Chemometric methods for simultaneous quantification of lactic,malic and fumaric acids

Lactic, fumaric and malic acids are commonly used in food and pharmaceutical industries. During microbial production of these compounds, it is important to determine their concentrations in the fermentation broth with a rapid and sensitive method. Spectrophotometry is commonly used. However, UV‐spectral overlap between these organic acids makes it difficult to determine each of them individually from the mixture. In order to overcome this problem, statistical methods, namely principal component regression (PCR) and partial least squares‐1 methods, were tested and compared with conventional HPLC techniques. The absorbance data matrix was obtained by measuring the absorbances of 21 ternary mixtures of lactic, fumaric and malic acids in a wavelength range of 210–260 nm. Calibration and validation were performed by using the data obtained in a mixture of these organic acids. The prediction abilities of the methods were tested by applying them to fermentation broths. The precision of the PCR method was better than that of the partial least squares‐1 method. In the PCR method, the correlation coefficients between actual and predicted concentrations of the organic acids were calculated as 0.970 for lactic acid and 0.996 for fumaric acid in fermentation broths. The concentration of malic acid was not detected due to its low concentration in samples. These results show that the PCR method can be applied for simultaneous determination of lactic, fumaric and malic acids in fermentation broths.     

Interaction of magnetite-based receptors in the beak with the visual system underlying 'fixed direction' responses in birds

Background

European robins, Erithacus rubecula, show two types of directional responses to the magnetic field: (1) compass orientation that is based on radical pair processes and lateralized in favor of the right eye and (2) so-called 'fixed direction' responses that originate in the magnetite-based receptors in the upper beak. Both responses are light-dependent. Lateralization of the 'fixed direction' responses would suggest an interaction between the two magnetoreception systems.

Results

Robins were tested with either the right or the left eye covered or with both eyes uncovered for their orientation under different light conditions. With 502 nm turquoise light, the birds showed normal compass orientation, whereas they displayed an easterly 'fixed direction' response under a combination of 502 nm turquoise with 590 nm yellow light. Monocularly right-eyed birds with their left eye covered were oriented just as they were binocularly as controls: under turquoise in their northerly migratory direction, under turquoise-and-yellow towards east. The response of monocularly left-eyed birds differed: under turquoise light, they were disoriented, reflecting a lateralization of the magnetic compass system in favor of the right eye, whereas they continued to head eastward under turquoise-and-yellow light.

Conclusion

'Fixed direction' responses are not lateralized. Hence the interactions between the magnetite-receptors in the beak and the visual system do not seem to involve the magnetoreception system based on radical pair processes, but rather other, non-lateralized components of the visual system.     

Left hemispheric advantage for numerical abilities in the bottlenose dolphin

In a two-choice discrimination paradigm, a bottlenose dolphin discriminated relational dimensions between visual numerosity stimuli under monocular viewing conditions. After prior binocular acquisition of the task, two monocular test series with different number stimuli were conducted. In accordance with recent studies on visual lateralization in the bottlenose dolphin, our results revealed an overall advantage of the right visual field. Due to the complete decussation of the optic nerve fibers, this suggests a specialization of the left hemisphere for analysing relational features between stimuli as required in tests for numerical abilities. These processes are typically right hemisphere-based in other mammals (including humans) and birds. The present data provide further evidence for a general right visual field advantage in bottlenose dolphins for visual information processing. It is thus assumed that dolphins possess a unique functional architecture of their cerebral asymmetries.     

Insertion/deletion polymorphism of the angiotensin converting enzyme gene in coronary artery disease in southern Turkey

Genetic factors are important in the pathogenesis of coronary artery disease (CAD). Angiotensin converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism is one of the genetic factor found to be related with CAD. We investigated the association between I/D polymorphism of the ACE gene and the presence of CAD. Three hundred and seven patients (187 males and 120 females, aged between 35-80, mean 54.3 +/-9.8 years) who underwent diagnostic coronary angiography were included in the study. ACE I/D polymorphism was detected by polymerase chain reaction. Of the 307, 176 had CAD. The most frequently observed genotype in all subjects was ID (47.9 %). However, in patients with CAD the frequency of II genotype was lower whereas DD genotype was higher compared to the controls (p < 0.05). The number of D allele carrying subjects were also higher (p < 0.05) in CAD patients. The logistic regression analysis indicated that the ACE D allele is an independent risk factor (odds ratio = 1.48, 95 % CI = 1.01-2.18, p < 0.05). In conclusion, the I/D polymorphism of ACE gene (carrying D allele) is an independent risk factor for CAD in the studied Turkish population.     

The avian 'prefrontal cortex' and cognition

Both mammals and birds can flexibly organize their behavior over time. In mammals, the mental operations generating this ability are called executive functions and are associated with the prefrontal cortex. The corresponding structure in birds is the nidopallium caudolaterale. Anatomical, neurochemical, electrophysiological and behavioral studies show these structures to be highly similar. The avian forebrain displays no lamination that corresponds to the mammalian neocortex, hence lamination does not seem to be a requirement for higher cognitive functions. Because all other aspects of the neural architecture of the mammalian and the avian prefrontal areas are extremely comparable, the freedom to create different neural architectures that generate prefrontal functions seems to be very limited.     

Effects of HA-1077 and Y-27632, two rho-kinase inhibitors, in the human umbilical artery

A role for the small G protein rho and rho-kinase has been shown in smooth muscle contraction regarding Ca⁺⁺ sensitivity. However, there are no data in the literature assessing how this system operates in human umbilical arteries (HUA). Therefore, we evaluated the effects of HA-1077 and Y-27632, two rho-kinase inhibitors, on agonist-(5-hydroxytryptamine [5-HT]) and depolarization-induced (KCl) contractions of HUA. HA-1077 and Y-27632 inhibited 5-HT-induced contractile responses at 10⁻⁴ M concentration but not at 10⁻⁵ M. HA-1077 at 10⁻⁴ M also significantly attenuated contractions induced by 20 mM KCl. In addition, HUA precontracted with 5-HT relaxed concentration dependently in response to HA-1077 and Y-27632. When precontracted with KCl, HUA also relaxed dose-dependently in response to HA-1077, but the maximal relaxation was significantly smaller than the response obtained when precontracted with 5-HT. To determine possible involvement of rho-kinase on agonist-induced intracellular calcium-mediated contractions, tissues were precontracted with 5-HT in Ca⁺⁺-free Krebs solution before cumulative addition of HA-1077 or Y-27632 (10⁻⁷ to 10⁻⁴ M). Both rho-kinase inhibitors relaxed HUA completely. Maximum relaxations of HUA to HA-1077 and Y-27632 were significantly larger than the responses seen in normal Krebs solution and were obtained with lower concentrations of the drugs considered to be more specific for rho-kinase inhibition. However, preincubation of HUA with HA-1077 or Y-27632 (10⁻⁵ M for both) did not affect the 5-HT-induced contractions in this medium. Finally, immunoblot experiments revealed the expression of rho-kinase isoform rockII protein in HUA. These results indicate that rhoA/rho-kinase pathway can contribute to agonist-induced contractions of HUA. However, this effect appears to be limited to intracellular calcium-induced contractions and may be more important in sustaining contractions rather than the initial phase of force development.     

FL3, a Synthetic Flavagline and Ligand of Prohibitins,Protects Cardiomyocytes via STAT3 from Doxorubicin Toxicity

Aims

The clinical use of doxorubicin for the treatment of cancer is limited by its cardiotoxicity. Flavaglines are natural products that have both potent anticancer and cardioprotective properties. A synthetic analog of flavaglines, FL3, efficiently protects mice from the cardiotoxicity of doxorubicin. The mechanism underlying this cardioprotective effect has yet to be elucidated.

Methods and Results

Here, we show that FL3 binds to the scaffold proteins prohibitins (PHBs) and thus promotes their translocation to mitochondria in the H9c2 cardiomyocytes. FL3 induces heterodimerization of PHB1 with STAT3, thereby ensuring cardioprotection from doxorubicin toxicity. This interaction is associated with phosphorylation of STAT3. A JAK2 inhibitor, WP1066, suppresses both the phosphorylation of STAT3 and the protective effect of FL3 in cardiomyocytes. The involvement of PHBs in the FL3-mediated cardioprotection was confirmed by means of small interfering RNAs (siRNAs) targeting PHB1 and PHB2. The siRNA knockdown of PHBs inhibits both phosphorylation of STAT3 and the cardioprotective effect of FL3.

Conclusion

Activation of mitochondrial STAT3/PHB1 complex by PHB ligands may be a new strategy against doxorubicin-induced cardiotoxicity and possibly other cardiac problems.