A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord

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Novel approach for fetal heart rate classification introducing grammatical evolution

Fetal heart rate (FHR) variations reflect the level of oxygenation and blood pressure of the fetus. Electronic Fetal Monitoring (EFM), the continuous monitoring of the FHR, was introduced into clinical practice in the late 1960s and since then it has been considered as an indispensable tool for fetal surveillance. However, EFM evaluation and its merit is still an open field of controversy, mainly because it is not consistently reproducible and effective. In this work, we present a novel method based on grammatical evolution to discriminate acidemic from normal fetuses, utilizing features extracted from the FHR signal during the minutes immediately preceding delivery. The proposed method identifies linear and nonlinear correlations among the originally extracted features and creates/constructs a set of new ones, which, in turn, feed a nonlinear classifier. The classifier, which also uses a hybrid method for training, along with the constructed features was tested using a set of real data achieving an overall performance of 90% (specificity = sensitivity = 90%).     

The Cretan type of non-deletional hereditary persistence of fetal hemoglobin [Aγ–158C→T] results from two independent gene conversion events

We report a new type of non-deletional hereditary persistence of fetal hemoglobin that is due to a C→T transition at position –158, relative to the Cap site of the human Aγ-globin gene. This mutation was identified in three unrelated adult cases presenting slightly elevated levels of fetal hemoglobin (Hb F), i.e. 2.9–5.1%, and normal hematological indices. Our sequencing results, from both polymerase chain reaction-amplified and subcloned DNA fragments, indicate that the Aγ–158C→T mutation occurred by two independent gene conversion events in the three cases studied. In addition, hematological and molecular data, including restriction fragment length polymorphism haplotyping in the β-globin gene cluster, extended haplotype analysis inside the γ-globin gene region and routine analysis of three tandem repeat loci (D1S80, 3′-HVR/apoB and F8vWf), led us to conclude that the Aγ–158C→T mutation in one of the three cases occurred recently in the parental germ line (P=99.47%), representing the first example of a de novo gene conversion event identified in humans. Received: 10 November 1997 / Accepted: 10 February 1998     

Design and synthesis of potent tyr(OMe)5-gonadotropin-releasing hormone (GnRH) analogues with modifications at positions 6, 9 and 10

We have recently reported the synthesis and the conformational properties of some Gonadotropin-releasing hormone (GnRH) analogues in which the tyrosine residue at position 5 is substituted with tyrosine-O-methyl (Keramida et al., Let. Pept. Sci., 3 (1996) 257/Matsoukas et al., Eur. J. Med. Chem., 32 (1997) 927). The analogue [Tyr-(OMe)⁵]-GnRH was found to exert a lower degree of desensitization than the native GnRH peptides in terms of pituitary gonadotropin (GTH) release in goldfish. Compared to GnRH, however, [Tyr-(OMe)⁵]-GnRH exerted a lower GTH-release potency in cultured goldfish pituitary fragments, and was bound with a lower binding affinity to the rat pituitary GnRH receptors. In order to increase the potency of [Tyr-(OMe)⁵]-GnRH, we have synthesized a group of GnRH peptides containing Tyr-(OMe)⁵ in combination with other substitutions at positions 6, 9 and 10 and we have estimated their binding affinity for the rat pituitary receptors and gonadotropin (GTH) release potency in the goldfish pituitary. A selected number of these analogues was also tested for their ability to induce ovulation in seabass. The important structural modifications that increased the binding and gonadotropic activity of [Tyr(OMe)⁵]-GnRH in vitro and in vivo were found to include the replacement of the proline at position 9 with azetidine, glycine amide terminus with an alkyl amide group and Gly⁶ residue with hydrophilic D-amino acids such as D-Arg⁶. Overall, the findings provide SAR information on a group of novel GnRH peptides that can be also used to induce ovulation in teleosts.     

A simple method to tune the gross antibacterial activity of cellulosic biomaterials

A very preliminary approach for grossly tuning the antibacterial activity of cellulosic fibers has been developed and its preliminary findings are described herein. The approach is universal for cellulosic-based substrates and first involves a physico-chemical adsorption phenomenon between fatty acid methyl esters (FAMEs) and cellulose. The cellulose biomaterials were in the form of disks 2 cm in diameter that were subjected to standard agar growth plates containing a gamut of gram positive and gram negative bacteria. Zones of inhibition were measured around the biomaterials which displayed a broad spectrum of antibacterial activity. This activity could be tuned simply by grossly changing the surface area of the cellulosic surface topology as indicated by the surface fibrillation of the microfibrils and hence the bioactive availability of the fatty acids. Thus, the potential application of these materials in the biomedical field appears promising.     

Superimposition of potent non-peptide AT1 receptor antagonists with angiotensin II

Summary The model of angiotensin II (ANG II) developed in our laboratory using a combination of NMR, fluorescence data and molecular graphics [Matsoukas, J.M. et al., J. Biol. Chem., 269 (1994) 5303] served as a template for a systematic superimposition of potent AT₁ receptor antagonists with ANG II. The key amino acids in this model, tyrosine, phenylalanine and histidine, form a charge-relay system. The studied ANG II AT₁ receptor antagonists were found to accommodate this relay system. The proposed model offers a motivation to synthetic chemists to develop ANG II antagonists that differ from the losartan prototype structure but possess an enhanced biological profile.     

Vibrational spectroscopy and X-ray diffraction methods to establish the differences between hardwood and softwood

FT-IR spectrometry and X-ray diffraction were applied to probe the differences between pulp fibers from Eucalyptus wood (hardwood) and Norway spruce wood (softwood). Wood processing was found to induce certain structural alterations within its components depending on the type of wood and the applied procedure. These differences were established by using techniques such as; spectral comparison of wood samples with those of individual component fractions, derivative spectroscopy, bands deconvolution, etc. FT-IR spectroscopy was shown to be an important tool that provided details about the structural characteristics of hardwood and softwood samples. Using second-derivative spectra and deconvolution processes small differences between spectra became apparent that allowed correlations to be made related to wood composition. In addition a correlation was established between the integral absorptions for the various bands and lignin content as well as the lignin/carbohydrate content. Relations between various spectral characteristics and the degree of crystallinity and sample composition were established.