Biology subjects

Kumar, N.

Publications and source records attributed to Kumar, N..

185 records · Page 11Linked to original sources

bioRxiv2018

Identification, expression analysis and molecular modeling of Iron deficiency specific clone 3 (Ids3) like gene in hexaploid wheat

Graminaceous plants secrete iron (Fe) chelators called mugineic acid family phytosiderophores (MAs) from their roots for solubilisation and mobilization of unavailable ferric (Fe3+) ions from the soil. The hydroxylated forms of these phytosiderophores have been found more efficient in chelation and subsequent uptake of minerals from soil which are available in very small quantities. The genes responsible for hydroxylation of phytosiderophores have been recognized as iron deficiency-specific clone 2 (Ids2) and iron deficiency-specific clone 3 (Ids3) in barley but their presence is not reported earlier in hexaploid wheat. Hence, the present investigation was done with the aim:(i) to search for the putative Hordeum vulgare Ids3 (HvIds3) ortholog in hexaploid wheat, (ii) physical mapping of HvIds3 ortholog on wheat chromosome using cytogenetic stocks developed in the background of wheat cultivar Chinese Spring and (iii) to analyze the effect of iron starvation on the expression pattern of this ortholog at transcription level. In the present investigation, a putative ortholog of HvIds3 gene was identified in hexaploid wheat using different bioinformatics tools. Further, protein structure of TaIDS3 was modelled using homology modeling and also evaluated modelled structure behavior on nanoseconds using molecular dynamics based approach. Additionally, the ProFunc results also predict the functional similarity between the proteins of HvIds3 and its wheat ortholog (TaIds3). The physical mapping study with the use of cytogenetic stocks confines TaIds3 in the telomeric region of chromosome 7AS which supports the results obtained by bioinformatics analysis. The relative expression analysis of TaIds3 indicated that the detectable expression of TaIds3 induces after 5th day of Fe-starvation and increases gradually up to 15th day and thereafter decreases till 35th day of Fe-starvation. This reflects that Fe deficiency directly regulates the induction of TaIds3 in the roots of hexaploid wheat.

genomics↗

bioRxiv2017

Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening

BackgroundCurrent professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance.\n\nResultsWe identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity.\n\nConclusionOur analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.

genetics↗

bioRxiv2017

Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacterxylosoxidans

The development of antibiotic resistance during treatment is a threat to patients and their environment. Insight in the mechanisms of resistance development is important for appropriate therapy and infection control. Here, we describe how through the application of mass spectrometry-based proteomics, a novel beta-lactamase Axc was identified as an indicator of acquired carbapenem resistance in a clinical isolate of Achromobacter xylosoxidans.\n\nComparative proteomic analysis of consecutively collected susceptible and a resistant isolates from the same patient revealed that high Axc protein levels were only observed in the resistant isolate. Heterologous expression of Axc in Escherichia coli significantly increased the resistance towards carbapenems. Importantly, direct Axc mediated hydrolysis of imipenem was demonstrated using pH shift assays and 1H-NMR, confirming Axc as a legitimate carbapenemase. Whole genome sequencing revealed that the susceptible and resistant isolates were remarkably similar.\n\nTogether these findings provide a molecular context for the fast development of meropenem resistance in A. xylosoxidans during treatment and demonstrate the use of mass spectrometric techniques in identifying novel resistance determinants.

microbiology↗

bioRxiv2017

Exosomes from Nef expressing monocytic cells restrict HIV-1 replication in infected cells through the assembly of stress granules

Exosomes are membranous vesicles secreted from almost all types of cells, carry proteins and nucleic acids and function as vehicles for intercellular communication. Cells infected with HIV-1 or expressing the viral Nef protein secrete more exosomes than uninfected cells or those not expressing this protein. We used stably transfected, Nef-expressing U937 human monocytic cells and exosomes purified from these cells to study their effects on HIV-1 infected and uninfected CD4+ T-cells. The Nef exosomes inhibited virus production from HIV-1 infected CD4+ T-cells, but caused activation induced cell death in uninfected bystander cells. Mutations in its conserved Arginine residues and in the secretion-modification-region failed to secrete Nef into exosomes. Cell lines expressing these mutant Nef proteins did not deliver it to the target CD4+ T-cells, and exosomes prepared from these mutant Nef-expressing cells also did not inhibit virus production. Nef exosomes inhibited virus production by inducing the assembly of stress granules in HIV-1 infected cells, which sequestered increased amounts of gag mRNA. This is a novel mechanism wherein we show the effects of exosomes on the assembly of stress granules and viral translational repression.

cell biology↗

bioRxiv2017

HiGlass: Web-based Visual Comparison And Exploration Of Genome Interaction Maps

We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at http://higlass.io and is also available as a containerized application that can be run on any platform.

bioinformatics↗