Candida albicans versus Candida dubliniensis: Why Is C. albicans More Pathogenic?

Candida albicans and Candida dubliniensis are highly related pathogenic yeast species. However, C. albicans is far more prevalent in human infection and has been shown to be more pathogenic in a wide range of infection models. Comparison of the genomes of the two species has revealed that they are very similar although there are some significant differences, largely due to the expansion of virulence-related gene families (e.g., ALS and SAP) in C. albicans, and increased levels of pseudogenisation in C. dubliniensis. Comparative global gene expression analyses have also been used to investigate differences in the ability of the two species to tolerate environmental stress and to produce hyphae, two traits that are likely to play a role in the lower virulence of C. dubliniensis. Taken together, these data suggest that C. dubliniensis is in the process of undergoing reductive evolution and may have become adapted for growth in a specialized anatomic niche

Amplification of TLO Mediator Subunit Genes Facilitate Filamentous Growth in Candida Spp

Funding: This work was funded by the National Institutes of Allergy and Infectious Disease (AI113390, LCM) and the National Institutes of General Medical Sciences (GM62483, LCM). The funders had no role in study design, data collection and analysis, decision topublish, or preparation of the manuscript.Non peer reviewedPublisher PD

Phenotypic screening, transcriptional profiling, and comparative genomic analysis of an invasive and non-invasive strain of Candida albicans

<p>Abstract</p> <p>Background</p> <p>Invasion of host tissue by the human fungal pathogen <it>Candida albicans </it>is an important step during the development of candidosis. However, not all <it>C. albicans </it>strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the <it>in vitro </it>phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence.</p> <p>Results</p> <p>In all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion <it>in vitro</it>. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an <it>in vitro </it>invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, <it>in vitro </it>transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal <it>in vitro </it>growth conditions.</p> <p>Conclusion</p> <p>Our data suggest that the reason for differential virulence of <it>C. albicans </it>strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes.</p

Ketones Prevent Oxidative Impairment of Hippocampal Synaptic Integrity through K\u3csub\u3eATP\u3c/sub\u3e Channels

Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (KATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of KATP channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the KATP channel activator diazoxide. Inhibition of KATP channels reversed ketone-evoked hippocampal protection, and genetic ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical component of KATP channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of KATP channels

The Candida albicans-Specific Gene EED1 Encodes a Key Regulator of Hyphal Extension

The extension of germ tubes into elongated hyphae by Candida albicans is essential for damage of host cells. The C. albicans-specific gene EED1 plays a crucial role in this extension and maintenance of filamentous growth. eed1Δ cells failed to extend germ tubes into long filaments and switched back to yeast growth after 3 h of incubation during growth on plastic surfaces. Expression of EED1 is regulated by the transcription factor Efg1 and ectopic overexpression of EED1 restored filamentation in efg1Δ. Transcriptional profiling of eed1Δ during infection of oral tissue revealed down-regulation of hyphal associated genes including UME6, encoding another key transcriptional factor. Ectopic overexpression of EED1 or UME6 rescued filamentation and damage potential in eed1Δ. Transcriptional profiling during overexpression of UME6 identified subsets of genes regulated by Eed1 or Ume6. These data suggest that Eed1 and Ume6 act in a pathway regulating maintenance of hyphal growth thereby repressing hyphal-to-yeast transition and permitting dissemination of C. albicans within epithelial tissues

Early Radio and X-Ray Observations of the Youngest Nearby Type Ia Supernova PTF 11kly (SN 2011fe)

On 2011 August 24 (UT) the Palomar Transient Factory (PTF) discovered PTF11kly (SN 2011fe), the youngest and most nearby Type Ia supernova (SN Ia) in decades. We followed this event up in the radio (centimeter and millimeter bands) and X-ray bands, starting about a day after the estimated explosion time.We present our analysis of the radio and X-ray observations, yielding the tightest constraints yet placed on the pre-explosion mass-loss rate from the progenitor system of this supernova. We find a robust limit of Ṁ ≾ 10^(−8)(w/100 km s^(−1))M_☉ yr^(−1) from sensitive X-ray non-detections, as well as a similar limit from radio data, which depends, however, on assumptions about microphysical parameters. We discuss our results in the context of single-degenerate models for SNe Ia and find that our observations modestly disfavor symbiotic progenitor models involving a red giant donor, but cannot constrain systems accreting from main-sequence or sub-giant stars, including the popular supersoft channel. In view of the proximity of PTF11kly and the sensitivity of our prompt observations, we would have to wait for a long time (a decade or longer) in order to more meaningfully probe the circumstellar matter of SNe Ia

Attitudes to Interprofessional Education Among Health Science Students Engaging in a Multidisciplinary Workshop Series

Introduction: Interprofessional education (IPE) provides an opportunity for students from single-professions to interact with other disciplines. Student attitude to IPE can impact engagement and change in attitude may provide an indicator of the impact of IPE. This study examines pre-workshop attitudes to IPE and change in attitude following a series of three IPE workshops. Methods: Preworkshop attitudes were examined using the Readiness for Interprofessional Learning Scale (RIPLS) and the Interprofessional Education Perception Scale (IEPS). The IEPS was repeated at the start of Workshop 1 and at the end of Workshop 3. Data were analyzed using linear regression analysis and linear mixed methods for repeated measures. Results: 405 students participated (pre-workshop n=122; workshop 1 n=244; workshop 3 n=236). Pre-workshop attitudinal scores were high. While male gender and studying medicine negatively predicted attitude across some domains, previous experience of a joint patient treatment session on clinical placement positively predicted attitude in the domain of Perception of Actual Cooperation (standardised Beta 0.283, p=0.005). Attitude to IPE improved across all domains of the IEPS from online preparation to the end of workshop 3 (pCompetency and Autonomy, and in the domain of Perceived Need for Cooperation improved only following online preparation, while the domain of Perception of Actual Cooperation improved following both online preparation and participation in the workshops. Discussion: The results presented reflect positively on student readiness for IPE. Attitudes were further improved following engagement in a structured series of IPE workshops

Exploring the Optical Transient Sky with the Palomar Transient Factory

The Palomar Transient Factory (PTF) is a wide-field experiment designed to investigate the optical transient and variable sky on time scales from minutes to years. PTF uses the CFH12k mosaic camera, with a field of view of 7.9 deg^2 and a plate scale of 1 asec/pixel, mounted on the the Palomar Observatory 48-inch Samuel Oschin Telescope. The PTF operation strategy is devised to probe the existing gaps in the transient phase space and to search for theoretically predicted, but not yet detected, phenomena, such as fallback supernovae, macronovae, .Ia supernovae and the orphan afterglows of gamma-ray bursts. PTF will also discover many new members of known source classes, from cataclysmic variables in their various avatars to supernovae and active galactic nuclei, and will provide important insights into understanding galactic dynamics (through RR Lyrae stars) and the Solar system (asteroids and near-Earth objects). The lessons that can be learned from PTF will be essential for the preparation of future large synoptic sky surveys like the Large Synoptic Survey Telescope. In this paper we present the scientific motivation for PTF and describe in detail the goals and expectations for this experiment.Comment: 15 pages, 6 figures, submitted to PAS

Love, artificiality and mass identification

How are we to understand the phenomenon of mass identification, epitomized in recent exhibitions of national feeling such as that of South Africa’s 2010 Football World Cup celebrations? Rather than focussing on the concepts of discourse and nationalism, or advancing an analysis of empirical data, this paper outlines a conceptual response to the challenge at hand, drawing on the tools of psychoanalytic theory. Three explanatory perspectives come to the fore. Firstly, such exhibitions of mass emotion might be understood as demonstrations of love, as examples of the libidinal ties that constitute and consolidate mass identification. Secondly, the marked artificiality of such displays of emotion and the fact of the ‘externality’ they entail might be seen, paradoxically, to be essential rather than inauthentic or secondary features of the displays in question. Thirdly, we might advance, via Lacan, that many of our most powerful emotions require not only recourse to the field of the inter-subjective, but reference also to the anonymous, ‘fictional’ framework of available symbolic forms

Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance

Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription. This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. This phenotype was reversed to varying degrees upon reintroduction of representative members of the alpha- and beta-TLO clades (i.e. TLO1 and TLO2), but not by TLO11, a gamma-clade representative. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in a range of cellular functions, including ergosterol biosynthesis, mitochondrial function, and redox homeostasis. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the control of ergosterol biosynthesis and mitochondrial function and may play a role in the responses of C. albicans to azole antifungal agents