Separating transformation in a problem on extremal decomposition of the complex plane

The paper is devoted to investigation of the problems of geometric function theory of a complex variable. A general problem of the description of extremal configurations maximizing the product of the inner radii of mutually non-overlapping domains is studied

Expression of genes of putative hexose transporters in the yeast Hansenula polymorpha are differentially regulated by glucose sensors Hxs1 and Gcr1

The first and limiting step of metabolism of glucose, the most widespread carbon and energy source for majority of cells, is the transport of this sugar across cytoplasmic membrane. In the eukaryotic cells glucose controls and ensures its own effective metabolism, acting as extracellular effector, regulating on transcriptional and translational levels amount, type and activity of corresponding hexose transporters. In this study we investigated regulation of expression of genes encoding hexose transporter homologues – НрHxt1, НрHxt2, НрHxt3 and putative fructose transporter – НрFrt1 by two glucose sensors НрGcr1 and НрHxs1 in methylotrophic yeast Hansenula polymorpha. We have demonstrated that putative glucose sensor НрGcr1 is involved in repression of the gene of functional low affinity hexose transporter НрHxt1 under glucose deficient conditions and participates in repression of genes of putative high affinity glucose transporters НрHxt2 and НрHxt3 under excess of this carbon source. It was shown that glucose sensor НрHxs1 is involved in induction of НрHxt1 expression. As a result of deletion of HpGCR1, but not НрHxS1, the gene of putative high affinity fructose transporter НрFRT1 is constitutively expressed independently of glucose pre­sence and its concentration in growth medium. Therefore, regulation of hexose (glucose and fructose) transport in methylotrophic yeast H. polymorpha at the level of gene expression is a complicated system of interac­ting regulatory and transporting elements where glucose sensors НрGcr1 and НрHxs1 act as the key factors

Modeling of molecular processes underlying Parkinson’s disease in cells of methylotrophic yeast Hansenula polymorpha

Abnormal oligomerisation and aggregation of the protein called alpha-synuclein (α-syn) are the key events in the pathogenesis of Parkinson’s disease (PD). Recent discoveries revealed cellular pathways that potentially relate neurodegenerative disease (ND) to abnormal functioning of mitochondria or anomalous glucose metabolism. In this study we describe for the first time strains of the thermotolerant methylotrophic yeast Hansenula polymorpha that produce human GFP-tagged α-syn as a new model of molecular processes leading to PD. We observed that NCYC495-SNCA wild-type strain did not form visible α-syn amyloid-like aggregates but exhibited plasma membrane perforations and cytoplasm leakage. gcr1-2-SNCA mutant strain deficient in catabolite repression and glucose transport exhibited enhanced aggregation of fluorescently tagged α-syn. However, the observed differences did not result from the impaired glucose metabolism as were observed in both α-syn-producing strains grown on glycerol. Production of α-syn was detrimental for both strains and decreased their growth rate on alternative carbon sources. Our data suggests that H. polymorpha may serve as an informative new yeast model for deciphering molecular mechanisms of PD that regulate amyloid formation and degradation under the influence of various extra- and intracellular factors