Time-dependent inhibition of sucrose sweetness with gymnemic acid: Mode of action

A time-dependent study of the sweet response of sucrose allows a Lineweaver-Burk type of plot (reciprocal of magnitude estimation rate versus reciprocal of sucrose concentration) to be obtained, from which considerable deviation is observed after inhibition of sweetness with gymnemic acid. The plots after inhibition do not appear to be analogous to any of the known forms of competitive, uncompetitive or non-competitive inhibition of enzyme kinetics. Rather a “mixed-type” of inhibition is suggested, combining the attributes of competitive and non-competitive inhibition.     

Contrast and range effects for category, magnitude and labeled magnitude scales in judgements of sweetness intensity

The labeled magnitude scale (LMS) is a verbally anchored quasi-logarithmically spaced response scale with properties similar to magnitude estimation. Three experiments examined whether the LMS showed context effects similar to those found with magnitude estimation and category scales. Two versions of the LMS were used, one anchored at the high end to the strongest imaginable sweetness and the other to the strongest imaginable oral sensation. In a simple contrast experiment, subjects judged the sweetness of a 10% sucrose fruit beverage in the context of a less sweet (5%) beverage or a more sweet (20%) beverage. Consistent with previous literature, the sweetness was judged more intense in the low context and less intense in the high context, for all scaling methods. In a second experiment, this effect persisted (although was smaller) when the contextual item preceded the to-be-rated item, a so-called 'reversed-pair' design. Once again, the effect was highly significant for all scaling methods. In a third experiment, a range effect was examined using wide and narrow ranges of concentration. Psychophysical functions were flatter in a wide context and steeper in a narrow context, consistent with previous observations on range-mapping bias. This result was obtained for all scales. In three common contextual effects, the labeled magnitude scale behaved similarly to other scaling procedures. Its application to comparisons across individuals may be limited if those individuals have different experiential contexts within which they make their judgements.     

Degrees of differential gene expression: detecting biologically significant expression differences and estimating their magnitudes

MOTIVATION: Many methods of identifying differential expression in genes depend on testing the null hypotheses of exactly equal means or distributions of expression levels for each gene across groups, even though a statistically significant difference in the expression level does not imply the occurrence of any difference of biological or clinical significance. This is because a mathematical definition of 'differential expression' as any non-zero difference does not correspond to the differential expression biologists seek. Furthermore, while some current methods account for multiple comparisons in hypothesis tests, they do not accordingly adjust estimates of the degrees to which genes are differentially expressed. Both problems lead to overstating the relevance of findings. RESULTS: Testing whether genes have relevant differential expression can be accomplished with customized null hypotheses, thereby redefining 'differential expression' in a way that is more biologically meaningful. When such tests control the false discovery rate, they effectively discover genes based on a desired quantile of differential gene expression. Estimation of the degree to which genes are differentially expressed has been corrected for multiple comparisons. AVAILABILITY: R code is freely available from http://www.davidbickel.com and may become available from www.r-project.org or www.bioconductor.org SUPPLEMENTARY INFORMATION: Applications to cancer microarrays, an application in the absence of differential expression, pseudocode, and a guide to customizing the methods may be found at www.davidbickel.com and www.mathpreprints.com     

Mitonuclear interactions: evolutionary consequences over multiple biological scales

Fundamental biological processes hinge on coordinated interactions between genes spanning two obligate genomes—mitochondrial and nuclear. These interactions are key to complex life, and allelic variation that accumulates and persists at the loci embroiled in such intergenomic interactions should therefore be subjected to intense selection to maintain integrity of the mitochondrial electron transport system. Here, we compile evidence that suggests that mitochondrial–nuclear (mitonuclear) allelic interactions are evolutionarily significant modulators of the expression of key health-related and life-history phenotypes, across several biological scales—within species (intra- and interpopulational) and between species. We then introduce a new frontier for the study of mitonuclear interactions—those that occur within individuals, and are fuelled by the mtDNA heteroplasmy and the existence of nuclear-encoded mitochondrial gene duplicates and isoforms. Empirical evidence supports the idea of high-resolution tissue- and environment-specific modulation of intraindividual mitonuclear interactions. Predicting the penetrance, severity and expression patterns of mtDNA-induced mitochondrial diseases remains a conundrum. We contend that a deeper understanding of the dynamics and ramifications of mitonuclear interactions, across all biological levels, will provide key insights that tangibly advance our understanding, not only of core evolutionary processes, but also of the complex genetics underlying human mitochondrial disease.     

Hydrolysis of sucrose octa-acetate: qualitative differences in taster and demistaster avoidance phenotypes

Calcium hydroxide and sodium hydroxide were used to hydrolysesucrose octa-acetate (SOA) as a means of evaluating the taster(Soa^a) and demitaster (Soa^c) allelic phenotypes of the geneticlocus Soa. The SWR/J (taster) inbred strain and the B6.SW Soa^a(taster) congenic strain were demonstrated to cease avoidingupon nearly complete hydrolysis of 10^–5 M SOA with calciumhydroxide Or sodium hydroxide and of 10^–4 M SOA with calciumhydroxide. The BALB/cByJ, C3HeB/FeJ and DBA/2J (demitaster)inbred strains were demonstrated to cease avoiding after onlya partial hydrolysis of 10^–3 M SOA using calcium hydroxide.It is suggested that specificity for the number or placementof the acetates of SOA underlies the difference between thetaster and demitaster phenotypes.     

Ontogenetic causes and mechanisms for formation of differences in number of fish scales

Fish squamation is developed in late ontogeny. Therefore, the conditions of development significantly affect its characteristics (number of scales). This study is aimed at considering the influence of external and internal factors on variation of the number of scales in fish. Acceleration of development results in decrease of the number of scales, while it increases with retardation. Experiments on regulation of thyroid status of fish showed that the certain mechanism of alteration of the number of scales is related with heterochrony, such as a shift of the timing of squamation. Accelerated development is caused by early scale development at smaller body length, while retarded development is characterized with later scale development and at greater body length. Data considering heterochrony as the possible reason for differences in the number of scales in related fish species are represented. Moreover, alterations of the distance between scales (morphogenetic count) can serve as another alteration mechanism of the number of scales in fish (especially phyletically distant species).     

Genetic and environmental influences on human psychological differences

Psychological researchers typically distinguish five major domains of individual differences in human behavior: cognitive abilities, personality, social attitudes, psychological interests, and psychopathology (Lubinski, 2000). In this article we: discuss a number of methodological errors commonly found in research on human individual differences; introduce a broad framework for interpreting findings from contemporary behavioral genetic studies; briefly outline the basic quantitative methods used in human behavioral genetic research; review the major criticisms of behavior genetic designs, with particular emphasis on the twin and adoption methods; describe the major or dominant theoretical scheme in each domain; and review behavioral genetic findings in all five domains. We conclude that there is now strong evidence that virtually all individual psychological differences, when reliably measured, are moderately to substantially heritable.     

Regional management units for marine turtles: a novel framework for prioritizing conservation and research across multiple scales

Background

Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques — including site-based monitoring, genetic analyses, mark-recapture studies and telemetry — can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges.

Methodology/Principal Findings

To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine- to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally.

Conclusions/Significance

The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework — including maps and supporting metadata — will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis.     

Mathematical and computational modeling in biology at multiple scales

A variety of topics are reviewed in the area of mathematical and computational modeling in biology, covering the range of scales from populations of organisms to electrons in atoms. The use of maximum entropy as an inference tool in the fields of biology and drug discovery is discussed. Mathematical and computational methods and models in the areas of epidemiology, cell physiology and cancer are surveyed. The technique of molecular dynamics is covered, with special attention to force fields for protein simulations and methods for the calculation of solvation free energies. The utility of quantum mechanical methods in biophysical and biochemical modeling is explored. The field of computational enzymology is examined.     

Observer-rated ataxia: rating scales for assessment of genetic differences in ethanol-induced intoxication in mice.

Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.0, and 3.25 g/kg) in nine inbred mouse strains. Each scale independently rates a single behavior. Raters, blinded to dose, scored four behaviors (splay of hind legs, wobbling, nose down, and belly drag) at each of four time points after injection. The severities of hind leg splaying and wobbling were quantifiable, whereas nose down and belly dragging were expressed in all-or-none fashion. Interrater reliabilities were substantial (0.75 0 at some time), but all doses were equally effective. Incidence of nose down and belly dragging behaviors increased strain dependently after ethanol, but strains did not differentially respond to dose. Ethanol-induced splaying was modestly, and negatively, genetically correlated with wobbling. Nose down and belly dragging tended to be associated with splaying and wobbling at later times. Four distinct ataxia-related behaviors were sensitive to ethanol. Strains differed in ethanol sensitivity for all measures. Modest strain mean correlations among behaviors indicate that these behaviors are probably under control of largely different genes and that ataxia rating scales should rate separate behaviors on discrete scales.     

Dissimilarity of stream insect assemblages: effects of multiple scales and spatial distances

In addition to the effects of environmental conditions, biotic assemblages may exhibit spatial structure depending on the scale of study. We tested whether the dissimilarity of stream insect assemblages is related to two types of spatial distances (stream corridor and overland distance), and evaluated the relative importance of diversity components at multiple spatial scales. Field data included assemblages of Ephemeroptera, Plecoptera, and Trichoptera found in 16 streams in four microbasins. We evaluated the relationship of the dissimilarity of assemblages with the distance types, using Mantel tests. In addition, we evaluated the relationships among the diversity components at multiple spatial scales, using additive partitioning analysis. The biological dissimilarities were correlated only with the geographical distances. Additive partitioning showed that the values of richness observed in the β1 (among Surber), β2 (among riffles), β3 (among streams), and β4 (among microbasins) were higher than those expected. The highest variation of the richness was found in β3 (30.6%). We conclude that stream faunas are distributed in patches all over the studied spatial extent, causing a weak relationship of biological dissimilarity with distance but important beta components when compared to a completely homogenous distribution of the fauna.     

Climate impacts at multiple scales: evidence for differential population responses in juvenile Chinook salmon

1. We explored differential population responses to climate in 18 populations of threatened spring-summer Chinook salmon Onchorynchus tshawytscha in the Salmon River basin, Idaho. 2. Using data from a long-term mark-release-recapture study of juvenile survival, we found that fall stream flow is the best predictor of average survival across all populations. 3. To determine whether all populations responded similarly to climate, we used a cluster analysis to group populations that had similar annual fluctuations in survival. The populations grouped into four clusters, and different environmental factors were important for different clusters. 4. Survival in two of the clusters was negatively correlated with summer temperature, and survival in the other two clusters was positively correlated with minimum fall stream flow, which in turn depends on snow pack from the previous winter. 5. Using classification and regression tree analysis, we identified stream width and stream temperature as key habitat factors that shape the responses of individual populations to climate. 6. Climate change will likely have different impacts on different populations within this metapopulation, and recognizing this diversity is important for accurately assessing risks.