113 research outputs found

    Benefit from decline: the primary transcriptome of Alteromonas macleodii str. Te101 during Trichodesmium demise

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    Interactions between co-existing microorganisms deeply affect the physiology of the involved organisms and, ultimately, the function of the ecosystem as a whole. Copiotrophic Alteromonas are marine gammaproteobacteria that thrive during the late stages of phytoplankton blooms in the marine environment and in laboratory co-cultures with cyanobacteria such as Trichodesmium. The response of this heterotroph to the sometimes rapid and transient changes in nutrient supply when the phototroph crashes is not well understood. Here, we isolated and sequenced the strain Alteromonas macleodii str. Te101 from a laboratory culture of Trichodesmium erythraeum IMS101, yielding a chromosome of 4.63 Mb and a single plasmid of 237 kb. Increasing salinities to ≥43 ppt inhibited the growth of Trichodesmium but stimulated growth of the associated Alteromonas. We characterized the transcriptomic responses of both microorganisms and identified the complement of active transcriptional start sites in Alteromonas at single-nucleotide resolution. In replicate cultures, a similar set of genes became activated in Alteromonas when growth rates of Trichodesmium declined and mortality was high. The parallel activation of fliA, rpoS and of flagellar assembly and growth-related genes indicated that Alteromonas might have increased cell motility, growth, and multiple biosynthetic activities. Genes with the highest expression in the data set were three small RNAs (Aln1a-c) that were identified as analogs of the small RNAs CsrB-C in E. coli or RsmX-Z in pathogenic bacteria. Together with the carbon storage protein A (CsrA) homolog Te101_05290, these RNAs likely control the expression of numerous genes in responding to changes in the environmentThis work was supported by the EU project MaCuMBA (grant agreement no. 311975) to WRH and FRVby the German Israeli Foundation grant no. 1133 to IB-F and WRHSupport of ML-P by a postdoctoral fellowship from the Valencian Consellería de Educació, Investigació, Cultura i Esport (APOSTD/2016/051)of SH by the China Scholarship Council is gratefully acknowledged

    A single nucleotide polymorphism in the p27Kip1 gene is associated with primary patency of lower extremity vein bypass grafts

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    ObjectiveFactors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27Kip1 gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency.MethodsThis was a retrospective genetic association study nested within a prospective cohort of 204 patients from three referral centers undergoing LEVBG for claudication or critical ischemia. The main outcome measure was primary vein graft patency.ResultsAll patients were followed up for a minimum of 1 year with duplex graft surveillance (median follow-up, 893 days; interquartile range, 539-1315). Genomic DNA was isolated and SNP analysis for the p27Kip1-838C>A variants was performed. Allele frequencies were correlated with graft outcome using survival analysis and Cox proportional hazards modeling. The p27Kip1-838C>A allele frequencies observed were CA, 53%; CC, 30%; and AA, 17%, satisfying Hardy-Weinberg equilibrium. Race (P = .025) and history of coronary artery disease (P = .027) were different across the genotypes; all other baseline variables were similar. Primary graft patency was greater among patients with the -838AA genotype (75% AA vs 55% CA/CC at 3 years; P = .029). In a Cox proportional hazards model including age, sex, race, diabetes, critical limb ischemia, redo (vs primary) bypass, vein type, and baseline C-reactive protein level, the p27Kip1-838AA genotype was significantly associated with higher graft patency (hazard ratio for failure, 0.4; 95% confidence interval, 0.17-0.93). Genotype was also associated with early (0-1 month) changes in graft lumen diameter by ultrasound imaging.ConclusionsThese data suggest that the p27Kip1-838C>A SNP is associated with LEVBG patency and, together with previous reports, underscore a central role for p27Kip1 in the generic response to vascular injury

    Energy Dose-Response in Selective Laser Trabeculoplasty: A Review

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    PRCIS: A literature review of SLT energy dose response found no definitive relationship between IOP reduction with respect to total or pulse energy, race, pigmentation, or application pattern. PURPOSE: Selective laser trabeculoplasty (SLT) is a safe and effective treatment for lowering intraocular pressure (IOP). While evidence is mounting for the advantage of its use as a first-line treatment for IOP reduction, the SLT procedures in use vary widely. The purpose of this literature review was to investigate if there were any relationships between SLT energy and efficacy for lowering IOP in the published literature. METHODS: A literature review was undertaken that included studies in which energy levels required for successful SLT treatment were investigated: in general, with respect to angle pigmentation, race or ethnicity, and treatment arc extent. RESULTS: There was no indication that higher (or lower) energy used in the treatment leads to greater (or less) IOP reduction. Similar results were obtained regarding level of trabecular meshwork (TM) pigmentation. Race was not found to be associated with altered dose response in SLT. There were indications that treating the full 360 degrees, as opposed to smaller arcs, could be beneficial for more IOP reduction. IOP reduction from SLT was found to be similar to that provided by topical medications. CONCLUSIONS: The optimal energy level of SLT needed for IOP reduction has not yet been definitively established, with all reported pulse energies resulting in similar IOP reduction. Furthermore, similar lack of conclusive findings exists regarding optimal SLT energy dosage for use in different races and degrees of TM pigmentation. This parameter, as well as each of the above-mentioned factors, requires further research

    A large margin algorithm for automated segmentation of white matter hyperintensity

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    Precise detection and quantification of white matter hyperintensity (WMH) is of great interest in studies of neurological and vascular disorders. In this work, we propose a novel method for automatic WMH segmentation with both supervised and semi-supervised large margin algorithms provided by the framework. The proposed algorithms optimize a kernel based max-margin objective function which aims to maximize the margin between inliers and outliers. We show that the semi-supervised learning problem can be formulated to learn a classifier and label assignment simultaneously, which can be solved efficiently by an iterative algorithm. The model is learned first via the supervised approach and then fine-tuned on a target image by using the semi-supervised algorithm. We evaluate our method on 88 brain fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images from subjects with vascular disease. Quantitative evaluation of the proposed approach shows that it outperforms other well known methods for WMH segmentation

    Identification of membrane-type 1 matrix metalloproteinase tyrosine phosphorylation in association with neuroblastoma progression

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    <p>Abstract</p> <p>Background</p> <p>Neuroblastoma is a pediatric tumor of neural crest cells that is clinically characterized by its variable evolution, from spontaneous regression to malignancy. Despite many advances in neuroblastoma research, 60% of neuroblastoma, which are essentially metastatic cases, are associated with poor clinical outcome due to the lack of effectiveness of current therapeutic strategies. Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), an enzyme involved in several steps in tumor progression, has previously been shown to be associated with poor clinical outcome for neuroblastoma. Based on our recent demonstration that MT1-MMP phosphorylation is involved in the growth of fibrosarcoma tumors, we examined the potential role of phosphorylated MT1-MMP in neuroblastoma progression.</p> <p>Methods</p> <p>Tyrosine phosphorylated MT1-MMP was immunostained on tissue microarray samples from 55 patients with neuroblastoma detected by mass screening (known to be predominantly associated with favourable outcome), and from 234 patients with standard diagnosed neuroblastoma. In addition, the effects of a non phosphorylable version of MT1-MMP on neuroblastoma cell migration and proliferation were investigated within three-dimensional collagen matrices.</p> <p>Results</p> <p>Although there is no correlation between the extent of tyrosine phosphorylation of MT1-MMP (pMT1-MMP) and MYCN amplification or clinical stage, we observed greater phosphorylation of pMT1-MMP in standard neuroblastoma, while it is less evident in neuroblastoma from mass screening samples (P = 0.0006) or in neuroblastoma samples from patients younger than one year (P = 0.0002). <it>In vitro </it>experiments showed that overexpression of a non-phosphorylable version of MT1-MMP reduced MT1-MMP-mediated neuroblastoma cell migration and proliferation within a three-dimensional type I collagen matrix, suggesting a role for the phosphorylated enzyme in the invasive properties of neuroblastoma cells.</p> <p>Conclusion</p> <p>Overall, these results suggest that tyrosine phosphorylated MT1-MMP plays an important role in neuroblastoma progression and that its expression is preferentially observed in tumor specimens from neuroblastoma patients showing poor clinical outcome.</p

    Clustering More than Two Million Biomedical Publications: Comparing the Accuracies of Nine Text-Based Similarity Approaches

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    We investigate the accuracy of different similarity approaches for clustering over two million biomedical documents. Clustering large sets of text documents is important for a variety of information needs and applications such as collection management and navigation, summary and analysis. The few comparisons of clustering results from different similarity approaches have focused on small literature sets and have given conflicting results. Our study was designed to seek a robust answer to the question of which similarity approach would generate the most coherent clusters of a biomedical literature set of over two million documents.We used a corpus of 2.15 million recent (2004-2008) records from MEDLINE, and generated nine different document-document similarity matrices from information extracted from their bibliographic records, including titles, abstracts and subject headings. The nine approaches were comprised of five different analytical techniques with two data sources. The five analytical techniques are cosine similarity using term frequency-inverse document frequency vectors (tf-idf cosine), latent semantic analysis (LSA), topic modeling, and two Poisson-based language models--BM25 and PMRA (PubMed Related Articles). The two data sources were a) MeSH subject headings, and b) words from titles and abstracts. Each similarity matrix was filtered to keep the top-n highest similarities per document and then clustered using a combination of graph layout and average-link clustering. Cluster results from the nine similarity approaches were compared using (1) within-cluster textual coherence based on the Jensen-Shannon divergence, and (2) two concentration measures based on grant-to-article linkages indexed in MEDLINE.PubMed's own related article approach (PMRA) generated the most coherent and most concentrated cluster solution of the nine text-based similarity approaches tested, followed closely by the BM25 approach using titles and abstracts. Approaches using only MeSH subject headings were not competitive with those based on titles and abstracts

    Investigation of Association between PFO Complicated by Cryptogenic Stroke and a Common Variant of the Cardiac Transcription Factor GATA4

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    Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke

    Calpains Mediate Integrin Attachment Complex Maintenance of Adult Muscle in Caenorhabditis elegans

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    Two components of integrin containing attachment complexes, UNC-97/PINCH and UNC-112/MIG-2/Kindlin-2, were recently identified as negative regulators of muscle protein degradation and as having decreased mRNA levels in response to spaceflight. Integrin complexes transmit force between the inside and outside of muscle cells and signal changes in muscle size in response to force and, perhaps, disuse. We therefore investigated the effects of acute decreases in expression of the genes encoding these multi-protein complexes. We find that in fully developed adult Caenorhabditis elegans muscle, RNAi against genes encoding core, and peripheral, members of these complexes induces protein degradation, myofibrillar and mitochondrial dystrophies, and a movement defect. Genetic disruption of Z-line– or M-line–specific complex members is sufficient to induce these defects. We confirmed that defects occur in temperature-sensitive mutants for two of the genes: unc-52, which encodes the extra-cellular ligand Perlecan, and unc-112, which encodes the intracellular component Kindlin-2. These results demonstrate that integrin containing attachment complexes, as a whole, are required for proper maintenance of adult muscle. These defects, and collapse of arrayed attachment complexes into ball like structures, are blocked when DIM-1 levels are reduced. Degradation is also blocked by RNAi or drugs targeting calpains, implying that disruption of integrin containing complexes results in calpain activation. In wild-type animals, either during development or in adults, RNAi against calpain genes results in integrin muscle attachment disruptions and consequent sub-cellular defects. These results demonstrate that calpains are required for proper assembly and maintenance of integrin attachment complexes. Taken together our data provide in vivo evidence that a calpain-based molecular repair mechanism exists for dealing with attachment complex disruption in adult muscle. Since C. elegans lacks satellite cells, this mechanism is intrinsic to the muscles and raises the question if such a mechanism also exists in higher metazoans

    Confirmation of Anopheles (Anopheles) calderoni Wilkerson, 1991 (Diptera: Culicidae) in Colombia and Ecuador through molecular and morphological correlation with topotypic material

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    The morphologically similar taxa Anopheles calderoni, Anopheles punctimacula, Anopheles malefactor and Anopheles guarao are commonly misidentified. Isofamilies collected in Valle de Cauca, Colombia, showed morphological characters most similar to An. calderoni, a species which has never previously been reported in Colombia. Although discontinuity of the postsubcostal pale spots on the costa (C) and first radial (R1) wing veins is purportedly diagnostic for An. calderoni, the degree of overlap of the distal postsubcostal spot on C and R1 were variable in Colombian specimens (0.003-0.024). In addition, in 98.2% of larvae, seta 1-X was located off the saddle and seta 3-C had 4-7 branches in 86.7% of specimens examined. Correlation of DNA sequences of the second internal transcribed spacer and mtDNA cytochrome c oxidase subunit I gene (COI) barcodes (658 bp of the COI gene) generated from Colombian progeny material and wild-caught mosquitoes from Ecuador with those from the Peruvian type series of An. calderoni confirmed new country records. DNA barcodes generated for the closely related taxa, An. malefactor and An. punctimacula are also presented for the first time. Examination of museum specimens at the University of the Valle, Colombia, revealed the presence of An. calderoni in inland localities across Colombia and at elevations up to 1113 m
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