Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Orangutan cultures and the evolution of material culture

Geographic variation in some aspects of chimpanzee behavior has been interpreted as evidence for culture. Here we document similar geographic variation in orangutan behaviors. Moreover, as expected under a cultural interpretation, we find a correlation between geographic distance and cultural difference, a correlation between the abundance of opportunities for social learning and the size of the local cultural repertoire, and no effect of habitat on the content of culture. Hence, great-ape cultures exist, and may have done so for at least 14 million years.     

Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster

Comparison of the genomes and proteomes of the two diptera Anopheles gambiae and Drosophila melanogaster, which diverged about 250 million years ago, reveals considerable similarities. However, numerous differences are also observed; some of these must reflect the selection and subsequent adaptation associated with different ecologies and life strategies. Almost half of the genes in both genomes are interpreted as orthologs and show an average sequence identity of about 56%, which is slightly lower than that observed between the orthologs of the pufferfish and human (diverged about 450 million years ago). This indicates that these two insects diverged considerably faster than vertebrates. Aligned sequences reveal that orthologous genes have retained only half of their intron/exon structure, indicating that intron gains or losses have occurred at a rate of about one per gene per 125 million years. Chromosomal arms exhibit significant remnants of homology between the two species, although only 34% of the genes colocalize in small "microsyntenic" clusters, and major interarm transfers as well as intra-arm shuffling of gene order are detected.     

Managing lead exposure and toxicity in cow-calf herds to minimize the potential for food residues.

Lead poisoning is commonly diagnosed in cattle. In this study, 3 groups of cattle from different herds accidentally exposed to discarded lead batteries on pasture were intensively studied to determine the extent and severity of exposure. The losses from acute death due to lead toxicity were substantial in all the 3 study groups at 12%, 17%, and 4%. Blood samples were taken from all cattle around the time of the first diagnosis and then later in 2 of the 3 herds to monitor the change in lead concentrations over time. Asymptomatic lead toxicosis was observed in these herds. In these 3 groups, between 4% and 12% of asymptomatic cattle had blood lead concentrations consistent with acute lead poisoning (> 0.35 ppm), and between 7% and 40% of these asymptomatic animals were in the high-normal range (0.1-0.35 ppm). Because of the consistently high number of asymptomatic cattle with elevated lead levels, all cattle potentially exposed to a lead source should be tested before sale or slaughter to minimize the entry of lead into the food chain. The blood lead concentrations, which were monitored for months after the initial diagnosis, decreased slowly after the cattle were removed from the lead source. The prolonged retention of lead may be due to continued release and absorption of lead from metal particles in the reticulum or rumen. The mean reduction in the lead level was 0.046 ppm (95% CI, 0.017-0.075 ppm) every 30 days for these 2 herds. Using a single-component exponential model, the half-life of lead in the animals retested from Herds 1 and 2 was highly variable. The median half-life was 63 days (interquartile range, 34-107 days). One out of 8 pregnant heifers with high blood levels had a stillborn calf. There were no abortions or calf mortalities in this group. Blood samples were'collected from the calves around the time of birth. The concentrations of lead in the blood of the calves exposed in utero were low (0.010-0.095 ppm).     

Enzootic bovine leukosis virus in Brazil

Summary A sero-epidemiological survey for antibodies to the glycoprotein of enzootic bovine leukosis virus showed that the infection is widely disseminated in the State of Rio de Janeiro, Brazil. Sera from 1,290 females and 154 males from 12 dairy herds were tested by the agar gel precipitin test. Seven hundred and one females (54.3%) and 68 males (44.2%) were found to have specific antibodies. These antibodies were demonstrated in all 7 age groups tested. The older age groups contained the highest percentage of reactors. The results are briefly discussed in relation to management practices and environmental conditions.

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El Virus De La Leucosis Bovina Enzootica En Brasil

Resumen Una encuesta suero-epidemiológica por anticuerpos contra la glicoproteina del virus de la leucosis bovina enzootica mostró que la infección está ampliamente diseminada en el Estado de Rio de Janeiro, Brasil. Sueros de 1290 hembras y 154 machos pertenecientes a 12 rebaños lecheros fueron examinados en la prueba de precipitación en agar. Se encontró que 701 hembras (54.3 por ciento) y 68 machos (44.2 por ciento) poseían anticuerpos específicos. Estos anticuerpos fueron demonstrados en todos los siete grupos de edad examinados. Los grupos de mas edad contenian un porcentaje mayor de reactores. Los resultados son discutidos brevemente en relación a las prácticas de manejo y a las condiciones ambientales locales.

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Virus De La Leucose Bovine Enzootique Au Bresil

Résumé Une enquête séro-épidémiologique pour la détection de la présence de la glycoproteine du virus de la leucose enzootique bovine a montré que cette affection est largement disséminée dans l'Etat de Rio de Janeiro, au Brésil. Des échantillons de sérum provenant de 1290 femelles et 154 mâles appartenant à 12 troupeaux laitiers ont été étudiés par précipitation en gélose—701 femelles (54,3 p. 100) et 68 mâles (44,2 p. 100) ont été reconnus comme possédant des anticorps spécifiques. Ces anticorps ont été mis en évidence dans la totalité des 7 groupes d'âges étudiés. Les groupes d'âges plus élevés contenaient le plus haut pourcentage d'animaux positifs. Les résultats sont brièvement discutés, dans leur relation avec les pratiques de l'élevage et les conditions de l'environnement.

     

Longevity of protective immunity to experimental bovine herpesvirus-1 infection following inoculation with a combination modified-live virus vaccine in beef calves

OBJECTIVE: To determine whether a combination viral vaccine containing modified-live bovine herpesvirus-1 (BHV-1) would protect calves from infection with a recent field isolate of BHV-1. DESIGN: Randomized controlled trial. ANIMALS: Sixty 4- to 6-month-old beef calves. PROCEDURE: Calves were inoculated with a placebo 42 and 20 days prior to challenge (group 1; n = 10) or with the combination vaccine 42 and 20 days prior to challenge (group 2; 10), 146 and 126 days prior to challenge (group 3; 10), 117 and 96 days prior to challenge (group 4; 10), 86 and 65 days prior to challenge (group 5; 10), or 126 days prior to challenge (group 6; 10). All calves were challenged with BHV-1 via aerosol. Clinical signs, immune responses, and nasal shedding of virus were monitored for 14 days after challenge. RESULTS: Vaccination elicited increases in BHV-1-specific IgG antibody titers. Challenge with BHV-1 resulted in mild respiratory tract disease in all groups, but vaccinated calves had less severe signs of clinical disease. Extent and duration of nasal BHV-1 shedding following challenge was significantly lower in vaccinated calves than in control calves. In calves that received 2 doses of the vaccine, the degree of protection varied with the interval between the last vaccination and challenge, as evidenced by increases in risk of clinical signs and extent and duration of viral shedding. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that this combination vaccine provided protection from infection with virulent BHV-1 and significantly reduced nasal shedding of the virus for at least 126 days after vaccination.     

Alterations in thyroid hormone concentrations in healthy sled dogs before and after athletic conditioning

OBJECTIVE: To determine effects of athletic conditioning on thyroid hormone concentrations in a population of healthy sled dogs. ANIMALS: 19 healthy adult sled dogs. PROCEDURE: Serum concentrations of thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), free T4 (fT4), free T3 (fT3), and autoantibodies directed against T3, T4, and thyroglobulin were measured in sled dogs that were not in training (ie, nonracing season) and again after dogs had been training at maximum athletic potential for 4 months. RESULTS: Analysis revealed significant decreases in T4 and fT4 concentrations and a significant increase in TSH concentration for dogs in the peak training state, compared with concentrations for dogs in the untrained state. Serum concentrations of T4 and fT4 were less than established reference ranges during the peak training state for 11 of 19 and 8 of 19 dogs, respectively; fT4 concentration was greater than the established reference range in 9 of 19 dogs in the untrained state. CONCLUSIONS AND CLINICAL RELEVANCE: Decreased total T4 and fT4 concentrations and increased serum concentrations of TSH were consistently measured during the peak training state in healthy sled dogs, compared with concentrations determined during the untrained state. Although thyroid hormone concentrations remained within the established reference ranges in many of the dogs, values that were outside the reference range in some dogs could potentially lead to an incorrect assessment of thyroid status. Endurance training has a profound impact on the thyroid hormone concentrations of competitive sled dogs.