A purine permease in Candida glabrata

Abstract Competition experiments revealed that adenine and guanine were transported by a purine permease in both Candida glabrata 4 and a C. glabrata 4 cytosine permease negative mutant. The C. glabrata 4 cytosine permease negative mutant was isolated using 5-fluorocytosine selection. This mutant no longer transported cytosine, but transported adenine and guanine. A transport system for hypoxanthine was not detected. Hence, in addition to the cytosine permease, a purine permease exists in C. glabrata . This differs from the purine cytosine permeases in Saccharomyces cereuisiae and Candida albicans which transport adenine, cytosine, guanine and hypoxanthine.     

Microbial biofilm inoculants benefit growth and yield of chrysanthemum varieties under protected cultivation through enhanced nutrient availability

Protected cultivation of ornamental flowers, as a commercial venture, becomes less profitable with excessive use of fertilizers. The present study examined the influence of microbial biofilm inoculants (Anabaena–Azotobacter, Anabaena–Trichoderma and Trichoderma–Azotobacter) on the availability of soil nutrients and structure of rhizosphere microbial communities in three varieties of chrysanthemum (var. White Star, Thai Chen Queen and Zembla). Varietal-specific responses in growth, enzyme activities, flower yield of plants and availability of soil nutrients were recorded. Dehydrogenase activity was highest in var. White Star treated with the Anabaena–Trichoderma biofilm inoculants. The Anabaena–Azotobacter inoculant enhanced the availability of nitrogen, phosphorus and micronutrients in the soil, besides 40–50% increase in soil organic carbon, as compared to carrier alone or no inoculation. PCR-DGGE profiling of the cyanobacterial communities and qPCR quantification of 16S rRNA abundance of bacteria, archaea and cyanobacteria in the rhizosphere soils, revealed the stronger influences of these inoculants, especially in var. Zembla. Principal Component Analysis (PCA) helped to illustrate that the enhanced microbe-mediated availability of soil macro-and micronutrients, except iron content (Fe), was the most influential factor facilitating improved plant growth and yield parameters. The Anabaena–Azotobacter, and Anabaena–Trichoderma biofilm inoculants, proved superior in all three chrysanthemum varieties.     

Therapeutic resistance of pancreatic cancer: Roadmap to its reversal

Pancreatic cancer is a lethal disease with limited opportunity for resectable surgery as the first choice for cure due to its late diagnosis and early metastasis. The desmoplastic stroma and cellular genetic or epigenetic alterations of pancreatic cancer impose physical and biological barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Here, we review the current therapeutic options for pancreatic cancer, and underlying mechanisms and potential reversal of therapeutic resistance, a hallmark of this deadly disease.     

Free energy calculations and molecular dynamics simulations of wild-type and variants of the DNA-EcoRI complex.

Molecular dynamics simulations and free energy calculations of the wild-type EcoRI-DNA complex and several variants have been performed in aqueous solvent. In general, he theoretical estimations of the free energy differences (DeltaDeltaA) qualitatively agree well with the corresponding experimental data. The modifications which were experimentally found unfavorable compared to the wild-type complex were also found to be so in theoretical estimates. The mutant where the amino group of the base Ade(6) was replaced by a hydrogen atom eliminating one H-bond between the DNA and the protein, was experimentally found to be more stable than the wild-type complex. It was speculated that the modification also caused a structural relaxation in the DNA making DeltaDeltaA favorable. Our theoretical estimate yields a positive DeltaDeltaA in this case, but the difference is small, and no significant local structural relaxation was observed. The major H-bonds between the DNA and the protein in the wild-type complex are found to be maintained in the different mutants although the specific and non-specific interaction energies between the interacting the DNA bases and the protein residues are different in different mutants. The interaction pattern of the other nearby nucleotides are significantly influenced by each modification. Thus, the alteration of the non-specific interactions may also play an indirect role in determining the specificity of the complex. The interaction of the Gua(4) of the DNA with the protein is found to be most sensitive to any alteration in the recognition site. Because Gua(4) is the nucleotide closest to the scissile bond, this extra sensitivity seems to play an important role in altering the functional activity of the complex.     

Homocysteine to Hydrogen Sulfide or Hypertension

Hyperhomocysteinemia, an increased level of plasma homocysteine, is an independent risk factor for the development of premature arterial fibrosis with peripheral and cerebro-vascular, neurogenic and hypertensive heart disease, coronary occlusion and myocardial infarction, as well as venous thromboembolism. It is reported that hyperhomocysteinemia causes vascular dysfunction by two major routes: (1) increasing blood pressure and, (2) impairing the vasorelaxation activity of endothelial-derived nitric oxide. The homocysteine activates metalloproteinases and induces collagen synthesis and causes imbalances of elastin/collagen ratio which compromise vascular elastance. The metabolites from hyperhomocysteinemic endothelium could modify components of the underlying muscle cells, leading to vascular dysfunction and hypertension. Homocysteine metabolizes in the body to produce H₂S, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine γ-lyase. Thus, reduced production of H₂S during hyperhomocysteinemia exemplifies hypertension and vascular diseases. In light of the present information, this review focuses on the mechanism of hyperhomocysteinemia-associated hypertension and highlights the novel modulatory role of H₂S to ameliorate hypertension.     

Influence of antibiotics and trace salts on lysine production by arthrobacter globiformis

A hydrocarbon utilizing strain of Arthrobacter globiformis Lb isolated from local soil has been found to yield lysine 3.4 g l^?1, keeping the medium optimal for pH, C- and N-sources. Addition of antibiotics and micronutrients to that optimal media stimulated cell growth and enhanced lysine yield.