Tumors and tumor-like lesions of the heart valves

Valvular tumors and tumor-like lesions may have similar morphological and clinical characteristics, and may place the patients at a high risk of stroke in different ways. From January 2004 to June 2008, 11 patients underwent surgery for a suspected valvular tumor. Valvular tumor and tumor-like lesions accounted for 0.32% of adult cardiac operations. Five (45.5%) valvular lesions were papillary fibroelastomas, one (9.1%) was myxoma, 2 (18.2%) were organized thrombi, and 3 (27.3%) were calcification lesions. There was a total of 5 (45.5%) atrioventricular valve lesions, 4 arising from the atrial side of the leaflets, and one from the ventricular side. All 5 (45.5%) semilunar valvular lesions were from the aortic valve. One (9.1%) lesion originated from the chorda tendinea of the mitral valve. All leaflet lesions were resected by a simple shave technique, and all the patients recovered favorably. Valvular tumor and tumor-like lesions are rare. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt therapeutic measures in view of the underlying diseases of the valvular lesions are essential to prevent potential embolic events

Identification of Roles for Peptide: N-Glycanase and Endo-β-N-Acetylglucosaminidase (Engase1p) during Protein N-Glycosylation in Human HepG2 Cells

BACKGROUND: During mammalian protein N-glycosylation, 20% of all dolichol-linked oligosaccharides (LLO) appear as free oligosaccharides (fOS) bearing the di-N-acetylchitobiose (fOSGN2), or a single N-acetylglucosamine (fOSGN), moiety at their reducing termini. After sequential trimming by cytosolic endo beta-N-acetylglucosaminidase (ENGase) and Man2c1 mannosidase, cytosolic fOS are transported into lysosomes. Why mammalian cells generate such large quantities of fOS remains unexplored, but fOSGN2 could be liberated from LLO by oligosaccharyltransferase, or from glycoproteins by NGLY1-encoded Peptide-N-Glycanase (PNGase). Also, in addition to converting fOSGN2 to fOSGN, the ENGASE-encoded cytosolic ENGase of poorly defined function could potentially deglycosylate glycoproteins. Here, the roles of Ngly1p and Engase1p during fOS metabolism were investigated in HepG2 cells. METHODS/PRINCIPAL FINDINGS: During metabolic radiolabeling and chase incubations, RNAi-mediated Engase1p down regulation delays fOSGN2-to-fOSGN conversion, and it is shown that Engase1p and Man2c1p are necessary for efficient clearance of cytosolic fOS into lysosomes. Saccharomyces cerevisiae does not possess ENGase activity and expression of human Engase1p in the png1Delta deletion mutant, in which fOS are reduced by over 98%, partially restored fOS generation. In metabolically radiolabeled HepG2 cells evidence was obtained for a small but significant Engase1p-mediated generation of fOS in 1 h chase but not 30 min pulse incubations. Ngly1p down regulation revealed an Ngly1p-independent fOSGN2 pool comprising mainly Man(8)GlcNAc(2), corresponding to approximately 70% of total fOS, and an Ngly1p-dependent fOSGN2 pool enriched in Glc(1)Man(9)GlcNAc(2) and Man(9)GlcNAc(2) that corresponds to approximately 30% of total fOS. CONCLUSIONS/SIGNIFICANCE: As the generation of the bulk of fOS is unaffected by co-down regulation of Ngly1p and Engase1p, alternative quantitatively important mechanisms must underlie the liberation of these fOS from either LLO or glycoproteins during protein N-glycosylation. The fully mannosylated structures that occur in the Ngly1p-dependent fOSGN2 pool indicate an ERAD process that does not require N-glycan trimming

Transcriptomic analysis of milk somatic cells in mastitis resistant and susceptible sheep upon challenge with Staphylococcus epidermidis and Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>The existence of a genetic basis for host responses to bacterial intramammary infections has been widely documented, but the underlying mechanisms and the genes are still largely unknown. Previously, two divergent lines of sheep selected for high/low milk somatic cell scores have been shown to be respectively susceptible and resistant to intramammary infections by <it>Staphylococcus spp</it>. Transcriptional profiling with an 15K ovine-specific microarray of the milk somatic cells of susceptible and resistant sheep infected successively by <it>S. epidermidis </it>and <it>S. aureus </it>was performed in order to enhance our understanding of the molecular and cellular events associated with mastitis resistance.</p> <p>Results</p> <p>The bacteriological titre was lower in the resistant than in the susceptible animals in the 48 hours following inoculation, although milk somatic cell concentration was similar. Gene expression was analysed in milk somatic cells, mainly represented by neutrophils, collected 12 hours post-challenge. A high number of differentially expressed genes between the two challenges indicated that more T cells are recruited upon inoculation by <it>S. aureus </it>than <it>S. epidermidis</it>. A total of 52 genes were significantly differentially expressed between the resistant and susceptible animals. Further Gene Ontology analysis indicated that differentially expressed genes were associated with immune and inflammatory responses, leukocyte adhesion, cell migration, and signal transduction. Close biological relationships could be established between most genes using gene network analysis. Furthermore, gene expression suggests that the cell turn-over, as a consequence of apoptosis/granulopoiesis, may be enhanced in the resistant line when compared to the susceptible line.</p> <p>Conclusions</p> <p>Gene profiling in resistant and susceptible lines has provided good candidates for mapping the biological pathways and genes underlying genetically determined resistance and susceptibility towards <it>Staphylococcus </it>infections, and opens new fields for further investigation.</p

Dynamic Expression of Cadherins Regulates Vocal Development in a Songbird

BACKGROUND: Since, similarly to humans, songbirds learn their vocalization through imitation during their juvenile stage, they have often been used as model animals to study the mechanisms of human verbal learning. Numerous anatomical and physiological studies have suggested that songbirds have a neural network called 'song system' specialized for vocal learning and production in their brain. However, it still remains unknown what molecular mechanisms regulate their vocal development. It has been suggested that type-II cadherins are involved in synapse formation and function. Previously, we found that type-II cadherin expressions are switched in the robust nucleus of arcopallium from cadherin-7-positive to cadherin-6B-positive during the phase from sensory to sensorimotor learning stage in a songbird, the Bengalese finch. Furthermore, in vitro analysis using cultured rat hippocampal neurons revealed that cadherin-6B enhanced and cadherin-7 suppressed the frequency of miniature excitatory postsynaptic currents via regulating dendritic spine morphology. METHODOLOGY/PRINCIPAL FINDINGS: To explore the role of cadherins in vocal development, we performed an in vivo behavioral analysis of cadherin function with lentiviral vectors. Overexpression of cadherin-7 in the juvenile and the adult stages resulted in severe defects in vocal production. In both cases, harmonic sounds typically seen in the adult Bengalese finch songs were particularly affected. CONCLUSIONS/SIGNIFICANCE: Our results suggest that cadherins control vocal production, particularly harmonic sounds, probably by modulating neuronal morphology of the RA nucleus. It appears that the switching of cadherin expressions from sensory to sensorimotor learning stage enhances vocal production ability to make various types of vocalization that is essential for sensorimotor learning in a trial and error manner

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

The Maslov index in weak symplectic functional analysis

We recall the Chernoff-Marsden definition of weak symplectic structure and give a rigorous treatment of the functional analysis and geometry of weak symplectic Banach spaces. We define the Maslov index of a continuous path of Fredholm pairs of Lagrangian subspaces in continuously varying Banach spaces. We derive basic properties of this Maslov index and emphasize the new features appearing.Comment: 34 pages, 13 figures, 45 references, to appear in Ann Glob Anal Geom. The final publication will be available at http://www.springerlink.com. arXiv admin note: substantial text overlap with arXiv:math/040613

Impact of Caveolin-1 Expression on the Prognosis of Transitional Cell Carcinoma of the Upper Urinary Tract

This study aimed to investigate the relationship of caveolin-1 expression with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT). Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 98 patients, who had undergone radical nephroureterectomy, were stained immunohistochemically using antibodies against caveolin-1. The expression pattern of caveolin-1 was compared with the clinicopathological variables. The caveolin-1 expression was significantly correlated with T stage (p<0.001) and grade (p=0.036). The survival rate of patients with caveolin-1 positive tumors was significantly lower than that of patients with caveolin-1 negative tumors (p<0.0001). The univariate analyses identified T stage, grade, and caveolin-1 expression as significant prognostic factors for cancer-specific survival, whereas the multivariate analyses indicated that T stage and caveolin-1 expression were independent prognostic factors. These results show that the increased expression of caveolin-1 is associated with tumor progression and poor prognosis in TCC-UUT, suggesting that caveolin-1 may play an important role in the progression of TCC-UUT

Joint disorder; a contributory cause to reproductive failure in beef bulls?

The lame sire, unsound for breeding, can cause substantial economic loss due to reduced pregnancies in the beef-producing herd

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

Environmental differences between sites control the diet and nutrition of the carnivorous plant Drosera rotundifolia

Background and aims: Carnivorous plants are sensitive to small changes in resource availability, but few previous studies have examined how differences in nutrient and prey availability affect investment in and the benefit of carnivory. We studied the impact of site-level differences in resource availability on ecophysiological traits of carnivory for Drosera rotundifolia L. Methods: We measured prey availability, investment in carnivory (leaf stickiness), prey capture and diet of plants growing in two bogs with differences in N deposition and plant available N: Cors Fochno (0.62 g m−2 yr.−1, 353 μg l−1), Whixall Moss (1.37 g m−2 yr.−1, 1505 μg l−1). The total N amount per plant and the contributions of prey/root N to the plants’ N budget were calculated using a single isotope natural abundance method. Results: Plants at Whixall Moss invested less in carnivory, were less likely to capture prey, and were less reliant on prey-derived N (25.5% compared with 49.4%). Actual prey capture did not differ between sites. Diet composition differed – Cors Fochno plants captured 62% greater proportions of Diptera. Conclusions: Our results show site-level differences in plant diet and nutrition consistent with differences in resource availability. Similarity in actual prey capture may be explained by differences in leaf stickiness and prey abundance