Search results for "570"
showing 10 items of 1074 documents
Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Frac…
2014
In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC50 value of 5 mu M and without cytotoxic effects against J774.1 macrophages at 100 mu M concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.
Pathogens and host immunity in the ancient human oral cavity.
2014
Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize: (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) the first evidence of ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing co…
Proteome-wide comparison between the amino acid composition of domains and linkers
2018
Objective Amino acid composition is a sequence feature that has been extensively used to characterize proteomes of many species and protein families. Yet the analysis of amino acid composition of protein domains and the linkers connecting them has received less attention. Here, we perform both a comprehensive full-proteome amino acid composition analysis and a similar analysis focusing on domains and linkers, to uncover domain- or linker-specific differential amino acid usage patterns. Results The amino acid composition in the 38 proteomes studied showcase the greater variability found in archaea and bacteria species compared to eukaryotes. When focusing on domains and linkers, we describe …
Bioassays to monitor taspase1 function for the identification of pharmacogenetic inhibitors
2011
Background Threonine Aspartase 1 (Taspase1) mediates cleavage of the mixed lineage leukemia (MLL) protein and leukemia provoking MLL-fusions. In contrast to other proteases, the understanding of Taspase1's (patho)biological relevance and function is limited, since neither small molecule inhibitors nor cell based functional assays for Taspase1 are currently available. Methodology/Findings Efficient cell-based assays to probe Taspase1 function in vivo are presented here. These are composed of glutathione S-transferase, autofluorescent protein variants, Taspase1 cleavage sites and rational combinations of nuclear import and export signals. The biosensors localize predominantly to the cytoplasm…
Reproducible and Consistent Quantification of the Saccharomyces cerevisiae Proteome by SWATH-mass spectrometry *
2015
Targeted mass spectrometry by selected reaction monitoring (S/MRM) has proven to be a suitable technique for the consistent and reproducible quantification of proteins across multiple biological samples and a wide dynamic range. This performance profile is an important prerequisite for systems biology and biomedical research. However, the method is limited to the measurements of a few hundred peptides per LC-MS analysis. Recently, we introduced SWATH-MS, a combination of data independent acquisition and targeted data analysis that vastly extends the number of peptides/proteins quantified per sample, while maintaining the favorable performance profile of S/MRM. Here we applied the SWATH-MS t…
The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10
2012
The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and β we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)—the constitutive α-secretase—is activated by meprin β through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin…
GH successful treatment in a female with a de novo 46,XX,add(X)(p36),t(X;Y)(p36.3;p11.2), growth impairment and SHOX-haploinsufficiency
2019
Abstract Children with chromosome translocations, concerning X chromosome, have a genetic pattern different from Turner syndrome; however, when a translocation involves the of part of X chromosome including short stature homeobox-containing Sex-determining Region Y gene, growth may be severely compromised. We describe the clinical case of a 2.2-year-old-female, arrived at our paediatric unit for a decrease of height velocity. The karyotype was 46,XX,add(X)(p36.3). Array comparative genomic hybridization showed a fragment of Y chromosome, extended from 8.803.981 (Yp11.2) to 28.767.604 (Yq11.23). The final karyotype was 46,XX,add(X)(p36),t(X;Y)(p36.3;p11.2). Fluorescence in situ Hybridization…
Quejas somáticas, conciencia emocional e inadaptación en población escolar
2015
Resumen: Introducción: Las quejas somáticas son frecuentes en la infancia. La investigación ha puesto de manifiesto su relación con la conciencia emocional y la inadaptación. El estudio tuvo 3 objetivos: 1) analizar la prevalencia de las quejas somáticas; 2) explorar las relaciones entre las variables evaluadas: quejas somáticas, diferenciar emociones, comunicar verbalmente emociones, no esconder emociones, conciencia corporal, atender emociones de otros, análisis de las propias emociones, inadaptación personal, inadaptación social, inadaptación familiar e inadaptación escolar, y 3) identificar variables predictoras de las quejas somáticas. Pacientes y métodos: Los participantes, selecciona…
Intervención psicológica en la adhesion al tratamiento de enfermedades crónicas pediátricas
2001
El presente trabajo analiza desde el punto de vista psicológico los problemas de cumplimiento del tratamiento en las enfermedades crónicas pediátricas. Se describe la repercusión del tema sobre la enfermedad, el médico responsable, el paciente y sus familiares, haciendo una mención especial a la complejidad del problema cuando se presenta en la población adolescente. Se revisan los factores que dificultan la adherencia a las prescripciones médicas, identificando aspectos relacionados con la enferm edad y el tratamiento, y variables cognitivas, emocionales, conductuales, familiares, sociales, culturales, organizacionales y económicas. Se realiza una propuesta de intervención psicológica que …
Editors’ corner: Anales de Pediatria annual report
2016
(2%), 29 AEP articles (4%), 101 images in paediatrics (15%) and 62 brief reports (9%). This last type of manuscript has been discontinued with the introduction of the new editorial standards and has been replaced by the scientific letters section. The number of manuscripts evaluated in the first four months of 2015 was similar to that for the same period from the previous year. There was an increase in the number of original articles submitted from 34.7% to 42.3%. Invited Editorials written by nationally and internationally recognised experts have increased, whilst letters to the editor have decreased. The rejection rate for 2014 as a whole was 56%, and in the first months of 2015 it rose t…