Holographic Charge Density Waves

We discuss a gravity dual of a charge density wave consisting of a U(1) gauge field and two scalar fields in the background of an AdS$_4$ Schwarzschild black hole together with an antisymmetric field (probe limit). Interactions drive the system to a phase transition below a critical temperature. We numerically compute the ground states characterized by modulated solutions for the gauge potential corresponding to a dynamically generated unidirectional charge density wave in the conformal field theory. Signatures of the holographic density waves are retrieved by studying the dynamical response to an external electric field. We find that this novel holographic state shares many common features with the standard condensed matter version of charge density wave systems.Comment: 5 pages, 2 figures; improved discussion, published versio

Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (∼1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as “probe compounds” and may have antifungal activity against other fungi

Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect Model

Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments

Chemical Compounds Identified Using the <i>C. elegans–Candida</i> Screen Tested in a Murine Model of Hematogenous Candidiasis

<p>(A) CAPE, (B) enoxacin, and (C) lapachol (from <a href="http://pubchem.ncbi.nlm.nih.gov" target="_blank">http://pubchem.ncbi.nlm.nih.gov</a>).</p

In Vitro Efficacy of CAPE, Enoxacin, and Lapachol in Biofilm Formation

<p>DAY185 formed biofilms on silicone squares in the presence of DMSO in PBS (A and F), caspofungin (B and G), CAPE (C and H), enoxacin (D and I), or lapachol (E and J). Silicone squares were observed for filament formation with a 40× oil emersion objective (A–E) and stained with concanavalin A-Alexa 488 to identify the cell membranes of DAY185 with confocal microscopy (F–J). All three compounds significantly decreased the dry mass of the silicone pads (<i>p</i> = 0.020 for caspofungin, CAPE, and lapachol; and <i>p</i> = 0.029 for enoxacin compared to DMSO in PBS control) (K).</p

Phenotypic Assay Detects Compounds with Antifungal Activity

<p>After exposure to strain C. albicans MLR62, <i>C. elegans glp-4;sek-1</i> nematodes were pipetted into 96-well plates that contained compounds from chemical libraries. Nematodes exposed to compounds that had antifungal efficacy (in this case, CAPE) had no fluorescence within the intestine (A), whereas nematodes exposed to compounds without antifungal efficacy did not demonstrate any movement (B) and developed filaments outside the nematodes (C). Roughly 25 worms were used per well.</p

Killing of C. elegans after Exposure to <i>Candida</i> Species

<div><p>(A) N2, <i>glp-4, or glp-4;sek-1</i> L4 nematodes feeding on E. coli OP50 were transferred to C. albicans strain DAY185 for 2 h and then transferred to pathogen-free liquid medium. Dead nematodes were counted and removed daily. N2 worms transferred from E. coli OP50 directly to liquid media were used as control. Survival of <i>glp-4;sek-1</i> is significantly shorter compared to the strain <i>glp-4</i> (<i>p</i> < 0.001).</p><p>(B) Survival of <i>C. elegans glp-4;sek-1</i> feeding on lawns of C. albicans ATCC#90028, C. parapsilosis ATCC#20019, or C. krusei ATCC#6258. <i>p</i> < 0.001 for each of the yeast strains compared to control nematodes that were exposed to E. coli OP50 (∼65 nematodes/group).</p></div

A Large GLC1C Greek Family with a Myocilin T377M Mutation: Inheritance and Phenotypic Variability

PURPOSE. POAG is a complex disease; therefore, families in which a glaucoma gene has been mapped may carry additional POAG genes. The goal of this study was to determine whether mutations in the myocilin (MYOC) gene on chromosome 1 are present in two POAG families, which have previously been mapped to the GLC1C locus on chromosome 3. METHODS. The three exons of MYOC were screened by denaturing (d)HPLC. Samples with heteroduplex peaks were sequenced. Clinical findings were compared with genotype status in all available family members over the age of 20 years. RESULTS. A T377M coding sequence change in MYOC was identified in family members of the Greek GLC1C family but not in the Oregon GLC1C family. Individuals carrying both the MYOC T377M variant and the GLC1C haplotype were more severely affected at an earlier age than individuals with just one of the POAG genes, suggesting that these two genes interact or that both contribute to the POAG phenotype in a cumulative way. (Invest Ophthalmol Vis Sci. 2006;47:620 -625