Ancient and essential: the assembly of iron-sulfur clusters in plants

In plants iron-sulfur (Fe-S) proteins are found in the plastids, mitochondria, cytosol and nucleus, where they are essential for numerous physiological and developmental processes. Recent mutant studies, mostly in Arabidopsis thaliana, have identified three pathways for the assembly of Fe-S clusters. The plastids harbor the SUF (sulfur mobilization) pathway and operate independently, whereas cluster assembly in the cytosol depends on the emerging CIA (cytosolic iron-sulfur cluster assembly) pathway and mitochondria. The latter organelles use the ISC (iron-sulfur cluster) assembly pathway. In all three pathways the assembly process can be divided into a first stage where S and Fe are combined on a scaffold protein, and a second stage in which the Fe-S cluster is transferred to a target protein. The second stage might involve different carrier proteins with specialized functions.     

Evaluating CASP4 predictions with physical energy functions

Physical energy scoring functions based on implicit solvation models are tested by evaluating predictions from the most recent CASP4 competition. The best performing scoring functions are identified along with the best protocol for preparing structures before energies are evaluated. Ranking of structures with the best scoring functions is compared across CASP4 targets to establish when physical scoring functions can be expected to reliably distinguish structures that are most similar to the native fold in a set of misfolded or unfolded protein conformations. The results are used to interpret previous studies where scoring functions were tested on the standard decoy sets by Park, Levitt, and Baker. We show that the best physical scoring functions can be applied successfully in automated consensus scoring applications where a single best conformation has to be selected from a set of structures from different sources. Finally, the potential for better protein structure scoring functions is discussed with a suggestion for an empirically parameterized linear combination of energy components.     

Testing the effects of diversity on ecosystem multifunctionality using a multivariate model

Most ecosystems provide multiple services, thus the impact of biodiversity losses on ecosystem functions may be considerably underestimated by studies that only address single functions. We propose a multivariate modelling framework for quantifying the relationship between biodiversity and multiple ecosystem functions (multifunctionality). Our framework consolidates the strengths of previous approaches to analysing ecosystem multifunctionality and contributes several advances. It simultaneously assesses the drivers of multifunctionality, such as species relative abundances, richness, evenness and other manipulated treatments. It also tests the relative importance of these drivers across functions, incorporates correlations among functions and identifies conditions where all functions perform well and where trade‐offs occur among functions. We illustrate our framework using data from three ecosystem functions (sown biomass, weed suppression and nitrogen yield) in a four‐species grassland experiment. We found high variability in performance across the functions in monocultures, but as community diversity increased, performance increased and variability across functions decreased.     

Additional gene ontology structure for improved biological reasoning

MOTIVATION: The Gene Ontology (GO) is a widely used terminology for gene product characterization in, for example, interpretation of biology underlying microarray experiments. The current GO defines term relationships within each of the independent subontologies: molecular function, biological process and cellular component. However, it is evident that there also exist biological relationships between terms of different subontologies. Our aim was to connect the three subontologies to enable GO to cover more biological knowledge, enable a more consistent use of GO and provide new opportunities for biological reasoning. RESULTS: We propose a new structure, the Second Gene Ontology Layer, capturing biological relations not directly reflected in the present ontology structure. Given molecular functions, these paths identify biological processes where the molecular functions are involved and cellular components where they are active. The current Second Layer contains 6271 validated paths, covering 54% of the molecular functions of GO and can be used to render existing gene annotation sets more complete and consistent. Applying Second Layer paths to a set of 4223 human genes, increased biological process annotations by 24% compared to publicly available annotations and reproduced 30% of them. AVAILABILITY: The Second GO is publicly available through the GO Annotation Toolbox (GOAT.no): http://www.goat.no.     

Biodiversity improves the ecological design of sustainable biofuel systems

For algal biofuels to become a commercially viable and sustainable means of decreasing greenhouse gas emissions, growers are going to need to design feedstocks that achieve at least three characteristics simultaneously as follows: attain high yields; produce high quality biomass; and remain stable through time. These three qualities have proven difficult to achieve simultaneously under the ideal conditions of the laboratory, much less under field conditions (e.g., outdoor culture ponds) where feedstocks are exposed to highly variable conditions and the crop is vulnerable to invasive species, disease, and grazers. Here, we show that principles from ecology can be used to improve the design of feedstocks and to optimize their potential for “multifunctionality.” We performed a replicated experiment to test these predictions under outdoor conditions. Using 80 ponds of 1,100 L each, we tested the hypotheses that polycultures would outperform monocultures in terms of the following functions: biomass production, yield of biocrude from biomass, temporal stability, resisting population crashes, and resisting invasions by unwanted species. Overall, species richness improved stability, biocrude yield, and resistance to invasion. While this suggests that polycultures could outperform monocultures on average, invasion resistance was the only function where polycultures outperformed the best single species in the experiment. Due to tradeoffs among different functions that we measured, no species or polyculture was able to maximize all functions simultaneously. However, diversity did enhance the potential for multifunctionality—the most diverse polyculture performed more functions at higher levels than could any of the monocultures. These results are a key finding for ecological design of sustainable biofuel systems because they show that while a monoculture may be the optimal choice for maximizing short‐term biomass production, polycultures can offer a more stable crop of the desired species over longer periods of time.     

Calculating luminous flux and lighting levels for domesticated mammals and birds

This paper considers whether photometric calculations using standard human spectral sensitivity data are satisfactory for applications with other species or whether it would be worthwhile to use bespoke spectral sensitivity functions for each species or group of species. Applications include the lighting of interior areas and the design of photometers. Published spectral sensitivity data for a number of domesticated animals (human, turkey, duck, chicken, cat, rat and mouse) were used to calculate lighting levels for each species and compared with those derived from standard CIE human photopic and scotopic functions. Calculations were made for spectral power distributions of daylight, incandescent light and 12 fluorescent sources commonly used to light interiors. The calculated lighting levels showed clear differences between species and the standard human. Assuming that the resulting effects on retinal illuminance determine the overall perception of the level of light, there may be applications where these differences are important. However, evidence is also presented that the magnitude of these inter-species effects are similar to, or smaller than, those arising from other optical, physiological and psychological factors, which are also likely to influence the resulting perception. It is also important to recognise that lighting-related parameters such as the good colour rendering of surfaces, the avoidance of glare from lamps and other factors that may be species related are sometimes of greater importance than the lighting levels. Our results suggest that a judicial choice of three spectral sensitivity functions would satisfy most circumstances. Firstly, where the overall sensitivity is maximal in the medium to long wavelengths, the standard CIE photopic function will suffice, chicken, turkey and duck fall in this category. Secondly, in a small number of cases where the sensitivity centres on the short to medium wavelengths, the CIE scotopic function should be used, e.g. for the scotopic cat, photopic rat and photopic mouse. Finally, where an animal is also sensitive to the UV region of the spectrum and there is a significant component of UV radiation, then an additional measure of the UV response should be included, as for the photopic rat and photopic mouse.     

Estimation and inference for a spline-enhanced population pharmacokinetic model

This article is motivated by an application where subjects were dosed three times with the same drug and the drug concentration profiles appeared to be the lowest after the third dose. One possible explanation is that the pharmacokinetic (PK) parameters vary over time. Therefore, we consider population PK models with time-varying PK parameters. These time-varying PK parameters are modeled by natural cubic spline functions in the ordinary differential equations. Mean parameters, variance components, and smoothing parameters are jointly estimated by maximizing the double penalized log likelihood. Mean functions and their derivatives are obtained by the numerical solution of ordinary differential equations. The interpretation of PK parameters in the model and its flexibility are discussed. The proposed methods are illustrated by application to the data that motivated this article. The model's performance is evaluated through simulation.     

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

We provide a comprehensive classification of the proteoglycan gene families and respective protein cores. This updated nomenclature is based on three criteria: Cellular and subcellular location, overall gene/protein homology, and the utilization of specific protein modules within their respective protein cores. These three signatures were utilized to design four major classes of proteoglycans with distinct forms and functions: the intracellular, cell-surface, pericellular and extracellular proteoglycans. The proposed nomenclature encompasses forty-three distinct proteoglycan-encoding genes and many alternatively-spliced variants. The biological functions of these four proteoglycan families are critically assessed in development, cancer and angiogenesis, and in various acquired and genetic diseases where their expression is aberrant.     

A method for the deductive and unique determination of the values of three parameters involved in fractional functions applicable to relaxation kinetics.

A novel method is proposed to determine deductively and uniquely the values of three parameters, a, b, and c in a fractional function of the form, y=a+bx/(c+x) where x and y are experimentally obtainable variables. This type of equation is frequently encountered in chemistry and biochemistry involving relaxation kinetics. The method of least squares with the Taylor expansion is employed for direct curve fitting of observed data to the fractional function. Approximate values of the parameters, which are always necessary prior to commending the above procedure, can be obtained by the method of rearrangement after canceling the denominator of fractional functions. This procedure is very simple, but very effective for estimating provisional values of the parameters. Deductive and unique determination of the parameters involved in the fractional function shown above can be accomplished for the first time by the combination of these two procedures. This method is extended to include the analysis of relaxation kinetic data such as those of temperature-jump method where the determination of equilibrium concentrations of reactants in addition to the three parameters is also necessary.     

从生态学的观点看城乡发展问题

阐述了城乡发展的意义,提出了城乡发展中所面临的人口、环境和资源等三大问题.为使城乡发展建立在科学的基础上,必须合理利用自然资源,保护生态环境,使得城乡生态系统的收支、结构和功能保持平衡,真正把城乡建成功能齐全、环境优美、生产发展和生活舒适的场所.     

Complex organization of promoter and enhancer elements regulate the tissue- and developmental stage-specific expression of the Drosophila melanogaster Gld gene

The Drosophila melanogaster Gld gene has multiple and diverse developmental and physiological functions. We report herein that interactions among proximal promoter elements and a cluster of intronically located enhancers and silencers specify the complex regulation of Gld that underlies its diverse functions. Gld expression in nonreproductive tissues is largely determined by proximal promoter elements with the exception of the embryonic labium where Gld is activated by an enhancer within the first intron. A nuclear protein, GPAL, has been identified that binds the Gpal elements in the proximal promoter region. Regulation of Gld in the reproductive organs is particularly complex, involving interactions among the Gpal proximal promoter elements, a unique TATA box, three distinct enhancer types, and one or more silencer elements. The three somatic reproductive organ enhancers each activate expression in male and female pairs of reproductive organs. One of these pairs, the male ejaculatory duct and female oviduct, are known to be developmentally homologous. We report evidence that the other two pairs of organs are developmentally homologous as well. A comprehensive model to explain the full developmental regulation of Gld and its evolution is presented.     

Ecosystem functions in natural and anthropogenic ecosystems across the East African coastal forest landscape

Habitat identity and landscape configuration significantly shape species communities and affect ecosystem functions. The conservation of natural ecosystems is of particular relevance in regions where landscapes have already been largely transformed into farmland and where habitats suffer under resource exploitation. The spillover of ecosystem functions from natural ecosystems into farmland may positively influence agricultural productivity and human livelihood quality. We measured three proxies of ecosystem functioning: Pollinator diversity (using pan traps), seed dispersal (with a seed removal experiment), and predation (using dummy caterpillars). We assessed these ecosystem functions in three forest types of the East African dry coastal forest (Brachystegia forest, Cynometra forest, and mixed forest), as well as in adjoining farmland and in plantations of exotic trees (Eucalyptus mainly). We measured ecosystem functions at 20 plots for each habitat type, and along gradients ranging from the forest into farmland. We also recorded various environmental parameters for each study plot. We did not find significant differences of ecosystem functions when combining all proxies assessed, neither among the three natural forest types, nor between natural forest and plantations. However, we found trends for single ecosystem functions. We identified highest pollinator diversity along the forest margin and in farmlands. Vegetation cover and blossom density affected the level of predation positively. Based on our findings, we suggest that flowering gardens around housings and woodlots across farmland areas support ecosystem functioning and thus improve human livelihood quality. We conclude that levels of overall ecosystem functions are affected by entire landscapes, and high landscape heterogeneity, as found in our case, might blur potential negative effects and trends arising from habitat destruction and degradation.     

Internal organization of large protein families: relationship between the sequence, structure, and function-based clustering

The protein universe can be organized in families that group proteins sharing common ancestry. Such families display variable levels of structural and functional divergence, from homogenous families, where all members have the same function and very similar structure, to very divergent families, where large variations in function and structure are observed. For practical purposes of structure and function prediction, it would be beneficial to identify sub-groups of proteins with highly similar structures (iso-structural) and/or functions (iso-functional) within divergent protein families. We compared three algorithms in their ability to cluster large protein families and discuss whether any of these methods could reliably identify such iso-structural or iso-functional groups. We show that clustering using profile-sequence and profile-profile comparison methods closely reproduces clusters based on similarities between 3D structures or clusters of proteins with similar biological functions. In contrast, the still commonly used sequence-based methods with fixed thresholds result in vast overestimates of structural and functional diversity in protein families. As a result, these methods also overestimate the number of protein structures that have to be determined to fully characterize structural space of such families. The fact that one can build reliable models based on apparently distantly related templates is crucial for extracting maximal amount of information from new sequencing projects.     

Mutations and regulatory anomalies effecting tumor cell immune functions

The immune system is capable of interacting with tumor cells in such a way as to lead to tumor cell death, and this knowledge has inspired therapies to manipulate patient immune systems to eradicate cancer. However, tumor cells are able to mitigate the antitumor immune response, a fact that has rarely been addressed in the design of immunotherapies. There are many different tumor cell immune functions that play a role in mitigating the antitumor immune response. In some cases, these functions appear to be intimately associated with the tumor cell abnormalities that lead to loss of growth control, such as the cases where classical tumor suppressor proteins regulate tumor cell immune function genes. In other cases, tumor cell mutations appear to affect only the antitumor response, such as tumor cell mutations that eliminate MHC class I expression. Here I review the bases for tumor cell immune functions, noting in particular where tumor cell mutations, the gold standard for identifying a tumor-specific function, are known to be responsible for the tumor cell immune function. This review also discusses other known regulatory anomalies, in the absence of a known mutation, that are apparently important for tumor development and that regulate tumor cell immune functions. Surprisingly, in many cases where the tumor cell immune function is well understood in terms of its effect on the antitumor immune response, the tumor abnormality underlying the tumor cell immune function is completely uncharacterized.     

Flavin-containing monooxygenases in plants: looking beyond detox

Flavin-containing monooxygenases (FMOs) are known in bacteria, yeast and mammals where they catalyze the transfer of one atom of molecular O(2) to low molecular weight substrates. The predominant physiological function of animal FMOs appears to be detoxification of a vast spectrum of xenobiotics but until recently very little was known about the function of FMOs in plants. In the last two to three years, genetic and biochemical characterization has shown that plant FMOs can catalyze specific steps in the biosynthesis of auxin or in the metabolism of glucosinolates, and, furthermore, have a role in pathogen defence. Thus, plant FMOs hint that further FMO functions might be identified also in non-plant organisms and could stimulate novel research in this area.     

Dynamics of nutrient-phytoplankton interaction in the presence of viral infection

The present paper deals with the problem of a nutrient-phytoplankton (N-P) populations where phytoplankton population is divided into two groups, namely susceptible phytoplankton and infected phytoplankton. Conditions for coexistence or extinction of populations are derived taking into account general nutrient uptake functions and Holling type-II functional response as an example. It is observed that the three component systems persist when the infected phytoplankton population is not able to consume nutrient.     

In silico determination of intracellular glycosylation and phosphorylation sites in human selectins: implications for biological function

Post-translational modifications provide the proteins with the possibility to perform functions in addition to those determined by their primary sequence. However, analysis of multifunctional protein structures in the environment of cells and body fluids is made especially difficult by the presence of other interacting proteins. Bioinformatics tools are therefore helpful to predict protein multifunctionality through the identification of serine and threonine residues wherein the hydroxyl group is likely to become modified by phosphorylation or glycosylation. Moreover, serines and threonines where both modifications are likely to occur can also be predicted (YinYang sites), to suggest further functional versatility. Structural modifications of hydroxyl groups of P-, E-, and L-selectins have been predicted and possible functions resulting from such modifications are proposed. Functional changes of the three selectins are based on the assumption that transitory and reversible protein modifications by phosphate and O-GlcNAc cause specific conformational changes and generate binding sites for other proteins. The computer-assisted prediction of glycosylation and phosphorylation sites in selectins should be helpful to assess the contribution of dynamic protein modifications in selectin-mediated inflammatory responses and cell-cell adhesion processes that are difficult to determine experimentally.