Posttranscriptional regulation of Fas (CD95) ligand killing activity by lipid rafts

Fas (CD95/Apo-1) ligand-mediated apoptosis induction of target cells is one of the major effector mechanisms by which cytotoxic lymphocytes (T cells and natural killer cells) kill their target cells. In T cells, Fas ligand expression is tightly regulated at a transcriptional level through the activation of a distinct set of transcription factors. Increasing evidence, however, supports an important role for posttranscriptional regulation of Fas ligand expression and activity. Lipid rafts are cholesterol- and sphingolipid-rich membrane microdomains, critically involved in the regulation of membrane receptor signaling complexes through the clustering and concentration of signaling molecules. Here, we now provide evidence that Fas ligand is constitutively localized in lipid rafts of FasL transfectants and primary T cells. Importantly, disruption of lipid rafts strongly reduces the apoptosis-inducing activity of Fas ligand. Localization to lipid rafts appears to be predominantly mediated by the characteristic cytoplasmic proline-rich domain of Fas ligand because mutations of this domain result in reduced recruitment to lipid rafts and attenuated Fas ligand killing activity. We conclude that Fas ligand clustering in lipid rafts represents an important control mechanism in the regulation of T cell-mediated cytotoxicity.

A Concept of Semantics Extraction from Web Data by Induction of Fuzzy Ontologies

Traditionally, ontologies describe knowledge representation in a denotational, formalized, and deductive way. In addition, in this paper, we propose a semiotic, inductive, and approximate approach to ontology creation. We define a conceptual framework, a semantics extraction algorithm, and a first proof of concept applying the algorithm to a small set of Wikipedia documents. Intended as an extension to the prevailing top-down ontologies, we introduce an inductive fuzzy grassroots ontology, which organizes itself organically from existing natural language Web content. Using inductive and approximate reasoning to reflect the natural way in which knowledge is processed, the ontology’s bottom-up build process creates emergent semantics learned from the Web. By this means, the ontology acts as a hub for computing with words described in natural language. For Web users, the structural semantics are visualized as inductive fuzzy cognitive maps, allowing an initial form of intelligence amplification. Eventually, we present an implementation of our inductive fuzzy grassroots ontology Thus,this paper contributes an algorithm for the extraction of fuzzy grassroots ontologies from Web data by inductive fuzzy classification.

A stochastic principle behind polar properties of condensed molecular matter

A statistical mechanics view leads to the conclusion that polar molecules allowed to populate a degree of freedom for orientational disorder in a condensed phase thermalize into a bi-polar state featuring zero net polarity. In cases of orientational disorder polar order of condensed molecular matter can only exist in corresponding sectors of opposite average polarities. Channel type inclusion compounds, single component molecular crystals, solid solutions, optically anomalous crystals, inorganic ionic crystals, biomimetic crystals and biological tissues investigated by scanning pyroelectric and phase sensitive second harmonic generation microscopy all showed domains of opposite polarities in their final grown state. For reported polar molecular crystal structures it is assumed that kinetic hindrance along one direction of the polar axis is preventing the formation of a bi-polar state, thus allowing for a kinetically controlled mono-domain state. In this review we summarize theoretical and experimental findings leading to far reaching conclusions on the polar state of solid molecular matter. “… no stationary state … of a system has an electrical dipole moment.” P. W. Anderson, Science, 1972, 177, 393.

The Draft Assembly of the Radically Organized Stylonychia lemnae Macronuclear Genome.

Stylonychia lemnae is a classical model single-celled eukaryote, and a quintessential ciliate typified by dimorphic nuclei: A small, germline micronucleus and a massive, vegetative macronucleus. The genome within Stylonychia's macronucleus has a very unusual architecture, comprised variably and highly amplified "nanochromosomes," each usually encoding a single gene with a minimal amount of surrounding noncoding DNA. As only a tiny fraction of the Stylonychia genes has been sequenced, and to promote research using this organism, we sequenced its macronuclear genome. We report the analysis of the 50.2-Mb draft S. lemnae macronuclear genome assembly, containing in excess of 16,000 complete nanochromosomes, assembled as less than 20,000 contigs. We found considerable conservation of fundamental genomic properties between S. lemnae and its close relative, Oxytricha trifallax, including nanochromosomal gene synteny, alternative fragmentation, and copy number. Protein domain searches in Stylonychia revealed two new telomere-binding protein homologs and the presence of linker histones. Among the diverse histone variants of S. lemnae and O. trifallax, we found divergent, coexpressed variants corresponding to four of the five core nucleosomal proteins (H1.2, H2A.6, H2B.4, and H3.7) suggesting that these ciliates may possess specialized nucleosomes involved in genome processing during nuclear differentiation. The assembly of the S. lemnae macronuclear genome demonstrates that largely complete, well-assembled highly fragmented genomes of similar size and complexity may be produced from one library and lane of Illumina HiSeq 2000 shotgun sequencing. The provision of the S. lemnae macronuclear genome sets the stage for future detailed experimental studies of chromatin-mediated, RNA-guided developmental genome rearrangements.

There is more than "more is up": Hand and foot responses reverse the vertical association of number magnitudes

Recent research in cognitive sciences shows a growing interest in spatial-numerical associations. The horizontal SNARC (spatial-numerical association of response codes) effect is defined by faster left-sided responses to small numbers and faster right-sided responses to large numbers in a parity judgment task. In this study we investigated whether there is also a SNARC effect for upper and lower responses. The grounded cognition approach suggests that the universal experience of "more is up" serves as a robust frame of reference for vertical number representation. In line with this view, lower hand responses to small numbers were faster than to large numbers (Experiment 1). Interestingly, the vertical SNARC effect reversed when the lower responses were given by foot instead of the hand (Experiments 2, 3, and 4). We found faster upper (hand) responses to small numbers and faster lower (foot) responses to large numbers. Additional experiments showed that spatial factors cannot account for the reversal of the vertical SNARC effect (Experiments 4 and 5). Our results question the view of "more is up" as a robust frame of reference for spatial-numerical associations. We discuss our results within a hierarchical framework of numerical cognition and point to a possible link between effectors and number representation.