The running coupling of 8 flavors and 3 colors

We compute the renormalized running coupling of SU(3) gauge theory coupled to N_f = 8 flavors of massless fundamental Dirac fermions. The recently proposed finite volume gradient flow scheme is used. The calculations are performed at several lattice spacings allowing for a controlled continuum extrapolation. The results for the discrete beta-function show that it is monotonic without any sign of a fixed point in the range of couplings we cover. As a cross check the continuum results are compared with the well-known perturbative continuum beta-function for small values of the renormalized coupling and perfect agreement is found.Comment: 15 pages, 17 figures, published versio

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

ObjectiveInhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.Study designA subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.ResultiNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.ConclusioniNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments

Cue Integration in Categorical Tasks: Insights from Audio-Visual Speech Perception

Previous cue integration studies have examined continuous perceptual dimensions (e.g., size) and have shown that human cue integration is well described by a normative model in which cues are weighted in proportion to their sensory reliability, as estimated from single-cue performance. However, this normative model may not be applicable to categorical perceptual dimensions (e.g., phonemes). In tasks defined over categorical perceptual dimensions, optimal cue weights should depend not only on the sensory variance affecting the perception of each cue but also on the environmental variance inherent in each task-relevant category. Here, we present a computational and experimental investigation of cue integration in a categorical audio-visual (articulatory) speech perception task. Our results show that human performance during audio-visual phonemic labeling is qualitatively consistent with the behavior of a Bayes-optimal observer. Specifically, we show that the participants in our task are sensitive, on a trial-by-trial basis, to the sensory uncertainty associated with the auditory and visual cues, during phonemic categorization. In addition, we show that while sensory uncertainty is a significant factor in determining cue weights, it is not the only one and participants' performance is consistent with an optimal model in which environmental, within category variability also plays a role in determining cue weights. Furthermore, we show that in our task, the sensory variability affecting the visual modality during cue-combination is not well estimated from single-cue performance, but can be estimated from multi-cue performance. The findings and computational principles described here represent a principled first step towards characterizing the mechanisms underlying human cue integration in categorical tasks

Monitoring frequency influences the analysis of resting behaviour in a forest carnivore

Resting sites are key structures for many mammalian species, which can affect reproduction, survival, population density, and even species persistence in human-modified landscapes. As a consequence, an increasing number of studies has estimated patterns of resting site use by mammals, as well as the processes underlying these patterns, though the impact of sampling design on such estimates remain poorly understood. Here we address this issue empirically, based on data from 21 common genets radiotracked during 28 months in Mediterranean forest landscapes. Daily radiotracking data was thinned to simulate every other day and weekly monitoring frequencies, and then used to evaluate the impact of sampling regime on estimates of resting site use. Results showed that lower monitoring frequencies were associated with major underestimates of the average number of resting sites per animal, and of site reuse rates and sharing frequency, though no effect was detected on the percentage use of resting site types. Monitoring frequency also had a major impact on estimates of environmental effects on resting site selection, with decreasing monitoring frequencies resulting in higher model uncertainty and reduced power to identify significant explanatory variables. Our results suggest that variation in monitoring frequency may have had a strong impact on intra- and interspecific differences in resting site use patterns detected in previous studies. Given the errors and uncertainties associated with low monitoring frequencies, we recommend that daily or at least every other day monitoring should be used whenever possible in studies estimating resting site use patterns by mammals

Persistence of single species of symbionts across multiple closelyrelated host species

Some symbiont species are highly host-specific, inhabiting only one or a very few host species, and typically have limited dispersal abilities. When they do occur on multiple host species, populations of such symbionts are expected to become genetically structured across these different host species, and this may eventually lead to new symbiont species over evolutionary timescales. However, a low number of dispersal events of symbionts between host species across time might be enough to prevent population structure and species divergence. Overall, processes of evolutionary divergence and the species status of most putative multi-host symbiont systems are yet to be investigated. Here, we used DNA metabarcoding data of 6,023 feather mites (a total of 2,225 OTU representative sequences) from 147 infracommunities (i.e., the assemblage consisting of all mites of different species collected from the same bird host individual) to investigate patterns of population genetic structure and species status of three different putative multi-host feather mite species Proctophyllodes macedo Vitzthum, 1922, Proctophyllodes motacillae Gaud, 1953, and Trouessartia jedliczkai (Zimmerman, 1894), each of which inhabits a variable number of different closely related wagtail host species (genus Motacilla). We show that mite populations from different host species represent a single species. This pattern was found in all the mite species, suggesting that each of these species is a multi-host species in which dispersal of mites among host species prevents species divergence. Also, we found evidence of limited evolutionary divergence manifested by a low but significant level of population genetic structure among symbiont populations inhabiting different host species. Our study agrees with previous studies showing a higher than expected colonization opportunities in host-specific symbionts. Indeed, our results support that these dispersal events would allow the persistence of multi-host species even in symbionts with limited dispersal capabilities, though additional factors such as the geographical structure of some bird populations may also play a role.This work was supported by the MINECO CGL2011-24466 to RJ and CGL2015-69650-P to RJ and DS

Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.

Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles), and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i) reduced trypsin binding activity, (ii) increased chaperone activity, and (iii) increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine) effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.Early Career Fellowship from the National Health and Medical Research Council GNT1012521(A.R.W.); Wellcome Trust Programme Grant (J.R.K., C.M.D.) 094425/Z/10/Z; Samsung GRO Grant (M.R.W.)This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013003

Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

<p>Abstract</p> <p>Background</p> <p>Tamoxifen (TAM) is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM) which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level <it>in vivo</it>.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge.</p> <p>Results</p> <p>A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE) in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns.</p> <p>Conclusion</p> <p>Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.</p

Increased searching and handling effort in tall swards lead to a Type IV functional response in small grazing herbivores

Understanding the functional response of species is important in comprehending the species’ population dynamics and the functioning of multi-species assemblages. A Type II functional response, where instantaneous intake rate increases asymptotically with sward biomass, is thought to be common in grazers. However, at tall, dense swards, food intake might decline due to mechanical limitations or if animals selectively forage on the most nutritious parts of a sward, leading to a Type IV functional response, especially for smaller herbivores. We tested the predictions that bite mass, cropping time, swallowing time and searching time increase, and bite rate decreases with increasing grass biomass for different-sized Canada geese (Branta canadensis) foraging on grass swards. Bite mass indeed showed an increasing asymptotic relationship with grass biomass. At high biomass, difficulties in handling long leaves and in locating bites were responsible for increasing cropping, swallowing, and searching times. Constant bite mass and decreasing bite rate caused the intake rate to decrease at high sward biomass after reaching an optimum, leading to a Type IV functional response. Grazer body mass affected maximum bite mass and intake rate, but did not change the shape of the functional response. As grass nutrient contents are usually highest in short swards, this Type IV functional response in geese leads to an intake rate that is maximised in these swards. The lower grass biomass at which intake rate was maximised allows resource partitioning between different-sized grazers. We argue that this Type IV functional response is of more importance than previously thought