Intercellular adhesion molecule-1 induction: A sensitive and quantitative marker for cardiac allograft rejection

ObjectivesRats with abdominal heterotopic heart transplants were studied to determine whether cardiac allograft rejection could be assessed by immunoscintigraphy targeting intercellular adhesion molecule-1 (ICAM-1), which was induced on allografted organ cells in association with rejection.BackgroundIt is important to detect early rejection before development of myocyte necrosis. Although a variety of methods for the detection of cardiac rejection have been investigated, histologic inspection of biopsied samples is still used routinely for clinical diagnosis of rejection.MethodsDA rat (RT-1a) hearts were transplanted into PVG rats (RT-1c). Immunohistologic examination of the allografts demonstrated that ICAM-1 induction on vascular endothelial cells was observed as early as 4 days after transplantation in this combination. Thirty-nine allografted rats and seven isografted rats were studied. One day after injection of 100 μCi of 111Inlabeled anti—ICAM-1 monoclonal antibody (1A29), planar images were obtained.ResultsRejecting allografts showed increased radiotracer uptake and could be identified on the images as early as 5 days after transplantation. In contrast, nonrejecting cardiac allografts and isografts did not show specific uptake. Mildly rejecting allografts, with mononuclear cell infiltration but without significant myocyte necrosis, could be scintigraphically identified, and the level of radiotracer uptake reflected the histologic severity of rejection. Accumulation of 111In-labeled monoclonal antibody of isotypematched irrelevant specificity was not detected in the rejecting allografts.ConclusionsThese data indicate that ICAM-1 induction can be assessed quantitatively by radioimmunoscintigraphy. Radioimmunoscintigraphy is a sensitive method for early detection and assessment of cardiac allograft rejection

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

1937: Abilene Christian College Bible Lectures - Full Text

Delivered in the auditorium of Abilene Christian College, Abilene, Texas, February 193

1940: Abilene Christian College Bible Lectures - Full Text

Delivered in the Auditorium of Abilene Christian College, February, 1940, Abilene, Texas. Published April, 1940 PRICE, $1.00 FIRM FOUNDATION PUBLISHING HOUSE Austin, Texas

Identification of Membrane Proteins in the Hyperthermophilic Archaeon Pyrococcus Furiosus Using Proteomics and Prediction Programs

Cell-free extracts from the hyperthermophilic archaeon Pyrococcus furiosus were separated into membrane and cytoplasmic fractions and each was analyzed by 2D-gel electrophoresis. A total of 66 proteins were identified, 32 in the membrane fraction and 34 in the cytoplasmic fraction. Six prediction programs were used to predict the subcellular locations of these proteins. Three were based on signal-peptides (SignalP, TargetP, and SOSUISignal) and three on transmembrane-spanning α-helices (TSEG, SOSUI, and PRED-TMR2). A consensus of the six programs predicted that 23 of the 32 proteins (72%) from the membrane fraction should be in the membrane and that all of the proteins from the cytoplasmic fraction should be in the cytoplasm. Two membrane-associated proteins predicted to be cytoplasmic by the programs are also predicted to consist primarily of transmembrane-spanning β-sheets using porin protein models, suggesting that they are, in fact, membrane components. An ATPase subunit homolog found in the membrane fraction, although predicted to be cytoplasmic, is most likely complexed with other ATPase subunits in the membrane fraction. An additional three proteins predicted to be cytoplasmic but found in the membrane fraction, may be cytoplasmic contaminants. These include a chaperone homolog that may have attached to denatured membrane proteins during cell fractionation. Omitting these three proteins would boost the membrane-protein predictability of the models to near 80%. A consensus prediction using all six programs for all 2242 ORFs in the P. furiosus genome estimates that 24% of the ORF products are found in the membrane. However, this is likely to be a minimum value due to the programs’ inability to recognize certain membrane-related proteins, such as subunits associated with membrane complexes and porin-type proteins

A formative study exploring perceptions of physical activity and physical activity monitoring among children and young people with cystic fibrosis and health care professionals

Background: Physical activity (PA) is associated with reduced hospitalisations and maintenance of lung function in patients with Cystic Fibrosis (CF). PA is therefore recommended as part of standard care. Despite this, there is no consensus for monitoring of PA and little is known about perceptions of PA monitoring among children and young people with CF. Therefore, the research aimed to explore patients’ perceptions of PA and the acceptability of using PA monitoring devices with children and young people with CF. Methods: An action research approach was utilised, whereby findings from earlier research phases informed subsequent phases. Four phases were utilised, including patient interviews, PA monitoring, follow-up patient interviews and health care professional (HCP) interviews. Subsequently, an expert panel discussed the study to develop recommendations for practice and future research. Results: Findings suggest that experiences of PA in children and young people with CF are largely comparable to their non-CF peers, with individuals engaging in a variety of activities. CF was not perceived as a barrier per se, although participants acknowledged that they could be limited by their symptoms. Maintenance of health emerged as a key facilitator, in some cases PA offered patients the opportunity to ‘normalise’ their condition. Participants reported enjoying wearing the monitoring devices and had good compliance. Wrist-worn devices and devices providing feedback were preferred. HCPs recognised the potential benefits of the devices in clinical practice. Recommendations based on these findings are that interventions to promote PA in children and young people with CF should be individualised and involve families to promote PA as part of an active lifestyle. Patients should receive support alongside the PA data obtained from monitoring devices. Conclusions: PA monitoring devices appear to be an acceptable method for objective assessment of PA among children and young people with CF and their clinicians. Wrist-worn devices, which are unobtrusive and can display feedback, were perceived as most acceptable. By understanding the factors impacting PA, CF health professionals will be better placed to support patients and improve health outcomes

Characterization of an Nmr Homolog That Modulates GATA Factor-Mediated Nitrogen Metabolite Repression in Cryptococcus neoformans

Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis

Comment letters to the National Commission on Commission on Fraudulent Financial Reporting, 1987 (Treadway Commission) Vol. 2

https://egrove.olemiss.edu/aicpa_sop/1662/thumbnail.jp