190 research outputs found
Dipyridamole plus aspirin versus aspirin alone in the secondary prevention after TIA or stroke: a meta-analysis by risk
Objectives: Our aim was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient
ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D.
Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on the comparison of A+D versus ASA were excluded.
Review methods: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification.
Results: A total of 7,612 patients (5 trials) were included in the analyses, 3,800 allocated to A+D and 3,812 to ASA alone. The trial-adjusted hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischemic heart disease,
aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke, HR 0.78 (95% CI 0.68 â 0.90).
Conclusion: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischemic stroke of presumed arterial origin in the secondary
prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk. ---------------------------7dc3521430776
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Halke
Sweet spheres: Succession and CAZyme expression of marine bacterial communities colonizing a mix of alginate and pectin particles
Polysaccharide particles are important substrates and microhabitats for marine bacteria. However, substrate-specific bacterial dynamics in mixtures of particle types with different polysaccharide composition, as likely occurring in natural habitats, are undescribed. Here, we studied the composition, functional diversity and gene expression of marine bacterial communities colonising a mix of alginate and pectin particles. Amplicon, metagenome and metatranscriptome sequencing revealed that communities on alginate and pectin particles significantly differed from their free-living counterparts. Unexpectedly, microbial dynamics on alginate and pectin particles were similar, with predominance of amplicon sequence variants (ASVs) from Tenacibaculum, Colwellia, Psychrobium and Psychromonas. Corresponding metagenome-assembled genomes (MAGs) expressed diverse alginate lyases, several co-localised in polysaccharide utilisation loci. Only a single, low-abundant MAG showed elevated transcript abundances of pectin-degrading enzymes. One specific Glaciecola ASV dominated the free-living fraction, possibly persisting on particle-derived oligomers through different glycoside hydrolases. Elevated ammonium uptake and metabolism signified nitrogen as important factor for degrading carbon-rich particles, whereas elevated methylcitrate and glyoxylate cycles suggested nutrient limitation in surrounding waters. The bacterial preference for alginate, whereas pectin primarily served as colonization scaffold, illuminates substrate-driven dynamics within mixed polysaccharide pools. These insights expand our understanding of bacterial niche specialisation and the biological carbon pump in macroalgae-rich habitats
Epicardial Ventricular Tachycardia Ablation for Which Patients?
With the widespread use of implantable cardioverter-defibrillators, an increasing number of patients present with ventricular tachycardia
(VT). Large multicentre studies have shown that ablation of VT successfully reduces recurrent VT and this procedure is being performed
by an increasing number of centres. However, for a number of reasons, many patients experience VT recurrence after ablation. One
important reason for VT recurrence is the presence of an epicardial substrate involved in the VT circuit which is not affected by
endocardial ablation. Epicardial access and ablation is now frequently performed either after failed endocardial VT ablation or as first-line
treatment in selected patients. This review will focus on the available evidence for identifying VT of epicardial origin, and discuss in which
patients an epicardial approach would be benefitial
ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures
ArachnoServer (www.arachnoserver.org) is a manually curated database providing information on the sequence, structure and biological activity of protein toxins from spider venoms. These proteins are of interest to a wide range of biologists due to their diverse applications in medicine, neuroscience, pharmacology, drug discovery and agriculture. ArachnoServer currently manages 1078 protein sequences, 759 nucleic acid sequences and 56 protein structures. Key features of ArachnoServer include a molecular target ontology designed specifically for venom toxins, current and historic taxonomic information and a powerful advanced search interface. The following significant improvements have been implemented in version 2.0: (i) the average and monoisotopic molecular masses of both the reduced and oxidized form of each mature toxin are provided; (ii) the advanced search feature now enables searches on the basis of toxin mass, external database accession numbers and publication date in ArachnoServer; (iii) toxins can now be browsed on the basis of their phyletic specificity; (iv) rapid BLAST searches based on the mature toxin sequence can be performed directly from the toxin card; (v) private silos can be requested from research groups engaged in venoms-based research, enabling them to easily manage and securely store data during the process of toxin discovery; and (vi) a detailed user manual is now available
Active Chromatin Marks Are Retained on X Chromosomes Lacking Gene or Repeat Silencing Despite XIST/Xist Expression in Somatic Cell Hybrids
X-chromosome inactivation occurs early in mammalian development and results in the inactive X chromosome acquiring numerous hallmarks of heterochromatin. While XIST is a key player in the inactivation process, the method of action of this ncRNA is yet to be determined.To assess which features of heterochromatin may be directly recruited by the expression and localization of the XIST RNA we have analyzed a mouse/human somatic cell hybrid in which expression of human and mouse XIST/Xist has been induced from the active X by demethylation. Such hybrids had previously been demonstrated to disconnect XIST/Xist expression from gene silencing and we confirm maintenance of X-linked gene expression, even close to the Xist locus, despite the localized expression of mouse Xist.Loss of the active chromatin marks H3 acetylation and H3 lysine 4 methylation was not observed upon XIST/Xist expression, nor was there a gain of DNA methylation; thus these marks of facultative heterochromatin are not solely dependent upon Xist expression. Cot-1 holes, regions of depleted RNA hybridization with a Cot-1 probe, were observed upon Xist expression; however, these were at reduced frequency and intensity in these somatic cells. Domains of human Cot-1 transcription were observed corresponding to the human chromosomes in the somatic cell hybrids. The Cot-1 domain of the X was not reduced with the expression of XIST, which fails to localize to the human X chromosome in a mouse somatic cell background. The human inactive X in a mouse/human hybrid cell also shows delocalized XIST expression and an ongoing Cot-1 domain, despite X-linked gene silencing. These results are consistent with recent reports separating Cot-1 silencing from genic silencing, but also demonstrate repetitive element expression from an otherwise silent X chromosome in these hybrid cells
Evolution from XIST-Independent to XIST-Controlled X-Chromosome Inactivation: Epigenetic Modifications in Distantly Related Mammals
X chromosome inactivation (XCI) is the transcriptional silencing of one X in female mammals, balancing expression of X genes between females (XX) and males (XY). In placental mammals non-coding XIST RNA triggers silencing of one X (Xi) and recruits a characteristic suite of epigenetic modifications, including the histone mark H3K27me3. In marsupials, where XIST is missing, H3K27me3 association seems to have different degrees of stability, depending on cell-types and species. However, the complete suite of histone marks associated with the Xi and their stability throughout cell cycle remain a mystery, as does the evolution of an ancient mammal XCI system. Our extensive immunofluorescence analysis (using antibodies against specific histone modifications) in nuclei of mammals distantly related to human and mouse, revealed a general absence from the mammalian Xi territory of transcription machinery and histone modifications associated with active chromatin. Specific repressive modifications associated with XCI in human and mouse were also observed in elephant (a distantly related placental mammal), as was accumulation of XIST RNA. However, in two marsupial species the Xi either lacked these modifications (H4K20me1), or they were restricted to specific windows of the cell cycle (H3K27me3, H3K9me2). Surprisingly, the marsupial Xi was stably enriched for modifications associated with constitutive heterochromatin in all eukaryotes (H4K20me3, H3K9me3). We propose that marsupial XCI is comparable to a system that evolved in the common therian (marsupial and placental) ancestor. Silent chromatin of the early inactive X was exapted from neighbouring constitutive heterochromatin and, in early placental evolution, was augmented by the rise of XIST and the stable recruitment of specific histone modifications now classically associated with XCI
Conformation Regulation of the X Chromosome Inactivation Center: A Model
X-Chromosome Inactivation (XCI) is the process whereby one, randomly chosen X becomes transcriptionally silenced in female cells. XCI is governed by the Xic, a locus on the X encompassing an array of genes which interact with each other and with key molecular factors. The mechanism, though, establishing the fate of the X's, and the corresponding alternative modifications of the Xic architecture, is still mysterious. In this study, by use of computer simulations, we explore the scenario where chromatin conformations emerge from its interaction with diffusing molecular factors. Our aim is to understand the physical mechanisms whereby stable, non-random conformations are established on the Xic's, how complex architectural changes are reliably regulated, and how they lead to opposite structures on the two alleles. In particular, comparison against current experimental data indicates that a few key cis-regulatory regions orchestrate the organization of the Xic, and that two major molecular regulators are involved
Plasticity of maritime pine (Pinus pinaster) wood-forming tissues during a growing season
Researchâą The seasonal effect is the most significant external source of variation affecting
vascular cambial activity and the development of newly divided cells, and hence
wood properties. Here, the effect of edapho-climatic conditions on the phenotypic
and molecular plasticity of differentiating secondary xylem during a growing season
was investigated.
âą Wood-forming tissues of maritime pine (Pinus pinaster) were collected from the
beginning to the end of the growing season in 2003. Data from examination of fibre
morphology, Fourier-transform infrared spectroscopy (FTIR), analytical pyrolysis, and
gas chromatography/mass spectrometry (GC/MS) were combined to characterize the
samples. Strong variation was observed in response to changes in edapho-climatic
conditions.
âą A genomic approach was used to identify genes differentially expressed during
this growing season. Out of 3512 studied genes, 19% showed a significant seasonal
effect. These genes were clustered into five distinct groups, the largest two representing
genes over-expressed in the early- or late-wood-forming tissues, respectively. The other
three clusters were characterized by responses to specific edapho-climatic conditions.
âą This work provides new insights into the plasticity of the molecular machinery
involved in wood formation, and reveals candidate genes potentially responsible for
the phenotypic differences found between early- and late-wood
New Strategy for Rapid Diagnosis and Characterization of Fungal Infections: The Example of Corneal Scrapings
PURPOSE: The prognosis of people infected with Fungi especially immunocompromised depends on rapid and accurate diagnosis to capitalize on time administration of specific treatments. However, cultures produce false negative results and nucleic-acid amplification techniques require complex post-amplification procedures to differentiate relevant fungal types. The objective of this work was to develop a new diagnostic strategy based on real-time polymerase-chain reaction high-resolution melting analysis (PCR-HRM) that a) detects yeasts and filamentous Fungi, b) differentiates yeasts from filamentous Fungi, and c) discriminates among relevant species of yeasts. METHODS: PCR-HRM detection limits and specificity were assessed with a) isolated strains; b) human blood samples experimentally infected with Fungi; c) blood experimentally infected with other infectious agents; d) corneal scrapings from patients with suspected fungal keratitis (culture positive and negative) and e) scrapings from patients with suspected bacterial, viral or Acanthamoeba infections. The DNAs were extracted and mixed with primers diluted in the MeltDoctorŸ HRM Master Mix in 2 tubes, the first for yeasts, containing the forward primer CandUn (5'CATGCCTGTTTGAGCGTC) and the reverse primer FungUn (5'TCCTCCGCTT ATTGATATGCT) and the second for filamentous Fungi, containing the forward primer FilamUn (5'TGCCTGTCCGAGCGTCAT) and FungUn. Molecular probes were not necessary. The yields of DNA extraction and the PCR inhibitors were systematically monitored. RESULTS: PCR-HRM detected 0.1 Colony Forming Units (CFU)/”l of yeasts and filamentous Fungi, differentiated filamentous Fungi from yeasts and discriminated among relevant species of yeasts. PCR-HRM performances were higher than haemoculture and sensitivity and specificity was 100% for culture positive samples, detecting and characterizing Fungi in 7 out 10 culture negative suspected fungal keratitis. CONCLUSIONS: PCR-HRM appears as a new, sensitive, specific and inexpensive test that detects Fungi and differentiates filamentous Fungi from yeasts. It allows direct fungal detection from clinical samples and experimentally infected blood in less than 2.30 h after DNA extraction
H19 Antisense RNA Can Up-Regulate Igf2 Transcription by Activation of a Novel Promoter in Mouse Myoblasts
It was recently shown that a long non-coding RNA (lncRNA), that we named the 91H RNA (i.e. antisense H19 transcript), is overexpressed in human breast tumours and contributes in trans to the expression of the Insulin-like Growth Factor 2 (IGF2) gene on the paternal chromosome. Our preliminary experiments suggested that an H19 antisense transcript having a similar function may also be conserved in the mouse. In the present work, we further characterise the mouse 91H RNA and, using a genetic complementation approach in H19 KO myoblast cells, we show that ectopic expression of the mouse 91H RNA can up-regulate Igf2 expression in trans despite almost complete unmethylation of the Imprinting-Control Region (ICR). We then demonstrate that this activation occurs at the transcriptional level by activation of a previously unknown Igf2 promoter which displays, in mouse tissues, a preferential mesodermic expression (Pm promoter). Finally, our experiments indicate that a large excess of the H19 transcript can counteract 91H-mediated Igf2 activation. Our work contributes, in conjunction with other recent findings, to open new horizons to our understanding of Igf2 gene regulation and functions of the 91H/H19 RNAs in normal and pathological conditions
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