Biology subjects

Nayak, T.

Publications and source records attributed to Nayak, T..

5 recordsLinked to original sources

bioRxiv2024

Rapid precision targeting of nanoparticles to lung via caveolae pumping system in endothelium

Modern medicine seeks precision targeting, imaging and therapy to maximize efficacy and avoid toxicities. Nanoparticles (NPs) have tremendous, yet unmet clinical potential to carry and deliver imaging and therapeutic agents systemically with tissue precision. But their size contributes to unwanted rapid scavenging by the reticulo-endothelial system (RES) and poor penetration of key endothelial cell (EC) barriers, both limiting target-tissue uptake, safety and efficacy. Here, we discover the extraordinary yet size-dependent ability of the EC caveolae pumping system (CPS) to deliver NPs rapidly and specifically into lungs. Gold and dendritic NPs are conjugated to aminopeptidase-P2 antibodies targeting caveolae of lung microvascular endothelium. SPECT-CT imaging and biodistribution analyses reveal that rat lungs extract most of the intravenously injected dose within minutes to achieve rapid blood clearance, high lung tissue concentrations well beyond peak blood levels, and precision lung imaging and targeting. Active transcytosis by caveolae greatly outperforms passive transvascular delivery and can even outpace RES scavenging. These results reveal how much ECs can both limit and promote tissue penetration of NPs and the power and limitations of the CPS. This study provides a new retargeting paradigm for small NPs to avoid RES uptake and achieve unprecedented rapid precision nanodelivery for future diagnostic and therapeutic applications.

bioengineering↗

bioRxiv2023

Loss of Myeloid Cell-Specific β2-Adrenergic Receptor Expression Ameliorates Cardiac Function and Remodeling after Acute Ischemia

Myeloid cells, including neutrophils, monocytes and macrophages, accumulate quickly after ischemic injury in the heart where they play integral roles in the regulation of inflammation and repair. We previously reported that deletion of {beta}2-adrenergic receptor ({beta}2AR) in all cells of hematopoietic origin resulted in generalized disruption of immune cell responsiveness to injury, but with unknown impact on myeloid cells specifically. To investigate this, we crossed floxed {beta}2AR (F/F) mice with myeloid cell-expressing Cre (LysM-Cre) mice to generate myeloid cell-specific {beta}2AR knockout mice (LB2) and subjected them to myocardial infarction (MI). Via echocardiography and immunohistochemical analyses, LB2 mice displayed better cardiac function and less fibrotic remodeling after MI than the control lines. Despite similar accumulation of myeloid cell subsets in the heart at 1-day post-MI, LB2 mice displayed reduced numbers of Nu by 4 days post-MI, suggesting LB2 hearts have enhanced capacity for Nu efferocytosis. Indeed, bone marrow-derived macrophage (BMDM)-mediated efferocytosis of Nu was enhanced in LB2-versus F/F-derived cells in vitro. Mechanistically, several pro-efferocytosis-related genes were increased in LB2 myeloid cells, with annexin A1 (Anxa1) in particular elevated in several myeloid cell types following MI. Accordingly, shRNA-mediated knockdown of Anxa1 in LB2 bone marrow prior to transplantation into irradiated LB2 mice reduced Mac-induced Nu efferocytosis in vitro and prevented the ameliorative effects of myeloid cell-specific {beta}2AR deletion on cardiac function and fibrosis following MI in vivo. Altogether, our data reveal a previously unrecognized role for {beta}2AR in the regulation of myeloid cell-dependent efferocytosis in the heart following injury.

immunology↗

bioRxiv2022

DepLink: an R Shiny app to systematically link genetic and pharmacologic dependencies of cancer

Large-scale genetic and pharmacologic dependency maps are generated to reveal genetic vulnerabilities and drug sensitivities of cancer. However, user-friendly software is needed to systematically link such maps. Here we present DepLink, an R Shiny server to identify genetic and pharmacologic perturbations that induce similar effects on cell viability or molecular changes. DepLink integrates heterogeneous datasets of genome-wide CRISPR loss-of-function screens, high-throughput pharmacologic screens, and perturbation expression signatures. The datasets are systematically connected by four complementary modules tailored for different query scenarios. In summary, DepLink enables easy navigation, visualization, and linkage of rapidly evolving cancer dependency maps.

bioinformatics↗

bioRxiv2022

Chlorpyrifos degradation by combined solar photo-Fenton and bacterial metabolism and simultaneous toxicity analysis in zebrafish (Danio rerio)

Chlorpyrifos (CP) is a widely used insecticide that has been used extensively, contributing towards a negative impact on public health concerns and associated ecosystems. Bioremediation is one of the key biological methods used for reducing these environmental toxicants. The present study examined the effectiveness of a combined process including solar photo-Fenton process followed by bacterial degradation using Ochrobactrum sp. CPD-03 for effective CP degradation in wastewater. Results showed that solar photo-Fenton treatment had CP degradation efficiency of ~42% in 4 h with a final degradation efficiency of ~92% in 96 h upon combined bacterial degradation. Simultaneous survivability of zebrafish (Danio rerio) was also studied during CP degradation. Compared to control, adult zebrafishes showed increased survivability following the addition of CPD-03 in water resulting a reduced CP concentration. CP toxicity in wastewater had caused acetylcholinesterase inhibition in zebrafish; however, this inhibition is due to absence of CP degrading bacteria. Therefore, a combined approach would influence for regulating CP degradation in wastewater along with simultaneous survival of Danio rerio.

microbiology↗

bioRxiv2019

Biodegradation of Chlorpyrifos and 3,5,6-trichloro-2-pyridinol (TCP) by Ochrobactrum sp. CPD-03: Insights from genome analysis on organophosphorus pesticidesdegradation, chemotaxis and PGPR activity

Chlorpyrifos (CP) is one of the worlds most widely used organophosphorous pesticides (OPs) in agriculture, has led to contaminate soil and water ecosystems along with human species. Here, we report a newly isolated strain, Ochrobactrum sp. CPD-03 form a paddy field which could degrade CP and its metabolite TCP (3,5,6-trichloro-2-pyridinol) in 48 hours with an efficiency of 85-88% in minimal salt medium. GC-MS analysis revealed possible metabolites during CP degradation. Whole genome analysis indicated the presence of arylesterase and existence of other genes accountable for xenobiotic compounds degradation. CPD-03 exhibited chemotactic features towards CP along with other OPs suggesting its versatile role for possible mineralization of these toxicants. Further screening of CPD-03 also displayed plant growth promoting activities. Taken altogether, our results highlight the potentials of this new isolate Ochrobactrum sp. CPD-03 in bioremediation and application in OP-contaminated ecosystem.

microbiology↗