Biology subjects

Mondal, S.

Publications and source records attributed to Mondal, S..

65 records · Page 4Linked to original sources

bioRxiv2020

RIG-I has a role in immunity against Haemonchus contortus, a gastrointestinal parasite in Ovis aries- a novel report.

RIG-I is associated to the DExD/H box RNA Helicases. It is a Pattern Recognition Receptor (PRR), playing a crucial role in the system and is a germ line encoded host sensor to perceive Pathogen Associated Molecular Patterns or PAMPs. So far reports were available for the role of RIG-I in antiviral immunity. This is the first report we have documented the role of RIG-I in parasitic immunity. Haemonchus contortus is a deadly parasite affecting sheep industry which has a tremendous economic importance and the parasite reported to be prevalent in the hot and humid agroclimatic region. We had characterized RIG-I gene in sheep (Ovis aries) and identified the important domains or binding site with Haemonchus contortus through in silico studies. Differential mRNA expression analysis revealed upregulation of RIG-I gene in abomassum of infected sheep compared to that of healthy sheep, further confirming the findings. Thus it is evident that in infected sheep, expression of RIG-I is triggered for binding to more pathogen (Haemonchus contortus). Genetic similar studies with human and other livestock species were conducted to reveal that sheep may be efficiently used a model organism for studying the role of RIG-I in antiparasitic immunity of human.

genomics↗

bioRxiv2020

Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model

The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, we have shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn3O4 NP) efficiently mimics glutathione peroxidase enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H2O2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. We further established the in vivo therapeutic efficacy of C-Mn3O4 nanozyme in a preclinical animal model of Huntingtons disease, a prevalent progressive neurodegenerative disorder, which has no effective medication till date. SUMMARYAlthough, nano-enzymes have shown lots of promises in the management of several diseases, two major concerns limit their clinical translation. Apart from the inherent toxicity of the constituent materials (e.g., cerium, vanadium, gold, etc.), activities of contemporary nanozymes are often inhibited in physiological milieu. Furthermore, most of them are incapable of incorporation into the cellular metabolic networks for functioning in tandem and parallel with natural enzymes, a major criteria for potential therapeutics. Here, we have shown that citrate-functionalized spherical Mn3O4 nanoparticles can efficiently mimic glutathione peroxidase (GPX) enzyme without the limitations of contemporary nanozymes, and effectively manage neurodegenerative Huntingtons disease in preclinical animal model. The choice of the material in the nanozyme lies on the fact that Mn is an essential micronutrient for mammals, and the stabilizing ligand citrate helps the nanoparticles to cross the blood-brain-barrier to reach brain. We have shown that the nanozyme can easily be incorporated in cellular antioxidant enzyme cascade. The specificity and efficacy of the nanozyme in the cascade was significantly higher compared to other reported nanozymes. We have justified our experimental findings with a detailed computational study. Understanding the mode of operation and management of Huntingtons disease in preclinical animal trial using a biocompatible (non-toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.

pharmacology and toxicology↗

bioRxiv2020

Tracking mitochondrial density and positioning along a growing neuronal process in individual C. elegans neuron using a long-term growth and imaging microfluidic device

The long cellular architecture of neurons requires regulation in part through transport and anchoring events to distribute intracellular organelles. During development, cellular and sub-cellular events such as organelle additions and their recruitment at specific sites on the growing axons occur over different time scales and often show inter-animal variability thus making it difficult to identify specific phenomena in population averages. To measure the variability in sub-cellular events such as organelle positions, we developed a microfluidic device to feed and immobilize C. elegans for high-resolution imaging over several days. The microfluidic device enabled long-term imaging of individual animals and allowed us to investigate organelle density using mitochondria as a testbed in a growing neuronal process in vivo. Sub-cellular imaging of an individual neuron in multiple animals, over 36 hours in our microfluidic device, shows the addition of new mitochondria along the neuronal process and an increase in the accumulation of synaptic vesicles at synapses, both organelles with important roles in neurons. Long-term imaging of individual C. elegans touch receptor neurons identifies addition of new mitochondria and interacts with other moving mitochondria only through fission and fusion events. The addition of new mitochondria takes place along the entire neuronal process length and the threshold for the addition of a new mitochondrion is when the average separation between the two pre-existing mitochondria exceeds 24 micrometers.

neuroscience↗

bioRxiv2020

Regulated distribution of mitochondria in touch receptor neurons of C. elegans influences touch response

Density of mitochondria and their localization at specific sub-cellular regions of the neurons is regulated by molecular motors, their adaptors and the cytoskeleton. However, the regulation of the mitochondrial density, the positioning of mitochondria along the neuronal process and the role of axonal mitochondria in neuronal function remain poorly understood. This study shows that the density of mitochondria in C. elegans touch receptor neuron processes remains constant through development. Simulations show that mitochondrial positioning along parts of the neuronal process that are devoid of synapses is regulated. Additionally, we also demonstrate that axonal mitochondria are necessary for maintaining touch responsiveness.

neuroscience↗

bioRxiv2020

Site-Specific Incorporation of Citrulline into Proteins in Mammalian Cells

Citrullination is a post-translational modification (PTM) of arginine that is crucial for several physiological processes, including gene regulation and neutrophil extracellular trap formation. Despite recent advances, studies of protein citrullination remain challenging due to the difficulty of accessing proteins homogeneously citrullinated at a specific site. Herein, we report a novel technology that enables the site-specific incorporation of citrulline (Cit) into proteins in mammalian cells. This approach exploits an E. coli-derived engineered leucyl tRNA synthetase-tRNA pair that incorporates a photocaged-citrulline (SM60) into proteins in response to a nonsense codon. Subsequently, SM60 is readily converted to Cit with light in vitro and in living cells. To demonstrate the utility of the method, we biochemically characterized the effect of incorporating Cit at two known autocitrullination sites in Protein Arginine Deiminase 4 (PAD4, R372 and R374) and showed that the R372Cit and R374Cit mutants are 181- and 9-fold less active than the wild-type enzyme. This powerful technology possesses immense potential to decipher the biology of citrullination.

biochemistry↗

bioRxiv2020

Aerial High-Throughput Phenotyping Enabling Indirect Selection for Grain Yield at the Early-generation Seed-limited Stages in Breeding Programs

Breeding programs for wheat and many other crops require one or more generations of seed increase before replicated yield trials can be sown. Extensive phenotyping at this stage of the breeding cycle is challenging due to the small plot size and large number of lines under evaluation. Therefore, breeders typically rely on visual selection of small, unreplicated seed increase plots for the promotion of breeding lines to replicated yield trials. With the development of aerial high-throughput phenotyping technologies, breeders now have the ability to rapidly phenotype thousands of breeding lines for traits that may be useful for indirect selection of grain yield. We evaluated early generation material in the irrigated bread wheat (Triticum aestivum L.) breeding program at the International Maize and Wheat Improvement Center to determine if aerial measurements of vegetation indices assessed on small, unreplicated plots were predictive of grain yield. To test this approach, two sets of 1,008 breeding lines were sown both as replicated yield trials and as small, unreplicated plots during two breeding cycles. Vegetation indices collected with an unmanned aerial vehicle in the small plots were observed to be heritable and moderately correlated with grain yield assessed in replicated yield trials. Furthermore, vegetation indices were more predictive of grain yield than univariate genomic selection, while multi-trait genomic selection approaches that combined genomic information with the aerial phenotypes were found to have the highest predictive abilities overall. A related experiment showed that selection approaches for grain yield based on vegetation indices could be more effective than visual selection; however, selection on the vegetation indices alone would have also driven a directional response in phenology due to confounding between those traits. A restricted selection index was proposed for improving grain yield without affecting the distribution of phenology in the breeding population. The results of these experiments provide a promising outlook for the use of aerial high-throughput phenotyping traits to improve selection at the early-generation seed-limited stage of wheat breeding programs.

genetics↗

bioRxiv2019

Genome-wide analysis of polymorphisms identified domestication-associated polymorphism desert carrying important rice grain size/weight QTL

Rice grain size and weight are major determinant of grain quality and yield and so have been under rigorous selection since domestication. However, genetic basis for contrasting grain size/weight trait among indian germplasm, and their association with domestication shaped evolutionary region is not studied before. To identify genetic basis of grain size/weight two long (LGG) and two short grain genotypes (SGG) were resequenced. LGG (LGR and Pusa Basmati 1121) differentiated from SGG (Sonasal and Bindli) by 504439 SNPs and 78166 InDels. The LRK gene cluster was significantly affected and a truncation mutation in the LRK8 kinase domain was uniquely associated with LGG. Phylogeny with 3000 diverse rice accessions revealed four sequenced genotypes belonged to japonica group and were at the edge of clades indicating source of genetic diversity available in Asian rice population. Five SNPs significantly were associated with grain size/weight and top three SNPs were validated in RIL mapping populations, suggesting this study as a valuable resource for high-throughput genotyping. A contiguous [~]6 Mb polymorphism desert region carrying a major grain weight QTL was identified on chromosome 5 in four sequenced genotypes. Further, among 3000, this region was identified as evolutionary important site with significant positive selection, elevated LD, and multiple selection sweeps, stabilising many domestication-related traits including grain size/weight. The aus group genotype retained more allelic variations in the desert region than japonica and indica, and likely to be one of the differentiation point for aus group. We suggest this desert region as an important evolutionary node that can be selected in breeding programs for improvement of grain yield and quality. All data and analysis can be accessed from RiceSzWtBase database.\n\nSignificance statementBeing an important trait, rice grain size/weight has been under rigorous selection since domestication. However, a link between this trait and domestication is not so directly established. In addition to characterization of novel grain size/weight-associated SNPs, in this study, [~] 6 Mb polymorphism desert region harboring major grain weight QTL was identified on chromosome 5, which turned out to be an evolutionary important site with multiple selection sweeps and introgression events, significantly correlated with domestication-related traits.

plant biology↗

bioRxiv2019

Genetic image-processing using regularized selection indices

High-throughput phenotyping (HTP) technologies can produce data on thousands of phenotypes per unit being monitored. These data can be used to breed for economically and environmentally relevant traits (e.g., drought tolerance); however, incorporating high-dimensional phenotypes in genetic analyses and in breeding schemes poses important statistical and computational challenges. To address this problem, we developed regularized selection indices; the methodology integrates techniques commonly used in high-dimensional phenotypic regressions (including penalization and rank-reduction approaches) into the selection index (SI) framework. Using extensive data from CIMMYTs (International Maize and Wheat Improvement Center) wheat breeding program we show that regularized SIs derived from hyper-spectral data offer consistently higher accuracy for grain yield than those achieved by canonical SIs, and by vegetation indices commonly used to predict agronomic traits. Regularized SIs offer an effective approach to leverage HTP data that is routinely generated in agriculture; the methodology can also be used to conduct genetic studies using high-dimensional phenotypes that are often collected in humans and model organisms including body images and whole-genome gene expression profiles.

genetics↗

bioRxiv2018

Use of Hyperspectral Reflectance-Derived Relationship Matrices for Genomic Prediction of Grain Yield in Wheat

Hyperspectral reflectance phenotyping and genomic selection are two emerging technologies that have the potential to increase plant breeding efficiency by improving prediction accuracy for grain yield. Hyperspectral cameras quantify canopy reflectance across a wide range of wavelengths that are associated with numerous biophysical and biochemical processes in plants. Genomic selection models utilize genome-wide marker or pedigree information to predict the genetic values of breeding lines. In this study, we propose a multi-kernel GBLUP approach to genomic selection that uses genomic marker-, pedigree-, and hyperspectral reflectance-derived relationship matrices to model the genetic main effects and genotype x environment (G x E) interactions across environments within a bread wheat (Triticum aestivum L.) breeding program. We utilized an airplane equipped with a hyperspectral camera to phenotype five differentially managed treatments of the yield trials conducted by the Bread Wheat Improvement Program, International Maize and Wheat Improvement Center (CIMMYT) at Ciudad Obregon, Mexico over four breeding cycles. We observed that single-kernel models using hyperspectral reflectance-derived relationship matrices performed similarly or superior to marker-and pedigree-based genomic selection models when predicting within and across environments. Multi-kernel models combining marker/pedigree information with hyperspectral reflectance phentoypes had the highest prediction accuracies; however, improvements in accuracy over marker-and pedigree-based models were marginal when correcting for days to heading. Our results demonstrates the potential of hyperspectral imaging in predicting grain yield within a multi-environment context, it also supports further studies on integration of hyperspectral reflectance phenotyping in breeding programs.

genomics↗

bioRxiv2017

Convection - Diffusion model of talking bacteria

Quorum sensing is cell to cell communication process through chemical signals formally known as autoinducers. When the concentration of quorum sensing molecules reached threshold concentration bacteria are in active state or quorum state. In this article, we propose a mathematical model of quorum sensing systems and study this biological system numerically. Moreover, we compare the different numerical scheme with the batch culture of P.aeruginosa. We observed a negative diffusion coefficient which plays an important role in the quorum sensing mechanism.

biophysics↗

bioRxiv2016

Kinetics of multi-substrate in Beauveria bassiana JUCHE22

The pattern of the biomass specific growth rate is an important focus for many biotechnological applications. Several control strategies have been employed to describe version of the exponential phase of growth of microorganisms. Moreover, in some bioprocesses there is more than one feeding substrates required for the specific growth. Hence, the problem of estimating multiple substrate consumption rates together with the specific growth rate of the microorganism becomes applicable. In this context, the dynamics behaviour of fed-batch process with multiple substrates (dextrose and peptone) and kinetics is further investigated in Beauveria bassiana. Different features of the proposed model are assessed by numerical simulation in different scenarios.

microbiology↗