Structure and function of glycosylated tandem repeats from Candida albicans Als adhesins.

Tandem repeat (TR) regions are common in yeast adhesins, but their structures are unknown, and their activities are poorly understood. TR regions in Candida albicans Als proteins are conserved glycosylated 36-residue sequences with cell-cell aggregation activity (J. M.

Lattice dynamics of orthorhombic perovskite yttrium manganite, YMnO(3).

The lattice dynamics of yttrium manganite (YMnO(3)) has been investigated by means of a shell model with pair-wise interionic interaction potential. The experimental data of crystal structure and Raman and infrared frequencies compare well with the lattice dynamical calculations. The phonon dispersion curves found along three high symmetry directions and the density of states of YMnO(3) have also been calculated from this model.

Unfolding individual als5p adhesion proteins on live cells.

Elucidating the molecular mechanisms behind the strength and mechanics of cell adhesion proteins is of central importance in cell biology and offers exciting avenues for the identification of potential drug targets. Here we use single-molecule force spectroscopy to investigate the adhesive and mechanical properties of the widely expressed Als5p cell adhesion protein from the opportunistic pathogen Candida albicans . We show that the forces required to unfold individual tandem repeats of the protein are in the 150-250 pN range, both on isolated molecules and on live cells.

The role of lattice distortions in determining the thermal properties of electron doped CaMnO(3).

We have investigated the thermal properties of electron doped perovskite manganite CaMnO(3), the end member ([Formula: see text]) of the Ruddlesden-Popper (RP) calcium manganates series with cation doping at the A-site. In this paper the functional relation between the lattice distortions and the thermal properties is determined and compared to available reports. The temperature dependence of the lattice specific heat (C(v(lattice))) of Ca(1-x)Ln(x)MnO(3) (x = 0.

Chlorine gas sensors using one-dimensional tellurium nanostructures.

Tellurium nanotubes have been grown by physical vapor deposition under inert environment at atmospheric pressure as well as under vacuum conditions. Different techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and optical absorption have been utilized for characterization of grown structures. Films prepared using both types of tellurium nanotubes were characterized for sensitivity to oxidizing and reducing gases and it was found that the relative response to gases depends on the microstructure.

The biochemical womb of schizophrenia: A review.

The conclusive identification of specific etiological factors or pathogenic processes in the illness of schizophrenia has remained elusive despite great technological progress. The convergence of state-of-art scientific studies in molecular genetics, molecular neuropathophysiology, in vivo brain imaging and psychopharmacology, however, indicates that we may be coming much closer to understanding the genesis of schizophrenia. In near future, the diagnosis and assessment of schizophrenia using biochemical markers may become a "dream come true" for the medical community as well as for the general population.

Disrupting vesicular trafficking at the endosome attenuates transcriptional activation by Gcn4.

The late endosome (MVB) plays a key role in coordinating vesicular transport of proteins between the Golgi complex, vacuole/lysosome, and plasma membrane. We found that deleting multiple genes involved in vesicle fusion at the MVB (class C/D vps mutations) impairs transcriptional activation by Gcn4, a global regulator of amino acid biosynthetic genes, by decreasing the ability of chromatin-bound Gcn4 to stimulate preinitiation complex assembly at the promoter. The functions of hybrid activators with Gal4 or VP16 activation domains are diminished in class D mutants as well, suggesting a broader defect in activation.

Transcriptional activation and increased mRNA stability contribute to overexpression of CDR1 in azole-resistant Candida albicans.

Many azole-resistant (AR) clinical isolates of Candida albicans display increased expression of the drug transporters CDR1 and CDR2. In this study, we evaluate the molecular mechanisms that contribute to the maintenance of constitutively high CDR1 transcript levels in two matched pairs of azole-susceptible (AS) and AR clinical isolates of C. albicans.

Polymicrobial bloodstream infections involving Candida species: analysis of patients and review of the literature.

Candida species are the 4th most common cause of nosocomial bloodstream infections in North America. It is not widely appreciated, however, that many of these infections are polymicrobial, that is, that bacteria and occasionally more than 1 species of Candida are present in the same blood culture bottle. Analysis of 2 groups of candidemic patients and a review of the literature were performed.

Candida albicans Als proteins mediate aggregation with bacteria and yeasts.

Candida albicans occupies a microniche on mucosal surfaces where diverse microbial populations interact within a biofilm. Because C. albicans is intimately involved with other microbes in this environment we studied the interactions of C.

Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1.

In contrast to the deregulated hepatocellular division that is a feature of many hepatic diseases and malignancies, physiologic liver growth during embryonic development and after partial hepatectomy (PH) in adults is characterized by tightly controlled cell proliferation. We used forward genetic screening in zebrafish to test the hypothesis that a similar genetic program governs physiologic liver growth during hepatogenesis and regeneration after PH. We identified the uhrf1 gene, a cell cycle regulator and transcriptional activator of top2a expression, as required for hepatic outgrowth and embryonic survival.

Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p.

Commensal and pathogenic states of Candida albicans depend on cell surface-expressed adhesins, including those of the Als family. Mature Als proteins consist of a 300-residue N-terminal region predicted to have an immunoglobulin (Ig)-like fold, a 104-residue conserved Thr-rich region (T), a central domain of a variable number of tandem repeats (TR) of a 36-residue Thr-rich sequence, and a heavily glycosylated C-terminal Ser/Thr-rich stalk region, also of variable length (N. K.

Efflux pumps in drug resistance of Candida.

The incidences of human pathogenic yeast Candida albicans and its related species acquiring resistance to antifungals have increased considerably, which poses serious problems towards its successful chemotherapy. The resistance of these pathogenic fungi is not restricted to the commonly used triazole compounds but is even encountered, though not often, with polyene derivatives as well. The efflux pump proteins belonging to ABC (ATP Binding Cassette) and MFS (Major Facilitators) super family are the most prominent contributors of multidrug resistance (MDR) in yeasts.

Chimeras of the ABC drug transporter Cdr1p reveal functional indispensability of transmembrane domains and nucleotide-binding domains, but transmembrane segment 12 is replaceable with the corresponding homologous region of the non-drug transporter Cdr3p.

The molecular basis of the broad substrate recognition and the transport of substrates by Cdr1p, a major drug efflux protein of Candida albicans, is not well understood. To investigate the role of transmembrane domains and nucleotide-binding domains (NBDs) of Cdr1p in drug transport, two sets of protein chimeras were constructed: one set between homologous regions of Cdr1p and the non-drug transporter Cdr3p, and another set consisting of Cdr1p variants comprising either two N- or two C-terminal NBDs of Cdr1p. The replacement of either the N- or the C-terminal half of Cdr1p by the homologous segments of Cdr3p resulted in non-functional recombinant strains expressing chimeric proteins.

Isolated thrombus-producing right ventricular outflow tract obstruction: an unusual presentation of primary antiphospholipid antibody syndrome.

Right ventricular outflow tract obstruction secondary to an isolated organized thrombus is a rare entity. Proper diagnosis of this condition is essential for the survival of such patients. We describe the case of a middle aged woman who presented with dyspnea and decreased effort tolerance, and was managed with surgical excision of a firm mass which was identified as organized thrombus.

Functional analysis of CaIPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans.

In the present study we describe the isolation and functional analysis of a sphingolipid biosynthetic gene, IPT1, of Candida albicans. The functional consequence of the disruption of both alleles of IPT1 was confirmed by mass analysis of its sphingolipid composition. The disruption of both alleles or a single allele of IPT1 did not lead to any change in growth phenotype or total sphingolipid, ergosterol, or phospholipid content of the mutant cells.

Alanine scanning of transmembrane helix 11 of Cdr1p ABC antifungal efflux pump of Candida albicans: identification of amino acid residues critical for drug efflux.

Objectives: To investigate the role of transmembrane segment 11 (TMS11) of Candida albicans drug resistance protein (Cdr1p) in drug extrusion.

Methods: We replaced each of the 21 putative residues of TMS11 with alanine by site-directed mutagenesis. The Saccharomyces cerevisiae AD1-8u(-) strain was used to overexpress the green fluorescent protein tagged wild-type and mutant variants of TMS11 of Cdr1p.

Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element.

Resistance to azole antifungal drugs in clinical isolates of the human fungal pathogen Candida albicans is often caused by constitutive overexpression of the CDR1 gene, which encodes a multidrug efflux pump of the ABC transporter superfamily. To understand the relevance of a recently identified negative regulatory element (NRE) in the CDR1 promoter for the control of CDR1 expression in the clinical scenario, we investigated the effect of mutation or deletion of the NRE on CDR1 expression in two matched pairs of azole-sensitive and resistant clinical isolates of C. albicans.

Inhibition of adherence and killing of Candida albicans with a 23-Mer peptide (Fn/23) with dual antifungal properties.

Candida albicans adheres to host tissue and then proliferates in order to establish a commensal as well as a pathogenic state. Specific adherence to proteins is provided by several surface adhesins of Candida. Two well-studied proteins, Als1p and Als5p, do not require energy for adherence to occur (dead as well as living cells adhere) and have a multiplier effect of cell-cell aggregation that mediates the formation of microcolonies of Candida cells.

Global cell surface conformational shift mediated by a Candida albicans adhesin.

Candida albicans maintains both commensal and pathogenic states in humans. Both states are dependent on cell surface-expressed adhesins, including those of the Als family. Heterologous expression of Als5p at the surface of Saccharomyces cerevisiae results in Als5p-mediated adhesion to various ligands, followed by formation of multicellular aggregates.

Degenerate peptide recognition by Candida albicans adhesins Als5p and Als1p.

Candida albicans and Saccharomyces cerevisiae expressing the adhesins Als5p or Als1p adhere to immobilized peptides and proteins that possess appropriate sequences of amino acids in addition to a sterically accessible peptide backbone. In an attempt to further define the nature of these targets, we surveyed the ability of yeast cells to adhere to 90- micro m-diameter polyethylene glycol beads coated with a 7-mer peptide from a library of 19(7) unique peptide-beads. C.

SRE1 and SRE2 are two specific steroid-responsive modules of Candida drug resistance gene 1 (CDR1) promoter.

CDR1 gene encoding an ATP-driven drug extrusion pump has been implicated in the development of azole-resistance in Candida albicans. Although the upregulation of CDR1 expression by various environmental factors has been documented, the molecular mechanism underlying such process is poorly understood. We have demonstrated earlier that the CDR1 promoter encompasses a large number of cis-regulatory elements, presumably mediating its response to various drugs.

Accessibility of the peptide backbone of protein ligands is a key specificity determinant in Candida albicans SRS adherence.

Candida albicans displays a high degree of specificity in selecting and adhering to targets in vivo. The features of target recognition are poorly understood and likely to involve more than the mere chemical composition of the ligand. Using an adherence assay in which protein and peptide ligands are covalently coupled to magnetic beads, the authors have previously described a new adherence mechanism in C.

Identification of a negative regulatory element which regulates basal transcription of a multidrug resistance gene CDR1 of Candida albicans.

We have earlier shown that transcriptional activation of the Candida drug resistance gene, CDR1, is linked to various stresses wherein a proximal promoter (-345 bp from the transcription start point (TSP)) was found to be predominantly more responsive. In this study we have examined basal expression of the CDR1 proximal promoter by employing a Renilla luciferase reporter system. We observed that upon sequential deletion of the proximal promoter, there was modulation in basal reporter activity.