In vivo imaging approaches in animal models of rheumatoid arthritis

The interaction of activated leukocytes with the rheumatoid synovial environment is a key process in arthritis. Understanding this process will play an important role in designing effective treatments. In vivo imaging approaches combined with molecular genetics in animal models provide important tools to address these issues. The present review will focus on approaches to in vivo imaging, with particular attention to approaches that are proving useful for, or have promise for, research on animal models of rheumatoid arthritis. These approaches will probably shed light on the specific local mechanisms involved in chronic inflammation and provide real time monitoring approaches to follow cellular and molecular events related to disease development

Rapid Typing of \u3ci\u3eMannheimia haemolytica\u3c/i\u3e Major Genotypes 1 and 2 Using MALDI-TOF Mass Spectrometry

Genotype 2 M. haemolytica predominantly associate over genotype 1 with the lungs of cattle with respiratory disease and ICEs containing antimicrobial resistance genes. Distinct protein masses were detected by MALDI-TOF MS between genotype 1 and 2 strains. MALDI-TOF MS could rapidly differentiate genotype 2 strains in veterinary diagnostic laboratories

Rapid Typing of \u3ci\u3eMannheimia haemolytica\u3c/i\u3e Major Genotypes 1 and 2 Using MALDI-TOF Mass Spectrometry

Genotype 2 M. haemolytica predominantly associate over genotype 1 with the lungs of cattle with respiratory disease and ICEs containing antimicrobial resistance genes. Distinct protein masses were detected by MALDI-TOF MS between genotype 1 and 2 strains. MALDI-TOF MS could rapidly differentiate genotype 2 strains in veterinary diagnostic laboratories

T cell receptor antagonism interferes with MHC clustering and integrin patterning during immunological synapse formation

T cell activation by nonself peptide–major histocompatibility complex (MHC) antigenic complexes can be blocked by particular sequence variants in a process termed T cell receptor antagonism. The inhibition mechanism is not understood, although such variants are encountered in viral infections and may aid immune evasion. Here, we study the effect of antagonist peptides on immunological synapse formation by T cells. This cellular communication process features early integrin engagement and T cell motility arrest, referred to as the “stop signal.” We find that synapses formed on membranes presenting antagonist–agonist complexes display reduced MHC density, which leads to reduced T cell proliferation that is not overcome by the costimulatory ligands CD48 and B7-1. Most T cells fail to arrest and crawl slowly with a dense ICAM-1 crescent at the leading edge. Similar aberrant patterns of LFA-1/ICAM-1 engagement in live T–B couples correlate with reduced calcium flux and IL-2 secretion. Hence, antagonist peptides selectively disable MHC clustering and the stop signal, whereas LFA-1 valency up-regulation occurs normally

Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability

This work was supported by National Institutes of Health Common Fund through a Nanomedicine Development Center PN2EY016586 (MLD, MPS). OH and KA were Cas-L coordinates T-cell actin cytoskeleton 2 supported by NIH grants R01 AI068963-01A2 and R01 AI088106-01A1. The Wellcome Trust and the Kennedy Institute of Rheumatology Trust supported MLD

Complete Genome Sequence of \u3ci\u3eMoraxella bovis\u3c/i\u3e Strain Epp-63 (300), an Etiologic Agent of Infectious Bovine Keratoconjunctivitis

We report here the complete closed genome sequence of Moraxella bovis strain Epp-63 (300) (Epp63). This strain was isolated from an infectious bovine keratoconjunctivitis (IBK) case in 1963. Since then, Epp63 has been used extensively for IBK research. Consequently, the genome sequence of Epp63 should help elucidate IBK host-pathogen interactions

The association of preoperative cardiac stress testing with 30-day death and myocardial infarction among patients undergoing kidney transplantation

BACKGROUND:Although periodic cardiac stress testing is commonly used to screen patients on the waiting list for kidney transplantation for ischemic heart disease, there is little evidence to support this practice. We hypothesized that cardiac stress testing in the 18 months prior to kidney transplantation would not reduce postoperative death, total myocardial infarction (MI) or fatal MI. METHODS:Using the United States Renal Data System, we identified ESRD patients ≥40 years old with primary Medicare insurance who received their first kidney transplant between 7/1/2006 and 11/31/2013. Propensity matching created a 1:1 matched sample of patients with and without stress testing in the 18 months prior to kidney transplantation. The outcomes of interest were death, total (fatal and nonfatal) MI or fatal MI within 30 days of kidney transplantation. RESULTS:In the propensity-matched cohort of 17,304 patients, death within 30 days occurred in 72 of 8,652 (0.83%) patients who underwent stress testing and in 65 of 8,652 (0.75%) patients who did not (OR 1.07; 95% CI: 0.79-1.45; P = 0.66). MI within 30 days occurred in 339 (3.9%) patients who had a stress test and in 333 (3.8%) patients who did not (OR 1.03; 95% CI: 0.89-1.21; P = 0.68). Fatal MI occurred in 17 (0.20%) patients who underwent stress testing and 15 (0.17%) patients who did not (OR 0.97; 95% CI: 0.71-1.32; P = 0.84). CONCLUSION:Stress testing in the 18 months prior to kidney transplantation is not associated with a reduction in death, total MI or fatal MI within 30 days of kidney transplantation

Quantitative Decoding of Interactions in Tunable Nanomagnet Arrays Using First Order Reversal Curves

To develop a full understanding of interactions in nanomagnet arrays is a persistent challenge, critically impacting their technological acceptance. This paper reports the experimental, numerical and analytical investigation of interactions in arrays of Co nanoellipses using the first-order reversal curve (FORC) technique. A mean-field analysis has revealed the physical mechanisms giving rise to all of the observed features: a shift of the non-interacting FORC-ridge at the low-H$_c$ end off the local coercivity H$_c$ axis; a stretch of the FORC-ridge at the high-H$_c$ end without shifting it off the H$_c$ axis; and a formation of a tilted edge connected to the ridge at the low-H$_c$ end. Changing from flat to Gaussian coercivity distribution produces a negative feature, bends the ridge, and broadens the edge. Finally, nearest neighbor interactions segment the FORC-ridge. These results demonstrate that the FORC approach provides a comprehensive framework to qualitatively and quantitatively decode interactions in nanomagnet arrays.Comment: 19 pages, 4 figures. 9 page supplemental material including 3 figure

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identification of \u3ci\u3eMoraxella bovoculi\u3c/i\u3e and \u3ci\u3eMoraxella bovis\u3c/i\u3e isolates from cattle

Infectious bovine keratoconjunctivitis (IBK) is an economically significant disease caused by Moraxella bovis. Moraxella bovoculi, although not reported to cause IBK, has been isolated from the eyes of cattle diagnosed with IBK. Identification of M. bovis and M. bovoculi can be performed using biochemical or DNA-based approaches, both of which may be time consuming and inconsistent between laboratories. We conducted a comparative evaluation of M. bovoculi and M. bovis identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with a database provided by Bruker Daltonics (termed the BDAL database), the BDAL database supplemented with spectra generated in our study (termed the UNLVDC database), and with PCR–restriction-fragment length polymorphism (PCR-RFLP) typing. M. bovoculi (n = 250) and M. bovis (n = 18) isolates from cattle with or without IBK were used. MALDI-TOF MS using the UNLVDC database correctly identified 250 of 250 (100%) of M. bovoculi and 17 of 18 (94%) of M. bovis isolates. With the BDAL database, MALDI-TOF MS correctly identified 249 of 250 (99%) of M. bovoculi and 7 of 18 (39%) of M. bovis isolates. In comparison, the PCR-RFLP test correctly identified 210 of 250 (84%) of M. bovoculi and 12 of 18 (66%) of M. bovis isolates. Thus, MALDI-TOF MS with the UNLVDC database was the most effective identification methodology for M. bovis and M. bovoculi isolates from cattle

Conflict, coexistence, or both? Cougar habitat selection, prey composition, and mortality in a multiple-use landscape

Western North America is experiencing remarkable human population growth and land-use change. Irrigation and associated cultivation have led to colonization of urban-wildland interface (UWI) environments by mule deer (Odocoileus hemionus), and consequently, cougars (Puma concolor). In the wake of these changes, human-wildlife conflicts have increased in tandem with questions about long-term species conservation. To address these concerns, we fit 79 cougars with radio-telemetry collars in the Oquirrh Mountains near Salt Lake City, Utah (2002–2010). Our goal was to evaluate variation in cougar habitat selection, diet, and cause-specific mortality in a landscape dominated by urban, military, and industrial activities. We used radio-telemetry data in concert with Re-source Selection Functions to address three hypotheses: (1) that cougars would select wildland over UWI land-uses; (2) prey composition would reflect differences in land-use; and (3) mortality would be predominantly human-caused. Cougars largely selected wildland habitats associated with seasonal mule deer presence, but contrary to expectation, they also selected habitats closer to urban and mined areas. Prey composition in the UWI did not differ from wildland habitats. Domestic ungulates represented only 2% of 540 recovered prey items and were found primarily in wildlands. Native ungulates comprised \u3e 90% of the total kill, irrespective of season or land-use, suggesting that use of UWI habitats was linked to mule deer presence. Cougar mortality was disproportionately due to natural causes in wildlands, but individuals that died of human causes in UWI habitats were more likely to be inexperienced hunters, supporting young kittens, or compromised by physical handicaps. In general, presence of mule deer was the key predictor of cougar habitat use, even in this highly disturbed, anthropogenically altered landscape. As such, management designed to reduce conflict and ensure conservation will need to focus on urban deer, land-use planning, and targeted education campaigns to reduce food subsidies