Roles of ADF/cofilin in actin polymerization and beyond

In collaboration or competition with many other actin-binding proteins, the actin-depolymerizing factor/cofilins integrate transmembrane signals to coordinate the spatial and temporal organization of actin filament assembly/disassembly (dynamics). In addition, newly discovered effects of these proteins in lipid metabolism, gene regulation, and apoptosis suggest that their roles go well beyond regulating the cytoskeleton

11/20/1945 C

Letter to father from Sumner T. Bernstein\u27s sister Helen passing along Sumner\u27s birthday wishes.https://digitalcommons.usm.maine.edu/sbernstein_correspondence/1143/thumbnail.jp

Detection and quantification of flow consistency in business process models

Business process models abstract complex business processes by representing them as graphical models. Their layout, as determined by the modeler, may have an effect when these models are used. However, this effect is currently not fully understood. In order to systematically study this effect, a basic set of measurable key visual features is proposed, depicting the layout properties that are meaningful to the human user. The aim of this research is thus twofold: first, to empirically identify key visual features of business process models which are perceived as meaningful to the user and second, to show how such features can be quantified into computational metrics, which are applicable to business process models. We focus on one particular feature, consistency of flow direction, and show the challenges that arise when transforming it into a precise metric. We propose three different metrics addressing these challenges, each following a different view of flow consistency. We then report the results of an empirical evaluation, which indicates which metric is more effective in predicting the human perception of this feature. Moreover, two other automatic evaluations describing the performance and the computational capabilities of our metrics are reported as well

Charge Reduction: An Intermediary Stage in the Process of Labelling Criminal Defendants

The interactionist perspective emphasizes the imperfect correspondence between alleged deviance and societal reactions. Moreover, it is asserted that values of reactors, statuses of the alleged deviant, and bureaucratic constraints of deviance processing organizations help explain some of that imperfection. Focusing on one intermediary deviance processing stage, i.e., plea bargaining, we explore the degree to which our data are consonant with interactionist assumptions. For a sample of 1,435 male and female criminal defendants, we find the favorability of the charge reduction outcome is partly explained by values of reactors, statuses of the defendant, and bureaucratic constraints of the court. Thus, our data are supportive of the general thrust of interactionist works. However, the relative size of each of these effects suggests that reformulations of that perspective should attend to the finding that ascribed statuses play far less of a determinative role, and organizational goals seem to play a more determinative role, suggesting that greater attention be paid to organizational variables

PLoS Biology—We're Open

With this first issue of PLoS Biology, the editors present the aims and scope of the journa

Density of the Notch ligand Delta1 determines generation of B and T cell precursors from hematopoietic stem cells

Notch signaling regulates multiple cell fate decisions by hematopoietic precursors. To address whether different amounts of Notch ligand influence lineage choices, we cultured murine bone marrow lin−Sca-1+c-kit+ cells with increasing densities of immobilized Delta1ext-IgG consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG1. We found that relatively lower densities of Delta1ext-IgG enhanced the generation of Sca-1+c-kit+ cells, Thy1+CD25+ early T cell precursors, and B220+CD43−/lo cells that, when cocultured with OP9 stroma cells, differentiated into CD19+ early B cell precursors. Higher densities of Delta1ext-IgG also enhanced the generation of Sca-1+c-kit+ precursor cells and promoted the development of Thy1+CD25+ cells, but inhibited the development of B220+CD43−/lo cells. Analyses of further isolated precursor populations suggested that the enhanced generation of T and B cell precursors resulted from the effects on multipotent rather than lymphoid-committed precursors. The results demonstrate the density-dependent effects of Delta1 on fate decisions of hematopoietic precursors at multiple maturational stages and substantiate the previously unrecognized ability of Delta1 to enhance the development of both early B and T precursor cells

Defining early steps in <i>Bacillus subtilis</i> biofilm biosynthesis

ABSTRACT The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide (EPS) that is critical for the architecture and function of the community. To date, our understanding of the biosynthetic machinery and the molecular composition of the EPS of B. subtilis remains unclear and incomplete. This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the EPS biosynthetic pathway. By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm EPS biosynthetic pathway. EpsL catalyzes the first phosphoglycosyl transferase step using uridine diphosphate (UDP)-di-N-acetyl bacillosamine as phospho-sugar donor. EpsD is a predicted GT-B fold (GT4 family) retaining glycosyl transferase that catalyzes the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP-N-acetyl glucosamine as the sugar donor. Thus, the study defines the first two monosaccharides at the reducing end of the growing EPS unit. In doing so, we provide the first evidence of the presence of bacillosamine in an EPS synthesized by a Gram-positive bacterium. IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. Here, we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide (EPS) synthesis pathway. Together, our studies and approaches provide the foundation for the sequential characterization of the steps in EPS biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenyl diphosphate-linked glycan substrates

Expression of Retina-Specific Genes by Mouse Retinoblastoma Cells

Purpose. Two cell lines derived from ocular tumors of a transgenic mouse expressing the SV40 large T antigen have been established as models of human retinoblastoma. One line, TM, originated from a metastasis, and the other, TE, originated from the primary tumor. The authors compared these two lines with the normal adult mouse eye by analysis of the expression of five photoreceptor cell-specific proteins: IRBP, opsin, rod-and cone-specific transducins, and S-antigen. The authors sought to determine which of these proteins was expressed qualitatively and to examine semi-quantitatively for changes in the levels of expression in the cell lines. Method. Western blot analysis was used to detect photoreceptor-specific intracellular or secreted proteins. Total RNA was prepared from cultured cells or from mouse adult whole eye. Specific messenger levels in total RNA were determined either by northern hybridization analysis or by a semi-quantitative polymerase chain reaction (PCR), coupled to complementary DNA (cDNA) substrates prepared from total RNA. Results. IRBP was present in the retinoblastoma cell lines and secreted into the medium. Neither S-antigen nor opsin were detectable by immunoblotting. IRBP and cone transducin mRNA were present in both cell lines. In contrast, opsin, rod transducin, and S-Antigen mRNAs were not detectable by PCR. /3-actin was present in the mRNA populations of whole eye and retinoblastoma. SV40 large T antigen mRNA was present only in retinoblastoma cells. Conclusions. IRBP and cone transducin expression in mouse retinoblastoma cells is independent of signaling provided direcdy or indirecdy dirough large T antigen or Rb ]0 5 regulatory cascades. The pattern of photoreceptor-specific gene expression is similar to that seen in human retinoblastoma cell lines. These murine-derived cell lines may be useful as a tool to study IRBP and cone transducin expression in vitro and to determine early retinoblast expression patterns in the mouse. Invest Ophthalmol Vis Sci. 1994;35:3931-3937. J. he sequence of events in visual transduction and retinal development involves a series of proteins, many of which are expressed in the photoreceptor cells

Defining functional DNA elements in the human genome

With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease

Mathematical images in advertising: constructing difference and shaping identity, in global consumer culture

Mathematics educators have long emphasised the importance of attitudes and feelings towards mathematics, as crucial in motivating (or not) its learning and use, and as influenced in turn by its social images. This paper is about images of mathematics. Our search for advertisements containing such images of in UK daily newspapers, during 2006-2008, found that 4.7% of editions included a ‘mathematical’ advert, compared with 1.7% in pilot work for 1994-2003. The incidence varied across type of newspaper, being correlated with class and gender profiles of the readership. Three-quarters of advertisements were classified as containing only very simple mathematics. ‘Semiotic-discursive’ analysis of selected advertisements suggests that they draw on mathematics not to inform, but to connote qualities like precision, certainty and authority. We discuss the discourse on mathematics in advertising as ‘quasi-pedagogic’ discourse, and argue that its oversimplified forms, being empty of mathematical content, become powerful means for regulating and ‘pedagogising’ today’s global consumers