The effects of administering different metaphylactic antimicrobials on growth performance and health outcomes of high-risk, newly received feedlot steers

Bovine respiratory disease (BRD) is the primary animal health concern facing feedlot producers. Many antimicrobial mitigation strategies are available, but few studies have compared feedlot performance during both the receiving and finishing periods following application of different antimicrobials used as metaphylaxis at arrival. The objective of this study was to compare antimicrobial metaphylaxis methods on clinical health and growth performance across both the receiving and finishing periods. A total of 238 multiple-sourced steers in two source blocks were used in a generalized complete block design. The four treatments included: 1) a negative control, 5 mL of sterile saline injected subcutaneously (CON); 2) subcutaneous administration of florfenicol at 40 mg/kg of BW (NUF); 3) subcutaneous administration of ceftiofur in the posterior aspect of the ear at 6.6 mg/kg of BW (EXC); and 4) subcutaneous administration of tulathromycin at 2.5 mg/kg of BW (DRA). The morbidity rate for the first treatment of BRD was decreased for the DRA and EXC treatments compared to CON and NUF (P \u3c 0.01). Additionally, average daily gain (ADG), dry matter intake (DMI), and gain-to-feed (G:F) were greater (P ≤ 0.02) in the DRA treatment during the receiving period compared to all other treatments. The ADG was also greater (P \u3c 0.05) for EXC than the CON treatment throughout the finishing period. Nonetheless, other growth performance variables did not differ among metaphylactic treatments during the finishing period (P ≥ 0.14). Likewise, no differences in carcass characteristics or liver abscess score were observed (P ≥ 0.18). All complete blood count (CBC) variables were affected by day (P ≤ 0.01) except mean corpuscular hemoglobin concentration (P = 0.29). Treatment × time interactions were observed for platelet count, white blood cell (WBC) count, monocyte count and percentage, and lymphocyte percentage (P ≤ 0.03). However, there were no observed hematological variables that differed among treatment (P ≥ 0.10). The results indicate that some commercially available antimicrobials labeled for metaphylactic use are more efficacious than others in decreasing morbidity rate

Metaphylactic antimicrobial effects on occurrences of antimicrobial resistance in \u3ci\u3eSalmonella enterica, Escherichia coli\u3c/i\u3e and \u3ci\u3eEnterococcus\u3c/i\u3e spp. measured longitudinally from feedlot arrival to harvest in high-risk beef cattle

Aims: Our objective was to determine how injectable antimicrobials affected populations of Salmonella enterica, Escherichia coli and Enterococcus spp. in feedlot cattle. Methods and Results: Two arrival date blocks of high-risk crossbred beef cattle (n = 249; mean BW = 244 kg) were randomly assigned one of four antimicrobial treatments administered on day 0: sterile saline control (CON), tulathromycin (TUL), ceftiofur (CEF) or florfenicol (FLR). Faecal samples were collected on days 0, 28, 56, 112, 182 and study end (day 252 for block 1 and day 242 for block 2). Hide swabs and subiliac lymph nodes were collected the day before and the day of harvest. Samples were cultured for antimicrobial-resistant Salmonella, Escherichia coli and Enterococcus spp. The effect of treatment varied by day across all targeted bacterial populations (p ≤ 0.01) except total E. coli. Total E. coli counts were greatest on days 112, 182 and study end (p ≤ 0.01). Tulathromycin resulted in greater counts and prevalence of Salmonella from faeces than CON at study end (p ≤ 0.01). Tulathromycin and CEF yielded greater Salmonella hide prevalence and greater counts of 128ERYR E. coli at study end than CON (p ≤ 0.01). No faecal Salmonella resistant to tetracyclines or third-generation cephalosporins were detected. Ceftiofur was associated with greater counts of 8ERYR Enterococcus spp. at study end (p ≤ 0.03). By the day before harvest, antimicrobial use did not increase prevalence or counts for all other bacterial populations compared with CON (p ≥ 0.13). Conclusions: Antimicrobial resistance (AMR) in feedlot cattle is not caused solely by using a metaphylactic antimicrobial on arrival, but more likely a multitude of environmental and management factors

An eScience-Bayes strategy for analyzing omics data

<p>Abstract</p> <p>Background</p> <p>The omics fields promise to revolutionize our understanding of biology and biomedicine. However, their potential is compromised by the challenge to analyze the huge datasets produced. Analysis of omics data is plagued by the curse of dimensionality, resulting in imprecise estimates of model parameters and performance. Moreover, the integration of omics data with other data sources is difficult to shoehorn into classical statistical models. This has resulted in <it>ad hoc </it>approaches to address specific problems.</p> <p>Results</p> <p>We present a general approach to omics data analysis that alleviates these problems. By combining eScience and Bayesian methods, we retrieve scientific information and data from multiple sources and coherently incorporate them into large models. These models improve the accuracy of predictions and offer new insights into the underlying mechanisms. This "eScience-Bayes" approach is demonstrated in two proof-of-principle applications, one for breast cancer prognosis prediction from transcriptomic data and one for protein-protein interaction studies based on proteomic data.</p> <p>Conclusions</p> <p>Bayesian statistics provide the flexibility to tailor statistical models to the complex data structures in omics biology as well as permitting coherent integration of multiple data sources. However, Bayesian methods are in general computationally demanding and require specification of possibly thousands of prior distributions. eScience can help us overcome these difficulties. The eScience-Bayes thus approach permits us to fully leverage on the advantages of Bayesian methods, resulting in models with improved predictive performance that gives more information about the underlying biological system.</p

Activation of PKA via asymmetric allosteric coupling of structurally conserved cyclic nucleotide binding domains

Cyclic nucleotide-binding (CNB) domains allosterically regulate the activity of proteins with diverse functions, but the mechanisms that enable the cyclic nucleotide-binding signal to regulate distant domains are not well understood. Here we use optical tweezers and molecular dynamics to dissect changes in folding energy landscape associated with cAMP-binding signals transduced between the two CNB domains of protein kinase A (PKA). We find that the response of the energy landscape upon cAMP binding is domain specific, resulting in unique but mutually coordinated tasks: one CNB domain initiates cAMP binding and cooperativity, whereas the other triggers inter-domain interactions that promote the active conformation. Inter-domain interactions occur in a stepwise manner, beginning in intermediate-liganded states between apo and cAMP-bound domains. Moreover, we identify a cAMP-responsive switch, the N3A motif, whose conformation and stability depend on cAMP occupancy. This switch serves as a signaling hub, amplifying cAMP-binding signals during PKA activation