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1.
Microbiol Resour Announc ; 11(7): e0109221, 2022 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-35658537

RESUMEN

We report the complete genome sequence of Salipaludibacillus sp. strain CUR1, which was isolated from Sambhar Lake (a soda lake) in Rajasthan, India. The whole-genome sequencing of this strain has been done to explore the industrially important hydrolytic and extracellular enzymes that can be active under high-salt and high-pH conditions.

2.
Comput Biol Med ; 147: 105758, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35763933

RESUMEN

BACKGROUND: The vaccines used against SARS-CoV-2 by now have been able to develop some neutralising antibodies in the vaccinated population and their effectiveness has been challenged by the emergence of the new strains with numerous mutations in the spike protein of SARS-CoV-2. Since S protein is the major immunogenic protein of the virus which contains Receptor Binding Domain (RBD) that interacts with the human Angiotensin-Converting Enzyme 2 (ACE2) receptors, any mutations in this region should affect the neutralisation potential of the antibodies leading to the immune evasion. Several variants of concern of the virus have emerged so far, amongst which the most critical are Delta and recently reported Omicron. In this study, we have mapped and reported mutations on the modelled RBD and evaluated binding affinities of various human antibodies with it. METHOD: Docking and molecular dynamics simulation studies have been used to explore the effect of mutations on the structure of RBD and RBD-antibody interaction. RESULTS: These analyses show that the mutations mostly at the interface of a nearby region lower the binding affinity of the antibody by ten to forty percent, with a downfall in the number of interactions formed as a whole. It implies the generation of immune escape variants. CONCLUSIONS: Notable mutations and their effect was characterised that explain the structural basis of antibody efficacy in Delta and a compromised neutralisation effect for the Omicron variant. Thus, our results pave the way for robust vaccine design that can be effective for many variants.


Asunto(s)
COVID-19 , Glicoproteína de la Espiga del Coronavirus , Humanos , Evasión Inmune , Mutación , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética
3.
Nanomaterials (Basel) ; 12(3)2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35159802

RESUMEN

In the last few decades, the vast potential of nanomaterials for biomedical and healthcare applications has been extensively investigated. Several case studies demonstrated that nanomaterials can offer solutions to the current challenges of raw materials in the biomedical and healthcare fields. This review describes the different nanoparticles and nanostructured material synthesis approaches and presents some emerging biomedical, healthcare, and agro-food applications. This review focuses on various nanomaterial types (e.g., spherical, nanorods, nanotubes, nanosheets, nanofibers, core-shell, and mesoporous) that can be synthesized from different raw materials and their emerging applications in bioimaging, biosensing, drug delivery, tissue engineering, antimicrobial, and agro-foods. Depending on their morphology (e.g., size, aspect ratio, geometry, porosity), nanomaterials can be used as formulation modifiers, moisturizers, nanofillers, additives, membranes, and films. As toxicological assessment depends on sizes and morphologies, stringent regulation is needed from the testing of efficient nanomaterials dosages. The challenges and perspectives for an industrial breakthrough of nanomaterials are related to the optimization of production and processing conditions.

4.
J Biomol Struct Dyn ; 40(11): 5189-5202, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-33403946

RESUMEN

SARS-CoV-2 has been efficient in ensuring that many countries are brought to a standstill. With repercussions ranging from rampant mortality, fear, paranoia, and economic recession, the virus has brought together countries to look at possible therapeutic countermeasures. With prophylactic interventions possibly months away from being particularly effective, a slew of measures and possibilities concerning the design of vaccines are being worked upon. We attempted a structure-based approach utilizing a combination of epitope prediction servers and Molecular dynamic (MD) simulations to develop a multi-epitope-based subunit vaccine that involves the two subunits of the spike glycoprotein of SARS-CoV-2 (S1 and S2) coupled with a substantially effective chimeric adjuvant to create stable vaccine constructs. The designed constructs were evaluated based on their docking with Toll-Like Receptor (TLR) 4. Our findings provide an epitope-based peptide fragment that can be a potential candidate for the development of a vaccine against SARS-CoV-2. Recent experimental studies based on determining immunodominant regions across the spike glycoprotein of SARS-CoV-2 indicate the presence of the predicted epitopes included in this study.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Glicoproteína de la Espiga del Coronavirus , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Epítopos de Linfocito B , Epítopos de Linfocito T , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas de Subunidad/inmunología
5.
Materials (Basel) ; 14(20)2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34683568

RESUMEN

Carbon nanomaterials (CNMs) have received tremendous interest in the area of nanotechnology due to their unique properties and flexible dimensional structure. CNMs have excellent electrical, thermal, and optical properties that make them promising materials for drug delivery, bioimaging, biosensing, and tissue engineering applications. Currently, there are many types of CNMs, such as quantum dots, nanotubes, nanosheets, and nanoribbons; and there are many others in development that promise exciting applications in the future. The surface functionalization of CNMs modifies their chemical and physical properties, which enhances their drug loading/release capacity, their ability to target drug delivery to specific sites, and their dispersibility and suitability in biological systems. Thus, CNMs have been effectively used in different biomedical systems. This review explores the unique physical, chemical, and biological properties that allow CNMs to improve on the state of the art materials currently used in different biomedical applications. The discussion also embraces the emerging biomedical applications of CNMs, including targeted drug delivery, medical implants, tissue engineering, wound healing, biosensing, bioimaging, vaccination, and photodynamic therapy.

6.
Protein J ; 39(5): 434-448, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33068234

RESUMEN

Despite diligent vaccination efforts, influenza virus infection remains a major cause for respiratory-related illness across the globe. The less-than-optimal immunity conferred by the currently prescribed seasonal vaccines and protracted production times warrant the development of novel vaccines. Induction of an epitope-focused antibody response targeting known neutralization epitopes is a viable strategy to enhance the breadth of protection against rapidly evolving infectious viruses. We report the development of a design framework to mimic the hemagglutinin (HA) head fragment of H1-subtype viruses by delineating the interaction network of invariant residues lining the receptor binding site (RBS); a site targeted by cross-reactive neutralizing antibodies. The incorporation of multiple sequence alignment information in our algorithm to fix the construct termini and engineer rational mutations facilitates the facile extension of the design to heterologous (subtype-specific) influenza strains. We evaluated our design protocol by generating head fragments from divergent influenza A H1N1 A/Puerto Rico/8/34 and pH1N1 A/California/07/2009 strains that share a sequence identity of only 74.4% within the HA1 subunit. The designed immunogens exhibited characteristics of a well-ordered protein, and bound conformation-specific RBS targeting antibodies with high affinity, a desirable feature for putative vaccine candidates. Additionally, the bacterial expression of these immunogens provides a low-cost, rapidly scalable alternative.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Subtipo H1N1 del Virus de la Influenza A/química , Imitación Molecular , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Vacunas contra la Influenza/química , Vacunas contra la Influenza/genética , Dominios Proteicos
7.
Biochemistry ; 58(13): 1738-1750, 2019 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-30843689

RESUMEN

Temperature-sensitive (Ts) mutants are important tools for understanding the role of essential gene(s), but their molecular basis is not well understood. We use CcdB ( Controller of Cell Death protein B) as a model system to explore the effects of Ts mutations on protein stability, folding, and ligand binding. Previously isolated Ts CcdB mutants fall broadly into two categories, namely, buried site (<5% accessibility) and active site (involved in DNA gyrase binding). Several mutants from each category were characterized. It was found that buried-site Ts mutants had decreased stability and foldability, higher aggregation propensity, and, in most cases, reduced affinity for gyrase at both permissive and restrictive temperatures. In contrast, exposed, active-site Ts mutants of CcdB exhibited stability either higher than or similar to that of the wild type and weakened inhibition of DNA gyrase function and/or reduced affinity for gyrase at a higher temperature. At all temperatures, Ts mutations at exposed, active-site residues primarily decrease specific activity without affecting protein levels, while Ts mutations at most buried residues decrease both specific activity and protein levels. Ts phenotypes in both cases arise because total activity is decreased below the threshold required for survival at the restrictive temperature but remains above it at the permissive temperatures. For several mutants, Ts phenotypes were ameliorated upon overexpression of the trigger factor chaperone, suggesting that Ts phenotypes may result from mutational effects on in vivo protein folding rather than on protein stability. This study delineates the diverse factors that contribute to Ts phenotypes. These insights can facilitate rational design of Ts mutants.


Asunto(s)
Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Escherichia coli/química , Escherichia coli/genética , Modelos Moleculares , Mutación , Fenotipo , Agregado de Proteínas , Conformación Proteica , Estabilidad Proteica , Desplegamiento Proteico , Temperatura
8.
J Hazard Mater ; 171(1-3): 268-72, 2009 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-19592157

RESUMEN

N,N-dimethylformamide (DMF) is a man-made compound that is widely used as a solvent for the synthesis of various organic compounds. In this study, a bacterial strain Paracoccus sp. DMF capable of using DMF as the sole carbon, nitrogen and energy source, was isolated from an enrichment culture developed using activated sludge from domestic waste water treatment unit as the source inoculum. The strain DMF was characterized by biochemical tests and 16S rDNA sequence analysis, to be belonging to the genus Paracoccus. Growth on DMF was accompanied with ammonia release and the total organic carbon (TOC) analysis indicated its extensive mineralization. Batch culture studies were conducted in the substrate range of 100-5000 mg L(-1) to determine the biokinetic constants. Strain Paracoccus sp. DMF could tolerate very high concentrations of DMF as the growth was observed even at 15000 mg L(-1). High (micro(max)) and (K(i)) showed the suitability of the strain for the treatment of DMF containing waste water. Transient accumulation of dimethylamine (DMA) in the medium during the growth on DMF and utilization of DMA and monomethylamine (MMA) as growth substrates by Paracoccus sp. strain DMF showed that the pathway of DMF degradation involves DMA and MMA as intermediates, ultimately leading to the formation of carbon dioxide (CO(2)) and ammonia (NH(3)).


Asunto(s)
Formamidas/química , Paracoccus/metabolismo , Aguas del Alcantarillado , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Amoníaco/química , Carbono/química , Dióxido de Carbono/química , ADN Ribosómico/química , Dimetilformamida , Cinética , Metilaminas/química , Filogenia , Plásmidos/metabolismo , Rhodococcus/metabolismo , Solventes/química
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