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1.
Soft Matter ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949520

RESUMO

Bioinspired soft actuators, capable of undergoing shape deformation in response to external triggers, hold great potential in fields such as soft robotics, artificial muscles, drug delivery, and smart switches. However, their widespread application is hindered by limitations in responsiveness, durability, and complex fabrication processes. In this study, we propose a new approach to tackle these challenges by developing a single-layer soft actuator that responds to multiple stimuli using a straightforward solution-casting method. This actuator comprises bio-polymer gelatin, bio-compatible PEDOT:PSS, and iron oxide (Fe3O4) nanoparticles. Our actuator exhibits responsiveness to a range of organic solvent vapors, including water vapor, light, and magnetic fields. Notably, it exhibits rapid and reversible bending in distinct directions in response to different vapors, bending upwards in the presence of water vapor and downwards in the presence of alcohol vapor. Moreover, exposure to infrared (IR) light induces a bending toward the light source. The incorporation of magnet-responsive Fe3O4 nanoparticles induces multi-functionality in the actuator. The actuation characteristics of the actuator are controlled by leveraging its responsiveness to dual stimuli, such as water vapor and magnetic fields, as well as light and magnetic fields. For the proof of concept, we showcase several potential applications of our multi-stimuli responsive soft actuator, including magnet-triggered electrical switches, cargo transportation, soft grippers, targeted drug delivery, energy harvesting, and bio-mimicry.

2.
Ther Innov Regul Sci ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954240

RESUMO

Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)3 Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives.

3.
South Asian J Cancer ; 13(2): 132-141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38919665

RESUMO

Atreye MajumdarSambit K. MohantyObjective This article identifies and evaluates the frequency of mutations in the BCR-ABL1 kinase domain (KD) of chronic myeloid leukemia (CML) patients who showed suboptimal response to their current tyrosine kinase inhibitor (TKI) regime and assesses their clinical value in further treatment decisions. Materials and Methods Peripheral and/or bone marrow were collected from 791 CML patients. Ribonucleic acid was extracted, reverse transcribed, and Sanger sequencing method was utilized to detect single-nucleotide variants (SNVs) in BCR-ABL1 KD. Results Thirty-eight different SNVs were identified in 29.8% ( n = 236/791) patients. T315I, E255K, and M244V were among the most frequent mutations detected. In addition, one patient harbored a novel L298P mutation. A subset of patients from the abovementioned harbored compound mutations (13.3%, n = 33/236). Follow-up data was available in 28 patients that demonstrated the efficacy of TKIs in correlation with mutation analysis and BCR-ABL1 quantitation. Molecular response was attained in 50% patients following an appropriate TKI shift. A dismal survival rate of 40% was observed in T315I-harboring patients on follow-up. Conclusion This study shows the incidence and pattern of mutations in one of the largest sets of Indian CML patients. In addition, our findings strengthen the prognostic value of KD mutation analysis among strategies to overcome TKI resistance.

4.
Expert Opin Ther Targets ; 28(5): 357-373, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38861226

RESUMO

INTRODUCTION: HIF-1α, a key player in medical science, holds immense significance in therapeutic approaches. This review delves into its complex dynamics, emphasizing the delicate balance required for its modulation. HIF-1α stands as a cornerstone in medical research, its role extending to therapeutic strategies. This review explores the intricate interplay surrounding HIF-1α, highlighting its critical involvement and the necessity for cautious modulation. AREAS COVERED: In sickle cell disease (SCD), HIF-1α's potential to augment fetal hemoglobin (HbF) production and mitigate symptoms is underscored. Furthermore, its role in cancer is examined, particularly its influence on survival in hypoxic tumor microenvironments, angiogenesis, and metastasis. The discussion extends to the intricate relationship between HIF-1α modulation and cancer risks in SCD patients, emphasizing the importance of balancing therapeutic benefits and potential hazards. EXPERT OPINION: Managing HIF-1α modulation in SCD patients requires a nuanced approach, considering therapeutic potential alongside associated risks, especially in exacerbating cancer risks. An evolutionary perspective adds depth, highlighting adaptations in populations adapted to low-oxygen environments and aligning cancer cell metabolism with primitive cells. The role of HIF-1α as a therapeutic target is discussed within the context of complex cancer biology and metabolism, acknowledging varied responses across diverse cancers influenced by intricate evolutionary adaptations.


Assuntos
Anemia Falciforme , Subunidade alfa do Fator 1 Induzível por Hipóxia , Terapia de Alvo Molecular , Neoplasias , Microambiente Tumoral , Humanos , Anemia Falciforme/fisiopatologia , Anemia Falciforme/tratamento farmacológico , Neoplasias/patologia , Neoplasias/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Hemoglobina Fetal/metabolismo , Neovascularização Patológica
5.
Cureus ; 16(5): e60152, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38864043

RESUMO

INTRODUCTION: People with visual impairments and blindness face challenges in performing regular tasks such as maintaining proper sanitation, which makes them vulnerable to intestinal parasitic infections. AIMS AND OBJECTIVES: This study aims to examine the prevalence and distribution of intestinal parasitic infections in children and adolescents with ocular diseases and to assess if the lockdown during the COVID-19 pandemic affected these rates. METHODS: This retrospective, hospital record-based study was conducted among children and adolescents attending the Regional Institute of Ophthalmology in Kolkata, India. It involved routine stool examinations as part of their treatment during 2019-2020. Early morning stool specimens were collected and brought to the institute laboratory in containers. Stools were examined under a microscope for cysts, ova, parasites, and adult worms. Findings were recorded in the laboratory record book. These data were then extracted into a spreadsheet and analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York). RESULTS: The prevalence of intestinal parasitic infections was 8.59% (59 out of 687 patients). Among those 59 positive cases, Ascaris lumbricoides, Giardia lamblia, Entamoeba histolytica, Trichuris trichiura, Taenia spp., Enterobius vermicularis, and Isospora belli were detected in 27 (45.8%), 15 (25.4%), 8 (13.6%), 6 (10.2%), 3 (5.1%), 2 (3.4%), and 1 (1.7%) patients, respectively. The positivity rate of stool samples was higher from September and thereafter from January to March. The sample positivity rate was higher post-pandemic and lockdown, but not statistically significant (11.5% vs. 5.3%; χ²=4.044, df=1, p=0.44). CONCLUSION: Ascaris lumbricoides was the most commonly observed intestinal parasite in children and adolescents with ocular disease in our setting. Seasonal variation was noted with higher case positivity at the end of the rainy season and thereafter in winter. Therefore, we propose to strengthen the routine deworming program during this period in Eastern India. Higher sample positivity after the pandemic may be attributed to school closures during the lockdown period, which might have caused some children to miss their routine deworming medication.

7.
Org Biomol Chem ; 22(21): 4326-4331, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38722080

RESUMO

Herein, we report a viable protocol to access furo[3,2-c]chromen-4-ones by engaging easily accessible 4-hydroxy coumarins as a three-atom CCO unit and thioamides as a C2 coupling partner, mediated by phenyliodine(III) diacetate (PIDA) at room temperature in a highly efficient and pot-/step-economical manner. This strategy not only avoids potential toxicity and tiresome workup conditions, but also features operational simplicity, a broad substrate scope, good functional group tolerance, high yields, easy scalability and exclusive selectivity. A mechanistic study has shown that this metal-free reaction is triggered by PIDA via activation of the ß-carbon of 4-hydroxy coumarin, followed by a nucleophilic addition/intramolecular cyclization/dethiohydration cascade. High-resolution mass spectra (HRMS) study confirms the key intermediates involved during the course of the reaction, elucidating the reaction pathways, and demonstrates the excellent regio- and chemoselectivity of this approach.

9.
Int J Nurs Pract ; : e13263, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747251

RESUMO

AIM: To assess the prevalence of non-communicable disease risk factors among the nursing staff and educate them on prevention. BACKGROUND: Nursing staff is integral to the Indian community healthcare systems. Recent studies report a high prevalence of non-communicable diseases in Indian nursing staff. Therefore, data on the prevalence of non-communicable disease risk factors among nursing staff are crucial for education on prevention. DESIGN: A cross-sectional digital survey-based study. METHOD: We invited 4435 nursing staff to attend our online survey. We used a customized questionnaire for data collection, including a digitized version of the Community-Based Assessment Checklist form. A score of >4 was considered high risk and warranted screening. RESULT: Among 682 nursing staff who attended, 70% had never undergone screening for non-communicable diseases. The prevalence of non-communicable disease risk factors was significantly higher in male nursing staff. In addition, logistic regression analysis showed that age, tobacco and alcohol use, increased waist circumference, physical inactivity and family history of non-communicable diseases were significant risk factors among nursing staff. CONCLUSION: The study findings suggest that the nursing staff have suboptimal self-health concerns on non-communicable diseases. This situation warrants continued medical education, awareness campaigns on adopting a healthy lifestyle and health promotion.

10.
Langmuir ; 40(21): 11206-11214, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38748983

RESUMO

Bioinspired smart polymeric materials that undergo three-dimensional shape deformation in response to specific stimuli have gained significant attention in the field of soft robotics and intelligent devices. Despite the substantial advancements in soft robotics, there is a growing demand for the design of multistimuli-responsive soft actuators using a single layer of material due to its reduced complexity and ease of manufacturing and durability. Here, we report the actuation characteristics of a single-layer, dual-responsive soft actuator that overcomes the commonly encountered delamination issues often associated with bilayer systems by incorporating PEDOT:PSS with cassava starch. This soft actuator exhibits deformations in response to various solvent vapors, such as water, alcohol, and acetone. Remarkably, it demonstrates opposite deformations upon exposure to water and alcohol vapors. Additionally, the actuator responds to light triggers and folds upon exposure to sunlight and infrared light. The degree of folding can be precisely controlled by adjusting the intensity of the light source. Furthermore, the periodic geometric patterns imposed on the surface of the actuator provide an additional handle to control the bending axis. For proof of concept, we leverage the actuation capabilities of our actuator to showcase a range of potential applications, including its usage in wearable textiles, crawler robots, smart curtains, push-and-pull machines, and smart lifts.

11.
Future Med Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38596902

RESUMO

Aim: p-Toluenesulfonic acid-(PTSA) and grinding-induced novel synthesis of ethylquinolin-thiazolo-triazole derivatives was performed using green chemistry. Materials & methods: Development of a nanoconjugate drug-delivery system of ethylquinolin-thiazolo-triazole was carried out with D-α-tocopheryl polyethylene glycol succinate (TPGS) and the formulation was further characterized by transmission electron microscopy, atomic force microscopy, dynamic light scattering and in vitro drug release assay. The effect of 3a nanoparticles was assessed against a cervical cancer cell line (HeLa) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect on apoptosis was determined. Results & discussion: The 3a nanoparticles triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing cellular uptake of micelles. Furthermore, in silico studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties and bioavailability of the enzyme tyrosine protein kinase. Conclusion: The 3a nanoparticles enhanced the therapeutic potential and have higher potential for targeted drug delivery against cervical cancer.

12.
ACS Omega ; 9(13): 14781-14790, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38585048

RESUMO

Dhatryadi Rasayana revitalizes the human body and helps in maintaining health with the elimination of ill effects of various diseases. The effective delivery systems for Rasayana may affect the profound effect of active principles in the body. The present study deals with investigation and evaluation of phytochemical constituents, physicochemical characteristics, along with antioxidant and immunomodulatory effects of Dhatryadi Rasayana in churna (powder) and granule formulations. Dhatryadi Rasayana churna and its granules were studied for various physicochemical parameters, e.g., moisture content, ash-value, acid-insoluble ash content, water-soluble extractive, alcohol-soluble extractive, bulk density, tapped density, angle of repose, Carr's index, Hausner's ratio, total sugar, reducing sugar, non-reducing sugar, heavy metals, total microbial load, etc. In vitro antioxidant potential of Dhatryadi Rasayana churna and its granules was determined by scavenging the DPPH and FRAP assays. The immunomodulatory activities of Dhatryadi Rasayana churna and its granules were studied in Wistar albino rats and the complete blood count (CBC), delayed-type hypersensitivity reaction (DTH), and hemagglutination antibody titer were assessed. Dhatryadi Rasayana churna contained alkaloids (0.50 ± 0.298% w/w), tannins (9.84 ± 1.527% w/w), saponins (4.18 ± 2.126% w/w), and flavonoids (9.34 ± 1.026% w/w), while its granules contained 11.08 ± 2.468% w/w total tannins, 2.40 ± 1.132% w/w alkaloids, and 12.46 ± 2.645% w/w total flavonoids. The DPPH scavenging effect was determined by IC50 (churna - 23.89 µg/mL; granules - 9.33 µg/mL), and the antioxidant capacity assessed by FRAP was 77.0 mmol/100 g equivalent of ascorbic acid for churna and 50 mmol/100 g equivalent of ascorbic acid for granules. Dhatryadi Rasayana churna and its granules reflected a significant immunostimulatory effect on both the cell-mediated and humoral immune systems in Wistar albino rats. Moreover, churna and granules of Dhatryadi Rasayana revealed significant antioxidant and immunomodulatory activities and these may be applied for treating different diseases as well as improving the immunity of the body.

13.
Sci Rep ; 14(1): 8457, 2024 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605072

RESUMO

A new series of imidazothiazole derivatives bearing thiazolidinone moiety (4a-g and 5a-d) were designed, synthesized and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer and anti-inflammatory activity, cardiomyopathy toxicity and hepatotoxicity. Compound 4c inhibited EGFR kinase at a concentration of 18.35 ± 1.25 µM, whereas standard drug erlotinib showed IC50 value of 06.12 ± 0.92 µM. The molecular docking, dynamics simulation and MM-GBSA binding energy calculations revealed strong interaction of compound 4c with binding site of EGFR. The synthesized compounds were evaluated for their anticancer activity by MTT assay against three human cancer cell lines A549 (Lung), MCF-7 (Breast), HCT116 (Colon), one normal human embryonic kidney cell line HEK293 and also for their EGFR kinase inhibitory activity. Few compounds of the series (4a, 4b, 4c) showed promising growth inhibition against all the tested cancer cell lines and against EGFR kinase. Among these, compound 4c was found to be most active and displayed IC50 value of 10.74 ± 0.40, 18.73 ± 0.88 against cancer cell lines A549 and MCF7 respectively whereas it showed an IC50 value of 96.38 ± 1.79 against HEK293 cell line indicating lesser cytotoxicity for healthy cell. Compounds 4a, 4b and 4c were also examined for their apoptosis inducing potential through AO/EB dual staining assay and it was observed that their antiproliferative activity against A549 cells is mediated via induction of apoptosis. Cardiomyopathy studies showed normal cardiomyocytes with no marked sign of pyknotic nucleus of compounds 4b and 4c. Hepatotoxicity studies of compounds 4b and 4c also showed normal architecture of hepatocytes. Compounds 4a-g and 5a-d were also evaluated for their in-vitro anti-inflammatory activity by protein albumin denaturation assay. Among the tested compounds 4a-d and 5a-b showed promising activity and were selected for in-vivo inflammatory activity against carrageenan rat paw edema test. Among these compounds, 4b was found to be most active in the series showing 84.94% inhibition, whereas the standard drug diclofenac sodium showed 84.57% inhibition. Compound 4b also showed low ulcerogenic potential and lipid peroxidation. Thus, compounds 4c and 4b could be a promising lead compounds for developing anticancer and anti-inflammatory agents with low toxicity and selectivity.


Assuntos
Antineoplásicos , Cardiomiopatias , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Ratos , Animais , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Células HEK293 , Antineoplásicos/química , Anti-Inflamatórios/farmacologia , Receptores ErbB/metabolismo , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Inibidores de Proteínas Quinases/química
14.
Environ Pollut ; 348: 123880, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554835

RESUMO

The study aimed to evaluate the potential of a novel isolated ureolytic Enterobacter hormaechei IITISM-SA3 in cadmium bioremoval through MICP. The optimization and modelling of the biotic and abiotic factors affecting the process of mineralization were also performed. In addition, the underlying mechanism of MICP-driven Cd mineralization under microbial-inclusive and cell-free conditions was revealed and supported through the characterization of the bio-precipitates obtained using various characterization techniques. The results indicated that the isolate could remove 97.18% Cd2+ of 11.4 ppm under optimized conditions of 36.86 h, pH 7.63, and biomass dose of 1.75 ml. Besides, the presence and absence of bacterial cells were found to influence both the morphologies and crystalline structures of precipitates. The precipitates obtained under microbial-inclusive conditions showed typical rhombohedral crystalline structures of the composition comprising CaCO3, CdCO3, and 0.67Ca0.33CdCO3. However, the crystalline nature of the precipitate reduced to a nano-sized granular structure in cell-free media. Unlike the cadmium mineralization process under microbial-inclusive media, where bacterial cells serve as nucleation sites for crystallization, the carbonate precipitation effectively captures Cd2+ through co-precipitation, chemisorption, or alternative mechanisms involving interactions between metal ions and CaCO3 under cell-free conditions. The findings presented suggest that using cell-free culture supernatant enriched with carbonate ions provides an avenue that could be harnessed for sustainable metal remediation.


Assuntos
Cádmio , Carbonato de Cálcio , Enterobacter , Carbonato de Cálcio/química , Cádmio/química , Precipitação Química , Carbonatos/química
16.
Nat Commun ; 15(1): 357, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191521

RESUMO

Accurate and cost-effective quantification of the carbon cycle for agroecosystems at decision-relevant scales is critical to mitigating climate change and ensuring sustainable food production. However, conventional process-based or data-driven modeling approaches alone have large prediction uncertainties due to the complex biogeochemical processes to model and the lack of observations to constrain many key state and flux variables. Here we propose a Knowledge-Guided Machine Learning (KGML) framework that addresses the above challenges by integrating knowledge embedded in a process-based model, high-resolution remote sensing observations, and machine learning (ML) techniques. Using the U.S. Corn Belt as a testbed, we demonstrate that KGML can outperform conventional process-based and black-box ML models in quantifying carbon cycle dynamics. Our high-resolution approach quantitatively reveals 86% more spatial detail of soil organic carbon changes than conventional coarse-resolution approaches. Moreover, we outline a protocol for improving KGML via various paths, which can be generalized to develop hybrid models to better predict complex earth system dynamics.

17.
ACS Appl Mater Interfaces ; 16(3): 3966-3977, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38224457

RESUMO

Multivapor-responsive biocompatible soft actuators have immense potential for applications in soft robotics and medical technology. We report fast, fully reversible, and multivapor-responsive controlled actuation of a pure cassava-starch-based film. Notably, this starch-based actuator sustains its actuated state for over 60 min with a continuous supply of water vapor. The durability of the film and repeatability of the actuation performance have been established upon subjecting the film to more than 1400 actuation cycles in the presence of water vapor. The starch-based actuators exhibit intriguing antagonistic actuation characteristics when exposed to different solvent vapors. In particular, they bend upward in response to water vapor and downward when exposed to ethanol vapor. This fascinating behavior opens up new possibilities for controlling the magnitude and direction of actuation by manipulating the ratio of water to ethanol in the binary solution. Additionally, the control of the bending axis of the starch-based actuator, when exposed to water vapor, is achieved by imprinting-orientated patterns on the surface of the starch film. The effect of microstructure, postsynthesis annealing, and pH of the starch solution on the actuation performance of the starch film is studied in detail. Our starch-based actuator can lift 10 times its own weight upon exposure to ethanol vapor. It can generate force ∼4.2 mN upon exposure to water vapor. To illustrate the vast potential of our cassava-starch-based actuators, we have showcased various proof-of-concept applications, ranging from biomimicry to crawling robots, locomotion near perspiring human skin, bidirectional electric switches, ventilation in the presence of toxic vapors, and smart lifting systems. These applications significantly broaden the practical uses of these starch-based actuators in the field of soft robotics.

18.
J Fluoresc ; 34(1): 227-244, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37195540

RESUMO

Highly emissive ternary Eu(III) complexes were synthesized with a tri-fluorinated ß-diketone as principal ligand and heterocyclic aromatic compounds as ancillary ligands to assess their utility as an illuminating material for display devices and other optoelectronics. The general characterizations, regarding the coordinating facets of complexes were accomplished via various spectroscopic techniques. Thermal stability was investigated via TGA/DTA. Photophysical analysis was accomplished by PL studies, Band gap value, color parameters and J-O analysis. DFT calculations were performed adopting geometrically optimized structure of complexes. Superb thermal stability has been achieved in complexes, which decides their concrete candidature for display devices. The bright red luminescence of complexes is ascribed to 5D0 → 7F2 transition of Eu(III) ion. Colorimetric parameters unlocked the applicability of complexes as warm light source and J-O parameters adequately summarized the coordinating surrounding around the metal ion. Various radiative properties were also evaluated which suggested the prospective use of complexes in lasers and other optoelectronic devices. The band gap and Urbach band tail, procured from absorption spectra, revealed the semiconducting behavior of synthesized complexes. DFT studies rendered the energies of FMO and various other molecular parameters. It can be summarized from the photophysical and optical analysis of synthesized complexes that these complexes are virtuous luminescent materials and possess potentiality to be used in diverse domain of display devices.

19.
Nature ; 625(7993): 101-109, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38093010

RESUMO

Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed1-6. However, missing from these measurements is the ability to routinely and easily spatially localize these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are tagged with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as an input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 µm spatial resolution and delivered whole-transcriptome data that are indistinguishable in quality from ordinary single-nucleus RNA-sequencing data. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualized receptor-ligand interactions driving B cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to almost any single-cell measurement technology. As a proof of principle, we performed multiomic measurements of open chromatin, RNA and T cell receptor (TCR) sequences in the same cells from metastatic melanoma, identifying transcription factor motifs driving cancer cell state transitions in spatially distinct microenvironments. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.


Assuntos
Código de Barras de DNA Taxonômico , Genômica , Animais , Humanos , Camundongos , Encéfalo/citologia , Encéfalo/metabolismo , Cromatina/genética , Cromatina/metabolismo , Código de Barras de DNA Taxonômico/métodos , Epigênese Genética , Perfilação da Expressão Gênica , Genômica/métodos , Melanoma/genética , Melanoma/patologia , Tonsila Palatina/citologia , Tonsila Palatina/metabolismo , Receptores de Antígenos de Linfócitos T/genética , RNA/genética , Análise de Célula Única/métodos , Transcriptoma/genética , Microambiente Tumoral , Hipocampo/citologia , Hipocampo/metabolismo , Análise da Expressão Gênica de Célula Única , Especificidade de Órgãos , Ligantes , Elementos de Resposta/genética , Fatores de Transcrição/metabolismo
20.
Nucleic Acids Res ; 52(D1): D174-D182, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37962376

RESUMO

JASPAR (https://jaspar.elixir.no/) is a widely-used open-access database presenting manually curated high-quality and non-redundant DNA-binding profiles for transcription factors (TFs) across taxa. In this 10th release and 20th-anniversary update, the CORE collection has expanded with 329 new profiles. We updated three existing profiles and provided orthogonal support for 72 profiles from the previous release's UNVALIDATED collection. Altogether, the JASPAR 2024 update provides a 20% increase in CORE profiles from the previous release. A trimming algorithm enhanced profiles by removing low information content flanking base pairs, which were likely uninformative (within the capacity of the PFM models) for TFBS predictions and modelling TF-DNA interactions. This release includes enhanced metadata, featuring a refined classification for plant TFs' structural DNA-binding domains. The new JASPAR collections prompt updates to the genomic tracks of predicted TF binding sites (TFBSs) in 8 organisms, with human and mouse tracks available as native tracks in the UCSC Genome browser. All data are available through the JASPAR web interface and programmatically through its API and the updated Bioconductor and pyJASPAR packages. Finally, a new TFBS extraction tool enables users to retrieve predicted JASPAR TFBSs intersecting their genomic regions of interest.


Assuntos
Bases de Dados Genéticas , Ligação Proteica , Fatores de Transcrição , Animais , Humanos , Camundongos , Bases de Dados Genéticas/normas , Bases de Dados Genéticas/tendências , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Plantas/genética
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