Structural basis for iron binding and release by a novel class of periplasmic iron-binding proteins found in gram-negative pathogens

We have determined the 1.35- and 1.45-A structures, respectively, of closed and open iron-loaded forms of Mannheimia haemolytica ferric ion-binding protein A. M. haemolytica is the causative agent in the economically important and fatal disease of cattle termed shipping fever. The periplasmic iron-binding protein of this gram-negative bacterium, which has homologous counterparts in many other pathogenic species, performs a key role in iron acquisition from mammalian host serum iron transport proteins and is essential for the survival of the pathogen within the host. The ferric (Fe(3+)) ion in the closed structure is bound by a novel asymmetric constellation of four ligands, including a synergistic carbonate anion. The open structure is ligated by three tyrosyl residues and a dynamically disordered solvent-exposed anion. Our results clearly implicate the synergistic anion as the primary mediator of global protein conformation and provide detailed insights into the molecular mechanisms of iron binding and release in the periplasm.     

Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against Candida species

New 2-substituted-phenyl-1H-benzimidazole-5-carboxylic acids (35, 38), ethyl-5-carboxylate (36), -5-carboxamides (37, 39),-5-carboxaldehyde (42), -5-chloro (40), -5-trifluoromethyl (41), and -5-carbonitriles (44-53, 55-67), -6-carbonitrile (54) were prepared and evaluated in vitro against Candida species. The cyano substituted compounds 53, 57, 58 and 61 exhibited the greatest activity with MIC values of 3.12 microg/mL, values similar to that of fluconazole.     

Increased risk of advanced prostate cancer associated with MnSOD Ala-9-Val gene polymorphism

We aimed to investigate the association between manganese superoxide dismutase (MnSOD) Ala-9-Val gene polymorphism and the initiation and/or progression of prostate cancer (PCa) as well as to evaluate its potential interactions with advanced age and smoking status. MnSOD Ala-9-Val gene polymorphism was carried out in 134 (mean age 64.1 ± 7.48) PCa patients and 159 (mean age 62.5 ± 7.53) healthy controls with serum prostate specific antigen (PSA) levels (<4 ng/ml) and normal digital rectal examination (DRE) findings in this prospectively designed study. PCa patients were classified as low stage disease (T₁ or T₂ and N₀M₀ stages) and high stage disease (T₃ or T₄ and N₀M₀ or N₁ or M₁ stages). Genotypes for MnSOD Ala-9-Val gene polymorphism were identified by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL). Despite lack of association between different genotypes of MnSOD Ala-9-Val gene polymorphism and the presence of PCa, patients with Ala/Ala genotype were at an increased risk of high stage disease compared with those with the Val/Val genotype [odds ratio (OR), 3.77; 95% CI, 1.30–10.94; P = 0.012]. However, no significant difference was observed in the distribution of each genotype among PCa patients, with respect to tumor grade. On the other hand, smoking status and aging did not seem to change the association between genotypes and PCa risk. Ala/Ala genotype of MnSOD polymorphism may have an effect on adverse features of PCa such as high stage disease.     

Effect of short-term interferon-β treatment on cytokines in multiple sclerosis: significant modulation of IL-17 and IL-23

Therapeutic effect of interferon-β (IFN-β) treatment has been associated with modulation of the balance between Th1, Th17, Th2 and regulatory T (Treg) cells, whereas the impact of disease modifying drugs on Th9-immunity in multiple sclerosis (MS) has not been studied. To investigate the short-term effects of IFN-β treatment on cytokines in MS, we determined serum levels of IL-17, IL-23, IL-10, IL-4, IFN-γ, IL-9 and TGF-β in relapsing remitting MS patients before and 2 months after IFN-β treatment by ELISA. MS patients showed increased IL-17, IL-23 and IL-4 levels and decreased IL-9 levels as compared to healthy controls. IFN-β treatment only reduced IL-17 and IL-23 levels, whereas the levels of other cytokines remained unchanged. IFN-β treatment appears to exert its earliest therapeutic effect on Th17-immunity. The influence of IL-9 on MS pathogenesis needs to be further studied.     

Yeast Flora during the Fermentation of Wines Made from Vitis viniferaL. cv. Emir and Kalecik Karasi Grown in Anatolia

Summary A study was conducted of the growth of Saccharomyces (S.) and non-Saccharomyces populations during alcoholic fermentation of Emir and Kalecik karasi grape varieties in the 1998 and 1999 vintages. Kloeckera (Kl.) apiculata, Kluyveromyces (K.) thermotolerans, S. cerevisiae and Candida (C.) pulcherrima were the dominant yeasts in fermentation of the 1998 vintage in Emir must. Kl. apiculata and K. thermotolerans proliferated at the beginning of the fermentation. The number of these yeasts eventually decreased when S. cerevisiae appeared as the dominant yeast on day four. But they remained until the end of the fermentation. Kl. apiculata, C. dattilla, C. pulcherrima, C. krusei and S. cerevisiae were found during the fermentation of the 1999 vintage Emir must. The count of S. cerevisiae was very high in the juice, but after skin fermentation and cold treatment, it disappeared and could not be isolated until day six of the fermentation. Kl. apiculata and C. dattilla were the dominant yeasts until S. cerevisiae started proliferation after the middle of the fermentation. Kl. apiculata, Metschnikowia (M.) pulcherrima, S. cerevisiae, C. holmii, C. valida, C. guillermondii and Candida sp. were isolated during the fermentation of Kalecik karasi must in 1998. Kl. apiculata, C. pulcherrima, S. cerevisiae, C. holmii and C. valida were identified in fermentation of must in the 1999 vintage. An erratum to this article is available at .     

Antioxidant status in cerebrovascular accident

Ischemia is associated with the pathological changes caused by the accumulation of reactive oxygen metabolites (ROM) in cerebrovascular accident (CVA). The aim of this study was to determine red cell copper/zinc-superoxide dismutase (Cu/Zn-SOD) and catalase activities and copper and zinc concentrations both in plasma and in red cells in CVA. Cu/Zn-SOD and catalase activities of 16 patients, with an average age of 64 yr, were measured spectrophotometrically; copper and zinc concentrations were determined by atomic absorption spectrophotometer. The results showed that Cu/Zn-SOD activity was increased markedly in patients compared to the young controls and reached a peak on the d 5 of the disease, whereas the catalase activity of the patients on d 3 and d 5 were in the normal range, but higher on d 10. The enzyme activities of the elderly group were generally increased compared to the young controls. Copper and zinc concentrations showed corresponding alterations. These findings suggested that the effects of oxidative stress in CVA might be reflected in red cell and plasma parameters. Presented at the III International Congress of Pathophysiology, Lahti, Finland, 28 June–3 July, 1998.     

Abaxial and Adaxial Stomatal Density, Stomatal Conductances and Water Status of Bean Primary Leaves as Affected by Paclobutrazol

The plant growth retardant, paclobutrazol at 8.5 or 17.0 μM concentrations effectively inhibited the stem elongation and primary leaf expansion of bean seedlings. Although the retardant reduced the relative water content in well-watered plants, the water and pressure potentials remained high in the primary leaves. K⁺, Na⁺, Mg²⁺ and Ca²⁺ contents in the primary leaves of the paclobutrazol-treated plants were not significantly different from those in the control. The stomatal density increased on both surfaces but the length of guard cells was not reduced significantly on the adaxial epidermes of the paclobutrazol-treated primary leaves. The inhibitory effect of paclobutrazol on the abaxial stomatal conductances became more pronounced with time during the light period but the adaxial surfaces displayed similar or slightly higher conductances than those of the control. The transpiration rate on a unit area basis did not change significantly or increased in the treated leaves thus the reduced water loss of paclobutrazol-treated plants was due to the reduced leaf area. Stomatal conductances of the adaxial surfaces responded more intensively to exogenous abscisic acid and the total leaf conductance decreased faster with increasing ABA concentration in the control than in the paclobutrazol-treated leaves. Paclobutrazol, an effective inhibitor of phytosterol biosynthesis, not only amplified the stomatal differentiation but increased the differences between the adaxial and abaxial stomatal conductances of the primary leaves.     

Flexural properties of repaired heat‐polymerising acrylic resin after wetting with monomer and acetone

doi:10.1111/j.1741‐2358.2009.00321.x
Flexural properties of repaired heat‐polymerising acrylic resin after wetting with monomer and acetone Objectives: Repair strength can be improved by treating fractured surfaces of a denture. Background: This study investigated flexural properties of heat‐polymerised acrylic resin specimens repaired with auto‐polymerising and visible light curing (VLC) resins after the repair surfaces were wetted with monomers or acetone. Materials and Methods: Fifty‐four specimens (65 × 10 × 2.5 mm) were prepared and 48 of them were sectioned to simulate denture fracture. Butt‐joint designed repair surfaces were wetted with heat‐, auto‐polymerising monomers and acetone for 180 s and repaired with auto‐polymerising and VLC resins. After repairs, specimens were subjected to three‐point bending test and flexural strength, strain, fracture load, modulus of elasticity and deflection values were recorded. Data were analysed with Student t and LSD tests (p ≤ 0.05). Results: Overall flexural strength, strain, fracture load and deflection values of specimens repaired with VLC resin were significantly higher than the specimens repaired with auto‐polymerising resin for all types of wetting agent (p < 0.05). Within the wetting agents, heat‐ and auto‐polymerising monomers produced the best mechanical properties, while wetting with acetone did not provide superior effect over both monomers. Conclusion: In clinical use, wetting the repair surfaces may result in stronger repairs. The use of bonding agent in VLC resin repairs in combination with wetting agent results in improved flexural properties.