Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
J Clin Microbiol ; 60(5): e0017822, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35465708

RESUMO

The ability to distinguish between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) is of ongoing interest due to differences in transmissibility, responses to vaccination, clinical prognosis, and therapy. Although detailed genetic characterization requires whole-genome sequencing (WGS), targeted nucleic acid amplification tests can serve a complementary role in clinical settings, as they are more rapid and accessible than sequencing in most laboratories. We designed and analytically validated a two-reaction multiplex reverse transcription-quantitative PCR (RT-qPCR) assay targeting spike protein mutations L452R, E484K, and N501Y in reaction 1 and del69-70, K417N, and T478K in reaction 2. This assay had 95 to 100% agreement with WGS for 502 upper respiratory tract swab samples collected between 26 April 2021 and 1 August 2021, consisting of 43 Alpha, 2 Beta, 20 Gamma, 378 Delta, and 59 non-VOC infections. Validation in a separate group of 230 WGS-confirmed Omicron variant samples collected in December 2021 and January 2022 demonstrated 100% agreement. This RT-qPCR-based approach can be implemented in clinical laboratories already performing SARS-CoV-2 nucleic acid amplification tests to assist in local epidemiological surveillance and clinical decision-making.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , Reação em Cadeia da Polimerase Multiplex , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Reversa , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
2.
Nat Commun ; 13(1): 5107, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042219

RESUMO

The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk.


Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , Genoma Viral , Estudo de Associação Genômica Ampla , Humanos , SARS-CoV-2/genética
3.
Bioconjug Chem ; 21(4): 653-62, 2010 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-20369815

RESUMO

Previously we reported emulsion polymerization of propylene sulfide with Pluronic F127 as an emulsifier, yielding nanoparticles (NPs) in the 25 nm size range. Immunologically functional NPs were prepared by adding an antigen-Pluronic conjugate to the polymerization mixture ( Reddy , S. T. , et al. ( 2007 ) Nat. Biotechnol. 25, 1159 ). We sought a more flexible scheme for conjugation of antigens and other biomolecules to the NP surfaces that would allow for milder reaction conditions than achievable during the polymerization step. Here, we present the synthesis of such functionalizable NPs in the form of NPs that carry thiol-reactive groups, to which thiol-containing antigens (peptide or protein) or other biomolecules can be conjugated under mild conditions to yield immunofunctional NPs. The Pluronic-stabilized poly(propylene sulfide) (PPS) NPs with thiol-reactive pyridyl disulfide groups are prepared in two steps by (1) emulsion polymerization of propylene sulfide in the presence of a carboxylate-Pluronic and (2) reaction of the carboxylic acid groups on the NP surface with cysteamine pyridyl disulfide and a water-soluble carbodiimide reagent. We choose pyridyl disulfide groups to have a reduction-sensitive disulfide bond linking the antigen to the NP surface, allowing efficient release of antigen inside the cell in response to the reductive conditions within the endosome. The functionalizable NPs are characterized by proton NMR, dynamic light scattering (DLS), UV/vis spectroscopy, and transmission electron microscopy (TEM). Conjugation of small molecules and protein to the NP surface is presented.


Assuntos
Dissulfetos/síntese química , Nanopartículas/química , Ovalbumina/química , Peptídeos/química , Piridinas/síntese química , Compostos de Sulfidrila/química , Biotina/química , Dissulfetos/química , Estrutura Molecular , Tamanho da Partícula , Piridinas/química
4.
medRxiv ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32766602

RESUMO

During COVID19 and other viral pandemics, rapid generation of host and pathogen genomic data is critical to tracking infection and informing therapies. There is an urgent need for efficient approaches to this data generation at scale. We have developed a scalable, high throughput approach to generate high fidelity low pass whole genome and HLA sequencing, viral genomes, and representation of human transcriptome from single nasopharyngeal swabs of COVID19 patients.

5.
Biomaterials ; 29(21): 3152-60, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18440063

RESUMO

The synthetic peptide RAD16-II has shown promise in tissue engineering and drug delivery. It has been studied as a vehicle for cell delivery and controlled release of IGF-1 to repair infarcted cardiac tissue, and as a scaffold to promote capillary formation for an in vitro model of angiogenesis. The structure of RAD16-II is hierarchical, with monomers forming long beta-sheets that pair together to form filaments; filaments form bundles approximately 30-60 nm in diameter; branching networks of filament bundles form macroscopic gels. We investigate the mechanics of shearing between the two beta-sheets constituting one filament, and between cohered filaments of RAD16-II. This shear loading is found in filament bundle bending or in tensile loading of fibers composed of partial-length filaments. Molecular dynamics simulations show that time to failure is a stochastic function of applied shear stress, and that for a given loading time behavior is elastic for sufficiently small shear loads. We propose a coarse-grained model based on Langevin dynamics that matches molecular dynamics results and facilities extending simulations in space and time. The model treats a filament as an elastic string of particles, each having potential energy that is a periodic function of its position relative to the neighboring filament. With insight from these simulations, we discuss strategies for strengthening RAD16-II and similar materials.


Assuntos
Modelos Moleculares , Oligopeptídeos/química , Proteínas/química , Algoritmos , Sequência de Aminoácidos , Simulação por Computador , Elasticidade , Interações Hidrofóbicas e Hidrofílicas , Cinética , Conformação Proteica , Estrutura Secundária de Proteína , Resistência ao Cisalhamento , Engenharia Tecidual
6.
J Endod ; 32(1): 14-6, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16410061

RESUMO

The use of nickel-titanium rotary instrument systems has gained popularity over the past 10 years. One of these instrument systems is the LightSpeed (LightSpeed Technology, Inc, San Antonio, TX). One drawback for all nickel-titanium rotary instruments is the incidence of instrument separation. The purpose of this study was to evaluate the incidence of nonretrievable instrument separation using the LightSpeed system in a clinical setting. A total of 3543 canals were treated over a 24 month period and during that time, 46 LightSpeed instruments were separated and found to be nonretrievable, resulting in a separation rate of 1.30%. This rate was lower than previous reported studies.


Assuntos
Instrumentos Odontológicos , Preparo de Canal Radicular/instrumentação , Ligas Dentárias , Falha de Equipamento , Reutilização de Equipamento , Humanos , Níquel , Titânio
7.
J Biomed Mater Res B Appl Biomater ; 101(6): 981-90, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23529940

RESUMO

Hydrogels formed from self-assembling synthetic oligopeptides have been studied for almost 2 decades for use in tissue engineering and drug delivery. Although a great deal has been learned about the microstructure of these materials, there remain questions about how peptide filaments are ordered to form a gel. These unanswered questions leave a disconnect between our understanding of the observed nanoscale mechanical properties of peptide filaments and the macroscale properties of the gels they constitute. This study helps to bridge this gap by examining the role of filament length and interfilament crosslinks in determining bulk mechanical properties. Microindentation was used for mechanical characterization, and microstructure was observed using thin-section transmission electron microscopy images of gels embedded in resin. Results suggest a gel structure in which filaments are not densely bundled as previously suggested and confirm that crosslinking can be an effective strategy to increase the stiffness of self-assembling oligopeptide gels.


Assuntos
Peptídeos/química , Fenômenos Biomecânicos , Reagentes de Ligações Cruzadas , Sistemas de Liberação de Medicamentos , Glutaral , Hidrogéis/química , Teste de Materiais , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Oligopeptídeos/química , Reologia , Estresse Mecânico , Engenharia Tecidual , Alicerces Teciduais/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA