The clinical and functional significance of c-Met in breast cancer: a review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.CMH-Y is funded by a Cancer Research UK Clinical Research Fellowship. JLJ is funded by the Breast Cancer Campaign Tissue Bank

Penetration of the Optic Nerve or Chiasm by Anterior Communicating Artery Aneurysms: Three Case Reports

Although large and giant aneurysms can induce visual disturbance by compression of the anterior visual pathway, splitting and penetration of the optic apparatus are extremely rare. The authors describe three patients who underwent clipping surgery for anterior communicating artery aneurysm infiltrating into the optic nerve or chiasm. These findings were suspected on preoperative magnetic resonance imaging and confirmed at surgery. Two aneurysms were ruptured and one unruptured. The authors review the literature and discuss the mechanism of cranial nerve penetration by an aneurysm.ArticleNEURO-OPHTHALMOLOGY. 35(3):128-132 (2011)journal articl

The effect of enteral and parenteral feeding on secretion of orexigenic peptides in infants

<p>Abstract</p> <p>Background</p> <p>The feeding in the first months of the life seems to influence the risks of obesity and affinity to some diseases including atherosclerosis. The mechanisms of these relations are unknown, however, the modification of hormonal action can likely be taken into account. Therefore, in this study the levels of ghrelin and orexin A - peripheral and central peptide from the orexigenic gut-brain axis were determined.</p> <p>Methods</p> <p>Fasting and one hour after the meal plasma concentrations of ghrelin and orexin were measured in breast-fed (group I; n = 17), milk formula-fed (group II; n = 16) and highly hydrolyzed, hypoallergic formula-fed (group III; n = 14) groups, age matched infants (mean 4 months) as well as in children with iv provision of nutrients (glucose - group IV; n = 15; total parenteral nutrition - group V; n = 14). Peptides were determined using EIA commercial kits.</p> <p>Results</p> <p>Despite the similar caloric intake in orally fed children the fasting ghrelin and orexin levels were significantly lower in the breast-fed children (0.37 ± 0.17 and 1.24 ± 0.29 ng/ml, respectively) than in the remaining groups (0.5 ± 0.27 and 1.64 ± 0.52 ng/ml, respectively in group II and 0.77 ± 0.27 and 2.04 ± 1.1 ng/ml, respectively, in group III). The postprandial concentrations of ghrelin increased to 0.87 ± 0.29 ng/ml, p < 0.002 and 0.76 ± 0.26 ng/ml, p < 0.01 in groups I and II, respectively as compared to fasting values. The decrease in concentration of ghrelin after the meal was observed only in group III (0.47 ± 0.24 ng/ml). The feeding did not influence the orexin concentration. In groups IV and V the ghrelin and orexin levels resembled those in milk formula-fed children.</p> <p>Conclusion</p> <p>The highly hydrolyzed diet strongly affects fasting and postprandial ghrelin and orexin plasma concentrations with possible negative effect on short- and long-time effects on development. Also total parenteral nutrition with the continuous stimulation and lack of fasting/postprandial modulation might be responsible for disturbed development in children fed this way.</p

Discovering functional linkages and uncharacterized cellular pathways using phylogenetic profile comparisons: a comprehensive assessment

<p>Abstract</p> <p>Background</p> <p>A widely-used approach for discovering functional and physical interactions among proteins involves phylogenetic profile comparisons (PPCs). Here, proteins with similar profiles are inferred to be functionally related under the assumption that proteins involved in the same metabolic pathway or cellular system are likely to have been co-inherited during evolution.</p> <p>Results</p> <p>Our experimentation with <it>E. coli </it>and yeast proteins with 16 different carefully composed reference sets of genomes revealed that the phyletic patterns of proteins in prokaryotes alone could be adequate enough to make reasonably accurate functional linkage predictions. A slight improvement in performance is observed on adding few eukaryotes into the reference set, but a noticeable drop-off in performance is observed with increased number of eukaryotes. Inclusion of most parasitic, pathogenic or vertebrate genomes and multiple strains of the same species into the reference set do not necessarily contribute to an improved sensitivity or accuracy. Interestingly, we also found that evolutionary histories of individual pathways have a significant affect on the performance of the PPC approach with respect to a particular reference set. For example, to accurately predict functional links in carbohydrate or lipid metabolism, a reference set solely composed of prokaryotic (or bacterial) genomes performed among the best compared to one composed of genomes from all three super-kingdoms; this is in contrast to predicting functional links in translation for which a reference set composed of prokaryotic (or bacterial) genomes performed the worst. We also demonstrate that the widely used random null model to quantify the statistical significance of profile similarity is incomplete, which could result in an increased number of false-positives.</p> <p>Conclusion</p> <p>Contrary to previous proposals, it is not merely the number of genomes but a careful selection of informative genomes in the reference set that influences the prediction accuracy of the PPC approach. We note that the predictive power of the PPC approach, especially in eukaryotes, is heavily influenced by the primary endosymbiosis and subsequent bacterial contributions. The over-representation of parasitic unicellular eukaryotes and vertebrates additionally make eukaryotes less useful in the reference sets. Reference sets composed of highly non-redundant set of genomes from all three super-kingdoms fare better with pathways showing considerable vertical inheritance and strong conservation (e.g. translation apparatus), while reference sets solely composed of prokaryotic genomes fare better for more variable pathways like carbohydrate metabolism. Differential performance of the PPC approach on various pathways, and a weak positive correlation between functional and profile similarities suggest that caution should be exercised while interpreting functional linkages inferred from genome-wide large-scale profile comparisons using a single reference set.</p

Quantitative Proteome Profiling of C. burnetii under Tetracycline Stress Conditions

The recommended antibiotic regimen against Coxiella burnetii, the etiological agent of Q fever, is based on a semi-synthetic, second-generation tetracycline, doxycycline. Here, we report on the comparison of the proteomes of a C. burnetii reference strain either cultured under control conditions or under tetracycline stress conditions. Using the MS-driven combined fractional diagonal chromatography proteomics technique, out of the 531 proteins identified, 5 and 19 proteins were found significantly up- and down-regulated respectively, under tetracycline stress. Although the predicted cellular functions of these regulated proteins did not point to known tetracycline resistance mechanisms, our data clearly reveal the plasticity of the proteome of C. burnetii to battle tetracycline stress. Finally, we raise several plausible hypotheses that could further lead to more focused experiments on studying tetracycline resistance in C. burnetii and thus reduced treatment failures of Q fever

piggyBac is an effective tool for functional analysis of the Plasmodium falciparum genome

<p>Abstract</p> <p>Background</p> <p>Much of the <it>Plasmodium falciparum </it>genome encodes hypothetical proteins with limited homology to other organisms. A lack of robust tools for genetic manipulation of the parasite limits functional analysis of these hypothetical proteins and other aspects of the <it>Plasmodium </it>genome. Transposon mutagenesis has been used widely to identify gene functions in many organisms and would be extremely valuable for functional analysis of the <it>Plasmodium </it>genome.</p> <p>Results</p> <p>In this study, we investigated the lepidopteran transposon, <it>piggyBac</it>, as a molecular genetic tool for functional characterization of the <it>Plasmodium falciparum </it>genome. Through multiple transfections, we generated 177 unique <it>P. falciparum </it>mutant clones with mostly single <it>piggyBac </it>insertions in their genomes. Analysis of <it>piggyBac </it>insertion sites revealed random insertions into the <it>P. falciparum </it>genome, in regards to gene expression in parasite life cycle stages and functional categories. We further explored the possibility of forward genetic studies in <it>P. falciparum </it>with a phenotypic screen for attenuated growth, which identified several parasite genes and pathways critical for intra-erythrocytic development.</p> <p>Conclusion</p> <p>Our results clearly demonstrate that <it>piggyBac </it>is a novel, indispensable tool for forward functional genomics in <it>P. falciparum </it>that will help better understand parasite biology and accelerate drug and vaccine development.</p