Constant Pharmacologic Effect and Chronopharmacology: Theoretical Aspects

The theoretical drug infusion rates requisite to obtain a constant pharmacologic effect are determined taking into account chronopharmacologic phenomena. The introduction of chronopharmacology into pharmacokinetic theory leads to a clocktime-dependent infusion rate. The infusion modulation depends both on type of chronophenomenon, chronopharmacokinetics or chronestesy, and plasma clearance rate of the drug. In the presence of chronestesy of a biosystem the pharmacologic effect can be maintained constant only when plasma drug clearance is fast enough to allow an adequate modulation of the plasma drug concentration. Although the established equations proceed from theoretical concept they could be useful for programming drug delivery systems.     

Testing attachment point theory: diatom attachment on microtextured polyimide biomimics

Abstract

This paper explores diatom attachment to a range of laser etched polyimide surfaces to directly test ‘attachment point theory’. Static bioassays were conducted on microtextured polyimide surfaces using four diatom species, Fallacia carpentariae, Nitzschia cf. paleacea, Amphora sp. and Navicula jeffreyi with cell sizes ranging from 1 – 14 μm. The microtextured polyimides were modelled from natural fouling resistant bivalve surfaces and had wavelengths above, below and at the same scale as the diatom cell sizes. Diatoms attached in significantly higher numbers to treatments where the numbers of attachment points was highest. The lowest diatom attachment occurred where cells were slightly larger than the microtexture wavelength, resulting in only two theoretical points of attachment. The results support attachment point theory and highlight the need to address larval/cell size in relation to the number of attachment points on a surface. Further studies examining a range of microtexture scales are needed to apply attachment point theory to a suite of fouling organisms and to develop structured surfaces to control the attachment and development of fouling communities.     

The CQ ratio of surface energy components influences adhesion and removal of fouling bacteria

The interaction energy between bacteria and substrata with different surface energies was modelled by the extended DLVO (Derjaguin, Landau, Verwey and Overbeek) theory. The modeling results revealed that the interaction energy has a strong correlation with the CQ (Chen and Qi) ratio, which is defined as the ratio of the Lifshitz–van der Waals (LW) apolar to the electron donor surface energy components of substrata. Both modeling and experimental results with different bacteria including P. fluorescens, Cobetia marina and Vibrio alginolyticus demonstrated that if the LW surface energy of bacteria is larger than that of water, which is the case for most bacteria, the number of adhered bacteria decreases with a decreasing CQ ratio while bacterial removal rate increases with a decreasing CQ ratio. However, if the LW surface energy of bacteria is less than that of water, the opposite results are obtained. The CQ ratio gives a clear direction for the design of anti-biofouling and biofouling-release coatings through surface modification.     

Pervasive selection or is it…? why are FST outliers sometimes so frequent?

It is now common for population geneticists to estimate F_ST for a large number of loci across the genome, before testing for selected loci as being outliers to the F_ST distribution. One surprising result of such F_ST scans is the often high proportion (>1% and sometimes >10%) of outliers detected, and this is often interpreted as evidence for pervasive local adaptation. In this issue of Molecular Ecolog, Fourcade et al. ( 2013 ) observe that a particularly high rate of F_ST outliers has often been found in river organisms, such as fishes or damselflies, despite there being no obvious reason why selection should affect a larger proportion of the genomes of these organisms. Using computer simulations, Fourcade et al. ( 2013 ) show that the strong correlation in co‐ancestry produced in long one‐dimensional landscapes (such as rivers, valleys, peninsulas, oceanic ridges or coastlines) greatly increases the neutral variance in F_ST, especially when the landscape is further reticulated into fractal networks. As a consequence, outlier tests have a high rate of false positives, unless this correlation can be taken into account. Fourcade et al.'s study highlights an extreme case of the general problem, first noticed by Robertson ( 1975a , b ) and Nei & Maruyama ( 1975 ), that correlated co‐ancestry inflates the neutral variance in F_ST when compared to its expectation under an island model of population structure. Similar warnings about the validity of outlier tests have appeared regularly since then but have not been widely cited in the recent genomics literature. We further emphasize that F_ST outliers can arise in many different ways and that outlier tests are not designed for situations where the genetic architecture of local adaptation involves many loci.     

The design of a peptide sequence to inhibit HIV replication: a search algorithm combining Monte Carlo and self-consistent mean field techniques

We developed a search algorithm combining Monte Carlo (MC) and self-consistent mean field techniques to evolve a peptide sequence that has good binding capability to the anticodon stem and loop (ASL) of human lysine tRNA species, tRNA^Lys3, with the ultimate purpose of breaking the replication cycle of human immunodeficiency virus-1. The starting point is the 15-amino-acid sequence, RVTHHAFLGAHRTVG, found experimentally by Agris and co-workers to bind selectively to hypermodified tRNA^Lys3. The peptide backbone conformation is determined via atomistic simulation of the peptide-ASL^Lys3 complex and then held fixed throughout the search. The proportion of amino acids of various types (hydrophobic, polar, charged, etc.) is varied to mimic different peptide hydration properties. Three different sets of hydration properties were examined in the search algorithm to see how this affects evolution to the best-binding peptide sequences. Certain amino acids are commonly found at fixed sites for all three hydration states, some necessary for binding affinity and some necessary for binding specificity. Analysis of the binding structure and the various contributions to the binding energy shows that: 1) two hydrophilic residues (asparagine at site 11 and the cysteine at site 12) “recognize” the ASL^Lys3 due to the VDW energy, and thereby contribute to its binding specificity and 2) the positively charged arginines at sites 4 and 13 preferentially attract the negatively charged sugar rings and the phosphate linkages, and thereby contribute to the binding affinity.     

The role of temperament in the relationship between morningness–eveningness and mood

Apart from differences in circadian phase position, individuals with different morningness–eveningness levels vary in many more characteristics. Particularly consistent relationships have been observed between morningness–eveningness and mood. Eveningness has been associated with disadvantageous mood, e.g. depressiveness in healthy individuals, and mood disorders. A concept of social jetlag suggests that evening subjects function in less advantageous environments due to discrepancies between internal and social time (societies promote morning-oriented functioning), which results in their lowered mood. Individual temperament, as defined by the Regulative Theory of Temperament (RTT), refers to the capacity of the human organism to meet environmental requirements – the greater the capacity, the less negative impact of external conditions. Thus, the aim of this study is to determine which RTT traits are linked to both morningness–eveningness and mood dimensions and to test whether they account for the relationship between morningness–eveningness and mood. A sample of 386 university students (267 female) aged between 19 and 47 (M?=?21.15, SD?=?4.23) years completed the University of Wales Institute of Science and Technology (UWIST) Mood Adjective Check List, Morningness–Eveningness Questionnaire and Formal Characteristics of Behaviour – Temperament Inventory. Analyses revealed lower endurance (EN) and higher emotional reactivity (ER) related to eveningness as well as to lower hedonic tone (HT), energetic arousal (EA) and to higher tense arousal (TA). Moreover, eveningness was associated with lower HT, EA and higher TA. Among RTT traits, EN was most strongly related to eveningness, and mediation analyses revealed that this temperamental trait fully mediated the relationship between eveningness and the three mood dimensions. The remaining RTT traits did not provide more explanation of the association between morningness–eveningness and mood than EN itself. If subjects did not differ in EN, the association between morningness–eveningness and mood was absent. EN is discussed as a protective factor against negative consequences of social jetlag and particularly lowered mood in evening individuals.     

Energy,ecology and the distribution of microbial life

Mechanisms that govern the coexistence of multiple biological species have been studied intensively by ecologists since the turn of the nineteenth century. Microbial ecologists in the meantime have faced many fundamental challenges, such as the lack of an ecologically coherent species definition, lack of adequate methods for evaluating population sizes and community composition in nature, and enormous taxonomic and functional diversity. The accessibility of powerful, culture-independent molecular microbiology methods offers an opportunity to close the gap between microbial science and the main stream of ecological theory, with the promise of new insights and tools needed to meet the grand challenges humans face as planetary engineers and galactic explorers. We focus specifically on resources related to energy metabolism because of their direct links to elemental cycling in the Earth''s history, engineering applications and astrobiology. To what extent does the availability of energy resources structure microbial communities in nature? Our recent work on sulfur- and iron-oxidizing autotrophs suggests that apparently subtle variations in the concentration ratios of external electron donors and acceptors select for different microbial populations. We show that quantitative knowledge of microbial energy niches (population-specific patterns of energy resource use) can be used to predict variations in the abundance of specific taxa in microbial communities. Furthermore, we propose that resource ratio theory applied to micro-organisms will provide a useful framework for identifying how environmental communities are organized in space and time.     

When growth models are not universal: evidence from marine invertebrates

The accumulation of body mass, as growth, is fundamental to all organisms. Being able to understand which model(s) best describe this growth trajectory, both empirically and ultimately mechanistically, is an important challenge. A variety of equations have been proposed to describe growth during ontogeny. Recently, the West Brown Enquist (WBE) equation, formulated as part of the metabolic theory of ecology, has been proposed as a universal model of growth. This equation has the advantage of having a biological basis, but its ability to describe invertebrate growth patterns has not been well tested against other, more simple models. In this study, we collected data for 58 species of marine invertebrate from 15 different taxa. The data were fitted to three growth models (power, exponential and WBE), and their abilities were examined using an information theoretic approach. Using Akaike information criteria, we found changes in mass through time to fit an exponential equation form best (in approx. 73% of cases). The WBE model predominantly overestimates body size in early ontogeny and underestimates it in later ontogeny; it was the best fit in approximately 14% of cases. The exponential model described growth well in nine taxa, whereas the WBE described growth well in one of the 15 taxa, the Amphipoda. Although the WBE has the advantage of being developed with an underlying proximate mechanism, it provides a poor fit to the majority of marine invertebrates examined here, including species with determinate and indeterminate growth types. In the original formulation of the WBE model, it was tested almost exclusively against vertebrates, to which it fitted well; the model does not however appear to be universal given its poor ability to describe growth in benthic or pelagic marine invertebrates.     

Multispecies coexistence of trees in tropical forests: spatial signals of topographic niche differentiation increase with environmental heterogeneity

Neutral and niche theories give contrasting explanations for the maintenance of tropical tree species diversity. Both have some empirical support, but methods to disentangle their effects have not yet been developed. We applied a statistical measure of spatial structure to data from 14 large tropical forest plots to test a prediction of niche theory that is incompatible with neutral theory: that species in heterogeneous environments should separate out in space according to their niche preferences. We chose plots across a range of topographic heterogeneity, and tested whether pairwise spatial associations among species were more variable in more heterogeneous sites. We found strong support for this prediction, based on a strong positive relationship between variance in the spatial structure of species pairs and topographic heterogeneity across sites. We interpret this pattern as evidence of pervasive niche differentiation, which increases in importance with increasing environmental heterogeneity.