FGF-21/FGF-21 receptor interaction and activation is determined by betaKlotho

Fibroblast growth factor-21 (FGF-21) is a metabolic regulator that can influence glucose and lipid control in diabetic rodents and primates. We demonstrate that betaKlotho is an integral part of an activated FGF-21-betaKlotho-FGF receptor (FGFR) complex thus a critical subunit of the FGF-21 receptor. Cells lacking betaKlotho did not respond to FGF-21; the introduction of betaKlotho to these cells conferred FGF-21-responsiveness and recapitulated the entire scope of FGF-21 signaling observed in naturally responsive cells. Interestingly, FGF-21-mediated effects are heparin independent suggesting that betaKlotho plays a role in FGF-21 activity similar to the one played by heparin in the signaling of conventional FGFs. Moreover, in addition to conferring specificity for FGF-21, betaKlotho appears to support FGF-19 activity and mediates the receptor selectivity profile of FGF-19. All together, these results indicate that betaKlotho and FGFRs form the cognate FGF-21 receptor complex, mediating FGF-21 cellular specificity and physiological effects.     

Removal of basic (Methylene Blue) and acid (Egacid Orange) dyes from waters by sorption on chemically treated wood shavings

Spruce wood shavings from Picea abies were used for an adsorptive removal of both basic as well as acid dyes from waters. The sorption properties of the sorbents were modified with HCl, Na(2)CO(3) and Na(2)HPO(4). The treatment of the wood sorbents with alkaline carbonate solution as well as with phosphate solution increased the sorption ability for the basic dye (Methylene Blue), whereas the treatment with mineral acid decreased the sorption ability for Methylene Blue to some extent. The opposite is true for the sorption of the acid dye--Egacid Orange. The maximum sorption capacities estimated from the Langmuir-Freundlich isotherms ranged from 0.060 to 0.165 mmol g(-1) for Methylene Blue, and from 0.045 to 0.513 mmol g(-1) for Egacid Orange. The basic dye sorption decreased at low pH values in accordance with a presupposed ion-exchange mechanism of the sorption. The sorption of acid dye, on the other hand, decreased with increasing pH. The presence of inorganic salts as well as surfactants exhibited only minor effects on the dye sorption.     

Acoustic rhinometry in humans: accuracy of nasal passage area estimates, and ability to quantify paranasal sinus volume and ostium size.

A comprehensive study that compared acoustic rhinometry (AR) data to computed tomography (CT) data was performed to evaluate the accuracy of AR measurements in estimating nasal passage area and to assess its ability of quantifying paranasal sinus volume and ostium size in live humans. Twenty nasal passages of 10 healthy adults were examined by using AR and CT. Actual cross-sectional areas of the nasal cavity, sinus ostia sizes, and maxillary and frontal sinus volumes were determined from CT sections perpendicular to the curved acoustic axis of the nasal passage. Nasal cavity volume (from nostril to choana) calculated from the AR-derived area-distance curve was compared with that from the CT-derived area-distance curve. AR measurements were also done on pipe models that featured a side branch (Helmholtz resonator of constant volume but two different neck diameters) simulating a paranasal sinus. In the anterior nasal cavity, there was good agreement between the cross-sectional areas determined by AR and CT. However, posterior to the sinus ostia, AR overestimated cross-sectional area. The difference between AR nasal volume and CT nasal volume was much smaller than the combined volume of the maxillary and frontal sinuses. The results suggest that AR measurements of the healthy adult nasal cavity are reasonably accurate to the level of the paranasal sinus ostia. Beyond this point, AR overestimates cross-sectional area and provides no quantitative data for sinus volume or ostium size. The effects of paranasal sinuses and acoustic resonances in the nasal cavity are not accounted for in the present AR algorithms.     

Emergence and spread of carbapenem-resistant Acinetobacter baumannii in a tertiary care hospital in Turkey

An intensive care unit (ICU)-based OXA-23-producing multiple-drug resistant Acinetobacter baumannii (MDRAB) outbreak was detected between October 2005 and October 2006. A total of 47 patients were infected/colonized with the outbreak strain. Clinical data were available from 37 patients. The all-cause mortality rate among the patients exposed to the epidemic strain was 35% (13/37). The outbreak strain and the resistance determinants were characterized both by microbiological methods and by molecular techniques. Cloning and sequencing experiments identified ISAbaI-associated bla(oxa-23) on the chromosome. Screening of imipenem-resistant Acinetobacter isolated from the ICU during the outbreak period with PCR identified 97 isolates as positive for the ISAbaI-bla(oxa-23) structure. Pulsed-field gel electrophoresis and plasmid analyses with selected nonrepetitive isolates revealed the clonality. Disk diffusion on cloxacillin-supplemented agar media and the real-time PCR experiments showed that outbreak isolates are overexpressing the ampC enzyme. This study highlights the occurrence of OXA-23-producing and ampC-overexpressing MDRAB in ICUs.     

Electrochemical study of the complexes of aspartame with Cu(II), Ni(II) and Zn(II) ions in the aqueous medium

The voltammetric behaviours of aspartame in the presence of some metal ions (Cu(II), Ni(II), Zn(II)) were investigated. In the presence of aspartame, copper ions reduced at two stages with quasi-reversible one-electron and, with increasing the aspartame (L) concentration, Cu(II)L(2) complex reduces at one-stage with irreversible two-electron reaction (-0.322 V). Zn(II)-aspartame complex (logbeta=3.70) was recognized by a cathodic peak at -1.320 V. Ni(II)-aspartame complex (logbeta=6.52) is reduced at the more positive potential (-0.87 V) than that of the hydrated Ni(II) ions (-1.088 V). In the case of the reduction of Ni(II) ions, aspartame serves as a catalyst. From electronic spectra data of the complexes, their stoichiometries of 1:2 (metal-ligand) in aqueous medium are determined. The greatness of these logarithmic values is agreement with Irwing-Williams series (NiZn).     

A new method of testing for Hardy-Weinberg equilibrium and ordering populations

The assumption of Hardy-Weinberg equilibrium (HWE) among alleles in a nonevolving population is of fundamental importance in genetic studies. Deviation from HWE in a population usually indicates inbreeding, stratification and sometimes problems in genotyping. In populations of affected individuals, these deviations can also provide evidence for association. In this paper, we introduce a measure based on the Kullback-Leibler discrimination information function that quantifies the deviation from HWE in a population. We use this measure to order populations. We also propose a test for HWE based on an estimate of this measure. The test is a statistically consistent test of the null hypothesis for all alternatives and is very easy to implement. Our proposed test statistic is compared with an earlier, widely used, test. Finally, the use of the proposed new test is shown in an illustrative example.     

Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents

Objectives: Obestatin has been initially characterized as a new peptide derived from the ghrelin precursor, which suppresses food intake and inhibits the orexigenic and prokinetic actions of ghrelin when injected peripherally or centrally in lean mice. However, reproducing these data remains controversial. Reasons for the disparity may be the use of different doses, routes, and animal models. We aimed to investigate the effects of peripheral and intracisternal (IC) injection of obestatin on feeding, gastric motility, and blood glucose in rats as well as in diet‐induced obese (DIO) mice. Research Methods and Procedures: Food intake and gastric emptying of a semi‐liquid caloric meal were measured after intraperitoneal (IP) injection of obestatin in rats and DIO mice. Gastric phasic motility and blood glucose were monitored in urethane‐anesthetized rats after IC or intravenous (IV) injection of obestatin. Results: Obestatin injected intraperitoneally at doses ranging from 0.1 to 3 mg/kg influenced neither acute food intake nor gastric emptying in rats. Obestatin injected intravenously at 0.3 or 3 mg/kg and IC at 7.5 or 30 µg/rat modified neither fasted gastric phasic motility nor blood glucose levels, while ghrelin (30 µg/kg, IV) increased and vagotomy suppressed gastric motility, and an oligosomatostatin analog (3 µg/rat, IC) decreased blood glucose. Obestatin, injected intraperitoneally (0.3 mg/kg) in DIO mice, did not alter feeding response to a fast, while urocortin 1 (10 µg/kg, IP) induced a 73.3% inhibition at 2 hours. Discussion: Our data demonstrate that peripheral administration of obestatin did not modify food intake in rats or obese mice or gastric motor function in rats.     

Macrosomic newborns of diabetic mothers are associated with increased aortic intima-media thickness and lipid concentrations

BACKGROUND/AIMS: Exposure to diabetes in utero has been established as a significant risk factor for some of components of metabolic syndrome. A few studies have examined relationship between the metabolic syndrome and echocardiographic left ventricular (LV) mass. We aimed to investigate relationship between abdominal aortic intima-media thickness (aIMT), LV mass and lipid profile in macrosomic newborns. METHODS: Abdominal aIMT was measured in 30 macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B) and 30 healthy neonates (group C). Lipid profile and LV mass were determined. RESULT: Mean aIMT was significantly higher in groups A and B (0.489 +/- 0.015, 0.466 +/- 0.019 mm, respectively) than in controls (0.375 +/- 0.024 mm). Weight-adjusted aIMT in group A was significantly higher than in groups B and C. Macrosomia was associated with increased lipid concentrations. Both LV mass indexed for BSA (body surface area) and birth weight measurements were significantly increased in group A compared with control. CONCLUSIONS: Macrosomic neonates of diabetic mothers have significant aIMT and LV mass indexed for BSA and birth weight with lipid alterations. It might play a role in the pathogenesis of atherosclerosis in adult life.     

Bisphenol A Promotes Cell Survival Following Oxidative DNA Damage in Mouse Fibroblasts

Bisphenol A (BPA) is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER) is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO₃) or laser irradiation as oxidative damaging agents. In experiments with KBrO₃, co-treatment with BPA partially reversed the KBrO₃-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.