Development of the interatrial wall during the ontogenesis of foetuses and children up to one year of age

Background: The foramen ovale, present in foetal interatrial septum, plays an important role during foetal life. During delivery, foramen ovale closes and becomes fossa ovalis, starting the pulmonary circulation. The aim of our study was to describe the growth of the interatrial wall and changes in location of the foramen ovale, and fossa ovalis during the ontogenesis in the human hearts.Materials and methods: The study was performed on post-mortem material obtained from 92 human hearts from 22nd week of foetal life up to 1 year of age, fixed in a 4% formalin solution.Results: The interatrial wall size in the studied development period was greater in the horizontal than in the vertical dimension. During ontogenesis up to 1 year old, the anterior and inferior parts of the interatrial wall increased their shares considerably by 8% and 6%, respectively. The percentage participation of foramen ovale in the interatrial wall construction in the foetal period formed more than 50% of its size and fairly decreased reaching in infants about 39%.Conclusions: Our study demonstrated that during ontogenesis, from the foetal period to infancy, the parts of the interatrial wall increase their dimensions unevenly. The foramen ovale growth is smaller, compared to the rest of the interatrial wall development. On the basis of our data we can assume that the foramen ovale centre tends to be found in the postero-inferior quadrant of the interatrial wall (foetuses) and in postero-superior quadrant of the interatrial wall — in infants

Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension

Purpose: To compare the intraocular pressure- (IOP-) lowering efficacy of fixed combinations travoprost 0.004%/timolol 0.5% and dorzolamide 2%/timolol 0.5% in patients with ocular hypertension or open-angle glaucoma. Methods: In this prospective, multicenter, double-masked, randomized clinical trial, 319 qualifying patients received either travoprost/timolol once daily in the morning (n = 157) or dorzolamide/timolol twice daily (n = 162). IOP was assessed morning and evening at 2 and 6 weeks. The primary outcome measure was mean diurnal IOP. Results: Baseline mean IOP values were similar between groups. Mean pooled diurnal IOP was significantly lower in the travoprost/timolol group (16.5 mmHg ± 0.23) than in the dorzolamide/timolol group (17.3 mmHg ± 0.23; P = 0.011). Mean IOP was significantly lower in the travoprost/timolol group compared to the dorzolamide/timolol group at the 9 AM time point both at Week 2 (P = 0.006) and Week 6 (P = 0.002). The travoprost/timolol combination produced mean IOP reductions from baseline of 35.3% to 38.5%, while the dorzolamide/timolol combination produced mean IOP reductions from baseline of 32.5% to 34.5%. Conclusions: The fixed combination travoprost 0.004%/timolol 0.5% dosed once daily in the morning demonstrated superior mean diurnal IOP-lowering efficacy compared to dorzolamide 2%/timolol 0.5% dosed twice daily in patients with ocular hypertension or open-angle glaucoma.publishersversionPeer reviewe

The impact of quantitative optimization of hybridization conditions on gene expression analysis.

BACKGROUND: With the growing availability of entire genome sequences, an increasing number of scientists can exploit oligonucleotide microarrays for genome-scale expression studies. While probe-design is a major research area, relatively little work has been reported on the optimization of microarray protocols. RESULTS: As shown in this study, suboptimal conditions can have considerable impact on biologically relevant observations. For example, deviation from the optimal temperature by one degree Celsius lead to a loss of up to 44% of differentially expressed genes identified. While genes from thousands of Gene Ontology categories were affected, transcription factors and other low-copy-number regulators were disproportionately lost. Calibrated protocols are thus required in order to take full advantage of the large dynamic range of microarrays.For an objective optimization of protocols we introduce an approach that maximizes the amount of information obtained per experiment. A comparison of two typical samples is sufficient for this calibration. We can ensure, however, that optimization results are independent of the samples and the specific measures used for calibration. Both simulations and spike-in experiments confirmed an unbiased determination of generally optimal experimental conditions. CONCLUSIONS: Well calibrated hybridization conditions are thus easily achieved and necessary for the efficient detection of differential expression. They are essential for the sensitive pro filing of low-copy-number molecules. This is particularly critical for studies of transcription factor expression, or the inference and study of regulatory networks.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Genetic Variations and Diseases in UniProtKB/Swiss-Prot: The Ins and Outs of Expert Manual Curation.

During the last few years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized, and made readily available through reliable online resources. The Swiss-Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss-Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss-Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype

Multiple functionally divergent and conserved copies of alpha tubulin in bdelloid rotifers.

BACKGROUND: Bdelloid rotifers are microscopic animals that have apparently survived without sex for millions of years and are able to survive desiccation at all life stages through a process called anhydrobiosis. Both of these characteristics are believed to have played a role in shaping several unusual features of bdelloid genomes discovered in recent years. Studies into the impact of asexuality and anhydrobiosis on bdelloid genomes have focused on understanding gene copy number. Here we investigate copy number and sequence divergence in alpha tubulin. Alpha tubulin is conserved and normally present in low copy numbers in animals, but multiplication of alpha tubulin copies has occurred in animals adapted to extreme environments, such as cold-adapted Antarctic fish. Using cloning and sequencing we compared alpha tubulin copy variation in four species of bdelloid rotifers and four species of monogonont rotifers, which are facultatively sexual and cannot survive desiccation as adults. Results were verified using transcriptome data from one bdelloid species, Adineta ricciae. RESULTS: In common with the typical pattern for animals, monogonont rotifers contain either one or two copies of alpha tubulin, but bdelloid species contain between 11 and 13 different copies, distributed across five classes. Approximately half of the copies form a highly conserved group that vary by only 1.1% amino acid pairwise divergence with each other and with the monogonont copies. The other copies have divergent amino acid sequences that evolved significantly faster between classes than within them, relative to synonymous changes, and vary in predicted biochemical properties. Copies of each class were expressed under the laboratory conditions used to construct the transcriptome. CONCLUSIONS: Our findings are consistent with recent evidence that bdelloids are degenerate tetraploids and that functional divergence of ancestral copies of genes has occurred, but show how further duplication events in the ancestor of bdelloids led to proliferation in both conserved and functionally divergent copies of this gene.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

\u3cem\u3ePhaeophleospora vochysiae\u3c/em\u3e Savi & Glienke sp. nov. Isolated from \u3cem\u3eVochysia divergens\u3c/em\u3e Found in the Pantanal, Brazil, Produces Bioactive Secondary Metabolites

Microorganisms associated with plants are highly diverse and can produce a large number of secondary metabolites, with antimicrobial, anti-parasitic and cytotoxic activities. We are particularly interested in exploring endophytes from medicinal plants found in the Pantanal, a unique and widely unexplored wetland in Brazil. In a bio-prospecting study, strains LGMF1213 and LGMF1215 were isolated as endophytes from Vochysia divergens, and by morphological and molecular phylogenetic analyses were characterized as Phaeophleospora vochysiae sp. nov. The chemical assessment of this species reveals three major compounds with high biological activity, cercoscosporin (1), isocercosporin (2) and the new compound 3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone (3). Besides the isolation of P. vochysiae as endophyte, the production of cercosporin compounds suggest that under specific conditions this species causes leaf spots, and may turn into a pathogen, since leaf spots are commonly caused by species of Cercospora that produce related compounds. In addition, the new compound 3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone showed considerable antimicrobial activity and low cytotoxicity, which needs further exploration

Antibacterial Activity of Endophytic Actinomycetes Isolated from the Medicinal Plant \u3cem\u3eVochysia divergens\u3c/em\u3e (Pantanal, Brazil)

Endophytic actinomycetes from medicinal plants produce a wide diversity of secondary metabolites (SM). However, to date, the knowledge about endophytes from Brazil remains scarce. Thus, we analyzed the antimicrobial potential of 10 actinomycetes isolated from the medicinal plant Vochysia divergens located in the Pantanal sul-mato-grossense, an unexplored wetland in Brazil. Strains were classified as belonging to the Aeromicrobium, Actinomadura, Microbacterium, Microbispora, Micrococcus, Sphaerisporangium, Streptomyces, and Williamsia genera, through morphological and 16S rRNA phylogenetic analyzes. A susceptibility analysis demonstrated that the strains were largely resistant to the antibiotics oxacillin and nalidixic acid. Additionally, different culture media (SG and R5A), and temperatures (28 and 36°C) were evaluated to select the best culture conditions to produce the active SM. All conditions were analyzed for active metabolites, and the best antibacterial activity was observed from metabolites produced with SG medium at 36°C. The LGMB491 (close related to Aeromicrobium ponti) extract showed the highest activity against methicillin-resistant Staphylococcus aureus (MRSA), with a MIC of 0.04 mg/mL, and it was selected for SM identification. Strain LGMB491 produced 1-acetyl-β-carboline (1), indole-3-carbaldehyde (2), 3-(hydroxyacetyl)-indole (4), brevianamide F (5), and cyclo-(L-Pro-L-Phe) (6) as major compounds with antibacterial activity. In this study, we add to the knowledge about the endophytic community from the medicinal plant V. divergens and report the isolation of rare actinomycetes that produce highly active metabolites

Insights into olfactory ensheathing cell development from a laser-microdissection and transcriptome-profiling approach.

Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridization, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific (that is, not expressed by Schwann cells). One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.Cambridge Commonwealth Trust Cambridge Philosophical Societ

Molecular Characterization and Patient Outcome of Melanoma Nodal Metastases and an Unknown Primary Site

Background Melanoma of unknown primary site (MUP) is not a completely understood entity with nodal metastases as the most common first clinical manifestation. The aim of this multicentric study was to assess frequency and type of oncogenic BRAF/NRAS/KIT mutations in MUP with clinically detected nodal metastases in relation to clinicopathologic features and outcome. Materials and Methods We analyzed series of 103 MUP patients (period: 1992-2010) after therapeutic lymphadenectomy (LND): 40 axillary, 47 groin, 16 cervical, none treated with BRAF inhibitors. We performed molecular characterization of BRAF/NRAS/KIT mutational status in nodal metastases using direct sequencing of respective coding sequences. Median follow-up time was 53 months. Results BRAF mutations were detected in 55 cases (53 %) (51 V600E, 93 %; 4 others, 7 %), and mutually exclusive NRAS mutations were found in 14 cases (14 %) (7 p.Q61R, 4 p.Q61K, 2 p.Q61H, 1 p.Q13R). We have not detected any mutations in KIT. The 5-year overall survival (OS) was 34 %; median was 24 months. We have not found significant correlation between mutational status (BRAF/NRAS) and OS; however, for BRAF or NRAS mutated melanomas we observed significantly shorter disease-free survival (DFS) when compared with wild-type melanoma patients (p = .04; 5-year DFS, 18 vs 19 vs 31 %, respectively). The most important factor influencing OS was number of metastatic lymph nodes >1 (p = .03). Conclusions Our large study on molecular characterization of MUP with nodal metastases showed that MUPs had molecular features similar to sporadic non-chronic-sun-damaged melanomas. BRAF/NRAS mutational status had negative impact on DFS in this group of patients. These observations might have potential implication for molecular-targeted therapy in MUPs