Search results for "DAS"
showing 10 items of 4164 documents
Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 t…
2010
Abstract The metalloproteases meprin α and β are expressed in several tissues, leukocytes, and cancer cells. In skin, meprins are located in separate layers of human epidermis indicating distinct physiological functions, supported by effects on cultured keratinocytes. Meprin β induces a dramatic change in cell morphology and a significant reduction in cell number, whereas in vitro evidence suggests a role for meprin α in basal keratinocyte proliferation. Meprins are secreted as zymogens that are activated by tryptic proteolytical processing. Here, we identify human kallikrein-related peptidases (KLKs) 4, 5, and 8 to be specific activators of meprins. KLK5 is capable of activating both metal…
Ancient proteins resolve the evolutionary history of Darwin's South American ungulates.
2015
No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as 'South American native ungulates'. To Charles Darwin, who first collected their remains, they included perhaps the 'strangest animal[s] ever discovered'. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago, or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria. Morphology-based analyses have proved unconvincing because convergences…
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…
The Metalloprotease Meprin β Generates Amino Terminal-truncated Amyloid β Peptide Species
2012
The amyloid β (Aβ) peptide, which is abundantly found in the brains of patients suffering from Alzheimer disease, is central in the pathogenesis of this disease. Therefore, to understand the processing of the amyloid precursor protein (APP) is of critical importance. Recently, we demonstrated that the metalloprotease meprin β cleaves APP and liberates soluble N-terminal APP (N-APP) fragments. In this work, we present evidence that meprin β can also process APP in a manner reminiscent of β-secretase. We identified cleavage sites of meprin β in the amyloid β sequence of the wild type and Swedish mutant of APP at positions p1 and p2, thereby generating Aβ variants starting at the first or seco…
The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra
2021
Abstract Background The Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report a proteomic analysis of Hydra head tissue leading to the identification of an astacin family proteinase as a Wnt processing factor. Results Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteo…
Proteomics of Galápagos Marine Iguanas Links Function of Femoral Gland Proteins to the Immune System
2020
Femoral glands secrete a wax-like substance on the inner side of lizard hind legs, which is thought to function as a mode of chemical communication. Though the minor volatile fraction is well studied, the major protein fraction remains enigmatic. Here, we use proteomics to analyze proteins in femoral gland secretions of the Galápagos marine iguana. Although we found no evidence for proteins and peptides involved in chemical communication, we found several immune-regulatory proteins which also demonstrate anti-microbial functions. Accordingly, we show that femoral gland proteins and peptides function as a barrier against microbial infection and may prevent the rapid degradation of volatile s…
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…
Del "dachgärten" al "green roofscape" (1970-2005). Aportación a la historia reciente del paisaje urbano
2007
El urbanismo suele considerar el paisaje urbano a pie de calle. Pero el umbral vertical de la urbe, el paisaje urbano que se descubre desde lo alto de una torre o sobrevolando la ciudad, apenas preocupa a nadie. Una de las alternativas paisajísticas al interminable panorama mineral conformado por las ciudades difusas del siglo XXI se puede encontrar en las nuevas cubiertas ajardinadas y en las nuevas perspectivas verdes que se ofrezcan desde los tejados. En este artículo cito unas cuantas terrazas ajardinadas (en alemán, dachgárten o terrassengárten) pero, sobre todo, me fijo en algunos proyectos de urbanismo verde que aspiran a hacer realidad el paisaje verde de altura (en inglés, green ro…
Alignment between standardized assessments and academic standards : the case of the Saber Mathematics Test in Colombia
2013
Resumen basado en el de la publicación Título, resumen y palabras clave en español e inglés Disponible la versión en inglés Análisis del concepto de alineación presentando los resultados de un estudio que examina el grado de alineación entre una evaluación estandarizada de matemáticas y unos estándares académicos. La alineación se examina usando el modelo de Webb y los resultados sugieren que el grado de alineación entre las evaluaciones estandarizadas y los estándares académicos no es el más adecuado y por lo tanto los resultados se deben interpretar con mucha cautela y se debe poner mucho cuidado con el tipo de decisiones que se toman con base en los resultados. ESP
Evaluación criterial: determinación de estándares de interpretación (EE) para pruebas de rendimiento educativo
2009
En este trabajo se presenta una revisión del estado de la cuestión acerca de los métodos para determinar estándares en pruebas de referencia criterial. Se analiza el concepto de estándar, sus componentes y los problemas implicados en las tareas de juicio en estos métodos. Se revisan los procedimientos para diseñar descriptores de estándares y los métodos para identificar puntuaciones de corte.