Nonlinear Bias and the Convective Fisher Equation

We combine random walks, growth and decay, and convection, in a Monte Carlo simulation to model 1D interface dynamics with fluctuations. The continuum limit corresponds to the deterministic Fisher equation with convection. We find qualitatively the same type of asymmetry, as well as velocity difference, for interface profiles moving in opposite directions. However a transition apparent in the mean-field (continuum) limit is not found in the Monte Carlo simulation.Comment: 2.5 pages (texed) with 4 postscript figures, TeX 3.14t

A Model for Using a Concept Inventory as a Tool for Students' Assessment and Faculty Professional Development

This essay describes how the use of a concept inventory has enhanced professional development and curriculum reform efforts of a faculty teaching community. The Host Pathogen Interactions (HPI) teaching team is composed of research and teaching faculty with expertise in HPI who share the goal of improving the learning experience of students in nine linked undergraduate microbiology courses. To support evidence-based curriculum reform, we administered our HPI Concept Inventory as a pre- and postsurvey to approximately 400 students each year since 2006. The resulting data include student scores as well as their open-ended explanations for distractor choices. The data have enabled us to address curriculum reform goals of 1) reconciling student learning with our expectations, 2) correlating student learning with background variables, 3) understanding student learning across institutions, 4) measuring the effect of teaching techniques on student learning, and 5) demonstrating how our courses collectively form a learning progression. The analysis of the concept inventory data has anchored and deepened the team's discussions of student learning. Reading and discussing students' responses revealed the gap between our understanding and the students' understanding. We provide evidence to support the concept inventory as a tool for assessing student understanding of HPI concepts and faculty development

Polyphasic taxonomy of Aspergillus section Candidi based on molecular, morphological and physiological data

Aspergillus section Candidi historically included a single white-spored species, A. candidus. Later studies clarified that other species may also belong to this section. In this study, we examined isolates of species tentatively assigned to section Candidi using a polyphasic approach. The characters examined include sequence analysis of partial β-tubulin, calmodulin and ITS sequences of the isolates, morphological and physiological tests, and examination of the extrolite profiles. Our data indicate that the revised section Candidi includes 4 species: A. candidus, A. campestris, A. taichungensis and A. tritici. This is strongly supported by all the morphological characteristics that are characteristic of section Candidi: slow growing colonies with globose conidial heads having white to yellowish conidia, conidiophores smooth, small conidiophores common, metulae present and covering the entire vesicle, some large Aspergillus heads with large metulae, presence of diminutive heads in all species, conidia smooth or nearly so with a subglobose to ovoid shape, and the presence of sclerotia in three species (A. candidus, A. taichungensis and A. tritici). Aspergillus tritici has been suggested to be the synonym of A. candidus previously, however, sequence data indicate that this is a valid species and includes isolates came from soil, wheat grain, flour and drums from India, Ghana, Sweden, The Netherlands and Hungary, making it a relatively widespread species. All species produce terphenyllins and candidusins and three species (A. candidus, A. campestris and A. tritici) produce chlorflavonins. Xanthoascins have only been found in A. candidus. Each of the species in section Candidi produce several other species specific extrolites, and none of these have been found in any other Aspergillus species. A. candidus has often been listed as a human pathogenic species, but this is unlikely as this species cannot grow at 37 °C. The pathogenic species may be A. tritici or white mutants of Aspergillus flavus

SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum

Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV), replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs) were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200–300 nm), and “vesicle packets” apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this “replication network” will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions

Toll-Like Receptor 3 (TLR3) Plays a Major Role in the Formation of Rabies Virus Negri Bodies

Human neurons express the innate immune response receptor, Toll-like receptor 3 (TLR3). TLR3 levels are increased in pathological conditions such as brain virus infection. Here, we further investigated the production, cellular localisation, and function of neuronal TLR3 during neuronotropic rabies virus (RABV) infection in human neuronal cells. Following RABV infection, TLR3 is not only present in endosomes, as observed in the absence of infection, but also in detergent-resistant perinuclear inclusion bodies. As well as TLR3, these inclusion bodies contain the viral genome and viral proteins (N and P, but not G). The size and composition of inclusion bodies and the absence of a surrounding membrane, as shown by electron microscopy, suggest they correspond to the previously described Negri Bodies (NBs). NBs are not formed in the absence of TLR3, and TLR3−/− mice—in which brain tissue was less severely infected—had a better survival rate than WT mice. These observations demonstrate that TLR3 is a major molecule involved in the spatial arrangement of RABV–induced NBs and viral replication. This study shows how viruses can exploit cellular proteins and compartmentalisation for their own benefit

Nuclear Kaiso Expression Is Associated with High Grade and Triple-Negative Invasive Breast Cancer

Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023), ERα negativity (p = 0.001), and the HER2-driven and basal/triple-negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC

Two Estrogen Response Element Sequences Near the PCNA Gene Are Not Responsible for Its Estrogen-Enhanced Expression in MCF7 Cells

The proliferating cell nuclear antigen (PCNA) is an essential component of DNA replication, cell cycle regulation, and epigenetic inheritance. High expression of PCNA is associated with poor prognosis in patients with breast cancer. The 5'-region of the PCNA gene contains two computationally-detected estrogen response element (ERE) sequences, one of which is evolutionarily conserved. Both of these sequences are of undocumented cis-regulatory function. We recently demonstrated that estradiol (E2) enhances PCNA mRNA expression in MCF7 breast cancer cells. MCF7 cells proliferate in response to E2.Here, we demonstrate that E2 rapidly enhanced PCNA mRNA and protein expression in a process that requires ERalpha as well as de novo protein synthesis. One of the two upstream ERE sequences was specifically bound by ERalpha-containing protein complexes, in vitro, in gel shift analysis. Yet, each ERE sequence, when cloned as a single copy, or when engineered as two tandem copies of the ERE-containing sequence, was not capable of activating a luciferase reporter construct in response to E2. In MCF7 cells, neither ERE-containing genomic region demonstrated E2-dependent recruitment of ERalpha by sensitive ChIP-PCR assays.We conclude that E2 enhances PCNA gene expression by an indirect process and that computational detection of EREs, even when evolutionarily conserved and when near E2-responsive genes, requires biochemical validation