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Paudel, R.

Publications and source records attributed to Paudel, R..

2 recordsLinked to original sources

Soil Resistomes in a Tropical Watershed are Indirectly Structured by Bacterial Community Interactions with Soil Properties

Soils are recognized as reservoirs of antibiotic resistance genes (ARGs) with the potential to transfer to clinical pathogens, creating antimicrobial resistance (AMR) that poses a threat to human health. While large-scale AMR surveys have profiled how diverse biomes shape soil resistomes, less is known about the influence of specific soil properties. Here, we combined metagenomics and 16S rRNA amplicon sequencing with isolate-based approaches to investigate drivers of soil AMR across a tropical watershed from beach to mountaintop in Waimea Valley, Oahu, Hawai{square}i. We leveraged functional- and taxonomic-classification of resistances to unravel how soil properties interact with bacterial taxa to structure resistomes. Metagenomic- and isolate-resistomes showed remarkable consistency, including a general gradient of increasing AMR from ridge to beach. Resistome functional composition was significantly correlated with total bacterial community structure. The relationship between resistances and soil properties was primarily dictated by taxonomic composition of each resistance. Rifampin- and Vancomycin-ARGs associated with Actinomycetes negatively correlated with soil physical properties, while resistant genes and isolates from Gammaproteobacteria positively correlated with enzymatic activity metrics. These findings indicate that soil properties structure the resistome indirectly through taxonomic filtering of microbial hosts and challenge the notion that AMR is decoupled from phylogenetic relatedness.

ecology↗

ADGRE5 ACTS AS A MELANOMA TUMOR SUPPRESSOR IN NATURALLY HYBRIDIZING XIPHOPHORUS.

Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus, is used to study hybrid dysfunction and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids. Melanoma development is due to hybrid inheritance of an oncogene, xmrk, and loss of a co-evolved tumor modifier. It was recently found that adgre5, a G protein-coupled receptor involved in cell adhesion, is a tumor regulator gene in naturally hybridizing Xiphophorus species X. birchmanni and X. malinche. We hypothesized that one of the two parental alleles of adgre5 is involved in regulation of cell proliferation, migration and melanomagenesis. Accordingly, we assessed the function of adgre5 alleles from each parental species of the melanoma-bearing hybrids using in vitro cell proliferation and migration assays. In addition, we expressed each adgre5 allele with the xmrk oncogene in transgenic medaka. We found that cells transfected with the X. birchmanni adgre5 exhibited decreased proliferation and migration compared to those with the X. malinche allele. Moreover, X. birchmanni allele of adgre5 completely inhibited melanoma development in xmrk transgenic medaka, while X. malinche adgre5 expression did not exhibit melanoma suppressive activity in medaka. These findings showed that adgre5 is a natural melanoma suppressor and provide new insight in melanoma etiology.

cancer biology↗