N-Acetylglucosamine Induces White to Opaque Switching, a Mating Prerequisite in Candida albicans

To mate, the fungal pathogen Candida albicans must undergo homozygosis at the mating-type locus and then switch from the white to opaque phenotype. Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans. Recently, however, it was demonstrated that high levels of CO2, equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox. Here, we demonstrate that a second signal, N-acetylglucosamine (GlcNAc), a monosaccharide produced primarily by gastrointestinal tract bacteria, also serves as a potent inducer of white to opaque switching and functions primarily through the Ras1/cAMP pathway and phosphorylated Wor1, the gene product of the master switch locus. Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans

The Wor1-like Protein Fgp1 Regulates Pathogenicity, Toxin Synthesis and Reproduction in the Phytopathogenic Fungus Fusarium graminearum

WOR1 is a gene for a conserved fungal regulatory protein controlling the dimorphic switch and pathogenicity determents in Candida albicans and its ortholog in the plant pathogen Fusarium oxysporum, called SGE1, is required for pathogenicity and expression of key plant effector proteins. F. graminearum, an important pathogen of cereals, is not known to employ switching and no effector proteins from F. graminearum have been found to date that are required for infection. In this study, the potential role of the WOR1-like gene in pathogenesis was tested in this toxigenic fungus. Deletion of the WOR1 ortholog (called FGP1) in F. graminearum results in greatly reduced pathogenicity and loss of trichothecene toxin accumulation in infected wheat plants and in vitro. The loss of toxin accumulation alone may be sufficient to explain the loss of pathogenicity to wheat. Under toxin-inducing conditions, expression of genes for trichothecene biosynthesis and many other genes are not detected or detected at lower levels in Δfgp1 strains. FGP1 is also involved in the developmental processes of conidium formation and sexual reproduction and modulates a morphological change that accompanies mycotoxin production in vitro. The Wor1-like proteins in Fusarium species have highly conserved N-terminal regions and remarkably divergent C-termini. Interchanging the N- and C- terminal portions of proteins from F. oxysporum and F. graminearum resulted in partial to complete loss of function. Wor1-like proteins are conserved but have evolved to regulate pathogenicity in a range of fungi, likely by adaptations to the C-terminal portion of the protein

Labrum repair combined with arthroscopic reduction of capsular volume in shoulder instability

We performed arthroscopic treatment of traumatic anterior and anteroinferior shoulder instability combining three procedures— labrum repair, reduction of capsular volume and suture of the rotator cuff interval—with the aim of analysing the results with regard to stability and function. Between January 1999 and December 2003, 27 patients underwent arthroscopic treatment for labrum repair with metal anchors, reduction of capsular volume through thermal capsulorrhaphy and suture of rotator cuff interval. These patients were evaluated in the pre- and postoperative period using the UCLA and Rowe scales and in the postoperative period using the ASES scale. During a mean follow-up period of 32.4 months (range 22–74 months) all shoulders remained stable. Using the UCLA scale, there was improvement from the preoperative period, with a mean score of 24.7, to the postoperative period, with a mean of 32.81. Improvement was also shown by the Rowe scale, with a mean score of 39.81 in the preoperative period and 90.74 in the postoperative period. On the ASES scale the mean score was 92.22. All shoulders remained stable and there was marked functional improvement in the patients who were treated. These results are comparable to those obtained with open surgery, observing similar patient selection criteria

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) in familial colorectal cancer

B ackground and aim: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a pigmented fundus lesion associated with familial adenomatous polyposis (FAP). CHRPE prevalence has been reported to be increased in subjects with familial or sporadic non-polyposis colorectal cancer (CRC), suggesting that some individuals with non-polyposis CRC have an attenuated form of FAP. Other studies have not confirmed these clinical observations and have failed to identify mutations in the gene responsible for FAP, but the reason for the discrepancy in relation to CHRPE prevalence has not been resolved. We determined the prevalence of CHRPE in subjects without CRC (negative control cohort), subjects with FAP (positive control cohort), and subjects with familial non-polyposis CRC (test cohort). Method: A cohort study consisting of 37 negative control subjects, 9 positive control subjects with documented APC gene mutations, and 36 test subjects with familial non-polyposis CRC but no identified pathogenic APC gene mutation. The diagnosis of hereditary non-polyposis colon cancer was excluded in the test cohort by testing for microsatellite instability in tumour tissue. Results: None of the 37 people in the negative control group had CHRPE. Five of nine (56%) patients with FAP had multiple CHRPE lesions. None of the 36 subjects in the test cohort had CHRPE lesions. Conclusions: Ophthalmoscopy may contribute to risk assessment in families with FAP but not in familial non-polyposis CRC. Care must be exercised when interpreting pigmented fundus lesions because 8–13% of subjects in each of the cohorts had pigmented retinal lesions that were not CHRPE. Bilateral lesions and lesions with a depigmented halo␣were the hallmarks of CHRPE associated with FAP.Celia S. Chen, Kerry D. Phillips, Scott Grist, Graeme Bennet, Jamie E. Craig, James S. Muecke, Graeme K. Suther