Changes in the mRNA expression of glycolysis-related enzymes of Candida albicans during inhibition of intramitochondrial catabolism under anaerobic condition.

Candida albicans can cause two major types of infections: superficial infection and systemic candidiasis. C. albicans infects diverse host niches, owing to a wide range of virulence factors and attributes, such as morphological transitions and phenotypic switching. C. albicans uses glycolysis, followed by alcoholic fermentation or mitochondrial respiration to rapidly generate ATP under aerobic conditions. In this study, we quantified the mRNA expression of several glycolysis-related enzymes associated with the initial phase of environmental changes using two strains: a type strain, NBRC 1385, and a strain from a patient with auto-brewery syndrome, LSEM 550. Additionally, we analyzed the regulation of a rate-limiting enzyme in glycolysis, phosphofructokinase 1 (PFK1). Our results showed that the mRNA expression of enzymes in the middle and last stages of glycolysis and alcoholic fermentation increased, and that of mitochondrial respiration enzymes decreased under short-term anaerobic conditions. Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) administration showed similar results under anaerobic conditions. Moreover, PFK1 maintained its regulatory effect under different conditions; no significant change was observed in its mRNA expression. Our results suggest that C. albicans obtains energy via carbohydrate catabolism in the early phase of environmental change and survives in various parts of the host.

Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial.

Consumption of fermented milk (FM) containing a probiotic, Lactobacillus gasseri SBT2055 (LG2055), previously showed a reduction in abdominal adiposity in a randomised controlled trial (RCT) using FM with 10(8) colony-forming units (cfu) of LG2055/g. However, whether the effectiveness is observed at lower concentrations, the recommended minimum or intermediate levels of probiotics (10(6) or 10(7) cfu/g, respectively), remains to be examined. A multi-centre, double-blind, parallel-group RCT was conducted using 210 healthy Japanese adults with large visceral fat areas (80·2 - 187·8 cm(2)). They were balanced for their baseline characteristics and randomly assigned to three groups receiving FM containing 10(7), 10(6) or 0 (control) cfu LG2055/g of FM, and were asked to consume 200 g FM/d for 12 weeks. Abdominal visceral fat areas, which were determined by computed tomography, at week 12, changed from baseline by an average of -8·5 % (95 % CI -11·9, -5·1; P< 0·01) in the 10(7) dose group, and by -8·2 % (95 % CI -10·8, -5·7; P< 0·01) in the 10(6) dose group. Other measures including BMI, waist and hip circumferences, and body fat mass were also significantly decreased from baseline at week 12 in both groups; interestingly, the cessation of taking FM for 4 weeks attenuated these effects. In the control group, none of these parameters significantly decreased from baseline. These findings demonstrate that consumption of LG2055 at doses as low as the order of 10(8) cfu/d exhibited a significant lowering effect on abdominal adiposity, and suggest that constant consumption might be needed to maintain the effect.

JPO1/CDCA7, a novel transcription factor E2F1-induced protein, possesses intrinsic transcriptional regulator activity.

JPO1/CDCA7 was originally identified as a c-Myc-responsive gene that participates in neoplastic transformation. Here, we report the identification of JPO1/CDCA7 as a direct transcriptional target of transcription factor E2F1. We demonstrated that overexpression of E2F1 by adenoviral-mediated gene transfer upregulated JPO1/CDCA7 mRNA expression in human cells. Analysis of human and mouse JPO1/CDCA7 promoter constructs showed that an E2F-responsive sequence was necessary for E2F1-induced activation of the JPO1/CDCA7 gene transcription. Among the members of the E2F family, E2F1 to E2F4, but not E2F5 or E2F6, activated the JPO1/CDCA7 reporter construct. Chromatin immunoprecipitation analysis demonstrated that E2F1, E2F2, and E2F4 specifically bound to an E2F-responsive sequence of the human JPO1/CDCA7 gene. Like JPO2/R1, which has a homologous transcriptional regulator domain, the C-terminal cysteine-rich region of JPO1/CDCA7 protein induced transcriptional activity in a mammalian one-hybrid assay. Taken together, our results suggest that JPO1/CDCA7 is a unique transcription regulator whose expression is activated by E2F1 as well as c-Myc.