Biology subjects

Shelke, A.

Publications and source records attributed to Shelke, A..

3 recordsLinked to original sources

bioRxiv2023

Uncertainty Quantification in Acoustic Impedance ofAtlantic Salmon Fish Scale using Scanning AcousticMicroscopy

Scanning Acoustic Microscopy (SAM) emerges as a versatile label-free imaging technology with broad applications in biomedical imaging, non-destructive testing, and material research. This article presents a framework for the estimation of stochastic impedance through SAM, with a particular focus on its application to the salmon fish scale. The framework leverages uncertain reflectance, marking its pioneering application to uncertainty quantification in the acoustic impedance of fish scales through acoustic responses. The study uses maximal overlap discrete wavelet transform, to decompose acoustic responses effectively and is further processed to predict the acoustic impedance. To establish the effectiveness of the proposed framework, well-known materials like a pair of target medium (polyvinylidene fluoride) and reference medium (polyimide) are employed for impedance characterization. Results demonstrate over 90%accuracy in PVDF impedance estimation, validating the framework. A stochastic impedance map, using Kriging with a Gaussian variogram, offers insights into the complex biomechanics of a fishs scale.

biophysics↗

bioRxiv2023

Spatial mapping of acoustic impedance of shrimp scale using multiple overlap discrete wavelet transform (moDWT)

There are lots of challenges associated with conventional optical observation of biological tissues, where specimens are typically sliced and stained for better contrast. In contrast, Scanning Acoustic Microscopy (SAM) is a versatile label-free imaging technology widely applied in various domains, including biomedical imaging, non-destructive testing, and material research. It excels in offering precise visualization of both surface and subsurface structures, providing valuable insights through visual inspection and quantitative analysis. Acknowledging the SAM, this paper presents acoustic impedance microscopy of the shrimp scale in a novel manner. The proposed technique aims to image the local distribution of cross-sectional acoustic impedance in biological tissue, which is a parameter closely related to sound speed and potentially valuable for tissue characterization. The study leverages advanced signal processing techniques, maximal overlap discrete wavelet transform (moDWT), to decompose acoustic responses effectively. The moDWT, with its ability to handle signals of various lengths without constraints, is highlighted as a promising approach. To determine shrimp scale impedance, we first establish the accuracy of the proposed algorithm using PVDF as the target and polyimide as reference material. The results indicate an algorithm accuracy exceeding 90%. An impedance map is generated through Gaussian process regression (GPR), which predicts the impedance over the complete domain, addressing spatial variations in biological specimens. The resulting acoustic impedance maps provide in-depth insights into the functional framework and advance our understanding of shrimp biomechanics.

biophysics↗

bioRxiv2022

Development of amidase-dependent pyrazinoic acid prodrugs with activity against pyrazinamide resistant Mycobacterium tuberculosis

Rapid emergence of drug resistance in Mycobacterium tuberculosis (Mtb) is one of the most significant healthcare challenges of our time. The cause of drug resistance is multifactorial, with the long course anti-tubercular therapy required to treat tuberculosis (TB) constituting a major contributing factor. Introduction of pyrazinamide (PZA) resulted in shortening of TB treatment from twelve to six months and consequently played a critical role in curbing drug resistance that developed over long course therapy. Nevertheless, because PZA is a prodrug activated by a nonessential amidase, PncA, resistance to PZA develops and frequently results in treatment failure. Here, we leveraged a whole cell drug screening approach to identify anti-tuberculars with unconventional mechanisms of action or activation that could be further developed into compounds effective at killing Mtb resistant to PZA. We discovered an amide containing prodrug, DG160, that was activated by the amidase, Rv2888c (AmiC). This amidase was capable of metabolizing a variety of amide containing compounds including a novel pyrazinoic acid-isoquinolin-1-amine prodrug, JSF-4302, which we developed as a potential PncA-independent replacement for PZA. As predicted, AmiC activation of JSF-4302 led to the generation of POA in Mtb including in a PZA resistant clinical isolate, thereby successfully delivering the active component of PZA while bypassing the need for activation by PncA. This work provides a framework for a new approach to drug development and prodrug activation in Mtb. SIGNIFICANCEPyrazinamide (PZA) is a vital component of Mycobacterium tuberculosis (Mtb) treatment since its inclusion shortened tuberculosis therapy by six months. However, PZA is a prodrug and resistance develops at a high frequency due to mutations in its activator PncA. Here, we present the discovery of amide-containing anti-tubercular prodrugs that are activated intracellularly by the Mtb amidase, AmiC. Taking advantage of this finding, we successfully designed and synthesized pyrazinoic acid (POA) prodrugs that were activated by AmiC and found that these compounds delivered intracellular POA to PZA- resistant Mtb isolates that contained a nonfunctional PncA. This new approach to prodrug development provides a method for delivering conjugated drugs into Mtb with the potential to overcome clinical drug resistance.

microbiology↗