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Reddy, A. P.

Publications and source records attributed to Reddy, A. P..

3 recordsLinked to original sources

Analysis of mouse lens morphological and proteomic abnormalities following depletion of βB3-crystallin

Crystallin proteins serve as both essential structural and as well as protective components of the ocular lens and are required for the transparency and light refraction properties of the organ. The mouse lens crystallin proteome is represented by A-, B-, {beta}A1-, {beta}A2-, {beta}A3-, {beta}A4-, {beta}B1-, {beta}B2-, {beta}B3-, {gamma}A-, {gamma}B-, {gamma}C-, {gamma}D-, {gamma}E, {gamma}F-, {gamma}N-, and {gamma}S-crystallin proteins encoded by 16 genes. Their mutations are responsible for lens opacification and early onset cataract formation. While many cataract-causing missense and nonsense mutations are known for these proteins, including the human CRYBB3 gene, the mammalian loss-of function model of the Crybb3 gene remains to be established. Herein, we generated the first mouse model via deletion of the Crybb3 promoter that abolished expression of the {beta}B3-crystallin. Histological analysis of lens morphology using newborn {beta}B3-crystallin-deficient lenses revealed disrupted lens morphology with early-onset phenotypic variability. In-depth lens proteomics at four time points (newborn, 3-weeks, 6-weeks, and 3-months) showed both down- and up-regulation of various proteins, with the highest divergence from control mice observed in 3-months lenses. Apart from the {beta}B3-crystallin, another protein Smarcc1/Baf155 was down-regulated in all four samples. In addition, downregulation of Hspe1, Pdlim1, Ast/Got, Lsm7, Ddx23, and Acad11 was found in three time points. Finally, we show that the {beta}B3-crystallin promoter region, which contains multiple binding sites for the transcription factors AP-2, c-Jun, c-Maf, Etv5, and Pax6 is activated by FGF2 in primary lens cell culture experiments. Together, these studies establish the mouse Crybb3 loss-of-function model and its disrupted crystallin and non-crystallin proteomes.

developmental biology↗

Prevalence and diversity of Helicobacter species in captive wild carnivores, and their implications for conservation management of endangered species

Helicobacter species colonize the gastrointestinal tract of various hosts, and have always been of interest due to their potential zoonotic transmission and impact on health of humans and animals. Comprehensive studies involving wild animals from different locations are lacking, hindering our understanding of their natural host range, prevalence, and genetic diversity. Here we investigated the prevalence and genetic diversity of Helicobacter species in thirteen wild carnivore species across twenty-two zoos and rescue centers in India by targeting partial 16S rRNA gene. We used sequences obtained from positive samples for phylogenetic analysis, and further evaluated factors influencing Helicobacter prevalence with generalised linear mixed models. We analysed 985 faecal samples of which 286 (29%) tested positive for Helicobacter, spanning all the host species included in this study. Helicobacter prevalence is strongly related to host species and location, and varied from 7.3% in common leopard to 80% in Indian fox. Phylogenetic analysis identified 59 unique genotypes clustered into 11 groups of three major Helicobacter types: enterohepatic, gastric, and unsheathed. Diverse Helicobacter species associated with diseases in humans and domestic animals were observed, such as H. canis, H. bilis, along with several novel strains/ species which require formal classification. Overall, this study highlights the wide occurrence and high genetic diversity of Helicobacter species in captive wild carnivores in India. Our findings underscore the need for regular health assessments in captive facilities to monitor Helicobacter infections, which could impact the health and management of endangered species. Future research should explore Helicobacter presence in biotic and abiotic factors in zoo and free-ranging populations following One Health approaches.

microbiology↗

High coverage genome sequencing and identification of genomic variants in Bengal tiger (Panthera tigris tigris)

Bengal tiger (Panthera tigris tigris), one of six extant tiger subspecies, occurs solely in the Indian subcontinent. Although endangered and threatened by various extinction risks, this is the most populous tiger subspecies with the highest genetic diversity and strongest chance of survival in the wild. Availability of high quality genomic information on this animal will help us understand its ability to adapt to different habitats and environmental changes, in addition to comparative studies with other subspecies. Here we report high coverage sequencing of the Bengal tiger genome and its mapping to the Amur tiger genome in order to discover single nucleotide to large structural variants. A total of 345 Gb, roughly equivalent to 144X coverage of the genome, was generated from 1,149,381,669 raw read pairs. Further, 990,060,729 clean read pairs, again equivalent to 115X coverage, were retained from the raw read data and considered for comparative analysis with the Amur tiger genome. This alignment showed that 97.35% of the bases mapped at 5X depth, 97.26% at 10X and 90.44% at 50X depth. We identified a total of 3,601,882 single nucleotide variants, 948 structural variants, 56,649 copy number variants and 1,760,347 simple sequence repeats. We report the first high coverage genome sequence of Bengal tiger with an overview of its genomic variants when compared to the Amur tiger genome. Of the several variants identified, we further have to assess and validate variants potentially associated with the ability of the animal to adapt to environmental changes, disease susceptibility and other important biological phenomena.

genomics↗