371 research outputs found
Hyper-complex four-manifolds from the Tzitz\'eica equation
It is shown how solutions to the Tzitz\'eica equation can be used to
construct a family of (pseudo) hyper-complex metrics in four dimensions.Comment: To be published in J.Math.Phy
Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the miR-155–induced GM populations displayed pathological features characteristic of myeloid neoplasia. Of possible relevance to human disease, miR-155 was found to be overexpressed in the bone marrow of patients with certain subtypes of acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress
Seasonal Adjustment Methods and the Determination of Turning Points of the EMU Business Cycle
In this paper, we investigate the impact of the adjustment for seasonal effects with different seasonal adjustment methods, the possible pre-treatment for calendar effects and the different order of aggregation and adjustment for the determination of the turning points of the European business cycle. The European business cycle is represented first by the GDP series (referring to the classical definition of a business cycle as fluctuations in the level of economic activity), and then by deviations from trend (which corresponds to the definition of the cycle as changing capacity utilisation). The turning points are determined using a mechanical procedure (Bry/Boschan methodology), which ensure that all series are treated alike. The comparison of turning points in the classical and growth cycles has brought the following results: 1.The order of seasonal adjustment and aggregation has only minor effects on the determined turning points of the European business cycle. 2.If the series are pretreated for calendar effects, turning points in the aggregated series can differ significantly. 3.It is not relevant whether the series were adjusted with a single method or with different methods (mixed aggregates)
MicroRNA-155 is induced during the macrophage inflammatory response
The mammalian inflammatory response to infection involves the induction of several hundred genes, a process that must be carefully regulated to achieve pathogen clearance and prevent the consequences of unregulated expression, such as cancer. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators that has also been linked to cancer. However, the relationship between inflammation, innate immunity, and miRNA expression is just beginning to be explored. In the present study, we use microarray technology to identify miRNAs induced in primary murine macrophages after exposure to polyriboinosinic:polyribocytidylic acid or the cytokine IFN-{beta}. miR-155 was the only miRNA of those tested that was substantially up-regulated by both stimuli. It also was induced by several Toll-like receptor ligands through myeloid differentiation factor 88- or TRIF-dependent pathways, whereas up-regulation by IFNs was shown to involve TNF-{alpha} autocrine signaling. Pharmacological inhibition of the kinase JNK blocked induction of miR-155 in response to either polyriboinosinic:polyribocytidylic acid or TNF-{alpha}, suggesting that miR-155-inducing signals use the JNK pathway. Together, these findings characterize miR-155 as a common target of a broad range of inflammatory mediators. Importantly, because miR-155 is known to function as an oncogene, these observations identify a potential link between inflammation and cancer
NF-κB dysregulation in microRNA-146a–deficient mice drives the development of myeloid malignancies
MicroRNA miR-146a has been implicated as a negative feedback regulator of NF-κB activation. Knockout of the miR-146a gene in C57BL/6 mice leads to histologically and immunophenotypically defined myeloid sarcomas and some lymphomas. The sarcomas are transplantable to immunologically compromised hosts, showing that they are true malignancies. The animals also exhibit chronic myeloproliferation in their bone marrow. Spleen and marrow cells show increased transcription of NF-κB–regulated genes and tumors have higher nuclear p65. Genetic ablation of NF-κB p50 suppresses the myeloproliferation, showing that dysregulation of NF-κB is responsible for the myeloproliferative disease
Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid
Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria
Promotion of Hendra virus replication by microRNA 146a
Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication. In this work, we demonstrate that Hendra virus makes use of a microRNA (miRNA) designated miR-146a, an NF-κB-responsive miRNA upregulated by several innate immune ligands, to favor its replication. miR-146a is elevated in the blood of ferrets and horses infected with Hendra virus and is upregulated by Hendra virus in human cells in vitro. Blocking miR-146a reduces Hendra virus replication in vitro, suggesting a role for this miRNA in Hendra virus replication. In silico analysis of miR-146a targets identified ring finger protein (RNF)11, a member of the A20 ubiquitin editing complex that negatively regulates NF-κB activity, as a novel component of Hendra virus replication. RNA interference-mediated silencing of RNF11 promotes Hendra virus replication in vitro, suggesting that increased NF-κB activity aids Hendra virus replication. Furthermore, overexpression of the IκB superrepressor inhibits Hendra virus replication. These studies are the first to demonstrate a host miRNA response to Hendra virus infection and suggest an important role for host miRNAs in Hendra virus disease
Tungstate Based Ceramics Obtained By Spark Plasma Sintering Method – Possible Material for Consolidation of Radioactive Wastes’ Components
The Spark Plasma Sintering method was used to produce high-density ceramics from tungstates SrWO4 and NaNd(WO4)2 with scheelite structure. These compounds are proposed as possible matrices for the consolidation of radwaste components. Powder samples were obtained by coprecipitation method and studied by X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). After sintering, the samples retained their phase identity (scheelite structure). The total duration of sintering was ∼ 13-15 min, the relative density was reached ∼ 92, 99%.
Keywords: Tungstates, RW, Spark Plasma Sintering, high density, microstructur
Investigation of the microstructure of the fine-grained YPO:Gd ceramics with xenotime structure after Xe irradiation
The paper reports on the preparation of xenotime-structured ceramics by the
Spark Plasma Sintering (SPS) method. Phosphates YGdPO
(YPO:Gd) were obtained by the sol-gel method. The synthesized nanopowders
are collected in large agglomerates 10-50 mkm in size. Ceramics has a
fine-grained microstructure and a high relative density (98.67%). The total
time of the SPS process was approximately 18 min. High-density sintered
ceramics YPO:Gd with a xenotime structure were irradiated with Xe
ions (E = 167 MeV) to fluences of - cm.
Complete amorphization at maximum fluence was not achieved. As the fluence
increases, an insignificant increase in the depth of the amorphous layer is
observed. According to the results of grazing incidence XRD (GIXRD), with an
increase in fluence from - cm, an
increase in the volume fraction of the amorphous structure from 20 to 70% is
observed. The intensity of XRD peak 200 YPO:Gd after recovery annealing
(700C, 18 h) reached a value of ~80% of the initial intensity I0.Comment: 16 pages, 10 figure
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