The linkage between the clinical and laboratory research domains is a key issue in translational research. Integration of clinicopathologic data alone is a major task given the number of data elements involved. For a translational research environment, it is critical to make these data usable at the point-of-need. Individual systems have been developed to meet the needs of particular projects though the need for a generalizable system has been recognized. Increased use of Electronic Medical Record data in translational research will demand generalizing the system for integrating clinical data to support the study of a broad range of human diseases. To ultimately satisfy these needs, we have developed a system to support multiple translational research projects. This system, the Data Warehouse for Translational Research (DW4TR), is based on a light-weight, patient-centric modularly-structured clinical data model and a specimen-centric molecular data model. The temporal relationships of the data are also part of the model. The data are accessed through an interface composed of an Aggregated Biomedical-Information Browser (ABB) and an Individual Subject Information Viewer (ISIV) which target general users. The system was developed to support a breast cancer translational research program and has been extended to support a gynecological disease program. Further extensions of the DW4TR are underway. We believe that the DW4TR will play an important role in translational research across multiple disease types.
Recruitment of Val-48/Met-90 mutations was not found to be synonymous with cross-resistance. Indeed, the majority of isolates with these mutations retained sensitivity to at least one protease inhibitor (Val-48, 86%; Met-90, 77%). The recruitment of accessory mutations may occur only after the selection of key resistance mutations. Furthermore, Met-90 was found to be a poor marker of cross-resistance in SQV-treated patients.
ABSTRACT31P NMR magnetization transfer measurements have been used to measure the steady state flux between P1 and ATP in yeast cells genetically modified to overexpress an adenine nucleotide translocase isoform. An increase in Pi -> ATP flux and apparent ratio of moles of ATP synthesized/ atoms of oxygen consumed (P:O ratio), when these cells were incubated with glucose, demonstrated that the reactions catalyzed by the translocase and F1Fo ATP synthase were readily reversible in vivo. However, when the same cells were incubated with ethanol alone, translocase overexpression had no effect on the measured Pi -> ATP flux or apparent P:O ratio, suggesting that the synthase was now operating irreversibly. 31P NMR magnetization transfer techniques have been used to measure directly the rate of ATP turnover in a variety of systems, including Escherichia coli (1, 2), yeast (3-8), rat brain (9), and the perfused rat heart (10-12). A primary objective of these studies, particularly those on the heart, has been to determine the extent to which the F1Fo ATP synthase is displaced from equilibrium and, thus, to assess its potential for exerting kinetic control over flux in mitochondrial oxidative phosphorylation (13). These measurements have also been used to determine the degree of mitochondrial coupling, as reflected by the apparent ratio of moles of ATP synthesized/ atoms of oxygen consumed (P:O ratio) (14).Previous magnetization transfer measurements of Pi --ATP flux in vivo, in which the contribution of the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) and phosphoglycerate kinase (PGK; EC 2.7.2.3) to this measured flux has been removed (see Fig. 1), have produced values for the apparent P:O ratio of between 2 and 3 (6, 12). The similarity of these values to those measured with isolated mitochondria catalyzing net ATP synthesis in vitro was taken to indicate that the reaction catalyzed by the mitochondrial ATP synthase is effectively irreversible in vivo and that the magnetization transfer experiment is measuring net ATP turnover. However, isotope exchange measurements on isolated rat heart and liver mitochondria have shown that the unidirectionality of ATP synthesis depends on the rate of respiration (15). At high rates of respiration, the reaction was unidirectional, whereas at low rates, it was near-toequilibrium. This study suggested that an exchange reaction between P1 and ATP should be observable in NMR magnetization transfer measurements in the perfused rat heart at low workloads (15). Determination of P:O ratios in isolated mitochondria and rat hepatocytes have shown that the P:O ratio also depends on the rate of respiration, being close to zero at low rates of respiration and approaching its maximal value at high rates of respiration (16-18). These latter studies undermine the value of the P:O ratio as an indicator of the irreversibility of the ATP synthase reaction in NMR magnetization transfer measurements. Both studies suggest that an ATP < Pi exchange reaction, catalyzed by...
Brachyspira hyodysenteriae is the principal cause of swine dysentery, a disease that threatens economic productivity of pigs in many countries as it can spread readily within and between farms, and only a small number of antimicrobials are authorized for treatment of pigs. In this study, we performed whole-genome sequencing (WGS) of 81 B. hyodysenteriae archived at the Animal and Plant Health Agency (APHA) from diagnostic submissions and herd monitoring in England and Wales between 2004 and 2015. The resulting genome sequences were analyzed alongside 34 genomes we previously published. Multi-locus sequence typing (MLST) showed a diverse population with 32 sequence types (STs) among the 115 APHA isolates, 25 of them identified only in England; while also confirming that the dominant European clonal complexes, CC8 and CC52, were common in the United Kingdom. A core-genome SNP tree typically clustered the isolates by ST, with isolates from some STs detected only within a specific region in England, although others were more widespread, suggesting transmission between different regions. Also, some STs were more conserved in their core genome than others, despite these isolates being from different holdings, regions and years. Minimum inhibitory concentrations to commonly used antimicrobials (Tiamulin, Valnemulin, Doxycycline, Lincomycin, Tylosin, Tylvalosin) were determined for 82 of the genome-sequenced isolates; genomic analysis revealed mutations generally correlated well with the corresponding resistance phenotype. There was a major swine dysentery intervention program in 2009–2010, and antimicrobial survival curves showed a significant reduction in sensitivity to tiamulin and valnemulin in isolates collected in and after 2010, compared to earlier isolates. This correlated with a significant increase in post-2009 isolates harboring the pleuromutilin resistance gene tva(A), which if present, may facilitate higher levels of resistance. The reduction in susceptibility of Brachyspira from diagnostic submissions to pleuromutilins, emphasizes the need for prudent treatment, control and eradication strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.