Morphological aspects of the euphonic voice

The high quality of a euphonic voice is the result of complex interactions between many organs and systems. Vibrating vocal folds play a crucial role in this process. Their physiological motion is conditioned by the presence of the layered structure of laryngeal mucosa. In this study, we assessed the degree of dysphonia according to the Union of European Phoniatrics (UEP) scale. Videoendoscopy (VLS) and videostroboscopic (VLSS) examination of the larynx was used to visualize the vibration of the vocal folds. Morphological assessment of the inter-membranous part of the vocal fold mucosa was carried out using material collected after surgical treatment (60%) or obtained from autopsy (40%). The samples were examined by light microscopy and transmission electron microscopy. In euphonic voices, 1° of dysphonia (UEP) and the physiological endoscopic (VLS) and stroboscopic (VLSS) findings of vocal folds were registered. No morphological or ultramorphological changes were observed in the cells of the multilayered flat epithelium, basal membrane or in the stroma. Unchanged epithelial cells were situated on the basal membrane with folds. Moreover, numerous pericytes, vessels with multiplication of basal membranes, scanty collagenous fibers, plasmatic cells and lymphocytes were seen. Morphological changes with signs of atrophy and polypoid degeneration of the vocal fold mucosa were found in only 3 (15%) patients.     

Phosphonic pseudopeptides as human neutrophil elastase inhibitors--a combinatorial approach

Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries-products of Ugi and Passerini multicomponent condensations-leading to the selection of new biologically active phosphonic pseudopeptides. As the starting isonitriles, 1-isocyanoalkylphosphonate diaryl ester derivatives were applied. The structure of the synthesized inhibitors was designed to target human neutrophil elastase, a serine protease whose uncontrolled activity may lead to development of several pathophysiological states such as rheumatoid arthritis, cystic fibrosis or tumor growth and invasion. After screening the inhibitory activity of our constructed libraries, the most active compounds were synthesized as single molecules. One of the obtained inhibitors, Cbz-Met-O-Met-Val(P)(OC(6)H(4)-p-Cl)(2), displayed apparent second-order inhibition value at 40,105M(-1)s(-1) as the diastereomers mixture. Inhibition potency and selectivity of action toward other serine proteases as well as the results of initial in vitro experiments regarding inhibitors influence on cancer cell proliferation are presented.     

Polymorphisms of fibronectin-1 (rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655) are not associated with bronchopulmonary dysplasia in preterm infants

Molecular and Cellular Biochemistry - Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved...     

The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.     

Nitroxyl (HNO) Reacts with Molecular Oxygen and Forms Peroxynitrite at Physiological pH: BIOLOGICAL IMPLICATIONS*

Nitroxyl (HNO), the protonated one-electron reduction product of NO, remains an enigmatic reactive nitrogen species. Its chemical reactivity and biological activity are still not completely understood. HNO donors show biological effects different from NO donors. Although HNO reactivity with molecular oxygen is described in the literature, the product of this reaction has not yet been unambiguously identified. Here we report that the decomposition of HNO donors under aerobic conditions in aqueous solutions at physiological pH leads to the formation of peroxynitrite (ONOO⁻) as a major intermediate. We have specifically detected and quantified ONOO⁻ with the aid of boronate probes, e.g. coumarin-7-boronic acid or 4-boronobenzyl derivative of fluorescein methyl ester. In addition to the major phenolic products, peroxynitrite-specific minor products of oxidation of boronate probes were detected under these conditions. Using the competition kinetics method and a set of HNO scavengers, the value of the second order rate constant of the HNO reaction with oxygen (k = 1.8 × 10⁴ m⁻¹ s⁻¹) was determined. The rate constant (k = 2 × 10⁴ m⁻¹ s⁻¹) was also determined using kinetic simulations. The kinetic parameters of the reactions of HNO with selected thiols, including cysteine, dithiothreitol, N-acetylcysteine, captopril, bovine and human serum albumins, and hydrogen sulfide, are reported. Biological and cardiovascular implications of nitroxyl reactions are discussed.     

A System for Heart Sounds Classification

The future of quick and efficient disease diagnosis lays in the development of reliable non-invasive methods. As for the cardiac diseases – one of the major causes of death around the globe – a concept of an electronic stethoscope equipped with an automatic heart tone identification system appears to be the best solution. Thanks to the advancement in technology, the quality of phonocardiography signals is no longer an issue. However, appropriate algorithms for auto-diagnosis systems of heart diseases that could be capable of distinguishing most of known pathological states have not been yet developed. The main issue is non-stationary character of phonocardiography signals as well as a wide range of distinguishable pathological heart sounds. In this paper a new heart sound classification technique, which might find use in medical diagnostic systems, is presented. It is shown that by combining Linear Predictive Coding coefficients, used for future extraction, with a classifier built upon combining Support Vector Machine and Modified Cuckoo Search algorithm, an improvement in performance of the diagnostic system, in terms of accuracy, complexity and range of distinguishable heart sounds, can be made. The developed system achieved accuracy above 93% for all considered cases including simultaneous identification of twelve different heart sound classes. The respective system is compared with four different major classification methods, proving its reliability.     

Vap (Vascular Associated Protein): a novel factor involved in erythropoiesis and angiogenesis

Both endothelial and erythroid cells are generated in the intermediate cell mass (ICM) during zebrafish embryogenesis, but the nature of the genes that contribute to the processes of erythrocyte maturation and blood vessel network formation is not fully understood. From our in situ-based screening, we have identified a novel factor, Vap (Vascular Associated Protein) that is predominantly expressed in the ICM, and subsequently enriched in endothelial cells. Vap expression in the ICM was drastically suppressed in the cloche mutant that has defects in both vasculogenesis and hematopoiesis, whereas Vap expression was not affected in the vlad tepes/gata1 mutant. Knockdown of Vap using anti-sense morpholinos (VAP-MO) not only resulted in decreased numbers of erythrocytes but also in the strong suppression of hemoglobin production. Further, we found that Vap knockdown caused the disorganization of the intersegmental vessels (ISVs), which show irregular branching. We propose that Vap plays an important role in the maturation of endothelial and erythroid cells in zebrafish.     

barx1 is necessary for ectomesenchyme proliferation and osteochondroprogenitor condensation in the zebrafish pharyngeal arches

Barx1 modulates cellular adhesion molecule expression and participates in specification of tooth-types, but little is understood of its role in patterning the pharyngeal arches. We examined barx1 expression during zebrafish craniofacial development and performed a functional analysis using antisense morpholino oligonucleotides. Barx1 is expressed in the rhombencephalic neural crest, the pharyngeal arches, the pectoral fin buds and the gut in contrast to its paralogue barx2, which is most prominently expressed in the arch epithelium. Additionally, barx1 transient expression was observed in the posterior lateral line ganglia and developing trunk/tail. We show that Barx1 is necessary for proliferation of the arch osteochondrogenic progenitors, and that morphants exhibit diminished and dysmorphic arch cartilage elements due to reductions in chondrocyte differentiation and condensation. Attenuation of Barx1 results in lost arch expression of osteochondrogenic markers col2a1, runx2a and chondromodulin, as well as odontogenic marker dlx2b. Further, loss of barx1 positively influenced gdf5 and chordin, markers of jaw joint patterning. FGF signaling is required for maintaining barx1 expression, and that ectopic BMP4 induces expression of barx1 in the intermediate region of the second pharyngeal arch. Together, these results indicate an essential role for barx1 at early stages of chondrogenesis within the developing zebrafish viscerocranium.