NIA

1 The effect of winter temperature and forest susceptibility on the rate of gypsy moth Lymantria dispar (L.) range expansion in the lower peninsula of Michigan was analysed using historical data on moth counts in a grid of pheromone-baited traps collected from 1985 to 1994 by the Michigan Department of Agriculture. The rate of spread was measured by the distance between population boundaries in consecutive years. Boundaries were estimated for population thresholds of 1, 3, 10, 30, and 100 moths per trap using a polar coordinate system. 2 The average rate of spread estimated using all population thresholds was 15.8 km/yr. 3 The rate of spread was higher in the northern part of the lower peninsula than in the southern part, despite lower minimum January temperatures in the north. 4 The rate of spread was positively correlated with forest susceptibility, which was higher in the north than in the south.

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf 2/2 embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf 2/2 embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo.

Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show that fusion proteins containing the coding sequence of Oct4 or Xlpou91 (the Xenopus homolog of Oct4) fused to activating regions, but not those fused to repressing regions, behave as Oct4, suppressing differentiation and promoting maintenance of undifferentiated phenotypes in vivo and in vitro. An Oct4 activation domain fusion supported embryonic stem cell self-renewal in vitro at lower concentrations than that required for Oct4 while alleviating the ordinary requirement for the cytokine LIF. At still lower levels of the fusion, LIF dependence was restored. We conclude that the necessary and sufficient function of Oct4 in promoting pluripotency is to activate specific t...

In contrast to the traditional relational semiotics, biosemiotics decisively deviates towards dynamical aspects of signs at the evolutionary and developmental time scales. The analysis of sign dynamics requires constructivism (in a broad sense) to explain how new components such as subagents, sensors, effectors, and interpretation networks are produced by developing and evolving organisms. Semiotic networks that include signs, tools, and subagents are multilevel, and this feature supports the plasticity , robustness, and evolvability of organisms. The origin of life is described here as the emergence of simple self-constructing semiotic networks that progressively increased the diversity of their components and relations. Primitive organisms have no capacity to classify and track objects; thus, we need to admit the existence of proto-signs that directly regulate activities of agents without being associated with objects. However, object recognition and handling became possible in eukaryotic species with the development of extensive rewritable epigenetic memory as well as sensorial and effector capacities. Semiotic networks are based on sequential and recursive construction, where each step produces components (i.e., agents, scaffolds, signs, and resources) that are needed for the following steps of construction. Construction is not limited to repair and reproduction of what already exists or is unambiguously encoded, it also includes production of new components and behaviors via learning and evolution. A special case is the emergence of new levels of organization known as metasystem transition. Multilevel semiotic networks reshape the phenotype of organisms by combining a mosaic of features developed via learning and evolution of cooperating and/or conflicting subagents.

A B S T R A C T In the era of the extended evolutionary synthesis, which no longer considers natural selection as the only leading factor of evolution, it is meaningful to revisit the legacy of biologists who discussed the role of alternative factors. Here we analyze the evolutionary views of Sergei Meyen (1935–1987), a paleobotanist who argued that the theory of evolution should incorporate a " nomothetical " approach which infers the laws of morphogenesis (i.e., form generation) from the observed patterns of variation in living organisms and in the fossil records. Meyen developed a theory of " repeated polymorphic sets " (RPSs), which he applied consistently to describe inter-organism variation in populations, intra-organism variation of metameric organs, variation of abnormalities, heterotopy, changes during embryo development, and inter-species variation within evolutionary lineages. The notion of RPS assumes the active nature of organisms that possess hidden morphogenic and behavioral capacities. Meyen's theory is compatible with Darwin's natural selection; however, Meyen emphasized the importance of other forms of selection (e.g., selection of developmental trajectories, habitats, and behaviors) in choosing specific elements from the RPS. Finally, Meyen developed a new typological concept of time, where time represents variability (i.e., change) of real objects such as living organisms or geological formations.

Transcription factors (TFs) bind to DNA and regulate the transcription of nearby genes. However, only a small fraction of TF binding sites have such regulatory effects. Here we search for the predictors of functional binding sites by carrying out a systematic computational screening of a variety of contextual factors (histone modifications, nuclear lamin-bindings, and cofactor bindings). We used regression analysis to test if contextual factors are associated with upregulation or downregulation of neighboring genes following the induction or knockdown of the 9 TFs in mouse embryonic stem (ES) cells. Functional TF binding sites appeared to be either active (i.e., bound by P300, CHD7, mediator, cohesin, and SWI/ SNF) or repressed (i.e., with H3K27me3 histone marks and bound by Polycomb factors). Active binding sites mediated the downregulation of nearby genes upon knocking down the activating TFs or inducing repressors. Repressed TF binding sites mediated the upregula-tion of nearby genes (e.g., poised developmental regulators) upon inducing TFs. In addition, repressed binding sites mediated repressive effects of TFs, identified by the downregulation of target genes after the induction of TFs or by the upregulation of target genes after the knockdown of TFs. The contextual factors associated with functions of DNA-bound TFs were used to improve the identification of candidate target genes regulated by TFs.

Functional information means an encoded network of functions in living organisms from molecular signaling pathways to an organism's behavior. It is represented by two components: code and an interpretation system, which together form a self-sustaining semantic closure. Semantic closure allows some freedom between components because small variations of the code are still interpretable. The interpretation system consists of inference rules that control the correspondence between the code and the function (phenotype) and determines the shape of the fitness landscape. The utility factor operates at multiple time scales: short-term selection drives evolution towards higher survival and reproduction rate within a given fitness landscape, and long-term selection favors those fitness landscapes that support adaptability and lead to evolutionary expansion of certain lineages. Inference rules make short-term selection possible by shaping the fitness landscape and defining possible directions of evolution, but they are under control of the long-term selection of lineages. Communication normally occurs within a set of agents with compatible interpretation systems, which I call communication system. Functional information cannot be directly transferred between communication systems with incompatible inference rules. Each biological species is a genetic communication system that carries unique functional information together with inference rules that determine evolutionary directions and constraints. This view of the relation between utility and inference can resolve the conflict between realism/positivism and pragmatism. Realism overemphasizes the role of inference in evolution of human knowledge because it assumes that logic is embedded in reality. Pragmatism substitutes usefulness for truth and therefore ignores the advantage of inference. The proposed concept of evolutionary pragmatism rejects the idea that logic is embedded in reality; instead, inference rules are constructed within each communication system to represent reality, and they evolve towards higher adaptability on a long time scale.

Background: The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution.

To examine transcription factor (TF) network(s), we created mouse ES cell lines, in each of which one of 50 TFs tagged with a FLAG moiety is inserted into a ubiquitously controllable tetracyclinerepressible locus. Of the 50 TFs, Cdx2 provoked the most extensive transcriptome perturbation in ES cells, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of up-regulated target genes. By contrast, genes down-regulated by CDX2 did not show CDX2 binding, but were enriched with binding sites for POU5F1, SOX2, and NANOG. Genes with binding sites for these core TFs were also down-regulated by the induction of at least 15 other TFs, suggesting a common initial step for ES cell differentiation mediated by interference with the binding of core TFs to their target genes. These ES cell lines provide a fundamental resource to study biological networks in ES cells and mice.