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1.
Langmuir ; 35(5): 1266-1272, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29801414

RESUMO

Development of antifouling films which selectively capture or target proteins of interest is essential for controlling interactions at the "bio/nano" interface. However, in order to synthesize biofunctional films from synthetic polymers that incorporate chemical "motifs" for surface immobilization, antifouling, and oriented biomolecule attachment, multiple reaction steps need to be carried out at the solid/liquid interface. EKx is a zwitterionic peptide that has previously been shown to have excellent antifouling properties. In this study, we recombinantly expressed EKx peptides and genetically encoded both surface attachment and antibody-binding motifs, before characterizing the resultant biopolymers by traditional methods. These peptides were then immobilized to organosilica nanoparticles for binding IgG, and subsequently capturing dengue NS1 as a model antigen from serum-containing solution. We found that a mixed layer of a short peptide (4.9 kDa) "backfilled" with a longer peptide terminated with an IgG-binding Z-domain (18 kDa) demonstrated selective capture of dengue NS1 protein down to ∼10 ng mL-1 in either PBS or 20% serum.


Assuntos
Incrustação Biológica/prevenção & controle , Imunoglobulina G/metabolismo , Peptídeos/metabolismo , Proteínas Recombinantes/metabolismo , Vírus da Dengue/química , Escherichia coli/genética , Proteínas Imobilizadas/genética , Proteínas Imobilizadas/metabolismo , Imunoglobulina G/química , Nanopartículas/química , Peptídeos/genética , Ligação Proteica , Domínios Proteicos , Engenharia de Proteínas/métodos , Proteínas Recombinantes/genética , Dióxido de Silício/química , Proteínas não Estruturais Virais/metabolismo
2.
Shoulder Elbow ; 10(1): 45-51, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29276537

RESUMO

Background: Optimal surgical treatment of lateral epicondylitis remains uncertain. Recently, radiofrequency microtenotomy (RFMT) has been proposed as a suitable treatment. We compared RFMT with standard open release (OR) in this prospective randomized controlled trial. Methods: In total, 41 patients with symptoms for at least 6 months were randomized into two groups: 23 patients had RFMT and 18 had OR. Two patients from RFMT withdrew. Each patient underwent Numerical Rating Scale (NRS) pain score, grip strength and Disabilities of the Arm, Shoulder and Hand (DASH) scores pre-operatively and at 6 weeks. Pain and DASH scores were repeated at 6 months and 12 months. Results: NRS pain scores improved by 4.8 points for RFMT and by 3.9 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Grip strength improved by 31% in the RFMT group compared to 38% in OR. There was no significant difference between the initial and 6 weeks scores or between treatments. At 1 year, DASH was 39.8 points for RFMT and 24.4 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Conclusions: Both groups showed significant improvements and similar benefit to the patient. The results of the present study do not show any benefit of RFMT over the standard OR. As a result of the extra expense of RFMT, we therefore recommend that OR is offered as the standard surgical management.

3.
Exp Appl Acarol ; 72(3): 303-315, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28752480

RESUMO

Cattle tick infestations remain an important burden for farmers in tropical area like in New Caledonia. With the development of acaricide resistance, tick vaccines should be an attractive alternative to control ticks but their efficacy needs to be improved. In this study three adjuvants were studied in an experimental tick vaccine with a Bm86 protein to assess their performance in terms of antibody productions and adverse reactions following vaccinations. The water-in-oil adjuvant ISA 61 VG led to higher antibody titers compared to a water-in-oil-in-water adjuvant ISA 201 VG and an aqueous polymeric adjuvant Montanide Gel 01. Vaccinations with these three adjuvants did not produce severe general reaction but an increase in skin thickness was observed especially with both oil-based emulsions. These results indicated that the water-in-oil adjuvant is the most interesting to use for this vaccine but local adverse reactions remain an issue.


Assuntos
Doenças dos Bovinos/prevenção & controle , Rhipicephalus/imunologia , Infestações por Carrapato/veterinária , Vacinas/imunologia , Animais , Formação de Anticorpos , Bovinos , Doenças dos Bovinos/imunologia , Glicoproteínas de Membrana , Nova Caledônia , Proteínas Recombinantes , Rhipicephalus/crescimento & desenvolvimento , Infestações por Carrapato/imunologia , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle
4.
Stud Health Technol Inform ; 235: 491-495, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28423841

RESUMO

Discovery of useful relationships between scholarly assets on the web is challenging, both in terms generating the right metadata around the assets, and in connecting all relevant digital entities in chain of provenance accessible to the whole community. This paper reports the development of a framework and tools enabling scholarly asset relationships to be expressed in a standard and open way, illustrated with use-cases of discovering new knowledge across cohort studies. The framework uses Research Objects for aggregation, distributed databases for storage, and distributed ledgers for provenance. Our proposal avoids management by a single central platform or organization, instead leveraging the use of existing resources and platforms across natural partnerships. Our proposed infrastructure will support a wide range of users from system administrators to researchers.


Assuntos
Redes de Comunicação de Computadores , Disseminação de Informação , Comunicação Acadêmica , Humanos , Metadados
5.
J Invest Dermatol ; 137(2): 430-439, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27697464

RESUMO

Proteases have pivotal roles in the skin's outermost layer, the epidermis. In the stratum corneum, serine proteases from the kallikrein-related peptidase (KLK) family have been implicated in several key homeostatic processes, including desquamation. However, the precise contribution of specific KLKs to each process remains unclear. To address this, we used a chemical biology approach and designed selective substrates and inhibitors for KLK7, the most abundant KLK protease in the stratum corneum. The resulting KLK7 inhibitor is the most potent inhibitor of this protease reported to date (Ki = 140 pM), and displays at least 1,000-fold selectivity over several proteases that are related by function (KLK5 and KLK14) or specificity (chymotrypsin). We then used substrates and inhibitors for KLK5, KLK7, and KLK14 to explore the activity of each protease in the stratum corneum using casein zymography and an ex vivo desquamation assay. These experiments provide the most detailed assessment of each KLK's contribution to corneocyte shedding in the plantar stratum corneum, revealing that inhibition of KLK7 alone is sufficient to block shedding, whereas KLK5 is also a major contributor. Collectively, these findings unveil chemical tools for studying KLK activity and demonstrate their potential for characterizing KLK biological functions in epidermal homeostasis.


Assuntos
Epiderme/metabolismo , Calicreínas/antagonistas & inibidores , Calicreínas/metabolismo , Humanos , Biblioteca de Peptídeos
6.
Stud Health Technol Inform ; 216: 320-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26262063

RESUMO

There is an important knowledge gap in food allergy management in understanding the factors that determine allergic reactions to food, in gathering objective reports of reactions in real time, and in accessing patients' reaction-histories during consultations. We investigate how eHealth methods can close this knowledge gap. We report experiences with an online tool for reporting allergic reactions that we have developed as a web application. This application has been successfully validated by participants from Ireland and the UK, and is currently being used in a pilot where participants report allergic reactions in near-real time.


Assuntos
Hipersensibilidade Alimentar/epidemiologia , Internet/organização & administração , Vigilância da População/métodos , Consulta Remota/organização & administração , Autocuidado/métodos , Software , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Sistemas On-Line , Prevalência , Autorrelato , Reino Unido/epidemiologia
9.
Biopolymers ; 100(5): 510-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24078181

RESUMO

Potent and specific enzyme inhibition is a key goal in the development of therapeutic inhibitors targeting proteolytic activity. The backbone-cyclized peptide, Sunflower Trypsin Inhibitor (SFTI-1) affords a scaffold that can be engineered to achieve both these aims. SFTI-1's mechanism of inhibition is unusual in that it shows fast-on/slow-off kinetics driven by cleavage and religation of a scissile bond. This phenomenon was used to select a nanomolar inhibitor of kallikrein-related peptidase 7 (KLK7) from a versatile library of SFTI variants with diversity tailored to exploit distinctive surfaces present in the active site of serine proteases. Inhibitor selection was achieved through the use of size exclusion chromatography to separate protease/inhibitor complexes from unbound inhibitors followed by inhibitor identification according to molecular mass ascertained by mass spectrometry. This approach identified a single dominant inhibitor species with molecular weight of 1562.4 Da, which is consistent with the SFTI variant SFTI-WCTF. Once synthesized individually this inhibitor showed an IC50 of 173.9 ± 7.6 nM against chromogenic substrates and could block protein proteolysis. Molecular modeling analysis suggested that selection of SFTI-WCTF was driven by specific aromatic interactions and stabilized by an enhanced internal hydrogen bonding network. This approach provides a robust and rapid route to inhibitor selection and design.


Assuntos
Helianthus , Inibidores da Tripsina , Helianthus/química , Ligação de Hidrogênio , Calicreínas , Peptídeos Cíclicos/química , Tripsina/química , Inibidores da Tripsina/química
10.
Biopolymers ; 2013 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-23494567

RESUMO

Potent and specific enzyme inhibition is a key goal in development of therapeutic inhibitors targeting proteolytic activity. The backbone-cyclised peptide, Sunflower Trypsin Inhibitor (SFTI-1) affords a scaffold that can be engineered to achieve both these aims. SFTI-1's mechanism of inhibition is unusual in that it shows fast-on/slow-off kinetics driven by cleavage and religation of a scissile bond. This phenomenon was used to select a nanomolar inhibitor of kallikrein related peptidase 7 (KLK7) from a versatile library of SFTI variants with diversity tailored to exploit distinctive surfaces present in the active site of serine proteases. Inhibitor selection was achieved through use of size exclusion chromatography to separate protease/inhibitor complexes from unbound inhibitors followed by inhibitor identification according to molecular mass ascertained by mass spectrometry. This approach identified a single dominant inhibitor species with molecular weight of 1562.4 Da, which is consistent with the SFTI variant SFTI-WCTF. Once synthesised individually this inhibitor showed an IC50 of 173.9±7.6 nM against chromogenic substrates and could block protein proteolysis. Molecular modelling analysis suggested that selection of SFTI-WCTF was driven by specific aromatic interactions and stabilised by an enhanced internal hydrogen bonding network. This approach provides a robust and rapid route to inhibitor selection and design. © 2013 Wiley Periodicals, Inc. Biopolymers, 2013.

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