Antifungal susceptibility of yeast bloodstream isolates collected during a 10-year period in Austria.

Background: Candida-associated infections put a significant burden on western healthcare systems. Development of (multi-)resistant fungi can become untreatable and threaten especially vulnerable target groups, such as the immunocompromised.

Objectives: We assessed antifungal susceptibility and explored possible influence factors of clinical Candida isolates collected from Austrian hospitals between 2007 and 2016.

Competition of Candida glabrata against Lactobacillus is Hog1 dependent.

Candida glabrata is a common human fungal commensal and opportunistic pathogen. This fungus shows remarkable resilience as it can form recalcitrant biofilms on indwelling catheters, has intrinsic resistance against azole antifungals, and is causing vulvovaginal candidiasis. As a nosocomial pathogen, it can cause life-threatening bloodstream infections in immune-compromised patients.

Sorbic acid stress activates the Candida glabrata high osmolarity glycerol MAP kinase pathway.

Weak organic acids such as sorbic acid are important food preservatives and powerful fungistatic agents. These compounds accumulate in the cytosol and disturb the cellular pH and energy homeostasis. Candida glabrata is in many aspects similar to Saccharomyces cerevisiae.

MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and displacing its positive regulators.

The aquaglyceroprin Fps1 is responsible for glycerol transport in yeast in response to changes in extracellular osmolarity. Control of Fps1 channel activity in response to hyperosmotic shock involves a redundant pair of regulators, Rgc1 (regulator of the glycerol channel 1) and Rgc2, and the MAPK Hog1 (high-osmolarity glycerol response 1). However, the mechanism by which these factors influence channel activity is unknown.

Efg1 Controls caspofungin-induced cell aggregation of Candida albicans through the adhesin Als1.

Echinocandin drugs such as caspofungin (CASP), micafungin, and anidulafungin inhibit fungal cell wall biogenesis by blocking Fks1-mediated β-glucan deposition into the cell surface. Candins have become suitable drugs to treat life-threatening diseases caused by several fungal species, including Candida albicans, that are pathogenic for humans. Here, we present the discovery of a novel CASP-induced flocculation phenotype of C.

Weak organic acid stress triggers hyperphosphorylation of the yeast zinc-finger transcription factor War1 and dampens stress adaptation.

Exposure of Saccharomyces cerevisiae to weak organic acids such as sorbate, propionate, or benzoate rapidly induces the plasma membrane ABC transporter Pdr12, requiring the Zn(II)(2)Cys(6) zinc-finger transcription factor War1. Weak acid stress rapidly triggers War1 phosphorylation but its role for War1 function is not clear yet. Here, we provide new insights into sorbate-induced phosphorylation of War1.

Functional genomics of drug-induced ion homeostasis identifies a novel regulatory crosstalk of iron and zinc regulons in yeast.

Pyrrolidine dithiocarbamate (PDTC), a known inhibitor of NFκB activation, has antioxidative as well as antiviral activities. PDTC is effective against several virus families, indicating that its antiviral mechanism targets host rather than viral functions. To investigate its mode of action, we used baker's yeast as a simple eukaryotic model system and two types of genome-wide analysis.

Weak organic acids trigger conformational changes of the yeast transcription factor War1 in vivo to elicit stress adaptation.

The Saccharomyces cerevisiae zinc cluster regulator War1 mediates an essential transcriptional and adaptive response to weak organic acid stress. Here we investigate the mechanism of War1 activation upon weak acid stress. We identified several gain-of-function WAR1 alleles mapping to the central War1 region.

Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors.

We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S.

The high-osmolarity glycerol response pathway in the human fungal pathogen Candida glabrata strain ATCC 2001 lacks a signaling branch that operates in baker's yeast.

The high-osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase pathway mediates adaptation to high-osmolarity stress in the yeast Saccharomyces cerevisiae. Here we investigate the function of HOG in the human opportunistic fungal pathogen Candida glabrata. C.

A genetic screen identifies mutations in the yeast WAR1 gene, linking transcription factor phosphorylation to weak-acid stress adaptation.

Exposure of the yeast Saccharomyces cerevisiae to weak organic acids such as the food preservatives sorbate, benzoate and propionate leads to the pronounced induction of the plasma membrane ATP-binding cassette (ABC) transporter, Pdr12p. This protein mediates efflux of weak acid anions, which is essential for stress adaptation. Recently, we identified War1p as the dedicated transcriptional regulator required for PDR12 stress induction.

Insulin regulation of glucokinase gene expression: evidence against a role for sterol regulatory element binding protein 1 in primary hepatocytes.

Liver key genes for carbohydrate and lipid homeostasis are regulated by insulin and glucose. The sterol regulatory-element binding protein-1c (SREBP-1c) has emerged as a mediator of insulin effects on gene transcription, particularly on glucokinase (GK). In this paper, we show that despite stimulation of GK promoter transcription by overexpression of mature SREBP-1c, insulin induced GK transcription at least 4h ahead of accumulation of mature SREBP-1c in the nucleus.

War1p, a novel transcription factor controlling weak acid stress response in yeast.

The Saccharomyces cerevisiae ATP-binding cassette (ABC) transporter Pdr12p effluxes weak acids such as sorbate and benzoate, thus mediating stress adaptation. In this study, we identify a novel transcription factor, War1p, as the regulator of this stress adaptation through transcriptional induction of PDR12. Cells lacking War1p are weak acid hypersensitive, since they fail to induce Pdr12p.

In vivo functional characterization of the aldolase B gene enhancer.

A 400-bp intronic enhancer fragment in conjunction with the proximal promoter of the aldolase B gene provided correct tissue-specific expression in transgenic mice together with hormonal regulation in the liver. We investigated in vivo and in cultured cells the contribution of the intronic regulatory sequences and their interaction with the promoter elements in controlling aldolase B gene expression. Transgene activity was completely abolished by disruption of the two hepatocyte nuclear factor 1 (HNF1) binding sites in the enhancer, whereas mutation of one HNF1 site had no effect in the liver but strongly decreased activity in the kidney.

Nucleoli, rRNA genes and ITS region in Posidonia oceanica (L.) Delile.

The maximum number of nucleoli was counted in interphase nuclei of Posidonia oceanica, and a restriction pattern of nuclear rDNA was obtained after digestion with four restriction endonucleases and Southern hybridization. P. oceanica has only one type of ribosomal gene whose size was estimated to be 18.

Characterization of the aldolase B intronic enhancer.

The aldolase B gene is transcribed at a high level in the liver, kidney, and small intestine. This high level of gene expression results from cooperation between a weak but liver-specific promoter and an intronic activator. A deletional study of this activator present in the first intron allowed us to ascribe the maximal enhancer function to a 400-base pair (bp) fragment (+1916 to + 2329).

Symmetrical periumbilical extension of a midline incision: a simple technique.

Background: Periumbilical extension of midline incision often results in an irregular, unaesthetic scar with beveled edges.

Technique: An Allis clamp is placed at the lateral margin of the umbilicus with subsequent medial traction. This straightens the proposed periumbilical incision, resulting in a symmetrical scar.

Endocervical curettage, cone margins, and residual adenocarcinoma in situ of the cervix.

Objective: To evaluate endocervical curettage (ECC) and cone margin involvement in the management of adenocarcinoma in situ of the cervix.

Methods: Forty-two women with adenocarcinoma in situ without any associated invasive component underwent 49 cervical conizations. The ECC, cone margin involvement, and residual endocervical glandular disease were evaluated in a retrospective descriptive study.

An intronic enhancer essential for tissue-specific expression of the aldolase B transgenes.

Expression in mice of transgenes directed by regulatory regions of the rat aldolase B gene requires the presence of a B element located in the first intron, while constructs devoid of this intronic enhancer are silent. Histo- and immunochemical staining of transgenic tissue sections showed that the longer transgene was expressed in the proximal tubular cells of the kidney, enterocytes located in small intestine villi and liver parenchymal cells. In the liver, a maximal expression was observed in perivenous hepatocytes, while the transgene was weakly active in periportal hepatocytes, which reproduced the pattern of functional zonation already reported for other glycolytic and gluconeogenic genes in the liver.

Bolus mitomycin C and 5-FU with sequential radiation for poor-prognosis locally advanced cervical cancer.

Forty patients with locally advanced cervical carcinoma were entered into a protocol utilizing the bolus administration of both mitomycin C (10 or 15 mg) on Day 1 and 5-fluorouracil (400 mg) on Day 1-5 followed by sequential pelvic irradiation on Day 6 between September 1980 and October 1985. All patients had poor-prognosis FIGO stage IB, IIB, IIIB, or IVA disease. Only patients with poor prognosis factors such as bulky tumor masses of 5 cm or greater noted on the initial physical exam (37 patients) or poorly differentiated histology (3 patients) were eligible for this study.

Stage II adenocarcinoma of the endometrium treated by two standard regimens of combined preoperative irradiation and surgery.

We retrospectively analyzed 77 patients with stage II endometrial carcinoma treated with standard regimens of preoperative radiotherapy (RT) and surgery (S). The age range was 31-74 years with a median of 56.3 years.

Mature cystic teratoma: a clinicopathologic evaluation of 517 cases and review of the literature.

Objective: To evaluate the clinical and pathologic presentation of mature cystic teratomas and the trends in management over a 14-year study period.

Methods: Tumor registry data and medical records between January 1, 1975 and December 31, 1989 were analyzed with respect to patient age, tumor size, bilaterality, malignant transformation, and treatment.

Results: Five hundred seventy-three tumors were removed from 517 patients.

Activity of the rat liver-specific aldolase B promoter is restrained by HNF3.

Although it contains binding sites for HNF1, NFY and C/EBP/DBP, the proximal promoter of the aldolase B gene is surprisingly weak when tested by transient transfection in differentiated hepatoma cells. This low activity could be due to overlapping between HNF1 and HNF3 binding sites in element PAB, from -127 to -103 bp with respect to the cap site. Replacement of the PAB region by a consensus HNF1 binding site unable to bind HNF3, results in a 30 fold activation of the promoter, in accordance with the hypothesis that activity of the wild-type promoter is normally restrained by HNF3 binding to PAB competitively with HNF1.

Wilms' tumor of the uterus. A case report.

Extrarenal Wilms' tumors (nephroblastomas) are considered rare, with only 36 cases reported to date. A primary Wilms' tumor of the uterus has been reported on two previous occasions. A third case is presented and the histologic features and histogenesis of the tumor discussed.