Spontaneous Mirror Symmetry Breaking in the Aldol Reaction and its Potential Relevance in Prebiotic Chemistry

The origin of the single chirality of most biomolecules is still a great puzzle. Carbohydrates could form in the formose reaction, which is proposed to be autocatalytic and contains aldol reaction steps. Based on our earlier observation of organoautocatalysis and spontaneous enantioenrichment in absence of deliberate chiral influences in the aldol reaction of acetone and p-nitrobenzaldehyde we suggest that a similar effect might be present also in the aldol reactions involved in gluconeogenesis. Herein we show that reactant precipitation observed in our earlier reported experiments does not affect the asymmetric autocatalysis in the aldol reaction we studied. We explain the phenomenon of spontaneous mirror symmetry breaking in such organocatalytic homogenous systems qualitatively by non-linear reaction network kinetics and classical transition state theory.     

Protective effects of a plant histaminase in myocardial ischaemia and reperfusion injury in vivo

Grass pea seedling histaminase (a copper-diamine oxidase) was found to exert a significant cardioprotection against post-ischaemic reperfusion damage. Electrocardiogram (ECG) recordings from the rats subjected in vivo to ischaemia and reperfusion showed ventricular tachycardia (VT) and ventricular fibrillations (VF) occurring in 9 out of 12 untreated rats whereas no ventricular arrhythmias were found under histaminase (80U/kg body weight) treatment (n=16 rats). Computer-assisted morphometry of the ischaemic reperfused hearts stained with nitroblue tetrazolium showed the extension of damaged myocardium (area at risk and infarct size) significantly reduced in rats treated with histaminase, in comparison with the non-treated rats, whereas no protection was found with the semicarbazide inactivated histaminase. Biochemical markers of ischaemia-reperfusion myocardial tissue damage: malonyldialdehyde (MDA), tissue calcium concentration, myeloperoxidase (MPO), and apoptosis indicator caspase-3 were significantly elevated in untreated post-ischaemic reperfused rats, but significantly reduced under histaminase protection. In conclusion, plant histaminase appears to protect hearts from ischaemia-reperfusion injury by more than one mechanism, essentially involving histamine oxidation, and possibly as reactive oxygen species scavenger, presenting good perspectives for a novel therapeutic approach in treatment of ischaemic heart pathology.     

GFAP and antibodies against NMDA receptor subunit NR2 as biomarkers for acute cerebrovascular diseases

We studied whether the serum levels of glial fibrillary acidic protein (GFAP) and of antibodies against the N‐methyl‐d ‐aspartate receptor subunit NR2 (NR2 R_NMDA) can discriminate between intracerebral haemorrhage (ICH) and ischaemic stroke (IS) in stroke patients. We prospectively recruited patients with suspected stroke (72 confirmed) and 52 healthy controls. The type of brain lesion (ICH or IS) was established using brain imaging. The levels of GFAP and of antibodies against NR2 R_NMDA were measured in blood samples obtained within 12 hrs after stroke onset and 24, 48 and 72 hrs and 1 and 2 weeks later using ELISA immunoassay. Improvement in diagnostic performance was assessed in logistic regression models designed to predict the diagnosis and the type of stroke. GFAP peaks early during haemorrhagic brain lesions (at significantly higher levels), and late in ischaemic events, whereas antibodies against NR2 R_NMDA have significantly higher levels during IS at all time‐points. Neither of the two biomarkers used on its own could sufficiently discriminate patients, but when they are used in combination they can differentiate at 12 hrs after stroke, between ischaemic and haemorrhagic stroke with a sensitivity and specificity of 94% and 91%, respectively.     

Flaxseed and dried tomato waste used together in laying hens diet

The aim of this study was to investigate the effects of simultaneous supplementation of laying hens with dietary sources of n-3 polyunsaturated fatty acids (PUFA) and carotenoids on egg quality, fatty acids and carotenoid profile of the egg yolk and on feed and yolk lipid peroxidation. A 6-week experiment was carried out with 53-week old laying hens (96 Tetra SL) assigned to a control and three treatment groups supplemented with 5% flaxseeds and different levels of dried tomato waste (DTW, 2.5%, 5.0% and 10.0%). Hens from the groups supplemented with 5% and 7.5% DTW had a significantly lower average daily feed intake and laying percentage as compared to the control. Increased doses of dietary DTW enhanced yolk Roche colour score in direct correlation with the enrichment of egg yolk in carotenoids but decreased their transfer efficiency from feed to egg. After 4 weeks, egg yolk from hens fed with 5% flaxseeds and 7.5% DTW had increased lutein and zeaxanthin levels (by 29% and 24%, respectively) and the colour score was 3.5 fold higher compared to the control group. As a result of the dietary supplementation with flaxseed, the n-3 fatty acid content was 3.1–3.7-fold higher in egg yolk compared with the control and the n-6/n-3 ratio decreased from 18.3 (control) to 4.1–5.4 in supplemented diets. Dietary supplementation with 5% DTW effectively prevented lipid oxidation of eggs enriched with n-3 PUFA, but the increase in DTW content depressed the absorption and deposition of n-3 PUFA in egg yolk.     

Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII

A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents.     

Non-Invasive MRI and Spectroscopy of mdx Mice Reveal Temporal Changes in Dystrophic Muscle Imaging and in Energy Deficits

In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein expression results in repeated muscle injury and chronic inflammation. Magnetic resonance imaging shows promise as a surrogate outcome measure in both DMD and rehabilitation medicine that is capable of predicting clinical benefit years in advance of functional outcome measures. The mdx mouse reproduces the dystrophin deficiency that causes DMD and is routinely used for preclinical drug testing. There is a need to develop sensitive, non-invasive outcome measures in the mdx model that can be readily translatable to human clinical trials. Here we report the use of magnetic resonance imaging and spectroscopy techniques for the non-invasive monitoring of muscle damage in mdx mice. Using these techniques, we studied dystrophic mdx muscle in mice from 6 to 12 weeks of age, examining both the peak disease phase and natural recovery phase of the mdx disease course. T2 and fat-suppressed imaging revealed significant levels of tissue with elevated signal intensity in mdx hindlimb muscles at all ages; spectroscopy revealed a significant deficiency of energy metabolites in 6-week-old mdx mice. As the mdx mice progressed from the peak disease stage to the recovery stage of disease, each of these phenotypes was either eliminated or reduced, and the cross-sectional area of the mdx muscle was significantly increased when compared to that of wild-type mice. Histology indicates that hyper-intense MRI foci correspond to areas of dystrophic lesions containing inflammation as well as regenerating, degenerating and hypertrophied myofibers. Statistical sample size calculations provide several robust measures with the ability to detect intervention effects using small numbers of animals. These data establish a framework for further imaging or preclinical studies, and they support the development of MRI as a sensitive, non-invasive outcome measure for muscular dystrophy.     

Integration and scaling of UV‐B radiation effects on plants: from molecular interactions to whole plant responses

A process based model integrating the effects of UV‐B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed that UV‐B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermal UV‐B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions between UV‐B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2–5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increased UV‐B radiation through molecular level processes and their consequences to whole plant growth and development.     

Morning-evening preference: sleep pattern spectrum and lifestyle habits among Japanese junior high school pupils

We surveyed the sleep-wake patterns and lifestyle habits in a sample of Japanese first to third year junior high school children (n=638, age 12 to 15 yrs), of whom 29.3% were evening type, 64.1% intermediate type, and 6.6% morning type in preference. The morningness-eveningness (M-E) score was lower (more evening typed), 16.1 vs. 15.4 in first compared to third year students. There were significant gender differences, with girls showing a greater evening preference. Evening preference was associated with longer sleep latency, shortened sleep duration during schooldays and weekends, bad morning feeling, and episodes of daytime sleepiness. In contrast, morning preference was associated with higher sleep drive and better sleep-wake parameters and lifestyle habits. Our results suggest the morning preference should be promoted among junior high school children to increase the likelihood of more regular sleep-wake patterns and lifestyle habits.