Insulin‐ and Exercise‐Stimulated Skeletal Muscle Blood Flow and Glucose Uptake in Obese Men

Objective: Insulin resistance in obese subjects results in the impaired use of glucose by insulin‐sensitive tissues, e.g., skeletal muscle. In the present study, we determined whether insulin resistance in obesity is associated with an impaired ability of exercise to stimulate muscle blood flow, oxygen delivery, or glucose uptake. Research Methods and Procedures: Nine obese (body mass index = 36 ± 2 kg/m²) and 11 age‐matched nonobese men (body mass index = 22 ± 1 kg/m²) performed one‐legged isometric exercise during hyperinsulinemia. Rates of femoral muscle blood flow, oxygen consumption, and glucose uptake were measured simultaneously in both legs using [¹⁵O]H₂O, [¹⁵O]O₂, [¹⁸F]fluoro‐deoxy‐glucose, and positron emission tomography. Results: The obese subjects exhibited resistance to insulin stimulation of glucose uptake in resting muscle, regardless of whether glucose uptake was expressed per kilogram of femoral muscle mass (p = 0.001) or per the total mass of quadriceps femoris muscle. At similar workloads, oxygen consumption, blood flow, and glucose uptake were lower in the obese than the nonobese subjects when expressed per kilogram of muscle, but similar when expressed per quadriceps femoris muscle mass. Discussion: We conclude that obesity is characterized by insulin resistance of glucose uptake in resting skeletal muscle regardless of how glucose uptake is expressed. When compared with nonobese individuals at similar absolute workloads and under identical hyperinsulinemic conditions, the ability of exercise to increase muscle oxygen uptake, blood flow, and glucose uptake per muscle mass is blunted in obese insulin‐resistant subjects. However, these defects are compensated for by an increase in muscle mass.     

Carbon balance and allocation of assimilated CO2 in Scots pine, Norway spruce, and Silver birch seedlings determined with gas exchange measurements and 14C pulse labelling

Carbon dioxide is released from the soil to the atmosphere in heterotrophic respiration when the dead organic matter is used for substrates for soil micro-organisms and soil animals. Respiration of roots and mycorrhiza is another major source of carbon dioxide in soil CO₂ efflux. The partitioning of these two fluxes is essential for understanding the carbon balance of forest ecosystems and for modelling the carbon cycle within these ecosystems. In this study, we determined the carbon balance of three common tree species in boreal forest zone, Scots pine, Norway spruce, and Silver birch with gas exchange measurements conducted in laboratory in controlled temperature and light conditions. We also studied the allocation pattern of assimilated carbon with ¹⁴C pulse labelling experiment. The photosynthetic light responses of the tree species were substantially different. The maximum photosynthetic capacity (P _max) was 2.21 μg CO₂ s⁻¹ g⁻¹ in Scots pine, 1.22 μg CO₂ s⁻¹ g⁻¹ in Norway spruce and 3.01 μg CO₂ s⁻¹ g⁻¹ in Silver birch seedlings. According to the pulse labelling experiments, 43–75% of the assimilated carbon remained in the aboveground parts of the seedlings. The amount of carbon allocated to root and rhizosphere respiration was about 9–26%, and the amount of carbon allocated to root and ectomycorrhizal biomass about 13–21% of the total assimilated CO₂. The ¹⁴CO₂ pulse reached the root system within few hours after the labelling and most of the pulse had passed the root system after 48 h. The transport rate of carbon from shoot to roots was fastest in Silver birch seedlings.     

Macroarthropod species richness and conservation priorities in Stratiotes aloides (L.) lakes

Species with narrow ranges and specialised traits are most at risk, and the extinction wave is further enhanced by coextinctions. We studied the conservation value and indicator potential of Stratiotes aloides, an aquatic macrophyte that has declined considerably in Europe. Our purpose was to determine whether S. aloides could be used as an indicator of a valuable habitat in terms of macroarthropod diversity and species richness. The potential occurrence of an internationally endangered Stratiotes-habitat specialist, the dragonfly Aeshna viridis, can increase the conservation value of plant colonies. S. aloides beds harboured diverse macroarthropod fauna often containing species of conservation concern, including A. viridis. Stratiotes is a potential indicator of a valuable habitat, and its indicator value is enhanced by the easy identification of the species. However, its use as an indicator of a defined macroarthropod community is limited because no particular community type is connected to it. We suggest that protecting Stratiotes simultaneously conserves valuable arthropod fauna, including A. viridis.     

Full Likelihood Analysis of Genetic Risk with Variable Age at Onset Disease—Combining Population-Based Registry Data and Demographic Information

Background

In genetic studies of rare complex diseases it is common to ascertain familial data from population based registries through all incident cases diagnosed during a pre-defined enrollment period. Such an ascertainment procedure is typically taken into account in the statistical analysis of the familial data by constructing either a retrospective or prospective likelihood expression, which conditions on the ascertainment event. Both of these approaches lead to a substantial loss of valuable data.

Methodology and Findings

Here we consider instead the possibilities provided by a Bayesian approach to risk analysis, which also incorporates the ascertainment procedure and reference information concerning the genetic composition of the target population to the considered statistical model. Furthermore, the proposed Bayesian hierarchical survival model does not require the considered genotype or haplotype effects be expressed as functions of corresponding allelic effects. Our modeling strategy is illustrated by a risk analysis of type 1 diabetes mellitus (T1D) in the Finnish population-based on the HLA-A, HLA-B and DRB1 human leucocyte antigen (HLA) information available for both ascertained sibships and a large number of unrelated individuals from the Finnish bone marrow donor registry. The heterozygous genotype DR3/DR4 at the DRB1 locus was associated with the lowest predictive probability of T1D free survival to the age of 15, the estimate being 0.936 (0.926; 0.945 95% credible interval) compared to the average population T1D free survival probability of 0.995.

Significance

The proposed statistical method can be modified to other population-based family data ascertained from a disease registry provided that the ascertainment process is well documented, and that external information concerning the sizes of birth cohorts and a suitable reference sample are available. We confirm the earlier findings from the same data concerning the HLA-DR3/4 related risks for T1D, and also provide here estimated predictive probabilities of disease free survival as a function of age.     

Genetic structure of the northwestern Russian wolf populations and gene flow between Russia and Finland

We examined the genetic diversity and structure of wolf populations in northwestern Russia. Populations in Republic of Karelia and Arkhangelsk Oblast were sampled during 1995–2000, and 43 individuals were genotyped with 10 microsatellite markers. Moreover, 118 previously genotyped wolves from the neighbouring Finnish population were used as a reference population. A relatively large amount of genetic variation was found in the Russian populations, and the Karelian wolf population tended to be slightly more polymorphic than the Arkhangelsk population. We found significant inbreeding (F = 0.094) in the Karelian, but not in the Arkhangelsk population. The effective size estimates of the Karelian wolf population based on the approximate Bayesian computation and linkage disequilibrium methods were 39.9 and 46.7 individuals, respectively. AMOVA-analysis and exact test of population differentiation suggested clear differentiation between the Karelian, Arkhangelsk and Finnish wolf populations. Indirect estimates of gene flow based on the level of population differentiation (ϕ _ST  = 0.152) and frequency of private alleles (0.029) both suggested a low level of gene flow between the populations (Nm = 1.4 and Nm = 3.7, respectively). Assignment analysis of Karelian and Finnish populations suggested an even lower number of recent migrants (less than 0.03) between populations, with a larger amount of migration from Finland to Karelia than vice versa. Our findings emphasise the role of physical obstacles and territorial behaviour in creating barriers to gene flow between populations in relatively limited geographical areas, even in large-bodied mammalian species with long-distance dispersal capabilities and an apparently continuous population structure.     

Genetic and potential non-genetic benefits increase offspring fitness of polyandrous females in non-resource based mating system

Background  

The adaptive significance of female polyandry is currently under considerable debate. In non-resource based mating systems, indirect, i.e. genetic benefits have been proposed to be responsible for the fitness gain from polyandry. We studied the benefits of polyandry in the Arctic charr (Salvelinus alpinus) using an experimental design in which the material investments by the sires and maternal environmental effects were controlled.     

Tumor necrosis factor alpha enhances influenza A virus-induced expression of antiviral cytokines by activating RIG-I gene expression

Epithelial cells of the lung are the primary targets for respiratory viruses. Virus-carried single-stranded RNA (ssRNA) can activate Toll-like receptors (TLRs) 7 and 8, whereas dsRNA is bound by TLR3 and a cytoplasmic RNA helicase, retinoic acid-inducible protein I (RIG-I). This recognition leads to the activation of host cell cytokine gene expression. Here we have studied the regulation of influenza A and Sendai virus-induced alpha interferon (IFN-alpha), IFN-beta, interleukin-28 (IL-28), and IL-29 gene expression in human lung A549 epithelial cells. Sendai virus infection readily activated the expression of the IFN-alpha, IFN-beta, IL-28, and IL-29 genes, whereas influenza A virus-induced activation of these genes was mainly dependent on pretreatment of A549 cells with IFN-alpha or tumor necrosis factor alpha (TNF-alpha). IFN-alpha and TNF-alpha induced the expression of the RIG-I, TLR3, MyD88, TRIF, and IRF7 genes, whereas no detectable TLR7 and TLR8 was seen in A549 cells. TNF-alpha also strongly enhanced IKK epsilon mRNA and protein expression. Ectopic expression of a constitutively active form of RIG-I (deltaRIG-I) or IKK epsilon, but not that of TLR3, enhanced the expression of the IFN-beta, IL-28, and IL-29 genes. Furthermore, a dominant-negative form of RIG-I inhibited influenza A virus-induced IFN-beta promoter activity in TNF-alpha-pretreated cells. In conclusion, IFN-alpha and TNF-alpha enhanced the expression of the components of TLR and RIG-I signaling pathways, but RIG-I was identified as the central regulator of influenza A virus-induced expression of antiviral cytokines in human lung epithelial cells.     

Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56

Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two‐hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N‐terminal CIP2A fragment (amino acids 1–560) at 3.0 Å resolution, and by subsequent structure‐based mutational analyses of the dimerization interface. We further describe that the CIP2A dimer interacts with the PP2A subunits B56α and B56γ. CIP2A binds to the B56 proteins via a conserved N‐terminal region, and dimerization promotes B56 binding. Intriguingly, inhibition of either CIP2A dimerization or B56α/γ expression destabilizes CIP2A, indicating opportunities for controlled degradation. These results provide the first structure–function analysis of the interaction of CIP2A with PP2A/B56 and have direct implications for its targeting in cancer therapy.     

Comparing Dirichlet normal surface energy of tooth crowns, a new technique of molar shape quantification for dietary inference, with previous methods in isolation and in combination

Inferred dietary preference is a major component of paleoecologies of extinct primates. Molar occlusal shape correlates with diet in living mammals, so teeth are a potentially useful structure from which to reconstruct diet in extinct taxa. We assess the efficacy of Dirichlet normal energy (DNE) calculated for molar tooth surfaces for reflecting diet. We evaluate DNE, which uses changes in normal vectors to characterize curvature, by directly comparing this metric to metrics previously used in dietary inference. We also test whether combining methods improves diet reconstructions. The study sample consisted of 146 lower (mandibular) second molars belonging to 24 euarchontan taxa. Five shape quantification metrics were calculated on each molar: DNE, shearing quotient, shearing ratio, relief index, and orientation patch count rotated (OPCR). Statistical analyses were completed for each variable to assess effects of taxon and diet. Discriminant function analysis was used to assess ability of combinations of variables to predict diet. Values differ significantly by diets for all variables, although shearing ratios and OPCR do not distinguish statistically between insectivores and folivores or omnivores and frugivores. Combined analyses were much more effective at predicting diet than any metric alone. Alone, relief index and DNE were most effective at predicting diet. OPCR was the least effective alone but is still valuable as the only quantitative measure of surface complexity. Of all methods considered, DNE was the least methodologically sensitive, and its effectiveness suggests it will be a valuable tool for dietary reconstruction.     

Parasites, sex, and clonal diversity in natural snail populations

Under the Red Queen hypothesis, host-parasite coevolution selects against common host genotypes. Although this mechanism might underlie the persistence of sexual reproduction, it might also maintain high clonal diversity. Alternatively, clonal diversity might be maintained by multiple origins of parthenogens from conspecific sexuals, a feature in many animal groups. Herein, we addressed the maintenance of overall genetic diversity by coevolving parasites, as predicted by the Red Queen hypothesis. We specifically examined the contribution of parasites to host clonal diversity and the frequency of sexually reproducing individuals in natural stream populations of Potamopyrgus antipodarum snails. We also tested the alternative hypothesis that clonal diversity is maintained by the input of clones by mutation from sympatric sexuals. Clonal diversity and the frequency of sexual individuals were both positively related to infection frequency. Surprisingly, although clones are derived by mutation from sexual snails, parasites explained more of the genotypic variation among parthenogenetic subpopulations. Our findings thus highlight the importance of parasites as drivers of clonal diversity, as well as sex.