Biology subjects

Raju, S.

Publications and source records attributed to Raju, S..

3 recordsLinked to original sources

bioRxiv2018

Continued circulation, recombination and evolution of the ancient subcontinent lineage despite predominance of the recent arctic-like lineage rabies viruses (RABV) in India

BackgroundRabies is an emerging and re-emerging lethal encephalitis causing 26,400 to 61,000 human deaths annually. Approximately 20,000 people die of rabies every year in India that accounts to 36% of the worlds rabies deaths. Rabies is endemic among domestic dogs in India and there are conflicting reports on the currently circulating RABV lineages in domestic dogs in India. Further, movement of humans and animals between Sri Lanka and southern coastal states of India was proposed to be a source of the emergence of variant RABV in India. For effective prevention and control of rabies in India it is essential to establish the genetic diversity and evolutionary dynamics of RBAV currently circulating in India.\n\nMethodsWe carried out molecular evolution and recombination analyses of nucleoprotein (N) and glycoprotein (G) genes of 26 RABV isolates from southern Indian states of Tamil Nadu and Goa.\n\nResultsWe found continued co-circulation of ancient subcontinent lineage despite predominance of the recent arctic-like lineage RABVs in southern India. The mean rate of nucleotide substitution in G and N genes was 1.32 x 10-3 and 1.91 x 10-4 substitutions/site/yr respectively. The study also found recombination in both N and G genes and a higher mean rate of evolutionary changes in G gene among Indian dog RABV isolates than those of lyssaviruses. The Indian subcontinent lineage RABV isolates investigated in this study clustered closely with other subcontinent lineage viruses from Sri Lanka highlighting the continued incursion and/or circulation of the variant subcontinent lineages of RABVs between India and Sri Lanka.\n\nConclusionWe report that there is enzootic viral establishment of two distinct RABV lineages in domestic dogs in India that are evolving at a greater rate.\n\nAuthor summaryRabies is a fatal viral disease that has no treatment and can only be prevented by post-exposure vaccination. In many parts of Asia and Africa, rabies continues to be a major public health threat almost always caused by dog bites. In this study, we investigated the genetic diversity and rate of evolution among rabies viruses isolated from dogs in India. We found that two distinct lineages of Rabies viruses (RABVs) namely the ancient subcontinent lineage and a more recent arctic-like lineage co-circulate among dogs in India. Notably, our study found that the dog rabies viruses in India are undergoing recombination and evolving at a higher rate than other lyssaviruses. Phylogenetic analysis revealed continued incursion and/or circulation of the variant subcontinent lineages of RABVs in India that might have been originated from Sri Lanka. Our study indicates that two distinct lineages of RABVs are maintained and currently circulate among dog population in India

microbiology↗

bioRxiv2018

A non-dimensional, two-parameter mechanical model reveals alterations in nuclear mechanics upon Hepatitis C Virus infection

Morphology of the nucleus is an important regulator of gene-expression. Nuclear morphology is in turn a function of the forces acting on it and the mechanical properties of the nuclear envelope. Here, we present a two-parameter, non-dimensional mechanical model of the nucleus that reveals a relationship among nuclear shape parameters such as projected area, surface area and volume. Our model fits the morphology of individual nuclei and predicts the ratio between forces and modulus in each nucleus. We analyzed the changes in nuclear morphology of liver cells due to Hepatitis C Virus (HCV) infection using this model. The model predicted a decrease in the elastic modulus of the nuclear envelope and an increase in the pre-tension in cortical actin as the causes for the change in nuclear morphology. These predictions were validated biomechanically by showing that liver cells expressing HCV proteins possessed enhanced cellular stiffness and reduced nuclear stiffness. Concomitantly, cells expressing HCV proteins showed down-regulation of lamin-A,C and up-regulation of actin, corroborating the predictions of the model. Our modelling assumptions are broadly applicable to adherent, monolayer cell cultures making the model amenable to investigate changes in nuclear mechanics due to other stimuli by merely measuring nuclear morphology. Towards this, we present two techniques, graphical and numerical, to use our model for predicting physical changes in the nucleus.

biophysics↗

bioRxiv2017

Reproducibility and repeatability of six high-throughput 16S rDNA sequencing protocols for microbiota profiling

Culture-independent molecular techniques and advances in next generation sequencing (NGS) technologies make large-scale epidemiological studies on microbiota feasible. A challenge using NGS is to obtain high reproducibility and repeatability, which is mostly attained through robust amplification. We aimed to assess the reproducibility of saliva microbiota by comparing triplicate samples. The microbiota was produced with simplified in-house 16S amplicon assays taking advantage of large number of barcodes. The assays included primers with Truseq (TS-tailed) or Nextera (NX-tailed) adapters and either with dual index or dual index plus a 6-nt internal index. All amplification protocols produced consistent microbial profiles for the same samples. Although, in our study, reproducibility was highest for the TS-tailed method. Five replicates of a single sample, prepared with the TS-tailed 1-step protocol without internal index sequenced on the HiSeq platform provided high alpha-diversity and low standard deviation (mean Shannon and Inverse Simpson diversity was 3.19 {+/-} 0.097 and 13.56 {+/-} 1.634 respectively). Large-scale profiling of microbiota can consistently be produced by all 16S amplicon assays. The TS-tailed-1S dual index protocol is preferred since it provides repeatable profiles on the HiSeq platform and are less labour intensive.

microbiology↗