Candida albicans, a commensal organism and a pathogen of humans, can switch stochastically between a white phase and an opaque phase without an intermediate phase. The white and opaque phases have distinct cell shapes and gene expression programs. Once switched, each phase is stable for many cell divisions. White-opaque switching is under a1-␣2 repression and therefore only happens in a or ␣ cells. Mechanisms that control the switching are unknown. Here, we identify Wor1 (white-opaque regulator 1) as a master regulator of white-opaque switching. The deletion of WOR1 blocks opaque cell formation. The ectopic expression of WOR1 converts all cells to stable opaque cells in a or ␣ cells. In addition, the ectopic expression of WOR1 in a͞␣ cells is sufficient to induce opaque cell formation. Importantly, WOR1 expression displays an all-or-none pattern. It is undetectable in white cells, and it is highly expressed in opaque cells. The ectopic expression of Wor1 induces the transcription of WOR1 from the WOR1 locus, which correlates with the switch to opaque phase. We present genetic evidence for feedback regulation of WOR1 transcription. The feedback regulation explains the bistable and stochastic nature of white-opaque switching.feedback regulation ͉ a1-␣2 repression C andida albicans is associated with humans both as a harmless commensal organism and a pathogen. In most humans, it is a normal part of the microflora in the gastrointestinal tract and in other parts of the body. However, when the host immune system is compromised, it can cause mucosal infections and life-threatening disseminated infections. The ability of C. albicans to undergo a yeast-to-hypha transition and high-frequency phenotypic switching provides the organism with a high degree of phenotypic diversity and the adaptability that is necessary to survive in different host environments (1). One of the high-frequency switching systems is white-opaque switching. White-opaque switching was first identified in a clinical isolate, WO-1, in which cells switched spontaneously between white and opaque phases (2). White phase cells appear round and form hemispherical, white colonies on solid agar, and opaque phase cells are elongated in cell shape with pimples on the surface and form flat, opaque colonies. Several features of white-opaque switching are particularly interesting (1, 3): (i) the transition involves only two phases, and there is not an intermediate phase, (ii) the transition is stochastic, generating heterogeneity in a cell population, and (iii) the phase is stable for many cell divisions, with daughter cells inheriting the phase of their mother cells. White-opaque switching occurs at a frequency of 10 Ϫ4 to 10 Ϫ5 per cell division, and opaque-white switching happens at a frequency of 5 ϫ 10 Ϫ4 per cell generation (4). Opaque cells are stable at 25°C. Upon shifting the temperature to 37°C, they switch en masse to white cells (5).White-opaque switching is under a1-␣2 repression (6). In C. albicans, cell type is determined by the MTL (mating type-li...

Endothelial cells are important constituents of blood vessels that play critical roles in cardiovascular homeostasis by regulating blood fluidity and fibrinolysis, vascular tone, angiogenesis, monocyte/leukocyte adhesion, and platelet aggregation. The normal vascular endothelium is taken as a gatekeeper of cardiovascular health, whereas abnormality of vascular endothelium is a major contributor to a plethora of cardiovascular ailments, such as atherosclerosis, aging, hypertension, obesity, and diabetes. Endothelial dysfunction is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and proinflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. The occurrence of endothelial dysfunction disrupts the endothelial barrier permeability that is a part of inflammatory response in the development of cardiovascular diseases. As such, abrogation of endothelial cell activation/inflammation is of clinical relevance. Recently, hydrogen sulfide (H 2 S), an entry as a gasotransmitter, exerts diverse biological effects through acting on various targeted signaling pathways. Within the cardiovascular system, the formation of H 2 S is detected in smooth muscle cells, vascular endothelial cells, and cardiomyocytes. Disrupted H 2 S bioavailability is postulated to be a new indicator for endothelial cell inflammation and its associated endothelial dysfunction. In this review, we will summarize recent advances about the roles of H 2 S in endothelial cell homeostasis, especially under pathological conditions, and discuss its putative therapeutic applications in endothelial inflammation-associated cardiovascular disorders.

DNA methylation is essential for epigenetic regulation of gene transcription and development in many animals, plants and fungi. We investigated whether DNA methylation plays a role in the development and secondary metabolism of Aspergillus flavus, identified the DmtA methyltransferase from A. flavus, and produced a dmtA knock-out mutant by replacing the dmtA coding sequence with the pyrG selectable marker. The A. flavus dmtA null mutant lines produced white fluffy mycelium in liquid medium, and displayed a slightly flavescent conidial pigmentation compared with the normal yellow of the wild-type strain when grown on agar. The ΔdmtA lines exhibited decreased conidiation and aflatoxin (AF) biosynthesis, compared with the wild-type line, suggesting that the DmtA knock-out affected the transcriptional level of genes in the AF cluster. In particular, sclerotia development and host colonization were altered in the dmtA null mutants. Green fluorescent protein tagging at the C-terminus of DmtA showed that DmtA localized to the nucleus and cytoplasm. DNA methylation content measurements in the dmtA mutants revealed no widespread DNA methylation in the mutants or wild-type lines. Thus, our findings suggest that DmtA, apart from being a C-5 cytosine methyltransferase in A. flavus, contributes to asexual development, aflatoxin biosynthesis, sclerotial production and virulence.