312 research outputs found

    Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis

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    Megakaryocytopoiesis is a complex differentiation process driven by the hormone thrombopoietin by which haematopoietic progenitor cells give rise to megakaryocytes, the giant bone marrow cells that in turn break down to form blood platelets. The Tribbles Pseudokinase 3 gene (TRIB3) encodes a pleiotropic protein increasingly implicated in the regulation of cellular differentiation programmes. Previous studies have hinted that TRIB3 could be also involved in megakaryocytopoiesis but its role in this process has so far not been investigated. Using cellular model systems of haematopoietic lineage differentiation here we demonstrate that TRIB3 is a negative modulator of megakaryocytopoiesis. We found that in primary cultures derived from human haematopoietic progenitor cells, thrombopoietin-induced megakaryocytic differentiation led to a time and dosedependent decrease in TRIB3 mRNA levels. In the haematopoietic cell line UT7/mpl, silencing of TRIB3 increased basal and thrombopoietin-stimulated megakaryocyte antigen expression, as well as basal levels of ERK1/2 phosphorylation. In primary haematopoietic cell cultures, silencing of TRIB3 facilitated megakaryocyte differentiation. In contrast, over-expression of TRIB3 in these cells inhibited the differentiation process. The in-vitro identification of TRIB3 as a negative regulator of megakaryocytopoiesis suggests that in-vivo this gene could be important for the regulation of platelet production

    Surgical reconstruction of the left main coronary artery with patch-angioplasty

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    <p>Abstract</p> <p>Background</p> <p>Conventional coronary artery bypass grafting (CABG) has been established as the treatment of choice for left main coronary artery (LMCA) stenosis However, the conventional grafting provides a retrograde perfusion to extensive myocardial area and leads prospectively to competitive flow of the non-occluded coronaries thus consuming the grafts. Surgical reconstruction of the LMCA with patch-angioplasty is an alternative method that eliminates these drawbacks.</p> <p>Methods</p> <p>Between February 1997 and July 2007, 37 patients with isolated LMCA stenosis were referred for surgical ostial reconstruction. In 27 patients (73%) surgical angioplasties have been performed. All patients were followed up clinically and with transesophageal echocardiography (TEE) and coronary angiography when required.</p> <p>Results</p> <p>In 10 patients (27%) a LMCA stenosis could not be confirmed. There were no early mortality or perioperative myocardial infarctions. The postoperative course was uneventful in all patients. In 25 patients, TEE demonstrated a wide open main stem flow pattern one to six months after reconstruction of the left main coronary artery with one patch mild aneurysmal dilated.</p> <p>Conclusions</p> <p>The surgical reconstruction with patch-angioplasty is a safe and effective method for the treatment of proximal and middle LMCA stenosis. Almost one third of the study group had no really LMCA stenosis: antegrade flow pattern remained sustained and the arterial grafts have been spared. In the cases of unclear or suspected LMCA stenosis, cardio-CT can be performed to unmask catheter-induced coronary spasm as the underlying reason for isolated LMCA stenosis.</p

    Computational identification of ubiquitylation sites from protein sequences

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    <p>Abstract</p> <p>Background</p> <p>Ubiquitylation plays an important role in regulating protein functions. Recently, experimental methods were developed toward effective identification of ubiquitylation sites. To efficiently explore more undiscovered ubiquitylation sites, this study aims to develop an accurate sequence-based prediction method to identify promising ubiquitylation sites.</p> <p>Results</p> <p>We established an ubiquitylation dataset consisting of 157 ubiquitylation sites and 3676 putative non-ubiquitylation sites extracted from 105 proteins in the UbiProt database. This study first evaluates promising sequence-based features and classifiers for the prediction of ubiquitylation sites by assessing three kinds of features (amino acid identity, evolutionary information, and physicochemical property) and three classifiers (support vector machine, <it>k</it>-nearest neighbor, and NaïveBayes). Results show that the set of used 531 physicochemical properties and support vector machine (SVM) are the best kind of features and classifier respectively that their combination has a prediction accuracy of 72.19% using leave-one-out cross-validation.</p> <p>Consequently, an informative physicochemical property mining algorithm (IPMA) is proposed to select an informative subset of 531 physicochemical properties. A prediction system UbiPred was implemented by using an SVM with the feature set of 31 informative physicochemical properties selected by IPMA, which can improve the accuracy from 72.19% to 84.44%. To further analyze the informative physicochemical properties, a decision tree method C5.0 was used to acquire if-then rule-based knowledge of predicting ubiquitylation sites. UbiPred can screen promising ubiquitylation sites from putative non-ubiquitylation sites using prediction scores. By applying UbiPred, 23 promising ubiquitylation sites were identified from an independent dataset of 3424 putative non-ubiquitylation sites, which were also validated by using the obtained prediction rules.</p> <p>Conclusion</p> <p>We have proposed an algorithm IPMA for mining informative physicochemical properties from protein sequences to build an SVM-based prediction system UbiPred. UbiPred can predict ubiquitylation sites accompanied with a prediction score each to help biologists in identifying promising sites for experimental verification. UbiPred has been implemented as a web server and is available at <url>http://iclab.life.nctu.edu.tw/ubipred</url>.</p

    Drift as a Force of Evolution: A Manipulationist Account

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    Can evolutionary theory be properly characterised as a “theory of forces”, like Newtonian mechanics? One common criticism to this claim concerns the possibility to conceive genetic drift as a causal process endowed by a specific magnitude and direction. In this article, we aim to offer an original response to this criticism by pointing out a connection between the notion of force and the notion of explanatory depth, as depicted in Hitchcock and Woodward’s manipulationist account of causal explanation. In a nutshell, our argument is that, since force-explanations can be consistently reframed as deep explanations and vice versa, and the notion of drift can be characterised in manipulationist terms as constitutively intervening in evolutionary deep explanations, then drift-explanations can be consistently reframed as force-explanations, and drift can be properly considered as a force of evolution. Insofar as similar considerations may be extended also to other evolutionary factors – chiefly selection –, our analysis offers an important support to the claim that evolutionary theory is a theory of forces.info:eu-repo/semantics/publishedVersio

    The contribution of cause-effect link to representing the core of scientific paper—The role of Semantic Link Network

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    The Semantic Link Network is a general semantic model for modeling the structure and the evolution of complex systems. Various semantic links play different roles in rendering the semantics of complex system. One of the basic semantic links represents cause-effect relation, which plays an important role in representation and understanding. This paper verifies the role of the Semantic Link Network in representing the core of text by investigating the contribution of cause-effect link to representing the core of scientific papers. Research carries out with the following steps: (1) Two propositions on the contribution of cause-effect link in rendering the core of paper are proposed and verified through a statistical survey, which shows that the sentences on cause-effect links cover about 65% of key words within each paper on average. (2) An algorithm based on syntactic patterns is designed for automatically extracting cause-effect link from scientific papers, which recalls about 70% of manually annotated cause-effect links on average, indicating that the result adapts to the scale of data sets. (3) The effects of cause-effect link on four schemes of incorporating cause-effect link into the existing instances of the Semantic Link Network for enhancing the summarization of scientific papers are investigated. The experiments show that the quality of the summaries is significantly improved, which verifies the role of semantic links. The significance of this research lies in two aspects: (1) it verifies that the Semantic Link Network connects the important concepts to render the core of text; and, (2) it provides an evidence for realizing content services such as summarization, recommendation and question answering based on the Semantic Link Network, and it can inspire relevant research on content computing

    The different stratospheric influence on cold-extremes in Eurasia and North America

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    The stratospheric polar vortex can influence the tropospheric circulation and thereby winter weather in the mid-latitudes. Weak vortex states, often associated with sudden stratospheric warmings (SSW), have been shown to increase the risk of cold-spells especially over Eurasia, but its role for North American winters is less clear. Using cluster analysis, we show that there are two dominant patterns of increased polar cap heights in the lower stratosphere. Both patterns represent a weak polar vortex but they are associated with different wave mechanisms and different regional tropospheric impacts. The first pattern is zonally symmetric and associated with absorbed upward-propagating wave activity, leading to a negative phase of the North Atlantic Oscillation (NAO) and cold-air outbreaks over northern Eurasia. This coupling mechanism is well-documented in the literature and is consistent with the downward migration of the northern annular mode (NAM). The second pattern is zonally asymmetric and linked to downward reflected planetary waves over Canada followed by a negative phase of the Western Pacific Oscillation (WPO) and cold-spells in Central Canada and the Great Lakes region. Causal effect network (CEN) analyses confirm the atmospheric pathways associated with this asymmetric pattern. Moreover, our findings suggest the reflective mechanism to be sensitive to the exact region of upward wave-activity fluxes and to be state-dependent on the strength of the vortex. Identifying the causal pathways that operate on weekly to monthly timescales can pave the way for improved sub-seasonal to seasonal forecasting of cold spells in the mid-latitudes

    Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace

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    BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. CONCLUSIONS/SIGNIFICANCE: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods

    A prospective investigation of rumination and executive control in predicting overgeneral autobiographical memory in adolescence

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    The CaR-FA-X model (Williams et al., 2007), or capture and rumination (CaR), functional avoidance (FA) and impaired executive control (X), is a model of overgeneral autobiographical memory. Two mechanisms of the model, rumination and executive control were examined in isolation and in interaction to investigate overgeneral autobiographical memory over time. Method: Across two time points, six months apart, a total of 149 adolescents (13-16 years) completed a minimal instruction autobiographical memory test, a measure of executive control with emotional and non-emotional stimuli, and measures of brooding rumination and reflective pondering. Results: It was found that executive control for emotional information was negatively associated with OGM, but only when reflective pondering levels were high. Conclusion: In the context of higher levels of reflective pondering, greater switch costs (i.e. lower executive control) when processing emotional information predict a decrease in OGM over time

    BarA-UvrY Two-Component System Regulates Virulence of Uropathogenic E. coli CFT073

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    Uropathogenic Escherichia coli (UPEC), a member of extraintestinal pathogenic E. coli, cause ∼80% of community-acquired urinary tract infections (UTI) in humans. UPEC initiates its colonization in epithelial cells lining the urinary tract with a complicated life cycle, replicating and persisting in intracellular and extracellular niches. Consequently, UPEC causes cystitis and more severe form of pyelonephritis. To further understand the virulence characteristics of UPEC, we investigated the roles of BarA-UvrY two-component system (TCS) in regulating UPEC virulence. Our results showed that mutation of BarA-UvrY TCS significantly decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract infection, chicken embryo killing assay, and cytotoxicity assay on human kidney and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene reduced the production of hemolysin, lipopolysaccharide (LPS), proinflammatory cytokines (TNF-α and IL-6) and chemokine (IL-8). The virulence phenotype was restored similar to that of wild-type by complementation of either barA or uvrY gene in trans. In addition, we discussed a possible link between the BarA-UvrY TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall, this study provides the evidences for BarA-UvrY TCS regulates the virulence of UPEC CFT073 and may point to mechanisms by which virulence regulations are observed in different ways may control the long-term survival of UPEC in the urinary tract
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