Validation of an ear tag–based accelerometer system for detecting grazing behavior of dairy cows

peer-reviewedThe objective of the study was to develop a grazing algorithm for an ear tag–based accelerometer system (Smartbow GmbH, Weibern, Austria) and to validate the grazing algorithm with data from a noseband sensor. The ear tag has an acceleration sensor, a radio chip, and temperature sensor for calibration and it can monitor rumination and detect estrus and localization. To validate the ear tag, a noseband sensor (RumiWatch, Itin and Hoch GmbH, Liestal, Switzerland) was used. The noseband sensor detects pressure and acceleration patterns, and, with a software program specific to the noseband, pressure and acceleration patterns are used to classify data into eating, ruminating, drinking, and other activities. The study was conducted at the University of Minnesota West Central Research and Outreach Center (Morris, MN) and at Teagasc Animal and Grassland Research and Innovation Centre (Moorepark, Fermoy, Co. Cork, Ireland). During May and June 2017, observational data from Minnesota and Ireland were used to develop the grazing algorithm. During September 2018, data were collected by the ear tag and noseband sensor from 12 crossbred cows in Minnesota for a total of 248 h and from 9 Holstein-Friesian cows in Ireland for a total of 248 h. A 2-sided t-test was used to compare the percentage of grazing and nongrazing time recorded by the ear tag and the noseband sensor. Pearson correlations and concordance correlation coefficients (CCC) were used to evaluate associations between the ear tag and noseband sensor. The percentage of total grazing time recorded by the ear tag and by the noseband sensor was 37.0% [95% confidence interval (CI): 32.1 to 42.0] and 40.5% (95% CI: 35.5 to 45.6), respectively, in Minnesota, and 35.4% (95% CI: 30.6 to 40.2) and 36.9% (95% CI: 32.1 to 41.8), respectively, in Ireland. The ear tag and noseband sensor agreed strongly for monitoring grazing in Minnesota (r = 0.96; 95% CI: 0.94 to 0.97, CCC = 0.95) and in Ireland (r = 0.92; 95% CI: 0.90 to 0.94, CCC = 0.92). The results suggest that there is potential for the ear tag to be used on pasture-based dairy farms to support management decision-making

Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1

The betaine/GABA transporter 1 (BGT1) is a member of the GABA transporter (GAT) family with still elusive function, largely due to a lack of potent and selective tool compounds. Based on modeling, we here present the design, synthesis and pharmacological evaluation of five novel conformationally restricted cyclic GABA analogs related to the previously reported highly potent and selective BGT1 inhibitor (1S,2S,5R)-5-aminobicyclo[3.1.0]hexane-2-carboxylic acid (bicyclo-GABA). Using [(3)H]GABA radioligand uptake assays at the four human GATs recombinantly expressed in mammalian cell lines, we identified bicyclo-GABA and its N-methylated analog (2) as the most potent and selective BGT1 inhibitors. Additional pharmacological characterization in a fluorescence-based membrane potential assay showed that bicyclo-GABA and 2 are competitive inhibitors, not substrates, at BGT1, which was validated by a Schild analysis for bicyclo-GABA (pK (B) value of 6.4). To further elaborate on the selectivity profile both compounds were tested at recombinant α(1)β(2)γ(2) GABA(A) receptors. Whereas bicyclo-GABA showed low micromolar agonistic activity, the N-methylated 2 was completely devoid of activity at GABA(A) receptors. To further reveal the binding mode of bicyclo-GABA and 2 binding hypotheses of the compounds were obtained from in silico-guided mutagenesis studies followed by pharmacological evaluation at selected BGT1 mutants. This identified the non-conserved BGT1 residues Q299 and E52 as the molecular determinants driving BGT1 activity and selectivity. The binding mode of bicyclo-GABA was further validated by the introduction of activity into the corresponding GAT3 mutant L314Q (38 times potency increase cf. wildtype). Altogether, our data reveal the molecular determinants for the activity of bicyclic GABA analogs, that despite their small size act as competitive inhibitors of BGT1. These compounds may serve as valuable tools to selectively and potently target BGT1 in order to decipher its elusive pharmacological role in the brain and periphery such as the liver and kidneys

Automatically generated, anatomically accurate meshes for cardiac electrophysiology problems.

Significant advancements in imaging technology and the dramatic increase in computer power over the last few years broke the ground for the construction of anatomically realistic models of the heart at an unprecedented level of detail. To effectively make use of high-resolution imaging datasets for modeling purposes, the imaged objects have to be discretized. This procedure is trivial for structured grids. However, to develop generally applicable heart models, unstructured grids are much preferable. In this study, a novel image-based unstructured mesh generation technique is proposed. It uses the dual mesh of an octree applied directly to segmented 3-D image stacks. The method produces conformal, boundary-fitted, and hexahedra-dominant meshes. The algorithm operates fully automatically with no requirements for interactivity and generates accurate volume-preserving representations of arbitrarily complex geometries with smooth surfaces. The method is very well suited for cardiac electrophysiological simulations. In the myocardium, the algorithm minimizes variations in element size, whereas in the surrounding medium, the element size is grown larger with the distance to the myocardial surfaces to reduce the computational burden. The numerical feasibility of the approach is demonstrated by discretizing and solving the monodomain and bidomain equations on the generated grids for two preparations of high experimental relevance, a left ventricular wedge preparation, and a papillary muscle