Endogenous tagging enables the study of proteins within their native regulatory context, typically using CRISPR to insert tag sequences directly into the gene sequence. Here, we introduce qTAG, a collection of repair cassettes that makes endogenous tagging more accessible. The cassettes support N- and C-terminal tagging with commonly used selectable markers and feature restriction sites for easy modification.
View Article and Find Full Text PDFAminocarbonylation reactions play a critical role in the synthesis of amides. Traditional aminocarbonylation processes often rely on carbon monoxide (CO) gas, a highly toxic and challenging reagent to handle. Recent advancements in CO surrogates address these challenges.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Mn coordinated by orthophosphate (Pi), metabolites, or peptides acts as a superoxide dismutase (SOD), and these Mn antioxidant complexes are universally accumulated in extremely radiation-resistant cell types across the tree of life. This behavior prompted design of decapeptide DP1 (DEHGTAVMLK) as a Mn ligand, and development of a highly potent Mn-antioxidant (MDP) containing [Pi] = 25 mM, and [DP1] = 3 mM, the ratio found in the radioresistant bacterium , with [Mn] = 1 mM. MDP is an exceptional antioxidant, both in vitro and in vivo, and has reinvigorated the development of radiation-inactivated whole-cell vaccines.
View Article and Find Full Text PDFIntroduction: Perinatal and maternal mortality rates remain high in India compared to global levels, and there is significant heterogeneity in outcomes across Indian states. Many mobile health (mHealth) interventions have been developed to improve maternal and infant health outcomes in India, however it is unclear how mHealth can best support women in this culturally and resource diverse setting. Therefore, we aimed to identify mHealth interventions targeting women and their families in the perinatal period in India, identify barriers and facilitators to their uptake, and future research directions.
View Article and Find Full Text PDFPurpose: The aims of this study were to determine whether point-of-order clinical decision support (CDS) based on the Wells criteria improves CT pulmonary angiography (CTPA) yield and utilization in hospitalized patients in an enterprise-wide health system and to identify yield-related factors.
Methods: This retrospective, institutional review board-approved, cross-sectional study in an urban, multi-institution health system included hospitalized patients undergoing CTPA 12 months before and after CDS implementation (entire cohort). The χ test was used to compare pulmonary embolism (PE) yield in patients in whom providers overrode versus followed CDS alerts after CDS implementation.
Seizure is among the most severe FDA black box warnings of neurotoxicity reported on drug labels. Gaining a better mechanistic understanding of off-targets causative of seizure will improve identification of potential seizure risks preclinically. In the present study, we evaluated an in vitro panel of 9 investigational (Cav2.
View Article and Find Full Text PDFThe emergence of pathologist-driven molecular reflex testing for tumoural biomarkers is a significant advancement in cancer diagnostics, facilitating targeted cancer therapy for our patients. Based on our experience, the Canadian landscape of pathologist-driven reflex biomarker testing for melanoma lacks standardization and is plagued by a lack of awareness by pathologists and clinicians. This paper comprehensively examines the approaches to reflex biomarker testing for melanoma patients across Canada, highlighting the regional variations in the criteria for initiating molecular testing, the biomarkers tested, and the molecular techniques employed.
View Article and Find Full Text PDFTuberculosis (TB) is an obstinate and infectious disease requiring a relatively longer treatment duration than other bacterial infections. The current treatment regime is prolonged and cumbersome, with adverse effects, often leading to nonadherence. The upsurge in TB's multidrug-resistant and extensively drug-resistant strains with evolved resistance to existing drugs has compounded the problems.
View Article and Find Full Text PDFPre-mRNA processing in eukaryotes involves capping, splicing, cleavage, and polyadenylation. Various proteins regulating this key transcriptional event in humans share considerable homology with proteins. Among these proteins, Pcf11 is a crucial component of the yeast CF IA sub-unit, and Ydh1 is part of the CPF sub-unit.
View Article and Find Full Text PDFLipid-based nanocarriers have emerged as promising vehicles for the delivery of various therapeutic agents, owing to their biocompatibility, stability, and ability to encapsulate both hydrophilic and hydrophobic drugs. Among these lipid-based nanocarriers, Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) have gained significant attention in the field of drug delivery. This comparative review aims to provide a comprehensive analysis of SLNs and NLCs, focusing on their formulation, physicochemical properties, drug-loading capacity, stability, and drug release profiles.
View Article and Find Full Text PDFMolecular profiling is a crucial aspect of cancer therapy selection, underscoring the necessity for representative sampling of both tumor and normal tissues. While much attention has been given to representative tumor sampling, there has been a notable lack of exploration into the issue of poor RNA quality in normal breast tissue processing. Normal breast tissue from the same patient is often used as a negative control for most "-omics" experiments.
View Article and Find Full Text PDFColorectal cancer (CRC) is one of the most common types of cancer with high incidence and mortality. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) is overexpressed in CRC. This study aims to explore the role of ERO1L in CRC progression and evaluate the anti-tumor efficacy of the combination treatment of ERO1L inhibition with endoplasmic reticulum (ER) stress-inducing therapies.
View Article and Find Full Text PDFMechanisms underpinning signals from genome-wide association studies remain poorly understood, particularly for noncoding variation and for complex diseases such as type 2 diabetes mellitus (T2D) where pathogenic mechanisms in multiple different tissues may be disease driving. One approach is to study relevant endophenotypes, a strategy we applied to the UBE2E2 locus where noncoding single nucleotide variants (SNVs) are associated with both T2D and visceral adiposity (a pathologic endophenotype). We integrated CRISPR targeting of SNV-containing regions and unbiased CRISPR interference (CRISPRi) screening to establish candidate cis-regulatory regions, complemented by genetic loss of function in murine diet-induced obesity or ex vivo adipogenesis assays.
View Article and Find Full Text PDFThe limited replicative potential of primary hepatocytes (Hep) is a major hurdle for obtaining sufficient quantity and quality hepatocytes during cell therapy in patients with liver failure. Intrahepatic cholangiocyte organoids (ICOs) derived from intrahepatic bile ducts differentiate into both hepatocytes and cholangiocytes . Here, we studied effects of transplanting ICOs and Hep in chronic liver injury mice models.
View Article and Find Full Text PDFPurpose: Posterior ankle Impingement (PAI) is a condition commonly affecting athletes and individuals engaged in activities involving repetitive ankle plantar flexion. This study aimed to evaluate the impact of nonsurgical management, excluding corticosteroid injections, on the functional outcomes of football players diagnosed with PAI.
Materials And Methods: Twenty male football Players between age group of 18-30 years, clinically diagnosed of PAI, were included in this longitudinal study.
To address the escalating demand for efficient CO separation technologies, we introduce novel membranes utilizing natural polymer guar gum (GG), conjugate polymer (poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)) PEDOT:PSS, and bimetallic PdPt nanoparticles. Bimetallic PdPt nanoparticles were synthesized using the wet chemical method and characterized using X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) techniques. The morphologies, chemical bonds, functional groups, and mechanical properties of the fabricated membranes were characterized using various techniques.
View Article and Find Full Text PDFA series of 1H-1,2,3-triazole-tethered spirocyclopropyl oxindole-isatin hybrids were synthesized using a copper-promoted click reaction and evaluated for their anti-proliferative activities against triple-negative breast cancer cell lines. The most potent compound in the series outperformed tamoxifen and 5-fluorouracil, with selectivity indices of 1.60 and 1.
View Article and Find Full Text PDFLeishmaniasis, a neglected tropical disease caused by various Leishmania species, poses a significant global health challenge, especially in resource-limited regions. Visceral Leishmaniasis (VL) stands out among its severe manifestations, and current drug therapies have limitations, necessitating the exploration of new, cost-effective treatments. This study utilized a comprehensive computational workflow, integrating traditional 2D-QSAR, q-RASAR, and molecular docking to identify novel anti-leishmanial compounds, with a focus on Glycyl-tRNA Synthetase (LdGlyRS) as a promising drug target.
View Article and Find Full Text PDFPhoton-counting computed tomography (PCCT) is an innovative mechanism used for imaging and provides higher spatial resolution and contrast sensitivity in comparison with the orthodox energy-integrating detectors (EIDs). Unlike EID-based CT systems, which indirectly convert X-ray photons to electrical signals, PCCT directly counts and quantifies each photon's energy, enhancing image quality and material separation. With all of these features, PCCT is especially useful for cardiovascular imaging, where it is essential to precisely observe cardiac tissues, vascular structures, and coronary arteries.
View Article and Find Full Text PDFCardiovasc Endocrinol Metab
March 2025
Glucagon-like peptide-1 (GLP-1) is a hormone involved in glucose homeostasis and satiety regulation. The review highlights the importance of understanding the interplay between GLP-1 and gastric motility. This paper explores the intricate connection between GLP-1 and delayed gastric emptying, specifically gastroparesis, and its implications in the context of pulmonary aspiration during anesthesia along with the potential effects of GLP-1 medications on absorption of other medications.
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