Anna K. Johnson

Most models of protein evolution are based upon proteins that form relatively rigid 3D structures. A significant fraction of proteins, the so-called disordered proteins, do not form rigid 3D structures and sample a broad conformational ensemble. Disordered proteins do not typically maintain long-range interactions, so the constraints on their evolution should be different than ordered proteins. To test this hypothesis, we developed and compared models of evolution for disordered and ordered proteins. Substitution matrices were constructed using the sequences of putative homologs for sets of experimentally characterized disordered and ordered proteins. Separate matrices, at three levels of sequence similarity (>85%, 85-60%, and 60-40%), were inferred for each type of protein structure. The substitution matrices for disordered and ordered proteins differed significantly at each level of sequence similarity. The disordered matrices reflected a greater likelihood of evolutionary changes, relative to the ordered matrices, and these changes involved nonconservative substitutions. Glutamic acid and asparagine were interesting exceptions to this result. Important differences between the substitutions that are accepted in disordered proteins relative to ordered proteins were also identified. In general, disordered proteins have fewer evolutionary constraints than ordered proteins. However, some residues like tryptophan and tyrosine are highly conserved in disordered proteins. This is due to their important role in forming protein-protein interfaces. Finally, the amino acid frequencies for disordered proteins, computed during the development of the matrices, were compared with amino acid frequencies for different categories of secondary structure in ordered proteins. The highest correlations were observed between the amino acid frequencies in disordered proteins and the solvent-exposed loops and turns of ordered proteins, supporting an emerging structural model for disordered proteins.

BACKGROUND: The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121-168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. RESULTS: No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749-6004 ng/ml) and 946 ng/ml (range: 554-1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%). CONCLUSIONS: The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route.

Two hundred eighty-seven lactating Newsham sows and their litters were used to determine the effects of intensive indoor (n = 147) and intensive outdoor (n = 140) production systems on sow and litter productivity and behavior. All sows were of contemporary age and fed a completely balanced sorghum-based diet. Behavior data were collected by live observation on 40 sows and litters (20 indoor and 20 outdoor) using a 5-min scan sample over a 4-h period in the afternoon (1400 to 1800). The durations of lying (90.0 vs 72.1 +/- 2.76% of time observed) and drinking (4.42 vs 1.41 +/- 0.6% of time observed) were higher (P < 0.01) among indoor than among outdoor lactating sows. Nursing interval and feeding and sitting behaviors were not different (P > 0.05) between production systems. Piglets spent more (P < 0.05) time walking (10.1 vs 5.2 +/- 1.72% of time observed) and engaged in play activity (5.0 vs 1.7 +/- 1.26% of time observed) when housed outdoors than indoors. Outdoor piglets had more (P < 0.05) nursing behaviors directed toward the sow (27.5 vs 20.3 +/- 2.02% of time observed) but time spent in contact with the sow did not differ between environments (38.8 vs 39.2 +/- 2.78% of time observed). Treatments did not influence (P > 0.05) any of the sow or piglet production parameters. In conclusion, outdoor-kept Newsham sows and their piglets showed a richer behavioral repertoire, but the diverse environments did not influence production parameters.

Transport losses (dead and nonambulatory pigs) present animal welfare, legal, and economic challenges to the US swine industry. The objectives of this review are to explore 1) the historical perspective of transport losses; 2) the incidence and economic implications of transport losses; and 3) the symptoms and metabolic characteristics of fatigued pigs. In 1933 and 1934, the incidence of dead and nonambulatory pigs was reported to be 0.08 and 0.16%, respectively. More recently, 23 commercial field trials (n = 6,660,569 pigs) were summarized and the frequency of dead pigs, nonambulatory pigs, and total transport losses at the processing plant were 0.25, 0.44, and 0.69% respectively. In 2006, total economic losses associated with these transport losses were estimated to cost the US pork industry approximately $46 million. Furthermore, 0.37 and 0.05% of the nonambulatory pigs were classified as either fatigued (nonambulatory, noninjured) or injured, respectively, in 18 of these trials (n = 4,966,419 pigs). Fatigued pigs display signs of acute stress (open-mouth breathing, skin discoloration, muscle tremors) and are in a metabolic state of acidosis, characterized by low blood pH and high blood lactate concentrations; however, the majority of fatigued pigs will recover with rest. Transport losses are a multifactorial problem consisting of people, pig, facility design, management, transportation, processing plant, and environmental factors, and, because of these multiple factors, continued research efforts are needed to understand how each of the factors and the relationships among factors affect the well-being of the pig during the marketing process.