Biology subjects

Patel, K. D.

Publications and source records attributed to Patel, K. D..

5 recordsLinked to original sources

bioRxiv2024

Nanofibrous Wound Dressing with a Smart Drug Delivery System: Poly(N-Isopropylacrylamide)-Conjugated Polycaprolactone Nanofibers Loaded with Curcumin

In response to clinical demands for advanced wound dressings, a "smart bandage" was developed by combining polycaprolactone (PCL) nanofibers and the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAAm). This bandage incorporates curcumin, an anti-inflammatory and antioxidant agent, to enhance wound healing. The LCST of PNIPAAm (32{degrees}C) enables an "on-off" drug delivery system, transitioning from a hydrophilic coil to a hydrophobic state. The nanofiber matrix was characterized using FTIR spectroscopy, SEM, water contact angle, and dynamic mechanical analysis. Curcumin release was assessed both above and below the LCST. The bandage is comfortable, easy to apply and remove, and promotes rapid wound healing. In vitro studies confirmed its non-toxicity to human dermal fibroblast cells. This "smart bandage" represents a significant advancement in wound care, with the potential to meet clinical requirements and enhance patient compliance, offering controlled drug delivery combined with the therapeutic benefits of curcumin.

bioengineering↗

bioRxiv2024

Antibiotic-induced Malassezia spp. expansion in infants promotes early-life immune dysregulation and airway inflammation in mice

Antibiotics have deleterious consequences for the gut microbiome and can increase the risk of childhood asthma. While the effects of antibiotics on the bacterial microbiome and asthma risk are well characterized, their impact on the fungal microbiome (mycobiome) remains vastly unexplored. We investigated the effect of antibiotic use on the gut mycobiome in an observational, prospective clinical study of young infants. Antibiotic treatment resulted in increased fungal abundance and expansion of the yeast Malassezia spp. Based on these findings, germ-free mouse pups were colonized with a defined consortium of mouse-derived bacteria (Oligo-MM12) with or without Malassezia restricta. Colonization with this yeast increased myeloid and lymphoid intestinal immune responses deemed critical in atopy development, and elevated airway inflammation in house-dust mite (HDM)-challenged mice. Further evaluation in eosinophil-deficient mice revealed that the observed immune response is partially dependent on this cell type. This translational work demonstrates that fungal overgrowth and expansion of Malassezia spp. are previously overlooked collateral effects of infant antibiotic use, which may offer a potential strategy to prevent or mitigate pediatric asthma and related conditions. One Sentence Summary: Antibiotic-induced Malassezia spp. expansion in infants promotes early-life immune dysregulation and airway inflammation in gnotobiotic mice.

immunology↗

bioRxiv2024

The structure of the monobactam-producing thioesterase domain of SulM forms a unique complex with the upstream carrier protein domain

Nonribosomal peptide synthetases (NRPSs) are responsible for the production of important biologically active peptides. The large, multidomain NRPSs operate through an assembly line strategy in which the growing peptide is tethered to carrier domains that deliver the intermediates to neighboring catalytic domains. While most NRPS domains catalyze standard chemistry of amino acid activation, peptide bond formation and product release, some canonical NRPS catalytic domains promote unexpected chemistry. The paradigm monobactam antibiotic sulfazecin is produced through the activity of a terminal thioesterase domain that catalyzes an unusual {beta}-lactam forming reaction in which the nitrogen of the C-terminal N-sulfo-2,3-diaminopropionate residue attacks its thioester tether to release the {beta}-lactam product. We have determined the structure of the thioesterase domain as both a free-standing domain and a didomain complex with the upstream holo peptidyl-carrier domain. The structure illustrates a constrained active site that orients the substrate properly for {beta}-lactam formation. In this regard, the structure is similar to the {beta}-lactone forming thioesterase domain responsible for the production of obafluorin. Analysis of the structure identifies features that are responsible for this four-membered ring closure and enable bioinformatic analysis to identify additional, uncharacterized {beta}-lactam-forming biosynthetic gene clusters by genome mining.

biochemistry↗

bioRxiv2021

A universal pocket in FAALs ensures redirection of fatty acid pool away from CoA-based activation

Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and accept holo-ACP unlike other members of the ANL superfamily remains elusive. We show FAALs have plugged the promiscuous canonical CoA-binding pockets and utilize highly selective alternative binding sites. These alternative pockets can distinguish adenosine 3, 5-bisphosphate-containing CoA from holo-ACP and thus FAALs can distinguish between CoA and holo-ACP. These exclusive features helped identify the omnipresence of FAAL-like proteins and their emergence in plants, fungi, and animals with unconventional domain organisations. The universal distribution of FAALs suggests they are parallelly evolved with FACLs for ensuring a CoA-independent activation and redirection of fatty acids towards lipidic metabolites.

biochemistry↗

bioRxiv2018

Real-Time Selective Sequencing with RUBRIC: Read Until with Basecall and Reference-Informed Criteria

The Oxford MinION, the first commercial nanopore sequencer, is also the first to implement molecule-by-molecule real-time selective sequencing or "Read Until". As DNA transits a MinION nanopore, real-time pore current data can be accessed and analyzed to provide active feedback to that pore. Fragments of interest are sequenced by default, while DNA deemed non-informative is rejected by reversing the pore bias to eject the strand, providing a novel means of background depletion and/or target enrichment. In contrast to the previously published pattern-matching Read Until approach, our RUBRIC method is the first example of real-time selective sequencing where on-line basecalling enables alignment against conventional nucleic acid references to provide the basis for sequence/reject decisions. We evaluate RUBRIC performance across a range of optimizable parameters, apply it to mixed human/bacteria and CRISPR/Cas9-cut samples, and present a generalized model for estimating real-time selection performance as a function of sample composition and computing configuration.

bioinformatics↗