Showing 341 - 350 of 722 Items

Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates

Date: 2007-10-01

Creator: Alix Coste

Anna Selmecki

Anja Forche

Dorothée Diogo

Marie Elisabeth, Bougnoux

Christophe D'Enfert

Judith Berman

Dominique Sanglard

Access: Open access

TAC1 (for transcriptional activator of CDR genes) is critical for the upregulation of the ABC transporters CDR1 and CDR2, which mediate azole resistance in Candida albicans. While a wild-type TAC1 allele drives high expression of CDR1/2 in response to inducers, we showed previously that TAC1 can be hyperactive by a gain-of-function (GOF) point mutation responsible for constitutive high expression of CDR1/2. High azole resistance levels are achieved when C. albicans carries hyperactive alleles only as a consequence of loss of heterozygosity (LOH) at the TAC1 locus on chromosome 5 (Chr 5), which is linked to the mating-type-like (MTL) locus. Both are located on the Chr 5 left arm along with ERG11 (target of azoles). In this work, five groups of related isolates containing azole-susceptible and -resistant strains were analyzed for the TAC1 and ERG11 alleles and for Chr 5 alterations. While recovered ERG11 alleles contained known mutations, 17 new TAC1 alleles were isolated, including 7 hyperactive alleles with five separate new GOF mutations. Single-nucleotide- polymorphism analysis of Chr 5 revealed that azole-resistant strains acquired TAC1 hyperactive alleles and, in most cases, ERG11 mutant alleles by LOH events not systematically including the MTL locus. TAC1 LOH resulted from mitotic recombination of the left arm of Chr 5, gene conversion within the TAC1 locus, or the loss and reduplication of the entire Chr 5. In one case, two independent TAC1 hyperactive alleles were acquired. Comparative genome hybridization and karyotype analysis revealed the presence of isochromosome 5L [i(5L)] in two azole-resistant strains. i(5L) leads to increased copy numbers of azole resistance genes present on the left arm of Chr 5, among them TAC1 and ERG11. Our work shows that azole resistance was due not only to the presence of specific mutations in azole resistance genes (at least ERG11 and TAC1) but also to their increase in copy number by LOH and to the addition of extra Chr 5 copies. With the combination of these different modifications, sophisticated genotypes were obtained. The development of azole resistance in C. albicans is therefore a powerful instrument for generating genetic diversity. Copyright © 2007, American Society for Microbiology. All Rights Reserved.


The Issue Focus of Online and Television Advertising in the 2016 Presidential Campaign

Date: 2020-01-01

Creator: Michael M. Franz

Erika Franklin Fowler

Travis Ridout

Meredith Yiran Wang

Access: Open access

Theories of campaign issue emphasis were developed in a pre-digital era. How well do these theories explain spending in the current era, when digital media allow for targeting of specific types of voters? In this research, we compare how the 2016 campaigns, both primary and general election, deployed television advertising with how they deployed online advertising. We suggest that, because online messages are targeted to specific viewer profiles much more than television messages, television ads should be more likely to discuss highly salient issues and valance issues than online ads. To test these ideas, we rely upon data from the Wesleyan Media Project, which tracked all televised political ads that aired in 2016, and our coding of data from Pathmatics, a company that tracks online advertising. We find, contrary to our expectations, that the predictors of issue discussion online and on television are largely similar.


IR divergences and Regge limits of subleading-color contributions to the four-gluon amplitude in N=4 SYM theory

Date: 2009-11-11

Creator: Stephen G. Naculich

Howard J. Schnitzer

Access: Open access

We derive a compact all-loop-order expression for the IR-divergent part of the = 4 SYM four-gluon amplitude, which includes both planar and all subleading-color contributions, based on the assumption that the higher-loop soft anomalous dimension matrices are proportional to the one-loop soft anomalous dimension matrix, as has been recently conjectured. We also consider the Regge limit of the four-gluon amplitude, and we present evidence that the leading logarithmic growth of the subleading-color amplitudes is less severe than that of the planar amplitudes. We examine possible 1/N 2 corrections to the gluon Regge trajectory, previously obtained in the planar limit from the BDS ansatz. The double-trace amplitudes have Regge behavior as well, with a nonsense-choosing Regge trajectory and a Regge cut which first emerges at three loops. © SISSA 2009.


Flow around phoronids: Consequnces of a neighbor to suspension feeders

Date: 1990-01-01

Creator: Amy S. Johnson

Access: Open access

This article is in Free Access Publication and may be downloaded using the “Download Full Text PDF” link at right. © 1990, by the Association for the Sciences of Limnology and Oceanography, Inc.


Mutation of an Arabidopsis Golgi membrane protein ELMO1 reduces cell adhesion

Date: 2021-05-01

Creator: Bruce D. Kohorn

Frances D.H. Zorensky

Jacob Dexter-Meldrum

Salem Chabout

Gregory, Mouille

Susan Kohorn

Access: Open access

Plant growth, morphogenesis and development involve cellular adhesion, a process dependent on the composition and structure of the extracellular matrix or cell wall. Pectin in the cell wall is thought to play an essential role in adhesion, and its modification and cleavage are suggested to be highly regulated so as to change adhesive properties. To increase our understanding of plant cell adhesion, a population of ethyl methanesulfonate-mutagenized Arabidopsis were screened for hypocotyl adhesion defects using the pectin binding dye Ruthenium Red that penetrates defective but not wild-type (WT) hypocotyl cell walls. Genomic sequencing was used to identify a mutant allele of ELMO1 which encodes a 20 kDa Golgi membrane protein that has no predicted enzymatic domains. ELMO1 colocalizes with several Golgi markers and elmo1-/- plants can be rescued by an ELMO1-GFP fusion. elmo1-/- exhibits reduced mannose content relative to WT but no other cell wall changes and can be rescued to WT phenotype by mutants in ESMERALDA1, which also suppresses other adhesion mutants. elmo1 describes a previously unidentified role for the ELMO1 protein in plant cell adhesion.


Semantic and perceptual effects on recognition memory: Evidence from ERP

Date: 2009-08-04

Creator: Erika Nyhus

Tim Curran

Access: Open access

The present experiments examined how semantic vs. perceptual encoding and perceptual match affect the processes involved in recognition memory. Experiment 1 examined the effects of encoding task and perceptual match between study and test fonts on recognition discrimination for words. Font fan was used to determine the effect of distinctiveness on perceptual match. The semantic encoding task and perceptual match for distinctive items led to better recognition memory. Event-related brain potentials (ERPs) recorded from the human scalp during recognition memory experiments have revealed differences between old (studied) and new (not studied) items that are thought to reflect the activity of memory-related brain processes. In Experiment 2, the semantic encoding task and perceptual match for distinctive words led to better recognition memory by acting on both familiarity and recollection processes, as purportedly indexed by the FN400 and parietal old/new effects. Combined these results suggest that the semantic encoding task and perceptual match for distinctive items aid recognition memory by acting on both familiarity and recollection processes. © 2009 Elsevier B.V. All rights reserved.


Regge behavior of gluon scattering amplitudes in N = 4 SYM theory

Date: 2008-05-01

Creator: Stephen G. Naculich

Howard J. Schnitzer

Access: Open access

It is shown that the four-gluon scattering amplitude for N = 4 supersymmetric Yang-Mills theory in the planar limit can be written, in both the weak- and strong-coupling limits, as a reggeized amplitude, with a parent trajectory and an infinite number of daughter trajectories. This result is not evident a priori, and relies crucially on the fact that the leading IR-divergence and the finite log2 (s / t)-dependent piece of the amplitude are characterized by the same function for all values of the coupling, as conjectured by Bern, Dixon, and Smirnov, and proved by Alday and Maldacena in the strong-coupling limit. We use the Alday-Maldacena result to determine the exact strong-coupling Regge trajectory. © 2007 Elsevier B.V. All rights reserved.


Rapid phenotypic and genotypic diversification after exposure to the oral host niche in candida albicans

Date: 2018-07-01

Creator: Anja Forche

Gareth Cromie

Aleeza C. Gerstein

Norma V. Solis

Tippapha, Pisithkul

Waracharee Srifa

Eric Jeffery

Darren Abbey

Scott G. Filler

Aimée M. Dudley

Judith Berman

Access: Open access

In vitro studies suggest that stress may generate random standing variation and that different cellular and ploidy states may evolve more rapidly under stress. Yet this idea has not been tested with pathogenic fungi growing within their host niche in vivo. Here, we analyzed the generation of both genotypic and phenotypic diversity during exposure of Candida albicans to the mouse oral cavity. Ploidy, aneuploidy, loss of heterozygosity (LOH), and recombination were determined using flow cytometry and double digest restriction site-associated DNA sequencing. Colony phenotypic changes in size and filamentous growth were evident without selection and were enriched among colonies selected for LOH of the GAL1 marker. Aneuploidy and LOH occurred on all chromosomes (Chrs), with aneuploidy more frequent for smaller Chrs and whole Chr LOH more frequent for larger Chrs. Large genome shifts in ploidy to haploidy often maintained one or more heterozygous disomic Chrs, consistent with random Chr missegregation events. Most isolates displayed several different types of genomic changes, suggesting that the oral environment rapidly generates diversity de novo. In sharp contrast, following in vitro propagation, isolates were not enriched for multiple LOH events, except in those that underwent haploidization and/or had high levels of Chr loss. The frequency of events was overall 100 times higher for C. albicans populations following in vivo passage compared with in vitro. These hyper-diverse in vivo isolates likely provide C. albicans with the ability to adapt rapidly to the diversity of stress environments it encounters inside the host.


Polar firn air reveals large-scale impact of anthropogenic mercury emissions during the 1970s

Date: 2009-09-22

Creator: Xavier Faïn

Christophe P. Ferrari

Aurélien Dommergue

Mary R. Albert

Mark, Battle

Jeff Severinghaus

Laurent Arnaud

Jean Marc Barnola

Warren Cairns

Carlo Barbante

Claude Boutron

Access: Open access

Mercury (Hg) is an extremely toxic pollutant, and its biogeochemical cycle has been perturbed by anthropogenic emissions during recent centuries. In the atmosphere, gaseous elemental mercury (GEM; Hg°) is the predominant form of mercury (up to 95%). Here we report the evolution of atmospheric levels of GEM in mid- to high-northern latitudes inferred from the interstitial air of firn (perennial snowpack) at Summit, Greenland. GEM concentrations increased rapidly after World War II from ≈1.5 ng m-3 reaching a maximum of ≈3 ng m-3 around 1970 and decreased until stabilizing at ≈1.7 ng m -3 around 1995. This reconstruction reproduces real-time measurements available from the Arctic since 1995 and exhibits the same general trend observed in Europe since 1990. Anthropogenic emissions caused a two-fold rise in boreal atmospheric GEM concentrations before the 1970s, which likely contributed to higher deposition of mercury in both industrialized and remotes areas. Once deposited, this toxin becomes available for methylation and, subsequently, the contamination of ecosystems. Implementation of air pollution regulations, however, enabled a large-scale decline in atmospheric mercury levels during the 1980s. The results shown here suggest that potential increases in emissions in the coming decades could have a similar large-scale impact on atmospheric Hg levels.


The state of cell wall pectin monitored by wall associated kinases: A model

Date: 2015-07-03

Creator: Bruce D. Kohorn

Access: Open access

The Wall Associated Kinases (WAKs) bind to both cross-linked polymers of pectin in the plant cell wall, but have a higher affinity for smaller fragmented pectins that are generated upon pathogen attack or wounding. WAKs are required for cell expansion during normal seedling development and this involves pectin binding and a signal transduction pathway involving MPK3 and invertase induction. Alternatively WAKs bind pathogen generated pectin fragments to activate a distinct MPK6 dependent stress response. Evidence is provided for a model for how newly generated pectin fragments compete for longer pectins to alter the WAK dependent responses.