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Kaat Kehoe Robert Verkerk Yani Sim Yannick Waumans Pieter Van der Veken Anne-Marie Lambeir Ingrid De Meester 《Analytical biochemistry》2013
Prolylcarboxypeptidase (PRCP, EC 3.4.16.2), a lysosomal carboxypeptidase, was discovered 45 years ago. However, research has been hampered by a lack of well-validated assays that are needed to measure low activities in biological samples. Two reversed-phase high-performance liquid chromatography (RP-HPLC) methods for quantifying PRCP activity in crude homogenates and plasma samples were optimized and validated. PRCP activity was determined by measuring the hydrolysis of N-benzyloxycarbonyl-l-proline (Z-Pro)-Phe. The enzymatically formed Z-Pro and Phe were measured independently under different HPLC conditions. The in-house methods showed good precision, linearity, accuracy, and specificity. Based on Michaelis–Menten constants, Z-Pro-Phe was chosen over Z-Pro-Ala as the substrate of preference. Cross-reactivity studies with dipeptidyl peptidases (DPPs) 2, 4, and 9 and prolyl oligopeptidase (PREP) confirmed the specificity of the PRCP activity assay. The average PRCP activity in plasma and serum of 32 healthy individuals was found to be 0.65 ± 0.02 and 0.72 ± 0.03 U/L, respectively. Both methods can be used to measure PRCP activity specifically in different biological samples and are well suited to evaluate PRCP inhibitors. These well-validated methods are valuable tools for studying PRCP’s role in cardiovascular diseases, stroke, inflammation, and metabolic syndrome. 相似文献
54.
Wendy E. Kaman Ingrid Voskamp-Visser Denise M.C. de Jongh Hubert P. Endtz Alex van Belkum John P. Hays Floris J. Bikker 《Analytical biochemistry》2013
Bacterial proteases play an important role in a broad spectrum of processes, including colonization, proliferation, and virulence. In this respect, bacterial proteases are potential biomarkers for bacterial diagnosis and targets for novel therapeutic protease inhibitors. To investigate these potential functions, the authors designed and used a protease substrate fluorescence resonance energy transfer (FRET) library comprising 115 short d- and l-amino-acid-containing fluorogenic substrates as a tool to generate proteolytic profiles for a wide range of bacteria. Bacterial specificity of the d-amino acid substrates was confirmed using enzymes isolated from both eukaryotic and prokaryotic organisms. Interestingly, bacterial proteases that are known to be involved in housekeeping and nutrition, but not in virulence, were able to degrade substrates in which a d-amino acid was present. Using our FRET peptide library and culture supernatants from a total of 60 different bacterial species revealed novel, bacteria-specific, proteolytic profiles, although in-species variation was observed for Pseudomonas aeruginosa, Porphyromonas gingivalis, and Staphylococcus aureus. Overall, the specific characteristic of our substrate peptide library makes it a rapid tool to high-throughput screen for novel substrates to detect bacterial proteolytic activity. 相似文献
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Ingrid E. Alvial Karine Orth Bárbara C. Durán Evelyn Álvarez Francisco A. Squeo 《Hydrobiologia》2013,709(1):11-25
The ecology of macroinvertebrate communities in arid regions is still poorly understood. Here we examined how the community structure varied at spatial and temporal scales in streams and tributaries of the Huasco River in semi-arid region of Northern Chile. We expected that macroinvertebrate distribution may be responding to natural processes of mineralization described for Chilean semiarid basins. The relationships among biotic and abiotic variables were assessed through multivariate techniques (principal component analysis, non-metric multidimensional scaling, canonical correspondence analysis), and a two-way analysis of similarity was used to evaluate differences between basins and years (2007, 2008, and 2009). Significant differences in community structure and physical–chemical variables between basins (Del Carmen and Del Tránsito) were found, but not between years. Altitude, Mn, Al, Ca, Na, HCO3, and dissolved oxygen were the variables that best accounted for the communities distribution. In particular, high metals concentration in El Transito basin should determine low density and diversity of macroinvertebrates. Chironomidae, Ephydridae, and Glossiphoniidae were associated to waters with high metals content and acidic pH, whereas Baetidae, Hydroptilidae, and Blephariceridae were associated to sites with more favorable physical–chemical conditions. These results contribute to understand the ecological patterns of macroinvertebrates in arid regions and should lead to conservation and monitoring plans for this remote place. 相似文献
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Ingrid Melle 《World psychiatry》2013,12(1):16-21
In the afternoon of July 22, 2011, Norwegian Anders Behring Breivik killed 77 persons, many of them children and youths, in two separate events. On August 24, 2012, he was sentenced to 21 years in prison. Breivik went through two forensic evaluations: the first concluded that he had a psychotic disorder, thus being legally unaccountable, whereas the second concluded that he had a personality disorder, thus being legally accountable. This article first describes Breivik's background and his crimes. This is followed by an overview of the two forensic evaluations, their methods, contents and disagreements, and how these issues were handled by the court in the verdict. Finally, the article focuses on some lessons psychiatrists can take from the case. 相似文献
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Christine Breynaert Tom Dresselaers Clémentine Perrier Ingrid Arijs Jonathan Cremer Leentje Van Lommel Kristel Van Steen Marc Ferrante Frans Schuit Séverine Vermeire Paul Rutgeerts Uwe Himmelreich Jan L. Ceuppens Karel Geboes Gert Van Assche 《PloS one》2013,8(7)
Introduction
Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS) ingestion, to mimic the relapsing nature of the human disease.Materials and Methods
C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total). Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis.Results
Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn’s colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS.Conclusions
Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn’s disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of inflammation and fibrosis. 相似文献58.
Ingrid C. Rulifson Ping Cao Li Miao David Kopecky Linda Huang Ryan D. White Kim Samayoa Jonitha Gardner Xiaosu Wu Kui Chen Trace Tsuruda Oliver Homann Helene Baribault Harvey Yamane Tim Carlson Jed Wiltzius Yang Li 《PloS one》2016,11(2)
Pancreatic amyloid formation by islet amyloid polypeptide (IAPP) is a hallmark pathological feature of type 2 diabetes. IAPP is stored in the secretory granules of pancreatic beta-cells and co-secreted with insulin to maintain glucose homeostasis. IAPP is innocuous under homeostatic conditions but imbalances in production or processing of IAPP may result in homodimer formation leading to the rapid production of cytotoxic oligomers and amyloid fibrils. The consequence is beta-cell dysfunction and the accumulation of proteinaceous plaques in and around pancreatic islets. Beta-site APP-cleaving enzyme 2, BACE2, is an aspartyl protease commonly associated with BACE1, a related homolog responsible for amyloid processing in the brain and strongly implicated in Alzheimer’s disease. Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. The result of proteolysis is modulation of human IAPP fibrillation and human IAPP protein degradation. These results suggest a potential therapeutic role for BACE2 in type 2 diabetes-associated hyperamylinaemia. 相似文献
59.
Alexander R. Gaos Rebecca L. Lewison Michael J. Liles Velkiss Gadea Eduardo Altamirano Ana V. Henríquez Perla Torres José Urteaga Felipe Vallejo Andres Baquero Carolina LeMarie Juan Pablo Mu?oz Jaime A. Chaves Catherine E. Hart Alejandro Pe?a de Niz Didiher Chácon Luis Fonseca Sarah Otterstrom Ingrid L. Ya?ez Erin L. LaCasella Amy Frey Michael P. Jensen Peter H. Dutton 《Ecology and evolution》2016,6(4):1251-1264
Prior to 2008 and the discovery of several important hawksbill turtle (Eretmochelys imbricata) nesting colonies in the EP (Eastern Pacific), the species was considered virtually absent from the region. Research since that time has yielded new insights into EP hawksbills, salient among them being the use of mangrove estuaries for nesting. These recent revelations have raised interest in the genetic characterization of hawksbills in the EP, studies of which have remained lacking to date. Between 2008 and 2014, we collected tissue samples from 269 nesting hawksbills at nine rookeries across the EP and used mitochondrial DNA sequences (766 bp) to generate the first genetic characterization of rookeries in the region. Our results inform genetic diversity, population differentiation, and phylogeography of the species. Hawksbills in the EP demonstrate low genetic diversity: We identified a total of only seven haplotypes across the region, including five new and two previously identified nesting haplotypes (pooled frequencies of 58.4% and 41.6%, respectively), the former only evident in Central American rookeries. Despite low genetic diversity, we found strong stock structure between the four principal rookeries, suggesting the existence of multiple populations and warranting their recognition as distinct management units. Furthermore, haplotypes EiIP106 and EiIP108 are unique to hawksbills that nest in mangrove estuaries, a behavior found only in hawksbills along Pacific Central America. The detected genetic differentiation supports the existence of a novel mangrove estuary “reproductive ecotype” that may warrant additional conservation attention. From a phylogeographic perspective, our research indicates hawksbills colonized the EP via the Indo‐Pacific, and do not represent relict populations isolated from the Atlantic by the rising of the Panama Isthmus. Low overall genetic diversity in the EP is likely the combined result of few rookeries, extremely small reproductive populations and evolutionarily recent colonization events. Additional research with larger sample sizes and variable markers will help further genetic understanding of hawksbill turtles in the EP. 相似文献
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