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.     

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.     

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.     

REV-ERBs: more than the sum of the individual parts

REV-ERB nuclear receptors have been believed to stabilize the circadian clock machinery through an accessory but dispensable feedback loop. Recent work now challenges this assumption by demonstrating that REV-ERBs are essential core clock components, in addition to serving as pivotal regulators of rhythmic metabolism.     

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.     

整体大于部分之和: 生态自组织斑图及其涌现属性

近30年来, 自组织理论已经发展成为解释生态系统呈现规则空间格局的有效理论。伴随着生态系统自发有序空间格局的生成, 自组织过程产生一系列的涌现属性, 这些特征对生态系统功能至关重要。在此, 我们将介绍这一正蓬勃发展的研究领域的主要理论进展。首先, 叙述了自组织这一概念的发展历程与定义, 详细阐述了自组织理论的两个经典理论框架: 图灵原理与相分离原理。然后, 根据几个典型的生态自组织研究案例, 描述了图灵原理与相分离原理在不同生态系统中的具体数学模型表达形式。接着, 分别阐述了图灵原理的涌现属性对生态系统功能以及相分离原理的涌现属性对细胞功能的作用。最后, 从多尺度自组织斑图、瞬态斑图和生物个体行为自组织3个方面对未来生态自组织理论发展方向进行了探讨。自组织研究在生态学与生物学研究中方兴未艾, 希望更多的学者在未来关注与参与该领域的发展。     

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).     

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.     

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.     

More than the sum of their parts: on the evolution of proteins from peptides

Despite their seemingly endless diversity, proteins adopt a limited number of structural forms. It has been estimated that 80% of proteins will be found to adopt one of only about 400 folds, most of which are already known. These folds are largely formed by a limited 'vocabulary' of recurring supersecondary structure elements, often by repetition of the same element and, increasingly, elements similar in both structure and sequence are discovered. This suggests that modern proteins evolved by fusion and recombination from a more ancient peptide world and that many of the core folds observed today may contain homologous building blocks. The peptides forming these building blocks would not in themselves have had the ability to fold, but would have emerged as cofactors supporting RNA-based replication and catalysis (the 'RNA world'). Their association into larger structures and eventual fusion into polypeptide chains would have allowed them to become independent of their RNA scaffold, leading to the evolution of a novel type of macromolecule: the folded protein.