Biology subjects

Prasad, M.

Publications and source records attributed to Prasad, M..

24 records · Page 2Linked to original sources

bioRxiv2019

Molecular characterization and differential expression reveal functional divergence of stress-responsive enzymes in C4 panicoid models, Setaria italica and Setaria viridis

Stress-responsive genes regulate the morpho-physiological as well as molecular responses of plants to environmental cues. In addition to known genes, there are several unknown genes underlying stress-responsive machinery. One such machinery is the sophisticated biochemical carbon-concentrating mechanism of the C4 photosynthetic pathway that enables the plants to survive in high temperatures, high light intensities and drought conditions. Despite the importance of C4 photosynthesis, no comprehensive study has been performed to identify and characterize the key enzymes involved in this process among sequenced Poaceae genomes. In the present study, five major classes of enzymes that are reported to play roles in C4 biochemical carbon-concentrating mechanism were identified in sequenced Poaceae genomes with emphasis on the model crops, Setaria italica and S. viridis. Further analysis revealed that segmental and tandem duplications have contributed to the expansion of these gene families. Comparative genome mapping and molecular dating provided insights into their duplication and divergence in the course of evolution. Expression profiling of candidate genes in contrasting S. italica cultivars subjected to abiotic stresses and hormone treatments showed distinct stress-specific upregulation of SiCaH1, Si{beta}CaH5, SiPEPC2, SiPPDK2, SiMDH8 and SiNADP-ME5 in the tolerant cultivar. Altogether, the study highlights key stress-responsive genes that could serve as potential candidates for elucidating their precise roles in stress tolerance. Key messageComprehensive analysis of stress-responsive gene families in C4 model plants, Setaria italica and S. viridis identified SiCaH1, SiPEPC2, SiPPDK2, SiMDH8 and SiNADP-ME5 as potential candidates for engineering abiotic stress tolerance.

plant biology↗

bioRxiv2019

Designing of a mini-core that effectively represents 3004 diverse accessions of rice

Genetic diversity provides foundation for plant breeding and genetic research. As part of the 3K Rice Genome Project, over 3000 rice genomes were recently sequenced. We added four Indian rice accessions to it and made original panel of 3004 accessions. However, large set of germplasms are difficult to preserve and evaluate. Construction of core and mini-core collections is an efficient method for managing genetic resources. This study aims to designing of mini-core comprised of 520 accessions representing original panel. The designed mini-core captured most of the SNPs and represented all phenotypes and geographical regions. The mini-core was validated using different statistical analyses and had representation from all major groups including japonica, indica, aus/boro and aromatic/basmati. GWAS analyses with mini-core panel efficiently reproduced the marker-traits association identified among original 3004 panel. Expression analysis of trait-associated genes highlights the relevance of such mini-core panel. Haplotype analysis could also validate our mini-core panel. Apart from mini-core, we identified few regional and varietal specific marker-trait associations which were not evident in original panel. In this era of large-scale sequencing projects, such a strategy of designing mini-core will be very useful.\n\nOne-sentence summaryDesigning of mini-core as manageable association panel that efficiently mirroring the large and diverse collection of 3004 rice accessions.

plant biology↗

bioRxiv2019

Blastula stage specification of avian neural crest

Cell fate specification defines the earliest steps towards a distinct cell lineage. Neural crest, a multipotent stem cell population, is thought to be specified from the ectoderm, but its varied contributions defy canons of segregation potential and challenges its embryonic origin. Aiming to resolve this conflict, we have assayed the earliest specification of neural crest using blastula stage chick embryos. Specification assays on isolated chick epiblast explants identify an intermediate region specified towards the neural crest cell fate. Furthermore, low density culture suggests that the specification of intermediate cells towards the neural crest lineage is independent of contact mediated induction. Finally, we have validated the regional identity of the intermediate region towards the neural crest cell fate using fate map studies in blastula stage chick embryos. Our results suggest a model of neural crest specification at blastula stage, with restricted ectoderm and mesoderm capacities.

developmental biology↗

bioRxiv2019

Connectional heterogeneity in the mouse auditory corticocollicular system

The auditory cortex (AC) sends long-range projections to virtually all subcortical structures important for hearing. One of the largest and most complex of these - the projection between AC and inferior colliculus (IC, the corticocollicular pathway) - has attracted attention due to its potential to alter IC response properties. The corticocollicular pathway comprises a component originating from layer 5, but recent evidence suggests a significant contribution from deep layer 6, constituting 25% of corticocollicular neurons in mouse. The functions of layer-specific corticocollicular projections are poorly understood. Here, using a combination of tracers and in vivo imaging, we observed that layer 5 and layer 6 corticocollicular neurons differ in their cortical areas of origin, as well as IC termination patterns. Layer 5 corticocollicular neurons are concentrated in primary AC areas while layer 6 corticocollicular neurons emanate from broad auditory and non-auditory areas of temporal cortex. In addition, layer 5 projects to three IC subdivisions with axo-somatic terminals in the central nucleus, while layer 6 projects to non-central nuclei and targets the most superficial layers. These findings suggest that layer 5 corticocollicular neurons form a direct connection between primary AC and IC while the layer 6 projection is more diffusely organized and carries non-auditory information to modulate IC.

neuroscience↗

bioRxiv2019

Differential regulation of native and learned behavior by creb1/crh-1 in Caenorhabditis elegans

1.Memory formation is crucial for the survival of animals. Here, we study the effect of different crh-1 (C. elegans homolog of mammalian CREB1) mutations on the ability of C. elegans to form long-term memory (LTM). Null mutants in creb1/crh-1 are defective in LTM formation across phyla. We show that specific isoforms of CREB1/CRH-1, CRH-1c and CRH-1e, are primarily responsible for memory related functions of the transcription factor in C. elegans. Silencing of CRH-1e expressing neurons during training for LTM formation abolishes the long-term memory of the animal. Further, CRH-1e expression in RIM or AVE neurons is sufficient to rescue long-term memory defects of creb1/crh-1 null mutants. We show that apart from being LTM defective, creb1/crh-1 null mutant animals show defects in native chemotaxis behavior. We characterize the amino acids K247 and K266 as responsible for the LTM related functions of CRH-1 while being dispensable for its native chemotaxis behavior. These findings provide insight into the spatial and temporal workings of a crucial transcription factor and can be further exploited to find CREB1 targets involved in the process of memory formation.

neuroscience↗

bioRxiv2018

The AP-1 complex regulates AXL expression and determines sensitivity to PI3Kα inhibition in esophagus and head and neck squamous cell carcinoma

AXL overexpression is a common resistance mechanism to anti-cancer therapies, including the resistance to BYL719 (Alpelisib) - the p110 isoform specific inhibitor of phosphoinositide 3-kinase (PI3K) - in esophagus and head and neck squamous cell carcinoma (ESCC, HNSCC respectively). However, the mechanisms underlying AXL overexpression in resistance to BYL719 remain elusive. Here we demonstrated that the AP-1 transcription factors, c-JUN and c-FOS, regulate AXL overexpression in HNSCC and ESCC. The expression of AXL was correlated with that of c-JUN both in HNSCC patients and in HNSCC and ESCC cell lines. Silencing of c-JUN and c-FOS expression in tumor cells downregulated AXL expression and enhanced the sensitivity of human papilloma virus positive (HPVPos) and negative (HPVNeg) tumor cells to BYL719 in vitro. Blocking of the c-JUN N-terminal kinase (JNK) using SP600125 in combination with BYL719 showed a synergistic anti-proliferative effect in vitro, which was accompanied by AXL downregulation and potent inhibition of the mTOR pathway. In vivo, the BYL719-SP600125 drug combination led to the arrest of tumor growth in cell line-derived and patient-derived xenograft models, and in syngeneic head and neck murine cancer models. Collectively, our data suggests that JNK inhibition in combination with anti-PI3K therapy is a new therapeutic strategy that should be tested in HPVPos and HPVNeg HNSCC and ESCC patients.

cancer biology↗