Resistance to Alpha/Beta Interferons Correlates with the Epizootic and Virulence Potential of Venezuelan Equine Encephalitis Viruses and Is Determined by the 5′ Noncoding Region and Glycoproteins

We compared the alpha/beta interferon (IFN-α/β) sensitivities of the TC-83 vaccine strain and 24 enzootic and epizootic Venezuelan equine encephalitis (VEE) isolates. The IFN-resistant or -sensitive phenotype correlated well with epizootic or enzootic potential. IFN-α/β resistance of Trinidad donkey (TRD) virus correlated with virulence determinants in the 5′ noncoding region and glycoproteins. Infection of mice lacking a functional IFN system with the IFN-sensitive TC-83 virus resulted in disease equivalent to that produced by the virulent, IFN-resistant TRD virus, further demonstrating that IFN resistance contributes to VEE virus virulence and is a biological marker of epizootic potential.     

GROWTH RATE VARIATION IN THE N:P REQUIREMENT RATIO OF PHYTOPLANKTON1

Theoretical considerations predict that the cell N:P ratio at transition from nitrogen limitation to phosphorus limitation of phytoplankton growth (critical ratio, R_c) varies, as a function of population growth rate. This prediction is confirmed by experimental, data from the literature along with new experimental data for the marine, prymnesiophyte Pavlova lutheri (Droop) Green. R_c passes through a maximum at intermediate growth rates for the three phytoplankton species for which data, are available, but there is significant interspecific variability in its value. There is no theoretical or experimental evidence to support the idea that the ratio of subsistence N and P cell quotas is equal to R_c over the range of growth rates, or that the subsistence quota ratio equals the ratio of the N and P cell quotas minus a storage fraction. Examination of N:P composition ratios can be used to determine which nutrient is limiting, but cannot be used to determine relative growth rates or competitive advantage between species limited by the same nutrient. Growth rates are determined by environmental conditions and by the cell quota of the limiting nutrient, without reference to the cell quota of the non-limiting nutrient.     

Mechanisms governing maintenance of Cdk1/cyclin B1 kinase activity in cells infected with human cytomegalovirus

Previous work has demonstrated dysregulation of key cell cycle components in human cytomegalovirus (HCMV)-infected human fibroblasts, resulting in cell cycle arrest (F. M. Jault, J.-M. Jault, F. Ruchti, E. A. Fortunato, C. L. Clark, J. Corbeil, D. D. Richman, and D. H. Spector, J. Virol. 69:6697-6704, 1995). The activation of the mitotic kinase Cdk1/cyclin B, which was detected as early as 8 h postinfection (p.i.) and maintained throughout the time course, was particularly interesting. To understand the mechanisms underlying the induction of this kinase activity, we have examined the pathways that regulate the activation of Cdk1/cyclin B1 complexes. The accumulation of the cyclin B1 subunit in HCMV-infected cells is the result of increased synthesis and reduced degradation of the protein. In addition, the catalytic subunit, Cdk1, accumulates in its active form in virus-infected cells. The decreased level of the Tyr15-phosphorylated form of Cdk1 in virus-infected fibroblasts is due in part to the down-regulation of the expression and activity of the Cdk1 inhibitory kinases Myt1 and Wee1. Increased degradation of Wee1 via the proteasome also accounts for its absence at 24 h p.i. At late times, we observed accumulation of the Cdc25 phosphatases that remove the inhibitory phosphates from Cdk1. Interestingly, biochemical fractionation studies revealed that the active form of Cdk1, a fraction of total cyclin B1, and the Cdc25 phosphatases reside predominantly in the cytoplasm of infected cells. Collectively, these data suggest that the maintenance of Cdk1/cyclin B1 activity observed in HCMV-infected cells can be explained by three mechanisms: the accumulation of cyclin B1, the inactivation of negative regulatory pathways for Cdk1, and the accumulation of positive factors that promote Cdk1 activity.     

Morphological Variation in Populations of <Emphasis Type="Italic">Eulemur albocollaris</Emphasis> and <Emphasis Type="Italic">E. fulvus rufus</Emphasis>

Sexual dimorphism in body size and canine weaponry is commonly associated with high levels of male-male competition. When group living species do not rely heavily on male-male competition for access to females, sperm competition may represent a viable alternative strategy. Unlike most haplorhine primates, lemurs are typically monomorphic in body weight and canine height. We assessed variability of body mass dimorphism and canine size dimorphism in brown lemurs using morphometric data from 3 populations in southeastern Madagascar: Eulemur fulvus rufus, E. albocollaris, and hybrids of the species. We found significant male-biased canine dimorphism in E. albocollaris in conjunction with body-size monomorphism. We observed similar patterns in the hybrids, but E. fulvus rufus exhibited significant female-biased size dimorphism and canine monomorphism. Testes volume was relatively high across study populations. Thus, sperm competition appears to be strong in brown lemurs. E. albocollaris males combine sperm competition with large canines, but not higher body mass, indicating a difference in sexual strategy from most lemurs. Patterns of body mass and canine size dimorphism are not uniform across brown lemur populations, indicating that future work on these populations can explicitly test models that predict relationships between size dimorphism and various types of competition.     

Two circadian timing circuits in Neurospora crassa cells share components and regulate distinct rhythmic processes

In Neurospora crassa, FRQ, WC-1, and WC-2 proteins comprise the core circadian FRQ-based oscillator that is directly responsive to light and drives daily rhythms in spore development and gene expression. However, physiological and biochemical studies have demonstrated the existence of additional oscillators in the cell that function in the absence of FRQ (collectively termed FRQ-less oscillators [FLOs]). Whether or not these represent temperature-compensated, entrainable circadian oscillators is not known. The authors previously identified an evening-peaking gene, W06H2 (now called clock-controlled gene 16 [ccg-16]), which is expressed with a robust daily rhythm in cells that lack FRQ protein, suggesting that ccg-16 is regulated by a FLO. In this study, the authors provide evidence that the FLO driving ccg-16 rhythmicity is a circadian oscillator. They find that ccg-16 rhythms are generated by a temperature-responsive, temperature-compensated circadian FLO that, similar to the FRQ-based oscillator, requires functional WC-1 and WC-2 proteins for activity. They also find that FRQ is not essential for rhythmic WC-1 protein levels, raising the possibility that this WCFLO is involved in the generation of WC-1 rhythms. The results are consistent with the presence of 2 circadian oscillators within Neurospora cells, which the authors speculate may interact with each other through the shared WC proteins.     

The role of previous exposure in the appetitive and consummatory effects of orexigenic neuropeptides

The ingestion of foods is comprised of two distinct phases of behavior: appetitive and consummatory. While most food intake paradigms include both phases, the intraoral intake test emphasizes the stereotyped consummatory-phase by infusing a liquid food directly into the oral cavity. Several hypothalamic peptides have been shown to increase intake of chow in standard food intake paradigms and the current experiments sought to test whether these peptides would increase food intake in the intraoral intake paradigm. NPY, melanin-concentrating hormone (MCH) and orexin-A were infused into the third ventricle (i3vt) in a counterbalanced latin-square design just prior to rats getting 0.1M sucrose solution infused via indwelling intraoral catheters and compared it to intake on bottle tests with access to the same sucrose solution. On the first day, each peptide increased intraoral intake relative to saline in the between-subjects comparison. Moreover, intake of sucrose following i3vt saline increased as a function of training. By the final day of the experiment, rats receiving saline consumed as much sucrose as rats receiving NPY, MCH, or orexin-A. This finding was conceptually replicated in the second experiment in which rats drank sucrose freely from a bottle on the home cage. A third experiment directly assessed the role of previous exposure in the sucrose intake induced by NPY. Those results confirm that repeated exposure to sucrose increases baseline intake and attenuates the hyperphagic effect of NPY. These results are consistent with two conclusions: (1) NPY, MCH, and orexin-A increase both appetitive and consummatory-phase ingestive behaviors on initial exposures; (2) repeated training interacts with the effects of these orexigenic peptides.     

Metabolic Syndrome and Changes in Body Fat From a Low‐fat Diet and/or Exercise Randomized Controlled Trial

It is difficult to identify the successful component(s) related to changes in metabolic syndrome (MetS) from lifestyle interventions: the weight loss, the behavior change, or the combination. The purpose of this study is to determine the effects of a weight‐stable randomized controlled trial of low‐fat diet and exercise, alone and in combination, on MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated low‐density lipoprotein cholesterol (LDL‐C) and low high‐density lipoprotein cholesterol (HDL‐C) were randomized into a 1‐year, weight‐stable trial with four treatment groups: control (C), diet (D), exercise (E), or diet plus exercise (D+E). MetS was defined using a continuous score. Changes in MetS score (ΔMetS) were compared between groups using analysis of covariance, stratified by gender and using two models, with and without baseline and change in percent body fat (ΔBF) as a covariate. In men, ΔMetS was higher for D vs. C (P = 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, ΔMetS was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P = 0.004). After adjusting for ΔBF, all differences between groups were attenuated and no longer significant. ΔMetS were associated with ΔBF for both men (P < 0.0001) and women (P = 0.004). After adjustment for ΔBF, low‐fat diet alone and in combination with exercise had no effect on MetS. The key component for MetS from low‐fat diet and/or increased physical activity appears to be body fat loss.     

Spatial heterogeneity in genetic relatedness among house sparrows along an urban-rural gradient as revealed by individual-based analysis

Understanding factors that shape patterns of kinship in sedentary species is important for evolutionary ecologists as well as conservation biologists. Yet, how patterns of relatedness are hierarchically structured in space remains poorly known, even in common species. Here, we use information from 16 polymorphic microsatellite DNA markers to study how small-scale kinship structure varies among house sparrows (Passer domesticus) along an urban-rural gradient. Average levels of relatedness were higher among urban individuals than among individuals from rural areas, suggesting lower rates of dispersal in more built-up habitats. Comparison of observed levels of relatedness with simulated distributions of known kinship values showed that central urban individuals had the highest proportion of closely related conspecifics in their immediate neighbourhood. Spatial auto-correlograms supported this small-scale genetic structure and further indicated stronger effects of genetic drift and/or limited dispersal in urban populations. Results of this study underscore the importance of individual-level analyses as a complementary approach to traditional population-level analyses when studying genetic population structure over small spatial scales.