The impact of resistance on the use of second-generation anticoagulants against rats on farms in Southern England

Resistance amongst rats to second-generation anticoagulants, notably difenacoum, has been recognised since the 1970s. Although initially considered to be of practical significance, doubts were subsequently expressed that the degree of resistance was sufficient to explain ineffective rodenticide treatments. Research published elsewhere demonstrated the overriding importance of poor poisoned bait consumption, caused by the influence of certain ecological factors on rat behaviour, in reducing the effectiveness of second-generation anticoagulant treatments on farms in southern England. In this paper we consider, however, the subtle effects of resistance to anticoagulants on treatment outcome. The prevalence of resistance was increased amongst survivors of treatments and bait consumption by resistant survivors was higher than amongst susceptible survivors. The overall prevalence and degree of resistance to second-generation anticoagulants does not, however, currently represent a practical problem. Nevertheless, selection favouring increased resistance remains a long-term threat to the effectiveness of both difenacoum and bromadiolone.     

Effect of dietary starch, fat, and bicarbonate content on exercise responses and serum creatine kinase activity in equine recurrent exertional rhabdomyolysis

To determine the effect of dietary starch, bicarbonate, and fat content on metabolic responses and serum creatine kinase (CK) activity in exercising Thoroughbreds with recurrent exertional rhabdomyolysis (RER), 5 RER horses were fed 3 isocaloric diets (28.8 Mcal/d [120.5 MJ/d]) for 3 weeks in a crossover design and exercised for 30 minutes on a treadmill 5 days/wk. On the last day of each diet, an incremental standardized exercise test (SET) was performed. The starch diet contained 40% digestible energy (DE) as starch and 5% as fat: the bicarbonate-starch diet was identical but was supplemented with sodium bicarbonate (4.2% of the pellet): and the fat diet provided 7% DE as starch and 20% as fat. Serum CK activity before the SET was similar among the diets. Serum CK activity (log transformed) after submaximal exercise differed dramatically among the diets and was greatest on the bicarbonate-starch diet (6.51 +/- 1.5) and lowest on the fat diet (5.71 +/- 0.6). Appreciable differences were observed in the severity of RER among individual horses. Postexercise plasma pH, bicarbonate concentration, and lactate concentration did not differ among the diets. Resting heart rates before the SET were markedly lower on the fat diet than on the starch diet. Muscle lactate and glycogen concentrations before and after the SET did not differ markedly among the diets. A high-fat, low-starch diet results in dramatically lower postexercise CK activity in severely affected RER horses than does a low-fat, high-starch diet without measurably altering muscle lactate and glycogen concentrations. Dietary bicarbonate supplementation at the concentration administered in this study did not prevent increased serum CK activity on a high-starch diet.     

Assessment of alterations in triglyceride and glycogen concentrations in muscle tissue of Alaskan sled dogs during repetitive prolonged exercise

OBJECTIVE: To assess changes in muscle glycogen (MG) and triglyceride (MT) concentrations in aerobically conditioned sled dogs during prolonged exercise. ANIMALS: 54 Alaskan sled dogs fed a high-fat diet. PROCEDURES: 48 dogs ran 140-km distances on 4 consecutive days (cumulative distance, up to 560 km); 6 dogs remained as nonexercising control animals. Muscle biopsies were performed immediately after running 140, 420, or 560 km (6 dogs each) and subsequently after feeding and 7 hours of rest. Single muscle biopsies were performed during recovery at 28 hours in 7 dogs that completed 560 km and at 50 and 98 hours in 7 and 6 dogs that completed 510 km, respectively. Tissue samples were analyzed for MG and MT concentrations. RESULTS: In control dogs, mean +/- SD MG and MT concentrations were 375 +/- 37 mmol/kg of dry weight (kgDW) and 25.9 +/- 10.3 mmol/kgDW, respectively. Compared with control values, MG concentration was lower after dogs completed 140 and 420 km (137 +/- 36 mmol/kgDW and 203 +/- 30 mmol/kgDW, respectively); MT concentration was lower after dogs completed 140, 420, and 560 km (7.4 +/- 5.4 mmol/kgDW; 9.6 +/- 6.9 mmol/kgDW, and 6.3 +/- 4.9 mmol/kgDW, respectively). Depletion rates during the first run exceeded rates during the final run. Replenishment rates during recovery periods were not different, regardless of distance; only MG concentration at 50 hours was significantly greater than the control value. CONCLUSIONS AND CLINICAL RELEVANCE: Concentration of MG progressively increased in sled dogs undergoing prolonged exercise as a result of attenuated depletion.     

Turkey origin reovirus-induced immune dysfunction in specific pathogen free and commercial turkey poults

Recently, pathogenesis studies, using genetically distinct turkey-origin reoviruses (TRVs), revealed that poults infected with certain TRV isolates had moderate to severe bursal atrophy, suggesting virus-induced immune dysfunction. In order to characterize the effect of TRV infection on the turkey immune system, classical assays were undertaken to quantify the humoral and cell-mediated immune responses in small Beltsville and broad-breasted white poults infected with the TRV isolate NC/SEP-R44/03. A marked effect on the cutaneous basophil hypersensitivity response, and on the antibody response to Newcastle disease virus (NDV) exposure, was noted in commercial and specific pathogen free (SPF) poults inoculated with NC/SEP-R44/03 at three days of age. Moderate to severe bursal atrophy, similar to that noted previously in SPF poults, occurred in commercial poults inoculated at three days of age. This immune dysfunction and bursal atrophy was not present in commercial poults inoculated at three weeks of age.     

Localization and genotyping of canine papillomavirus in canine inverted papillomas

Numerous canine papillomaviruses (CPVs) have been identified (CPV1–23). CPV1, 2, and 6 have been associated with inverted papillomas (IPs). We retrieved 19 IPs from 3 histopathology archives, and evaluated and scored koilocytes, inclusion bodies, giant keratohyalin granules, cytoplasmic pallor, ballooning degeneration, and parakeratosis. IHC targeting major capsid proteins of PV was performed, and CPV genotyping was achieved by PCR testing. Tissue localization of CPV DNA and RNA was studied by chromogenic and RNAscope in situ hybridization (DNA-CISH, RNA-ISH, respectively). IPs were localized to the limbs (50%), trunk (30%), and head (20%), mainly as single nodules (16 of 19). In 15 of 19 cases, immunopositivity was detected within the nuclei in corneal and subcorneal epidermal layers. PCR revealed CPV1 in 11 IPs and CPV2 DNA in 3 IPs. Overall, 14 of 17 cases were positive by both DNA-CISH and RNA-ISH, in accord with PCR results. A histologic score >5 was always obtained in cases in which the viral etiology was demonstrated by IHC, DNA-CISH, and RNA-ISH. IHC and molecular approaches were useful to ascertain the viral etiology of IPs. Although IHC is the first choice for diagnostic purposes, ISH testing allows identification of PV type and the infection phase. RNA-ISH seems a promising tool to deepen our understanding of the pathogenesis of different PV types in animal species.     

Abrupt decrease in tropical Pacific sea surface salinity at end of Little Ice Age

A 420-year history of strontium/calcium, uranium/calcium, and oxygen isotope ratios in eight coral cores from the Great Barrier Reef, Australia, indicates that sea surface temperature and salinity were higher in the 18th century than in the 20th century. An abrupt freshening after 1870 occurred simultaneously throughout the southwestern Pacific, coinciding with cooling tropical temperatures. Higher salinities between 1565 and 1870 are best explained by a combination of advection and wind-induced evaporation resulting from a strong latitudinal temperature gradient and intensified circulation. The global Little Ice Age glacial expansion may have been driven, in part, by greater poleward transport of water vapor from the tropical Pacific.     

Computational design of proteins targeting the conserved stem region of influenza hemagglutinin

We describe a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule. Favorable interactions between disembodied amino acid residues and the target surface are identified and used to anchor de novo designed interfaces. The method was used to design proteins that bind a conserved surface patch on the stem of the influenza hemagglutinin (HA) from the 1918 H1N1 pandemic virus. After affinity maturation, two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity. Further, HB80 inhibits the HA fusogenic conformational changes induced at low pH. The crystal structure of HB36 in complex with 1918/H1 HA revealed that the actual binding interface is nearly identical to that in the computational design model. Such designed binding proteins may be useful for both diagnostics and therapeutics.