Increased circulating heat shock protein 70 levels in pregnant asthmatics

Asthma is one of the most common diseases complicating pregnancy and represents a risk factor for several maternal and perinatal complications. The natural history of asthma is known to change in pregnancy, but very few data are available in the terms of pathomechanism of this change during gestation. Circulating heat shock protein 70 (Hsp70) levels are decreased in healthy pregnancy, which might reflect physiological immunotolerance. The aim of our study was to determine the serum levels of Hsp70 in asthmatic women during gestation. Forty pregnant women with bronchial asthma and 40 healthy pregnant women matched for maternal and gestational age were involved in this case-control study. Serum Hsp70 levels were measured using the ELISA Kit of R&D Systems. Spirometry and oxygen saturation measurements were performed in asthmatic patients. In asthmatic pregnant women, an increase of serum Hsp70 levels was observed compared to healthy pregnant women (median (25–75 percentile): 0.44 ng/ml (0.36–0.53) versus 0.21 ng/ml (0–0.27), p < 0.001). Fetal birth weight of asthmatic mothers was significantly smaller than of healthy controls, but in the normal range (3,230 g (2,690–3,550) versus 3,550 g (3,450–3,775), p < 0.05). A statistically significant negative correlation between maternal age and serum Hsp70 concentrations (Spearman R = −0.48, p = 0.0018) and a significant positive correlation between gestational age and serum Hsp70 levels (Spearman R = 0.83, p < 0.001) were detected in healthy pregnant women. In conclusion, this study proves an elevation of circulating Hsp70 levels during asthmatic pregnancy compared to healthy pregnant women. However, further studies are warranted to determine the role of circulating Hsp70 in the pathogenesis of maternal and perinatal complications of asthma in pregnancy.     

Restriction of the enzymatic hydrolysis of steam-pretreated spruce by lignin and hemicellulose

The presence of lignin is known to reduce the efficiency of the enzymatic hydrolysis of lignocellulosic raw materials. On the other hand, solubilization of hemicellulose, especially of xylan, is known to enhance the hydrolysis of cellulose. The enzymatic hydrolysis of spruce, recognized among the most challenging lignocellulosic substrates, was studied by commercial and purified enzymes from Trichoderma reesei. Previously, the enzymatic hydrolysis of steam pretreated spruce has been studied mainly by using commercial enzymes and no efforts have been taken to clarify the bottlenecks by using purified enzyme components.Steam-pretreated spruce was hydrolyzed with a mixture of Celluclast and Novozym 188 to obtain a hydrolysis residue, expectedly containing the most resistant components. The pretreated raw material and the hydrolysis residue were analyzed for the enrichment of structural bottlenecks during the hydrolysis. Lignin was removed from these two materials with chlorite delignification method in order to eliminate the limitations caused by lignin. Avicel was used for comparison as a known model substrate. Mixtures of purified enzymes were used to investigate the hydrolysis of the individual carbohydrates: cellulose, glucomannan and xylan in the substrates. The results reveal that factors limiting the hydrolysis are mainly due to the lignin, and to a minor extent by the lack of accessory enzymes. Removal of lignin doubled the hydrolysis degree of the raw material and the residue, and reached close to 100% of the theoretical within 2 days. The presence of xylan seems to limit the hydrolysability, especially of the delignified substrates. The hydrolysis results also revealed significant hemicellulose impurities in the commonly used cellulose model substrate, making it questionable to use Avicel as a model cellulose substrate for hydrolysis experiments.     

Reactive oxygen species, Ca2+ signaling and mitochondrial NAD(P)H level in adrenal glomerulosa cells

The acute effects of ultraviolet light, the superoxide-generating xanthine-xanthine oxidase system and H(2)O(2) to on calcium signaling and mitochondrial pyridine nucleotide metabolism were investigated in rat glomerulosa cells. UV light induced the formation of superoxide, that, similar to exogenously applied superoxide and H(2)O(2), decreased the level of mitochondrial NAD(P)H. Free radical scavengers antagonized this effect of UV light. Extracellularly generated superoxide elicited Ca(2+) transients and inhibited angiotensin II-induced cytoplasmic Ca(2+) signaling. Low intensity UV light did not affect basal [Ca(2+)] and failed to influence Ca(2+) signaling induced by depolarization or store depletion. UV light of the same low power reduced both cytoplasmic and mitochondrial Ca(2+) signals induced by angiotensin II. The lack of UV effect on inositol phosphate formation indicates that the inhibition of cytoplasmic Ca(2+) signaling is due to reduced Ca(2+) release from InsP(3)-sensitive stores. Decreased mitochondrial Ca(2+) uptake may be attributed to UV-induced perturbation of the perimitochondrial microdomain.     

4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17beta-hydroxysteroid dehydrogenase. Part 3. Identification of lead candidate

A series of 4,5-disubstituted cis-pyrrolidinones was investigated as inhibitors of 17beta-HSD II for the treatment of osteoporosis. Biochemical data for several compounds are given. Compound 42 was selected as the lead candidate.     

The Autism Psychodynamic Evaluation of Changes (APEC) scale: A reliability and validity study on a newly developed standardized psychodynamic assessment for youth with Pervasive Developmental Disorders

The present study was designed to examine the reliability and validity of the Autism Psychodynamic Evaluation of Changes (APEC) scale, developed to assess the evolution in individuals with autism under treatment. The APEC scale focuses on the key role of impairment in body image construction, which requires cross-modal sensory integration through emotional communication with motor representations. Thus, the body image construction is associated simultaneously with spatial and temporal organization and allows the emergence of self- and others-representations. The use of the APEC scale, with its seven domains (expression of emotion in relationships, eye contact, body image, graphic productions, exploration of space and objects, time perception, and verbal language), underlines the importance in autistic disorder of anxieties related to body and spatial representations, and of impairment in the body ego construction which is closely linked to the emergence of individuation/separation processes. This study was conducted on 73 children and adolescents with autistic disorder. They were recruited in day care facilities where two caregivers independently gave their ratings based on their clinical observation on a daily basis during the same month. Analyses included assessing construct validity through correspondence analyses and inter-rater reliability using kappa coefficients. The APEC scale offers a reliable and validated psychodynamic assessment of interest for professionals (such as child psychiatrists, caregivers, therapists or teachers) and researchers working with children, adolescents and adults with autistic disorder, especially in the follow-up of their evolution. The APEC scale provides an approach at the interface of psychoanalysis and neuroscience, and is also of interest for clinical and developmental psychology. Using the APEC scale in a range of different practical and research settings will foster links between psychoanalytic perspectives and educational training for children with autistic disorder, and will contribute to the dialogue between psychoanalysis, neuroscience and psychology.     

The role of the N-terminal loop in the function of the colicin E7 nuclease domain

Colicin E7 (ColE7) is a metallonuclease toxin of Escherichia coli belonging to the HNH superfamily of nucleases. It contains highly conserved amino acids in its HHX₁₄NX₈HX₃H ββα-type metal ion binding C-terminal active centre. However, the proximity of the arginine at the N-terminus of the nuclease domain of ColE7 (NColE7, 446–576) is necessary for the hydrolytic activity. This poses a possibility of allosteric activation control in this protein. To obtain more information on this phenomenon, two protein mutants were expressed, i.e. four and 25 N-terminal amino acids were removed from NColE7. The effect of the N-terminal truncation on the Zn²⁺ ion and DNA binding as well as on the activity was investigated in this study by mass spectrometry, synchrotron-radiation circular dichroism and fluorescence spectroscopy and agarose gel mobility shift assays. The dynamics of protein backbone movement was simulated by molecular dynamics. Semiempirical quantum chemical calculations were performed to obtain better insight into the structure of the active centre. The longer protein interacted with both Zn²⁺ ion and DNA more strongly than its shorter counterpart. The results were explained by the structural stabilization effect of the N-terminal amino acids on the catalytic centre. In agreement with this, the absence of the N-terminal sequences resulted in significantly increased movement of the backbone atoms compared with that in the native NColE7: in ΔN25-NColE7 the amino acid strings between residues 485–487, 511–515 and 570–571, and in ΔN4-NColE7 those between residues 467–468, 530–535 and 570–571.     

Synthesis of lipid II phosphonate analogues

Simple analogues of lipid II were synthesized from 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-β-d-glucopyranose using conjugate addition onto ethylidene bisphosphonate and subsequent Wadsworth–Horner–Emmons reaction with long chain aliphatic aldehydes.     

Investigation of glycosylating properties of 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranosyl derivatives. Synthesis of a new sulfonic acid mimetic of the sialyl Lewis X tetrasaccharide

Glycosylation reactions of the ethylthio, bromo and chloro derivatives of 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranose were studied applying different acceptors under different conditions. Elimination side-reactions affording exo- and endoglycals occured in all cases, however, with different proportions. Glycosyl chloride donor was applied to glycosylate a trisaccharide acceptor obtaining a new sulfonic acid mimetic of the sialyl Lewis X tetrasaccharide in high yield.