed that the expression of IL-6 was higher in the precursors of Mo-DCs leading to their impaired migration. In addition, expression of CCR7 which is responsible for DCs migration was found to be lower in MM-Mo-DCs. The chromatin permissiveness as observed by H3K4me3 histone modification at the Ccr7 promoter in MM-Mo-DCs was significantly lower than those in MM-SC-DCs. Levels of Zbtb46- a hall mark DC transcription factor mRNA was also found to be reduced in MM-Mo-DCs. Cytotoxic T cells generated from MM-SC-DCs from autologous naïve T cells exhibited reduced antitumor activity because the T cells were exhausted. Blocking of CTLA-4 on autologous T cells could partially restore T cell proliferation and activation. Thus, a combination of MM-SC-DC vaccine and anti-CTLA-4 antibody may serve as a better candidate for immunotherapy of MM. This study has implications in increasing the efficacy of cancer immunotherapy in MM

Exploring diffuse radio emission in galaxy clusters and groups with the uGMRT and the SKA

Diffuse radio emission has been detected in a considerable number of galaxy clusters and groups, revealing the presence of pervasive cosmic magnetic fields, and of relativistic particles in the large-scale structure (LSS) of the Universe. Since cluster radio emission is faint and steep spectrum, its observations are largely limited by the instrument sensitivity and frequency of observation, leading to a dearth of information, more so for lower-mass systems. The unprecedented sensitivity of recently commissioned low-frequency radio telescope arrays, aided by the development of advanced calibration and imaging techniques, have helped in achieving unparalleled image quality. At the same time, the development of sophisticated numerical simulations and the availability of supercomputing facilities have paved the way for high-resolution numerical modeling of radio emission, and the structure of the cosmic magnetic fields in LSS, leading to predictions matching the capabilities of observational facilities. In view of these rapidly-evolving scenerio in modeling and observations, in this review, we summarise the role of the new telescope arrays and the development of advanced imaging techniques and discuss the detections of various kinds of cluster radio sources. In particular, we discuss observations of the cosmic web in the form of supercluster filaments, studies of emission in poor clusters and groups of galaxies, and of ultra-steep spectrum sources. We also review the current theoretical understanding of various diffuse cluster radio sources and the associated magnetic field and polarization. As the statistics of detections improve along with our theoretical understanding, we update the source classification schemes based on their intrinsic properties. We conclude by summarising the role of the upgraded GMRT and our expectations from the upcoming Square Kilometre Array (SKA) observatories.Comment: 32 pages, 10 figures, accepted for publication in the Journal of Astrophysics and Astronomy (JoAA) (to appear in the special issue on "Indian participation in the SKA"

Identification and validation of insertion–deletion polymorphisms in pigeonpea

Completely sequenced plant genomes provide scope for designing a large number of genome wide insertion–deletion (InDel) markers, which are useful in various aspects of crop breeding and genetic analysis. With the objective of developing InDel markers from pigeonpea genome, the re-sequencing data of eight MAGIC parental lines were used to identify InDels using Dindel software. As a result, a total of 102,181 InDels were identified. Of these 70158 InDels were found unique. The higher number of InDels were found in intergenic (43%) followed by upstream (26%) and downstream (24%) regions. A total of 6.93 % of Indels were found in the genic region. Out of 70158 InDels, 2,426 (1032 Insertions and 1394 deletions) with ≥20 bp size among different parental lines were selected. Average distribution of selected 2426 InDels was found 220 InDels/LG with maximum number of InDels on CcLG11 (385 InDels) and minimum number of In- Dels on CcLG05 (70 InDels). A set of 293 InDels could assess genetic diversity and establish phylogenetic relationships among 16 parental lines of different mapping populations. Validation of these primer pairs on parental lines of different mapping population resulted in higher amplification success rate (≥83%) with almost 52.04% polymorphism rate among parental lines on 3% agarose gel. The number of alleles per locus ranged from 2 to 9 with an average of 3.8 alleles. Further, to track the genome of parents in complex funnel crossing scheme of pigeonpea MAGIC population at 28-two way, 14-four way and 7-eigth way stages, we have identified unique InDel primers for each of the 8 MAGIC parents. The result showed that InDel markers with their high polymorphic potential in comparison to SSR markers would be preferred candidate markers in various marker-based applications in pigeonpea genetics and breeding

Genome‐wide analysis of epigenetic and transcriptional changes associated with heterosis in pigeonpea

Hybrids are extensively used in agriculture to deliver an increase in yield, yet the molecular basisof heterosis is not well understood. Global DNA methylation analysis, transcriptome analysis andsmall RNA profiling were aimed to understand the epigenetic effect of the changes in geneexpression level in the two hybrids and their parental lines. Increased DNA methylation wasobserved in both the hybrids as compared to their parents. This increased DNA methylation inhybrids showed that majority of the 24-nt siRNA clusters had higher expression in hybrids thanthe parents. Transcriptome analysis revealed that various phytohormones (auxin and salicylicacid) responsive hybrid-MPV DEGs were significantly altered in both the hybrids in comparison toMPV. DEGs associated with plant immunity and growth were overexpressed whereas DEGsassociated with basal defence level were repressed. This antagonistic patterns of gene expressionmight contribute to the greater growth of the hybrids. It was also noticed that some common aswell as unique changes in the regulatory pathways were associated with heterotic growth inboth the hybrids. Approximately 70% and 67% of down-regulated hybrid-MPV DEGs werefound to be differentially methylated in ICPH 2671 and ICPH 2740 hybrid, respectively. Thisreflected the association of epigenetic regulation in altered gene expressions. Our findings alsorevealed that miRNAs might play important roles in hybrid vigour in both the hybrids byregulating their target genes, especially in controlling plant growth and development, defenceand stress response pathways. The above finding provides an insight into the molecularmechanism of pigeonpea heterosis

Molecular mapping of seed protein content in pigeonpea – a drought tolerant crop of the semi-arid tropics

Pigeonpea is a uniquely drought and heat tolerant crop that provides a major source of dietary protein to nearly a billion people in the tropical and semi-arid tropics of the world. Despite its importance as a source of dietary protein the genetic control of its seed protein content (SPC) is poorly understood. The present study used high density linkage maps to identify quantitative trait loci (QTL) associated with SPC and its relationship with 100-seed weight (HSW), seed yield (SY), days to first flower (DTFF) and growth habit (GH). Five F2 mapping populations segregating for SPS including ICP 11605 × ICP 14209, ICP 8863 × ICP 11605, HPL 24 × ICP 11605, ICP 5529 × ICP 11605 and ICP 8863 × ICPL 87119 were genotyped using genotyping-by-sequencing and phenotyped for the traits. The average inter-marker distance on the population-specific maps varied from 1.6cM to 3.5cM.On the basis of the population-specific and consensus linkage maps, 48main effect QTLs (M-QTLs)with phenotypic variance explained (PVE) ranging from 0.7 to 23.5% were detected across five populations, of which 15 M-QTLs were major (PVE≥10). Twenty seven of the M-QTLs could be collapsed into six consensus QTL regions. In addition, 34 epistatic QTLs (E-QTLs) with PVE ranging from 6.3% to 69.8% were detected across populations. Co-localization of M-QTLs and E-QTLs affecting SPC and the agronomic traits explained the genetic basis of the significant (P < 0.05) correlations of SPC with HSW (r2 = 0.22 to 0.30), SY (r2 = -0.18 to -0.28), DTFF (r2 = -0.17 to -0.31) and GH (r2 = 0.18 to 0.34). The quantitative nature of genetic control of SPC and its relationship with agronomic traits suggest that marker-assisted recurrent selection or genomic selection would be effective for the simultaneous improvement of SPC and other important traits

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

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

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