Evolutionary Events in a Mathematical Sciences Research Collaboration Network

This study examines long-term trends and shifting behavior in the collaboration network of mathematics literature, using a subset of data from Mathematical Reviews spanning 1985-2009. Rather than modeling the network cumulatively, this study traces the evolution of the "here and now" using fixed-duration sliding windows. The analysis uses a suite of common network diagnostics, including the distributions of degrees, distances, and clustering, to track network structure. Several random models that call these diagnostics as parameters help tease them apart as factors from the values of others. Some behaviors are consistent over the entire interval, but most diagnostics indicate that the network's structural evolution is dominated by occasional dramatic shifts in otherwise steady trends. These behaviors are not distributed evenly across the network; stark differences in evolution can be observed between two major subnetworks, loosely thought of as "pure" and "applied", which approximately partition the aggregate. The paper characterizes two major events along the mathematics network trajectory and discusses possible explanatory factors.Comment: 30 pages, 14 figures, 1 table; supporting information: 5 pages, 5 figures; published in Scientometric

Synthesis and antibacterial activities of marine natural product ianthelliformisamines and subereamine synthetic analogues

Marine sponges of the genus Suberea produce variety of brominated tyrosine alkaloids which display diverse range of biological activities including antiproliferative, antimicrobial and antimalarial activities. In continuation of our search for biologically active marine natural products for antibacterial compounds, we report here the synthesis and evaluation of biological activity of panel of ianthelliformisamines and subereamine analogues using the literature known acid-amine coupling reaction. Several derivatives of Ianthelliformisamine were achieved by the coupling of Boc-protected polyamine chain with brominated aromatic acrylic acid derivatives by varying the bromine substituents on aromatic acid derivatives, amine spacer as well as geometry of the double bond, and then Boc-deprotection using TFA. Similarly, subereamine analogues were also synthesized employing coupling reaction between various brominated phenyl acrylic acids with commercially available chiral amino ester derivatives followed by ester hydrolysis. We screened these synthetic analogues for antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. One of the compound 7c showed bactericidal activity against Staphylococcus aureus with an IC50 value of 3.8 μM (MIC = 25 μM)

Polarization of Diploid Daughter Cells Directed by Spatial Cues and GTP Hydrolysis of Cdc42 in Budding Yeast

<div><p>Cell polarization occurs along a single axis that is generally determined by a spatial cue. Cells of the budding yeast exhibit a characteristic pattern of budding, which depends on cell-type-specific cortical markers, reflecting a genetic programming for the site of cell polarization. The Cdc42 GTPase plays a key role in cell polarization in various cell types. Although previous studies in budding yeast suggested positive feedback loops whereby Cdc42 becomes polarized, these mechanisms do not include spatial cues, neglecting the normal patterns of budding. Here we combine live-cell imaging and mathematical modeling to understand how diploid daughter cells establish polarity preferentially at the pole distal to the previous division site. Live-cell imaging shows that daughter cells of diploids exhibit dynamic polarization of Cdc42-GTP, which localizes to the bud tip until the M phase, to the division site at cytokinesis, and then to the distal pole in the next G1 phase. The strong bias toward distal budding of daughter cells requires the distal-pole tag Bud8 and Rga1, a GTPase activating protein for Cdc42, which inhibits budding at the cytokinesis site. Unexpectedly, we also find that over 50% of daughter cells lacking Rga1 exhibit persistent Cdc42-GTP polarization at the bud tip and the distal pole, revealing an additional role of Rga1 in spatiotemporal regulation of Cdc42 and thus in the pattern of polarized growth. Mathematical modeling indeed reveals robust Cdc42-GTP clustering at the distal pole in diploid daughter cells despite random perturbation of the landmark cues. Moreover, modeling predicts different dynamics of Cdc42-GTP polarization when the landmark level and the initial level of Cdc42-GTP at the division site are perturbed by noise added in the model.</p> </div

Ranges of parameters in the simulations.

<p>Ranges of parameters in the simulations.</p

Localization of Gic2-PBD-RFP and Cdc3-GFP in the diploids homozygous for <i>bud8Δ rga1Δ</i> and <i>bud8Δ</i>.

<p>Imaging was performed as in Fig. 4 except in <i>bud8Δ</i> (HPY2370) and <i>rga1Δ bud8Δ</i> (HPY2371) cells. Arrows denote the Cdc3 ring splitting and arrowheads denote Gic2-PBD-RFP enriched at the proximal pole. Note: Gic2-PBD-RFP became enriched at a site adjacent to the Cdc3 ring in the <i>bud8Δ</i> daughter cell, whereas it appeared within the Cdc3 ring in <i>rga1Δ bud8Δ</i> daughter cell. Numbers indicate times (in min) from the first image. Size bars, 3 µm.</p

Localization of Gic2-PBD-RFP and Cdc3-GFP in <i>rga1Δ</i> cells.

<p><b>A.</b> In <i>rga1Δ</i> cells (HPY2204), Gic2-PBD-RFP localized continuously to (a) the proximal pole or (b) the distal pole from cytokinesis to the next G1 phase. Arrows in (a) & (b) denote the Cdc3 ring splitting and an arrowhead in (a) denotes Gic2-PBD-RFP enriched at the division site (as well as the bud tip). Numbers indicate times (in min) from the first image. Size bars, 3 µm. <b>B.</b> Localization pattern of Gic2-PBD-RFP (red) prior to, during, and after cytokinesis (Cdc3-GFP in green) is summarized from time-lapse imagings of wild type (n = 15), <i>rga1Δ</i> (n = 19), <i>bud8Δ</i> (n = 7) and <i>rga1Δ bud8Δ</i> (n = 8). The proximal-pole localization pattern (marked with 2*) of <i>rga1Δ</i> or <i>rga1Δ bud8Δ</i> daughter cells is different from those seen in wild type and <i>bud8Δ</i> cells (see text for details).</p

Mathematical modeling of Cdc42 polarization in diploid daughter cells deleted for <i>RGA1</i>, <i>BUD8</i> or <i>BUD9</i>.

<p><b>Aa.</b> Coordinates are the same as in Fig. 2 (wild type) but the GTP hydrolysis rate of Cdc42 in the <i>rga1Δ</i> mutant is assumed to be about the same along the perimeter. See parameters in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056665#pone-0056665-t002" target="_blank">Table 2</a>. <b>Ab–Ac.</b> Spatiotemporal dynamics of Cdc42-GTP leading to budding at (b) the proximal pole or (c) the distal pole in <i>rga1Δ</i> daughter cells. The horizontal axis represents the time window from 0 to 10 min. The 2D steady-state distribution of Cdc42-GTP is displayed on the right to each simulation. <b>B.</b> Spatiotemporal dynamics of Cdc42-GTP in diploid <i>bud8Δ</i> (top) and <i>bud9Δ</i> (bottom) mutants. The horizontal axis represents the time window from 0 to 20 min. The 2D steady-state distribution of Cdc42-GTP is displayed on the right to each simulation. Note: Cdc42-GTP became polarized at a site adjacent to the center of the proximal pole in <i>bud8Δ</i> (see 20 min time point), unlike in <i>rga1Δ</i> (see Fig. 7A, b).</p

Time-lapse microscopy of Cdc42-GTP polarization in wild-type a/α diploids.

<p><b>A.</b> A schematics diagram of the bipolar budding pattern. M and D stand for mother and daughter cells, respectively. Red arrows depict the axis of cell polarity. <b>B.</b> Localization of Gic2-PBD-RFP and Cdc3-GFP in diploid wild-type cells (HPY2353). An arrowhead marks Gic2-PBD-RFP localized to the proximal pole in the daughter cell. Numbers indicate time (in min) from the first image. Size bars, 3 µm.</p

Localization of Bud8 in large-budded cells of the wild type (HPY1680) and <i>rga1Δ</i> (HPY2205) carrying YEpGFP-BUD8F.

<p>Representative images are shown for each pattern (A-D) and the percentage (mean ± SD) of each pattern is shown from three independent experiments (n = 160–230). Student's t-test was performed to compare the distal-pole localization in wild type and <i>rga1Δ</i> (P = 0.006).</p

Specific parameters used for simulations.

<p>Specific parameters used for simulations.</p