Variability of in vivo reference point indentation in skeletally mature inbred rats.

Bone Biology Laboratory [LINK]http://www.iupui.edu/~bonelab[/LINK]Reference point indentation (RPI) has emerged as a novel tool to measure material-level biomechanical properties in vivo. Human studies have been able to differentiate fracture versus non-fracture patients while a dog study has shown the technique can differentiate drug treatment effects. The goal of this study was to extend this technology to the in vivo measurement of rats, one of the most common animal models used to study bone, with assessment of intra- and inter-animal variability. Seventy-two skeletally mature male Sprague-Dawley rats were subjected to in vivo RPI on the region between the tibial diaphysis and proximal metaphysis. RPI data were assessed using a custom MATLAB program to determine several outcome parameters, including first cycle indentation distance (ID-1st), indentation distance increase (IDI), total indentation distance (TID), first cycle unloading slope (US-1st), and first cycle energy dissipation (ED-1st). Intra-animal variability ranged from 13-21% with US-1st and Tot Ed 1st-L being the least variable properties and IDI the most highly variable. Inter-animal variability ranged from 16% (US-1st) to 25% (ED-1st 31 and IDI). Based on these data, group size estimates would need to range from 9-18/group to achieve sufficient power for detecting a 25% difference in a two-group experiment. Repeat tests on the contralateral limb of a small cohort of animals (n=17) showed non-significant differences over 28 days ranging from -6% to -18%. These results provide important data on RPI variability (intra- and inter-animal) in rats that can be used to properly power future experiments using this technique.Funding for this study was provided by NIH (AR 62002 and DK100093) and the Indiana Clinical and Translational Science Institute fellowship program. The authors would like to thank Joey Wallace and David Burr for helpful comments on early drafts of this manuscript

Planting Food or Fuel: Developing an Interdisciplinary Approach to Understanding the Role of Culture in Farmers’ Decisions to Grow Second-Generation Biofuel Feedstock Crops

Recent interest in biofuels as an alternative energy source has spurred considerable changes in agricultural practice worldwide. These changes will be more pronounced as second-generation biofuels, such as switch grass, gain prominence; this article examines the cultural factors associated with the decisions U.S. farmers face in targeting crops for fuel production instead of food. Through an interdisciplinary assessment of the dynamics of farmers' behavior, developed herein is a theoretical framework to analyze how farmers grapple with shifting expectations of their function.National Science Foundation EPS-0903806, KU-Transportation Research Institut

Higher measured than modeled ozone production at increased NOx levels in the Colorado Front Range

Abstract. Chemical models must correctly calculate the ozone formation rate, P(O3), to accurately predict ozone levels and to test mitigation strategies. However, air quality models can have large uncertainties in P(O3) calculations, which can create uncertainties in ozone forecasts, especially during the summertime when P(O3) is high. One way to test mechanisms is to compare modeled P(O3) to direct measurements. During summer 2014, the Measurement of Ozone Production Sensor (MOPS) directly measured net P(O3) in Golden, CO, approximately 25 km west of Denver along the Colorado Front Range. Net P(O3) was compared to rates calculated by a photochemical box model that was constrained by measurements of other chemical species and that used a lumped chemical mechanism and a more explicit one. Median observed P(O3) was up to a factor of 2 higher than that modeled during early morning hours when nitric oxide (NO) levels were high and was similar to modeled P(O3) for the rest of the day. While all interferences and offsets in this new method are not fully understood, simulations of these possible uncertainties cannot explain the observed P(O3) behavior. Modeled and measured P(O3) and peroxy radical (HO2 and RO2) discrepancies observed here are similar to those presented in prior studies. While a missing atmospheric organic peroxy radical source from volatile organic compounds co-emitted with NO could be one plausible solution to the P(O3) discrepancy, such a source has not been identified and does not fully explain the peroxy radical model–data mismatch. If the MOPS accurately depicts atmospheric P(O3), then these results would imply that P(O3) in Golden, CO, would be NOx-sensitive for more of the day than what is calculated by models, extending the NOx-sensitive P(O3) regime from the afternoon further into the morning. These results could affect ozone reduction strategies for the region surrounding Golden and possibly other areas that do not comply with national ozone regulations. Thus, it is important to continue the development of this direct ozone measurement technique to understand P(O3), especially under high-NOx regimes

Compromised vertebral structural and mechanical properties associated with progressive kidney disease and the effects of traditional pharmacological interventions

BACKGROUND/AIMS: Patients with chronic kidney disease mineral and bone disorder (CKD-MBD) have a significantly higher vertebral and non-vertebral fracture risk than the general population. Several preclinical models have documented altered skeletal properties in long bones, but few data exist for vertebral bone. The goal of this study was to examine the effects of progressive CKD on vertebral bone structure and mechanics and to determine the effects of treatment with either bisphosphonates or anti-sclerostin antibody in groups of animals with high or low PTH. METHODS: Animals with progressive kidney disease were left untreated, treated with calcium to lower PTH, zoledronic acid to lower remodeling without affecting PTH, anti-sclerostin antibody, or anti-sclerostin antibody plus calcium. Non-diseased, untreated littermates served as controls. Vertebral bone morphology (trabecular and cortical) and mechanical properties (structural and material-level) were assessed at 35 weeks of age by microCT and mechanical testing, respectively. RESULTS: CKD with high PTH resulted in 6-fold higher bone formation rate, significant reductions in the amount of trabecular and cortical bone, and compromised whole bone mechanical properties in the vertebra compared to normal animals. Treatments that reduced bone remodeling were effective in normalizing vertebral structure and mechanical properties only if the treatment reduced serum PTH. Similarly, treatment with anti-sclerostin antibody was effective in enhancing bone mass and mechanical properties but only if combined with PTH-suppressive treatment. CONCLUSIONS: CKD significantly altered both cortical and trabecular bone properties in the vertebra resulting in compromised mechanical properties and these changes can be normalized by interventions that involve reductions in PTH levels

Evaluation of Responses to Vaccination of Angus Cattle for Four Viruses that Contribute to Bovine Respiratory Disease Complex

Initial antibody titers are maternally-derived from colostrum, then decay with age. Change in antibody titer levels were compared between four viruses contributing to the Bovine Respiratory Disease Complex (BRDC), and evaluation of response to vaccination indicated that antibody production will not occur when high levels of maternal antibodies are present. The maternal antibodies were found to decay with calf age for each of the four viruses, which allowed for the estimation of a maximum circulating titer level under which a positive antibody response to vaccination could occur. Phenotypic correlations were calculated between the antibody titers for the four viruses across multiple time points. Results indicate a difference in the response to vaccination between the four virus antigen

Electronic monitoring for improved accountability in western Pacific tuna longline fisheries

The collection of accurate fisheries catch data is critical to ensuring sustainable management of tuna fisheries, mitigating their environmental impacts and for managing transboundary fish stocks. These challenges are exemplified by the western Pacific tuna longline fishery, who's management includes >26 nations, but is informed by critically low coverage of fishing activities by scientific observers. The gap in observer data could be filled by electronic monitoring (EM), but there are few trials that span multiple nations. A large-scale trial of EM systems on tuna longliners based in Palau, Federated States of Micronesia and the Republic of the Marshall Islands, is reported on. Comparisons are made of catch rates of market and bycatch species in corresponding EM, logbook and human observer data. Retained species were under-reported in logbooks by up to three times and discards of many species were not reported in logbooks. Discards identified in the EM data included threatened species such as marine turtles. Catch rate estimates from EM data were comparable to those estimated by human observers. EM data recorded a higher species diversity of catches than logbook data. Analysis of the EM data indicated clusters of bycatch that were associated with specific fishing practices. These results suggest further expansion of EM could inform improved management of both target and bycatch species. Ultimately greater coverage of EM data could contribute to reconciling debates in international stock allocation schemes and support actions to reduce the impacts of the fishery on threatened bycatch species

Axonemal structures reveal mechanoregulatory and disease mechanisms

Motile cilia and flagella beat rhythmically on the surface of cells to power the flow of fluid and to enable spermatozoa and unicellular eukaryotes to swim. In humans, defective ciliary motility can lead to male infertility and a congenital disorder called primary ciliary dyskinesia (PCD), in which impaired clearance of mucus by the cilia causes chronic respiratory infections1. Ciliary movement is generated by the axoneme, a molecular machine consisting of microtubules, ATP-powered dynein motors and regulatory complexes2. The size and complexity of the axoneme has so far prevented the development of an atomic model, hindering efforts to understand how it functions. Here we capitalize on recent developments in artificial intelligence-enabled structure prediction and cryo-electron microscopy (cryo-EM) to determine the structure of the 96-nm modular repeats of axonemes from the flagella of the alga Chlamydomonas reinhardtii and human respiratory cilia. Our atomic models provide insights into the conservation and specialization of axonemes, the interconnectivity between dyneins and their regulators, and the mechanisms that maintain axonemal periodicity. Correlated conformational changes in mechanoregulatory complexes with their associated axonemal dynein motors provide a mechanism for the long-hypothesized mechanotransduction pathway to regulate ciliary motility. Structures of respiratory-cilia doublet microtubules from four individuals with PCD reveal how the loss of individual docking factors can selectively eradicate periodically repeating structures

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