Src: more than the sum of its parts

The Src family of protooncoproteins is required for prc through at least two phases of the cell cycle and for sc cell-type-specific functions. Recent crystal structures of fragments of two representatives reveal a compact am their Src-homology 3 (SH3), SH2 and catalytic domai embodies an unexpected mechanism of regulation. Th. the enzymatic activity of Src is controlled by intramol associations between the SH2 domain and C-tail and SH3 domain and a surprising internal target. The stn highlight a mechanism by which substrates can comp internal sequences for binding to the SH3 and SH2 do thereby stimulating kinase activity. This implies that distinction between upstream activators and downstre will sometimes be ambiguous.     

A whole more than the sum of its synthetic parts.

Synthetic biology is the realization of systems with desired behavior using biological materials. A recent addition to the field is a bipartite consortium of the bacterium Escherichia coli in which each species harbors complementary gene circuits that actuate only when both are present above a critical density. This bacterial "consensus" system, functional in liquid, solid, and biofilm niches, represents a novel strategy that raises the bar in terms of the specificity and complexity of tasks performed by engineered organisms.     

Modularity and intra-floral integration in metameric organisms: plants are more than the sum of their parts

Within-individual variation in virtually every conceivable morphological and functional feature of reiterated structures is a pervasive feature of plant phenotypes. In particular, architectural effects, regular, repeatable patterns of intra-individual variation in form and function that are associated with position are nearly ubiquitous. Yet, flowers also are predicted to be highly integrated. For animal-pollinated plants, the coordination of multiple organs within each flower is required to achieve the complex functions of pollinator attraction and orientation, pollen donation and pollen receipt. To the extent that pollinators may select for multiple independent functions, phenotypic integration within flowers may also be modular. That is, subsets of floral structures may be integrated but vary independently of other subsets of structures that are themselves integrated. How can phenotypic integration and modularity be understood within the context of architectural effects? This essay reviews recent research on patterns of floral integration and modularity and explores the potential for spatial and temporal changes in the selective environment of individual flowers to result in positional variation in patterns of morphological integration.     

Dystrophin: More than just the sum of its parts

Dystrophin is one of a number of large cytoskeleton associated proteins that connect between various cytoskeletal elements and often are tethered to the membrane through other transmembrane protein complexes. These cytolinker proteins often provide structure and support to the cells where they are expressed, and mutations in genes encoding these proteins frequently gives rise to disease. Dystrophin is no exception in any of these respects, providing connections between a transmembrane complex known as the dystrophin–glycoprotein complex and the underlying cytoskeleton. The most established connection and possibly the most important is that to F-actin, but more recently evidence has been forthcoming of connections to membrane phospholipids, intermediate filaments and microtubules. Moreover it is becoming increasingly clear that the multiple spectrin-like repeats in the centre of the molecule, that had hitherto been thought to be largely redundant, harbour binding activities that have a significant impact on dystrophin functionality. This functionality is particularly apparent when assessed by the ability to rescue the dystrophic phenotype in mdx mice. This review will focus on the relatively neglected but functionally vital coiled-coil region of dystrophin, highlighting the structural relationships and interactions of the coiled-coil region and providing new insights into the functional role of this region.     

Episodic encoding is more than the sum of its parts: an fMRI investigation of multifeatural contextual encoding

Episodic memories are characterized by their contextual richness, yet little is known about how the various features comprising an episode are brought together in memory. Here we employed fMRI and a multidimensional source memory procedure to investigate processes supporting the mnemonic binding of item and contextual information. Volunteers were scanned while encoding items for which the contextual features (color and location) varied independently, allowing activity elicited at the time of study to be segregated according to whether both, one, or neither feature was successfully retrieved on a later memory test. Activity uniquely associated with successful encoding of both features was identified in the intra-parietal sulcus, a region strongly implicated in the support of attentionally mediated perceptual binding. The findings suggest that the encoding of disparate features of an episode into a common memory representation requires that the features be conjoined in a common perceptual representation when the episode is initially experienced.     

Multi-scale phenotyping of leaf expansion in response to environmental changes: the whole is more than the sum of parts

The leaf is a multi-scale dynamic unit that is determined by mechanisms at different organizational scales (cell, tissue, whole leaf and whole plant) and affected by both internal (genotype) and external (environmental) determinisms. The recent development of phenotyping platforms and imaging techniques provides new insights into the temporal and spatial patterns of leaf growth as affected by those determinisms. Conclusions about the overriding mechanisms often depend on the considered organizational scale and of time resolution which varies from minutes to several weeks. Analyses of leaf growth responses to environmental conditions have revealed robust emerging properties at whole plant or whole leaf scales. They have highlighted that the control of individual leaf expansion is more complex than merely the sum of cellular processes, and the control at the whole plant level is more complex than the sum of individual leaf expansions. However, in many cases, the integrated leaf-growth variable can be simplified to a limited set of underlying variables to be measured for comparative analyses of leaf growth or modelling purposes.     

137 DNA nanostructure serum stability: greater than the sum of their parts

DNA cages hold tremendous potential to encapsulate and selectively release therapeutic drugs, and can provide useful tools to probe the size and shape dependence of nucleic acid delivery (McLaughlin & Sleiman, H. F., 2011). These structures have been shown to site-specifically present ligands, small molecule drugs, or antisense/siRNA motifs, in order to increase their therapeutic efficiency (Li & Fan, C. 2012). One of the major barriers towards their in vivo applications is the susceptibility of their strands towards nuclease degradation. A number of chemical strategies have been used to block nuclease digestion of oligonucleotides and improve potency, such as the use of a phosphorothioate backbone, 2´-O-methyl, locked nucleic acids, and short hybrid gapmers. However, the synthesis of these oligonucleotides is often complicated and expensive, driving the need for simple modifications to enhance serum stability and address in vivo biodistribution. We show here a simple method to significantly enhance the nuclease stability of DNA strands, through introduction of commercially available, single-endmodifications (Conway & Sleiman 2013). We use these oligonucleotides to construct DNA cages in a single step and in quantitative yields. Even in single-stranded form, these cages stabilize their component strands towards nucleases, with mean lifetimes as long as 62?h in 10 % (v/v) fetal bovine serum (FBS). We examine the effect of other DNA-end modifications on nuclease susceptibility. Finally, we show the ligation of these single-stranded cages into topologically interesting catenane ‘necklaces,’ with mean lifetimes in serum of ～200?h.     

Energetics of muscle contraction: the whole is less than the sum of its parts

Understanding muscle energetics is a problem in optimizing supply of ATP to the demands of ATPases. The complexity of reactions and their fluxes to achieve this balance is greatly reduced by recognizing constraints imposed by the integration of common metabolites at fixed stoichiometry among modular units. ATPase is driven externally. Oxidative phosphorylation and glycogenolysis are the suppliers. We focus on their regulation which involves different controls, but reduces to two principles that enable facile experimental analysis of the supply and demand fluxes. The ratio of concentration of phosphocreatine (PCr) to ATP, not their individual values, sets the range of achievable concentrations of ADP in resting and active muscle (at fixed pH) in different cell types. This principle defines the fraction of available flux of oxidative phosphorylation utilized (at fixed enzyme activities). Then the kinetics of PCr recovery defines the kinetics of oxygen supply and substrate utilization. The second principle is the constancy of PCr and H(+) (lactate) production by glycogenolysis due to the coupling of ATPase and glycolysis. This principle enables glycogenolytic flux to be measured from intracellular proton loads. Further simplification occurs because the magnitude of the interacting fluxes and metabolite concentrations are specified within narrow limits when both the resting and active fluxes are quantified. Thus there is a small set of rules for assessing and understanding the thermodynamics and kinetics of muscle energetics.     

A number no greater than the sum of its parts: the use and abuse of heritability

Though widely used in quantitative genetics, in the study of human variation perhaps no statistic is more easily misinterpreted than heritability. While the contribution of genetic heritage to complex biological and behavioral phenotypes cannot be lightly dismissed, nonetheless we remain profoundly ignorant of how that legacy plays out in any environmental context. To be sure, it is not reducible to a single number. Nor does the preference among anthropologists for analyzing biological rather than behavioral phenotypes improve what heritability can reasonably say about the sources of human variation. This paper discusses the meaning of heritability, the methods for its estimation, the fallacies underlying its misuse, and its utility for inquiries in evolutionary anthropology and epidemiology. Progress in anthropological genetics will be realized through greater sophistication in study designs, including the measurement of environmental (physical and sociocultural) variation and the judicious choice of phenotypes for study. Elucidating the ontogenetic processes underlying adaptive plasticity is particularly critical to understanding the evolution of human biological variation. Such advancements will also shed light on the feasibility of genotype-targeted biomedical treatments. Failure to appreciate the limits of such approaches can divert resources from demonstrably effective environmentally based health interventions that benefit entire populations. Simplistic notions of genetic determinism should be challenged for the sake of our theories and the well-being of larger communities. As exemplified by the work of Frank B. Livingstone, anthropological genetics is at its best when incorporating anthropology into the study of human phenotypic variation.     

Elevational diversity of terrestrial rainforest herbs: when the whole is less than the sum of its parts

We studied the species richness of herbaceous terrestrial plant species along an elevational gradient at 250–2425 m a.s.l. in evergreen tropical forest in Central Sulawesi, Indonesia. We recorded 302 species belonging to 51 families. Ferns and lycophytes contributed 62% of the species, followed by monocots with 24% and dicots with 14%. Overall herb species richness did not show any particular relation with elevation, while the richness of ferns increased significantly with elevation, monocots did not show a pattern, and dicots showed a hump-shaped pattern with maximum richness at 1800 m. These patterns in turn were only partly reflected in the patterns of the individual plant families making up each group. The independence of different taxa was also reflected in their relationships to environmental factors (temperature, precipitation, and area): although, each single family was related to one or several factors, at the group level and at the overall level these trends were lost. These results show that interpreting diversity at higher taxonomic level may overlook important information at the family level and raises the biologically intriguing question whether overall patterns of diversity result from a random accumulation of group-specific patterns or if there is some interaction between groups (e.g., via competition and niche-pre-emption).     

Bushmeat and bycatch: the sum of the parts

In many developing countries, the killing of wild animals for commercial purposes (the bushmeat trade) is a significant factor in the reduction of biodiversity, and probably represents a major threat to the survival of many more populations than we know. This includes marine species such as cetaceans, sea turtles and sirenians ("marine bushmeat"), which are often neglected in the discussion of this issue. Estimating the impact of the bushmeat trade anywhere is problematic because even the most thorough visual surveys of meat markets cannot easily translate an observed quantity of butchered products into the number of animals killed. In this issue of Molecular Ecology, Baker et al. provide a powerful new tool for such assessments: molecular identification of commercially available products from a depleted population of minke whales in South Korea is combined with genotyping and novel capture-recapture methods to estimate not only the number of individuals taken, but also the persistence of the resulting products in the marketplace.