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In the last 15 years, the mesocercariae of Alaria alata have frequently been reported in the wild boar during routine Trichinella inspections made compulsory for the trade of venison meat in Europe. If these studies have focused primarily on mesocercariae isolated from meat, few works have been done so far to understand the circulation of the parasite in natural conditions especially in the intermediate hosts. This study focuses on the second intermediate hosts of this parasite assessing the suitability of two amphibian groups-brown frogs and water frogs sensu lato-for mesocercarial infection on an area where A. alata has already been identified in water snails and wild boars. During this study, both groups showed to be suitable for mesocercarial infection, with high prevalence and parasite burdens. Prevalence was higher in the brown frog group (56.9 versus 11.54 % for water frogs) which would indicate that it is a preferential group for infection on the study area, though reasons for this remain to be investigated. No significant difference among prevalences was observed between tadpoles and frogs. This study, the first focusing on A. alata in these amphibians in Europe, provides further information on circulation of this parasite in natura. [ABSTRACT FROM AUTHOR]

Demographic rates can vary not only with measured individual characters like age, sex and mass but also with unmeasured individual variables like behaviour, genes and health., Predictions from population models that include measured individual characteristics often differ from models that exclude them. Similarly, unmeasured individual differences have the potential to impact predictions from population models. However, unmeasured individual differences are rarely included in population models., We construct stage- and age-structured models (where stage is mass) of a roe deer population, which are parameterized from statistical functions that either include, or ignore, unmeasured individual differences., We found that mass and age structures substantially impacted model parameters describing population dynamics, as did temporal environmental variation, while unmeasured individual differences impacted parameters describing population dynamics to a much smaller extent once individual heterogeneity related to mass and age has been included in the model. We discuss how our assumptions (unmeasured individual differences only in mean trait values) could have influenced our findings and under what circumstances unmeasured individual differences could have had a larger impact on population dynamics., There are two reasons explaining the relative small influence of unmeasured individual differences on population dynamics in roe deer. First, individual body mass and age both capture a large amount of individual differences in roe deer. Second, in large populations of long-lived animals, the average quality of individuals (independent of age and mass) within the population is unlikely to show substantial variation over time, unless rapid evolution is occurring. So even though a population consisting of high-quality individuals would have much higher population growth rate than a population consisting of low-quality individuals, the probability of observing a population consisting only of high-quality individuals is small. [ABSTRACT FROM AUTHOR]

The predictive adaptive response (PAR) hypothesis proposes that animals adjust their physiology and developmental trajectory during early life in anticipation of their future environments. Accordingly, when environmental conditions in early life match environmental conditions during adulthood, individual fitness should be greater. Here, we test this hypothesis in a long-lived mammal, the roe deer, using data from two contrasting populations, intensively monitored for more than 35 years. In the highly productive site, the fitness of female roe deer increased with the quality of environment during adulthood and, contrary to predictions of PAR, individuals born in good conditions always outperformed those born under poor conditions. In the resource-limited site, the fitness of female roe deer born in poor years was better than those born in good conditions in poor years when the animals were adult, but not in good years. Although consistent with predictions of PAR, we showed that this pattern is likely to be a consequence of increased viability selection during the juvenile stage for animals born in poor years. While PARs are often advanced in evolutionary medicine, our findings suggest that detailed biological processes should be investigated before drawing conclusions about the existence of this phenomenon. [ABSTRACT FROM AUTHOR]

: This study of a French deer population reveals the demographic costs associated with the failure of a herbivore to modify its life cycle timing to respond to a warming world. [ABSTRACT FROM AUTHOR]

In seasonal environments, parturition of most vertebrates generally occurs within a short time-window each year. This synchrony is generally interpreted as being adaptive, as early born young survive better over the critical season than late born young. Among large herbivores, the factors involved in driving among- and within-individual variation in parturition date are poorly understood. We explored this question by analyzing the relative importance of attributes linked to female quality (longevity, median adult body mass and cohort), time-dependent attributes linked to female condition (reproductive success the previous year, relative annual body mass and offspring cohort (year)), and age in shaping observed variation in parturition date of roe deer. A measure of quality combining the effects of female longevity and median adult body mass accounted for 11% of the observed among-individual variation in parturition date. Females of 2 yr old give birth 5 d later than older females. Our study demonstrates that high quality (heavy and long-lived) females give birth earlier than low quality females. Temporally variable attributes linked to female condition, such as reproductive success in the previous year and relative annual body mass, had no detectable influence on parturition date. We conclude that parturition date, a crucial determinant of reproductive success, is shaped by attributes linked to female quality rather than by time-dependent attributes linked to female condition in income breeders (individuals that rely on current resource intake rather than on accumulated body reserves to offset the increased energy requirements due to reproduction) such as roe deer. [ABSTRACT FROM AUTHOR]

There is increasing evidence that environmental conditions experienced early in life can markedly affect an organism's life history, but the pathways by which early environment influences adult phenotype are poorly known. We used long-term data from two roe deer (Capreolus capreolus) populations (Chizé and Trois-Fontaines, France) to investigate the direct and indirect (operating through fawn body mass) effects of environmental conditions during early life on adult body mass. We found that environmental conditions (population size and spring temperatures) around birth influenced body mass of adult females through both direct and indirect effects in both populations. The occurrence of direct effects means that, for a given fawn body mass, adult female mass decreases with adverse conditions in early life. In contrast, we found no evidence for direct effects of early-life conditions on adult body mass of males, suggesting the existence of sex-specific long-term responses of body mass to stressful early conditions. Our results provide evidence that early environmental conditions influence the adult phenotype through persistent effects over the body development in wild mammal populations. [ABSTRACT FROM AUTHOR]

The impact of parasites on population dynamics is well documented, but less is known on how host population density affects parasite spread. This relationship is difficult to assess because of confounding effects of social structure, population density, and environmental conditions that lead to biased among-population comparisons. Here, we analyzed the infestation by two groups of nematodes (gastro-intestinal (GI) strongyles and Trichuris) in the roe deer ( Capreolus capreolus) population of Trois Fontaines (France) between 1997 and 2007. During this period, we experimentally manipulated population density through changes in removals. Using measures collected on 297 individuals, we quantified the impact of density on parasite spread after taking into account possible influences of date, age, sex, body mass, and weather conditions. The prevalence and abundance of eggs of both parasites in females were positively related to roe deer density, except Trichuris in adult females. We also found a negative relationship between parasitism and body mass, and strong age and sex-dependent patterns of parasitism. Prime-age adults were less often parasitized and had lower fecal egg counts than fawns or old individuals, and males were more heavily and more often infected than females. Trichuris parasites were not affected by weather, whereas GI strongyles were less present after dry and hot summers. In the range of observed densities, the observed effect of density likely involves a variation of the exposure rate, as opposed to variation in host susceptibility. [ABSTRACT FROM AUTHOR]

Declines in survival and reproduction with age are prevalent in wild vertebrates, but we know little about longitudinal changes in behavioral, morphological, or physiological variables that may explain these demographic declines. We compared age-related variation in body mass of adult females in three free-living ungulate populations that have been the focus of long-term, individual-based research: bighorn sheep (Ovis canadensis) at Ram Mountain, Canada; roe deer (Capreolus capreolus) at Trois Fontaines, France; and Soay sheep (Ovis aries) on St. Kilda, Scotland. We use two recently proposed approaches to separate contributions to age-dependent variation at the population level from within-individual changes and between-individual selective disappearance. Selective disappearance of light individuals in all three populations was most evident at the youngest and oldest ages. In later adulthood, bighorn sheep and roe deer showed a continuous decline in body mass that accelerated with age while Soay sheep showed a precipitous decrease in mass in the two years preceding death. Our results highlight the importance of mass loss in explaining within-individual demographic declines in later adulthood in natural populations. They also reveal that the pattern of senescence, and potentially also the processes underlying demographic declines in late life, can differ markedly across related species with similar life histories. [ABSTRACT FROM AUTHOR]

In polygynous mammals, sex-specific patterns of body growth are linked to divergent selection pressures on male and female body size, resulting in sexual dimorphism (SD). For males, reproductive success is generally linked to body size, hence, males should prioritise early growth. For females, reproductive success is linked to resource availability, so they may adopt a more conservative growth tactic. Using longitudinal monitoring of known-age animals in two contrasting populations and an allometric approach to disentangle the relative contribution of structural size and physiological condition to SD, we addressed these issues in the weakly polygynous roe deer. Despite very different environmental conditions, we found remarkably similar patterns in the two populations in the mass - size allometric relationship at each life history stage, suggesting that relative allocation to structural size and physiological condition is highly constrained. SD in structural size (indexed by hind foot length) involved sex-specific growth trajectories governed by a single mass - size allometric relationship during the juvenile stage, such that males were both bigger and heavier than females. In contrast, SD in physiological condition (indexed by the allometric relationship between body mass and hind foot length, expressed as body mass for a given body size) developed markedly during the sub-adult stage in relation to sex differences in the timing of first reproduction. Among adults, males were heavier for a given size than females, suggesting that, relative to females, males express a capital breeder tactic, accumulating fat reserves to offset reproductive costs. By the senescent stage, SD in physiological condition had disappeared, with both sexes governed by a single allometric relationship, suggesting more rapid senescence in males than females. Individuals born into poor cohorts were generally lighter for a given size, indicating growth priority for skeletal size over physiological condition in both sexes. However, sex differences in cohort effects among sub-adults resulted in lower size-specific SD in poor cohorts, indicating that body condition of sub-adult females is buffered against environmental harshness. We conclude that sex-differences in reproductive tactics impose constraints on the ontogeny of SD in roe deer, leading to sex-specific trajectories in structural size and physiological condition. [ABSTRACT FROM AUTHOR]

Background: Data on spatial genetic patterns may provide information about the ecological and behavioural mechanisms underlying population structure. Indeed, social organization and dispersal patterns of species may be reflected by the pattern of genetic structure within a population. Methodology/Principal Findings: We investigated the fine-scale spatial genetic structure of a roe deer (Capreolus capreolus) population in Trois-Fontaines (France) using 12 microsatellite loci. The roe deer is weakly polygynous and highly sedentary, and can form matrilineal clans. We show that relatedness among individuals was negatively correlated with geographic distance, indicating that spatially proximate individuals are also genetically close. More unusually for a large mammalian herbivore, the link between relatedness and distance did not differ between the sexes, which is consistent with the lack of sex-biased dispersal and the weakly polygynous mating system of roe deer. Conclusions/Significance: Our results contrast with previous reports on highly polygynous species with male-biased dispersal, such as red deer, where local genetic structure was detected in females only. This divergence between species highlights the importance of socio-spatial organization in determining local genetic structure of vertebrate populations. [ABSTRACT FROM AUTHOR]

Little is known about traits under sexual selection in territorial mammals with low sexual size dimorphism. We examined the potential for sexual selection on male body mass and antler length in the European roe deer Capreolus capreolus, a territorial ungulate in which males are less than 10% heavier than females. Independently, both body mass and antler length (irrespective of age) had a positive effect on male yearly breeding success. However, when corrected for body mass, antler length at a given mass only had a slight effect on male breeding success. This suggests that: (1) ‘bigger is better’ and (2) sexual selection is responsible for at least part of the observed variation in body mass and antler length in roe deer. High body mass and large antlers may be advantageous to males for two reasons: (1) they enhance fighting ability and dominance, so allowing males to defend better their territory and hence access mates, and (2) they attract females because they are honest signals of male phenotypic quality. This suggests that, even in weakly dimorphic ungulate species, sexual selection may lead to a marked influence of body mass on male breeding success, as long as body mass is also strongly selected in females. [ABSTRACT FROM AUTHOR]

We quantified the repeatability of .900 individual measures of hind foot length from 2 French populations of roe deer (Capreolus capreolus) monitored by capture-recapture. We found a high repeatability (i.e., high intra-class correlation, 0.76, 95% CI = 0.72- 0.83 and 0.92, 95% CI = 0.91-0.95) in both populations. We also found that inexperienced observers reached a high level of intra- (1.00, 95% CI = 0.96-1.00) and inter-observer repeatability (0.99, 95% CI = 0.98-1.00) when measuring hind foot length of harvested animals with a tool specifically designed for this task. Managers should pay particular attention to limit measurement errors because unreliable measurements require an increased sample size to assess individual variation and can mask biological patterns. [ABSTRACT FROM AUTHOR]

Spatial distribution in mammals, and thereby home range size, is influenced by many different factors including body size, sex, age, reproductive status, season, availability of forage, availability of water, fragmentation of landscape, trophic level and intra- and inter-specific competition. Using linear mixed models, we looked for factors shaping the variation in size of spring-summer and winter home ranges for 51 radio-collared adult female roe deer at Trois Fontaines forest, Champagne–Ardenne, France (1996–2005). Home range size of females was larger in winter than in spring–summer, decreased with age, and decreased with increasing quality. Females in low quality areas adjusted the size of their home range to include more patches of habitat so that all female deer obtained similar amounts of food resources (total biomass of 6.73±2.34 tons (mean±SE) for each home range). Such adjustments of home range size in response to patchiness of resources led to marked between-female variation in home range size. Our results demonstrate that roe deer females have different tactics of habitat use according to spatial variations in habitat quality so that females get similar food resources in highly productive environments such as the Trois Fontaines forest. [ABSTRACT FROM AUTHOR]

We investigated age-specific variation in male yearly breeding success (YBS) using genetic estimates obtained from 2 populations of a territorial ungulate, the European roe deer (Capreolus capreolus). YBS in both populations was markedly age-structured, with 3 distinct stages, supporting the dome-shaped pattern of variation commonly reported for age-dependent variation in life-history traits of ungulates. YBS was low at 2 years of age, peaked at 3-8 years of age, and tended to decline afterwards (senescence). Most males successfully reproduced for the 1st time at 3 years of age, which is well after their physiological maturity. The few successful young males (i.e., 2 year olds) were likely fast-growing individuals that could successfully hold a territory. The high variance in YBS and antler size for old males at Bogesund, Sweden, suggests that only some males of this age class are able to maintain large antlers and, hence, retain their territories. [ABSTRACT FROM AUTHOR]

1. Environmental conditions shape population growth through their impact on demographic parameters. While knowledge has accumulated concerning the effects of population density and climatic conditions, a topical question now concerns how predation and harvest influence demographic parameters and population growth (λ). 2. We performed a comparative demographic analysis based on projection matrix models for female roe deer. Population-specific matrices were parameterized based on longitudinal data from five intensively monitored populations in Norway and France, spanning a large variability in environmental characteristics such as densities of large predators, hunter harvest and seasonality. 3. As expected for a large iteroparous vertebrate, temporal variation was invariably higher in recruitment than in adult survival, and the elasticity of adult survival was consistently higher than that of recruitment. However, the relative difference in elasticity of λ to recruitment and adult survival varied strongly across populations, and was closely correlated with adult survival. 4. Different traits accounted for most of the variance in λ in different ecological settings. Adult survival generally contributed more in populations with low mean adult survival and low mean growth rate during the study period. Hunters and predators (Eurasian lynx and red foxes) occurred in two of our study populations and contributed substantially to the variance in λ, accounting for a total of 35% and 70% in the two populations respectively. 5. Across populations, we did not find any evidence that roe deer increased their reproductive output when faced with harsh conditions, resulting in some populations having negative growth rates. 6. Generation time, a measure of the speed of the life-history cycle, increased from less than 4 years in the most productive population (‘roe deer heaven’) to more than 6 years in declining populations facing predation from lynx, red fox and hunters (‘roe deer hell’), and was tightly and inversely correlated with λ. Such a deceleration of the life cycle in declining populations might be a general feature in large herbivores. 7. Our results shows that the plethora of environmental conditions faced by populations of large herbivores also induce high intraspecific variation in their ranking along the ‘fast–slow’ continuum of life-history tactics. [ABSTRACT FROM AUTHOR]

We examined the relationship between survival of roe deer ( Capreolus capreolus) fawns at Trois Fontaines, Champagne-Ardennes, France, and factors related to bed-site selection (predator avoidance and thermoregulation) and maternal food resources (forage availability in the maternal home range). Previous studies have demonstrated that at small scales, the young of large herbivores select bed sites independently from their mothers, although this selection takes place within the limits of their mother’s home range. Fawn survival was influenced largely by the availability of good bed sites within the maternal home range, not by the fawn’s selection of bed sites; however, selection for thermal cover when selecting bed sites positively influenced survival of young fawns. Typical features of a good home range included close proximity to habitat edges, which is related to forage accessibility for roe deer. The availability of bed sites changed as fawns aged, probably due to an increased mobility of the fawn or a different use of the home range by the mother; sites offering high concealment and thermal protection became less available in favor of areas with higher forage accessibility. Despite the minor influence of bed-site selection on survival, roe deer fawns strongly selected their bed sites according to several environmental factors linked to predator avoidance and thermoregulation. Fawns selected for sites providing concealment, light penetration, and avoided signs of wild boar ( Sus scrofa) activity. Avoidance of sites with high light penetration by young fawns positively affected their survival, confirming a negative effect on thermoregulation due to reduced thermal cover. Selection for light penetration by older fawns was less clear. We discuss these results in the context of cross-generational effects in habitat selection across multiple scales, and the potential influence of the ‘ghost of predation past’. [ABSTRACT FROM AUTHOR]

Heterozygosity-fitness correlations (HFCs) are increasingly reported but the underlying mechanisms causing HFCs are generally poorly understood. Here, we test for HFCs in roe deer ( Capreolus capreolus) using 22 neutral microsatellites widely distributed in the genome and four microsatellites in genes that are potentially under selection. Juvenile survival was used as a proxy for individual fitness in a population that has been intensively studied for 30 years in northeastern France. For 222 juveniles, we computed two measures of genetic diversity: individual heterozygosity ( H), and mean d2 (relatedness of parental genomes). We found a relationship between genetic diversity and fitness both for the 22 neutral markers and two candidate genes: IGF1 (Insulin-like Growth Factor I) and NRAMP (natural resistance-associated macrophage protein). Statistical evidence and the size of genetic effects on juvenile survival were comparable to those reported for early development and cohort variation, suggesting a substantial influence of genetic components on fitness in this roe deer population. For the 22 neutral microsatellites, a correlation with fitness was revealed for mean d2, but not for H, suggesting a possible outbreeding advantage. This heterosis effect could have been favored by introduction of genetically distant (Hungarian) roe deer to the population in recent times and, possibly, by the structuring of the population into distinct clans. The locus-specific correlations with fitness may be driven by growth rate advantages and resistance to diseases known to exist in the studied population. Our analyses of neutral and candidate gene markers both suggest that the observed HFCs are likely mainly due to linkage with dominant or overdominant loci that affect fitness ("local" effect) rather than to a genome-wide relationship with homozygosity due to inbreeding ("general" effect). [ABSTRACT FROM AUTHOR]

Identifying factors shaping secondary sexual traits is essential in understanding how their variation may influence male fitness. Little information is available on the allocation of resources to antler growth in territorial ungulates with low sexual size dimorphism. We investigated phenotypic and environmental factors affecting both absolute and relative antler size of male roe deer in three contrasting populations in France and Sweden. In the three populations, we found marked age-specific variation in antler size, with an increase in both absolute and relative antler size between yearling and prime-age stages, followed by a decrease (senescence) for males older than 7 years. Antler size increased allometrically with body mass. This increase was particularly strong for senescent males, suggesting the evolution of two reproductive tactics: heavy old males invested particularly heavily in antler growth (potentially remaining competitive for territories), whereas light old males grew small antlers (potentially abandoning territory defense). Finally, environmental conditions had little effect on antler size: only population density negatively affected absolute antler size in one of the three populations. Antler size may therefore provide an honest signal of male phenotypic quality in roe deer. We discuss the implications of these results in terms of territory tenure and mating competition. [ABSTRACT FROM AUTHOR]

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Animals in seasonal environments are affected by climate in very different ways depending on season and part of the climatic effects operates indirectly through the plants. Vegetation conditions in spring and summer are regarded as decisive for the reproductive success and the offspring's condition of large herbivores, but objective ways to determine key periods during the growing season have not been done often due to limitations in plant data. Using satellite data (NDVI), we determined how plant productivity from birth to fall influences the following winter body mass of roe deer fawns. We do this in two populations, the first inhabiting the low productive Chizé reserve in south western France with an oceanic climate and the second from Trois Fontaines, a highly productive forest with continental climate in east France. The effect of plant productivity was similar for male and female fawn mass, as expected from the weak intensity of sexual selection in roe deer life history traits. We found contrasting results between sites, with a strong effect of plant productivity in spring (April-May) in the Chizé population, but no effect in the Trois Fontaines population. The relatively low variability in winter fawn body mass could account for the absence of NDVI effects at Trois Fontaines. However, such results might also point to a limitation in the use of the NDVI, since the relationship between the canopy and the plant productivity at the ground level might be weak in the highly productive forest of Trois Fontaines. [ABSTRACT FROM AUTHOR]

1. Temporal and spatial variation can strongly affect life-history traits, but few studies to date have quantified the importance of the interplay between temporal and spatial components of population dynamics. 2. We analysed spatiotemporal variation in early survival of roe deer fawns over 15 years (1985–99) in an intensively monitored population in western France at two spatial scales: the maternal home range (a few tens of hectares) and the forest stand (a few hundreds of hectares). 3. Spatial variation in resource availability interacted with temporal variation to shape fawn survival. In good years, survival was not influenced by habitat quality (being 0·68 in the rich oak stand with hornbeam coppices vs. 0·64 in the poorer part of the reserve). At the home range scale, early survival of fawns during good years decreased with increasing occurrence of preferred plant species in the rich habitat; there was no effect in the poor habitat. 4. During bad years, however, there was a positive relationship between the occurrence of preferred plant species and survival of fawns in the poor habitat, whereas no relationship occurred in the rich habitat. Spatial variation in early survival during bad years was significant at the plot scale (from 0·19 to 0·40 in the poor habitat and from 0·49 to 0·61 in the rich habitat) even after accounting for the forest stand variations (from 0·27 to 0·51). The occurrence of key plant species therefore limits female reproductive success only in the poor habitat under harsh conditions. 5. Our findings highlight the crucial role of spatiotemporal interactions in shaping individual fitness in mammalian populations, and underline the importance of the scale of analysis when characterizing ecological processes. [ABSTRACT FROM AUTHOR]

How mothers allocate resources to offspring is central to understanding life history strategies. High quality mothers are predicted to favour investment in sons over daughters when to do so increases inclusive fitness. This is the case in ungulates with polygynous mating systems, where reproductive success is more variable among males than females, but information is scarce on sex allocation in less polygynous species. Here, for the weakly dimorphic roe deer, we show that as maternal capacity to invest increases, mothers increase allocation to daughters more than to sons, so that relative allocation to daughters increases markedly with increasing maternal quality. This cannot be explained by a between sex difference in growth priority, hence we conclude that this is evidence for active maternal discrimination. Further, we demonstrate that condition differences between offspring persist to adulthood. For high quality mothers of weakly polygynous species, daughters may be more valuable than sons. [ABSTRACT FROM AUTHOR]

We analyzed spatial variations in movements and survival in a roe deer (Capreolus capreolus) population (Chizé, western France) by using recent developments of multistate Capture-mark-recapture modeling in order to estimate transition and survival probabilities of individuals living in three habitats of contrasting quality. Irrespective of both population density and sex, habitat quality did not influence survivorship of prime-age or senescent roe deer. Likewise, habitat quality did not influence fawn survival at low density. On the other hand, fawn survival at high density was 20% higher in the resource-rich hornbeam-dominant coppices than in the other poorer habitats. We found, as expected, that fawns were mobile, whereas adults of both sexes were highly sedentary. Movements of roe deer among habitats were markedly influenced by habitat quality. Transition probabilities of individuals from the rich hornbeam coppices toward other habitats were lower than transition probabilities of individuals from the poor beech stand or from the medium-quality maple dominant coppices toward the rich hornbeam coppices. [ABSTRACT FROM AUTHOR]

Although extreme weather events--such as hurricanes--cause obvious changes in landscape and tree cover, the impact of such events on population dynamics of ungulates has not yet been measured accurately. We report a first quantification of the demographic consequences on roe deer (Capreolus capreolus) of the strongest hurricane (Lothar) that France has suffered in centuries. Based on long-term monitoring (>20 yr) of known-age individuals in 2 populations, we found that Lothar had no detectable negative effect on age- and sex-specific survival rates, except perhaps for old females. Likewise, although Lothar occurred during the time in the roe deer reproductive cycle when embryos are implanted, we found no evidence of a decrease in either the pregnancy rate or litter size. Our results show that roe deer populations are resistant to this kind of extreme weather event. The consequences for wildlife management are direct and important: (1) the hunting bag was low in 2000 due to restricted hunter access, and (2) the main effect of hurricane Lothar was to create openings within large forests that are good habitat for roe deer. We suggest that Lothar will paradoxally have a positive effect on roe deer population dynamics. [ABSTRACT FROM AUTHOR]

Patterns of sex ratio variation and maternal investment reported in the literature are often inconsistent. This could be due to intra- and inter-specific variation in social systems, but may also be a result of the a posteriori nature of much of this type of analysis or the testing of models which are inappropriate. Two recent papers reported directly opposed results concerning variation in offspring sex ratios in relation to maternal condition in roe deer, interpreting the results as support for the Trivers and Willard model and for the local resource competition hypothesis, respectively. In this paper, we present data on offspring sex ratios and early juvenile body weight from two long-term studies of this species to test predictions arising from these two models concerning sex biases in litter composition and maternal care. First, we observed no consistent pattern of sex differences in an index of weaning weight or body weight at 1 month old in either population, indicating a lack of sex bias in maternal care. However, in one population, higher maternal body weight was associated with higher juvenile body weight of daughters, but not of sons. Secondly, we found a negative, but not statistically significant, relationship between maternal body weight and litter sex ratio such that heavier females tended to produce more daughters and lighter females to produce more sons. These results indicate that roe females which have additional investment potential available do not invest it in sons, as predicted by the Trivers and Willard model. Our results may provide some support that roe deer are subject to local resource competition acting at the level of the individual mother; however, the fact that particular trends in sex ratio data can be explained in functional terms provides no indication that they are actually adaptive. [ABSTRACT FROM AUTHOR]

Examines factors that affect the body mass of roe deer fawns during winter. First-year survival and age at sexual maturity of northern ungulates; Population dynamics and management of ungulates during winter in two enclosed populations with contrasting climatic and demographic characteristics; Density-dependence; Sexual selection.

Time- and sex-specific summer survival of roe deer fawns was estimated using capture-mark-recapture methods in two enclosed populations living in contrasting conditions. The population of Trois Fontaines (eastern France) was roughly constant in size throughout the study period, while in Chizé (western France), the population experienced frequent summer droughts and numbers decreased continuously during the study. Early survival of fawns was low and highly variable over the years at both Chizé and Trois Fontaines, and demonstrated marked variations between cohorts that need to be taken into account when modelling roe deer population dynamics. In Trois Fontaines, fawn survival was positively correlated with early body growth and total rainfall in May and June. In Chizé, fawn survival decreased with increasing density and tended to increase with increasing rainfall in May and June and adult female body mass. These factors explained more than 75% of the variability in early survival observed in both populations. Variation between cohorts had different consequences for the two populations. At Trois Fontaines, cohort variation was limited to a numerical effect on early survival. However at Chizé, cohort variation was long-lasting and affected the phenotypic quality of survivors at later ages, and thereby future survival and breeding abilities (both numerical and quality effects). Male and female fawns had similar survival over their first summer in both populations. This result contrasts with the lower survival of young males often observed in ungulates. Two ultimate causes can be proposed to account for the low and variable survival of roe deer fawns over the first summer: the high energy expenditures incurred by does during each breeding attempt and/or the low absolute body size of newborn roe deer fawns. [ABSTRACT FROM AUTHOR]

In most species of vertebrates, teeth play a central role in the long-term performance of individuals. However, patterns of tooth development have been little investigated as an indicator of animal performance. We filled this gap using data collected during long-term capture-mark-recapture monitoring of 1152 roe deer fawns at Chizé, western France. This population fluctuated greatly in size during the 27 years of monitoring, offering a unique opportunity to assess how the eruption patterns of front teeth perform as indicator of animal performance. We used three indices of the eruption of permanent front teeth, the simplest being whether or not incisor I2 has erupted, and the most complex being a 12-level factor distinguishing the different stages of tooth eruption. We also assessed the relevance of these indices as compared to fawn body mass, a widely used indicator of animal performance of deer populations. Dental indices and body mass were positively correlated (all r > 0.62). Similarly to body mass, all indices based on tooth eruption patterns responded to changes of population size and can be reliably used to assess the relationship between roe deer and their environment. We found a linear decrease in body mass with increasing population size (r² = 0.54) and a simultaneous delay in tooth development (r² = 0.48-0.55 from the least to the most accurate indicator). However, tooth development would be not further delayed in years with the highest densities (>15 adult roe deer/100 ha). A path analysis supported the population density effect on tooth eruption patterns being mainly determined by the effect of population size on body mass. Our study provides managers with simple indices (e.g., presence-absence of I2) that provide a technically more easy way to standardize measurements of deer density-dependent responses over large geographical and temporal scales than would be possible with body mass. [ABSTRACT FROM AUTHOR]

Abstract: We have investigated a series of phenolic diaryl amino piperidine delta opioid receptor agonists, establishing the importance of the phenol functional group and substitution on the piperdine nitrogen for delta agonist activity and selectivity versus the mu and kappa opioid receptors. This study uncovered compounds with improved agonist potency and selectivity compared to the standard, non-peptidic delta agonist SNC-80. In vivo anti-nociceptive activity of analog 8e in two rodent models is discussed, demonstrating the potential of delta agonists to provide a novel mechanism for pain relief. [Copyright &y& Elsevier]

Abstract: The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH– without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N 6-amino moiety favors the inhibition of DNMT3b2 enzyme. [Copyright &y& Elsevier]

Abstract: Potent SAH analogues with constrained homocysteine units have been designed and synthesized as inhibitors of human DNMT enzymes. The five membered (2S,4S)-4-mercaptopyrrolidine-2-carboxylic acid, in 1a, was a good replacement for homocysteine, while the corresponding six-member counterpart was less active. Further optimization of 1a, changed the selectivity profile of these inhibitors. A Chloro substituent at the 2-position of 1a, compound 1d, retained potency against DNMT1, while N6 alkylation, compound 7a, conserved DNMT3b2 activity. The concomitant substitutions of 1a at both 2- and N6 positions reduced activity against both enzymes. [Copyright &y& Elsevier]

Abstract: Analogues of the clinical compound MGCD0103 (A) were designed and synthesized. These compounds inhibit recombinant human HDAC1 with IC50 values in the sub-micromolar range. In human cancer cells growing in culture these compounds induce hyperacetylation of histones, cause expression of the tumor suppressor protein p21WAF1/CIP1, and inhibit cellular proliferation. Lead molecule of the series, compound 25 is metabolically stable, possesses favorable pharmacokinetic characteristics and is orally active in vivo in different mouse tumor xenograft models. [Copyright &y& Elsevier]

Abstract: Osteomyelitis is a difficult to treat bacterial infection of the bone. Delivering antibacterial agents to the bone may overcome the difficulties in treating this illness by effectively concentrating the antibiotic at the site of infection and by limiting the toxicity that may result from systemic exposure to the large doses conventionally used. Using bisphosphonates as osteophilic functional groups, different forms of fluoroquinolone esters were synthesized and evaluated for their ability to bind bone and to release the parent antibacterial agent. Bisphosphonated glycolamide fluoroquinolone esters were found to present a profile consistent with effective and rapid bone binding and efficient release of the active drug moiety. They were assessed for their ability to prevent bone infection in vivo and were found to be effective when the free fluoroquinolones were not. [Copyright &y& Elsevier]

Abstract: The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase. [Copyright &y& Elsevier]

Abstract: Leukotriene biosynthesis inhibitors have potential as therapeutic agents for asthma and inflammatory diseases. A novel series of substituted coumarin derivatives has been synthesized and the structure–activity relationship was evaluated with respect to their ability to inhibit the formation of leukotrienes via the human 5-lipoxygenase enzyme. [Copyright &y& Elsevier]

A variety of ω-substituted alkanoic acid (2-amino-phenyl)-amides were designed and synthesized. These compounds were shown to inhibit recombinant human histone deacetylases (HDACs) with IC50 values in the low micromolar range and induce hyperacetylation of histones in whole cells. They induced expression of p21WAF1/Cip1 and caused cell-cycle arrest in human cancer cells. Compounds in this class showed efficacy in human tumor xenograft models. [Copyright &y& Elsevier]

The predictive adaptive response (PAR) hypothesis proposes that animals adjust their physiology and developmental trajectory during early life in anticipation of their future environments. Accordingly, when environmental conditions in early life match environmental conditions during adulthood, individual fitness should be greater. Here, we test this hypothesis in a long-lived mammal, the roe deer, using data from two contrasting populations, intensively monitored for more than 35 years. In the highly productive site, the fitness of female roe deer increased with the quality of environment during adulthood and, contrary to predictions of PAR, individuals born in good conditions always outperformed those born under poor conditions. In the resource-limited site, the fitness of female roe deer born in poor years was better than those born in good conditions in poor years when the animals were adult, but not in good years. Although consistent with predictions of PAR, we showed that this pattern is likely to be a consequence of increased viability selection during the juvenile stage for animals born in poor years. While PARs are often advanced in evolutionary medicine, our findings suggest that detailed biological processes should be investigated before drawing conclusions about the existence of this phenomenon.

Births are highly synchronized among females in many mammal populations in temperate areas. Although laying date for a given female is also repeatable within populations of birds, limited evidence suggests low repeatability of parturition date for individual females in mammals, and between-population variability in repeatability has never, to our knowledge, been assessed. We quantified the repeatability of parturition date for individual females in five populations of roe deer, which we found to vary between 0.54 and 0.93. Each year, some females gave birth consistently earlier in the year, whereas others gave birth consistently later. In addition, all females followed the same lifetime trajectory for parturition date, giving birth progressively earlier as they aged. Giving birth early should allow mothers to increase offspring survival, although few females managed to do so. The marked repeatability of parturition date in roe deer females is the highest ever reported for a mammal, suggesting low phenotypic plasticity in this trait.

Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered antibiotics. Targeting antibiotics to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. By taking advantage of the affinity of the bisphosphonate group for bone mineral, we have prepared a set of 13 bisphosphonated antibacterial prodrugs based on eight different linkers tethered to the free amino functionality on fluoroquinolone antibiotics. While all but one of the prodrugs were shown in vitro to be effective and rapid bone binders (over 90% in 1 h), only eight of them demonstrated the capacity to significantly regenerate the parent drug. In a rat model of the disease, a selected group of agents demonstrated their ability to prevent osteomyelitis when used in circumstances under which the parent drug had already been cleared and is thus inactive.

The design, synthesis, and biological evaluation of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide 8 (MGCD0103) is described. Compound 8 is an isotype-selective small molecule histone deacetylase (HDAC) inhibitor that selectively inhibits HDACs 1-3 and 11 at submicromolar concentrations in vitro. 8 blocks cancer cell proliferation and induces histone acetylation, p21 (cip/waf1) protein expression, cell-cycle arrest, and apoptosis. 8 is orally bioavailable, has significant antitumor activity in vivo, has entered clinical trials, and shows promise as an anticancer drug.

Nonselective inhibitors of human histone deacetylases (HDAC) are known to have antitumor activity in mice in vivo, and several of them are under clinical investigation. The first of these, Vorinostat (SAHA), has been approved for treatment of cutaneous T-cell lymphoma. Questions remain concerning which HDAC isotype(s) are the best to target for anticancer activity and whether increased efficacy and safety will result with an isotype-selective HDAC inhibitor. We have developed an isotype-selective HDAC inhibitor, MGCD0103, which potently targets human HDAC1 but also has inhibitory activity against HDAC2, HDAC3, and HDAC11 in vitro. In intact cells, MGCD0103 inhibited only a fraction of the total HDAC activity and showed long-lasting inhibitory activity even upon drug removal. MGCD0103 induced hyperacetylation of histones, selectively induced apoptosis, and caused cell cycle blockade in various human cancer cell lines in a dose-dependent manner. MGCD0103 exhibited potent and selective antiproliferative activities against a broad spectrum of human cancer cell lines in vitro, and HDAC inhibitory activity was required for these effects. In vivo, MGCD0103 significantly inhibited growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors. Our findings suggest that the isotype-selective HDAC inhibition by MGCD0103 is sufficient for antitumor activity in vivo and that further clinical investigation is warranted.