Genetic parameters for growth, reproductive and maternal traits in a multibreed meat sheep population

The genetic parameters for growth, reproductive and maternal traits in a multibreed meat sheep population were estimated by applying the Average Information Restricted Maximum Likelihood method to an animal model. Data from a flock supported by the Programa de Melhoramento Genético de Caprinos e Ovinos de Corte (GENECOC) were used. The traits studied included birth weight (BW), weaning weight (WW), slaughter weight (SW), yearling weight (YW), weight gain from birth to weaning (GBW), weight gain from weaning to slaughter (GWS), weight gain from weaning to yearling (GWY), age at first lambing (AFL), lambing interval (LI), gestation length (GL), lambing date (LD - number of days between the start of breeding season and lambing), litter weight at birth (LWB) and litter weight at weaning (LWW). The direct heritabilities were 0.35, 0.81, 0.65, 0.49, 0.20, 0.15 and 0.39 for BW, WW, SW, YW, GBW, GWS and GWY, respectively, and 0.04, 0.06, 0.10, 0.05, 0.15 and 0.11 for AFL, LI, GL, LD, LWB and LWW, respectively. Positive genetic correlations were observed among body weights. In contrast, there was a negative genetic correlation between GBW and GWS (-0.49) and GBW and GWY (-0.56). Positive genetic correlations were observed between AFL and LI, LI and GL, and LWB and LWW. These results indicate a strong maternal influence in this herd and the presence of sufficient genetic variation to allow mass selection for growth traits. Additive effects were of little importance for reproductive traits, and other strategies are necessary to improve the performance of these animals.     

Design, synthesis, and pharmacological evaluation of new neuroactive pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives with in vivo hypnotic and analgesic profile

The present study describes the synthesis and pharmacological profiles of four novel pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives 2-5, which were structurally designed by using the sedative and analgesic drug zolpidem 1 as lead compound. The heterotricyclic system present in the target compounds 2-5 was constructed in good yields, exploiting a regioselective hetero Diels-Alder reaction of the key azabutadiene derivative 7 and functionalized N-phenylmaleimides 9-12. Additionally, we identified that 1-methyl-7-(4-nitrophenyl)-3-phenyl-3,6,7,8-tetrahydropyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8-dione derivative (LASSBio-873, 5) presented not only the most potent ability to promote sedation, which was similar to that induced by the standard benzodiazepine drug midazolam, but also potent central antinociceptive effect.     

Species distribution models in climate change scenarios are still not useful for informing policy planning: an uncertainty assessment using fuzzy logic

We compared the effect of general circulation models and greenhouse gas emission scenarios on the uncertainty associated with models predicting changes in areas favourable to animal species. Given that mountain species are particularly at risk due to climate warming, we selected one amphibian (Baetic midwife toad), one reptile (Lataste's viper), one bird (Bonelli's eagle), and one mammal (Iberian wild goat) present in Spanish mountains to model their distributional response to climate change during this century. Climate forecasts for the whole century were provided by the Agencia Estatal de Meteorología (AEMET; National Meteorological Agency) of Spain, which adapted the general circulation models CGCM2 and ECHAM4 and produced expected temperature and precipitation values for Spain according to the A2 and B2 emission scenarios. We constructed separate models of the species response to spatial, topographic, human, and climate variables using current values of the corresponding variables. We predicted future areas favourable to the species by replacing the current climate values with those expected according to each climate change scenario, while keeping spatial, topographic and human variables constant. Fuzzy logic was used to compute the coincidence between predictions for different emission scenarios in the same global circulation model, and the consistency between predictions for the same emission scenario applying different general circulation models. In general, coincidences were higher than consistencies and, thus, discrepancies between predictions were more attributable to uncertainty in global circulation models, i.e. our insufficient knowledge concerning the effect of the oceans and atmosphere on climate, than to the putative effect of different emission scenarios on future climates. Our conclusion is that species distribution models in climate warming scenarios are still not useful for informing emission policy planning, although they have great potential as tools once consistencies become higher than coincidences.     

Caffeine and CSC,adenosine A2A antagonists,offer neuroprotection against 6-OHDA-induced neurotoxicity in rat mesencephalic cells

In this study, the cytoprotective effects of caffeine (CAF) and 8-(3-chlorostyryl)-caffeine (CSC), A_2A receptor antagonists, were tested against 6-OHDA-induced cytotoxicity, in rat mesencephalic cells. Both drugs significantly increased the number of viable cells, after their exposure to 6-OHDA, as measured by the MTT assay. While nitrite levels in the cells were drastically increased by 6-OHDA, their concentrations were brought toward normality after CAF or CSC, indicating that both drugs block 6-OHDA-induced oxidative stress which leads to free radicals generation. A complete blockade of 6-OHDA-induced lipid peroxidation, considered as a major source of DNA damage, was observed after cells treatment with CAF or CSC. 6-OHDA decreased the number of normal cells while increasing the number of apoptotic cells. In the CAF plus 6-OHDA group, a significant recover in the number of viable cells and a decrease in the number of apoptotic cells were seen, as compared to the group treated with 6-OHDA alone. A similar effect was observed after cells exposure to CSC in the presence of 6-OHDA. Unexpectedly, while a significant lower number of activated microglia was observed after cells exposure to CAF plus 6-OHDA, this was not the case after cells exposure to CSC under the same conditions. While CAF lowered the percentage of reactive astrocytes increased by 6-OHDA, CSC presented no effect. The effects of these drugs were also examined on the releases of myeloperoxidase (MPO), an inflammatory marker, and lactate dehydrogenase (LDH), a marker for cytotoxicity, in human neutrophils, in vitro. CSC and CAF (0.1, 1 and 10 μg/ml) produced inhibitions of the MPO release from PMA-stimulated cells, ranging from 45 to 83%. In addition, CSC and CAF (5, 50 and 100 μg/ml) did not show any cytotoxicity in the range of concentrations used, as determined by the LDH assay. All together, our results showed a strong neuroptrotection afforded by caffeine or CSC, on rat mesencephalic cells exposed to 6-OHDA. Furthermore, CSC and caffeine actions, inhibiting MPO as well as LDH releases, would contribute to their possible benefit in the treatment of neurodegenerative diseases, including DP. These effects are partially due to the ability of these A_2A antagonists to decrease the cells free radicals production and oxidative stress, that are major components of 6-OHDA-induced cytotoxicity.     

Assessing the potential range expansion of the exotic monk parakeet in Spain

In this study we determine favourable areas for the monk parakeet, Myiopsitta monachus , in peninsular Spain to account for its current distribution and predict its future course according to its potential range. We applied a favourability function based on generalized linear models using the presence/absence of breeding colonies of the species and the values of a set of variables on the 5167 UTM 10 × 10 km squares comprising the study area. We calculated the factor of distribution change in presences predicted by the model, and grouped the variables into explanatory factors performing a variation partitioning to assess the explanatory power of each factor. Our model included six predictors to explain the presence and absence of the species. These predictors were grouped into three factors: human activity, climate, and topography. Purely human influences accounted for 63.8% of the variation of the final model, while topographical variables explained 15.2% and climate only 5.7%. We obtained a high distribution change factor in which the presences of the species were predicted to increase between two- and sevenfold. Taking into account highly favourable squares, we conclude that the species is still absent in more than 72% of potential settlement areas, and thus we expect a continuous increase in the distribution of the species. Human activity is the main force moulding the distribution of the species, and lies behind its fast expansion, which is not only active, but is also passive via releases and escapes. We identified the areas of likely future expansion of the exotic monk parakeet in Spain. The pest status of the species in its native range, together to its distribution trend, should be taken into account by wildlife agencies to consider options for management.     

Geographical variation in temporal and spatial vocalization patterns of male harbour seals in the mating season

In the aquatically mating harbour seal, Phoca vitulina, oestrous females show marked differences in spatial and temporal distribution between geographical areas. This suggests that the males' display behaviour may also vary between areas. We recorded male vocalizations in two areas, the Moray Firth and Orkney, U.K. In the Moray Firth, females haul out on a few intertidal sandbars and travel along predictable routes to forage at sea. In Orkney, female haul out sites are much less influenced by tidal availability and females are much more dispersed. In the Moray Firth, males vocalized only during a short mating season, from 1 July to 12 August. Vocalizations varied significantly with the tide, the peak at high tide clearly coinciding with the period when most females were in the water. In contrast, vocalizations in Orkney were significantly related to both tidal and diel patterns. We suggest that the timing of male vocalizations reflects differences in female availability between sites. In the inner Moray Firth, vocalizations were heard throughout the females' range, whereas vocalizations in Orkney were heard only in two discrete areas. However, at both sites the density of vocalizing males was highest in narrow channels and/or along predictable female travel routes. Therefore, males clearly adapt their temporal and spatial behaviour patterns to variations in female distribution and density. These results suggest that male mating strategies in aquatically mating pinnipeds are more variable than was previously envisaged. Copyright 1999 The Association for the Study of Animal Behaviour.     

Application of multivariate resolution methods to the study of biochemical and biophysical processes

Multivariate resolution methods make up a set of mathematical tools that may be applied to the analysis and interpretation of spectroscopic data recorded when monitoring a physical or chemical process with multichannel detectors. The goal of resolution methods is the recovery of chemical and/or physical information from the experimental data. Such data include, for example, the number of intermediates present in a reaction, the rate or equilibrium constants, and the spectra for each one of those intermediates. Multivariate resolution methods have been shown to be useful for the study of biophysical and biochemical processes such as folding/unfolding of proteins or nucleic acids. The present article reviews the most frequently used resolution methods, the limitations on their use, and their latest applications in protein and nucleic acid research.     

Molecular dynamics simulation of highly charged proteins: comparison of the particle-particle particle-mesh and reaction field methods for the calculation of electrostatic interactions

Molecular dynamics (MD) simulations of the activation domain of porcine procarboxypeptidase B (ADBp) were performed to examine the effect of using the particle-particle particle-mesh (P3M) or the reaction field (RF) method for calculating electrostatic interactions in simulations of highly charged proteins. Several structural, thermodynamic, and dynamic observables were derived from the MD trajectories, including estimated entropies and solvation free energies and essential dynamics (ED). The P3M method leads to slightly higher atomic positional fluctuations and deviations from the crystallographic structure, along with somewhat lower values of the total energy and solvation free energy. However, the ED analysis of the system leads to nearly identical results for both simulations. Because of the strong similarity between the results, both methods appear well suited for the simulation of highly charged globular proteins in explicit solvent. However, the lower computational demand of the RF method in the present implementation represents a clear advantage over the P3M method.     

TopBP1 localises to centrosomes in mitosis and to chromosome cores in meiosis

Topoisomerase IIbeta binding protein 1 (TopBP1), previously shown to localise to sites of DNA damage and to stalled replication forks, has been implicated in DNA replication and in DNA damage response. In this work we showed that TopBP1 was localised in structures other than stalled replication forks. In late mitosis TopBP1 localises to centrosomes in a manner similar to other DNA damage response proteins such as BRCA1 and p53. Spindle checkpoint activation does not affect this centrosomal localisation. Moreover, in the testis, we detected high levels of TopBP1 associated with meiotic prophase chromosome cores and the X-Y pair. Together, these data suggest a direct role of TopBP1 during both mitosis and meiotic prophase I.