Human TOP1 residues implicated in species specificity of HIV-1 infection are required for interaction with BTBD2, and RNAi of BTBD2 in old world monkey and human cells increases permissiveness to HIV-1 infection

Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5 restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM) virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5 splice variant TRIM5 in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction.

Multispecies Epidemiologic Surveillance Study after an Outbreak of Yersiniosis at an African Green Monkey Research Facility.

After an outbreak of Yersinia enterocolitica at a NHP research facility, we performed a multispecies investigation of the prevalence of Yersinia spp. in various mammals that resided or foraged on the grounds of the facility, to better understand the epizootiology of yersiniosis. Blood samples and fecal and rectal swabs were obtained from 105 captive African green monkeys (AGM), 12 feral cats, 2 dogs, 20 mice, 12 rats, and 3 mongooses. Total DNA extracted from swab suspensions served as template for the detection of Y. enterocolitica DNA by real-time PCR. Neither Y. enterocolitica organisms nor their DNA were detected from any of these samples. However, Western blotting revealed the presence of Yersinia antibodies in plasma. The AGM samples revealed a seroprevalence of 91% for Yersinia spp. and of 61% for Y. enterocolitica specifically. The AGM that were housed in cages where at least one fatality occurred during the outbreak (clinical group) had similar seroprevalence to that of AGM housed in unaffected cages (nonclinical group). However, the nonclinical group was older than the clinical group. In addition, 25%, 100%, 33%, 10%, and 10% of the sampled local cats, dogs, mongooses, rats, and mice, respectively, were seropositive. The high seroprevalence after this outbreak suggests that Y. enterocolitica was transmitted effectively through the captive AGM population and that age was an important risk factor for disease. Knowledge regarding local environmental sources of Y. enterocolitica and the possible role of wildlife in the maintenance of yersiniosis is necessary to prevent and manage this disease.

El Test de Ramsey y las lógicas condicionales

Frank Ramsey (1931) estableció ciertas condiciones que deberían cumplirse a fin de evaluar las proposiciones condicionales, conocidas hoy como Test de Ramsey (TR) En este trabajo se muestra que las teorías sobre condicionales contrafácticos de Chisholmj, Stalnaker y D. Lewis, satisfacen el TR y la incompatibilidad de TR con la Teoría de la revisión de creencias (AGM). En la última sección se analiza el comportamiento del TR en la propuesta de G. Grocco y L. Fariñas del Cerro, basada en una generalización del cálculo de Secuentes pero introduciendo la novedad de secuencias auxiliares cuya noción de consecuencia es no-monótona.

El Test de Ramsey y las lógicas condicionales

Frank Ramsey (1931) estableció ciertas condiciones que deberían cumplirse a fin de evaluar las proposiciones condicionales, conocidas hoy como Test de Ramsey (TR) En este trabajo se muestra que las teorías sobre condicionales contrafácticos de Chisholmj, Stalnaker y D. Lewis, satisfacen el TR y la incompatibilidad de TR con la Teoría de la revisión de creencias (AGM). En la última sección se analiza el comportamiento del TR en la propuesta de G. Grocco y L. Fariñas del Cerro, basada en una generalización del cálculo de Secuentes pero introduciendo la novedad de secuencias auxiliares cuya noción de consecuencia es no-monótona.

El Test de Ramsey y las lógicas condicionales

Frank Ramsey (1931) estableció ciertas condiciones que deberían cumplirse a fin de evaluar las proposiciones condicionales, conocidas hoy como Test de Ramsey (TR) En este trabajo se muestra que las teorías sobre condicionales contrafácticos de Chisholmj, Stalnaker y D. Lewis, satisfacen el TR y la incompatibilidad de TR con la Teoría de la revisión de creencias (AGM). En la última sección se analiza el comportamiento del TR en la propuesta de G. Grocco y L. Fariñas del Cerro, basada en una generalización del cálculo de Secuentes pero introduciendo la novedad de secuencias auxiliares cuya noción de consecuencia es no-monótona.

Antiangiogenic therapy of transgenic mice impairs de novo tumor growth.

Angiogenesis is activated during multistage tumorigenesis prior to the emergence of solid tumors. Using a transgenic mouse model, we have tested the proposition that treatment with angiogenesis inhibitors can inhibit the progression of tumorigenesis after the switch to the angiogenic phenotype. In this model, islet cell carcinomas develop from multifocal, hyperproliferative nodules that show the histological hallmarks of human carcinoma in situ. Mice were treated with a combination of the angiogenesis inhibitor AGM-1470 (TNP-470), the antibiotic minocycline, and interferon alpha/beta. The treatment regimen markedly attenuated tumor growth but did not prevent tumor formation; tumor volume was reduced to 11% and capillary density to 40% of controls. The proliferation index of tumor cells in treated and control mice was similar, whereas the apoptotic index was doubled in treated tumors. This study shows that de novo tumor progression can be restricted solely by antiangiogenic therapy. The results suggest that angiogenesis inhibitors represent a valid component of anticancer strategies aimed at progression from discrete stages of tumorigenesis and demonstrate that transgenic mouse models can be used to evaluate efficacy of candidate antiangiogenic agents.

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27, Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29); JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38, [Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency 44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.

Pseudo-contractions in belief revision

Belief Revision addresses the problem of how to change epistemic states, usually represented in the literature by sets of logical sentences. Solid theoretical results were consolidated with the AGM paradigm, which deals with theories (logically closed sets of sentences). After that, the theory was extended to belief bases, that is, arbitrary sets of sentences. Besides all this theoretical framework, AI researchers face serious difficulties when trying to implement belief revision systems. One of the major complications is the closure required by AGM theory, which cannot be easily computed. Even belief bases, which do not require closure, seem to be improper for practical purposes, since their changes are usually very rigid (syntax dependent). Some operations, known as pseudo-contractions, are in the middle ground between belief set change and belief base change. In the present work we have proposed a new pseudo-contraction operation, studied its properties and characterized it. We have also found connections between this operator and some other pseudo-contractions.

Feedbacks between vegetation pattern and resource loss dramatically decrease ecosystem resilience and restoration potential in a simple dryland model

Conceptual frameworks of dryland degradation commonly include ecohydrological feedbacks between landscape spatial organization and resource loss, so that decreasing cover and size of vegetation patches result in higher water and soil losses, which lead to further vegetation loss. However, the impacts of these feedbacks on dryland dynamics in response to external stress have barely been tested. Using a spatially-explicit model, we represented feedbacks between vegetation pattern and landscape resource loss by establishing a negative dependence of plant establishment on the connectivity of runoff-source areas (e.g., bare soils). We assessed the impact of various feedback strengths on the response of dryland ecosystems to changing external conditions. In general, for a given external pressure, these connectivity-mediated feedbacks decrease vegetation cover at equilibrium, which indicates a decrease in ecosystem resistance. Along a gradient of gradual increase of environmental pressure (e.g., aridity), the connectivity-mediated feedbacks decrease the amount of pressure required to cause a critical shift to a degraded state (ecosystem resilience). If environmental conditions improve, these feedbacks increase the pressure release needed to achieve the ecosystem recovery (restoration potential). The impact of these feedbacks on dryland response to external stress is markedly non-linear, which relies on the non-linear negative relationship between bare-soil connectivity and vegetation cover. Modelling studies on dryland vegetation dynamics not accounting for the connectivity-mediated feedbacks studied here may overestimate the resistance, resilience and restoration potential of drylands in response to environmental and human pressures. Our results also suggest that changes in vegetation pattern and associated hydrological connectivity may be more informative early-warning indicators of dryland degradation than changes in vegetation cover.

Drought and grazing combined: Contrasting shifts in plant interactions at species pair and community level

The combined effects of drought stress and grazing pressure on shaping plant–plant interactions are still poorly understood, while this combination is common in arid ecosystems. In this study we assessed the relative effect of grazing pressure and slope aspect (drought stress) on vegetation cover and soil functioning in semi-arid Mediterranean grassland–shrublands in southeastern Spain. Moreover, we linked these two stress factors to plant co-occurrence patterns at species-pair and community levels, by performing C-score analyses. Vegetation cover and soil functioning decreased with higher grazing pressure and more south-facing (drier) slopes. At the community level, plants at south-facing slopes were negatively associated at no grazing but positively associated at low grazing pressure and randomly associated at high grazing pressure. At north-facing slopes, grazing did not result in a shift in the direction of the association. In contrast, analysis of pairwise species co-occurrence patterns showed that the dominant species Stipa tenacissima and Anthyllis cytisoides shifted from excluding each other to co-occurring with increasing grazing pressure at north-facing slopes. Our findings highlight that for improved understanding of plant interactions along stress gradients, interactions between species pairs and interactions at the community level should be assessed, as these may reveal contrasting results.

Belief revision for adaptive negotiation agents

Existing negotiation agents are primitive in terms of what they can learn and how responsive they are towards the changing negotiation contexts. These weaknesses can be alleviated if an expressive representation language is used to represent negotiation contexts and a sound inference mechanism is applied to reason about the preferential changes arising in these negotiation contexts. This paper illustrates a novel adaptive negotiation agent model, which is underpinned by the well-known AGM belief revision logic. Our preliminary experiments show that the performance of the belief-based adaptive negotiation agents is promising.

Influências genéticas nas características da carcaça e carne em bovinos

Tese de Doutoramento em Ciências Veterinárias - Especialidade de Produção Animal

Qualidade da carne de ovinos puros e cruzados criados no Semiárido Nordestino brasileiro.

Resumo: A procura por carne de qualidade tem proporcionado ao setor de ovinocultura a adoção por técnicas de produção que possam contribuir para disponibilizar ao mercado produtos que atendam as necessidades dos consumidores, que se tornam cada vez mais exigentes quanto à aquisição de produtos que possam trazer benefícios a saúde. Assim, objetivou-se determinar a qualidade da carne de ovinos puros e cruzados criados no semiárido Nordestino. Utilizaram-se 30 cordeiros machos e fêmeas, oriundos dos cruzamentos Morada Nova x Morada Nova, Rabo Largo x Morada Nova e Santa Inês x Morada Nova, alojados em baias e alimentados com dieta a base de capim Canarana, milho farelo de soja e calcário. Os animais foram abatidos com peso médio de 24 kg de peso vivo e as carcaças mantidas em câmara frigorífica a 4?C, por 24 horas. Após esse período, foi seccionado o músculo Longissimus dorsi que foi embalado, identificado e armazenado a 20?C. Foram determinados os atributos físicos de capacidade de retenção de água, perda de peso por cocção e força de cisalhamento; os atributos químicos como umidade, proteína, cinza, lipídios e colesterol; avaliações subjetivas da carcaça como cor, marmoreio, textura da carne, distribuição da gordura, espessura da gordura e área de olho de lombo; os sensoriais de dureza, suculência, sabor, aroma e aceitação global e o perfil de ácidos graxos. O delineamento utilizado foi em esquema fatorial 3x2 (três grupos genéticos e dois sexos) e as médias comparadas pelo teste de Duncan a 5%. Não houve diferença (p>0,05) entre os genótipos para a composição química da carne, exceto para a variável lipídio (p<0,05). Para as características subjetivas da carcaça o genótipo influenciou (p<0,05) nas variáveis cor, marmoreio e textura da carne. O genótipo promoveu efeito (p<0,05) para as características físicas de capacidade de retenção de água e perda de peso por cocção. Os atributos sensoriais não sofreram efeitos (p>0,05) dos genótipos avaliados. Os genótipos influenciaram (p<0,05) as concentrações dos ácidos graxos saturados, monoinsaturados e poli-insaturados assim como, nas relações ?3:?6 e AGM:AGS. O fator sexo influenciou (p<0,05) nas variáveis umidade, força de cisalhamento, dureza, ácidos graxos desejáveis e relação ?3:?6. O cruzamento entre raças nativas mostrou-se com potencial para a produção de carne de qualidade, a raça Morada Nova melhorou os atributos físico-químicos da carne e em seu perfil lipídico e, o fator sexo melhorou o atributo maciez dando destaque a carne das fêmeas. Abstract: The demand for quality meat products has given the sheep industry sector productions techniques that can contribute providing the market with products that supply the needs of consumers require, who are becoming more demanding as the acquisition of differentiated and bring health benefits. The objective was to evaluate the quality of the pure sheep meat and cross bred in the semiarid Northeast of Brazil. It was used 30 male lambs and female, that came from crosses Morada Nova x Morada Nova, Rabo Largo x Morada Nova and Santa Ines x Morada Nova, housed in pens and fed a diet of grass Canarana, corn soybean meal and limestone. The animals were slaughtered at average weight of 24 kg, live weight, and carcasses kept in refrigeration chamber at 4 ° C for 24 hours. After this period the Longissimus dorsi muscle was selected, packaged, labeled and stored at 20˚C. The physical attributes were determined such as water holding capacity, cooking weight loss and shear force; the chemical attributes such as moisture, protein, ash, lipids and cholesterol; Subjective evaluations such as color, marbling, meat texture, fat distribution, fat thickness and loin eye area; the hardness sensory, juiciness, flavor, aroma and global acceptance and fatty acid profile. The design was a 3x2 factorial arrangement (three genetic groups and two genders) and the measures compared by Duncan test at 5%. There was no difference (p> 0.05) between genotypes for the chemical composition of meat, except for the lipid variable (p <0.05). To the subjective characteristics of the carcass, the genotype influenced (p <0.05) in the variables color, marbling and meat texture. The genotype promoted significant effect (p <0.05) for the physical characteristics, water retention capacity and weight loss on cooking. The sensory attributes did not suffer significant effects (p> 0.05) of the evaluated genotypes. The genotypes influenced (p <0.05) in the concentrations of saturated fatty acids, monounsaturated and polyunsaturated as well as in the relations ω3: ω6 and AGM:AGS. The gender factor influenced (P <0.05) in the variables moisture, shear strength, hardness, desirable fatty acids and relation ω3: ω6. The cross between native breeds showed up with potential for quality meat production, the Morada Nova improved the physical and chemical attributes of the flesh and in their lipid profiles and sex factor improved softness attribute highlighting the meat of females.