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1.
J Microsc ; 284(3): 214-232, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34333776

RESUMEN

Active virosomes (AVs) are derivatives of viruses, broadly similar to 'parent' pathogens, with an outer envelope that contains a bespoke genome coding for four to five viral proteins capable of eliciting an antigenic response. AVs are essentially novel vaccine formulations that present on their surface selected viral proteins as antigens. Once administered, they elicit an initial 'anti-viral' immune response. AVs are also internalised by host cells where their cargo viral genes are used to express viral antigen(s) intracellularly. These can then be transported to the host cell surface resulting in a second wave of antigen exposure and a more potent immuno-stimulation. A new 3D correlative microscopy approach is used here to provide a robust analytical method for characterisation of Zika- and Chikungunya-derivatised AV populations including vesicle size distribution and variations in antigen loading. Manufactured batches were compared to assess the extent and nature of batch-to-batch variations. We also show preliminary results that verify antigen expression on the surface of host cells. We present here a reliable and efficient high-resolution 3D imaging regime that allows the evaluation of the microstructure and biochemistry of novel vaccine formulations such as AVs.


A novel combination of microscopies involving X-ray and laser light has been developed at the correlative cryo-imaging beamline B24 of the UK synchrotron which can be used to analyse across- and within-batch variability of active virosome vaccine formulations. We use 3D fluorescence imaging to localise viral components within vaccine vesicles and soft X-ray tomography to characterise sample variability and impact upon delivery to cells. Moreover, we offer the next step in automation of data processing and evaluation to further enable rapid assessment of exosome-based vaccines. Active virosome vaccines are suspensions of membrane-bounded vesicles that carry antigens and genetic material from select viral pathogens. These elicit both an initial immune response through their introduction and a subsequent sustained antigenic potential via gene expression in host cells. In this case, as in all novel vaccine formulations, rapid assessment and batch standardisation are of paramount importance for the medical community and the methods described here provide a robust way of quick and efficient assessment and validation of formulations during research and development and at the production stages.


Asunto(s)
Vacunas , Proteínas Virales/química , Proteínas Virales/genética , Infección por el Virus Zika , Virus Zika , Humanos , Microscopía Fluorescente , Temperatura , Tomografía por Rayos X , Desarrollo de Vacunas , Proteínas Virales/metabolismo , Virosomas
2.
Cardiol Young ; 29(10): 1278-1281, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31475645

RESUMEN

We report a case of a 13-year-old male with trisomy 21 in Southwestern Ontario, Canada, who presented with bilateral pneumonia, pericardial effusion, and peripheral oedema. The pericardial effusion did not respond to standard treatment options. Evaluation revealed severe dietary restriction, consistent with kwashiorkor. Hospital course was complicated by severe hypoalbuminaemia, hypocalcaemia, hypomagnesaemia, and hypophosphataemia. The pericardial effusion and other findings resolved gradually upon slow introduction of a well-balanced diet and adequate caloric and protein intake. Kwashiorkor is an unusual cause of pericardial effusion and can be overlooked especially in developed countries. It is a type of protein-calorie malnutrition often seen in children of impoverished countries and famine. It is a result of insufficient protein intake in the context of adequate caloric intake. Pericardial effusion not responding to usual treatment is a challenge, and other aetiologies must be considered. Malnutrition is often underdiagnosed or misdiagnosed in developed countries with devastating outcomes if unrecognised. This makes it imperative to consider this diagnosis, recognise potential risk factors, and be prepared to accurately assess overall nutritional status.


Asunto(s)
Ecocardiografía/métodos , Kwashiorkor/complicaciones , Derrame Pericárdico/diagnóstico , Pericardio/diagnóstico por imagen , Adolescente , Diagnóstico Diferencial , Humanos , Kwashiorkor/diagnóstico , Masculino , Derrame Pericárdico/etiología
3.
PLoS Comput Biol ; 14(3): e1005873, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29543799

RESUMEN

It is generally acknowledged that, for reproducibility and progress of human genomic research, data sharing is critical. For every sharing transaction, a successful data exchange is produced between a data consumer and a data provider. Providers of human genomic data (e.g., publicly or privately funded repositories and data archives) fulfil their social contract with data donors when their shareable data conforms to FAIR (findable, accessible, interoperable, reusable) principles. Based on our experiences via Repositive (https://repositive.io), a leading discovery platform cataloguing all shared human genomic datasets, we propose guidelines for data providers wishing to maximise their shared data's FAIRness.


Asunto(s)
Bases de Datos Genéticas/normas , Genoma Humano/genética , Genómica/normas , Difusión de la Información , Humanos
4.
PLoS Biol ; 14(3): e1002418, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27011302

RESUMEN

There is no unified place where genomics researchers can search through all available raw genomic data in a way similar to OMIM for genes or Uniprot for proteins. With the recent increase in the amount of genomic data that is being produced and the ever-growing promises of precision medicine, this is becoming more and more of a problem. DNAdigest is a charity working to promote efficient sharing of human genomic data to improve the outcome of genomic research and diagnostics for the benefit of patients. Repositive, a social enterprise spin-out of DNAdigest, is building an online platform that indexes genomic data stored in repositories and thus enables researchers to search for and access a range of human genomic data sources through a single, easy-to-use interface, free of charge.


Asunto(s)
Bases de Datos Genéticas , Genómica , Difusión de la Información
5.
Artículo en Inglés | MEDLINE | ID: mdl-18001902

RESUMEN

There is an unmet medical need for a more reliable and earlier assessment of patients suspected of having a deep vein thrombosis. We describe a novel approach which is developing a highly reliable, accurate, portable and handheld prototype medical diagnostic device to improve radically the speed, accuracy and reliability with which DVT and related blood clotting conditions can be assessed. The device will measure whole blood concentration of D-dimer, a recognized biomarker of increased blood clotting activity, and through innovation in the development of a novel detection, measurement and reporting system, will offer the opportunity to use the test in the point of care setting. The device combines innovation in antibody bio-engineering for high specificity immunoassay-based diagnostics and nano/micro engineered impedimetric analysis electrodes incorporating a biocompatible polymer substrate with development of a disposable microfluidic manifold specifically enabling diagnostics at the point-of-first-contact.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/análisis , Inmunoensayo/métodos , Trombosis de la Vena/sangre , Especificidad de Anticuerpos , Materiales Biocompatibles/química , Biomarcadores/sangre , Impedancia Eléctrica , Humanos , Inmunoensayo/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Sistemas de Atención de Punto , Polímeros/química , Trombosis de la Vena/diagnóstico
6.
Nanomedicine (Lond) ; 1(4): 499-504, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17716155

RESUMEN

Cenamps' highly talented and commercially experienced team work closely with business leaders to stimulate and manage market-led innovation, enabling businesses to develop new products and services as well as strengthen the regional economic foundation, R&D capabilities and performance. Cenamps achieves this by establishing new state-of-the-art R&D facilities and applied research projects for developing new technologies that will yield significant societal, economic and commercial benefits.


Asunto(s)
Biotecnología/organización & administración , Financiación Gubernamental/organización & administración , Industrias/organización & administración , Nanomedicina/organización & administración , Organizaciones sin Fines de Lucro/organización & administración , Investigación/organización & administración , Inglaterra , Emprendimiento/organización & administración
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