αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function.

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Huang, Claire Yu-Mei; Zhang, Chuansheng; Ho, Tammy Szu-Yu; Oses-Prieto, Juan; Burlingame, Alma L; Lalonde, Joshua; Noebels, Jeffrey L; Leterrier, Christophe; Rasband, Matthew N

2017-11-22

Spectrins form a submembranous cytoskeleton proposed to confer strength and flexibility to neurons and to participate in ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Neuronal spectrin cytoskeletons consist of diverse β subunits and αII spectrin. Although αII spectrin is found in neurons in both axonal and somatodendritic domains, using proteomics, biochemistry, and superresolution microscopy, we show that αII and βIV spectrin interact and form a periodic AIS cytoskeleton. To determine the role of spectrins in the nervous system, we generated Sptan1 f/f mice for deletion of CNS αII spectrin. We analyzed αII spectrin-deficient mice of both sexes and found that loss of αII spectrin causes profound reductions in all β spectrins. αII spectrin-deficient mice die before 1 month of age and have disrupted AIS and many other neurological impairments including seizures, disrupted cortical lamination, and widespread neurodegeneration. These results demonstrate the importance of the spectrin cytoskeleton both at the AIS and throughout the nervous system. SIGNIFICANCE STATEMENT Spectrin cytoskeletons play diverse roles in neurons, including assembly of excitable domains such as the axon initial segment (AIS) and nodes of Ranvier. However, the molecular composition and structure of these cytoskeletons remain poorly understood. Here, we show that αII spectrin partners with βIV spectrin to form a periodic cytoskeleton at the AIS. Using a new αII spectrin conditional knock-out mouse, we show that αII spectrin is required for AIS assembly, neuronal excitability, cortical lamination, and to protect against neurodegeneration. These results demonstrate the broad importance of spectrin cytoskeletons for nervous system function and development and have important implications for nervous system injuries and diseases because disruption of the spectrin cytoskeleton is a common molecular pathology. Copyright © 2017 the authors 0270-6474/17/3711311-12$15.00/0.

An Adaptable Spectrin/Ankyrin-Based Mechanism for Long-Range Organization of Plasma Membranes in Vertebrate Tissues.

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Bennett, Vann; Lorenzo, Damaris N

2016-01-01

Ankyrins are membrane-associated proteins that together with their spectrin partners are responsible for micron-scale organization of vertebrate plasma membranes, including those of erythrocytes, excitable membranes of neurons and heart, lateral membrane domains of columnar epithelial cells, and striated muscle. Ankyrins coordinate functionally related membrane transporters and cell adhesion proteins (15 protein families identified so far) within plasma membrane compartments through independently evolved interactions of intrinsically disordered sequences with a highly conserved peptide-binding groove formed by the ANK repeat solenoid. Ankyrins are coupled to spectrins, which are elongated organelle-sized proteins that form mechanically resilient arrays through cross-linking by specialized actin filaments. In addition to protein interactions, cellular targeting and assembly of spectrin/ankyrin domains also critically depend on palmitoylation of ankyrin-G by aspartate-histidine-histidine-cysteine 5/8 palmitoyltransferases, as well as interaction of beta-2 spectrin with phosphoinositide lipids. These lipid-dependent spectrin/ankyrin domains are not static but are locally dynamic and determine membrane identity through opposing endocytosis of bulk lipids as well as specific proteins. A partnership between spectrin, ankyrin, and cell adhesion molecules first emerged in bilaterians over 500 million years ago. Ankyrin and spectrin may have been recruited to plasma membranes from more ancient roles in organelle transport. The basic bilaterian spectrin-ankyrin toolkit markedly expanded in vertebrates through gene duplications combined with variation in unstructured intramolecular regulatory sequences as well as independent evolution of ankyrin-binding activity by ion transporters involved in action potentials and calcium homeostasis. In addition, giant vertebrate ankyrins with specialized roles in axons acquired new coding sequences by exon shuffling. We speculate that

Increased [32P]-phosphorylation of tryptic peptides of erythrocyte spectrin in Duchenne muscular dystrophy

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Mabry, M.E.; Roses, A.D.

1981-01-01

Increased [32P]-incorporation in tryptic peptides of the erythrocyte membrane protein spectrin Band 2 in Duchenne muscular dystrophy (DMD) was studied in a consecutive series of 10 matched DMD/control pairs. Spectrin was [32P]-phosphorylated by cyclic AMP-independent endogenous membrane protein kinase in the presence of [gamma-32P]ATP. [32P]-labeled spectrin was isolated, purified, and subjected to tryptic cleavage with excess trypsin. The resulting peptides were separated on a high-resolution 5%/15% stacking SDS--polyacrylamide gel electrophoresis system. Liquid scintillation counting was performed on sequential slices of unstained gels. A broad [32P]-labeled band containing a number of [32P]-polypeptides was found to be more highly [32P]-phosphorylated in DMD patients than in their matched controls. This band migrated with an apparent molecular mass of 4.8-5.2 kilodaltons and contained approximately 55% of total [32P] radioactivity covalently bound to spectrin peptides. These data demonstrated an increased [32P]-phosphorylation of an identifiable tryptic peptide fraction in DMD that is consistent with previous reports of increased spectrin Band 2 [32P]-phosphorylation in DMD

Increased (/sup 32/P)-phosphorylation of tryptic peptides of erythrocyte spectrin in Duchenne muscular dystrophy

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Mabry, M.E.; Roses, A.D.

Increased (32P)-incorporation in tryptic peptides of the erythrocyte membrane protein spectrin Band 2 in Duchenne muscular dystrophy (DMD) was studied in a consecutive series of 10 matched DMD/control pairs. Spectrin was (32P)-phosphorylated by cyclic AMP-independent endogenous membrane protein kinase in the presence of (gamma-32P)ATP. (32P)-labeled spectrin was isolated, purified, and subjected to tryptic cleavage with excess trypsin. The resulting peptides were separated on a high-resolution 5%/15% stacking SDS--polyacrylamide gel electrophoresis system. Liquid scintillation counting was performed on sequential slices of unstained gels. A broad (32P)-labeled band containing a number of (32P)-polypeptides was found to be more highly (32P)-phosphorylated in DMD patients than in their matched controls. This band migrated with an apparent molecular mass of 4.8-5.2 kilodaltons and contained approximately 55% of total (32P) radioactivity covalently bound to spectrin peptides. These data demonstrated an increased (32P)-phosphorylation of an identifiable tryptic peptide fraction in DMD that is consistent with previous reports of increased spectrin Band 2 (32P)-phosphorylation in DMD.

Lesions of entorhinal cortex produce a calpain-mediated degradation of brain spectrin in dentate gyrus. I. Biochemical studies.

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Seubert, P; Ivy, G; Larson, J; Lee, J; Shahi, K; Baudry, M; Lynch, G

1988-09-06

Lesions of the rat entorhinal cortex cause extensive synaptic restructuring and perturbation of calcium regulation in the dentate gyrus of hippocampus. Calpain is a calcium-activated protease which has been implicated in degenerative phenomena in muscles and in peripheral nerves. In addition, calpain degrades several major structural neuronal proteins and has been proposed to play a critical role in the morphological changes observed following deafferentation. In this report we present evidence that lesions of the entorhinal cortex produce a marked increase in the breakdown of brain spectrin, a substrate for calpain, in the dentate gyrus. Two lines of evidence indicate that this effect is due to calpain activation: (i) the spectrin breakdown products observed following the lesion are indistinguishable from calpain-generated spectrin fragments in vitro; and (ii) their appearance can be reduced by prior intraventricular in fusion of leupeptin, a calpain inhibitor. Levels of spectrin breakdown products are increased as early as 4 h post-lesion, reach maximal values at 2 days, and remain above normal to some degree for at least 27 days. In addition, a small but significant increase in spectrin proteolysis is also observed in the hippocampus contralateral to the lesioned side in the first week postlesion. At 2 days postlesion the total spectrin immunoreactivity (native polypeptide plus breakdown products) increases by 40%, suggesting that denervation of the dentate gyrus produces not only an increased rate of spectrin degradation but also an increased rate of spectrin synthesis. These results indicate that calpain activation and spectrin degradation are early biochemical events following deafferentation and might well participate in the remodelling of postsynaptic structures. Finally, the magnitude of the observed effects as well as the stable nature of the breakdown products provide a sensitive assay for neuronal pathology.

βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons.

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Efimova, Nadia; Korobova, Farida; Stankewich, Michael C; Moberly, Andrew H; Stolz, Donna B; Wang, Junling; Kashina, Anna; Ma, Minghong; Svitkina, Tatyana

2017-07-05

Dendritic spines are postsynaptic structures in neurons often having a mushroom-like shape. Physiological significance and cytoskeletal mechanisms that maintain this shape are poorly understood. The spectrin-based membrane skeleton maintains the biconcave shape of erythrocytes, but whether spectrins also determine the shape of nonerythroid cells is less clear. We show that βIII spectrin in hippocampal and cortical neurons from rodent embryos of both sexes is distributed throughout the somatodendritic compartment but is particularly enriched in the neck and base of dendritic spines and largely absent from spine heads. Electron microscopy revealed that βIII spectrin forms a detergent-resistant cytoskeletal network at these sites. Knockdown of βIII spectrin results in a significant decrease in the density of dendritic spines. Surprisingly, the density of presynaptic terminals is not affected by βIII spectrin knockdown. However, instead of making normal spiny synapses, the presynaptic structures in βIII spectrin-depleted neurons make shaft synapses that exhibit increased amplitudes of miniature EPSCs indicative of excessive postsynaptic excitation. Thus, βIII spectrin is necessary for formation of the constricted shape of the spine neck, which in turn controls communication between the synapse and the parent dendrite to prevent excessive excitation. Notably, mutations of SPTNB2 encoding βIII spectrin are associated with neurodegenerative syndromes, spinocerebellar ataxia Type 5, and spectrin-associated autosomal recessive cerebellar ataxia Type 1, but molecular mechanisms linking βIII spectrin functions to neuronal pathologies remain unresolved. Our data suggest that spinocerebellar ataxia Type 5 and spectrin-associated autosomal recessive cerebellar ataxia Type 1 pathology likely arises from poorly controlled synaptic activity that leads to excitotoxicity and neurodegeneration. SIGNIFICANCE STATEMENT Dendritic spines are small protrusions from neuronal

Image-based model of the spectrin cytoskeleton for red blood cell simulation.

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Fai, Thomas G; Leo-Macias, Alejandra; Stokes, David L; Peskin, Charles S

2017-10-01

We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three-dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protect against failure in the case of a red cell subjected to an applied strain. The methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.

Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.

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Stefano Lise

Full Text Available β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5, an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1. In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome.

A hanging drop culture method to study terminal erythroid differentiation.

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Gutiérrez, Laura; Lindeboom, Fokke; Ferreira, Rita; Drissen, Roy; Grosveld, Frank; Whyatt, David; Philipsen, Sjaak

2005-10-01

To design a culture method allowing the quantitative and qualitative analysis of terminal erythroid differentiation. Primary erythroid progenitors derived either from mouse tissues or from human umbilical cord blood were differentiated using hanging drop cultures and compared to methylcellulose cultures. Cultured cells were analyzed by FACS to assess differentiation. We describe a practical culture method by adapting the previously described hanging drop culture system to conditions allowing terminal differentiation of primary erythroid progenitors. Using minimal volumes of media and small numbers of cells, we obtained quantitative terminal erythroid differentiation within two days of culture in the case of murine cells and 4 days in the case of human cells. The established methods for ex vivo culture of primary erythroid progenitors, such as methylcellulose-based burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) assays, allow the detection of committed erythroid progenitors but are of limited value to study terminal erythroid differentiation. We show that the application of hanging drop cultures is a practical alternative that, in combination with clonogenic assays, enables a comprehensive assessment of the behavior of primary erythroid cells ex vivo in the context of genetic and drug-induced perturbations.

A study of membrane protein defects and alpha hemoglobin chains of red blood cells in human beta thalassemia

International Nuclear Information System (INIS)

Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.; Guetarni, D.; Bachir, D.; Colonna, P.; Beuzard, Y.

1989-01-01

The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with [ 3 H]N-ethylmaleimide. This pool of soluble alpha chains was 0.067 ± 0.017% of hemoglobin in blood of normal adult, 0.11 ± 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using [ 3 H]N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups

Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells

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Miller, B.A.; Perrine, S.P.; Antognetti, G.; Perlmutter, D.H.; Emerson, S.G.; Sieff, C.; Faller, D.V.

1987-01-01

The effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes

Activated Fps/Fes tyrosine kinase regulates erythroid differentiation and survival.

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Sangrar, Waheed; Gao, Yan; Bates, Barbara; Zirngibl, Ralph; Greer, Peter A

2004-10-01

A substantial body of evidence implicates the cytoplasmic protein tyrosine kinase Fps/Fes in regulation of myeloid differentiation and survival. In this study we wished to determine if Fps/Fes also plays a role in the regulation of erythropoiesis. Mice tissue-specifically expressing a "gain-of-function" mutant fps/fes transgene (fps(MF)) encoding an activated variant of Fps/Fes (MFps), were used to explore the in vivo biological role of Fps/Fes. Erythropoiesis in these mice was assessed by hematological analysis, lineage marker analysis, bone-marrow colony assays, and biochemical approaches. fps(MF) mice displayed reductions in peripheral red cell counts. However, there was an accumulation of immature erythroid precursors, which displayed increased survival. Fps/Fes and the related Fer kinase were both detected in early erythroid progenitors/blasts and in mature red cells. Fps/Fes was also activated in response to erythropoietin (EPO) and stem cell factor (SCF), two critical factors in erythroid development. In addition, increased Stat5A/B activation and reduced Erk1/2 phosphorylation was observed in fps(MF) primary erythroid cells in response to EPO or SCF, respectively. These data support a role for Fps/Fes in regulating the survival and differentiation of erythroid cells through modulation of Stat5A/B and Erk kinase pathways induced by EPO and SCF. The increased numbers and survival of erythroid progenitors from fps(MF) mice, and their differential responsiveness to SCF and EPO, implicates Fps/Fes in the commitment of multilineage progenitors to the erythroid lineage. The anemic phenotype in fps(MF) mice suggests that downregulation of Fps/Fes activity might be required for terminal erythroid differentiation.

Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells

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Zita Garate

2015-12-01

Full Text Available Pyruvate kinase deficiency (PKD is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. We generated PKD induced pluripotent stem cells (PKDiPSCs from peripheral blood mononuclear cells (PB-MNCs of PKD patients by non-integrative Sendai viral vectors. PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR. Notably, we found allele specificity of HR led by the presence of a single-nucleotide polymorphism. High numbers of erythroid cells derived from gene-edited PKDiPSCs showed correction of the energetic imbalance, providing an approach to correct metabolic erythroid diseases and demonstrating the practicality of this approach to generate the large cell numbers required for comprehensive biochemical and metabolic erythroid analyses.

Hemozoin (malarial pigment directly promotes apoptosis of erythroid precursors.

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Abigail A Lamikanra

2009-12-01

Full Text Available Severe malarial anemia is the most common syndrome of severe malaria in endemic areas. The pathophysiology of chronic malaria is characterised by a striking degree of abnormal development of erythroid precursors (dyserythropoiesis and an inadequate erythropoietic response in spite of elevated levels of erythropoietin. The cause of dyserythropoiesis is unclear although it has been suggested that bone-marrow macrophages release cytokines, chemokines or lipo-peroxides after exposure to hemozoin, a crystalloid form of undigested heme moieties from malarial infected erythrocytes, and so inhibit erythropoiesis. However, we have previously shown that hemozoin may directly inhibit erythroid development in vitro and the levels of hemozoin in plasma from patients with malarial anemia and hemozoin within the bone marrow was associated with reduced reticulocyte response. We hypothesized that macrophages may reduce, not enhance, the inhibitory effect of hemozoin on erythropoiesis. In an in vitro model of erythropoiesis, we now show that inhibition of erythroid cell development by hemozoin isolated from P. falciparum is characterised by delayed expression of the erythroid markers and increased apoptosis of progenitor cells. Crucially, macrophages appear to protect erythroid cells from hemozoin, consistent with a direct contribution of hemozoin to the depression of reticulocyte output from the bone marrow in children with malarial anemia. Moreover, hemozoin isolated from P. falciparum in vitro inhibits erythroid development independently of inflammatory mediators by inducing apoptotic pathways that not only involve activation of caspase 8 and cleavage of caspase 3 but also loss of mitochondrial potential. Taken together these data are consistent with a direct effect of hemozoin in inducing apoptosis in developing erythroid cells in malarial anemia. Accumulation of hemozoin in the bone marrow could therefore result in inadequate reticulocytosis in children that

The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

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Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming; Wang, Yan; Wang, Jie; Li, Yang; Suriguga,; Zhang, Guang-Yao; Yi, Zong-Chun

2012-01-01

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.

The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

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Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming; Wang, Yan; Wang, Jie; Li, Yang; Suriguga,; Zhang, Guang-Yao; Yi, Zong-Chun, E-mail: yizc@buaa.edu.cn

2012-11-15

Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.

The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

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Uziel, Orit; Kanfer, Gil; Beery, Einat; Yelin, Dana; Shepshelovich, Daniel; Bakhanashvili, Mary; Nordenberg, Jardena; Lahav, Meir

2014-01-01

Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway

The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

Energy Technology Data Exchange (ETDEWEB)

Uziel, Orit, E-mail: Oritu@clalit.org.il [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Kanfer, Gil [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Beery, Einat [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Yelin, Dana; Shepshelovich, Daniel [Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Bakhanashvili, Mary [Unit of Infectious Diseases, Sheba Medical Center, Tel-Hashomer (Israel); Nordenberg, Jardena [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Endocrinology Laboratory, Beilinson Medical Center, Petah-Tikva (Israel); Lahav, Meir [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel)

2014-07-18

Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.

Selective toxicity of dihydroartemisinin on human CD34+ erythroid cell differentiation

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Finaurini, Sara; Ronzoni, Luisa; Colancecco, Alessandra; Cattaneo, Alessandra; Cappellini, Maria Domenica; Ward, Stephen A.; Taramelli, Donatella

2010-01-01

Artemisinins are safely used in the combination therapy for uncomplicated malaria, but their employment during pregnancy is still controversial. In fact, animal studies reported that the active metabolite, dihydroartemisinin (DHA), causes embryonic erythrocytes depletion, when the treatment is performed during a critical period of time. The present study investigates the effect of DHA on human developmental erythropoiesis in order to characterize the target erythroid stage and to predict the window of susceptibility in human pregnancy. As a model for human developmental erythropoiesis, peripheral blood purified, CD34+ cells were committed towards erythrocytes and DHA (0.5 or 2 μM) was added to different erythroid stages during 14 days culture. Erythroid differentiation was investigated by cytofluorimetric analysis of Glycophorin A expression, by morphological analysis and erythroid globin gene expression analysis with real-time PCR. It was found that the effect of DHA was dependent on the maturation stage of erythroid cells. In fact when DHA was added to the pro- and basophilic erythroblasts caused a significant dose-dependent inhibition of cell proliferation and a significant delay of erythroid differentiation, as measured by morphological analysis, expression of Glycophorin A by immunofluorescence and of erythroid globin genes by real-time PCR. In contrast, the inhibition of stem cells and of early progenitors was transient and masked by the subsequent exponential cell growth. No effect was observed on mature erythroid stages. This is the first demonstration that DHA affects human erythropoiesis in vitro, in a dose- and time-dependent manner; the target population seems to be the pro-erythroblast and basophilic erythroblast stage, suggesting that DHA toxicity is limited to primitive human erythropoiesis. These findings outline the relevance of DHA dosage and timing to prevent embryotoxicity and support current WHO recommendations of avoiding malaria treatment

Antisense myb inhibition of purified erythroid progenitors in development and differentiation is linked to cycling activity and expression of DNA polymerase alpha

International Nuclear Information System (INIS)

Valtieri, M.; Venturelli, D.; Care, A.; Fossati, C.; Pelosi, E.; Labbaye, C.; Mattia, G.; Gewirtz, A.M.; Calabretta, B.; Peschle, C.

1991-01-01

These studies aimed to determine the expression and functional role of c-myb in erythroid progenitors with different cycling activities. In the first series of experiments the erythroid burst-forming unit (BFU-E) and colony-forming unit (CFU-E) populations from adult peripheral blood (PB), bone marrow (BM), and embryonic-fetal liver (FL) were treated with either c-myb antisense oligomers or 3H-thymidine (3H-TdR). A direct correlation was always observed between the inhibitory effect of anti-myb oligomers and the level of cycling activity. Thus, the inhibitory effect of antisense c-myb on the number of BFU-E colonies was 28.3% +/- 15.8% in PB, 53.4% +/- 9.3% in BM, and 68.2% +/- 24.5% in FL. Both adult and embryonic CFU-E were markedly inhibited. Using purified PB progenitors, we observed a similar pattern, although with slightly lower inhibitory effects. In the 3H-TdR suicide assay the killing index of BFU-E was 8.9% +/- 4.2% in PB, 29.4% +/- 6.5% in BM, and 40.1% +/- 9.6% in FL. The values for adult and embryonic CFU-E were 55.7% +/- 7.9% and 60.98% +/- 6.6%, respectively. We then investigated the kinetics of c-myb mRNA level during the erythroid differentiation of purified adult PB and FL BFU-E, as evaluated in liquid-phase culture by reverse transcription-polymerase chain reaction. Adult erythroid precursors showed a gradual increase of c-myb mRNA from day 4 through day 8 of culture and a sharp decrease at later times, whereas the expression of c-myb mRNA and protein in differentiation embryonic precursors peaked 2 days earlier. In both cases, c-myb mRNA level peaked at the CFU-E stage of differentiation. Finally, highly purified adult PB BFU-E were stimulated into cycling by a 3-day treatment with interleukin-3 in liquid phase: both the sensitivity to c-myb antisense oligomers and the 3H-TdR suicide index showed a gradual, strictly parallel increase

Studies of globin gene expression in differentiating erythroid cells

International Nuclear Information System (INIS)

Sullivan, T.D.

1985-01-01

The author has addressed questions concerning globin gene expression and the loss of protein synthesis in the terminal stages of erythroid development. (1) The hypothesis that the rate of cell division affects the relative synthesis of γ and β globin in erythroid cells was investigated. The effect of hydroxyurea, aminopterin, or low culture temperature on the in vitro growth of erythroid progenitor cells and on the relative synthesis of γ and β globin was measured. No consistent change in γ globin synthesis was detected. (2) The hypothesis that the ratio of γ and β globin synthesis decreases during erythroid maturation because of differential mRNA stability was investigated. The half-lives of γ and β globin mRNAs and γ and β globin protein synthesis were measured in cultured reticulocytes. γ and β globin mRNAs were assayed by solution hybridization and by in vitro translation. Globin synthesis was determined by 3 H-leucine incorporation into the γ and β globin chains. γ and β globin mRNAs decay with similar half-lives in cultured reticulocytes. Therefore, the change in the ratio of γ and β globin synthesis during erythroid maturation cannot be explained by differences in mRNA stability and is likely to result from asynchronous transcription of the genes. These data suggest that protein synthesis in maturing reticulocytes is not limited by the quantity of mRNA but by the availability of translation factors. (3) The hypothesis was tested that the initiation factor GEF becomes limiting for protein synthesis during reticulocyte maturation

Serum-free Erythroid Differentiation for Efficient Genetic Modification and High-Level Adult Hemoglobin Production.

Science.gov (United States)

Uchida, Naoya; Demirci, Selami; Haro-Mora, Juan J; Fujita, Atsushi; Raines, Lydia N; Hsieh, Matthew M; Tisdale, John F

2018-06-15

In vitro erythroid differentiation from primary human cells is valuable to develop genetic strategies for hemoglobin disorders. However, current erythroid differentiation methods are encumbered by modest transduction rates and high baseline fetal hemoglobin production. In this study, we sought to improve both genetic modification and hemoglobin production among human erythroid cells in vitro . To model therapeutic strategies, we transduced human CD34 + cells and peripheral blood mononuclear cells (PBMCs) with lentiviral vectors and compared erythropoietin-based erythroid differentiation using fetal-bovine-serum-containing media and serum-free media. We observed more efficient transduction (85%-93%) in serum-free media than serum-containing media (20%-69%), whereas the addition of knockout serum replacement (KSR) was required for serum-free media to promote efficient erythroid differentiation (96%). High-level adult hemoglobin production detectable by electrophoresis was achieved using serum-free media similar to serum-containing media. Importantly, low fetal hemoglobin production was observed in the optimized serum-free media. Using KSR-containing, serum-free erythroid differentiation media, therapeutic adult hemoglobin production was detected at protein levels with β-globin lentiviral transduction in both CD34 + cells and PBMCs from sickle cell disease subjects. Our in vitro erythroid differentiation system provides a practical evaluation platform for adult hemoglobin production among human erythroid cells following genetic manipulation.

Acute erythroid neoplastic proliferations. A biological study based on 62 patients.

Science.gov (United States)

Domingo-Claros, Alicia; Larriba, Itziar; Rozman, Maruja; Irriguible, Dolors; Vallespí, Teresa; Aventin, Anna; Ayats, Ramon; Millá, Fuensanta; Solé, Francesc; Florensa, Lourdes; Gallart, Miquel; Tuset, Esperanza; Lopez, Carmen; Woessner, Soledad

2002-02-01

The terms acute erythroleukemia and AML-M6 are defined in the FAB classification as proliferations of dysplastic erythroid elements mixed with blasts of myeloid origin, but pure erythroid leukemias are not included. The recent WHO classification has a category of acute myeloid leukemia not otherwise categorized, which includes acute erythroid leukemia (M6) of two subtypes: M6a-erythroleukemia (erythroid/myeloid) and M6b-pure erythroid leukemia. The aims of this co-operative study were to discover the incidences of these different subtypes, and pay special attention to the morphology of these entities. We reviewed a series of 62 patients with erythroid neoplastic proliferations. Previous medical history, age, sex, peripheral blood and bone marrow cell counts, cytochemical stains, immunophenotype, and cytogenetics were evaluated at presentation. We analyzed the incidence of erythrocyte, leukocyte and platelet abnormalities in the peripheral blood. In bone marrow we analyzed dysplastic features of erythroblasts, granulocytic elements and the megakaryocytic lineage. Fifty-three patients met the criteria of M6a subtype of the WHO classification, and 2 were classified as having pure erythremia (M6b); 7 cases could not be classified according to the WHO criteria. Fifty-five patients presented with de novo acute leukemia, and seven patients had secondary acute leukemia. The most frequent dysplastic features in blood smears were: schistocytes, tear-drop and pincered cells in erythrocytes; hypogranulation and hyposegmentation in leukocytes; gigantism and hypogranulation in platelets. In bone marrow, megaloblastic changes, multinuclearity, karyorrhexis and basophilic stippling in erythroblasts; hypogranulation and gigantism in granulocytic series, and micromegakaryocytes and unconnected nuclei in megakarocytes were the most dysplastic features. A positive PAS reaction and increase of bone marrow iron with ring sideroblasts were common features. Trilineage dysplasia was

Non-resonant triple alpha reaction rate at low temperature

Energy Technology Data Exchange (ETDEWEB)

Itoh, T.; Tamii, A.; Aoi, N.; Fujita, H.; Hashimoto, T.; Miki, K.; Ogata, K. [Research Center for Nuclear Physics, Osaka University, Ibaraki, Osaka 567-0047 (Japan); Carter, J.; Donaldson, L.; Sideras-Haddad, E. [Schools of Physics, University of Witwatersrand, Johannesburg 2050 (South Africa); Furuno, T.; Kawabata, T. [Departments of Physics, Kyoto University, Sakyo, Kyoto, 606-8502 (Japan); Kamimura, M. [RIKEN Nishina Center, Wako, Saitama, 351-0198 (Japan); Nemulodi, F.; Neveling, R.; Smit, F. D.; Swarts, C. [iThemba Laboratory for Accelerator Based Sciences Somerset, West, 7129 (South Africa)

2014-05-02

Our experimental goal is to study the non-resonant triple alpha reaction rate at low temperture (T < 10{sup 8} K). The {sup 13}C(p,d) reaction at 66 MeV has been used to probe the alpha-unbound continuum state in {sup 12}C just below the 2{sup nd} 0{sup +} state at 7.65 MeV. The transition strength to the continuum state is predicted to be sensitive to the non-resonant triple alpha reaction rate. The experiment has been performed at iThemba LABS. We report the present status of the experiment.

TMEM14C is required for erythroid mitochondrial heme metabolism.

Science.gov (United States)

Yien, Yvette Y; Robledo, Raymond F; Schultz, Iman J; Takahashi-Makise, Naoko; Gwynn, Babette; Bauer, Daniel E; Dass, Abhishek; Yi, Gloria; Li, Liangtao; Hildick-Smith, Gordon J; Cooney, Jeffrey D; Pierce, Eric L; Mohler, Kyla; Dailey, Tamara A; Miyata, Non; Kingsley, Paul D; Garone, Caterina; Hattangadi, Shilpa M; Huang, Hui; Chen, Wen; Keenan, Ellen M; Shah, Dhvanit I; Schlaeger, Thorsten M; DiMauro, Salvatore; Orkin, Stuart H; Cantor, Alan B; Palis, James; Koehler, Carla M; Lodish, Harvey F; Kaplan, Jerry; Ward, Diane M; Dailey, Harry A; Phillips, John D; Peters, Luanne L; Paw, Barry H

2014-10-01

The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.

The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells

Energy Technology Data Exchange (ETDEWEB)

Suriguga,; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun, E-mail: yizc@buaa.edu.cn

2013-12-15

Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. - Highlights: • Catechol enhanced hemin-induced hemoglobin accumulation. • COMT-catalyzed methylation acted as detoxication of catechol. • COMT involved in catechol-enhanced erythroid differentiation.

The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells

International Nuclear Information System (INIS)

Suriguga,; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun

2013-01-01

Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. - Highlights: • Catechol enhanced hemin-induced hemoglobin accumulation. • COMT-catalyzed methylation acted as detoxication of catechol. • COMT involved in catechol-enhanced erythroid differentiation

New human erythrocyte protein with binding sites for both spectrin and calmodulin

International Nuclear Information System (INIS)

Gardner, K.; Bennett, V.

1986-01-01

A new cytoskeletal protein that binds calmodulin has been purified to greater than 95% homogeneity from human erythrocyte cytoskeletons. The protein is a heterodimer with subunits of 103,000 and 97,000 and M/sub r/ = 197,000 calculated from its Stokes radius of 6.9 nm and sedimentation coefficient of 6.8. A binding affinity of this protein for calmodulin has been estimated to be 230 nM by displacement of two different concentrations of 125 I-azidocalmodulin with increasing concentrations of unmodified calmodulin followed by Dixon plot analysis. This protein is present in red cells at approximately 30,000 copies per cell and contains a very tight binding site(s) on cytoskeletons. The protein can be only partially solubilized from isolated cytoskeletons in buffers containing high salt, but can be totally solubilized from red cell ghost membranes by extraction in low ionic strength buffers. Affinity purified IgG against this calmodulin-binding protein identifies crossreacting polypeptide(s) in brain, kidney, testes and retina. Visualization of the calmodulin-binding protein by negative staining, rotary shadowing and unidirectional shadowing indicate that it is a flattened circular molecule with molecular height of 5.4 nm and a diameter of 12.4 nm. Preliminary cosedimentation studies with purified spectrin and F-actin indicate that the site of interaction of this calmodulin-binding protein with the cytoskeleton resides on spectrin

Massive splenomegaly in acute erythroid leukaemia (FAB Class-M6): an unusual presentation.

Science.gov (United States)

Sherazi, Syed Furqan Haider; Butt, Zeeshan

2012-09-01

AML-M6 has a peak incidence in the seventh decade with slight male preponderance, and can also present at a younger age. The usual features are anaemia, thrombocytopenia, malaise, fatigue, easy bruising, epistaxis and petechiae. Splenomegaly may occur in 20-40 % of the cases but massive splenomegaly is rare presentation and have been only reported once in humans and once in animals. A 22 year Asian female, presented with fatigue, pallor, mild jaundice, exertional dyspnoea, epigastric pain, tender right hypochondrium and massive splenomegaly. Investigations revealed anaemia and thrombocytopenia, tear drop cells, basophilic stippling, piokilocytosis and anisochromia; increased uric acid and LDH. Abdominal ultrasound showed enlarged liver (22cm) and spleen (20cm). Bone marrow aspiration revealed 51% erythroid and 24% non-erythroid precursors, depressed leukopoeisis and megakarypoeisis. Erythroblasts were PAS and CD71 positive and also reacted to Antihaemoglobin-Antibody. This report highlights characteristic features and diagnostic criteria of erythroleukaemia, differential diagnosis of massive splenomegaly and their rare association.

Detection and characterization of partially unfolded oligomers of the SH3 domain of α-Spectrin

NARCIS (Netherlands)

Casares, S.; Sadqi, M.; López-Mayorga, O.; Conejero-Lara, F.; van Nuland, N.A.J.

2004-01-01

For the purpose of equilibrium and kinetic folding-unfolding studies, the SH3 domain of α-spectrin (spc-SH3) has long been considered a classic two-state folding protein. In this work we have indeed observed that the thermal unfolding curves of spc-SH3 measured at pH 3.0 by differential scanning

Protein 4.1 and its interaction with other cytoskeletal proteins in Xenopus laevis oogenesis.

Science.gov (United States)

Carotenuto, Rosa; Petrucci, Tamara C; Correas, Isabel; Vaccaro, Maria C; De Marco, Nadia; Dale, Brian; Wilding, Martin

2009-06-01

In human red blood cells, protein 4.1 (4.1R) is an 80-kDa polypeptide that stabilizes the spectrin-actin network and anchors it to the plasma membrane. In non-erythroid cells there is a great variety of 4.1R isoforms, mainly generated by alternative pre-mRNA splicing, which localize at various intracellular sites, including the nucleus. We studied protein 4.1R distribution in relation to beta-spectrin, actin and cytokeratin during Xenopus oogenesis. Immunoprecipitation experiments indicate that at least two isoforms of protein 4.1R are present in Xenopus laevis oocytes: a 56-kDa form in the cytoplasm and a 37-kDa form in the germinal vesicle (GV). Antibodies to beta-spectrin reveal two bands of 239 and 100 kDa in the cytoplasm. Coimmunoprecipitation experiments indicate that both the 37- and 56-kDa isoforms of protein 4.1R associate with the 100-kDa isoform of beta-spectrin. Moreover, the 56-kDa form coimmunoprecipitates with a cytokeratin of the same molecular weight. Confocal immunolocalization shows that protein 4.1R distribution is in the peripheral cytoplasm, in the mitochondrial cloud (MC) and in the GV of previtellogenic oocytes. In the cytoplasm of vitellogenic oocytes, a loose network of fibers stained by the anti-protein 4.1R antibody spreads across the cytoplasm. beta-Spectrin has a similar distribution. Protein 4.1R was found to colocalize with actin in the cortex of oocytes in the form of fluorescent dots. Double immunolocalization of protein 4.1R and cytokeratin depicts two separate networks that overlap throughout the whole cytoplasm. Protein 4.1R filaments partially colocalize with cytokeratin in both the animal and vegetal hemispheres. We hypothesize that protein 4.1R could function as a linker protein between cytokeratin and the actin-based cytoskeleton.

The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells.

Science.gov (United States)

Suriguga; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun

2013-12-15

Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. © 2013.

Enhancement of erythroid colony growth in culture by hemin

International Nuclear Information System (INIS)

Porter, P.N.; Meints, R.H.; Mesner, K.

1979-01-01

Hemin was found to enhance the growth of murine erythroid colonies in culture. In the presence of 100 mU/ml erythropoietin (EPO), the addition of hemin (0.05-0.2 mM) resulted in the growth of twice as many colonies as were obtained with EPO alone. Hemin also significantly increased erythroid colony formation in culture in the absence of added EPO. Hemoblobin synthesis as measured by the incorporation of 59 Fe into cyclohexanone extractable heme was augmented in culture by hemin. Neither Δ-aminolevulinic acid, a hemin precursor, nor FeCl 3 increased colony number. (author)

The apical scaffold big bang binds to spectrins and regulates the growth of Drosophila melanogaster wing discs.

Science.gov (United States)

Forest, Elodie; Logeay, Rémi; Géminard, Charles; Kantar, Diala; Frayssinoux, Florence; Heron-Milhavet, Lisa; Djiane, Alexandre

2018-03-05

During development, cell numbers are tightly regulated, ensuring that tissues and organs reach their correct size and shape. Recent evidence has highlighted the intricate connections between the cytoskeleton and the regulation of the key growth control Hippo pathway. Looking for apical scaffolds regulating tissue growth, we describe that Drosophila melanogaster big bang (Bbg), a poorly characterized multi-PDZ scaffold, controls epithelial tissue growth without affecting epithelial polarity and architecture. bbg -mutant tissues are smaller, with fewer cells that are less apically constricted than normal. We show that Bbg binds to and colocalizes tightly with the β-heavy-Spectrin/Kst subunit at the apical cortex and promotes Yki activity, F-actin enrichment, and the phosphorylation of the myosin II regulatory light chain Spaghetti squash. We propose a model in which the spectrin cytoskeleton recruits Bbg to the cortex, where Bbg promotes actomyosin contractility to regulate epithelial tissue growth. © 2018 Forest et al.

Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability.

Science.gov (United States)

Smith, Alyson S; Nowak, Roberta B; Zhou, Sitong; Giannetto, Michael; Gokhin, David S; Papoin, Julien; Ghiran, Ionita C; Blanc, Lionel; Wan, Jiandi; Fowler, Velia M

2018-05-08

The biconcave disk shape and deformability of mammalian RBCs rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. Nonmuscle myosin II (NMII) motors exert force on diverse F-actin networks to control cell shapes, but a function for NMII contractility in the 2D spectrin-F-actin network of RBCs has not been tested. Here, we show that RBCs contain membrane skeleton-associated NMIIA puncta, identified as bipolar filaments by superresolution fluorescence microscopy. MgATP disrupts NMIIA association with the membrane skeleton, consistent with NMIIA motor domains binding to membrane skeleton F-actin and contributing to membrane mechanical properties. In addition, the phosphorylation of the RBC NMIIA heavy and light chains in vivo indicates active regulation of NMIIA motor activity and filament assembly, while reduced heavy chain phosphorylation of membrane skeleton-associated NMIIA indicates assembly of stable filaments at the membrane. Treatment of RBCs with blebbistatin, an inhibitor of NMII motor activity, decreases the number of NMIIA filaments associated with the membrane and enhances local, nanoscale membrane oscillations, suggesting decreased membrane tension. Blebbistatin-treated RBCs also exhibit elongated shapes, loss of membrane curvature, and enhanced deformability, indicating a role for NMIIA contractility in promoting membrane stiffness and maintaining RBC biconcave disk cell shape. As structures similar to the RBC membrane skeleton exist in many metazoan cell types, these data demonstrate a general function for NMII in controlling specialized membrane morphology and mechanical properties through contractile interactions with short F-actin in spectrin-F-actin networks.

Erythroid differentiation of fetal, newborn and adult haemopoietic stem cells

International Nuclear Information System (INIS)

Rencricca, N.J.; Howard, D.; Kubanek, B.; Stohlman, F.; Department of Biological Sciences, University of Lowell, Lowell, Massachusetts, USA)

1976-01-01

Erythroid regeneration was studied in lethally irradiated mice given transplants containing equivalent numbers of haemopoietic stem cells (i.e. CFU) from fetal liver, neonatal marrow or adult marrow. Adult marrow was taken from normal control mice, whose CFU for the most part were not in active cell cycle, as well as from phenylhydrazine-treated groups whose CFU were in similar state of proliferation (i.e. approximately 40-50% in DNA synthesis) as those derived from fetal liver and neonatal marrow. Splenic and femoral radioiron ( 59 Fe) incorporation were measured at intervals after transplantation and were found to begin earliest in mice given fetal liver, then in animals given neonatal marrow and latest in recipients of adult marrow. Peripheral reticulocytes showed a similar pattern of recovery. The data reported herein suggest that the differences in erythroid regeneration evoked by transplants of fetal liver, neonatal marrow or adult marrow, are not solely attributed to the degree of proliferation in the pluripotential stem cell compartment. These data may, however, suggest a shorter doubling time for cells comprising the fetal and newborn committed erythroid compartments. (author)

Erythroid differentiation of fetal, newborn, and adult haemopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Rencricca, N J; Howard, D; Kubanek, B; Stohlman, F [Boston Univ., Mass. (USA). School of Medicine; Department of Biological Sciences, University of Lowell, Lowell, Massachusetts, USA)

1976-01-01

Erythroid regeneration was studied in lethally irradiated mice given transplants containing equivalent numbers of haemopoietic stem cells (i.e. CFU) from fetal liver, neonatal marrow or adult marrow. Adult marrow was taken from normal control mice, whose CFU for the most part were not in active cell cycle, as well as from phenylhydrazine-treated groups whose CFU were in similar state of proliferation (i.e. approximately 40-50% in DNA synthesis) as those derived from fetal liver and neonatal marrow. Splenic and femoral radioiron (/sup 59/Fe) incorporation were measured at intervals after transplantation and were found to begin earliest in mice given fetal liver, then in animals given neonatal marrow and latest in recipients of adult marrow. Peripheral reticulocytes showed a similar pattern of recovery. The data reported herein suggest that the differences in erythroid regeneration evoked by transplants of fetal liver, neonatal marrow or adult marrow, are not solely attributed to the degree of proliferation in the pluripotential stem cell compartment. These data may, however, suggest a shorter doubling time for cells comprising the fetal and newborn committed erythroid compartments.

Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis

KAUST Repository

Barbarani, Gloria; Ronchi, Antonella; Ruoppolo, Margherita; Santorelli, Lucia; Steinfelder, Robert; Elangovan, Sudharshan; Fugazza, Cristina; Caterino, Marianna

2017-01-01

are accompanied with a reduced survival of Sox6-/- red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark

Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis

KAUST Repository

Barbarani, Gloria

2017-10-20

The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6-/- red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation. To obtain an overview on processes downstream to Sox6 expression, we performed a differential proteomic analysis on human erythroid K562 cells overexpressing Sox6. Sox6-overexpression induces dysregulation of 64 proteins, involved in cytoskeleton remodeling and in protein synthesis, folding and trafficking, key processes for erythroid maturation. Moreover, 43 out of 64 genes encoding for differentially expressed proteins contain within their proximal regulatory regions sites that are bound by SOX6 according to ENCODE ChIP-seq datasets and are possible direct SOX6 targets. SAR1B, one of the most induced proteins upon Sox6 overexpression, shares a conserved regulatory module, composed by a double SOX6 binding site and a GATA1 consensus, with the adjacent SEC24 A gene. Since both genes encode for COPII components, this element could concur to the coordinated expression of these proteins during erythropoiesis.

Bmi-1 Regulates Extensive Erythroid Self-Renewal

Directory of Open Access Journals (Sweden)

Ah Ram Kim

2015-06-01

Full Text Available Red blood cells (RBCs, responsible for oxygen delivery and carbon dioxide exchange, are essential for our well-being. Alternative RBC sources are needed to meet the increased demand for RBC transfusions projected to occur as our population ages. We previously have discovered that erythroblasts derived from the early mouse embryo can self-renew extensively ex vivo for many months. To better understand the mechanisms regulating extensive erythroid self-renewal, global gene expression data sets from self-renewing and differentiating erythroblasts were analyzed and revealed the differential expression of Bmi-1. Bmi-1 overexpression conferred extensive self-renewal capacity upon adult bone-marrow-derived self-renewing erythroblasts, which normally have limited proliferative potential. Importantly, Bmi-1 transduction did not interfere with the ability of extensively self-renewing erythroblasts (ESREs to terminally mature either in vitro or in vivo. Bmi-1-induced ESREs can serve to generate in vitro models of erythroid-intrinsic disorders and ultimately may serve as a source of cultured RBCs for transfusion therapy.

Dimethyl sulfoxide-inducible cytoplasmic factor involved in erythroid differentiation in mouse erythroleukemia (Friend) cells

International Nuclear Information System (INIS)

Watanabe, T.; Oishi, M.

1987-01-01

A previous report described an intracellular factor (differentiation-inducing factor I, or DIF-I) that seem to play a role in erythroid differentiation in mouse erythroleukemia (MEL) cells. The authors have detected another erythroid-inducing factor in cell-free extracts from dimethyl sulfoxide- or hexamethylenebis(acetamide)-treated MEL cells, which acts synergistically with DIF-I. The partially purified factor (termed DIF-II) triggered erythroid differentiation when introduced into undifferentiated MEL cells that had been potentiated by the induction of DIF-I. The activity in the extracts appeared in an inducible manner after addition of dimethyl sulfoxide or hexamethylenebis(acetamide), reached a maximum at 6 hr, and then rapidly decreased. The induction was inhibited by phorbol 12-myristate 13-acetate and also by cycloheximide. No induction was observed in a mutant MEL cell line defective in erythroid differentiation. These characteristics are consistent with the supposition that DIF-II is one of the putative dimethyl sulfoxide-inducible factors detected in previously reported cell-fusion and cytoplast-fusion experiments. The role of DIF-II in MEL-cell differentiation and in vitro differentiation in general is discussed

PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis.

Science.gov (United States)

Ryu, Moon-Suhn; Zhang, Deliang; Protchenko, Olga; Shakoury-Elizeh, Minoo; Philpott, Caroline C

2017-05-01

Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC-binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin.

Recombinant human parvovirus B19 vectors: erythroid cell-specific delivery and expression of transduced genes.

Science.gov (United States)

Ponnazhagan, S; Weigel, K A; Raikwar, S P; Mukherjee, P; Yoder, M C; Srivastava, A

1998-06-01

A novel packaging strategy combining the salient features of two human parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno-associated virus type 2 (AAV), was developed to achieve erythroid cell-specific delivery as well as expression of the transduced gene. The development of such a chimeric vector system was accomplished by packaging heterologous DNA sequences cloned within the inverted terminal repeats of AAV and subsequently packaging the DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles were assembled, as evidenced by electron microscopy as well as DNA slot blot analyses. The hybrid vector failed to transduce nonerythroid human cells, such as 293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia cell line which can be infected by B19 virus following erythroid differentiation with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A. Srivastava, J. Virol. 67:562-566, 1993) but lacks the putative receptor for AAV (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N. C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111-1122, 1996), were readily transduced by this vector. The hybrid vector was also found to specifically target the erythroid population in primary human bone marrow cells as well as more immature hematopoietic progenitor cells following erythroid differentiation, as evidenced by selective expression of the transduced gene in these target cells. Preincubation with anticapsid antibodies against B19 virus, but not anticapsid antibodies against AAV, inhibited transduction of primary human erythroid cells. The efficiency of transduction of primary human erythroid cells by the recombinant B19 virus vector was significantly higher than that by the recombinant AAV vector. Further development of the AAV-B19 virus hybrid vector system should prove beneficial in gene therapy protocols aimed at the correction of inherited and

Recombinant Human Parvovirus B19 Vectors: Erythroid Cell-Specific Delivery and Expression of Transduced Genes

Science.gov (United States)

Ponnazhagan, Selvarangan; Weigel, Kirsten A.; Raikwar, Sudhanshu P.; Mukherjee, Pinku; Yoder, Mervin C.; Srivastava, Arun

1998-01-01

A novel packaging strategy combining the salient features of two human parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno-associated virus type 2 (AAV), was developed to achieve erythroid cell-specific delivery as well as expression of the transduced gene. The development of such a chimeric vector system was accomplished by packaging heterologous DNA sequences cloned within the inverted terminal repeats of AAV and subsequently packaging the DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles were assembled, as evidenced by electron microscopy as well as DNA slot blot analyses. The hybrid vector failed to transduce nonerythroid human cells, such as 293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia cell line which can be infected by B19 virus following erythroid differentiation with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A. Srivastava, J. Virol. 67:562–566, 1993) but lacks the putative receptor for AAV (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N. C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111–1122, 1996), were readily transduced by this vector. The hybrid vector was also found to specifically target the erythroid population in primary human bone marrow cells as well as more immature hematopoietic progenitor cells following erythroid differentiation, as evidenced by selective expression of the transduced gene in these target cells. Preincubation with anticapsid antibodies against B19 virus, but not anticapsid antibodies against AAV, inhibited transduction of primary human erythroid cells. The efficiency of transduction of primary human erythroid cells by the recombinant B19 virus vector was significantly higher than that by the recombinant AAV vector. Further development of the AAV-B19 virus hybrid vector system should prove beneficial in gene therapy protocols aimed at the correction of inherited

Human Cord Blood and Bone Marrow CD34+ Cells Generate Macrophages That Support Erythroid Islands.

Directory of Open Access Journals (Sweden)

Eyayu Belay

Full Text Available Recently, we developed a small molecule responsive hyperactive Mpl-based Cell Growth Switch (CGS that drives erythropoiesis associated with macrophages in the absence of exogenous cytokines. Here, we compare the physical, cellular and molecular interaction between the macrophages and erythroid cells in CGS expanded CD34+ cells harvested from cord blood, marrow or G-CSF-mobilized peripheral blood. Results indicated that macrophage based erythroid islands could be generated from cord blood and marrow CD34+ cells but not from G-CSF-mobilized CD34+ cells. Additional studies suggest that the deficiency resides with the G-CSF-mobilized CD34+ derived monocytes. Gene expression and proteomics studies of the in vitro generated erythroid islands detected the expression of erythroblast macrophage protein (EMP, intercellular adhesion molecule 4 (ICAM-4, CD163 and DNASE2. 78% of the erythroblasts in contact with macrophages reached the pre reticulocyte orthochromatic stage of differentiation within 14 days of culture. The addition of conditioned medium from cultures of CD146+ marrow fibroblasts resulted in a 700-fold increase in total cell number and a 90-fold increase in erythroid cell number. This novel CD34+ cell derived erythroid island may serve as a platform to explore the molecular basis of red cell maturation and production under normal, stress and pathological conditions.

Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density

DEFF Research Database (Denmark)

Barres, Romain; Osler, Megan E; Yan, Jie

2009-01-01

-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-alpha (TNF-alpha) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non......-CpG methylation of PGC-1alpha and decreased mtDNA and PGC-1alpha mRNA. We provide evidence for PGC-1alpha hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1alpha promoter....

Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST.

Science.gov (United States)

Perkins, Emma M; Suminaite, Daumante; Clarkson, Yvonne L; Lee, Sin Kwan; Lyndon, Alastair R; Rothstein, Jeffrey D; Wyllie, David J A; Tanaka, Kohichi; Jackson, Mandy

2016-10-15

Clinical phenotypes of spinocerebellar ataxia type-5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxia type-1 (SPARCA1) are mirrored in mice lacking β-III spectrin (β-III-/-). One function of β-III spectrin is the stabilization of the Purkinje cell-specific glutamate transporter EAAT4 at the plasma membrane. In β-III-/- mice EAAT4 levels are reduced from an early age. In contrast levels of the predominant cerebellar glutamate transporter GLAST, expressed in Bergmann glia, only fall progressively from 3 months onwards. Here we elucidated the roles of these two glutamate transporters in cerebellar pathogenesis mediated through loss of β-III spectrin function by studying EAAT4 and GLAST knockout mice as well as crosses of both with β-III-/- mice. Our data demonstrate that EAAT4 loss, but not abnormal AMPA receptor composition, in young β-III-/- mice underlies early Purkinje cell hyper-excitability and that subsequent loss of GLAST, superimposed on the earlier deficiency of EAAT4, is responsible for Purkinje cell loss and progression of motor deficits. Yet the loss of GLAST appears to be independent of EAAT4 loss, highlighting that other aspects of Purkinje cell dysfunction underpin the pathogenic loss of GLAST. Finally, our results demonstrate that Purkinje cells in the posterior cerebellum of β-III-/- mice are most susceptible to the combined loss of EAAT4 and GLAST, with degeneration of proximal dendrites, the site of climbing fibre innervation, most pronounced. This highlights the necessity for efficient glutamate clearance from these regions and identifies dysregulation of glutamatergic neurotransmission particularly within the posterior cerebellum as a key mechanism in SCA5 and SPARCA1 pathogenesis.

Drosophila sosie functions with βH-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability

Science.gov (United States)

Urwyler, Olivier; Cortinas-Elizondo, Fabiola; Suter, Beat

2012-01-01

Summary Morphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of βH-Spectrin, it appears that cortical βH-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse. PMID:23213377

Drosophila sosie functions with β(H)-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability.

Science.gov (United States)

Urwyler, Olivier; Cortinas-Elizondo, Fabiola; Suter, Beat

2012-10-15

Morphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of β(H)-Spectrin, it appears that cortical β(H)-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse.

Effect of radiographic contrast media on the spectrin/band3-network of the membrane skeleton of erythrocytes.

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Ralf-Peter Franke

Full Text Available The membrane of red blood cells consists of a phospholipid bilayer with embedded membrane proteins and is associated on the cytoplasmatic side with a network of proteins, the membrane skeleton. Band3 has an important role as centre of the functional complexes e.g. gas exchange complex and as element of attachment for the membrane skeleton maintaining membrane stability and flexibility. Up to now it is unclear if band3 is involved in the morphology change of red blood cells after contact with radiographic contrast media. The study revealed for the first time that Iopromide induced markedly more severe alterations of the membrane skeleton compared to Iodixanol whose effects were similar to erythrocytes suspended in autologous plasma. A remarkable clustering of band3 was found associated with an accumulation of band3 in spicules and also a sequestration of band3 to the extracellular space. This was evidently accompanied by a gross reduction of functional band3 complexes combined with a dissociation of spectrin from band3 leading to a loss of homogeneity of the spectrin network. It could be demonstrated for the first time that RCM not only induced echinocyte formation but also exocytosis of particles at least coated with band3.

Effect of Radiographic Contrast Media on the Spectrin/Band3-Network of the Membrane Skeleton of Erythrocytes

Science.gov (United States)

Franke, Ralf-Peter; Scharnweber, Tim; Fuhrmann, Rosemarie; Wenzel, Folker; Krüger, Anne; Mrowietz, Christof; Jung, Friedrich

2014-01-01

The membrane of red blood cells consists of a phospholipid bilayer with embedded membrane proteins and is associated on the cytoplasmatic side with a network of proteins, the membrane skeleton. Band3 has an important role as centre of the functional complexes e.g. gas exchange complex and as element of attachment for the membrane skeleton maintaining membrane stability and flexibility. Up to now it is unclear if band3 is involved in the morphology change of red blood cells after contact with radiographic contrast media. The study revealed for the first time that Iopromide induced markedly more severe alterations of the membrane skeleton compared to Iodixanol whose effects were similar to erythrocytes suspended in autologous plasma. A remarkable clustering of band3 was found associated with an accumulation of band3 in spicules and also a sequestration of band3 to the extracellular space. This was evidently accompanied by a gross reduction of functional band3 complexes combined with a dissociation of spectrin from band3 leading to a loss of homogeneity of the spectrin network. It could be demonstrated for the first time that RCM not only induced echinocyte formation but also exocytosis of particles at least coated with band3. PMID:24586837

Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.

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Ryo Kurita

Full Text Available Transfusion of red blood cells (RBCs is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.

THE EFFECTS OF IL-1 AND IL-4 ON THE EPO-INDEPENDENT ERYTHROID PROGENITOR IN POLYCYTHEMIA-VERA

NARCIS (Netherlands)

DEWOLF, JTM; HENDRIKS, DW; ESSELINK, MT; HALIE, MR; VELLENGA, E

1994-01-01

Human recombinant interleukin-1 (IL-1) was studied for its effects on the erythroid progenitors from normal subjects and from patients with polycythaemia vera (PV). No supportive effect of IL-1 was noticed on the normal, erythropoietin (Epo) dependent, erythroid burst-forming unit (BFU-E) using

Measurement of $\\alpha_{s}$ and the non-strange spectral functions in hadronic $\\tau$ decays with OPAL

CERN Document Server

Menke, S

1999-01-01

The spectral functions of the vector current and the axial-vector current have been measured in hadronic tau decays using the OPAL detector at LEP. Within the framework of the Operator Product Expansion a simultaneous determination of the strong coupling constant alpha /sub s/, the non-perturbative operators of dimension 6 and 8 and of the gluon condensate has been performed. Different perturbative descriptions have been compared to the data. The Contour Improved Fixed Order Perturbation Theory gives alpha /sub s/(m/sub tau //sup 2/)=0.348+or-0.009/sub exp/+or-0.019/sub theo/ at the tau - mass scale and alpha /sub s/(m/sub Z//sup 2/)=0.1219+or-0.0010/sub exp/+or-0.0017/sub theo/ at the Z/sup 0/-mass scale. The values obtained for alpha /sub s/(m/sub Z//sup 2/) using Fixed Order Perturbation Theory or Renormalon Chain Resummation are 2.3and 4.1 smaller, respectively. The `running' of the strong coupling between s /sub 0/ approximately=1.3 GeV/sup 2/ and s/sub 0/=m/sub tau //sup 2/ has been tested from direct f...

Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions.

Science.gov (United States)

Zhang, Feng-Lin; Shen, Guo-Min; Liu, Xiao-Ling; Wang, Fang; Zhao, Ying-Ze; Zhang, Jun-Wu

2012-08-01

Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type-specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia-induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34(+) haematopoietic stem/progenitor cells. Enforced HIF1α expression increased GATA1 expression, while HIF1α knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)-PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up-regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1α or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl(2) induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1α or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1-mediated GATA1 up-regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

Science.gov (United States)

Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

2017-07-01

Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyherbal EMSA ERITIN Promotes Erythroid Lineages and Lymphocyte Migration in Irradiated Mice

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Ibrahim Mansur

2016-01-01

Full Text Available Radiotherapy is commonly used to kill malignant cells, but it can significantly deplete hematopoietic and splenic erythroblasts. Radioprotective agents are therefore very important in clinical radiotherapy. We examined the effect of poly-herbal EMSA ERITIN on immunological responses when administered to sublethally irradiated mice with the aim of highlighting promotes erythroid lineages and lymphocytes migration in irradiated mice with the parameter are TER119+CD123+in bone marrow and SDF-1 in bone marrow and spleen organ. Normal BALB/c mice were sublethally irradiated with 600 rad. EMSA ERITIN was administered orally at different doses:(1.04, 3.125 and 9.375 mg/g body weight for 15 days. On day 16 erythroid lineages (TER-119+CD123+ were observed in bone marrow and lymphocytes migration by the production of SDF-1 in spleen and bone marrow. Lymphocytes migration was indicated by the production of SDF-1 in spleen and bone marrow using flow cytometry analysis. EMSA ERITIN increased the generation of erythroid lineage cells marked by TER119+CD123+ and promoted lymphocyte migration by increasing SDF-1 production in bone marrow and spleen. EMSA ERITIN appears to be a powerful medicinal herb with potential as a food supplement to normalize homeostasis and erythropoiesis after radiation.

Choosing an alpha radiation weighting factor for doses to non-human biota

International Nuclear Information System (INIS)

Chambers, Douglas B.; Osborne, Richard V.; Garva, Amy L.

2006-01-01

The risk to non-human biota from exposure to ionizing radiation is of current international interest. In calculating radiation doses to humans, it is common to multiply the absorbed dose by a factor to account for the relative biological effectiveness (RBE) of the radiation type. However, there is no international consensus on the appropriate value of such a factor for weighting doses to non-human biota. This paper summarizes our review of the literature on experimentally determined RBEs for internally deposited alpha-emitting radionuclides. The relevancy of each experimental result in selecting a radiation weighting factor for doses from alpha particles in biota was judged on the basis of criteria established a priori. We recommend a nominal alpha radiation weighting factor of 5 for population-relevant deterministic and stochastic endpoints, but to reflect the limitations in the experimental data, uncertainty ranges of 1-10 and 1-20 were selected for population-relevant deterministic and stochastic endpoints, respectively

Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion

DEFF Research Database (Denmark)

Falchi, Mario; Varricchio, Lilian; Martelli, Fabrizio

2015-01-01

Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages...... in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions...... with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the...

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

Science.gov (United States)

Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

2015-01-01

Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

Human primary erythroid cells as a more sensitive alternative in vitro hematological model for nanotoxicity studies: Toxicological effects of silver nanoparticles.

Science.gov (United States)

Rujanapun, Narawadee; Aueviriyavit, Sasitorn; Boonrungsiman, Suwimon; Rosena, Apiwan; Phummiratch, Duangkamol; Riolueang, Suchada; Chalaow, Nipon; Viprakasit, Vip; Maniratanachote, Rawiwan

2015-12-01

Although immortalized cells established from cancerous cells have been widely used for studies in nanotoxicology studies, the reliability of the results derived from immortalized cells has been questioned because of their different characteristics from normal cells. In the present study, human primary erythroid cells in liquid culture were used as an in vitro hematological cell model for investigation of the nanotoxicity of silver nanoparticles (AgNPs) and comparing the results to the immortalized hematological cell lines HL60 and K562. The AgNPs caused significant cytotoxic effects in the primary erythroid cells, as shown by the decreased cell viability and induction of intracellular ROS generation and apoptosis, whereas they showed much lower cytotoxic and apoptotic effects in HL60 and K562 cells and did not induced ROS generation in these cell lines. Scanning electron microcopy revealed an interaction of AgNPs to the cell membrane in both primary erythroid and immortalized cells. In addition, AgNPs induced hemolysis in the primary erythroid cells in a dose-dependent manner, and transmission electron microcopy analysis revealed that AgNPs damaged the erythroid cell membrane. Taken together, these results suggest that human primary erythroid cells in liquid culture are a more sensitive alternative in vitro hematological model for nanotoxicology studies. Copyright © 2015 Elsevier B.V. All rights reserved.

The continuous UV flux of Alpha Lyrae - Non-LTE results

Science.gov (United States)

Snijders, M. A. J.

1977-01-01

Non-LTE calculations for the ultraviolet C I and Si I continuous opacity show that LTE results overestimate the importance of these sources of opacity and underestimate the emergent flux in Alpha Lyr. The largest errors occur between 1100 and 1160 A, where the predicted flux in non-LTE is as much as 50 times larger than in LTE, in reasonable accord with Copernicus observations. The discrepancy between LTE models and observations has been interpreted to result from the existence of a chromosphere. Until a self-consistent non-LTE model atmosphere becomes available, such an interpretation is premature.

Dynamics of GATA1 binding and expression response in a GATA1-induced erythroid differentiation system

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Deepti Jain

2015-06-01

Full Text Available During the maturation phase of mammalian erythroid differentiation, highly proliferative cells committed to the erythroid lineage undergo dramatic changes in morphology and function to produce circulating, enucleated erythrocytes. These changes are caused by equally dramatic alterations in gene expression, which in turn are driven by changes in the abundance and binding patterns of transcription factors such as GATA1. We have studied the dynamics of GATA1 binding by ChIP-seq and the global expression responses by RNA-seq in a GATA1-dependent mouse cell line model for erythroid maturation, in both cases examining seven progressive stages during differentiation. Analyses of these data should provide insights both into mechanisms of regulation (early versus late targets and the consequences in cell physiology (e.g., distinctive categories of genes regulated at progressive stages of differentiation. The data are deposited in the Gene Expression Omnibus, series GSE36029, GSE40522, GSE49847, and GSE51338.

A Rare Case of Pure Erythroid Sarcoma in a Pediatric Patient: Case Report and Literature Review

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Pablo Manresa

2017-12-01

Full Text Available We describe an exceptional case of erythroid sarcoma in a pediatric patient as a growing orbital mass with no evidence of morphologic bone marrow involvement, who was finally diagnosed of pure erythroid sarcoma based on histopathology and flow cytometry criteria. We discuss the contribution of standardized eight-color flow cytometry as a rapid and reliable diagnostic method. The use of normal bone marrow databases allowed us to identify small aberrant populations in bone marrow and later confirm the diagnosis in the neoplastic tissue.

MiR-27a Promotes Hemin-Induced Erythroid Differentiation of K562 Cells by Targeting CDC25B

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Dongsheng Wang

2018-03-01

Full Text Available Background/Aims: MicroRNAs (miRNAs play a crucial role in erythropoiesis. MiR-23a∼27a∼24-2 clusters have been proven to take part in erythropoiesis via some proteins. CDC25B (cell division control Cdc2 phosphostase B is also the target of mir-27a; whether it regulates erythropoiesis and its mechanism are unknown. Methods: To evaluate the potential role of miR-27a during erythroid differentiation, we performed miR-27a gain- and loss-of-function experiments on hemin-induced K562 cells. We detected miR-27a expression after hemin stimulation at different time points. At the same time, the γ-globin gene also was measured via real-time PCR. According to the results of the chips, we screened the target protein of miR-27a through a dual-luciferase reporter assay and identified it via Western blot analyses. To evaluate the function of CDC25B, benzidine staining and flow cytometry were employed to detect the cell differentiation and cell cycle. Results: We found that miR-27a promotes hemin-induced erythroid differentiation of human K562 cells by targeting cell division cycle 25 B (CDC25B. Overexpression of miR-27a promotes the differentiation of hemin-induced K562 cells, as demonstrated by γ-globin overexpression. The inhibition of miR-27a expression suppresses erythroid differentiation, thus leading to a reduction in the γ-globin gene. CDC25B was identified as a new target of miR-27a during erythroid differentiation. Overexpression of miR-27a led to decreased CDC25B expression after hemin treatment, and CDC25B was up-regulated when miR-27a expression was inhibited. Moreover, the inhibition of CDC25B affected erythroid differentiation, as assessed by γ-globin expression. Conclusion: This study is the first report of the interaction between miR-27a and CDC25B, and it improves the understanding of miRNA functions during erythroid differentiation.

Nuclear RNA sequencing of the mouse erythroid cell transcriptome.

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Jennifer A Mitchell

Full Text Available In addition to protein coding genes a substantial proportion of mammalian genomes are transcribed. However, most transcriptome studies investigate steady-state mRNA levels, ignoring a considerable fraction of the transcribed genome. In addition, steady-state mRNA levels are influenced by both transcriptional and posttranscriptional mechanisms, and thus do not provide a clear picture of transcriptional output. Here, using deep sequencing of nuclear RNAs (nucRNA-Seq in parallel with chromatin immunoprecipitation sequencing (ChIP-Seq of active RNA polymerase II, we compared the nuclear transcriptome of mouse anemic spleen erythroid cells with polymerase occupancy on a genome-wide scale. We demonstrate that unspliced transcripts quantified by nucRNA-seq correlate with primary transcript frequencies measured by RNA FISH, but differ from steady-state mRNA levels measured by poly(A-enriched RNA-seq. Highly expressed protein coding genes showed good correlation between RNAPII occupancy and transcriptional output; however, genome-wide we observed a poor correlation between transcriptional output and RNAPII association. This poor correlation is due to intergenic regions associated with RNAPII which correspond with transcription factor bound regulatory regions and a group of stable, nuclear-retained long non-coding transcripts. In conclusion, sequencing the nuclear transcriptome provides an opportunity to investigate the transcriptional landscape in a given cell type through quantification of unspliced primary transcripts and the identification of nuclear-retained long non-coding RNAs.

The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

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Lo, Raymond; Matthews, Jason, E-mail: jason.matthews@utoronto.ca

2013-07-15

Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

International Nuclear Information System (INIS)

Lo, Raymond; Matthews, Jason

2013-01-01

Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

A common signaling pathway is activated in erythroid cells expressing high levels of fetal hemoglobin: a potential role for cAMP-elevating agents in β-globin disorders

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Ikuta T

2013-12-01

Full Text Available Tohru Ikuta,1 Yuichi Kuroyanagi,1 Nadine Odo,1 Siyang Liu21Department of Anesthesiology and Perioperative Medicine, 2Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA, USABackground: Although erythroid cells prepared from fetal liver, cord blood, or blood from β-thalassemia patients are known to express fetal hemoglobin at high levels, the underlying mechanisms remain elusive. We previously showed that cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in primary erythroid cells. Here we report that cAMP signaling contributes to high-level fetal hemoglobin expression in erythroid cells prepared from cord blood and β-thalassemia.Methods: The status of the cAMP signaling pathway was investigated using primary erythroid cells prepared from cord blood and the mononuclear cells of patients with β-thalassemia; erythroid cells from adult bone marrow mononuclear cells served as the control.Results: We found that intracellular cAMP levels were higher in erythroid cells from cord blood and β-thalassemia than from adult bone marrow. Protein kinase A activity levels and cAMP-response element binding protein phosphorylation were higher in erythroid cells from cord blood or β-thalassemia than in adult bone marrow progenitors. Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin expression, were not consistently activated in cord blood or β-thalassemia erythroid cells. When cAMP signaling was activated in adult erythroid cells, fetal hemoglobin was induced at high levels and associated with reduced expression of BCL11A, a silencer of the β-globin gene.Conclusion: These results suggest that activated cAMP signaling may be a common mechanism among erythroid cells with high fetal hemoglobin levels, in part because of downregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP-elevating agents may prove to be an important signaling mechanism to

Carbon monoxide induced erythroid differentiation of K562 cells mimics the central macrophage milieu in erythroblastic islands.

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Shlomi Toobiak

Full Text Available Growing evidence supports the role of erythroblastic islands (EI as microenvironmental niches within bone marrow (BM, where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule--CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage.Based on the above, the study hypothesized CO to have a role in erythroid maturation. Thus, the effect of CO gas as a potential erythroid differentiation inducer on the common model for erythroid progenitors, K562 cells, was explored. Cells were kept under oxygen lacking environment to mimic BM conditions. Nitrogen anaerobic atmosphere (N₂A served as control for CO atmosphere (COA. Under both atmospheres cells proliferation ceased: in N₂A due to cell death, while in COA as a result of erythroid differentiation. Maturation was evaluated by increased glycophorin A expression and Hb concentration. Addition of 1%CO only to N₂A, was adequate for maintaining cell viability. Yet, the average Hb concentration was low as compared to COA. This was validated to be the outcome of diversified maturation stages of the progenitor's population.In fact, the above scenario mimics the in vivo EI conditions, where at any given moment only a minute portion of the progenitors proceeds into terminal differentiation. Hence, this model might provide a basis for further molecular investigations of the EI structure/function relationship.

Selective association of a fragment of the knob protein with spectrin, actin and the red cell membrane.

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Kilejian, A; Rashid, M A; Aikawa, M; Aji, T; Yang, Y F

1991-02-01

The knob protein of Plasmodium falciparum is essential for the formation of knob-like protrusions on the host erythrocyte membrane. A functional domain of the knob protein was identified. This peptide formed stable complexes with the two major red cell skeletal proteins, spectrin and actin. When introduced into resealed normal erythrocytes, the peptide associated selectively with the cytoplasmic surface of the membrane and formed knob-like electron dense deposits. Knobs are thought to play an important role in the immunopathology of P. falciparum infections. Our findings provide a first step towards understanding the molecular basis for selective membrane changes at knobs.

Myelo-erythroid commitment after burn injury is under β-adrenergic control via MafB regulation.

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Hasan, Shirin; Johnson, Nicholas B; Mosier, Michael J; Shankar, Ravi; Conrad, Peggie; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

2017-03-01

Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by β-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (lin neg Sca1 + cKit + ), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). β-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB + cells in multipotent progenitors, but also influenced myelo-erythroid bifurcation by increasing the MEPs and reducing the granulocyte monocyte progenitors in the bone marrow of burn mice. Furthermore, similar results were observed in burn patients' peripheral blood mononuclear cell-derived ex vivo culture system, demonstrating that commitment stage of erythropoiesis is impaired in burn patients and intervention with propranolol (nonselective β1,2-adrenergic blocker) increases MEPs. Also, MafB + cells that were significantly increased following standard burn care could be mitigated when propranolol was administered to burn patients, establishing the mechanistic regulation of erythroid commitment by myeloid regulatory transcription factor MafB. Overall, results demonstrate that β-adrenergic blockers following burn injury can redirect the hematopoietic commitment toward erythroid lineage by lowering MafB expression in multipotent progenitors and be of potential therapeutic value to increase erythropoietin responsiveness in burn patients. Copyright © 2017 the American Physiological Society.

RECOMBINANT HUMAN MAST-CELL GROWTH-FACTOR SUPPORTS ERYTHROID COLONY FORMATION IN POLYCYTHEMIA-VERA IN THE PRESENCE AND ABSENCE OF ERYTHROPOIETIN AND SERUM

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MULLER, EW; DEWOLF, JTM; HENDRIKS, DW; ESSELINK, MT; HALIE, MR; VELLENGA, E

The effect of mast cell growth factor (MGF) was studied on erythropoietin (Epo)-dependent and Epo-independent (''spontaneous'') erythroid colony formation in patients with polycythemia vera (PV). MGF stimulated both Epo-dependent and Epo-independent erythroid colony formation from PV peripheral

Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

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Gemma Aragonès

Full Text Available Non-alcoholic fatty liver disease (NAFLD causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS and steatohepatitis (NASH cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients.We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30 and morbidly obese women (n = 97 with or without NAFLD.We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate had the highest accuracy in diagnosing liver steatosis.These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH.

CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells.

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Laurie A Steiner

Full Text Available CTCF and cohesinSA-1 are regulatory proteins involved in a number of critical cellular processes including transcription, maintenance of chromatin domain architecture, and insulator function. To assess changes in the CTCF and cohesinSA-1 interactomes during erythropoiesis, chromatin immunoprecipitation coupled with high throughput sequencing and mRNA transcriptome analyses via RNA-seq were performed in primary human hematopoietic stem and progenitor cells (HSPC and primary human erythroid cells from single donors.Sites of CTCF and cohesinSA-1 co-occupancy were enriched in gene promoters in HSPC and erythroid cells compared to single CTCF or cohesin sites. Cell type-specific CTCF sites in erythroid cells were linked to highly expressed genes, with the opposite pattern observed in HSPCs. Chromatin domains were identified by ChIP-seq with antibodies against trimethylated lysine 27 histone H3, a modification associated with repressive chromatin. Repressive chromatin domains increased in both number and size during hematopoiesis, with many more repressive domains in erythroid cells than HSPCs. CTCF and cohesinSA-1 marked the boundaries of these repressive chromatin domains in a cell-type specific manner.These genome wide data, changes in sites of protein occupancy, chromatin architecture, and related gene expression, support the hypothesis that CTCF and cohesinSA-1 have multiple roles in the regulation of gene expression during erythropoiesis including transcriptional regulation at gene promoters and maintenance of chromatin architecture. These data from primary human erythroid cells provide a resource for studies of normal and perturbed erythropoiesis.

Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

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Reed Christopher

2009-11-01

Full Text Available Abstract Background MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1. Total RNA from Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA. Profiling studies of messenger RNA (mRNA in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

Fusion of ZMYND8 and RELA genes in acute erythroid leukemia

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Panagopoulos, Ioannis; Micci, Francesca; Thorsen, Jim

2013-01-01

Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap. A ZMYND8-RELA fusion was ranked first. RT...

Parvovirus B19 integration into human CD36+ erythroid progenitor cells.

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Janovitz, Tyler; Wong, Susan; Young, Neal S; Oliveira, Thiago; Falck-Pedersen, Erik

2017-11-01

The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular pathways of early CD105-positive erythroid cells as compared with CD34-positive common precursor cells by flow cytometric cell-sorting and gene expression profiling

International Nuclear Information System (INIS)

Machherndl-Spandl, S; Suessner, S; Danzer, M; Proell, J; Gabriel, C; Lauf, J; Sylie, R; Klein, H-U; Béné, M C; Weltermann, A; Bettelheim, P

2013-01-01

Special attention has recently been drawn to the molecular network of different genes that are responsible for the development of erythroid cells. The aim of the present study was to establish in detail the immunophenotype of early erythroid cells and to compare the gene expression profile of freshly isolated early erythroid precursors with that of the CD34-positive (CD34 + ) compartment. Multiparameter flow cytometric analyses of human bone marrow mononuclear cell fractions (n=20) defined three distinct early erythroid stages. The gene expression profile of sorted early erythroid cells was analyzed by Affymetrix array technology. For 4524 genes, a differential regulation was found in CD105-positive erythroid cells as compared with the CD34 + progenitor compartment (2362 upregulated genes). A highly significant difference was observed in the expression level of genes involved in transcription, heme synthesis, iron and mitochondrial metabolism and transforming growth factor-β signaling. A comparison with recently published data showed over 1000 genes that as yet have not been reported to be upregulated in the early erythroid lineage. The gene expression level within distinct pathways could be illustrated directly by applying the Ingenuity software program. The results of gene expression analyses can be seen at the Gene Expression Omnibus repository

Identification of Cell Type-Specific Differences in Erythropoietin Receptor Signaling in Primary Erythroid and Lung Cancer Cells.

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Ruth Merkle

2016-08-01

Full Text Available Lung cancer, with its most prevalent form non-small-cell lung carcinoma (NSCLC, is one of the leading causes of cancer-related deaths worldwide, and is commonly treated with chemotherapeutic drugs such as cisplatin. Lung cancer patients frequently suffer from chemotherapy-induced anemia, which can be treated with erythropoietin (EPO. However, studies have indicated that EPO not only promotes erythropoiesis in hematopoietic cells, but may also enhance survival of NSCLC cells. Here, we verified that the NSCLC cell line H838 expresses functional erythropoietin receptors (EPOR and that treatment with EPO reduces cisplatin-induced apoptosis. To pinpoint differences in EPO-induced survival signaling in erythroid progenitor cells (CFU-E, colony forming unit-erythroid and H838 cells, we combined mathematical modeling with a method for feature selection, the L1 regularization. Utilizing an example model and simulated data, we demonstrated that this approach enables the accurate identification and quantification of cell type-specific parameters. We applied our strategy to quantitative time-resolved data of EPO-induced JAK/STAT signaling generated by quantitative immunoblotting, mass spectrometry and quantitative real-time PCR (qRT-PCR in CFU-E and H838 cells as well as H838 cells overexpressing human EPOR (H838-HA-hEPOR. The established parsimonious mathematical model was able to simultaneously describe the data sets of CFU-E, H838 and H838-HA-hEPOR cells. Seven cell type-specific parameters were identified that included for example parameters for nuclear translocation of STAT5 and target gene induction. Cell type-specific differences in target gene induction were experimentally validated by qRT-PCR experiments. The systematic identification of pathway differences and sensitivities of EPOR signaling in CFU-E and H838 cells revealed potential targets for intervention to selectively inhibit EPO-induced signaling in the tumor cells but leave the responses in

EzrA: a spectrin-like scaffold in the bacterial cell division machinery

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Robert M Cleverley

2015-01-01

Full Text Available Much progress has been made in identifying the components of the divisome, the assembly of proteins that undertakes the vital process of cell division in bacteria. However, how the highly interdependent processes on either side of the membrane are coordinated during division is a major unresolved question. How is the degradation and synthesis of the cell wall on the outside of the cell coordinated with cytokinesis and membrane fission, which are driven from the inside of the cell by the tubulin homologue FtsZ? A possible key mediator of such coordination is the membrane protein EzrA, as it interacts both with FtsZ and the penicillin binding proteins (PBPs that synthesize peptidoglycan. Cleverley et al. [Nature Communications (2014 5, 5421] have recently solved the crystal structure of the cytoplasmic domain of B. subtilis EzrA, which points to an important scaffolding role for EzrA in the divisome. The structure resembles the eukaryotic, cytoskeletal spectrin proteins, which link actin filaments in the cytoskeleton and also connect the actin cytoskeleton to membrane-bound integrin proteins.

Erythroid cells in vitro: from developmental biology to blood transfusion products.

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Migliaccio, Anna Rita; Whitsett, Carolyn; Migliaccio, Giovanni

2009-07-01

Red blood cells (RBCs) transfusion plays a critical role in numerous therapies. Disruption of blood collection by political unrest, natural disasters and emerging infections and implementation of restrictions on the use of erythropoiesis-stimulating agents in cancer may impact blood availability in the near future. These considerations highlight the importance of developing alternative blood products. Knowledge about the processes that control RBC production has been applied to the establishment of culture conditions allowing ex-vivo generation of RBCs in numbers close to those (2.5 x 10 cells/ml) present in a transfusion, from cord blood, donated blood units or embryonic stem cells. In addition, experimental studies demonstrate that such cells protect mice from lethal bleeding. Therefore, erythroid cells generated ex vivo may be suitable for transfusion provided they can be produced safely in adequate numbers. However, much remains to be done to translate a theoretical production of approximately 2.5 x 10 RBCs in the laboratory into a 'clinical grade production process'. This review summarizes the state-of-the-art in establishing ex-vivo culture conditions for erythroid cells and discusses the most compelling issues to be addressed to translate this progress into a clinical grade transfusion product.

Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin/Adducin

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Fu, Chenglai; Xu, Jing; Li, Ruo-Jing; Crawford, Joshua A.; Khan, A. Basit; Ma, Ting Martin; Cha, Jiyoung Y.; Snowman, Adele M.; Pletnikov, Mikhail V.

2015-01-01

The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells. SIGNIFICANCE STATEMENT We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function. PMID:26245967

Age- dependent effect of Alzheimer’s risk variant of CLU on EEG alpha rhythm in non-demented adults

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Natalya ePonomareva

2013-12-01

Full Text Available Polymorphism in the genomic region harboring the CLU gene (rs11136000 has been associated with the risk for Alzheimer’s disease (AD. CLU C allele is assumed to confer risk for AD and the allele T may have a protective effect.We investigated the influence of the AD-associated CLU genotype on a common neurophysiological trait of brain activity (resting-state alpha-rhythm activity in non-demented adults and elucidated whether this influence is modified over the course of aging. We examined quantitative EEG (qEEG in cohort of non-demented individuals (age range 20-80 divided into young (age range 20-50 and old (age range 51-80 cohorts and stratified by CLU polymorphism. To rule out the effect of the ApoE genotype on EEG characteristics, only subjects without the ApoE epsilon4 allele were included in the study.The homozygous presence of the AD risk variant CLU CC in non-demented subjects was associated with an increase of alpha3 absolute power. Moreover, the influence of CLU genotype on alpha3 was found to be higher in the subjects older than 50 years of age. The study also showed age-dependent alterations of alpha topographic distribution that occur independently of the CLU genotype.The increase of upper alpha power has been associated with hippocampal atrophy in patients with mild cognitive impairment (Moretti et al., 2012a. In our study, the CLU CC- dependent increase in upper alpha rhythm, particularly enhanced in elderly non-demented individuals, may imply that the genotype is related to preclinical dysregulation of hippocampal neurophysiology in aging and that this factor may contribute to pathogenesis of AD.

Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia.

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Tomonaga, M; Jinnai, I; Tagawa, M; Amenomori, T; Nishino, K; Yao, E; Nonaka, H; Kuriyama, K; Yoshida, Y; Matsuo, T

1987-02-01

The bone marrow of a patient with acute undifferentiated leukemia developed unique colonies after a 14-day culture in erythropoietin (EPO)-containing methylcellulose. The colonies consisted of 20 to 200 nonhemoglobinized large blast cells. Cytogenetic analysis of single colonies revealed hypotetraploid karyotypes with several marker chromosomes that were identical to those found in directly sampled bone marrow. The concurrently formed erythroid bursts showed only normal karyotypes. No leukemic colony formation was observed in other culture systems with either colony-stimulating activity (CSA) or phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). The leukemic colonies exhibited a complete EPO-dose dependency similar to that of the patient's normal BFU-E. Although cytochemical and immunologic marker studies of the bone marrow cells failed to clarify the cell lineage of the leukemic cells with extraordinarily large cell size, ultrastructural study revealed erythroid differentiation such as siderosome formation in the cytoplasm and ferritin particles in the rhophecytosis invaginations. These findings indicate that the patient had poorly differentiated erythroid leukemia and that some of the clonogenic cells might respond to EPO in vitro. Corresponding to this biological feature, the leukemic cells were markedly decreased in number in response to repeated RBC transfusions, and partial remission was obtained. These observations suggest that erythroid leukemia distinct from erythroleukemia (M6) with a myeloblastic component, can develop as a minor entity of human acute leukemia.

Reduction of erythroid progenitors in protein-energy malnutrition.

Science.gov (United States)

Borelli, Primavera; Blatt, Solange; Pereira, Juliana; de Maurino, Beatriz Beutler; Tsujita, Maristela; de Souza, Ana Cristina; Xavier, José Guilherme; Fock, Ricardo Ambrósio

2007-02-01

Protein-energy malnutrition is a syndrome in which anaemia together with multivitamin and mineral deficiency may be present. The pathophysiological mechanisms involved have not, however, yet been completely elucidated. The aim of the present study was to evaluate the pathophysiological processes that occur in this anaemia in animals that were submitted to protein-energy malnutrition, in particular with respect to Fe concentration and the proliferative activity of haemopoietic cells. For this, histological, histochemical, cell culture and immunophenotyping techniques were used. Two-month-old male Swiss mice were submitted to protein-energy malnutrition with a low-protein diet (20 g/kg) compared with control diet (400 g/kg). When the experimental group had attained a 20 % loss of their original body weight, the animals from both groups received, intravenously, 20 IU erythropoietin every other day for 14 d. Malnourished animals showed a decrease in red blood cells, Hb concentration and reticulocytopenia, as well as severe bone marrow and splenic atrophy. The results for serum Fe, total Fe-binding capacity, transferrin and erythropoietin in malnourished animals were no different from those of the control animals. Fe reserves in the spleen, liver and bone marrow were found to be greater in the malnourished animals. The mixed colony-forming unit assays revealed a smaller production of granulocyte-macrophage colony-forming units, erythroid burst-forming units, erythroid colony-forming units and CD45, CD117, CD119 and CD71 expression in the bone marrow and spleen cells of malnourished animals. These findings suggest that, in this protein-energy malnutrition model, anaemia is not caused by Fe deficiency or erythropoietin deficiency, but is a result of ineffective erythropoiesis.

Biosynthesis of heme in immature erythroid cells. The regulatory step for heme formation in the human erythron

International Nuclear Information System (INIS)

Gardner, L.C.; Cox, T.M.

1988-01-01

Heme formation in reticulocytes from rabbits and rodents is subject to end product negative feedback regulation: intracellular free heme has been shown to control acquisition of transferrin iron for heme synthesis. To identify the site of control of heme biosynthesis in the human erythron, immature erythroid cells were obtained from peripheral blood and aspirated bone marrow. After incubation with human 59Fe transferrin, 2-[14C]glycine, or 4-[14C]delta-aminolevulinate, isotopic incorporation into extracted heme was determined. Addition of cycloheximide to increase endogenous free heme, reduced incorporation of labeled glycine and iron but not delta-aminolevulinate into cell heme. Incorporation of glycine and iron was also sensitive to inhibition by exogenous hematin (Ki, 30 and 45 microM, respectively) i.e. at concentrations in the range which affect cell-free protein synthesis in reticulocyte lysates. Hematin treatment rapidly diminished incorporation of intracellular 59Fe into heme by human erythroid cells but assimilation of 4-[14C]delta-aminolevulinate into heme was insensitive to inhibition by hematin (Ki greater than 100 microM). In human reticulocytes (unlike those from rabbits), addition of ferric salicylaldehyde isonicotinoylhydrazone, to increase the pre-heme iron pool independently of the transferrin cycle, failed to promote heme synthesis or modify feedback inhibition induced by hematin. In human erythroid cells (but not rabbit reticulocytes) pre-incubation with unlabeled delta-aminolevulinate or protoporphyrin IX greatly stimulated utilization of cell 59Fe for heme synthesis and also attenuated end product inhibition. In human erythroid cells heme biosynthesis is thus primarily regulated by feedback inhibition at one or more steps which lead to delta-aminolevulinate formation

Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy.

Science.gov (United States)

Benz, Peter M; Merkel, Carla J; Offner, Kristin; Abeßer, Marco; Ullrich, Melanie; Fischer, Tobias; Bayer, Barbara; Wagner, Helga; Gambaryan, Stepan; Ursitti, Jeanine A; Adham, Ibrahim M; Linke, Wolfgang A; Feller, Stephan M; Fleming, Ingrid; Renné, Thomas; Frantz, Stefan; Unger, Andreas; Schuh, Kai

2013-08-12

In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.

Water quality - Measurement of gross alpha activity in non-saline water - Thick source method. 2. ed.

International Nuclear Information System (INIS)

2007-01-01

This International Standard specifies a method for the determination of gross alpha activity in non-saline waters for alpha-emitting radionuclides which are not volatile at 350 degree Centigrade. It is possible to determine supported volatile radionuclides measured to an extent determined by half-life, matrix retention (of the volatile species) and the duration of measurement (counting time). The method is applicable to raw and potable waters. The range of application depends on the amount of suspended matter in the water and on the performance characteristics (background count rate and counting efficiency) of the counter. Gross alpha radioactivity is determined by using proportional counting or solid scintillation counting on water residue deposited on a planchet. Due to the strong absorption of the residue deposit, it is considered that the alpha emission from the surface is proportional to the alpha activity of the deposit. Gross alpha determination is not an absolute determination of the sample alpha radioactive content, but a relative determination referring to a specific alpha emitter which constitutes the standard calibration source. This type of determination is also known as alpha index. The sample is acidified to stabilize it, evaporated almost to dryness, converted to the sulfate form and then ignited at 350 degree Centigrade. A portion of the residue is transferred to a planchet and the alpha activity measured by counting in an alpha-particle detector or counting system previously calibrated against an alpha-emitting standard and the alpha activity concentration calculated. The paper provides information about scope, normative references, symbols, definitions and units, principle, reagents and equipment, procedure, contamination check, expression of results and test report

Characterization of a 65 kDa NIF in the nuclear matrix of the monocot Allium cepa that interacts with nuclear spectrin-like proteins.

Science.gov (United States)

Pérez-Munive, Clara; Blumenthal, Sonal S D; de la Espina, Susana Moreno Díaz

2012-01-01

Plant cells have a well organized nucleus and nuclear matrix, but lack orthologues of the main structural components of the metazoan nuclear matrix. Although data is limited, most plant nuclear structural proteins are coiled-coil proteins, such as the NIFs (nuclear intermediate filaments) in Pisum sativum that cross-react with anti-intermediate filament and anti-lamin antibodies, form filaments 6-12 nm in diameter in vitro, and may play the role of lamins. We have investigated the conservation and features of NIFs in a monocot species, Allium cepa, and compared them with onion lamin-like proteins. Polyclonal antisera against the pea 65 kDa NIF were used in 1D and 2D Western blots, ICM (imunofluorescence confocal microscopy) and IEM (immunoelectron microscopy). Their presence in the nuclear matrix was analysed by differential extraction of nuclei, and their association with structural spectrin-like proteins by co-immunoprecipitation and co-localization in ICM. NIF is a conserved structural component of the nucleus and its matrix in monocots with Mr and pI values similar to those of pea 65 kDa NIF, which localized to the nuclear envelope, perichromatin domains and foci, and to the nuclear matrix, interacting directly with structural nuclear spectrin-like proteins. Its similarities with some of the proteins described as onion lamin-like proteins suggest that they are highly related or perhaps the same proteins.

Erythroid differentiation and commitment in rat erythroleukemia cells with hypertonic culture conditions.

OpenAIRE

Yamaguchi, Y; Kluge, N; Ostertag, W; Furusawa, M

1981-01-01

Cell cultures of 7,12-dimethylbenz[a]anthracene-induced rat erythroleukemia can be stimulated to synthesize hemoglobin when cultured in hypertonic media. During hypertonic treatment the intracellular osmotic conditions immediately readjust to those of the extracellular medium. None of the Friend virus-induced mouse erythroleukemia cell lines was inducible for differentiation with the same hypertonic culture conditions used for rat cells. Earliest commitment to erythroid terminal differentiati...

Possible interaction between B1 retrotransposon-containing sequences and β(major) globin gene transcriptional activation during MEL cell erythroid differentiation.

Science.gov (United States)

Vizirianakis, Ioannis S; Tezias, Sotirios S; Amanatiadou, Elsa P; Tsiftsoglou, Asterios S

2012-01-01

Repetitive sequences consist of >50% of mammalian genomic DNAs and among these SINEs (short interspersed nuclear elements), e.g. B1 elements, account for 8% of the mouse genome. In an effort to delineate the molecular mechanism(s) involved in the blockade of the in vitro differentiation program of MEL (murine erythroleukaemia) cells by treatment with methylation inhibitors, we detected a DNA region of 559 bp in chromosome 7 located downstream of the 3'-end of the β(major) globin gene (designated B1-559) with unique characteristics. We have fully characterized this B1-559 region that includes a B1 element, several repeats of ATG initiation codons and consensus DNA-binding sites for erythroid-specific transcription factors NF-E2 (nuclear factor-erythroid-derived 2), GATA-1 and EKLF (erythroid Krüppel-like factor). Fragments derived from B1-559 incubated with nuclear extracts form protein complexes in both undifferentiated and differentiated MEL cells. Transient reporter-gene experiments in MEL and human erythroleukaemia K-562 cells with recombinant constructs containing B1-559 fragments linked to HS-2 (hypersensitive site-2) sequences of human β-globin gene LCR (locus control region) indicated potential cooperation upon erythropoiesis and globin gene expression. The possible interaction between the B1-559 region and β(major) globin gene transcriptional activation upon execution of erythroid MEL cell differentiation programme is discussed. © The Author(s) Journal compilation © 2012 Portland Press Limited

Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex.

Science.gov (United States)

Ganaie, Safder S; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve; Qiu, Jianming

2017-05-01

Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases.

Two different in vitro growth patterns for erythroid precursors in 18 patients with pure erythrocytosis

International Nuclear Information System (INIS)

Clement, S.; Eberlin, A.; Najean, Y.; Chedeville, A.

1982-01-01

Growth patterns of marrow and blood erythroid progenitors were studied in 18 cases of pure erythrocytosis using different doses of erythropoietin. 8 cases demonstrated ''spontaneous'' growth of CFU-E and blood BFU-E as observed in myeloproliferative disorders, but without an excess of circulating CFU-GM. 3 of these patients also had other symptoms of a pan-myelopathy. All these cases showed good sensitivity to 32 P myelo-suppression. 10 cases demonstrated growth patterns of erythroid progenitors similar to those observed in normal subjects, except for an excess of blood BFU-E, which suggests an abnormality of homeostatic regulation. In 5 of these cases, myelo-suppression was not effective. It is suggested that a stem cell study could differentiate patients with pure erythrocytosis due to ''autonomous'' abnormal stem cell growth from cases due to abnormal regulation factors, and that such a discrimination might be usefull for the choice of theraphy. (authors)

Identification of a human erythroid progenitor cell population which expresses the CD34 antigen and binds the plant lectin Ulex europaeus I.

Science.gov (United States)

Unverzagt, K L; Martinson, J; Lee, W; Stiff, P J; Williams, S; Bender, J G

1996-01-01

Two and three color flow cytometry of normal human bone marrow was used to identify CD34+ progenitor cells and examine their binding to the plant lectin Ulex europaeus I (Ulex). In normal bone marrow, 48.48 +/- 17.4% of the CD34+ cells bind to Ulex. Two color flow cytometry was used to sort CD34 + cells, and subsets of CD34+ cells, CD34+ Ulex+ and CD34+ Ulex-. These populations were sorted into colony assays to assess myeloid (CFU-GM) and erythroid (BFU-E) progenitors. The CD34+ Ulex+ subset was 84 +/- 14% BFU-E colonies (mean +/- S.D.) and had the highest cloning efficiency of 28 +/- 13%. Three color analysis of CD34+ Ulex+ cells showed staining with other erythroid (CD71, GlyA) antibodies and lack of stain. ing with myeloid (CD13, CD45RA) antibodies. These studies confirmed the erythroid characteristics of this subpopulation.

Music genre preference and tempo alter alpha and beta waves in human non-musicians

Directory of Open Access Journals (Sweden)

Hunter Gentry

2013-10-01

Full Text Available This study examined the effects of music genre and tempo on brain activation patterns in 10 nonmusicians.Two genres (rock and jazz and three tempos (slowed, medium/normal, andquickened were examined using EEG recording and analyzed through Fast Fourier Transform(FFT analysis. When participants listened to their preferred genre, an increase in alpha waveamplitude was observed. Alpha waves were not significantly affected by tempo. Beta waveamplitude increased significantly as the tempo increased. Genre had no effect on beta waves. Thefindings of this study indicate that genre preference and artificially modified tempo do affectalpha and beta wave activation in non-musicians listening to preselected songs.

Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria

NARCIS (Netherlands)

Houwerzijl, E. J.; Pol, H-W D.; Blom, N. R.; van der Want, J. J. L.; de Wolf, J. Thm; Vellenga, E.

Recent studies in erythroid cells have shown that autophagy is an important process for the physiological clearance of mitochondria during terminal differentiation. However, autophagy also plays an important role in removing damaged and dysfunctional mitochondria. Defective mitochondria and impaired

Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

OpenAIRE

McMahon, Laura W.; Zhang, Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

2009-01-01

Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellu...

Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia.

OpenAIRE

Jaako, Pekka; Debnath, Shubhranshu; Olsson, Karin; Zhang, Y; Flygare, Johan; Lindström, M S; Bryder, David; Karlsson, Stefan

2015-01-01

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of Mdm2, the main negative regulator of p53, by the 5S ribonucleoprot...

Universality in all-{alpha}{sup Prime} order corrections to BPS/non-BPS brane world volume theories

Energy Technology Data Exchange (ETDEWEB)

Hatefi, Ehsan, E-mail: ehatefi@ictp.it [International Centre for Theoretical Physics, Strada Costiera 11, Trieste (Italy); Park, I.Y., E-mail: inyongpark05@gmail.com [Department of Natural and Physical Sciences, Philander Smith College, Little Rock, AR 72223 (United States)

2012-11-21

Knowledge of all-{alpha}{sup Prime} higher derivative corrections to leading order BPS and non-BPS brane actions would serve in future endeavor of determining the complete form of the non-abelian BPS and tachyonic effective actions. In this paper, we note that there is a universality in the all-{alpha}{sup Prime} order corrections to BPS and non-BPS branes. We compute amplitudes between one Ramond-Ramond C-field vertex operator and several SYM gauge/scalar vertex operators. Specifically, we evaluate in closed form string correlators of two-point amplitudes A{sup C{phi}}, A{sup CA}, a three-point amplitude A{sup C{phi}{phi}}, and a four-point amplitude A{sup C{phi}{phi}{phi}}. We carry out pole and contact term analysis. In particular we reproduce some of the contact terms and the infinite massless poles of A{sup C{phi}{phi}{phi}} by SYM vertices obtained through the universality.

Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

Science.gov (United States)

Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

2014-01-01

To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible. Copyright © 2014 Elsevier Inc. All rights reserved.

Numerical simulation of alpha-quartz under non-hydrostatic compression. Memory glass and five-coordinated crystalline phases

OpenAIRE

Badro, James; Barrat, Jean-Louis; Gillet, Philippe

1996-01-01

The behavior of $\\alpha$-quartz under hydrostatic and non-hydrostatic high-pressure conditions has been investigated in Molecular Dynamics simulations of silica in order to clarify the role of non-hydrostatic stresses in the amorphization process. It is shown that the amorphization threshold is not modified if the stress along the {\\bf c} direction is lowered, so that the mean amorphization pressure can effectively be lowered under non-hydrostatic conditions. On the other hand, the applicatio...

Exploring non-stationarity patterns in schizophrenia: neural reorganization abnormalities in the alpha band

Science.gov (United States)

Núñez, Pablo; Poza, Jesús; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Molina, Vicente; Hornero, Roberto

2017-08-01

Objective. The aim of this paper was to characterize brain non-stationarity during an auditory oddball task in schizophrenia (SCH). The level of non-stationarity was measured in the baseline and response windows of relevant tones in SCH patients and healthy controls. Approach. Event-related potentials were recorded from 28 SCH patients and 51 controls. Non-stationarity was estimated in the conventional electroencephalography frequency bands by means of Kullback-Leibler divergence (KLD). Relative power (RP) was also computed to assess a possible complementarity with KLD. Main results. Results showed a widespread statistically significant increase in the level of non-stationarity from baseline to response in all frequency bands for both groups. Statistically significant differences in non-stationarity were found between SCH patients and controls in beta-2 and in the alpha band. SCH patients showed more non-stationarity in the left parieto-occipital region during the baseline window in the beta-2 band. A leave-one-out cross validation classification study with feature selection based on binary stepwise logistic regression to discriminate between SCH patients and controls provided a positive predictive value of 72.73% and negative predictive value of 78.95%. Significance. KLD can characterize transient neural reorganization during an attentional task in response to novelty and relevance. Our findings suggest anomalous reorganization of neural dynamics in SCH during an oddball task. The abnormal frequency-dependent modulation found in SCH patients during relevant tones is in agreement with the hypothesis of aberrant salience detection in SCH. The increase in non-stationarity in the alpha band during the active task supports the notion that this band is involved in top-down processing. The baseline differences in the beta-2 band suggest that hyperactivation of the default mode network during attention tasks may be related to SCH symptoms. Furthermore, the classification

Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply.

Science.gov (United States)

Yang, Zhigang; Yao, Hong; Fei, Fei; Li, Yuwei; Qu, Jie; Li, Chunyuan; Zhang, Shiwu

2018-04-01

During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels. In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia. An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.

Induction of erythroid differentiation in human erythroleukemia cells by depletion of malic enzyme 2.

Directory of Open Access Journals (Sweden)

Jian-Guo Ren

2010-09-01

Full Text Available Malic enzyme 2 (ME2 is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel

Effect of temperature on the collective clusterization of non-alpha conjugate nuclei

International Nuclear Information System (INIS)

Kaur, Manpreet; Singh, BirBikram; Patra, S.K.; Gupta, R.K.

2017-01-01

In the present work, we report on the role of temperature on the collective clusterization process in non-alpha conjugate systems 21,22 Ne (N≠ Z) in the ground state and at the temperature equivalent to the excitation energy given by Ikeda diagram. Further, to study the impact of increasing temperature on the clustering, these effects are studied in the CN 21 Ne* and 22 Ne* formed in 10 B+ 11 B and 11 B+ 11 B reactions, respectively, with reference to experimental data

Expression of assayable residual stem cell damage in erythroid differentiation

International Nuclear Information System (INIS)

Huebner, G.E.; Miller, M.E.; Cronkite, E.P.

1985-01-01

In rodents, residual damage is inducible in hematopoietic stem cells by exposure to ionizing radiation or alkylating agents. This damage can b e assayed in mice by transferring bone marrow into lethally irradiated syngeneic recipients and subsequently measuring the incremental increase of-( 125 I)iodo-2'-deoxyuridine incorporation in spleens. In this study, bone marrow from mice treated 3 weeks previously with Methylnitrosourea (50 mg/kg) or 450 rad was injected into recipients in order to determine possible residual effects of treatment of erythroid cell differentiation following stem cell seeding. Such effects were detected by a reduced amount of 59 Fe incorporation into spleens, thus indicatin g transfer of residual stem cell damage to differentiating cells. (orig.)

Characterization of human erythroid burst-promoting activity derived from bone marrow conditioned media

International Nuclear Information System (INIS)

Porter, P.N.; Ogawa, M.

1982-01-01

Bone marrow conditioned media (BMCM) increases burst number and the incorporation of 59 Fe into heme by bursts when peripheral blood or bone marrow cells are cultured at limiting serum concentrations. Burst-promoting activity (BPA) has now been purified approximately 300-fold from this source by ion-exchange chromatography on DEAE-Sephadex and absorption chromatography on hydroxyapatite agarose gel. Marrow BPA increased burst number and hemoglobin (Hb) synthesis in a dose-dependent manner. A larger increase in Hb synthesis than in burst number was consistently observed, which was probably a consequence of the increase in the number of cells per burst that occurs in the presence of BPA. The role of BPA in culture could be distinguished from erythropoietin (Ep), since no bursts grew in the absence of Ep, whether or not BPA was present, and since it had no effect on the growth of erythroid colonies scored at day 5 of culture. Our purified fraction did not support the growth of CFU-C in culture. Activity was stable at temperatures of 70 degrees C or lower for 10 min; exposure to 80 degrees C resulted in approximately 50% loss of activity. BPA was completely inactivated by treatment at 100 degrees C for 10 min. Thus, human bone marrow cells produce a heat-sensitive factor that specifically promotes the growth of early erythroid progenitors in culture

Role of band 3 in the erythrocyte membrane structural changes under thermal fluctuations -multi scale modeling considerations.

Science.gov (United States)

Pajic-Lijakovic, Ivana

2015-12-01

An attempt was made to discuss and connect various modeling approaches on various time and space scales which have been proposed in the literature in order to shed further light on the erythrocyte membrane rearrangement caused by the cortex-lipid bilayer coupling under thermal fluctuations. Roles of the main membrane constituents: (1) the actin-spectrin cortex, (2) the lipid bilayer, and (3) the trans membrane protein band 3 and their course-consequence relations were considered in the context of the cortex non linear stiffening and corresponding anomalous nature of energy dissipation. The fluctuations induce alternating expansion and compression of the membrane parts in order to ensure surface and volume conservation. The membrane structural changes were considered within two time regimes. The results indicate that the cortex non linear stiffening and corresponding anomalous nature of energy dissipation are related to the spectrin flexibility distribution and the rate of its changes. The spectrin flexibility varies from purely flexible to semi flexible. It is influenced by: (1) the number of band 3 molecules attached to single spectrin filaments, and (2) phosphorylation of the actin-junctions. The rate of spectrin flexibility changes depends on the band 3 molecules rearrangement.

Genetic manipulation of RPS5 gene expression modulates the initiation of commitment of MEL cells to erythroid maturation: Implications in understanding ribosomopathies.

Science.gov (United States)

Vizirianakis, Ioannis S; Papachristou, Eleni T; Andreadis, Panagiotis; Zopounidou, Elena; Matragkou, Christina N; Tsiftsoglou, Asterios S

2015-07-01

Impairment of ribosome biogenesis contributes to the molecular pathophysiology of ribosomopathies by deregulating cell-lineage specific proliferation, differentiation and apoptosis decisions of haematopoietic progenitor cells. Here, using pro-erythroblast-like murine erythroleukemia (MEL) cells, a model system of erythroid maturation, we aimed to investigate whether genetic manipulation of RPS5 expression affects the capacity of cells to grow and differentiate in culture. Parental MEL cells stably transfected with full length RPS5 cDNA in sense (MEL-C14 culture) or antisense (MEL-antisenseRPS5 culture) orientation, as well as MEL cells transiently transfected with siRNAs specific for RPS5 gene silencing (MEL-RPS5siRNA culture) were assessed for their ability to fully execute their erythroid maturation program in culture. The data obtained thus far indicate that: a) MEL-antisenseRPS5 exhibit a pronounced delay in the initiation of differentiation, as well as an impairment of commitment, since the continuous presence of the inducer in culture is required for the cells to fully execute their erythroid maturation program. b) RNAi-mediating silencing of RPS5 gene expression resulted in the inability of MEL cells to differentiate; however, when these cells were allowed to recapitulate normal RPS5 gene expression levels they regained their differentiation capacity by accumulating high proportion of erythroid mature cells. c) Interestingly the latter, is accompanied by morphological changes of cells and an impairment of their proliferation and apoptosis potential. Such data for the first time correlate the RPS5 gene expression levels with the differentiation capacity of MEL cells in vitro, a fact that might also have implications in understanding ribosomopathies.

Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells

Energy Technology Data Exchange (ETDEWEB)

Lin, Hui-Hsuan [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Chou, Fen-Pi [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Wang, Chau-Jong [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Hsuan, Shu-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China); Wang, Cheng-Kun [E-Chyun Dermatology Clinic, No.70, Sec. 3, Jhonghua E. Rd., East District, Tainan, Taiwan (China); Chen, Jing-Hsien [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China)

2011-02-01

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in A549 cells. HIF-1{alpha} plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1{alpha} was correlated with a rapid ubiquitin-dependent degradation of HIF-1{alpha}, and was accompanied by increased expressions of hydroxyl-HIF-1{alpha} and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1{alpha} inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGF{beta}1/PHD2/HIF-1{alpha} pathway, as demonstrated by the transfection of TGF{beta}1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1{alpha} transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.

Proteomic analysis of erythroid differentiation induced by hexamethylene bisacetamide in murine erythroleukemia cells

Czech Academy of Sciences Publication Activity Database

Petrák, J.; Myslivcová, D.; Man, Petr; Čmejlová, J.; Čmejla, R.; Vyoral, D.

2007-01-01

Roč. 35, - (2007), s. 193-202 ISSN 0301-472X R&D Projects: GA MŠk LC545 Grant - others:CZ(CZ) 023736; GA ČR(CZ) GA303/04/0003; GA MŠk(CZ) LC06044 Institutional research plan: CEZ:AV0Z50200510 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : murine erythroleukemia cells * erythroid differentiation * hexamethylene bisacetamide Subject RIV: EE - Microbiology, Virology Impact factor: 3.147, year: 2007

The non-linear power spectrum of the Lyman alpha forest

International Nuclear Information System (INIS)

Arinyo-i-Prats, Andreu; Miralda-Escudé, Jordi; Viel, Matteo; Cen, Renyue

2015-01-01

The Lyman alpha forest power spectrum has been measured on large scales by the BOSS survey in SDSS-III at z∼ 2.3, has been shown to agree well with linear theory predictions, and has provided the first measurement of Baryon Acoustic Oscillations at this redshift. However, the power at small scales, affected by non-linearities, has not been well examined so far. We present results from a variety of hydrodynamic simulations to predict the redshift space non-linear power spectrum of the Lyα transmission for several models, testing the dependence on resolution and box size. A new fitting formula is introduced to facilitate the comparison of our simulation results with observations and other simulations. The non-linear power spectrum has a generic shape determined by a transition scale from linear to non-linear anisotropy, and a Jeans scale below which the power drops rapidly. In addition, we predict the two linear bias factors of the Lyα forest and provide a better physical interpretation of their values and redshift evolution. The dependence of these bias factors and the non-linear power on the amplitude and slope of the primordial fluctuations power spectrum, the temperature-density relation of the intergalactic medium, and the mean Lyα transmission, as well as the redshift evolution, is investigated and discussed in detail. A preliminary comparison to the observations shows that the predicted redshift distortion parameter is in good agreement with the recent determination of Blomqvist et al., but the density bias factor is lower than observed. We make all our results publicly available in the form of tables of the non-linear power spectrum that is directly obtained from all our simulations, and parameters of our fitting formula

PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors

Directory of Open Access Journals (Sweden)

Schmidt Enrico K

2004-05-01

Full Text Available Abstract Background Erythropoietin is a multifunctional cytokine which regulates the number of erythrocytes circulating in mammalian blood. This is crucial in order to maintain an appropriate oxygen supply throughout the body. Stimulation of primary human erythroid progenitors (PEPs with erythropoietin (Epo leads to the activation of the mitogenic kinases (MEKs and Erks. How this is accomplished mechanistically remained unclear. Results Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 kinase (PI3K family, PI3K gamma, are activated in response to minimal Epo concentrations. Surprisingly, three structurally different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo. Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf inhibition and insensitive to PI3K and PKC inhibitors. Conclusions These unexpected findings contrast with previous results in human primary cells using Epo at supraphysiological concentrations and open new doors to eventually understanding how low Epo concentrations mediate the moderate proliferation of erythroid progenitors under homeostatic blood oxygen levels. They indicate that the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk. Instead, MEKs and Erks are signal mediators of PI3K, probably the recently described PI3K gamma, through a Raf-independent signaling pathway which requires PKC activity. It is likely that higher concentrations of Epo that are induced by hypoxia, for example, following blood loss, lead to additional mitogenic signals which greatly accelerate erythroid progenitor proliferation.

Knockdown of μ-calpain in Fanconi Anemia, FA-A, cells by siRNA Restores αII Spectrin levels and Corrects Chromosomal Instability and Defective DNA Interstrand Cross-link Repair†

OpenAIRE

Zhang, Pan; Sridharan, Deepa; Lambert, Muriel W.

2010-01-01

We have previously shown that there is a deficiency in the structural protein, nonerythroid α spectrin (αIISp), in cells from patients with Fanconi anemia (FA). These studies indicate that this deficiency is due to reduced stability of αIISp and correlates with decreased repair of DNA interstrand cross-links and chromosomal instability in FA cells. An important factor in the stability of αIISp is its susceptibility to cleavage by the protease, μ-calpain. We hypothesized that increased μ-calpa...

Effects of TNF-alpha on Endothelial Cell Collective Migration

Science.gov (United States)

Chen, Desu; Wu, Di; Helim Aranda-Espinoza, Jose; Losert, Wolfgang

2013-03-01

Tumor necrosis factor (TNF-alpha) is a small cell-signaling protein usually released by monocytes and macrophages during an inflammatory response. Previous work had shown the effects of TNF-alpha on single cell morphology, migration, and biomechanical properties. However, the effect on collective migrations remains unexplored. In this work, we have created scratches on monolayers of human umbilical endothelial cells (HUVECs) treated with 25ng/mL TNF-alpha on glass substrates. The wound healing like processes were imaged with phase contrast microscopy. Quantitative analysis of the collective migration of cells treated with TNF-alpha indicates that these cells maintain their persistent motion and alignment better than untreated cells. In addition, the collective migration was characterized by measuring the amount of non-affine deformations of the wound healing monolayer. We found a lower mean non-affinity and narrower distribution of non-affinities upon TNF-alpha stimulation. These results suggest that TNF-alpha introduces a higher degree of organized cell collective migration.

Erythroid cell mitochondria receive endosomal iron by a "kiss-and-run" mechanism.

Science.gov (United States)

Hamdi, Amel; Roshan, Tariq M; Kahawita, Tanya M; Mason, Anne B; Sheftel, Alex D; Ponka, Prem

2016-12-01

In erythroid cells, more than 90% of transferrin-derived iron enters mitochondria where ferrochelatase inserts Fe 2+ into protoporphyrin IX. However, the path of iron from endosomes to mitochondrial ferrochelatase remains elusive. The prevailing opinion is that, after its export from endosomes, the redox-active metal spreads into the cytosol and mysteriously finds its way into mitochondria through passive diffusion. In contrast, this study supports the hypothesis that the highly efficient transport of iron toward ferrochelatase in erythroid cells requires a direct interaction between transferrin-endosomes and mitochondria (the "kiss-and-run" hypothesis). Using a novel method (flow sub-cytometry), we analyze lysates of reticulocytes after labeling these organelles with different fluorophores. We have identified a double-labeled population definitively representing endosomes interacting with mitochondria, as demonstrated by confocal microscopy. Moreover, we conclude that this endosome-mitochondrion association is reversible, since a "chase" with unlabeled holotransferrin causes a time-dependent decrease in the size of the double-labeled population. Importantly, the dissociation of endosomes from mitochondria does not occur in the absence of holotransferrin. Additionally, mutated recombinant holotransferrin, that cannot release iron, significantly decreases the uptake of 59 Fe by reticulocytes and diminishes 59 Fe incorporation into heme. This suggests that endosomes, which are unable to provide iron to mitochondria, cause a "traffic jam" leading to decreased endocytosis of holotransferrin. Altogether, our results suggest that a molecular mechanism exists to coordinate the iron status of endosomal transferrin with its trafficking. Besides its contribution to the field of iron metabolism, this study provides evidence for a new intracellular trafficking pathway of organelles. Copyright © 2016 Elsevier B.V. All rights reserved.

Dihydroartemisinin inhibits the human erythroid cell differentiation by altering the cell cycle

International Nuclear Information System (INIS)

Finaurini, Sara; Basilico, Nicoletta; Corbett, Yolanda; D’Alessandro, Sarah; Parapini, Silvia; Olliaro, Piero; Haynes, Richard K.; Taramelli, Donatella

2012-01-01

Artemisinin derivatives such as dihydroartemisinin (DHA) induce significant depletion of early embryonic erythroblasts in animal models. We have reported previously that DHA specifically targets pro-erythroblasts and basophilic erythroblasts, when human CD34+ stem cells are differentiated toward the erythroid lineage, indicating that a window of susceptibility to artemisinins may exist also in human developmental erythropoiesis during pregnancy. To better investigate the toxicity of artemisinin derivatives, the structure–activity relationship was evaluated against the K562 leukaemia cell line, used as a model for differentiating early human erythroblasts. All artemisinins derivatives, except deoxyartemisinin, inhibited both spontaneous and induced erythroid differentiation, confirming that the peroxide bridge is responsible for the erythro-toxicity. On the contrary, cell growth was markedly reduced by DHA, artemisone and artesunate but not by artemisinin, 10-deoxoartemisinin or deoxy-artemisinin. The substituent at position C-10 is responsible only for the anti-proliferative effect, since 10-deoxoartemisinin did not reduce cell growth but arrested the differentiation of K562 cells. In particular, the results showed that DHA resulted the most potent and rapidly acting compound of the drug family, causing (i) the decreased expression of GpA surface receptors and the down regulation the γ-globin gene; (ii) the alteration of S phase of cell cycle and (iii) the induction of programmed cell death of early erythroblasts in a dose dependent manner within 24 h. In conclusion, these findings confirm that the active metabolite DHA is responsible for the erythro-toxicity of most of artemisinins used in therapy. Thus, as long as no further clinical data are available, current WHO recommendations of avoiding malaria treatment with artemisinins during the first trimester of pregnancy remain valid.

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway.

Science.gov (United States)

Ha, Ae Wha; Kim, Woo Kyoung

2017-06-01

Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly ( P concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly ( P antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia

DEFF Research Database (Denmark)

Vannucchi, Alessandro M; Pancrazzi, Alessandro; Antonioli, Elisabetta

2004-01-01

markers of ET, namely PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P = 0.......009). The frequency of abnormalities of PRV-1, EEC, or Mpl was similar in monoclonal and polyclonal subjects (respectively, 28%, 48%, 75%, and 37%, 27%, 63%), and none of them correlated with thrombosis. We conclude that the exploited epigenetic markers constitute independent phenotypic variations...

A survey of the alpha-nucleon interaction

International Nuclear Information System (INIS)

Ali, S.; Ahmad, A.A.Z.; Ferdous, N.

1984-10-01

A survey of the alpha-nucleon interaction is made. The experimental work on angular distributions of differential scattering cross-sections and polarizations in proton-alpha and neutron-alpha scattering is described. The phenomenological approach which includes the study of both local and non-local potentials reproducing the experimental alpha-nucleon scattering data, is discussed. Basic studies of the alpha-nucleon interaction attempting to build an interaction between an alpha particle and a nucleon from first principles are then described. A critical discussion of the results with some concluding remarks suggesting the direction for further investigation is made. (author)

Activity monitoring of alpha-bearing wastes

International Nuclear Information System (INIS)

Birkhoff, G.; Bondar, L.

1980-01-01

The paper aims at the survey on the actual situation in activity monitoring of alpha-bearing wastes. Homogeneous materials such as liquid-, gaseous- and homogeneous solid wastes are amenable to destructive analyses of representative samples. Available destructive analyses methods are sensitive and precise enough to cope with all requirements in alpha-waste monitoring. The more difficult problems are encountered with alpha-contaminated solids, when representative sampling is not practicable. Non-destructive analysis techniques are applied for monitoring this category of solid wastes. The techniques for nondestructive analysis of alpha-bearing wastes are based on the detection of gamma and/or neutron-emission of actinides. Principles and a theory of non-destructive radiometric assay of plutonium contaminated solid waste streams are explained. Guidelines for the calibration of instruments and interpretation of experimental data are given. Current theoretical and experimental development work in this problem area is reviewed. Evaluations concerning capabilities and limitations of monitoring systems for alpha-bearing solid wastes are very complex and out of the scope of this paper

AlphaScreen-based homogeneous assay using a pair of 25-residue artificial proteins for high-throughput analysis of non-native IgG.

Science.gov (United States)

Senga, Yukako; Imamura, Hiroshi; Miyafusa, Takamitsu; Watanabe, Hideki; Honda, Shinya

2017-09-29

Therapeutic IgG becomes unstable under various stresses in the manufacturing process. The resulting non-native IgG molecules tend to associate with each other and form aggregates. Because such aggregates not only decrease the pharmacological effect but also become a potential risk factor for immunogenicity, rapid analysis of aggregation is required for quality control of therapeutic IgG. In this study, we developed a homogeneous assay using AlphaScreen and AF.2A1. AF.2A1 is a 25-residue artificial protein that binds specifically to non-native IgG generated under chemical and physical stresses. This assay is performed in a short period of time. Our results show that AF.2A1-AlphaScreen may be used to evaluate the various types of IgG, as AF.2A1 recognizes the non-native structure in the constant region (Fc region) of IgG. The assay was effective for detection of non-native IgG, with particle size up to ca. 500 nm, generated under acid, heat, and stirring conditions. In addition, this technique is suitable for analyzing non-native IgG in CHO cell culture supernatant and mixed with large amounts of native IgG. These results indicate the potential of AF.2A1-AlphaScreen to be used as a high-throughput evaluation method for process monitoring as well as quality testing in the manufacturing of therapeutic IgG.

The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro

NARCIS (Netherlands)

von Lindern, M.; Zauner, W.; Mellitzer, G.; Steinlein, P.; Fritsch, G.; Huber, K.; Löwenberg, B.; Beug, H.

1999-01-01

Although erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation. In avian erythroid progenitors, steroid hormones cooperate with tyrosine kinase receptors

Parvovirus B19 Replication and Expression in Differentiating Erythroid Progenitor Cells.

Directory of Open Access Journals (Sweden)

Gloria Bua

Full Text Available The pathogenic Parvovirus B19 (B19V is characterized by a strict adaptation to erythroid progenitor cells (EPCs, a heterogeneous population of differentiating cells with diverse phenotypic and functional properties. In our work, we studied the dynamics of B19V infection in EPCs in dependence on the cell differentiation stage, in terms of distribution of infected cells, synthesis of viral nucleic acids and production of infectious virus. EPCs at early differentiation stage led to an abortive infection, without viral genome replication and a very low transcriptional activity. EPCs at later stages were permissive, with highest levels of viral replicative activity at day 9 (+3.0 Log from 2 to 48 hpi and lower levels at day 18 (+1.5 Log from 2 to 48 hpi. B19V DNA increment was in accordance with the percentage of cells positive to flow-FISH assay (41.4% at day 9, 1.1% at day 18. Quantitation of total RNA indicated a close association of genome replication and transcription with viral RNA accumulation within infected cells related to viral DNA increase during the course of infection. Analysis of the different classes of mRNAs revealed two distinct pattern of genome expression profile with a fine regulation in the frequency utilization of RNA processing signals: an early phase, when cleavage at the proximal site leading to a higher relative production of mRNA for NS protein, and a late phase, when cleavage at the distal site was more frequent leading to higher relative abundance of mRNA for VP and 11 kDA proteins. Infectious virus was released from cells at day 6-15, but not at day 18. Our results, providing a detailed description of B19V replication and expression profile in differentiating EPCs, highlight the very tight adaptation of B19V to a specific cellular target defined both by its erythroid lineage and its differentiation stage.

Parvovirus B19 Replication and Expression in Differentiating Erythroid Progenitor Cells

Science.gov (United States)

Bua, Gloria; Manaresi, Elisabetta; Bonvicini, Francesca; Gallinella, Giorgio

2016-01-01

The pathogenic Parvovirus B19 (B19V) is characterized by a strict adaptation to erythroid progenitor cells (EPCs), a heterogeneous population of differentiating cells with diverse phenotypic and functional properties. In our work, we studied the dynamics of B19V infection in EPCs in dependence on the cell differentiation stage, in terms of distribution of infected cells, synthesis of viral nucleic acids and production of infectious virus. EPCs at early differentiation stage led to an abortive infection, without viral genome replication and a very low transcriptional activity. EPCs at later stages were permissive, with highest levels of viral replicative activity at day 9 (+3.0 Log from 2 to 48 hpi) and lower levels at day 18 (+1.5 Log from 2 to 48 hpi). B19V DNA increment was in accordance with the percentage of cells positive to flow-FISH assay (41.4% at day 9, 1.1% at day 18). Quantitation of total RNA indicated a close association of genome replication and transcription with viral RNA accumulation within infected cells related to viral DNA increase during the course of infection. Analysis of the different classes of mRNAs revealed two distinct pattern of genome expression profile with a fine regulation in the frequency utilization of RNA processing signals: an early phase, when cleavage at the proximal site leading to a higher relative production of mRNA for NS protein, and a late phase, when cleavage at the distal site was more frequent leading to higher relative abundance of mRNA for VP and 11 kDA proteins. Infectious virus was released from cells at day 6–15, but not at day 18. Our results, providing a detailed description of B19V replication and expression profile in differentiating EPCs, highlight the very tight adaptation of B19V to a specific cellular target defined both by its erythroid lineage and its differentiation stage. PMID:26845771

Liquid scintillation alpha spectrometry techniques

International Nuclear Information System (INIS)

McKlveen, J.W.; McDowell, W.J.

1984-01-01

Accurate, quantitative determinations of alpha emitting nuclides by conventional plate counting methods are difficult, because of sample self-absorption problems in counting and because of non-reproducible losses in conventional sample separation methods. Liquid scintillation alpha spectrometry offers an attractive alternative with no sample self-absorption or geometry problems and with 100% counting efficiency. Sample preparation may include extraction of the alpha emitter of interest by a specific organic phase-soluble compound directly into the liquid scintillation counting medium. Detection electronics use energy and pulse-shape discrimination, to yield alpha spectra without beta and gamma background interference. Specific procedures have been developed for gross alpha, uranium, plutonium, thorium and colonium assay. Possibilities for a large number of other applications exist. Accuracy and reproducibility are typically in the 1% range. Backgrounds of the order of 0.01 cpm are readily achievable. The paper will present an overview of liquid scintillation alpha counting techniques and some of the results achieved for specific applications. (orig.)

Life cycle-dependent cytoskeletal modifications in Plasmodium falciparum infected erythrocytes.

Directory of Open Access Journals (Sweden)

Hui Shi

Full Text Available Plasmodium falciparum infection of human erythrocytes is known to result in the modification of the host cell cytoskeleton by parasite-coded proteins. However, such modifications and corresponding implications in malaria pathogenesis have not been fully explored. Here, we probed the gradual modification of infected erythrocyte cytoskeleton with advancing stages of infection using atomic force microscopy (AFM. We reported a novel strategy to derive accurate and quantitative information on the knob structures and their connections with the spectrin network by performing AFM-based imaging analysis of the cytoplasmic surface of infected erythrocytes. Significant changes on the red cell cytoskeleton were observed from the expansion of spectrin network mesh size, extension of spectrin tetramers and the decrease of spectrin abundance with advancing stages of infection. The spectrin network appeared to aggregate around knobs but also appeared sparser at non-knob areas as the parasite matured. This dramatic modification of the erythrocyte skeleton during the advancing stage of malaria infection could contribute to the loss of deformability of the infected erythrocyte.

Life cycle-dependent cytoskeletal modifications in Plasmodium falciparum infected erythrocytes.

Science.gov (United States)

Shi, Hui; Liu, Zhuo; Li, Ang; Yin, Jing; Chong, Alvin G L; Tan, Kevin S W; Zhang, Yong; Lim, Chwee Teck

2013-01-01

Plasmodium falciparum infection of human erythrocytes is known to result in the modification of the host cell cytoskeleton by parasite-coded proteins. However, such modifications and corresponding implications in malaria pathogenesis have not been fully explored. Here, we probed the gradual modification of infected erythrocyte cytoskeleton with advancing stages of infection using atomic force microscopy (AFM). We reported a novel strategy to derive accurate and quantitative information on the knob structures and their connections with the spectrin network by performing AFM-based imaging analysis of the cytoplasmic surface of infected erythrocytes. Significant changes on the red cell cytoskeleton were observed from the expansion of spectrin network mesh size, extension of spectrin tetramers and the decrease of spectrin abundance with advancing stages of infection. The spectrin network appeared to aggregate around knobs but also appeared sparser at non-knob areas as the parasite matured. This dramatic modification of the erythrocyte skeleton during the advancing stage of malaria infection could contribute to the loss of deformability of the infected erythrocyte.

Measurement of alpha-fetoprotein in maternal serum: three commercial radioimmunoassay kits and two non-commercial radioimmunoassays compared

International Nuclear Information System (INIS)

Forest, J.C.; Verreault, F.; Pouliot, M.

1982-01-01

We evaluated three commercial radioimmunoassay kits (Amersham, Dainabot, Clinical Assays) and two non-commercial methods for determining alpha-fetoprotein in maternal serum during pregnancy. All five procedures were found to be acceptable with respect to practicability, sensitivity, linearity, and precision. Similar results were obtained with Dainabot, Clinical Assays, and the two non-commercial methods, but the Amersham method revealed a proportional error, results being about 20% lower than those by the other methods. Use of the international unit system is suggested for reporting results for AFP, to facilitate comparison between methods and laboratories

Alpha-Concave Hull, a Generalization of Convex Hull

OpenAIRE

Asaeedi, Saeed; Didehvar, Farzad; Mohades, Ali

2013-01-01

Bounding hull, such as convex hull, concave hull, alpha shapes etc. has vast applications in different areas especially in computational geometry. Alpha shape and concave hull are generalizations of convex hull. Unlike the convex hull, they construct non-convex enclosure on a set of points. In this paper, we introduce another generalization of convex hull, named alpha-concave hull, and compare this concept with convex hull and alpha shape. We show that the alpha-concave hull is also a general...

Erythroid Kruppel-like factor (EKLF) is recruited to the γ-globin gene promoter as a co-activator and is required for γ-globin gene induction by short-chain fatty acid derivatives

Science.gov (United States)

Perrine, Susan P.; Mankidy, Rishikesh; Boosalis, Michael S.; Bieker, James J.; Faller, Douglas V.

2011-01-01

Objectives The erythroid Kruppel-like factor (EKLF) is an essential transcription factor for β-type globin gene switching, and specifically activates transcription of the adult β-globin gene promoter. We sought to determine if EKLF is also required for activation of the γ-globin gene by short-chain fatty acid (SCFA) derivatives, which are now entering clinical trials. Methods The functional and physical interaction of EKLF and co-regulatory molecules with the endogenous human globin gene promoters was studied in primary human erythroid progenitors and cell lines, using chromatin immunoprecipitation (ChIP) assays and genetic manipulation of the levels of EKLF and co-regulators. Results and conclusions Knockdown of EKLF prevents SCFA-induced expression of the γ-globin promoter in a stably expressed μLCRβprRlucAγprFluc cassette, and prevents induction of the endogenous γ-globin gene in primary human erythroid progenitors. EKLF is actively recruited to endogenous γ-globin gene promoters after exposure of primary human erythroid progenitors, and murine hematopoietic cell lines, to SCFA derivatives. The core ATPase BRG1 subunit of the human SWI/WNF complex, a ubiquitous multimeric complex that regulates gene expression by remodeling nucleosomal structure, is also required for γ-globin gene induction by SCFA derivatives. BRG1 is actively recruited to the endogenous γ-globin promoter of primary human erythroid progenitors by exposure to SCFA derivatives, and this recruitment is dependent upon the presence of EKLF. These findings demonstrate that EKLF, and the co-activator BRG1, previously demonstrated to be required for definitive or adult erythropoietic patterns of globin gene expression, are co-opted by SCFA derivatives to activate the fetal globin genes. PMID:19220418

Alpha damage in non-reference waste form matrix materials

International Nuclear Information System (INIS)

Burnay, S.G.

1987-05-01

Although bitumen is the matrix material currently used for European α-bearing intermediate level waste streams, polymer and polymer-modified cement matrices could have advantages over bitumen for such wastes. Two organic matrix systems have been studied - an epoxide resin, and an epoxide modified cement. Alpha irradiations were carried out by incorporating 241 Am at approx. 0.9 Ci/l. Comparisons have been made with unirradiated material and with materials which had been γ-irradiated to the same dose as the α-irradiated samples. Measurements were made of dimensional changes, mechanical properties and the leaching behaviour of 241 Am and 137 Cs. A limited amount of swelling (< 3%) was observed in α-irradiated epoxide resin; none was observed in the epoxide modified cement. Gamma irradiation to 300 kGy has no significant effect on the mechanical properties of either system. However, alpha irradiation to the same dose produced significant changes in flexural strength, an increase for the polymer and a decrease for the polymer-cement. Leaching in these systems was found to be a diffusion-controlled process; alpha irradiation to approx. 250 kGy has little effect on the leaching behaviour of either system. (author)

Serum alpha fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance

NARCIS (Netherlands)

de Wit, R; Collette, L; Sylvester, R; de Mulder, PHM; Sleijfer, DT; Huinink, WWT; Kaye, SB; van Oosterom, AT; Boven, E; Stoter, G

It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a

Effects of central imidazolinergic and alpha2-adrenergic activation on water intake

Directory of Open Access Journals (Sweden)

Sugawara A.M.

2001-01-01

Full Text Available Non-adrenergic ligands that bind to imidazoline receptors (I-R, a selective ligand that binds to alpha2-adrenoceptors (alpha2-AR and mixed ligands that bind to both receptors were tested for their action on water intake behavior of 24-h water-deprived rats. All drugs were injected into the third cerebral ventricle. Except for agmatine (80 nmol, mixed ligands binding to I-R/alpha2-AR such as guanabenz (40 nmol and UK 14304 (20 nmol inhibited water intake by 65% and up to 95%, respectively. The selective non-imidazoline alpha2-AR agonist, alpha-methylnoradrenaline, produced inhibition of water intake similar to that obtained with guanabenz, but at higher doses (80 nmol. The non-adrenergic I-R ligands histamine (160 nmol, mixed histaminergic and imidazoline ligand and imidazole-4-acetic acid (80 nmol, imidazoline ligand did not alter water intake. The results show that selective, non-imidazoline alpha2-AR activation suppresses water intake, and suggest that the action on imidazoline sites by non-adrenergic ligands is not sufficient to inhibit water intake.

Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia.

Science.gov (United States)

Jaako, P; Debnath, S; Olsson, K; Zhang, Y; Flygare, J; Lindström, M S; Bryder, D; Karlsson, S

2015-11-01

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile, it is not clear whether this mechanism solely mediates the p53-dependent component found in DBA. To approach this question, we crossed our mouse model for RPS19-deficient DBA with Mdm2(C305F) knock-in mice that have a disrupted 5S RNP-Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2(C305F) reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP-Mdm2 interaction also led to selective defect in erythropoiesis. Our findings highlight the sensitivity of erythroid progenitor cells to aberrations in p53 homeostasis mediated by the 5S RNP-Mdm2 interaction. Finally, we provide evidence indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may contribute to functional decline of the hematopoietic system in a cell-autonomous manner over time.

Does alpha 1-acid glycoprotein act as a non-functional receptor for alpha 1-adrenergic antagonists?

Science.gov (United States)

Qin, M; Oie, S

1994-11-01

The ability of a variety of alpha 1-acid glycoproteins (AAG) to affect the intrinsic activity of the alpha 1-adrenergic antagonist prazosin was studied in rabbit aortic strip preparations. From these studies, the activity of AAG appears to be linked to their ability to bind the antagonist. However, a capability to bind prazosin was not the only requirement for this effect. The removal of sialic acid and partial removal of the galactose and mannose residues by periodate oxidation of human AAG all but eliminated the ability of AAG to affect the intrinsic pharmacologic activity of prazosin, although the binding of prazosin was not significantly affected. The presence of bovine AAG, a protein that has a low ability to bind prazosin, reduced the effect of human AAG on prazosin activity. Based upon these results, we propose that AAG is able to bind in the vicinity of the alpha 1-adrenoceptors, therefore extending the binding region for antagonists in such a way as to decrease the ability of the antagonist to interact with the receptor. The carbohydrate side-chains are important for the binding of AAG in the region of the adrenoceptor.

Prospective identification of erythroid elements in cultured peripheral blood.

Science.gov (United States)

Miller, J L; Njoroge, J M; Gubin, A N; Rodgers, G P

1999-04-01

We have developed a prospective approach to identify the generation of erythroid cells derived from cultured peripheral blood mononuclear cells (PBMC) by monitoring the expression of the cell surface protein CD48. Unpurified populations of PBMC obtained from the buffy coats of normal volunteers were grown in suspension culture in the absence or presence of erythropoietin. A profile of surface CD48 expression permitted a flow cytometric identification of erythropoietin responsive populations at various stages of their maturation. In the absence of erythropoietin (EPO) supplemented media, the CD48- cells represented <5% of the total population of PBMC remaining in culture. In cultures supplemented with 1 U/mL EPO, the mean percentage of CD48- cells increased to 34.7 + 14.9% (p < 0.01) after 14 days in culture. Coordinated CD34 and CD71 (transferrin receptor) expression, morphology, gamma-globin transcription, and colony formation in methylcellulose were observed during the 14-day culture period. Flow cytometric monitoring of bulk cultured PBMC provides a simple and reliable means for the prospective or real-time study of human erythropoiesis.

Eto2/MTG16 and MTGR1 are heteromeric corepressors of the TAL1/SCL transcription factor in murine erythroid progenitors

Energy Technology Data Exchange (ETDEWEB)

Cai, Ying; Xu, Zhixiong; Xie, Jingping [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Ham, Amy-Joan L. [Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Koury, Mark J. [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Tennessee Valley VA Healthcare System, Nashville, TN 37212 (United States); Hiebert, Scott W. [Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Brandt, Stephen J., E-mail: stephen.brandt@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Tennessee Valley VA Healthcare System, Nashville, TN 37212 (United States)

2009-12-11

The TAL1 (or SCL) gene, originally discovered through its involvement by a chromosomal translocation in T-cell acute lymphoblastic leukemia, encodes a basic helix-loop-helix (bHLH) transcription factor essential for hematopoietic and vascular development. To identify its interaction partners, we expressed a tandem epitope-tagged protein in murine erythroleukemia (MEL) cells and characterized affinity-purified Tal1-containing complexes by liquid chromatography-tandem mass spectrometry analysis. In addition to known interacting proteins, two proteins related to the Eight-Twenty-One (ETO) corepressor, Eto2/Mtg16 and Mtgr1, were identified from the peptide fragments analyzed. Tal1 interaction with Eto2 and Mtgr1 was verified by coimmunoprecipitation analysis in Tal1, Eto2-, and Mtgr1-transfected COS-7 cells, MEL cells expressing V5 epitope-tagged Tal1 protein, and non-transfected MEL cells. Mapping analysis with Gal4 fusion proteins demonstrated a requirement for the bHLH domain of Tal1 and TAF110 domain of Eto2 for their interaction, and transient transfection and glutathione S-transferase pull-down analysis showed that Mtgr1 and Eto2 enhanced the other's association with Tal1. Enforced expression of Eto2 in differentiating MEL cells inhibited the promoter of the Protein 4.2 (P4.2) gene, a direct target of TAL1 in erythroid progenitors, and transduction of Eto2 and Mtgr1 augmented Tal1-mediated gene repression. Finally, chromatin immunoprecipitation analysis revealed that Eto2 occupancy of the P4.2 promoter in MEL cells decreased with differentiation, in parallel with a decline in Eto2 protein abundance. These results identify Eto2 and Mtgr1 as authentic interaction partners of Tal1 and suggest they act as heteromeric corepressors of this bHLH transcription factor during erythroid differentiation.

Eto2/MTG16 and MTGR1 are heteromeric corepressors of the TAL1/SCL transcription factor in murine erythroid progenitors

International Nuclear Information System (INIS)

Cai, Ying; Xu, Zhixiong; Xie, Jingping; Ham, Amy-Joan L.; Koury, Mark J.; Hiebert, Scott W.; Brandt, Stephen J.

2009-01-01

The TAL1 (or SCL) gene, originally discovered through its involvement by a chromosomal translocation in T-cell acute lymphoblastic leukemia, encodes a basic helix-loop-helix (bHLH) transcription factor essential for hematopoietic and vascular development. To identify its interaction partners, we expressed a tandem epitope-tagged protein in murine erythroleukemia (MEL) cells and characterized affinity-purified Tal1-containing complexes by liquid chromatography-tandem mass spectrometry analysis. In addition to known interacting proteins, two proteins related to the Eight-Twenty-One (ETO) corepressor, Eto2/Mtg16 and Mtgr1, were identified from the peptide fragments analyzed. Tal1 interaction with Eto2 and Mtgr1 was verified by coimmunoprecipitation analysis in Tal1, Eto2-, and Mtgr1-transfected COS-7 cells, MEL cells expressing V5 epitope-tagged Tal1 protein, and non-transfected MEL cells. Mapping analysis with Gal4 fusion proteins demonstrated a requirement for the bHLH domain of Tal1 and TAF110 domain of Eto2 for their interaction, and transient transfection and glutathione S-transferase pull-down analysis showed that Mtgr1 and Eto2 enhanced the other's association with Tal1. Enforced expression of Eto2 in differentiating MEL cells inhibited the promoter of the Protein 4.2 (P4.2) gene, a direct target of TAL1 in erythroid progenitors, and transduction of Eto2 and Mtgr1 augmented Tal1-mediated gene repression. Finally, chromatin immunoprecipitation analysis revealed that Eto2 occupancy of the P4.2 promoter in MEL cells decreased with differentiation, in parallel with a decline in Eto2 protein abundance. These results identify Eto2 and Mtgr1 as authentic interaction partners of Tal1 and suggest they act as heteromeric corepressors of this bHLH transcription factor during erythroid differentiation.

Effects of low-level (1.0 R) x-irradiation on the erythroid response of the rat bone marrow

International Nuclear Information System (INIS)

Gong, J.K.; Glomski, C.A.; Frederiksen, N.L.; Lawson, A.J.; Daley, J.P.

1976-01-01

The levels of normoblasts in the bone marrow of six groups of female Sprague--Dawley rats previously exposed to a 1.0 R dose of x rays were compared with those in sham-exposed animals at intervals from 14 hr to 10 weeks postirradiation. Four parameters were analyzed, the percentage of normoblasts in Wright's Giemsa stained marrow smears, and the number of erythroid precursors per milligram of isolated marrow sample, per whole femur, and per entire skeleton. The studies were based on marrow examinations and on 59 Fe tracer data. At all intervals except the earliest, [14 hr], significant elevations in the percentage of normoblasts were found in the bone marrow. In addition, at 6 and 10 weeks postirradiation increases were found in the number of normoblasts in the isolated marrow samples, whole femurs, and total skeletons. When compared 81 hr after phlebotomy, subnormal increases in normoblast levels were found in all four parameters of the irradiated subjects. The results suggest that x irradiation at this dose level can induce an abnormal marrow function manifested by an elevated number of normoblasts and, after phlebotomy, by a subnormal proliferation of the erythroid precursors

Enhanced inhibition of parvovirus B19 replication by cidofovir in extendedly exposed erythroid progenitor cells.

Science.gov (United States)

Bonvicini, Francesca; Bua, Gloria; Manaresi, Elisabetta; Gallinella, Giorgio

2016-07-15

Human parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying haematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500μM (viral inhibition 82%) and in serially infected EPCs cultures with passage of the virus progeny, constantly under drug exposure (viral inhibition 99%). In addition, a potent inhibitory effect against B19V (viral inhibition 92%) was assessed in a short-term infection of EPCs treated with CDV 500μM 1day before viral infection. In the evaluated experimental conditions, the enhanced effect of CDV against B19V might be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population. Copyright © 2016 Elsevier B.V. All rights reserved.

[Update on the biology of heme synthesis in erythroid cells].

Science.gov (United States)

Fujiwara, Tohru; Harigae, Hideo

2015-02-01

Heme is a prosthetic group of hemoproteins playing important roles in oxygen transport, detoxification, circadian rhythm, microRNA processing, regulation of transcription, and translation. The majority of heme (-85%) is synthesized in red blood cells mainly for hemoglobin production, whereas hepatocytes account for most of the rest, functioning primarily in the synthesis of cytochrome P450 enzymes and mitochondrial respiratory enzymes. Thus, failure of heme biosynthesis causes severe inherited or acquired disorders in humans, including porphyria and sideroblastic anemia. The heme biosynthetic pathway is composed of eight enzymes that work in either mitochondria or the cytoplasm, which have been extensively researched and frequently reviewed. On the other hand, the mechanisms governing transport and intracellular trafficking of heme intermediates, as well as their potential links to human diseases, are poorly understood. Herein, we focus on recent understanding of the heme biosynthetic pathway and on human disorders due to defective heme synthesis in erythroid cells, such as X-linked sideroblastic anemia and erythropoietic protoporphyria.

Synergistic Effect of Sodium Butyrate and Thalidomide in the Induction of Fetal Hemoglobin Expression in Erythroid Progenitors Derived from Cord Blood CD133 + Cells

Directory of Open Access Journals (Sweden)

Ali Dehghanifard

2012-07-01

Full Text Available Background: The use of drugs with the ability to induce production of fetal hemoglobin as a novel therapeutic approach in treating β-Hemoglobinopathies is considered. γ-globin gene expression inducer drugs including sodium butyrate and thalidomide can reduce additional α-globin chains accumulation in erythroid precursors. Materials and Methods: In this experimental study, MACS kit was used to isolate CD133+ cells of umbilical cord blood. Further, the effect of two drugs of thalidomide and sodium butyrate were separately and combined studied on the induction of quantitative expression of β-globin and γ-globin genes in erythroid precursor cells derived from CD133+ stem cells in-vitro. For this purpose, the technique SYBR green Real-time PCR was used.Results: Flow cytometry results showed that approximately 95% of purified cells were CD133+. Real-time PCR results also showed the increased levels of γ-globin mRNA in the cell groups treated with thalidomide, sodium butyrate and combination of drugs as 2.6 and 1.2 and 3.5 times respectively, and for β-globin gene, it is respectively 1.4 and 1.3 and 1.6 times compared with the control group (p<0.05.Conclusion: The study results showed that the mentioned drug combination can act as a pharmaceutical composition affecting the induction of fetal hemoglobin expression in erythroid precursor cells derived from CD133 + cells.

Radial-velocity variations in Alpha Ori, Alpha Sco, and Alpha Her

International Nuclear Information System (INIS)

Smith, M.A.; Patten, B.M.; Goldberg, L.

1989-01-01

Radial-velocity observations of Alpha Ori, Alpha Sco A, and Alpha Her A are used to study radial-velocity periodicities in M supergiants. The data refer to several metallic lines in the H-alpha region and to H-alpha itself. It is shown that Alpha Ori and Alpha Sco A have cycle lengths of about 1 yr and semiamplitudes of 2 km/s. It is suggested that many semiregular red supergiant varibles such as Alpha Ori may be heading toward chaos. All three stars show short-term stochastic flucutations with an amplitude of 1-2 km/s. It is found that the long-term variability of H-alpha velocities may be a consequence of intermittent failed ejections. 58 refs

Sustained enhancement of OCTN1 transporter expression in association with hydroxyurea induced gamma-globin expression in erythroid progenitors

OpenAIRE

Walker, Aisha L.; Ofori-Acquah, Solomon

2016-01-01

The clinical benefits of hydroxyurea treatment in patients with sickle cell disease (SCD) are due largely to increased gamma-globin expression. However, mechanisms that control gamma-globin expression by hydroxyurea in erythroid progenitors are incompletely understood. Here, we investigated the role of two hydroxyurea transporters, urea transporter B (UTB) and organic cation/carnitine transporter 1 (OCTN1), in this process. Endogenous expression of both transporters peaked towards the end of ...

Heme and erythropoieis: more than a structural role.

Science.gov (United States)

Chiabrando, Deborah; Mercurio, Sonia; Tolosano, Emanuela

2014-06-01

Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated with that of alpha (α) and beta (β)-globin, resulting in the production of hemoglobin, a tetramer of 2α- and 2β-globin chains, and heme as the prosthetic group. Heme is not only the structural component of hemoglobin, but it plays multiple regulatory roles during the differentiation of erythroid precursors since it controls its own synthesis and regulates the expression of several erythroid-specific genes. Heme is synthesized in developing erythroid progenitors by the stage of proerythroblast, through a series of eight enzymatic reactions divided between mitochondria and cytosol. Defects of heme synthesis in the erythroid lineage result in sideroblastic anemias, characterized by microcytic anemia associated to mitochondrial iron overload, or in erythropoietic porphyrias, characterized by porphyrin deposition in erythroid cells. Here, we focus on the heme biosynthetic pathway and on human erythroid disorders due to defective heme synthesis. The regulatory role of heme during erythroid differentiation is discussed as well as the heme-mediated regulatory mechanisms that allow the orchestration of the adaptive cell response to heme deficiency. Copyright© Ferrata Storti Foundation.

Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

DEFF Research Database (Denmark)

Järås, Marcus; Johnels, Petra; Agerstam, Helena

2009-01-01

OBJECTIVE: The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. MATERIALS AND METHODS: We investigated...... and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. RESULTS: Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells...... and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under...

Diagnostics of red-shifted H-alpha line emission from a C-class flare with full non-LTE radiative and hydrodynamic approach

Science.gov (United States)

Druett, M. K.; Zharkova, V. V.; Scullion, E.; Zharkov, S.; Matthews, S. A.

2016-12-01

We analyse H-alpha line profiles with strong redshifts during the C1.8 flare on 1st July 2012 obtained from the Swedish Solar Telescope (SST) closely resembling the previous observations (Wuelser and Marti, 1989). The flare has a magnetic field configuration with two levels of loop structures. The kernels with red shifts are observed in one of the H-alpha ribbons in the south-west location formed after the main impulse recorded in the north-east. The locations of H-alpha kernels with red shifts reveal close temporal and spatial correlation with weaker HXR signatures and coincide with the locations of coronal jets observed with AIA/SDO. For interpretation we apply a revised 1D hydrodynamic and non-LTE (NLTE) radiative model for 5 level plus continuum model hydrogen atom (Druett & Zharkova, 2016) considering radiative, thermal and non-thermal excitation and ionisation by beam electrons with the updated beam densities (Zharkova & Dobranskis, 2016) and analytical excitation/ionisation rates (Zharkova& Kobylinskijj, 1993). We find the simultaneous solutions of steady state and radiative transfer equations in all optically-thick lines and continua. The electron and ion temperatures, ambient density and macrovelocity of the ambient plasma are derived from a 1D hydrodynamic model with initial condition of the pre-flaring photosphere for the two fluid ambient plasma heated by beam electrons (Zharkova & Zharkov, 2007). We simulate distributions over precipitation depth of ionisation and departure coefficients for all the hydrogen atom transitions including the deviation of ionisation from Saha equation affected by non-thermal electron beams. We show that in the very first seconds after the beam onset Balmer line profiles are sensitive to the effect of beam electrons. The combination of the additional ionisation caused by beam electrons leading to a very strong Stark effect in Balmer lines with the hydrodynamic heating and formation of a low temperature shock in the

Electron diffraction study of {alpha}-AlMnSi crystals including non-crystallographic axes

Energy Technology Data Exchange (ETDEWEB)

Song, G.L.; Bursill, L.A.

1997-06-01

The structure of crystalline {alpha}-AlMnSi is examined by electron diffraction. Six distinct zone axes are examined, including both normal crystallographic and non-crystallographic zones axes, allowing the space group symmetry to be studied. Electron diffraction patterns characteristic of Pm3-bar were obtained for thicker specimens. However, for very thin specimens, as used for HRTEM imaging, the electron diffraction patterns were characteristic of Im3-bar space group symmetry. The structural basis of the Pm3-bar to Im3-bar transformation may be understood in terms of an analysis of the icosahedral structural elements located at the corners and body-centers of the cubic unit cell. A method for indexing the non-crystallographic zone axis diffraction patterns is described. An electron diffraction pattern of the 5-fold axis of the quasicrystalline phase i-AlMnSi is also included; this is compared with the experimental results and calculations for the [0{tau}1] axis of Pm3-bar and Im3-bar crystalline phases. 26 refs., 4 tabs., 7 figs.

Alpha particle analysis using PEARLS spectrometry

International Nuclear Information System (INIS)

McKlveen, J.W.; Klingler, G.W.; McDowell, W.J.; Case, G.N.

1984-01-01

Alpha particle assay by conventional plate-counting methods is difficult because chemical separation, tracer techniques, and/or self-absorption losses in the final sample may cause either non-reproducible results or create unacceptable errors. PEARLS (Photon-Electron Rejecting Alpha Liquid Scintillation) Spectrometry is an attractive alternative since radionuclides may be extracted into a scintillator in which there would be no self-absorption or geometry problems and in which up to 100% chemical recovery and counting efficiency is possible. Sample preparation may include extraction of the alpha emitter of interest by a specific organic-phase-soluble compound directly into the liquid scintillator. Detection electronics use energy and pulse-shape discrimination to provide discrete alpha spectra and virtual absence of beta and gamma backgrounds. Backgrounds on the order of 0.01 cpm are readily achievable. Accuracy and reproducibility are typically in the 100 +-1% range. Specific procedures have been developed for gross alpha, uranium, plutonium, thorium, and polonium assay. This paper will review liquid scintillation alpha counting methods and reference some of the specific applications. 8 refs., 1 fig

Salivary Alpha-Amylase Correlates with Subjective Heat Pain Perception.

Science.gov (United States)

Wittwer, Amrei; Krummenacher, Peter; La Marca, Roberto; Ehlert, Ulrike; Folkers, Gerd

2016-06-01

Self-reports of pain are important for an adequate therapy. This is a problem with patients and infants who are restricted in providing an accurate verbal estimation of their pain. Reliable, real-time, economical, and non-invasive physiological correlates might contribute to a more comprehensive description of pain. Salivary alpha-amylase constitutes one candidate biomarker, which reflects predominantly sympathetic nervous system alterations under stressful conditions and can be measured non-invasively. The current study investigated the effects of acute heat pain on salivary alpha-amylase activity. Heat pain tolerance was measured on the non-dominant forearm. Participants completed visual analog scales on pain intensity and unpleasantness. Saliva samples were collected directly after pain induction. Twenty-seven healthy volunteers were recruited for this study. While salivary alpha-amylase levels correlated positively with intensity and unpleasantness ratings in response to acute heat pain stimuli, there was no corresponding association with pain tolerance. Salivary alpha-amylase is suggested to be an indirect physiologic correlate of subjective heat pain perception. Future studies should address the role of salivary alpha-amylase depending on the origin of pain, the concerned tissue, and other pain assessment methods. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Protolytic properties and complexation of DL-alpha-alanine and DL-alpha-valine and their dipeptides in aqueous and micellar solutions of surfactants

NARCIS (Netherlands)

Chernyshova, O. S.; Boychenko, Oleksandr; Abdulrahman, H.; Loginova, L. P.

In this work we investigated the effect of the micellar media of anionic (sodium dodecylsulfate, SDS), cationic (cetylpiridinium chloride, CPC) and non-ionic (Brij-35) surfactants on the protolytic properties of amino acids DL-alpha-alanine, DL-alpha-valine and dipeptides

alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.

Science.gov (United States)

Livingstone, Phil D; Srinivasan, Jayaraman; Kew, James N C; Dawson, Lee A; Gotti, Cecilia; Moretti, Milena; Shoaib, Mohammed; Wonnacott, Susan

2009-02-01

Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta2* selective) elicited [(3)H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta2* nAChRs. However, insensitivity of nicotine-evoked [(3)H]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha6beta2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [(3)H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta2* and alpha7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.

alpha-Globin genes: thalassemic and structural alterations in a Brazilian population

Directory of Open Access Journals (Sweden)

M.R.S.C. Wenning

2000-09-01

Full Text Available Seven unrelated patients with hemoglobin (Hb H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, aaNcoI, alphaIcalpha and alphaTSaudialpha was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(aaT]. Among the 27 patients with structural alterations, 15 (of Italian descent had Hb Hasharon (alpha47Asp->His associated with the -alpha3.7 deletion, 4 (of Italian descent were heterozygous for Hb J-Rovigo (alpha53Ala->Asp, 4 (3 Blacks and 1 Caucasian were heterozygous for Hb Stanleyville-II (alpha78Asn->Lys associated with the alpha+-thalassemia, 1 (Black was heterozygous for Hb G-Pest (alpha74Asp->Asn, 1 (Caucasian was heterozygous for Hb Kurosaki (alpha7Lys->Glu, 1 (Caucasian was heterozygous for Hb Westmead (alpha122His->Gln, and 1 (Caucasian was the carrier of a novel silent variant (Hb Campinas, alpha26Ala->Val. Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.

Calpain expression and activity during lens fiber cell differentiation.

Science.gov (United States)

De Maria, Alicia; Shi, Yanrong; Kumar, Nalin M; Bassnett, Steven

2009-05-15

In animal models, the dysregulated activity of calcium-activated proteases, calpains, contributes directly to cataract formation. However, the physiological role of calpains in the healthy lens is not well defined. In this study, we examined the expression pattern of calpains in the mouse lens. Real time PCR and Western blotting data indicated that calpain 1, 2, 3, and 7 were expressed in lens fiber cells. Using controlled lysis, depth-dependent expression profiles for each calpain were obtained. These indicated that, unlike calpain 1, 2, and 7, which were most abundant in cells near the lens surface, calpain 3 expression was strongest in the deep cortical region of the lens. We detected calpain activities in vitro and showed that calpains were active in vivo by microinjecting fluorogenic calpain substrates into cortical fiber cells. To identify endogenous calpain substrates, membrane/cytoskeleton preparations were treated with recombinant calpain, and cleaved products were identified by two-dimensional difference electrophoresis/mass spectrometry. Among the calpain substrates identified by this approach was alphaII-spectrin. An antibody that specifically recognized calpain-cleaved spectrin was used to demonstrate that spectrin is cleaved in vivo, late in fiber cell differentiation, at or about the time that lens organelles are degraded. The generation of the calpain-specific spectrin cleavage product was not observed in lens tissue from calpain 3-null mice, indicating that calpain 3 is uniquely activated during lens fiber differentiation. Our data suggest a role for calpains in the remodeling of the membrane cytoskeleton that occurs with fiber cell maturation.

Protein kinase C alpha controls erythropoietin receptor signaling.

NARCIS (Netherlands)

M.M. von Lindern (Marieke); M. Parren-Van Amelsvoort (Martine); T.B. van Dijk (Thamar); E. Deiner; B. Löwenberg (Bob); E. van den Akker (Emile); S. van Emst-de Vries (Sjenet); P.J. Willems (Patrick); H. Beug (Hartmut)

2000-01-01

textabstractProtein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We

Reggeon field theory for alpha (0)>1

CERN Document Server

Amati, Daniele; Le Bellac, M; Marchesini, G

1976-01-01

The asymptotic behaviour of the scattering amplitude is obtained when the pomeron has intercept alpha (0) larger than one. The reggeon field theory is studied by introducing a lattice in impact parameter space. Use is made of a previous result showing that asymptotically the dynamics is controlled at each lattice site ( alpha '=0 case) by a two-level structure. This leads to a non-Hermitean Hamiltonian expressed in terms of spin operators in which the intersite interaction term is proportional to the pomeron slope alpha '. The spectrum of such a system shows a degenerate ground state for alpha (0)> alpha /sub c/>or approximately=1 and a continuum with vanishing excitation gap at alpha (0)= alpha /sub c/. The vacuum does not change structure at the critical value. The criticality is shown by an order parameter which is given by the matrix element of a field operator between the vacuum and its degenerate companion. The nature of this critical phenomenon is better understood by continuously transforming the Hami...

Delayed Mesoderm and Erythroid Differentiation of Murine Embryonic Stem Cells in the Absence of the Transcriptional Regulator FUBP1

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Josephine Wesely

2017-01-01

Full Text Available The transcriptional regulator far upstream binding protein 1 (FUBP1 is essential for fetal and adult hematopoietic stem cell (HSC self-renewal, and the constitutive absence of FUBP1 activity during early development leads to embryonic lethality in homozygous mutant mice. To investigate the role of FUBP1 in murine embryonic stem cells (ESCs and in particular during differentiation into hematopoietic lineages, we generated Fubp1 knockout (KO ESC clones using CRISPR/Cas9 technology. Although FUBP1 is expressed in undifferentiated ESCs and during spontaneous differentiation following aggregation into embryoid bodies (EBs, absence of FUBP1 did not affect ESC maintenance. Interestingly, we observed a delayed differentiation of FUBP1-deficient ESCs into the mesoderm germ layer, as indicated by impaired expression of several mesoderm markers including Brachyury at an early time point of ESC differentiation upon aggregation to EBs. Coculture experiments with OP9 cells in the presence of erythropoietin revealed a diminished differentiation capacity of Fubp1 KO ESCs into the erythroid lineage. Our data showed that FUBP1 is important for the onset of mesoderm differentiation and maturation of hematopoietic progenitor cells into the erythroid lineage, a finding that is supported by the phenotype of FUBP1-deficient mice.

Biodegradable films containing {alpha}-tocopherol/{beta}-cyclodextrin complex; Filmes biodegradaveis contendo {alpha}-tocoferol complexado em {beta}-ciclodextrina

Energy Technology Data Exchange (ETDEWEB)

Motta, Caroline; Martelli, Silvia M.; Soldi, Valdir, E-mail: vsoldi@qmc.ufsc.br [Lab. de Materiais Polimericos (POLIMAT), Dept. de Quimica, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Barreto, Pedro L.M. [Lab. de Reologia (REOLAB), Dept. de Ciencia e Tecnologia de Alimentos, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil)

2011-07-01

The growing environmental concern about pollution and the need to reduce dependence of plastic industry in relation to non-renewable resources has increased the interest of both researchers and industry in the use of biopolymers. In this work {beta}-cyclodextrin/{alpha}-tocopherol complexes were prepared and characterized. In order to obtain polymeric active biofilms, the {beta}-cyclodextrin/{alpha}-tocopherol complex was incorporated into a polymeric matrix of carboxymethylcellulose. The {beta}-cyclodextrin/{alpha}-tocopherol complex was characterized through of X-ray diffraction and thermogravimetric analysis. The physicochemical properties of the films incorporated with the complex were evaluated through mechanical and colorimetric analysis and moisture sorption isotherm. (author)

User's guide for SLWDN9, a code for calculating flux-surfaced-averaging of alpha densities, currents, and heating in non-circular tokamaks

International Nuclear Information System (INIS)

Hively, L.M.; Miley, G.M.

1980-03-01

The code calculates flux-surfaced-averaged values of alpha density, current, and electron/ion heating profiles in realistic, non-circular tokamak plasmas. The code is written in FORTRAN and execute on the CRAY-1 machine at the Magnetic Fusion Energy Computer Center

Role of the mitochondrial amino acid pool in the differential sensitivity of erythroid and myeloid cells to chloramphenicol

International Nuclear Information System (INIS)

Abou-Khalil, S.; Abou-Khalil, W.H.; Whitney, P.L.; Yunis, A.A.

1986-01-01

Previous studies in the authors laboratory have suggested that mitochondrial amino acid (AA) pool is involved in the differential sensitivity of erythroid and myeloid cells to chloramphenicol (CAP). The present study examines the role of AA pool by analysis of its composition and testing the effects of its major components. The endogenous AA composition of isolated mitochondria protein was determined using a JEOL 5AH AA analyzer. L-( 14 C) leucine incorporation into mitochondrial protein was used to measure the rate of protein synthesis. Analysis of the endogenous pool in erythroleukemia (EM) and chloroleukemia (CM) mitochrondria showed similar total amount of AAs. However, some AAs were present in significantly higher or lower quantity within EM and CM (i.e. EM had about 2-fold higher glycine content). When compensating for each low AA addition of that particular acid to the reaction medium, only glycine and serine had significant effect. Thus, the addition of increasing concentrations of glycine or serine enhanced the sensitivity to CAP from 14% to 49-51% in CM but not in EM. Other AAs gave little or no effect. Since glycine is one of the first reactants in heme biosynthesis within mitochondria and is interconvertible with serine, it would appear that erythroid cells sensitivity to CAP is determined by the mitochondrial glycine-serine pool and may be somehow related of the pathway to heme biosynthesis in these cells

Non-specific interference of certain components of tissue culture media with the radioimmunoassay of rat alpha-foetoprotein

International Nuclear Information System (INIS)

Dambuyant, C.; Sizaret, Ph.

1975-01-01

Interferences of 'Williams' tissue culture medium used for cultivating rat hepatocytes upon rat alpha-foetoprotein (AFP) radioimmunoassay have been investigated. They are not due to foetal calf serum proteins which are added as growth factor and can be abolished by dialysis which appears to be necessary for the distinction between AFP non-producer and low-producer cell lines. Of the three major groups of non-mineral components examined, amino acid solution played a major role. When individual amino acids were examined using the double antibody technique, arginine was found to interfere predominantly; its dose-response curve was parallel to that of rat AFP which confirmed that an immunological identity between two substances cannot be established on the basis of parallelism as the only criterion

Protein kinase C alpha controls erythropoietin receptor signaling

NARCIS (Netherlands)

von Lindern, M.; Parren-van Amelsvoort, M.; van Dijk, T.; Deiner, E.; van den Akker, E.; van Emst-de Vries, S.; Willems, P.; Beug, H.; Löwenberg, B.

2000-01-01

Protein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We analyzed the effect of PKC inhibitors

Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

International Nuclear Information System (INIS)

McMahon, Laura W.; Zhang Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

2009-01-01

Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellular hypersensitivity to DNA interstrand cross-linking agents. An increased number of chromosomal aberrations were observed and, following treatment with a DNA interstrand cross-linking agent, mitomycin C, cells showed decreased cell growth and survival and decreased formation of damage-induced αIISp and XPF nuclear foci. Thus depletion of αIISp in normal cells leads to a number of defects observed in FA cells, such as chromosome instability and a deficiency in cross-link repair.

The effect of ceruloplasmin on erythroid precursor cells in the marrow of irradiated mice

International Nuclear Information System (INIS)

Suda, Toshio; Miura, Yasusada; Ozawa, Keiya; Yamada, Masaaki.

1981-01-01

The effect of ceruloplasmine on erythroid colony forming unit (CFU-e) of irradiated mice was investigated. Whole body #betta# ray irradiation of 100rad decreased the number of CFU-e from 154 to 40 per 4 * 10 4 myeloid nucleated cells. When human #betta#-globulin of 1 mg/kg or ceruloplasmin of 1 mg/kg was administrated immediately after irradiation, the number of CFU-e increased to that of more than normal and normal value in 2 days, respectively. In the case where ceruloplasmin was begun to administrated 7 days before irradiation, though the CFU-e number decreased from 144 to 44, the number increased to 317 after 2 days, and gradually decreased to the normal value by 16 days after irradiation. (Nakanishi, T)

Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse.

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Sreoshi Chatterjee

Full Text Available Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA in C57BL/6 mice after 5-6 weeks. Using the double in vivo biotinylation (DIB technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71 monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline. Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA.

A comparative ultrastructural and molecular biological study on Chlamydia psittaci infection in alpha-1 antitrypsin deficiency and non-alpha-1 antitrypsin deficiency emphysema versus lung tissue of patients with hamartochondroma

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Mogilevski Grigori

2004-09-01

Full Text Available Abstract Background Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients. Methods Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6 or non-alpha-1 antitrypsin deficiency emphysema (n = 34 or wedge resection for hamartochondroma (n = 14 were examined by transmission electron microscopy and PCR. Results In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR. Conclusions These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process

Comparison of different methods for erythroid differentiation in the K562 cell line.

Science.gov (United States)

Shariati, Laleh; Modaress, Mehran; Khanahmad, Hossein; Hejazi, Zahra; Tabatabaiefar, Mohammad Amin; Salehi, Mansoor; Modarressi, Mohammad Hossein

2016-08-01

To compare methods for erythroid differentiation of K562 cells that will be promising in the treatment of beta-thalassemia by inducing γ-globin synthesis. Cells were treated separately with: RPMI 1640 medium without glutamine, RPMI 1640 medium without glutamine supplemented with 1 mM sodium butyrate, RPMI 1640 medium supplemented with 1 mM sodium butyrate, 25 µg cisplatin/ml, 0.1 µg cytosine arabinoside/ml. The highest differentiation (84 %) with minimum toxicity was obtained with cisplatin at 15 µg /ml. Real-time RT-PCR showed that expression of the γ-globin gene was significantly higher in the cells differentiated with cisplatin compared to undifferentiated cells (P < 0.001). Cisplatin is useful in the experimental therapy of ß-globin gene defects and can be considered for examining the basic mechanism of γ-reactivation.

Decontamination of alpha contaminated metallic waste by cerium IV redox process

International Nuclear Information System (INIS)

Shah, J.G.; Dhami, P.S.; Gandhi, P.M.; Wattal, P.K.

2012-01-01

Decontamination of alpha contaminated metallic waste is an important aspect in the management of waste generated during dismantling and decommissioning of nuclear facilities. Present work on cerium redox process targets decontamination of alpha contaminated metallic waste till it qualifies for the non alpha waste category for disposal in near surface disposal facility. Recovery of the alpha radio nuclides and cerium from aqueous secondary waste streams was also studied deploying solvent extraction process and established. The alpha-lean secondary waste stream has been immobilised in cement based matrix for final disposal. (author)

Erythroid Differentiation Regulator 1 as a Novel Biomarker for Hair Loss Disorders.

Science.gov (United States)

Woo, Yu Ri; Hwang, Sewon; Jeong, Seo Won; Cho, Dae Ho; Park, Hyun Jeong

2017-02-03

Erythroid differentiation regulator 1 (Erdr1) is known to be involved in the inflammatory process via regulating the immune system in many cutaneous disorders, such as psoriasis and rosacea. However, the role of Erdr1 in various hair loss disorders remains unclear. The aim of this study was to investigate the putative role of Erdr1 in alopecias. Skin samples from 21 patients with hair loss disorders and five control subjects were retrieved, in order to assess their expression levels of Erdr1. Results revealed that expression of Erdr1 was significantly downregulated in the epidermis and hair follicles of patients with hair loss disorders, when compared to that in the control group. In particular, the expression of Erdr1 was significantly decreased in patients with alopecia areata. We propose that Erdr1 downregulation might be involved in the pathogenesis of hair loss, and could be considered as a novel biomarker for hair loss disorders.

Heme and erythropoieis: more than a structural role

OpenAIRE

Chiabrando, Deborah; Mercurio, Sonia; Tolosano, Emanuela

2014-01-01

Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated with that of alpha (α) and beta (β)-globin, resulting in the production of hemoglobin, a tetramer of 2α- and 2β-globin chains, and heme as the prosthetic group. Heme is not only the structural component of hemoglobin, but it plays multiple regulatory roles during the differentiation of erythroid precursors since it controls its own ...

Case Study - Alpha

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Stephen Leybourne

2016-11-01

Full Text Available This case study was developed from an actual scenario by Dr. Steve Leybourne of Boston University.  The case documents the historical evolution of an organization, and has been used successfully in courses dealing with organizational and cultural change, and the utilization of ‘soft skills’ in project-based management. This is a short case, ideal for classroom use and discussion.  The issues are easily accessible to students, and there is a single wide ranging question that allows for the inclusion of many issues surrounding strategic decision-making, and behavioural and cultural change. Alpha was one of the earlier companies in the USA to invest in large, edge-of-town superstores, with plentiful free vehicle parking, selling food and related household products. Alpha was created in the 1950s as a subsidiary of a major publicly quoted retail group.  It started business by opening a string of very large discount stores in converted industrial and warehouse premises in the south of the United States. In the early days shoppers were offered a limited range of very competitively priced products. When Alpha went public in 1981 it was the fourth largest food retailer in the US, selling an ever-widening range of food and non-food products.  Its success continued to be based on high volume, low margins and good value for money, under the slogan of ‘Alpha Price.’

Far-Infrared and Millimeter Continuum Studies of K-Giants: Alpha Boo and Alpha Tau

Science.gov (United States)

Cohen, Martin; Carbon, Duane F.; Welch, William J.; Lim, Tanya; Forster, James R.; Goorvitch, David; Thigpen, William (Technical Monitor)

2002-01-01

We have imaged two normal, non-coronal, infrared-bright K-giants, alpha Boo and alpha Tau, in the 1.4-millimeter and 2.8-millimeter continuum using BIMA. These stars have been used as important absolute calibrators for several infrared satellites. Our goals are: (1) to probe the structure of their upper photospheres; (2) to establish whether these stars radiate as simple photospheres or possess long-wavelength chromospheres; and (3) to make a connection between millimeter-wave and far-infrared absolute flux calibrations. To accomplish these goals we also present ISO Long Wavelength Spectrometer (LWS) measurements of both these K-giants. The far-infrared and millimeter continuum radiation is produced in the vicinity of the temperature minimum in a Boo and a Tau, offering a direct test of the model photospheres and chromospheres for these two cool giants. We find that current photospheric models predict fluxes in reasonable agreement with those observed for those wavelengths which sample the upper photosphere, namely less than or equal to 170 micrometers in alpha Tau and less than or equal to 125 micrometers in alpha Boo. It is possible that alpha Tau is still radiative as far as 0.9 - 1.4 millimeters. We detect chromospheric radiation from both stars by 2.8 millimeters (by 1.4 millimeters in alpha Boo), and are able to establish useful bounds on the location of the temperature minimum. An attempt to interpret the chromospheric fluxes using the two-component "bifurcation model" proposed by Wiedemann et al. (1994) appears to lead to a significant contradiction.

Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes.

Science.gov (United States)

Benedetto, Alessandro; Lozano-Soldevilla, Diego; VanRullen, Rufin

2017-12-04

Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus-related. Furthermore, stimulus-related responses can be phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase-locked activity can be measured via reverse-correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus-related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low-luminance viewing, the stimulus-related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase-locked part of the alpha response (echo function), but weaker or absent in the induced (non-phase-locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus-related alpha expression. We suggest that stimulus-related alpha activity is crucial in determining human temporal segmentation abilities. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

{alpha}{sub s} from the non-perturbatively renormalised lattice three-gluon vertex

Energy Technology Data Exchange (ETDEWEB)

Alles, B. [Pisa Univ. (Italy). Dipt. di Fisica; Henty, D.S. [Department of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom); Panagopoulos, H. [Department of Natural Sciences, University of Cyprus, CY-1678 Nicosia (Cyprus); Parrinello, C. [Department of Mathematical Sciences, University of Liverpool, Liverpool L69 3BX (United Kingdom); Pittori, C. [L.P.T.H.E., Universite de Paris Sud, Centre d`Orsay, 91405 Orsay (France); Richards, D.G. [Department of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom)]|[Fermilab, P.O. Box 500, Batavia, IL 60510 (United States)

1997-09-29

We compute the running QCD coupling on the lattice by evaluating two-point and three-point off-shell gluon Green`s functions in a fixed gauge and imposing non-perturbative renormalisation conditions on them. Our exploratory study is performed in the quenched approximation at {beta}=6.0 on 16{sup 4} and 24{sup 4} lattices. We show that, for momenta in the range 1.8-2.3 GeV, our coupling runs according to the two-loop asymptotic formula, allowing a precise determination of the corresponding {Lambda} parameter. The role of lattice artifacts and finite-volume effects is carefully analysed and these appear to be under control in the momentum range of interest. Our renormalisation procedure corresponds to a momentum subtraction scheme in continuum field theory, and therefore lattice perturbation theory is not needed in order to match our results to the anti M anti S scheme, thus eliminating a major source of uncertainty in the determination of {alpha} {sub anti} {sub M} {sub anti} {sub S}. Our method can be applied directly to the unquenched case. (orig.). 20 refs.

Expression and function of hypoxia inducible factor-1 alpha in human melanoma under non-hypoxic conditions

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Joshi Sandeep S

2009-11-01

Full Text Available Abstract Background Hypoxia inducible factor-1 alpha (HIF-1α protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP, vertical growth phase (VGP and metastatic (MET melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part of the oxygen-dependent regulation domain in WM1366 and WM9 melanoma cells. Over-expression of HIF-1α and its splice variant in the RGP cell line SbCl2 resulted in a small increase in soft agar colony formation and a large increase in matrigel invasion relative to control transfected cells. Knockdown of HIF-1α expression by siRNA in the MET WM9 melanoma cell line resulted in a large decrease in both soft agar colony formation and matrigel invasion relative to cells treated with non-specific siRNA. There is a high level of ERK1/2 phosphorylation in WM9 cells, indicating an activated Ras-Raf-MEK-ERK1/2 MAPK pathway. Treatment of WM9 cells with 30 μM U0126 MEK inhibitor, decreased ERK1/2 phosphorylation and resulted in a decrease in HIF-1α expression. However, a 24 h treatment with 10 μM U0126 totally eliminated Erk1/2 phosphorylation, but did not change HIF-1alpha levels. Furthermore, siRNA knockdown of MEK siRNA did not change HIF-1alpha levels. Conclusion We speculate that metabolic products of U0126 decrease HIF-1alpha expression through "off target" effects. Overall our data suggest that increased HIF-1α expression under normoxic conditions contributes to some of the malignant phenotypes exhibited by human melanoma cells. The expanded role of HIF-1α in melanoma biology increases

Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis

NARCIS (Netherlands)

von Lindern, M.; Deiner, E. M.; Dolznig, H.; Parren-van Amelsvoort, M.; Hayman, M. J.; Mullner, E. W.; Beug, H.

2001-01-01

Primary erythroid progenitors can be expanded by the synergistic action of erythropoietin (Epo), stem cell factor (SCF) and glucocorticoids. While Epo is required for erythropoiesis in general, glucocorticoids and SCF mainly contribute to stress erythropoiesis in hypoxic mice. This ability of normal

Distribution of alpha3, alpha5 and alpha(v) integrin subunits in mature and immature human oocytes.

Science.gov (United States)

Capmany, G; Mart, M; Santaló, J; Bolton, V N

1998-10-01

The distribution of three integrin subunits, alpha3, alpha5 and alpha(v), in immature and mature human oocytes has been examined using immunofluorescence and confocal microscopy. The results demonstrate that both alpha5 and alpha(v) are present at the germinal vesicle stage, while alpha3 was only detected in oocytes after germinal vesicle breakdown, in metaphase I and II stage oocytes. The cortical concentration of integrin subunits alpha3 and alpha5 is consistent with their localization in the oolemma. In contrast, the homogeneous distribution of alpha(v) throughout the oocyte suggests the existence of cytoplasmic reservoirs of this protein in the oocyte.

Combined zidovudine and interferon-alpha treatment in patients with AIDS-associated Kaposi's sarcoma

NARCIS (Netherlands)

de Wit, R.; Danner, S. A.; Bakker, P. J.; Lange, J. M.; Eeftinck Schattenkerk, J. K.; Veenhof, C. H.

1991-01-01

The effectiveness of addition of interferon-alpha (IFN-alpha) to zidovudine in patients with AIDS-associated Kaposi's sarcoma was assessed in a non-randomized, phase II clinical trial. Twenty-one patients were treated with oral zidovudine (600 mg daily) and IFN-alpha was increased to 18 MU daily for

Natural killer cells recognize friend retrovirus-infected erythroid progenitor cells through NKG2D-RAE-1 interactions In Vivo.

Science.gov (United States)

Ogawa, Tatsuya; Tsuji-Kawahara, Sachiyo; Yuasa, Takae; Kinoshita, Saori; Chikaishi, Tomomi; Takamura, Shiki; Matsumura, Haruo; Seya, Tsukasa; Saga, Toshihiko; Miyazawa, Masaaki

2011-06-01

Natural killer (NK) cells function as early effector cells in the innate immune defense against viral infections and also participate in the regulation of normal and malignant hematopoiesis. NK cell activities have been associated with early clearance of viremia in experimental simian immunodeficiency virus and clinical human immunodeficiency virus type 1 (HIV-1) infections. We have previously shown that NK cells function as major cytotoxic effector cells in vaccine-induced immune protection against Friend virus (FV)-induced leukemia, and NK cell depletion totally abrogates the above protective immunity. However, how NK cells recognize retrovirus-infected cells remains largely unclear. The present study demonstrates a correlation between the expression of the products of retinoic acid early transcript-1 (RAE-1) genes in target cells and their susceptibility to killing by NK cells isolated from FV-infected animals. This killing was abrogated by antibodies blocking the NKG2D receptor in vitro. Further, the expression of RAE-1 proteins on erythroblast surfaces increased early after FV inoculation, and administration of an RAE-1-blocking antibody resulted in increased spleen infectious centers and exaggerated pathology, indicating that FV-infected erythroid cells are recognized by NK cells mainly through the NKG2D-RAE-1 interactions in vivo. Enhanced retroviral replication due to host gene-targeting resulted in markedly increased RAE-1 expression in the absence of massive erythroid cell proliferation, indicating a direct role of retroviral replication in RAE-1 upregulation.

Quantum 1/f noise in non-degerate semiconductors and emission statistics of alpha particles

International Nuclear Information System (INIS)

Kousik, G.S.

1985-01-01

Charged particle scattering is accompanied by the emission of soft photons. Handel's theory of 1/f noise, based on the infrared divergent coupling of the system to the electromagnetic field or other elementary excitations, states that the current associated with a beam of scattered particles will exhibit 1/f noise. The fraction of the particles scattered with an energy loss epsilon to soft photon emission is proportional to 1/epsilon and herein lies the origin of the quantum theory of 1/f noise. The 1/f noise caused by mobility fluctuations in semiconductors is related to the scattering cross section fluctuation given by Handel's theory, through the relaxation time. Chapters Two through Five of this dissertation presents the results of the detailed calculation of mobility fluctuation 1/f noise and Hooge parameter in nondegenerate semiconductors. Numerical results are given for silicon and gallium arsenide. Data obtained from extensive measurements on counting techniques for alpha-particles radioactive decay from a source containing 94 Pu 239 , 95 Am 241 and 96 Cm 244 are presented in Chapters Six and Seven of this dissertation. These data show that the statistics are non-Poissonian for large counting times (of the order of 1000 minutes) contrary to the popular belief that alpha-decay is an example of Poissonian statistics. Measurements of the Allan variance indicated the presence of a slow Lorentzian flicker noise and 1/f noise and the magnitude of the noise for large counting times is considerably larger than that predicted by Poissonian statistics

Lack of co-ordinate expression of the alpha1(I) and alpha1(III) procollagen genes in fibroblast clonal cultures.

Science.gov (United States)

Yamaguchi, Y; Crane, S; Zhou, L; Ochoa, S M; Falanga, V

2000-12-01

Several extracellular matrix genes, most notably alpha1(I) and alpha1(III) procollagen, are reported to be co-ordinately expressed in cultures of dermal fibroblasts. However, it remains unclear whether the expression of these genes is truly co-ordinate or whether it may be the result of averaging the phenotypic expression of different fibroblast subpopulations present within each culture. Objectives To determine by Northern analysis the correlation between alpha1(I) and alpha1(III) procollagen mRNA levels in clonal populations of human dermal fibroblasts. As previously described, clonal cultures were derived from parent strains of human dermal fibroblasts by a microscopically controlled dilution technique and by stimulation of single cells with low oxygen tension in the early phases of clonal growth. In agreement with previous reports, we found that baseline steady-state levels of alpha1(I) procollagen mRNA were co-ordinately regulated with the alpha1(III) procollagen mRNA in 26 parent strains (r = 0. 9003; P ordinate regulation observed in non-clonal cultures, suggesting that these two genes operate under different sets of regulatory controls. This clonal heterogeneity may provide additional flexibility to the process of tissue repair and fibroblast clonal expansion.

The use of the long-range alpha detector (LRAD) for alpha emission surveys at active and inactive firing sites

International Nuclear Information System (INIS)

Mason, C.F.V.; Allander, K.S.; Bounds, J.A.; Garner, S.E.; Walter, K.J.

1994-01-01

Surveys were carried out at five different firing sites at Los Alamos National Laboratory to measure residual alpha emissions in earth contaminated with natural and depleted uranium. This contamination is caused by controlled experimental explosions during testing of the non fissile components of nuclear weapons. Two conclusions were reached: the first is that post shot clearing of the experimental areas is effective at removing contamination and the second is that the diminution of alpha emissions due to aging is small

Fluorescence Quenching of Alpha-Fetoprotein by Gold Nanoparticles: Effect of Dielectric Shell on Non-Radiative Decay

Science.gov (United States)

Zhu, Jian; Li, Jian-Jun; Wang, A.-Qing; Chen, Yu; Zhao, Jun-Wu

2010-09-01

Fluorescence quenching spectrometry was applied to study the interactions between gold colloidal nanoparticles and alpha-fetoprotein (AFP). Experimental results show that the gold nanoparticles can quench the fluorescence emission of adsorbed AFP effectively. Furthermore, the intensity of fluorescence emission peak decreases monotonously with the increasing gold nanoparticles content. A mechanism based on surface plasmon resonance-induced non-radiative decay was investigated to illuminate the effect of a dielectric shell on the fluorescence quenching ability of gold nanoparticles. The calculation results show that the increasing dielectric shell thickness may improve the monochromaticity of fluorescence quenching. However, high energy transfer efficiency can be obtained within a wide wavelength band by coating a thinner dielectric shell.

The determination of $\\alpha_s$ by the ALPHA collaboration

CERN Document Server

Bruno, Mattia

2016-01-01

We review the ALPHA collaboration strategy for obtaining the QCD coupling at high scale. In the three-flavor effective theory it avoids the use of perturbation theory at $\\alpha > 0.2$ and at the same time has the physical scales small compared to the cutoff $1/a$ in all stages of the computation. The result $\\Lambda_\\overline{MS}^{(3)}=332(14)$~MeV is translated to $\\alpha_\\overline{MS}(m_Z)=0.1179(10)(2)$ by use of (high order) perturbative relations between the effective theory couplings at the charm and beauty quark "thresholds". The error of this perturbative step is discussed and estimated as $0.0002$.

Current generation by alpha particles interacting with lower hybrid waves in TOKAMAKS

International Nuclear Information System (INIS)

Belikov, V.S.; Kolesnichenko, Ya.I.; Lisak, M.; Anderson, D.

1990-01-01

The problem of the influence of fusion generated alpha particles on lower-hybrid-wave current drive is examined. Analysis is based on a new equation for the LH-wave-fast ion interaction which is derived by taking into consideration the non-zero value of the longitudinal wave number. The steady-state velocity distribution function for high energy alpha particles is found. The alpha current driven by LH-waves as well as the RF-power absorbed by alpha particle are calculated. (authors)

Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.

Science.gov (United States)

Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S; Martin, Pamela M

2014-05-13

Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Human globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Targeted Gene Deletion Demonstrates that Cell Adhesion MoleculeICAM-4 is Critical for Erythroblastic Island Formation

Energy Technology Data Exchange (ETDEWEB)

Lee, Gloria; Lo, Annie; Short, Sarah A.; Mankelow, Tosti J.; Spring, Frances; Parsons, Stephen F.; Mohandas, Narla; Anstee, David J.; Chasis, Joel Anne

2006-02-15

Erythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule-4 (ICAM-4), animmunoglobulin superfamily member, participates in island formation. Earlier, we identified alpha V integrins as ICAM-4 counter receptors. Since macrophages express alpha V, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knockout mice and developed quantitative, live cell techniques for harvesting intact islands and for reforming islands in vitro. We observed a 47 percent decrease in islands reconstituted from ICAM-4 null marrow compared to wild type. We also found a striking decrease in islands formed in vivo in knockout mice. Further, peptides that block ICAM-4 alpha V adhesion produced a 53-57 percent decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage alpha V functions in island integrity. Importantly, we documented that alpha V integrin is expressed in macrophages isolated from erythro blastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/alpha V adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis.

Measurement of the Strong Coupling Constant $\\alpha_s$ and the Vector and Axial-Vector Spectral Functions in Hadronic Tau Decays

CERN Document Server

Ackerstaff, K; Allison, J; Altekamp, N; Anderson, K J; Anderson, S; Arcelli, S; Asai, S; Ashby, S F; Axen, D A; Azuelos, Georges; Ball, A H; Barberio, E; Barlow, R J; Bartoldus, R; Batley, J Richard; Baumann, S; Bechtluft, J; Behnke, T; Bell, K W; Bella, G; Bentvelsen, Stanislaus Cornelius Maria; Bethke, Siegfried; Betts, S; Biebel, O; Biguzzi, A; Bird, S D; Blobel, Volker; Bloodworth, Ian J; Bobinski, M; Bock, P; Böhme, J; Boutemeur, M; Braibant, S; Bright-Thomas, P G; Brown, R M; Burckhart, Helfried J; Burgard, C; Bürgin, R; Capiluppi, P; Carnegie, R K; Carter, A A; Carter, J R; Chang, C Y; Charlton, D G; Chrisman, D; Ciocca, C; Clarke, P E L; Clay, E; Cohen, I; Conboy, J E; Cooke, O C; Couyoumtzelis, C; Coxe, R L; Cuffiani, M; Dado, S; Dallavalle, G M; Davis, R; De Jong, S; del Pozo, L A; de Roeck, A; Desch, Klaus; Dienes, B; Dixit, M S; Doucet, M; Dubbert, J; Duchovni, E; Duckeck, G; Duerdoth, I P; Eatough, D; Estabrooks, P G; Etzion, E; Evans, H G; Fabbri, Franco Luigi; Fanfani, A; Fanti, M; Faust, A A; Fiedler, F; Fierro, M; Fischer, H M; Fleck, I; Folman, R; Fürtjes, A; Futyan, D I; Gagnon, P; Gary, J W; Gascon, J; Gascon-Shotkin, S M; Geich-Gimbel, C; Geralis, T; Giacomelli, G; Giacomelli, P; Gibson, V; Gibson, W R; Gingrich, D M; Glenzinski, D A; Goldberg, J; Gorn, W; Grandi, C; Gross, E; Grunhaus, Jacob; Gruwé, M; Hanson, G G; Hansroul, M; Hapke, M; Hargrove, C K; Hartmann, C; Hauschild, M; Hawkes, C M; Hawkings, R; Hemingway, Richard J; Herndon, M; Herten, G; Heuer, R D; Hildreth, M D; Hill, J C; Hillier, S J; Hobson, P R; Höcker, Andreas; Homer, R James; Honma, A K; Horváth, D; Hossain, K R; Howard, R; Hüntemeyer, P; Igo-Kemenes, P; Imrie, D C; Ishii, K; Jacob, F R; Jawahery, A; Jeremie, H; Jimack, Martin Paul; Joly, A; Jones, C R; Jovanovic, P; Junk, T R; Karlen, D A; Kartvelishvili, V G; Kawagoe, K; Kawamoto, T; Kayal, P I; Keeler, Richard K; Kellogg, R G; Kennedy, B W; Klier, A; Kluth, S; Kobayashi, T; Kobel, M; Koetke, D S; Kokott, T P; Kolrep, M; Komamiya, S; Kowalewski, R V; Kress, T; Krieger, P; Von Krogh, J; Kyberd, P; Lafferty, G D; Lanske, D; Lauber, J; Lautenschlager, S R; Lawson, I; Layter, J G; Lazic, D; Lee, A M; Lefebvre, E; Lellouch, Daniel; Letts, J; Levinson, L; Liebisch, R; List, B; Littlewood, C; Lloyd, A W; Lloyd, S L; Loebinger, F K; Long, G D; Losty, Michael J; Ludwig, J; Liu, D; Macchiolo, A; MacPherson, A L; Mannelli, M; Marcellini, S; Markopoulos, C; Martin, A J; Martin, J P; Martínez, G; Mashimo, T; Mättig, P; McDonald, W J; McKenna, J A; McKigney, E A; McMahon, T J; McPherson, R A; Meijers, F; Menke, S; Merritt, F S; Mes, H; Meyer, J; Michelini, Aldo; Mihara, S; Mikenberg, G; Miller, D J; Mir, R; Mohr, W; Montanari, A; Mori, T; Nagai, K; Nakamura, I; Neal, H A; Nellen, B; Nisius, R; O'Neale, S W; Oakham, F G; Odorici, F; Ögren, H O; Oreglia, M J; Orito, S; Pálinkás, J; Pásztor, G; Pater, J R; Patrick, G N; Patt, J; Pérez-Ochoa, R; Petzold, S; Pfeifenschneider, P; Pilcher, J E; Pinfold, James L; Plane, D E; Poffenberger, P R; Poli, B; Polok, J; Przybycien, M B; Rembser, C; Rick, Hartmut; Robertson, S; Robins, S A; Rodning, N L; Roney, J M; Roscoe, K; Rossi, A M; Rozen, Y; Runge, K; Runólfsson, O; Rust, D R; Sachs, K; Saeki, T; Sahr, O; Sang, W M; Sarkisyan-Grinbaum, E; Sbarra, C; Schaile, A D; Schaile, O; Scharf, F; Scharff-Hansen, P; Schieck, J; Schmitt, B; Schmitt, S; Schöning, A; Schörner-Sadenius, T; Schröder, M; Schumacher, M; Schwick, C; Scott, W G; Seuster, R; Shears, T G; Shen, B C; Shepherd-Themistocleous, C H; Sherwood, P; Siroli, G P; Sittler, A; Skuja, A; Smith, A M; Snow, G A; Sobie, Randall J; Söldner-Rembold, S; Sproston, M; Stahl, A; Stephens, K; Steuerer, J; Stoll, K; Strom, D; Ströhmer, R; Tafirout, R; Talbot, S D; Tanaka, S; Taras, P; Tarem, S; Teuscher, R; Thiergen, M; Thomson, M A; Von Törne, E; Torrence, E; Towers, S; Trigger, I; Trócsányi, Z L; Tsur, E; Turcot, A S; Turner-Watson, M F; Van Kooten, R; Vannerem, P; Verzocchi, M; Vikas, P; Voss, H; Wäckerle, F; Wagner, A; Ward, C P; Ward, D R; Watkins, P M; Watson, A T; Watson, N K; Wells, P S; Wermes, N; White, J S; Wilson, G W; Wilson, J A; Wyatt, T R; Yamashita, S; Yekutieli, G; Zacek, V; Zer-Zion, D

1999-01-01

The spectral functions of the vector current and the axial-vector current have been measured in hadronic tau decays using the OPAL detector at LEP. Within the framework of the Operator Product Expansion a simultaneous determination of the strong coupling constant alpha_s, the non-perturbative operators of dimension 6 and 8 and of the gluon condensate has been performed. Different perturbative descriptions have been compared to the data. The Contour Improved Fixed Order Perturbation Theory gives alpha_s(mtau**2) = 0.348 +- 0.009 +- 0.019 at the tau-mass scale and alpha_s(mz**2) = 0.1219 +- 0.0010 +- 0.0017 at the Z-mass scale. The values obtained for alpha_s(mz**2) using Fixed Order Perturbation Theory or Renormalon Chain Resummation are 2.3% and 4.1% smaller, respectively. The running of the strong coupling between s_0 ~1.3 GeV**2 and s_0 = mtau**2 has been tested from direct fits to the integrated differential hadronic decay rate R_tau. A test of the saturation of QCD sum rules at the tau-mass scale has been...

In vitro cytotoxicity of alpha conjugates for human pancreatic cancer cell lines

International Nuclear Information System (INIS)

Qu, C.; Li, Y.; Rizvi, M.A.; Allen, B.; Samra, J.; Smith, R.

2003-01-01

Targeted Alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The aim of this study is to demonstrate the cytotoxicity of different alpha conjugates in vitro to human metastatic pancreatic cancer cell lines (CAPAN-1, CFPAN-1 and PANC-1). We are labeling the C595 and J591 (non-specific controls) monoclonal antibodies (Mabs) with 213 Bi were performed according to the standard methods in our laboratory. 213 Bi-C595 is specifically cytotoxic to CAPAN-1, CFPAN-1 and PANC-1cell lines in a concentration-dependent fashion. While non-specific alpha conjugates only killed very small fractions of pancreatic cancer cells. These alpha conjugates might be useful agents for the treatment of micro-metastases in pancreatic cancer patients with over-expression of the targeted receptors

Patterns of cortisol and alpha-amylase reactivity to psychosocial stress in maltreated women.

Science.gov (United States)

Mielock, Alyssa S; Morris, Matthew C; Rao, Uma

2017-02-01

Childhood maltreatment can trigger enduring changes in major stress response systems, particularly in the context of major depressive disorder (MDD). However, the relative impact of maltreatment versus MDD on hypothalamic-pituitary-adrenal axis and sympathetic-adrenal-medullary system stress reactivity is not well understood. This study examined salivary cortisol and alpha-amylase responses to the Trier Social Stress Test (TSST) in 26 maltreated (15 with current MDD) and 26 non-maltreated (17 with current MDD) women. Maltreated women showed greater anticipatory cortisol reactivity during the TSST protocol compared to non-maltreated women. Maltreated women also showed rapid deceleration in cortisol levels. Whereas non-maltreated women showed initial declines in alpha-amylase levels but rapidly increasing alpha-amylase levels during the TSST protocol, maltreated women did not exhibit changes in alpha-amylase levels during the TSST protocol. Contrary to expectation, MDD did not impact cortisol or alpha-amylase responses. The present study is limited by retrospective report of childhood maltreatment, cross-sectional design, and modest sample sizes. These findings suggest that childhood maltreatment plays a greater role driving alterations in cortisol and alpha-amylase stress reactivity than MDD. Understanding the biological embedding of maltreatment is critical for elucidating mechanisms linking these experiences to risk for negative mental and physical health outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Contribution of ankyrin-band 3 complexes to the organization and mechanical properties of the membrane skeleton of human erythrocyte

Energy Technology Data Exchange (ETDEWEB)

Shen, B.W. [Argonne National Lab., IL (United States). Biological and Medical Research Div.

1995-02-01

To understand the role of ankyrin-band 3 complexes in the organization of the spectrin-based membrane skeleton and its contribution to the mechanical properties of human erythrocytes, intact skeletons and single-layered skeleton leaflets were prepared from intact and physically sheared membrane ghosts, expanded in low salt buffer, and examined by transmission electron microscopy. While the structures of intact skeletons and single-layered skeleton leaflets shared many common features, including rigid junctional complexes of spectrin, actin, and band 4.1; short stretches ({approximately}50 {angstrom}) of flexible spectrin filaments; and globular masses of ankyrin-band 3 complexes situated close to the middle of the spectrin filaments, the definition of structural units in the intact skeleton is obscured by the superposition of the two layers. However, the spatial disposition of structural elements can be clearly defined in the images of the single-layered skeleton leaflets. Partially expanded skeletal leaflets contain conglomerates of ankyrin-band 3 complexes arranged in a circular or clove-leaf configuration that straddles multiple strands of thick spectrin cables, presumably reflecting the association of ankyrin-band 3 complexes on neighboring spectrin tetramers as well as the lateral association of the spectrin filaments. Hyperexpansion of the skeleton leaflets led to dissociation of the conglomerates of ankyrin-band 3 complexes, full-extension of the spectrin tetramers, and separation of the individual strands of spectrin tetramers. Clearly defined stands of spectrin tetramers in the hyperexpanded single-layered skeletal leaflets often contained two sets of globular protein masses that divided the spectrin tetramers into three segments of approximately equal length.

Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics.

OpenAIRE

Liebhaber, S A; Kan, Y W

1981-01-01

The alpha-globin polypeptide is encoded by two adjacent genes, alpha 1 and alpha 2. In the normal diploid state (alpha alpha/alpha alpha) all four alpha-globin genes are expressed. Loss or dysfunction of one or more of these genes leads to deficient alpha-globin production and results in alpha-thalassemia. We present a technique to differentially assess the steady-state levels of the alpha 1- and alpha-2-globin messenger RNA (mRNA) transcripts and thus delineate the relative level of expressi...

Delineating SPTAN1 associated phenotypes: from isolated epilepsy to encephalopathy with progressive brain atrophy.

Science.gov (United States)

Syrbe, Steffen; Harms, Frederike L; Parrini, Elena; Montomoli, Martino; Mütze, Ulrike; Helbig, Katherine L; Polster, Tilman; Albrecht, Beate; Bernbeck, Ulrich; van Binsbergen, Ellen; Biskup, Saskia; Burglen, Lydie; Denecke, Jonas; Heron, Bénédicte; Heyne, Henrike O; Hoffmann, Georg F; Hornemann, Frauke; Matsushige, Takeshi; Matsuura, Ryuki; Kato, Mitsuhiro; Korenke, G Christoph; Kuechler, Alma; Lämmer, Constanze; Merkenschlager, Andreas; Mignot, Cyril; Ruf, Susanne; Nakashima, Mitsuko; Saitsu, Hirotomo; Stamberger, Hannah; Pisano, Tiziana; Tohyama, Jun; Weckhuysen, Sarah; Werckx, Wendy; Wickert, Julia; Mari, Francesco; Verbeek, Nienke E; Møller, Rikke S; Koeleman, Bobby; Matsumoto, Naomichi; Dobyns, William B; Battaglia, Domenica; Lemke, Johannes R; Kutsche, Kerstin; Guerrini, Renzo

2017-09-01

De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutations. Using different molecular genetic techniques, we identified 20 patients with a pathogenic or likely pathogenic SPTAN1 variant and reviewed their clinical, genetic and imaging data. SPTAN1 de novo alterations included seven unique missense variants and nine in-frame deletions/duplications of which 12 were novel. The recurrent three-amino acid duplication p.(Asp2303_Leu2305dup) occurred in five patients. Our patient cohort exhibited a broad spectrum of neurodevelopmental phenotypes, comprising six patients with mild to moderate intellectual disability, with or without epilepsy and behavioural disorders, and 14 patients with infantile epileptic encephalopathy, of which 13 had severe neurodevelopmental impairment and four died in early childhood. Imaging studies suggested that the severity of neurological impairment and epilepsy correlates with that of structural abnormalities as well as the mutation type and location. Out of seven patients harbouring mutations outside the α/β spectrin heterodimerization domain, four had normal brain imaging and three exhibited moderately progressive brain and/or cerebellar atrophy. Twelve of 13 patients with mutations located within the spectrin heterodimer contact site exhibited severe and progressive brain, brainstem and cerebellar atrophy, with hypomyelination in most. We used fibroblasts from five patients to study spectrin aggregate formation by Triton-X extraction and immunocytochemistry followed by fluorescence microscopy. αII/βII aggregates and αII spectrin in the insoluble protein fraction were observed in fibroblasts derived from patients with the mutations p.(Glu2207del), p.(Asp2303_Leu2305dup) and p.(Arg2308_Met2309dup

Structural details (kinks and non-alpha conformations) in transmembrane helices are intrahelically determined and can be predicted by sequence pattern descriptors.

Science.gov (United States)

Rigoutsos, Isidore; Riek, Peter; Graham, Robert M; Novotny, Jiri

2003-08-01

One of the promising methods of protein structure prediction involves the use of amino acid sequence-derived patterns. Here we report on the creation of non-degenerate motif descriptors derived through data mining of training sets of residues taken from the transmembrane-spanning segments of polytopic proteins. These residues correspond to short regions in which there is a deviation from the regular alpha-helical character (i.e. pi-helices, 3(10)-helices and kinks). A 'search engine' derived from these motif descriptors correctly identifies, and discriminates amongst instances of the above 'non-canonical' helical motifs contained in the SwissProt/TrEMBL database of protein primary structures. Our results suggest that deviations from alpha-helicity are encoded locally in sequence patterns only about 7-9 residues long and can be determined in silico directly from the amino acid sequence. Delineation of such variations in helical habit is critical to understanding the complex structure-function relationships of polytopic proteins and for drug discovery. The success of our current methodology foretells development of similar prediction tools capable of identifying other structural motifs from sequence alone. The method described here has been implemented and is available on the World Wide Web at http://cbcsrv.watson.ibm.com/Ttkw.html.

Penetration of HEPA filters by alpha recoil aerosols

International Nuclear Information System (INIS)

McDowell, W.J.; Seeley, F.G.; Ryan, M.T.

1976-01-01

The self-scattering of alpha-active substances has long been recognized and is attributed to expulsion of aggregates of atoms from the surface of alpha-active materials by alpha emission recoil energy, and perhaps to further propulsion of these aggregates by subsequent alpha recoils. Workers at the University of Lowell recently predicted that this phenomenon might affect the retention of alpha-active particulate matter by HEPA filters, and found support in experiments with 212 Pb. Tests at Oak Ridge National Laboratory have confirmed that alpha-emitting particulate matter does penetrate high-efficiency filter media, such as that used in HEPA filters, much more effectively than do non-radioactive or beta-gamma active aerosols. Filter retention efficiencies drastically lower than the 99.9 percent quoted for ordinary particulate matter were observed with 212 Pb, 253 Es, and 238 Pu sources, indicating that the phenomenon is common to all of these and probably to all alpha-emitting materials of appropriate half-life. Results with controlled air-flow through filters in series are consistent with the picture of small particles dislodged from the ''massive'' surface of an alpha-active material, and then repeatedly dislodged from positions on the filter fibers by subsequent alpha recoils. The process shows only a small dependence on the physical form of the source material. Oxide dust, nitrate salt, and plated metal all seem to generate the recoil particles effectively. The amount penetrating a series of filters depends on the total amount of activity in the source material, its specific activity, and the length of time of air flow

The alpha-particle irradiator set up at the ISS for radiobiological studies on targeted and non-targeted effects

International Nuclear Information System (INIS)

Esposito, G.; Antonelli, F.; Belli, M.; Campa, A.; Simone, G.; Sorrentino, E.; Tabocchini, M.A.

2008-01-01

In this paper we describe the alpha-particle irradiator that has been set up at the Istituto Superiore di Sanita (ISS) for controlled exposure of cultured mammalian cells. It can be equipped with two different sources, namely 2'4'4'Cm and 2'4'1'Am, allowing irradiation at different dose-rates (typically 1-100 mGy/min). The irradiator has dimensions small enough to be inserted into a standard cell culture incubator to perform irradiation of cultured cells in physiological conditions. The dose uniformity is such that the variations in the irradiation area are less than ± 12% of the average dose value on different irradiation areas up to ∼ 25 cm'2. Moreover, in the framework of the FP6 Euratom Integrated Project Non-targeted effects of ionizing radiation (NOTE), Petri dishes were realized for housing permeable membrane insert(s) to be used in co-culture experiments. Aluminium shields were also realized for half shield irradiation experiments. The alpha-particle irradiator of the ISS has been successfully used for studying DNA damage, namely double strand breaks (DSB, as measured by the γ-H2AX assay), in directly hit and in bystander primary human fibroblasts [it

Non-destructive alpha-particle activation analysis of P, Cl, K and Ca in marine macro-alga samples using synthetic multielement reference material as comparative standard

International Nuclear Information System (INIS)

Iwata, Y.; Naitoh, H.; Suzuki, N.

1992-01-01

A Synthetic Reference Material (SyRM) composed with accurately known amounts of 12 elements has been prepared. The elemental composition of the SyRM is closely similar to that of marine macro-algae sample. The elemental composition of the SyRM was regulated by the starting materials used for the synthesis. The SyRM was used as a comparative standard for non-destructive alpha-particle activation analysis of marine macro-alga samples. P, Cl, K and Ca were determined simultaneously without correction for alpha range due to difference in the elemental composition between the analytical samples and the comparative standard. (author) 19 refs.; 4 tabs

Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing V alpha 1 or V alpha 14 elements.

Science.gov (United States)

Mahotka, C; Hansen-Hagge, T E; Bartram, C R

1995-10-01

Human acute lymphoblastic leukemia cell lines represent valuable tools to investigate distinct steps of the complex regulatory pathways underlying T cell receptor recombination and expression. A case in point are V delta 2D delta 3 and subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic pre-B cells as well as in normal lymphopoiesis. The functional expression of these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by alternative splicing events. In this report we show that alternative splicing at cryptic splice donor sites within V elements is not a unique feature of hybrid TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR, alternatively spliced products were observed in TCR alpha recombinations containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral blood cells and thymocytes, the leukemia cell line JM expressing functional V alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA species.

Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha.

Science.gov (United States)

Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

1995-09-15

Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogenesis of asthma; however, little is known of its direct effect on smooth muscle reactivity. We investigated the effect of TNF alpha on the responsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased responsiveness to electrical field stimulation (113 +/- 8, 110 +/- 4 and 112 +/- 2% respectively) compared to control (99 +/- 2%) (P 0.05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%, n = 3, P = 0.38). These results show that TNF alpha causes an increase in responsiveness of human bronchial tissue and that this occurs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiveness.

Novel Bioinformatics-Based Approach for Proteomic Biomarkers Prediction of Calpain-2 & Caspase-3 Protease Fragmentation: Application to βII-Spectrin Protein

Science.gov (United States)

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges; Kobeissy, Firas

2017-01-01

The crucial biological role of proteases has been visible with the development of degradomics discipline involved in the determination of the proteases/substrates resulting in breakdown-products (BDPs) that can be utilized as putative biomarkers associated with different biological-clinical significance. In the field of cancer biology, matrix metalloproteinases (MMPs) have shown to result in MMPs-generated protein BDPs that are indicative of malignant growth in cancer, while in the field of neural injury, calpain-2 and caspase-3 proteases generate BDPs fragments that are indicative of different neural cell death mechanisms in different injury scenarios. Advanced proteomic techniques have shown a remarkable progress in identifying these BDPs experimentally. In this work, we present a bioinformatics-based prediction method that identifies protease-associated BDPs with high precision and efficiency. The method utilizes state-of-the-art sequence matching and alignment algorithms. It starts by locating consensus sequence occurrences and their variants in any set of protein substrates, generating all fragments resulting from cleavage. The complexity exists in space O(mn) as well as in O(Nmn) time, where N, m, and n are the number of protein sequences, length of the consensus sequence, and length per protein sequence, respectively. Finally, the proposed methodology is validated against βII-spectrin protein, a brain injury validated biomarker.

ALPHA/AMPU, Radionuclide Radioactivity from Alpha Spectrometer Measurements

International Nuclear Information System (INIS)

Sill, D.S.

1990-01-01

1 - Description of program or function: The two computer programs, ALPHA and AMPU, take raw data obtained from alpha spectrometry and from these calculate activities and uncertainties of the radionuclides present in the sample. ALPHA determines activities of any alpha emitter in a sample that has been directly precipitated with NdF 3 . AMPU determines the Pu-239, Pu-238,and Am-241 activities using Pu-236 and Am-243 tracers. 2 - Method of solution: These programs propagate all random and systematic uncertainties, found anywhere in the experimental process, to the final result. The result is rounded and is in decimal agreement with the uncertainty. 3 - Restrictions on the complexity of the problem: In ALPHA, a chemical yield of 98% is assumed

Resting alpha activity predicts learning ability in alpha neurofeedback

Directory of Open Access Journals (Sweden)

Wenya eNan

2014-07-01

Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

Interactions between an alpha-helix and a beta-sheet. Energetics of alpha/beta packing in proteins.

Science.gov (United States)

Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A

1985-12-05

Conformational energy computations have been carried out to determine the favorable ways of packing a right-handed alpha-helix on a right-twisted antiparallel or parallel beta-sheet. Co-ordinate transformations have been developed to relate the position and orientation of the alpha-helix to the beta-sheet. The packing was investigated for a CH3CO-(L-Ala)16-NHCH3 alpha-helix interacting with five-stranded beta-sheets composed of CH3CO-(L-Val)6-NHCH3 chains. All internal and external variables for both the alpha-helix and the beta-sheet were allowed to change during energy minimization. Four distinct classes of low-energy packing arrangements were found for the alpha-helix interacting with both the parallel and the anti-parallel beta-sheet. The classes differ in the orientation of the axis of the alpha-helix relative to the direction of the strands of the right-twisted beta-sheet. In the class with the most favorable arrangement, the alpha-helix is oriented along the strands of the beta-sheet, as a result of attractive non-bonded side-chain-side-chain interactions along the entire length of the alpha-helix. A class with nearly perpendicular orientation of the helix axis to the strands is also of low energy, because it allows similarly extensive attractive interactions. In the other two classes, the helix is oriented diagonally relative to the strands of the beta-sheet. In one of them, it interacts with the convex surface near the middle of the saddle-shaped twisted beta-sheet. In the other, it is oriented along the concave diagonal of the beta-sheet and, therefore, it interacts only with the corner regions of the sheet, so that this packing is energetically less favorable. The packing arrangements involving an antiparallel and a parallel beta-sheet are generally similar, although the antiparallel beta-sheet has been found to be more flexible. The major features of 163 observed alpha/beta packing arrangements in 37 proteins are accounted for in terms of the computed

Radiation-induced structural changes in membrane proteins of human erythrocytes and ghosts and the relation to cellular morphology

Energy Technology Data Exchange (ETDEWEB)

Schuurhuis, G.J.; Hommes, J.; Vos, J.; Molenaar, I.; Konings, A.W.T. (Rijksuniversiteit Groningen (Netherlands))

1984-02-01

Isolated human erythrocytes and ghosts were irradiated with X-rays under different experimental conditions and the effect examined with regard to the structure of membrane proteins and morphology of whole cells and ghosts. From sodium dodecyl sulphate/polyacrylamide gel electrophoresis it is concluded that spectrin (band 1 and 2) is the most radiosensitive of the membrane proteins examined. X-irradiation of cells and ghosts induced covalent cross-linking of a small fraction of membrane proteins. In the protein aggregates thus formed spectrin was found to be the major component. Molecular disulphide (-SS-) bridges seemed to account for part of the cross-links observed. Some nondisulphide cross-links were found, especially when ghosts were irradiated. Significant amounts of spectrin aggregates were formed during post-irradiation incubation at 37/sup 0/C but not at 4/sup 0/C. In the intact cell a transformation in shape from discocyte to echinocyte accompanied the process of post-irradiation spectrin aggregation. The characteristics of both processes, such as their reversibility with adenosine, point to a metabolic involvement. It is shown that there is no causal relationship between the two phenomena observed. Possible causes of the post-irradiation effects and the parallelism with similar processes in non-irradiated metabolically depleted cells are discussed.

Radiation-induced structural changes in membrane proteins of human erythrocytes and ghosts and the relation to cellular morphology

International Nuclear Information System (INIS)

Schuurhuis, G.J.; Hommes, J.; Vos, J.; Molenaar, I.; Konings, A.W.T.

1984-01-01

Isolated human erythrocytes and ghosts were irradiated with X-rays under different experimental conditions and the effect examined with regard to the structure of membrane proteins and morphology of whole cells and ghosts. From sodium dodecyl sulphate/polyacrylamide gel electrophoresis it is concluded that spectrin (band 1 and 2) is the most radiosensitive of the membrane proteins examined. X-irradiation of cells and ghosts induced covalent cross-linking of a small fraction of membrane proteins. In the protein aggregates thus formed spectrin was found to be the major component. Molecular disulphide (-SS-) bridges seemed to account for part of the cross-links observed. Some nondisulphide cross-links were found, especially when ghosts were irradiated. Significant amounts of spectrin aggregates were formed during post-irradiation incubation at 37 0 C but not at 4 0 C. In the intact cell a transformation in shape from discocyte to echinocyte accompanied the process of post-irradiation spectrin aggregation. The characteristics of both processes, such as their reversibility with adenosine, point to a metabolic involvement. It is shown that there is no causal relationship between the two phenomena observed. Possible causes of the post-irradiation effects and the parallelism with similar processes in non-irradiated metabolically depleted cells are discussed. (author)

Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha-1 Foundation DNA and Tissue Bank

Directory of Open Access Journals (Sweden)

Adriano R Tonelli

2009-12-01

Full Text Available Adriano R Tonelli1, Farshid Rouhani1, Ning Li2, Pam Schreck1, Mark L Brantly11Alpha-1 Research Program, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Department of Epidemiology and Biostatistics, University of Florida, Gainesville, Florida, USAIntroduction: Intravenous augmentation therapy with purified intravenous alpha-1 antitrypsin replaces the deficient protein and is the only currently approved treatment for alpha-1 antitrypsin deficiency (AATD related lung disease. While augmentation therapy has been available for more than 20 years, there are a limited number of studies evaluating the effect of augmentation on lung function.Material and methods: We examined the decline in forced expiratory volume in one second (FEV1 in patients enrolled in the Alpha-1 Foundation DNA and Tissue Bank in relation to the use or not of alpha-1 antitrypsin augmentation therapy. For the purpose of our analysis we included 164 patients with AATD and PI ZZ genotype.Results: Mean age of the patients was 60 years, 52% were females, 94% were white and 78% ex-smokers. The mean FEV1 at baseline was 1.7 L and the mean FEV1 % of predicted was 51.3%. The mean follow-up time was 41.7 months. A total of 124 (76% patients received augmentation therapy (augmented group while 40 patients (24% did not received it (non-augmented group. When adjusted by age at baseline, sex, smoking status, baseline FEV1 % of predicted, the mean overall change in FEV1 was 47.6 mL/year, favoring the augmented group (?FEV1 10.6 ± 21.4 mL/year in comparison with the non-augmented group (?FEV1 −36.96 ± 12.1 mL/year (P = 0.05. Beneficial ?FEV1 were observed in ex-smokers and the group with initial FEV1 % of predicted of <50%. No differences were observed in mortality.Conclusions: In conclusion, augmentation therapy improves lung function in subjects with AATD when adjusted by age, gender, smoking status and baseline FEV1 % of predicted. The beneficial

Analysis of Maxi-K alpha subunit splice variants in human myometrium

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Morrison John J

2004-09-01

Full Text Available Abstract Background Large-conductance, calcium-activated potassium (Maxi-K channels are implicated in the modulation of human uterine contractions and myometrial Ca2+ homeostasis. However, the regulatory mechanism(s governing the expression of Maxi-K channels with decreased calcium sensitivity at parturition are unclear. The objectives of this study were to investigate mRNA expression of the Maxi-K alpha subunit, and that of its splice variants, in human non-pregnant and pregnant myometrium, prior to and after labour onset, to determine whether altered expression of these splice variants is associated with decreased calcium sensitivity observed at labour onset. Methods Myometrial biopsies were obtained at hysterectomy (non-pregnant, NP, and at Caesarean section, at elective (pregnant not-in-labour, PNL and intrapartum (pregnant in-labour, PL procedures. RNA was extracted from all biopsies and quantitative real-time RT-PCR was used to investigate for possible differential expression of the Maxi-K alpha subunit, and that of its splice variants, between these functionally-distinct myometrial tissue sets. Results RT-PCR analysis identified the presence of a 132 bp and an 87 bp spliced exon of the Maxi-K alpha subunit in all three myometrial tissue sets. Quantitative real-time PCR indicated a decrease in the expression of the Maxi-K alpha subunit with labour onset. While there was no change in the proportion of Maxi-K alpha subunits expressing the 87 bp spliced exon, the proportion of alpha subunits expressing the 132 bp spliced exon was significantly increased with labour onset, compared to both non-pregnant and pregnant not-in-labour tissues. An increased proportion of 132 bp exon-containing alpha subunit variants with labour onset is of interest, as channels expressing this spliced exon have decreased calcium and voltage sensitivities. Conclusions Our findings suggest that decreased Maxi-K alpha subunit mRNA expression in human myometrium at

Molecular basis for nondeletion alpha-thalassemia in American blacks. Alpha 2(116GAG----UAG).

OpenAIRE

Liebhaber, S A; Coleman, M B; Adams, J G; Cash, F E; Steinberg, M H

1987-01-01

An American black woman was found to have the phenotype of moderately severe alpha-thalassemia normally associated with the loss of two to three alpha-globin genes despite an alpha-globin gene map that demonstrated the loss of only a single alpha-globin gene (-alpha/alpha alpha). Several individuals in her kindred with normal alpha-globin gene mapping studies (alpha alpha/alpha alpha) had mild alpha-thalassemia hematologic values consistent with the loss of one to two alpha-globin genes. Thes...

Assessment of statistic analysis in non-radioisotopic local lymph node assay (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example.

Science.gov (United States)

Takeyoshi, Masahiro; Sawaki, Masakuni; Yamasaki, Kanji; Kimber, Ian

2003-09-30

The murine local lymph node assay (LLNA) is used for the identification of chemicals that have the potential to cause skin sensitization. However, it requires specific facility and handling procedures to accommodate a radioisotopic (RI) endpoint. We have developed non-radioisotopic (non-RI) endpoint of LLNA based on BrdU incorporation to avoid a use of RI. Although this alternative method appears viable in principle, it is somewhat less sensitive than the standard assay. In this study, we report investigations to determine the use of statistical analysis to improve the sensitivity of a non-RI LLNA procedure with alpha-hexylcinnamic aldehyde (HCA) in two separate experiments. Consequently, the alternative non-RI method required HCA concentrations of greater than 25% to elicit a positive response based on the criterion for classification as a skin sensitizer in the standard LLNA. Nevertheless, dose responses to HCA in the alternative method were consistent in both experiments and we examined whether the use of an endpoint based upon the statistical significance of induced changes in LNC turnover, rather than an SI of 3 or greater, might provide for additional sensitivity. The results reported here demonstrate that with HCA at least significant responses were, in each of two experiments, recorded following exposure of mice to 25% of HCA. These data suggest that this approach may be more satisfactory-at least when BrdU incorporation is measured. However, this modification of the LLNA is rather less sensitive than the standard method if employing statistical endpoint. Taken together the data reported here suggest that a modified LLNA in which BrdU is used in place of radioisotope incorporation shows some promise, but that in its present form, even with the use of a statistical endpoint, lacks some of the sensitivity of the standard method. The challenge is to develop strategies for further refinement of this approach.

Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

DEFF Research Database (Denmark)

Nordentoft, Iver Kristiansen; Jeppesen, Per Bendix; Nielsen, Anders Lade

2007-01-01

In the present study we investigate the expression levels of cytosolic phospholipase A2 alpha (cPLA2alpha) interacting histone acetyl transferase proteins TIP60alpha and TIP60beta in non-diabetic C57BL wild-type mice and obese type 2 diabetic KKAy model mice. The aim was to test our hypothesis...

Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells.

Science.gov (United States)

Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

2017-07-15

Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-pp,. cap alpha cap alpha. and p. cap alpha. elastic scattering at high energies and Chou-Yang conjecture

Energy Technology Data Exchange (ETDEWEB)

Saleem, M.; Fazal-e-Aleem; Rifique, M.

1987-03-01

The recent experimental measurements for anti-pp and ..cap alpha cap alpha.. elastic scattering at high energies have shown that the Chou-Yang conjecture regarding the relationship between the electromagnetic and the hadronic form factor of a particle is only an approximation. A new ansatz has been proposed to obtain hadronic form factors of proton and the ..cap alpha..-particle. These form factors have been used to explain the various characteristics of anti-pp, ..cap alpha cap alpha.. and p..cap alpha.. elastic scattering at high energies.

Contribution to the study of alpha-alpha interaction; Contribution a l'etude de l'interaction alpha - alpha

Energy Technology Data Exchange (ETDEWEB)

Darriulai, P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1965-03-01

Two sets of measurements of the {alpha}-{alpha} elastic scattering differential cross section are presented. The first set - angular distributions from 50 up to 120 MeV - shows two new resonances, 6{sup +} and 8{sup +}, at 25 and 57 MeV. Complex phase shifts are extracted from the data and a phenomenological potential is given. A description of the 3 {alpha}-particle 0{sup +} states in C{sup 12} is made with this interaction potential. The second set - excitation curves between 20 and 50 MeV - allows investigation of the Be{sup 8} level structure within this energy range - It identifies the 16.6 and 16.9 MeV states as 2{sup +}, but the rise of inelastic processes at higher energies makes further identification of spins and parities more and more difficult. (author) [French] Deux series de mesures de la section efficace differentielle de diffusion {alpha}-{alpha} sont presentees. La premiere - distributions angulaires entre 50 et 120 MeV - fait apparaitre deux nouvelles resonances, 6{sup +} et 8{sup +}, a 25 et 57 MeV d'excitation. Des dephasages complexes en sont extraits et un potentiel phenomenologique est presente. Une etude des etats 0{sup +} a parentage (3{alpha}) de {sup 12}C est faite a partir de ce potentiel. La seconde - courbes d'excitation s'etendant de 20 a 50 MeV - met en evidence la structure de {sup 8}Be dans cette region. Elle montre que les niveaux a 16,6 et 16,9 MeV sont des 2{sup +} mais l'importance des processus inelastiques rend difficile l'identification des niveaux d'excitation plus elevee. (auteur)

A new model and gas sensitivity of non-equilibrium xSnO2-(1-x)alpha-Fe2O3 nanopowders prepared by mechanical alloying

DEFF Research Database (Denmark)

Zhu, W.; Tan, O.K.; Jiang, Jianzhong

1998-01-01

)alpha-Fe2O3 materials. This model can explain non only the lattice expansion of the milled samples, but also takes into account the charge balance by adding oxygen dangling bonds at the particle surfaces, which can be visualized in the nano-sized powders. The thich film gas sensors made by such mechanically......Nano-sized xSnO2-(1-x)alpha-Fe2O3 materials have been prepared using the high energy ball milling technique and their structural and gas sensing properties have been characterized. Based on experimental results, we propose a new structure model, xxx, forthese non-equilibrium, nano-sized xSnO2-(1-x...... alloyed materials have high ethanol gas sensitivity values of 289 in air and 1016 in nitrogen at 1000 p.p.m. and very good gas selectivity to ethanol over CO and H2 gases. It is believed that the high ethanol gas sensitivity of these materials is related to the enormous defects such as O- and O2- dangling...

Investigation of the Pygmy Dipole Resonance in (alpha, alpha 'gamma) coincidence experiments

NARCIS (Netherlands)

Savran, D.; Babilon, M.; van den Berg, A. M.; Harakeh, M. N.; Hasper, J.; Wortche, H. J.; Zilges, A.

2007-01-01

We report on first results from experiments using the (alpha, alpha'gamma) reaction at E alpha = 136 MeV to investigate bound electric dipole (El) excitations building the so-called Pygmy Dipole Resonance (PDR) in the semi-magic nucleus Ce-140. The method of (alpha, alpha'gamma) allows the

Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.

Science.gov (United States)

Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R

2005-04-01

The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations.

Directory of Open Access Journals (Sweden)

José B Oliveira-Martins

Full Text Available The cellular form of the prion protein, PrP(C, undergoes extensive proteolysis at the alpha site (109K [see text]H110. Expression of non-cleavable PrP(C mutants in transgenic mice correlates with neurotoxicity, suggesting that alpha-cleavage is important for PrP(C physiology. To gain insights into the mechanisms of alpha-cleavage, we generated a library of PrP(C mutants with mutations in the region neighbouring the alpha-cleavage site. The prevalence of C1, the carboxy adduct of alpha-cleavage, was determined for each mutant. In cell lines of disparate origin, C1 prevalence was unaffected by variations in charge and hydrophobicity of the region neighbouring the alpha-cleavage site, and by substitutions of the residues in the palindrome that flanks this site. Instead, alpha-cleavage was size-dependently impaired by deletions within the domain 106-119. Almost no cleavage was observed upon full deletion of this domain. These results suggest that alpha-cleavage is executed by an alpha-PrPase whose activity, despite surprisingly limited sequence specificity, is dependent on the size of the central region of PrP(C.

Developmental expression of the alpha-skeletal actin gene

Directory of Open Access Journals (Sweden)

Vonk Freek J

2008-06-01

Full Text Available Abstract Background Actin is a cytoskeletal protein which exerts a broad range of functions in almost all eukaryotic cells. In higher vertebrates, six primary actin isoforms can be distinguished: alpha-skeletal, alpha-cardiac, alpha-smooth muscle, gamma-smooth muscle, beta-cytoplasmic and gamma-cytoplasmic isoactin. Expression of these actin isoforms during vertebrate development is highly regulated in a temporal and tissue-specific manner, but the mechanisms and the specific differences are currently not well understood. All members of the actin multigene family are highly conserved, suggesting that there is a high selective pressure on these proteins. Results We present here a model for the evolution of the genomic organization of alpha-skeletal actin and by molecular modeling, illustrate the structural differences of actin proteins of different phyla. We further describe and compare alpha-skeletal actin expression in two developmental stages of five vertebrate species (mouse, chicken, snake, salamander and fish. Our findings confirm that alpha-skeletal actin is expressed in skeletal muscle and in the heart of all five species. In addition, we identify many novel non-muscular expression domains including several in the central nervous system. Conclusion Our results show that the high sequence homology of alpha-skeletal actins is reflected by similarities of their 3 dimensional protein structures, as well as by conserved gene expression patterns during vertebrate development. Nonetheless, we find here important differences in 3D structures, in gene architectures and identify novel expression domains for this structural and functional important gene.

Ground state solutions for non-local fractional Schrodinger equations

Directory of Open Access Journals (Sweden)

Yang Pu

2015-08-01

Full Text Available In this article, we study a time-independent fractional Schrodinger equation with non-local (regional diffusion $$ (-\\Delta^{\\alpha}_{\\rho}u + V(xu = f(x,u \\quad \\text{in }\\mathbb{R}^{N}, $$ where $\\alpha \\in (0,1$, $N > 2\\alpha$. We establish the existence of a non-negative ground state solution by variational methods.

Alpha?fetoprotein elevation in NUT midline carcinoma: a case report

OpenAIRE

D?Ambrosio, Lorenzo; Palesandro, Erica; Moretti, Marina; Pelosi, Giuseppe; Fabbri, Alessandra; Carnevale Schianca, Fabrizio; Aglietta, Massimo; Grignani, Giovanni

2017-01-01

Background Nuclear protein in testis (NUT) midline carcinoma is a rarely diagnosed and potentially under-recognized type of squamous carcinoma that is considered one of the most aggressive human solid tumors. Alpha-fetoprotein elevation has been associated with chronic liver diseases and a limited number of cancers. In particular, in presence of a mediastinal mass in a young man, alpha-fetoprotein elevation is considered nearly pathognomonic of a non-seminoma germ-cell tumor. Case presentatio...

THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

Energy Technology Data Exchange (ETDEWEB)

Hayes, Matthew [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France); Oestlin, Goeran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Schaerer, Daniel [CNRS, IRAP, 14, avenue Edouard Belin, F-31400 Toulouse (France); Verhamme, Anne; Orlitova, Ivana [Geneva Observatory, University of Geneva, 51 Chemin des Maillettes, CH-1290 Versoix (Switzerland); Mas-Hesse, J. Miguel; Oti-Floranes, Hector [Centro de Astrobiologia (CSIC-INTA), Departamento de Astrofisica, POB 78, 28691 Villanueva de la Canada (Spain); Adamo, Angela [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Atek, Hakim [Laboratoire d' Astrophysique, Ecole Polytechnique Federale de Lausanne (EPFL), Observatoire, CH-1290 Sauverny (Switzerland); Cannon, John M. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Herenz, E. Christian [Leibniz-Institut fuer Astrophysik (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Kunth, Daniel [Institut d' Astrophysique de Paris, UMR 7095 CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France); Laursen, Peter, E-mail: matthew@astro.su.se [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark)

2013-03-10

We report on new imaging observations of the Lyman alpha emission line (Ly{alpha}), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly{alpha}, H{alpha}, and the far ultraviolet continuum. We show that Ly{alpha} is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, R{sub P20}, Ly{alpha} radii are larger than those of H{alpha} by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Ly{alpha}-to-FUV radii is 2.9. This suggests that much of the Ly{alpha} light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly{alpha} compared to H{alpha}, {xi}{sub Ly{alpha}} = R {sup Ly{alpha}}{sub P20}/R {sup H{alpha}}{sub P20}, we find {xi}{sub Ly{alpha}} to be uncorrelated with total Ly{alpha} luminosity. However, {xi}{sub Ly{alpha}} is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly{alpha} photons throughout the interstellar medium and drive a large extended Ly{alpha} halo.

Intrahepatic hematoma: hepatic lesion in a newborn with high {alpha}-fetoprotein level

Energy Technology Data Exchange (ETDEWEB)

Lam, Chiu Ying Flora; Chan, Kui Fai; Fan, Tsz Wo; Kwok, Chong Hei Philip; Chan, Chi Hum Susan; Tsang, Tsz Kan [Queen Elizabeth Hospital, Department of Radiology and Imaging, Hong Kong (China)

2005-11-01

Hepatic hematomas are relatively common in fetuses and neonates; most are subcapsular in location. Sometimes their imaging features can be non-specific, so differentiation from other aggressive lesions like hepatoblastoma can be difficult, especially if there is a concurrent high {alpha}-fetoprotein level. We report a case of intrahepatic hematoma with a rising {alpha}-fetoprotein level. (orig.)

Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary

DEFF Research Database (Denmark)

Fenger, M; Johnsen, A H

1988-01-01

Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well...... (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders...... amidated POMC-related peptides are present in normal human pituitary. It also shows that cleavage in vivo at all dibasic amino acids but one, takes place at the N-terminal POMC region; the exception is at the POMC-(49-50) N-terminal of the gamma MSH sequence. The pattern of peptides produced suggests...

Synthesis and antimicrobial evaluation of new 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinones.

Science.gov (United States)

Güzeldemirci, Nuray Ulusoy; Ilhan, Eser; Küçükbasmaci, Omer; Satana, Dilek

2010-01-01

New 4-thiazolidinone derivatives of benzilic acid (alpha,alpha-diphenyl-alpha-hydroxyacetic acid) have been synthesized and evaluated for antibacterial and antifungal activities. The reaction of 1- (alpha,alpha-diphenyl-alpha-hydroxy)acetyl-4-alkyl/arylthiosemicarbazides with ethyl 2-bromopropionate gave 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinone derivatives. Their antibacterial and antifungal activities were evaluated against S. aureus ATCC 29213, P. aeruginosa ATCC 27853, E. coli ATCC 25922, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, T. mentagrophytes var. erinacei NCPF 375, M. gypseum NCPF 580 and T. tonsurans NCPF 245. 3e, 3f, 3g and 3h showed the highest antibacterial activity. Particularly 3a and 3e showed the highest antifungal activities against C. parapsilosis ATCC 22019, T. tonsurans NCPF 245 and M. gypseum NCPF 580.

Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response

NARCIS (Netherlands)

Cino, E.A.; Wong-ekkabut, J.; Karttunen, M.E.J.; Choy, W.-Y.

2011-01-01

Intrinsically disordered proteins (IDPs) are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTa) and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2), with a common binding partner, Kelch-like

Nuclear Track Detector Characterization via Alpha-Spectrometry for Radioprotection Use

Energy Technology Data Exchange (ETDEWEB)

Morelli, D.; Imme, G.; Catalano, R. [Dipartimento di Fisica e Astronomia, Universita degli Studi di Catania, via S. Sofia, 64- 95123 Catania (Italy); Istituto Nazionale di Fisica Nucleare - Sezione di Catania, via S. Sofia, 64- 95123 Catania (Italy); Aranzulla, M. [Istituto Nazionale Geofisica e Vulcanologia - Sezione di Catania, piazza Roma, 2- 95127 Catania (Italy); Tazzer, A. L. Rosselli; Mangano, G. [Dipartimento di Fisica e Astronomia, Universita degli Studi di Catania, via S. Sofia, 64- 95123 Catania (Italy)

2011-12-13

Solid Nuclear Track Detectors (SNTDs), CR-39 type, are usually adopted to monitor radon gas concentrations. In order to characterize the detectors according to track geometrical parameters, detectors were irradiated inside a vacuum chamber by alpha particles at twelve energy values, obtained by different Mylar foils in front of a {sup 241}Am source. The alpha energy values were verified using a Si detector. After the exposure to the alpha particles, the detectors were chemically etched to enlarge the tracks, which were then analyzed by means of a semiautomatic system composed of an optical microscope equipped with a CCD camera connected to a personal computer to store images. A suitable routine analyzed the track parameters: major and minor axis length and mean grey level, allowing us to differentiate tracks according to the incident alpha energy and then to individuate the discrimination factors for radon alpha tracks. The combined use of geometrical and optical parameters allows one to overcome the ambiguity in the alpha energy determination due to the non-monotonicity of each parameter versus energy. After track parameter determination, a calibration procedure was performed by means of a radon chamber. The calibration was verified through an inter-comparing survey.

Lyman Alpha Control

CERN Document Server

Nielsen, Daniel Stefaniak

2015-01-01

This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

Alpha-tocopherol inhibits pore formation in oxidized bilayers

NARCIS (Netherlands)

Boonnoy, P.; Karttunen, M.; Wong-Ekkabut, J.

2017-01-01

In biological membranes, alpha-tocopherols (α-toc; vitamin E) protect polyunsaturated lipids from free radicals. Although the interactions of α-toc with non-oxidized lipid bilayers have been studied, their effects on oxidized bilayers remain unknown. In this study, atomistic molecular dynamics (MD)

Alpha - Skew Pi - Armendariz Rings

Directory of Open Access Journals (Sweden)

Areej M Abduldaim

2018-03-01

Full Text Available In this article we introduce a new concept called Alpha-skew Pi-Armendariz rings (Alpha - S Pi - ARas a generalization of the notion of Alpha-skew Armendariz rings.Another important goal behind studying this class of rings is to employ it in order to design a modern algorithm of an identification scheme according to the evolution of using modern algebra in the applications of the field of cryptography.We investigate general properties of this concept and give examples for illustration. Furthermore, this paperstudy the relationship between this concept and some previous notions related to Alpha-skew Armendariz rings. It clearly presents that every weak Alpha-skew Armendariz ring is Alpha-skew Pi-Armendariz (Alpha-S Pi-AR. Also, thisarticle showsthat the concepts of Alpha-skew Armendariz rings and Alpha-skew Pi- Armendariz rings are equivalent in case R is 2-primal and semiprime ring.Moreover, this paper proves for a semicommutative Alpha-compatible ringR that if R[x;Alpha] is nil-Armendariz, thenR is an Alpha-S Pi-AR. In addition, if R is an Alpha - S Pi -AR, 2-primal and semiprime ring, then N(R[x;Alpha]=N(R[x;Alpha]. Finally, we look forwardthat Alpha-skew Pi-Armendariz rings (Alpha-S Pi-ARbe more effect (due to their properties in the field of cryptography than Pi-Armendariz rings, weak Armendariz rings and others.For these properties and characterizations of the introduced concept Alpha-S Pi-AR, we aspire to design a novel algorithm of an identification scheme.

Role of Frontal Alpha Oscillations in Creativity

Science.gov (United States)

Lustenberger, Caroline; Boyle, Michael R.; Foulser, A. Alban; Mellin, Juliann M.; Fröhlich, Flavio

2015-01-01

Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent EEG data suggests that cortical oscillations in the alpha frequency band (8 – 12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a fundamental role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking, a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40Hz-tACS was used in instead of 10Hz-tACS to rule out a general “electrical stimulation” effect. No significant change in the Creativity Index was found for such frontal gamma stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

The tree-alpha Faddeev calculation on 12C bound states with a Pauli correct alpha-alpha potential

International Nuclear Information System (INIS)

Kamada, Hiroyuki; Oryu, Shinsho

1986-01-01

The three-alpha model of 12 C is investigated by the Faddeev formalism with the UIM alpha-alpha potential, in which the Pauli effect between two-alpha system was taken into account adequately. The potential can reproduce the on- and off-shell effects of the alpha-alpha interaction by the rank-4 separable type for the S-wave, the rank-3 one for the D-wave, and the rank-2 one for the G-wave, in which two of the ranks in the S-wave, and one in the D-wave are prepared to eliminate the Pauli forbidden states. We obtained three even states J π = 0 + , 2 + , 4 + , and two odd states 1 - , 3 - , below the alpha- 8 Be(0 + g.s) threshold energy. The even parity states gain larger binding energies than those which have been obtained by former Faddeev calculation with the rank-1 Kukulin and Neudatchin (KN) potential. On the other hand, for the odd parity states, we obtained smaller binding energies than the former one. It is found that our Faddeev calculation with the UIM potential does not miss any important low-lying levels of 12 C, in which any spurious states do not appear. (author)

Synthesis of tritiated 1-alpha-methadol and 1-alpha-acetylmethadol

Energy Technology Data Exchange (ETDEWEB)

Thang, D.C.; Nam, N.H.; Pontikis, R. (Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Fernand Widal, 75 - Paris (France)); Pichat, L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

1982-04-01

dl-Methadone was resolved by crystallization of its ammonium d- ..cap alpha.. -bromocamphor-..pi..-sulfonate salt to give d-methadone. The latter in ethyl acetate solution was reduced with tritium gas to 1-..cap alpha..-methadol /sup 3/H in presence of Adams platinum oxide at normal temperature and pressure. Acetylation of 1-..cap alpha..-carbinol hydrochloride by means of acetyl chloride afforded 1-..cap alpha..-acetylmethadol /sup 3/H, specific activity: 20 Ci/mMole. The positions and extent of tritium labelling were determined by /sup 3/H NMR spectroscopy.

Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson's Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque.

Directory of Open Access Journals (Sweden)

James B Koprich

Full Text Available Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 1012 gp/ml, this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform.

General synthesis of C-glycosyl amino acids via proline-catalyzed direct electrophilic alpha-amination of C-glycosylalkyl aldehydes.

Science.gov (United States)

Nuzzi, Andrea; Massi, Alessandro; Dondoni, Alessandro

2008-10-16

Non-natural axially and equatorially linked C-glycosyl alpha-amino acids (glycines, alanines, and CH2-serine isosteres) with either S or R alpha-configuration were prepared by D- and L-proline-catalyzed (de >95%) alpha-amination of C-glycosylalkyl aldehydes using dibenzyl azodicarboxylate as the electrophilic reagent.

Radiobiological long-term accumulation of environmental alpha radioactivity in extracted human teeth and animal bones in Malaysia

International Nuclear Information System (INIS)

Almayahi, B.A.; Tajuddin, A.A.; Jaafar, M.S.

2014-01-01

In this study, the radiobiological analysis of natural alpha emitters in extracted human teeth and animal bones from Malaysia was estimated. The microdistributions of alpha particles in tooth and bone samples were measured using CR-39 alpha-particle track detectors. The lowest and highest alpha emission rates in teeth in the Kedah and Perak states were 0.0080 ± 0.0005 mBq cm −2 and 0.061 ± 0.008 mBq cm −2 , whereas those of bones in the Perlis and Kedah states were 0.0140 ± 0.0001 mBq cm −2 and 0.7700 ± 0.0282 mBq cm −2 , respectively. The average alpha emission rate in male teeth was 0.0209 ± 0.0008 mBq cm −2 , whereas that of female teeth was 0.0199 ± 0.0010 mBq cm −2 . The alpha emission rate in teeth is higher in smokers (0.0228 ± 0.0008 mBq cm −2 ) than in non-smokers (0.0179 ± 0.0008 mBq cm −2 ). Such difference was found statistically significant (p < 0.01). - Highlights: • Alpha emission rates in teeth from smokers slightly higher than non-smokers. • Difference between alpha rates in male and female tooth not statistically significant. • Alpha particles have the same effect at any age. • Difference between alpha rates in bones was statistically significant

Nanodosimetry and nanodosimetric-based models of radiation action for radon alpha particles

International Nuclear Information System (INIS)

1992-01-01

The objective of our research work is to provide -- with the aid of biophysical models of radiation action -- information on human risks following exposure to radon alpha particles. The approach proposed consists of (1) developing appropriate models (parametric and non-parametric) for alpha radiation induction of relevant end points (survival, cellular transformation), (2) providing an accurate physical characterization of the particle tracks in terms of nanodosimetric distributions, (3) supporting the models by detailed, molecular studies of the direct and indirect effects of alpha particles on DNA. Activities in the second year of this project are described

Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and lactating rats.

Science.gov (United States)

Frye, Cheryl A; Walf, Alicia A

2004-07-01

The 5alpha-reduced metabolite of progesterone (P), 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), may mediate progestins' effects to reduce depressive behavior of female rats in part through actions in the hippocampus. To investigate, forced swim test behavior and plasma and hippocampal progestin levels were assessed in groups of rats expected to differ in their 3alpha,5alpha-THP levels due to endogenous differences (pregnant and postpartum), administration of a 5alpha-reductase inhibitor (finasteride; 50 mg/kg sc), and/or gestational stress [prenatal stress (PNS)], an animal model of depression. Pregnant rats had higher plasma and hippocampal 3alpha,5alpha-THP levels and less depressive behavior (decreased immobility, increased struggling and swimming) in the forced swim test than did postpartum rats. Finasteride, compared to vehicle-administration, reduced plasma and hippocampal 3alpha,5alpha-THP levels and increased depressive behavior (increased immobility, decreased struggling and swimming). PNS was associated with lower hippocampal, but not plasma, 3alpha,5alpha-THP levels and increased swimming compared to that observed in control rats. Together, these data suggest that 3alpha,5alpha-THP in the hippocampus may mediate antidepressive behavior of female rats.

Inclusive-jet photoproduction at HERA and determination of alphas

CERN Document Server

Abramowicz, H.

2012-11-01

Inclusive-jet cross sections have been measured in the reaction ep->e+jet+X for photon virtuality Q2 17 GeV and -1 < etajet < 2.5. In addition, measurements of double-differential inclusive-jet cross sections are presented as functions of ETjet in different regions of etajet. Next-to-leading-order QCD calculations give a good description of the measurements, except for jets with low ETjet and high etajet. The influence of non-perturbative effects not related to hadronisation was studied. Measurements of the ratios of cross sections using different jet algorithms are also presented; the measured ratios are well described by calculations including up to O(alphas2) terms. Values of alphas(Mz) were extracted from the measurements and the energy-scale dependence of the coupling was determined. The value of alphas(Mz) extracted from the measurements based on the kT jet algorithm is alphas(Mz) = 0.1206 +0.0023 -0.0022 (exp.) +0.0042 -0.0035 (th.); the results from the anti-kT and SIScone algorithms are compat...

HRTEM study of {alpha}-AlMnSi crystals including non-crystallographic projection axes

Energy Technology Data Exchange (ETDEWEB)

Song, G.L.; Bursill, L.A.

1997-06-01

The structure of {alpha}-AlMnSi is examined by atomic resolution high-resolution transmission electron microscopy (HRTEM) and computer-based image matching techniques. Six distinct zone axes are examined; including both normal crystallographic and non-crystallographic zones axes of the structural motifs, which have m3-bar 5 icosahedral symmetry. The results provide a sound basis for understanding HRTEM images of the quasicrystalline alloy i-AlMnSi; thus it was examined to what extent the requirements for obtaining so-called structure images of complex alloy structures may be met experimentally and define when the images may be reliably interpreted on the basis of computer simulation and image-matching at about 0.17nm resolution. Most difficulty was experienced in obtaining the experimental images, especially for the non-crystallographic zones, which are very sensitive to slight changes in orientation off the desired zone axis or projection, the rate at which the crystal thickness is increasing (wedge-angle) and the orientation of the surfaces of the specimen. Surface amorphous layers due to oxidation and/or electron-induced irradiation damage also limit the efficiency of the HRTEM analysis. For the thin specimens used for HRTEM, both the electron diffraction patterns and the HRTEM images are characteristic of Im3-bar space group symmetry. It is suggested that this Im3-bar symmetry may be an example of a statistical symmetry, where the local symmetry is close to Pm3-bar but the average symmetry is Im3-bar. The transition from Pm3-bar to Im3-bar may be understood in terms of an analysis of small changes in the outer shells of the large icosahedral structural elements which are located at the corners and body-centers of the cubic unit cell. 21 refs., 3 tabs., 10 figs.

Lens proteome map and alpha-crystallin profile of the catfish Rita rita.

Science.gov (United States)

Mohanty, Bimal Prasanna; Bhattacharjee, Soma; Das, Manas Kumar

2011-02-01

Crystallins are a diverse group of proteins that constitute nearly 90% of the total soluble proteins of the vertebrate eye lens and these tightly packed crystallins are responsible for transparency of the lens. These proteins have been studied in different model and non-model species for understanding the modifications they undergo with ageing that lead to cataract, a disease of protein aggregation. In the present investigation, we studied the lens crystallin profile of the tropical freshwater catfish Rita rita. Profiles of lens crystallins were analyzed and crystallin proteome maps of Rita rita were generated for the first time. alphaA-crystallins, member of the alpha-crystallin family, which are molecular chaperons and play crucial role in maintaining lens transparency were identified by 1- and 2-D immunoblot analysis with anti-alphaA-crystallin antibody. Two protein bands of 19-20 kDa were identified as alphaA-crystallins on 1-D immunoblots and these bands separated into 10 discrete spots on 2-D immunoblot. However, anti-alphaB-crystallin and antiphospho-alphaB-crystallin antibodies were not able to detect any immunoreactive bands on 1- and 2-D immunoblots, indicating alphaB-crystallin was either absent or present in extremely low concentration in Rita rita lens. Thus, Rita rita alpha-crystallins are more like that of the catfish Clarias batrachus and the mammal kangaroo in its alphaA- and alphaB-crystallin content (contain low amount from 5-9% of alphaB-crystallin) and unlike the dogfish, zebrafish, human, bovine and mouse alpha-crystallins (contain higher amount of alphaB-crystallin from 25% in mouse and bovine to 85% in dogfish). Results of the present study can be the baseline information for stimulating further investigation on Rita rita lens crystallins for comparative lens proteomics. Comparing and contrasting the alpha-crystallins of the dogfish and Rita rita may provide valuable information on the functional attributes of alphaA- and alphaB-isoforms, as

The heavy quarkonium spectrum at order $m\\alpha_{s}^{5}\\ln\\alpha_{s}$

CERN Document Server

Brambilla, Nora; Soto, Joan; Vairo, Antonio

1999-01-01

We compute the complete leading-log terms of the next-to-next-to-next-to-leading-order corrections to potential NRQCD. As a by-product we obtain the leading logs at $O(m\\alpha_s^5)$ in the heavy quarkonium spectrum. These leading logs, when $\\Lambda_{QCD} \\ll m\\alpha_s^2$, give the complete $O(m\\alpha_s^5 \\ln \\alpha_s)$ corrections to the heavy quarkonium spectrum.

Radon Daughters Background Reduction in Alpha Particles Counting System

International Nuclear Information System (INIS)

Dadon, S. S.; Pelled, O.; Orion, I.

2014-01-01

The ABPC method is using a serially occurring events of the beta decay of the 214Bi fallow by alpha decay of the 214Po that take place almost simultaneously to detect the Pseudo Coincidence Event (PCE) from the RDP, and to subtract them from the gross alpha counts. 267 This work showed that it is possible to improve the efficiency of RDP background reduction, including subtracting the 218Po contribution by using the ABPC method based on a single solid state silicon PIPS detector. False counts percentage obtained at the output of the PCE circuit were smaller than 0.1%. The results show that the PCE circuit was not influenced by non RDP alpha emitters. The PCE system did not reduce the non PCE of the 218Po. After 20 minutes the 218Po was strongly decayed, and its contribution became negligible. In order to overcome this disadvantage, a mathematical matching calculations for the 214Po and the 218Po decay equations were employed, and a constant ratio of the APo214(0) / APo218(0) was obtained. This ratio can be used to estimate the count rate of the 218Po at the first 20 minutes, and to subtract it from the total count rate in order to obtain correct RDP reduction

Crystalline anhydrous {alpha},{alpha}-trehalose (polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose: A calorimetric study

Energy Technology Data Exchange (ETDEWEB)

Pinto, Susana S. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: susanapinto@ist.utl.pt; Diogo, Herminio P. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: hdiogo@ist.utl.pt; Moura-Ramos, Joaquim J. [Centro de Quimica-Fisica Molecular, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: mouraramos@ist.utl.pt

2006-09-15

The mean values of the standard massic energy of combustion of crystalline anhydrous {alpha},{alpha}-trehalose (C{sub 12}H{sub 22}O{sub 11}, polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose (C{sub 12}H{sub 26}O{sub 13}) measured by static-bomb combustion calorimetry in oxygen, at the temperature T=298.15K, are {delta}{sub c}u{sup o}=-(16434.05+/-4.50)J.g{sup -1} and {delta}{sub c}u{sup o}=-(14816.05+/-3.52)J.g{sup -1}, respectively. The standard (p{sup o}=0.1MPa) molar enthalpy of formation of these compounds were derived from the corresponding standard molar enthalpies of combustion, respectively, {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 22}O{sub 11},cr)=-(2240.9+/-3.9)kJ.mol{sup -1}, and {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 26}O{sub 13},cr)=-(2832.6+/-3.6)kJ.mol{sup -1}. The values of the standard enthalpies of formation obtained in this work, together with data on enthalpies of solution at infinite dilution ({delta}{sub sol}H{sup {approx}}) for crystalline dihydrate and amorphous anhydrous trehalose, allow a better insight on the thermodynamic description of the trehalose system which can provide, together with the future research on the subject, a contribution for understanding the metabolism in several organisms, as well as the phase transition between the different polymorphs.

Reconstruction of spin-tensor of 4. 43 MeV state density matrix of the /sup 12/C nucleus in the /sup 12/C(. cap alpha. ,. cap alpha. sub(1). gamma. sub(4,43))/sup 12/C reaction at Esub(. cap alpha. )=25 MeV

Energy Technology Data Exchange (ETDEWEB)

Gurevich, G.S.; Lebedev, V.M.; Orlova, N.V.; Spasskij, A.V.; Teplov, I.B.; Shakhvorostova, G.V.; Belkina, M.R. (Moskovskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Yadernoj Fiziki)

1984-01-01

The results of measuring double differential cross sections of the reaction of inelastic scattering 24.8 MeV ..cap alpha..-particles sup(12)C(..cap alpha.., ..cap alpha..sub(1)..gamma..sub(4.43))sup(12)C in different planes of ..gamma..-quantum escape relatively to the plane of the reaction phisub(..gamma..)=30, 60 and 90 deg are presented. Non-monochromaticity of the beam made up 1%. Functions of angular correlation of the reaction are measured for four angles THETAsub(..cap alpha..)=21, 39, 59 and 135 deg corresponding to maxima of differential cross section in angular distribution of inelastically scattered ..cap alpha..-particles and for THETAsub(..cap alpha..)=89 deg corresponding to the minimum of angular distribution. The results of measurements permit to reconstruct all the components of irreducible spin-tensors of the matrix of state density 4.43 MeV (2/sup +/) formed in this reaction. The values of populations of substates by the projection of the spin of this state are obtained. The analysis of the obtained results testify to the fact that mechanism of inelastic scattering is not reduced to impulse approximation and mechanisms associated with delay in interaction do not make noticeable contribution for the given angles of ..cap alpha..-particle escape.

Energy dependence of event shapes and of $\\alpha_s$ at LEP 2

CERN Document Server

Abreu, P; Adye, T; Adzic, P; Albrecht, Z; Alderweireld, T; Alekseev, G D; Alemany, R; Allmendinger, T; Allport, P P; Almehed, S; Amaldi, Ugo; Amapane, N; Amato, S; Anassontzis, E G; Andersson, P; Andreazza, A; Andringa, S; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barbiellini, Guido; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Beillière, P; Belokopytov, Yu A; Belous, K S; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Bizouard, M A; Bloch, D; Blom, H M; Bonesini, M; Bonivento, W; Boonekamp, M; Booth, P S L; Borgland, A W; Borisov, G; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Boyko, I; Bozovic, I; Bozzo, M; Branchini, P; Brenke, T; Brenner, R A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschbeck, Brigitte; Buschmann, P; Cabrera, S; Caccia, M; Calvi, M; Camporesi, T; Canale, V; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Chapkin, M M; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cieslik, K; Collins, P; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crépé, S; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Davenport, Martyn; Da Silva, W; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Min, A; De Paula, L S; Dijkstra, H; Di Ciaccio, Lucia; Dolbeau, J; Doroba, K; Dracos, M; Drees, J; Dris, M; Duperrin, A; Durand, J D; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Ellert, M; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fanourakis, G K; Fassouliotis, D; Fayot, J; Feindt, Michael; Fenyuk, A; Ferrari, P; Ferrer, A; Ferrer-Ribas, E; Ferro, F; Fichet, S; Firestone, A; Flagmeyer, U; Föth, H; Fokitis, E; Fontanelli, F; Franek, B J; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gamblin, S; Gandelman, M; García, C; Gaspar, C; Gaspar, M; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Ghodbane, N; Gil, I; Glege, F; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; González-Caballero, I; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Grahl, J; Graziani, E; Green, C; Grimm, H J; Gris, P; Grosdidier, G; Grzelak, K; Günther, M; Guy, J; Hahn, F; Hahn, S; Haider, S; Hallgren, A; Hamacher, K; Hansen, J; Harris, F J; Hedberg, V; Heising, S; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Heuser, J M; Higón, E; Holmgren, S O; Holt, P J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hughes, G J; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, P E; Joram, C; Juillot, P; Kapusta, F; Karafasoulis, K; Katsanevas, S; Katsoufis, E C; Keränen, R; Kersevan, Borut P; Khomenko, B A; Khovanskii, N N; Kiiskinen, A P; King, B J; Kinvig, A; Kjaer, N J; Klapp, O; Klein, H; Kluit, P M; Kokkinias, P; Koratzinos, M; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Krammer, Manfred; Kriznic, E; Krstic, J; Krumshtein, Z; Kubinec, P; Kurowska, J; Kurvinen, K L; Lamsa, J; Lane, D W; Langefeld, P; Lapin, V; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Leinonen, L; Leisos, A; Leitner, R; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Lethuillier, M; Libby, J; Liko, D; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; Lopes, J H; López, J M; López-Fernandez, R; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Mahon, J R; Maio, A; Malek, A; Malmgren, T G M; Maltezos, S; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Masik, J; Mazzucato, F; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; McPherson, G; Meroni, C; Meyer, W T; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Moch, M; Møller, R; Mönig, K; Monge, M R; Moreau, X; Morettini, P; Morton, G A; Müller, U; Münich, K; Mulders, M; Mulet-Marquis, C; Muresan, R; Murray, W J; Muryn, B; Myatt, Gerald; Myklebust, T; Naraghi, F; Nassiakou, M; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Némécek, S; Neufeld, N; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nikolenko, M; Nomokonov, V P; Normand, Ainsley; Nygren, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Orazi, G; Österberg, K; Ouraou, A; Paganoni, M; Paiano, S; Pain, R; Paiva, R; Palacios, J; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Pegoraro, M; Peralta, L; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Phillips, H T; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Ratoff, P N; Read, A L; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Reinhardt, R; Renton, P B; Resvanis, L K; Richard, F; Rídky, J; Rinaudo, G; Røhne, O M; Romero, A; Ronchese, P; Rosenberg, E I; Rosinsky, P; Roudeau, Patrick; Rovelli, T; Royon, C; Ruhlmann-Kleider, V; Ruiz, A; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sampsonidis, D; Sannino, M; Schneider, H; Schwemling, P; Schwering, B; Schwickerath, U; Schyns, M A E; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Sekulin, R L; Shellard, R C; Sheridan, A; Siebel, M; Simard, L C; Simonetto, F; Sissakian, A N; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Sopczak, André; Sosnowski, R; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stanic, S; Stevenson, K; Stocchi, A; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tegenfeldt, F; Terranova, F; Thomas, J; Timmermans, J; Tinti, N; Tkatchev, L G; Todorova-Nová, S; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tzamarias, S; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; Van der Velde, C; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Van Lysebetten, A; Van Vulpen, I B; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Verzi, V; Vilanova, D; Vitale, L; Vlasov, E; Vodopyanov, A S; Vollmer, C F; Voulgaris, G; Vrba, V; Wahlen, H; Walck, C; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G R; Winter, M; Witek, M; Wolf, G; Yi, J; Yushchenko, O P; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zucchelli, G C; Zumerle, G

1999-01-01

Infrared and collinear safe event shape distributions and their mean values are determined using the data taken at ve di erent centre of mass energies above $M_Z$ with the DELPHI detector at LEP. From the event shapes, the strong coupling $\\alpha_s$ is extracted in $O(\\alpha^2_s)$, NLLA and a combined scheme using hadronisation corrections evaluated with fragmentation model generators as well as using an analytical power ansatz. Comparing these measurements to those obtained at MZ, the energy dependence (running) of $\\alpha_s$ is accessible. The logarithmic energy slope of the inverse strong coupling is measured to be $d\\alpha_{s}^{-1}/d log(E_{cm}) = 1.39 \\pm 0.34(stat) \\pm 0.17(syst)$, in good agreement with the QCD expectation of 1.27.

Alpha Blockers

Science.gov (United States)

... quickly, but their effects last only a few hours. Long-acting medications take longer to work, but their effects last longer. Which alpha blocker is best for you depends on your health and the condition being treated. Alpha blockers are ...

Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.

Directory of Open Access Journals (Sweden)

Alison L McCormack

Full Text Available The protein alpha-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal alpha-synuclein burden. Here, feasibility and safety of alpha-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA directed against alpha-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of alpha-synuclein mRNA and protein in the infused (left vs. untreated (right hemisphere and revealed a significant 40-50% suppression of alpha-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in alpha-synuclein. Infusion with alpha-synuclein siRNA, while lowering alpha-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i the number and phenotype of nigral dopaminergic neurons, and (ii the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-alpha-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics.

Alpha neurofeedback training improves SSVEP-based BCI performance

Science.gov (United States)

Wan, Feng; Nuno da Cruz, Janir; Nan, Wenya; Wong, Chi Man; Vai, Mang I.; Rosa, Agostinho

2016-06-01

Objective. Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) can provide relatively easy, reliable and high speed communication. However, the performance is still not satisfactory, especially in some users who are not able to generate strong enough SSVEP signals. This work aims to strengthen a user’s SSVEP by alpha down-regulating neurofeedback training (NFT) and consequently improve the performance of the user in using SSVEP-based BCIs. Approach. An experiment with two steps was designed and conducted. The first step was to investigate the relationship between the resting alpha activity and the SSVEP-based BCI performance, in order to determine the training parameter for the NFT. Then in the second step, half of the subjects with ‘low’ performance (i.e. BCI classification accuracy <80%) were randomly assigned to a NFT group to perform a real-time NFT, and the rest half to a non-NFT control group for comparison. Main results. The first step revealed a significant negative correlation between the BCI performance and the individual alpha band (IAB) amplitudes in the eyes-open resting condition in a total of 33 subjects. In the second step, it was found that during the IAB down-regulating NFT, on average the subjects were able to successfully decrease their IAB amplitude over training sessions. More importantly, the NFT group showed an average increase of 16.5% in the SSVEP signal SNR (signal-to-noise ratio) and an average increase of 20.3% in the BCI classification accuracy, which was significant compared to the non-NFT control group. Significance. These findings indicate that the alpha down-regulating NFT can be used to improve the SSVEP signal quality and the subjects’ performance in using SSVEP-based BCIs. It could be helpful to the SSVEP related studies and would contribute to more effective SSVEP-based BCI applications.

Differences in adjustment between individuals with alpha-1 antitrypsin deficiency (AATD)-associated COPD and non-AATD COPD.

Science.gov (United States)

Holm, Kristen E; Borson, Soo; Sandhaus, Robert A; Ford, Dee W; Strange, Charlie; Bowler, Russell P; Make, Barry J; Wamboldt, Frederick S

2013-04-01

Smokers who have severe alpha-1 antitrypsin deficiency (AATD) are at risk for developing COPD earlier in life than smokers without AATD, and are likely to experience challenges adjusting to their illness because they are in a highly productive life stage when they are diagnosed with COPD. This study examined whether individuals with AATD-associated COPD differ from individuals with non-AATD COPD with regard to depression, anxiety, dyspnea, and health-related quality of life (HRQL). Cross-sectional data were collected via self-report questionnaires completed by 480 individuals with non-AATD COPD and 578 individuals with AATD-associated COPD under protocols with IRB approval. Multiple linear regression models were used to test whether individuals with non-AATD COPD differed from individuals with AATD-associated COPD with regard to depression, anxiety, dyspnea, and HRQL. All models adjusted for demographic and health characteristics. Individuals with AATD-associated COPD did not report more symptoms of depression or anxiety; however, they did report more dyspnea (B = 0.31, 95% CI = 0.16 to 0.47, p < 0.001) and impairment in HRQL (B = 4.75, 95% CI = 2.10 to 7.41, p < 0.001) than other individuals with COPD. Individuals with AATD-associated COPD were more likely to be a member of a couple (rather than single) and had a higher level of education when compared to individuals with non-AATD COPD. Resources available to persons with AATD-associated COPD, such as being in a serious relationship and having higher education, may offset the effect of age when considering symptoms of depression and anxiety in patients with COPD.

Differences in Adjustment between Individuals with Alpha-1 Antitrypsin Deficiency (AATD) Associated COPD and Non-AATD COPD

Science.gov (United States)

Holm, Kristen E.; Borson, Soo; Sandhaus, Robert A.; Ford, Dee W.; Strange, Charlie; Bowler, Russell P.; Make, Barry J.; Wamboldt, Frederick S.

2013-01-01

Smokers who have severe alpha-1 antitrypsin deficiency (AATD) are at risk for developing COPD earlier in life than smokers without AATD, and are likely to experience challenges adjusting to their illness because they are in a highly productive life stage when they are diagnosed with COPD. This study examined whether individuals with AATD-associated COPD differ from individuals with non-AATD COPD with regard to depression, anxiety, dyspnea, and health-related quality of life (HRQL). Cross-sectional data were collected via self-report questionnaires completed by 480 individuals with non-AATD COPD and 578 individuals with AATD-associated COPD under protocols with IRB approval. Multiple linear regression models were used to test whether individuals with non-AATD COPD differed from individuals with AATD-associated COPD with regard to depression, anxiety, dyspnea, and HRQL. All models adjusted for demographic and health characteristics. Individuals with AATD-associated COPD did not report more symptoms of depression or anxiety; however, they did report more dyspnea (B = 0.31, 95% CI = 0.16 to 0.47, p < 0.001) and impairment in HRQL (B = 4.75, 95% CI = 2.10 to 7.41, p < 0.001) than other individuals with COPD. Individuals with AATD-associated COPD were more likely to be a member of a couple (rather than single) and had a higher level of education when compared to individuals with non-AATD COPD. Resources available to persons with AATD-associated COPD, such as being in a serious relationship and having higher education, may offset the effect of age when considering symptoms of depression and anxiety in patients with COPD. PMID:23547634

Orientational relationships between phases in the {gamma}{yields}{alpha} transformations for uranium-molybdenum alloys; Relations d'orientation entre phases dans les transformations {gamma}{yields}{alpha} des alliages uranium-molybdene

Energy Technology Data Exchange (ETDEWEB)

Brun, G [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1966-04-01

A crystallographic study has been made of the {gamma} {yields} {alpha} + {gamma} transformation in the alloy containing 3 per cent by weight of molybdenum using electronic micro-diffraction; it has been possible to establish the orientational relationships governing the germination of the {alpha} phase in the {gamma} phase. One finds: (111){gamma} // (100) {alpha}, (112-bar){gamma} // (010) {alpha}, (11-bar 0){gamma} // (001){alpha}. By choosing a monoclinic lattice containing the same number of atoms as the orthorhombic lattice for defining the {gamma} mother phase, the change in structure has been explained by adding a homogeneous (112-bar){gamma} [111]{gamma} shearing deformation to a heterogeneous deformation brought about by slipping of the atoms which are not situated at the nodes of this lattice. The identity of the orientation relationships {gamma}/{alpha} and {gamma}/{alpha}''b and the loss of coherence {gamma} /{alpha} as a function of temperature or of time lead to the conclusion that, in the range studied, the {gamma} {yields} {alpha} transformation begins with a martensitic process and continues by germination and growth. (author) [French] Une etude cristallographique de la transformation {gamma} {yields} {alpha} + {gamma} dans l'alliage {alpha} 3 pour cent en poids de Mo, effectuee par microdiffraction electronique a permis d'etablir les relations d'orientation regissant la germination de {alpha} dans {gamma}. On a: (111){gamma} // (100){alpha}, (112-bar){gamma} // (010){alpha}, (11-bar 0){gamma} // (001){alpha}. En choisissant pour decrire la phase mere {gamma} une maille monoclinique contenant le meme nombre d'atomes que la maille orthorhombique {alpha}, le changement de structure a ete explique en superposant a une deformation homogene par cisaillement (112-bar){gamma} [111]{gamma} une deformation heterogene par glissement des atomes non situes aux noeuds de cette maille. L identite des relations d'orientation {gamma}/{alpha} et {gamma} /{alpha

Uranium analysis in Cypriot groundwaters by total alpha-radiometry and alpha-spectroscopy

International Nuclear Information System (INIS)

Efstathiou, Maria; Kiliari, Tasoula; Pashalidis, Ioannis

2011-01-01

Two different alpha-radiometric methods (e.g. alpha-spectroscopy and alpha-particle counting) have been applied to the determination of uranium in Cypriot groundwater samples after separation of the radionuclides by cation exchange using Chelex-100 and its electrodeposition on stainless steel planchettes. The data obtained were compared to show the advantages and disadvantages of the two radiometric methods, determine the alpha-radioactivity concentration and the radiation dose associated with the use of the studied groundwaters. Calibration of the methods was performed by means of uranium standard solutions and the corresponding data were used to evaluate linear range, detector efficiency, detection limits, value of the information obtained, and time of analysis of the methods. Comparison of the data obtained from calibration and natural sample measurements has shown that alpha-particle counting with a simple alpha-radiometer (equipped with a semiconductor detector) may offer only an activity value and not detailed information about the isotopic composition but it is the fastest method and the method of choice if only a screening method for the alpha-radioactivity measurement is required. Based on the alpha-radioactivity data, the corresponding radiation dose was estimated for situations where the groundwaters are used for drinking water purposes.

Influence of fast alpha diffusion and thermal alpha buildup on tokamak reactor performance

International Nuclear Information System (INIS)

Uckan, N.A.; Tolliver, J.S.; Houlberg, W.A.; Attenberger, S.E.

1988-01-01

The effect of fast alpha diffusion and thermal alpha accumulation on the confinement capability of a candidate Engineering Test Reactor plasma (Tokamak Ignition/Burn Experimental Reactor) in achieving ignition and steady-state driven operation has been assessed using both global and 1-1/2-dimensional transport models. Estimates are made of the threshold for radial diffusion of fast alphas and thermal alpha buildup. It is shown that a relatively low level of radial transport, when combined with large gradients in the fast alpha density, leads to a significant radial flow with a deleterious effect on plasma performance. Similarly, modest levels of thermal alpha concentration significantly influence the ignition and steady-state burn capability

ABO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination.

Science.gov (United States)

Nakajima, T; Sano, R; Takahashi, Y; Watanabe, K; Kubo, R; Kobayashi, M; Takahashi, K; Takeshita, H; Kominato, Y

2016-01-01

Recent investigation of transcriptional regulation of the ABO genes has identified a candidate erythroid cell-specific regulatory element, named the +5·8-kb site, in the first intron of ABO. Six haplotypes of the site have been reported previously. The present genetic population study demonstrated that each haplotype was mostly linked with specific ABO alleles with a few exceptions, possibly as a result of hybrid formation between common ABO alleles. Thus, investigation of these haplotypes could provide a clue to further elucidation of ABO alleles. © 2015 International Society of Blood Transfusion.

[Age-related change in the alpha-tocopherolquinone/alpha-tocopherol ratio in the rat erythrocyte membrane].

Science.gov (United States)

Yanagawa, K; Takeda, H; Matsumiya, T; Takasaki, M

1999-05-01

alpha-Tocopherol (alpha-Toc), a lipophilic phenolic antioxidant that is localized mainly in the biomembrane, protects cells against oxidation-associated cytotoxicity by prevention of membrane lipid peroxidation, maintenance of the redox balance intracellular thiols and stabilization of the membrane structure. We investigated the age-related changes in redox dynamics of alpha-Toc in plasma and erythrocyte membrane of an elderly (66 weeks old) and young group (10 weeks old). Total, alpha-, beta + gamma-, delta-Toc and alpha-tocopherolquinone (alpha-TocQ) in plasma and erythrocyte membrane were determined by high-performance liquid chromatography (HPLC) with a series of multiple coulometric working electrodes (CWE). Rat venous blood sample was divided into plasma and erythrocyte layers by centrifugation, and then erythrocyte membrane sample was prepared according to the method of Dodge et al. under a stream of nitrogen. In plasma, total and alpha-Toc concentrations were increased, and beta + gamma-, delta-Toc and alpha-TocQ concentrations were decreased age-dependently. In the erythrocyte membrane, total, alpha-TocQ concentrations and three fractions of tocopherols decreased age-dependently. Also, a decrease in the alpha-TocQ/alpha-Toc ratio in erythrocyte membrane was observed in the elderly group. These findings suggest that the alpha-Toc uptake in erythrocyte membrane and utilization rate of alpha-Toc in erythrocyte membrane decline age-dependently. This decline may promote membrane lipid peroxidation. alpha-Toc redox dynamics in erythrocyte membrane were useful to investigate the pathophysiology of aging mechanisms related to oxidative stress.

Field study of alpha characterization of a D ampersand D site using long-range alpha detectors

International Nuclear Information System (INIS)

Rawool-Sullivan, M.W.; Allander, K.S.; Bounds, J.A.; Koster, J.E.; MacArthur, D.W.; Sprouse, L.L.; Stout, D.; Vaccarella, J.A.; Vu, T.Q.

1994-01-01

A successful and cost-effective D ampersand D effort relies upon an accurate, real-time, in situ, and non-destructive method of characterization of contamination both before and after the decontamination process. Detector systems based on long-range alpha detection (LRAD) technology meet these criteria. Currently, LANL is in the process of investigating, designing, or building various surface monitors, various pipe monitors, and glove-box monitors. This paper describes the field studies conducted using detectors based on LRAD technology

Identification of a novel bile acid in swans, tree ducks, and geese: 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid.

Science.gov (United States)

Kakiyama, Genta; Iida, Takashi; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio; Hagey, Lee R; Schteingart, Claudio D; Hofmann, Alan F

2006-07-01

By HPLC, a taurine-conjugated bile acid with a retention time different from that of taurocholate was found to be present in the bile of the black-necked swan, Cygnus melanocoryphus. The bile acid was isolated and its structure, established by (1)H and (13)C NMR and mass spectrometry, was that of the taurine N-acyl amidate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid. The compound was shown to have chromatographic and spectroscopic properties that were identical to those of the taurine conjugate of authentic 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid, previously synthesized by us from ursodeoxycholic acid. By HPLC, the taurine conjugate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid was found to be present in 6 of 6 species in the subfamily Dendrocygninae (tree ducks) and in 10 of 13 species in the subfamily Anserinae (swans and geese) but not in other subfamilies in the Anatidae family. It was also not present in species from the other two families of the order Anseriformes. 3alpha,7alpha,15alpha-Trihydroxy-5beta-cholan-24-oic acid is a new primary bile acid that is present in the biliary bile acids of swans, tree ducks, and geese and may be termed 15alpha-hydroxy-chenodeoxycholic acid.

Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi's sarcoma

NARCIS (Netherlands)

de Wit, R.; Schattenkerk, J. K.; Boucher, C. A.; Bakker, P. J.; Veenhof, K. H.; Danner, S. A.

1988-01-01

The effectiveness and antiretroviral activities of interferon-alpha in AIDS-related Kaposi's sarcoma was assessed in a non-randomised, phase-II clinical trial. 28 patients were treated with high-dose (27-36 MU) human recombinant interferon-alpha 2a subcutaneously every day for 8 weeks. In patients

Four-body problem for four bound alpha particles in 16O

International Nuclear Information System (INIS)

Osman, A.

1980-02-01

The alpha cluster model is used in considering the 16 O nucleus as a bound state of four alpha particles. This problem is represented by integral equations which are exact effective two-particle equations. These equations have the form of two-particle Lippmann-Schwinger equations. The separable expressions are used in approximating the scattering amplitudes in the separable potential model to include also few and small non-separable rest parts of the interactions. The integral equations obtained are manageable and suitable for computations. Numerical calculations are carried out for the 16 O nucleus, with the structure of four bound alpha particles. The obtained binding energy of 16 O with that structure is 16.86 MeV which is in good agreement with the experimental value. (author)

Buffett's Alpha

DEFF Research Database (Denmark)

Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

Sterol synthesis. A novel reductive rearrangement of an alpha,beta-unsaturated steroidal epoxide; a new chemical synthesis of 5alpha-cholest-8(14)-en-3beta, 15alpha-diol.

Science.gov (United States)

Parish, E J; Schroepfer, G J

1977-04-01

Reduction of 3beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with either lithium triethylboro-hydride or lithium aluminum hydride (4 molar excess) gave 5-alpha-cholest-8(14)-en-3beta,15alpha-diol in high yield. Reduction of the epoxy ester with lithium triethylborodeuteride or lithium aluminum deuteride (4 molar excess) gave [7alpha-2-H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol. Reduction of 2beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with a large excess (24 molar excess) of lithium aluminum hydride gave, in addition to the expected 5alpha-cholest-8(14)-en-3beta,15alpha-diol, a significant yield (33%) of 5alpha-cholest-8(14)-en-3beta-o1. Reduction of the epoxy ester with a large excess (24 molar excess) of lithium aluminum deuteride gave [7alpha-2H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol and 5alpha-cholest-8(14)-en-3beta-o1 which contained two atoms of stably bound deuterium.

Non-Perturbative Formulation of Time-Dependent String Solutions

CERN Document Server

Alexandre, J; Mavromatos, Nikolaos E; Alexandre, Jean; Ellis, John; Mavromatos, Nikolaos E.

2006-01-01

We formulate here a new world-sheet renormalization-group technique for the bosonic string, which is non-perturbative in the Regge slope alpha' and based on a functional method for controlling the quantum fluctuations, whose magnitudes are scaled by the value of alpha'. Using this technique we exhibit, in addition to the well-known linear-dilaton cosmology, a new, non-perturbative time-dependent background solution. Using the reparametrization invariance of the string S-matrix, we demonstrate that this solution is conformally invariant to alpha', and we give a heuristic inductive argument that conformal invariance can be maintained to all orders in alpha'. This new time-dependent string solution may be applicable to primordial cosmology or to the exit from linear-dilaton cosmology at large times.

Delineating SPTAN1 associated phenotypes

DEFF Research Database (Denmark)

Syrbe, Steffen; Harms, Frederike L; Parrini, Elena

2017-01-01

De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutati...

Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

Directory of Open Access Journals (Sweden)

Pascariello Caterina

2008-05-01

Full Text Available Abstract Background Aldehyde dehydrogenase (ALDH is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007. The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively. As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a. Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA. Conclusion Our study, comparing surface antigen expression of

Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

Science.gov (United States)

Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

2009-10-15

Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

Drugs interacting with alpha adrenoceptors

NARCIS (Netherlands)

van Zwieten, P. A.

1989-01-01

Alpha adrenoceptors should be divided into various subtypes, comprising pre/postsynaptic and alpha 1/alpha 2-subpopulations, respectively. This classification implicates important functional differences between the various alpha-receptor subtypes, including certain differences in signal transduction

Non-Rutherford cross-sections for alpha elastic scattering off Z = 28-38 elements in the energy range up to 10 MeV

Science.gov (United States)

Gurbich, A. F.; Bokhovko, M. V.

2018-04-01

The alpha elastic scattering cross-sections for Ni, Cu, and Y were measured at the energies above the onset of the non-Rutherford scattering. The obtained experimental data along with data from literature were incorporated into the theoretical analysis in the framework of the optical model. The optimization of the model parameters provided a basis for the calculations of the differential cross-sections for Z = 28-38 elements in the energy range up to 10 MeV. The obtained cross sections were made available for common use through the SigmaCalc web site at http://sigmacalc.iate.obninsk.ru/.

Penetration of HEPA filters by alpha recoil aerosols

International Nuclear Information System (INIS)

McDowell, W.J.; Seeley, F.G.; Ryan, M.T.

1976-01-01

Tests at Oak Ridge National Laboratory confirmed that alpha-emitting particulate matter does penetrate high-efficiency filter medium, identical to that used in HEPA filters, much more effectively than do non-radioactive or beta-gamma active aerosols. Filter retention efficiencies drastically lower than the 99.97 percent quoted for ordinary particulate matter have been observed with 212 Pb, 253 Es, and 238 Pu sources, indicating that the phenomenon is common to all of these and probably to all alpha-emitting materials of appropriate half-life. Results with controlled air-flow through filters in series are consistent with the picture of small particles dislodged from the ''massive'' surface of an alpha-active material, and then repeatedly dislodged from positions on the filter fibers, by the alpha recoils. The process shows only a small dependence on the physical form of the source material. Oxide dust, nitrate salt, and plated metal all seem to generate the recoil particles effectively. The amount penetrating a series of filters depends on the total amount of activity in the source material, its specific activity, and the length of time of air flow. Dependence on the air flow velocity is slight. It appears that this phenomenon has not been observed in previous experiments with alpha-active aerosols because the tests did not continue for a sufficiently long time. A theoretical model of the process has been developed, amenable to computer handling, that should allow calculation of the rate constants associated with the transfer through and release of radioactive material from a filter system by this process

Alpha radioactivity in tobacco leaves: Effect of fertilizers

Energy Technology Data Exchange (ETDEWEB)

Nain, Mahabir [Department of Physics, Government College Karnal, Haryana 132001 (India)], E-mail: mnain@rediffmail.com; Chauhan, R.P. [Department of Physics, National Institute of Technology, Kurukshetra 136119 (India); Chakarvarti, S.K. [Department of Applied Physics, NIT, Kurukshetra 136119 (India)

2008-08-15

The link between cigarette smoke and cancer has long been established. Smokers are 10 times at a greater risk of developing lung cancer than that of non-smokers. The toxicity in tobacco is considered mainly due to the presence of chemi-toxins like nicotine, tar, aromatic hydrocarbons, sterols and many other materials leading to mutagenicity and carcinogenicity. There are many reports on the presence of naturally occurring radionuclides viz., {sup 210}Po and {sup 210}Pb in tobacco. Investigations on alpha-emitting radionuclides, especially on {sup 210}Po have gained significant importance as alpha interactions with chromosomes of cells may contribute to early arteriosclerosis developments in tobacco smokers. Due to relatively high activity concentration of {sup 210}Po and {sup 210}Pb that are found in tobacco and its product cigarette can increase the internal intake of both the radionuclides and their concentrations in lung tissues. This causes an increase in the internal radiation dose which enhances the instances of lung cancer. Many workers have tried to explain the role of {sup 210}Po in tobacco in the epidemiological investigation of cancer and tumour formation. In the present work, the estimation of alpha radioactivity in tobacco leaves taken from tobacco plants grown using different types of chemical fertilizers like diammonium phosphate (DAP), zinc sulphate, potash, super phosphate, urea etc. in varying amounts before the plantation of the seedlings has been made. For these measurements we used {alpha}-sensitive LR-115 type II plastic track detectors. The results indicate an increase in alpha radioactivity with the use of some fertilizers.

Functional role of frontal alpha oscillations in creativity.

Science.gov (United States)

Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

2015-06-01

Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Ng, Stanley K.L. [Singapore Immunology Network A-STAR (Singapore); Neo, Soek-Ying, E-mail: neo_soek_ying@sics.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Yap, Yann-Wan [Singapore Immunology Network A-STAR (Singapore); Karuturi, R. Krishna Murthy; Loh, Evelyn S.L. [Genome Institute of Singapore A-STAR (Singapore); Liau, Kui-Hin [Department of General Surgery, Tan Tock Seng Hospital (Singapore); Ren, Ee-Chee, E-mail: ren_ee_chee@immunol.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore (Singapore)

2009-09-18

Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2{alpha}) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2{alpha} mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2{alpha} was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2{alpha} can modulate HCC cell growth.

Alpha-in-air monitor for continuous monitoring based on alpha to beta ratio

International Nuclear Information System (INIS)

Somayaji, K.S.; Venkataramani, R.; Swaminathan, N.; Pushparaja

1997-01-01

Measurement of long-lived alpha activity collected on a filter paper in continuous air monitoring of ambient working environment is difficult due to interference from much larger concentrations of short-lived alpha emitting daughter products of 222 Rn and 220 Rn. However, the ratio between the natural alpha and beta activity is approximately constant and this constancy of the ratio is used to discriminate against short-lived natural radioactivity in continuous air monitoring. Detection system was specially designed for the purpose of simultaneous counting of alpha and beta activity deposited on the filter paper during continuous monitoring. The activity ratios were calculated and plotted against the monitoring duration up to about six hours. Monitoring was carried out in three facilities with different ventilation conditions. Presence of any long-lived alpha contamination on the filter paper results in increase in the alpha to beta ratio. Long-lived 239 Pu contamination of about 16 DAC.h could be detected after about 45 minutes of commencement of the sampling. The experimental results using prototype units have shown that the approach of using alpha to beta activity ratio method to detect long-lived alpha activity in the presence of short-lived natural activity is satisfactory. (author)

Alpha-bungarotoxin binding to target cell in a developing visual system by carboxylated nanodiamond

Energy Technology Data Exchange (ETDEWEB)

Liu, K-K; Chen, P-Y; Lee, Tony J F; Chao, J-I [Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien 970, Taiwan (China); Chen, M-F [Neuro-Medical Scientific Center, Tzu Chi General Hospital, Hualien 970, Taiwan (China); Cheng, C-L [Department of Physics, National Dong Hwa University, Hualien 974, Taiwan (China); Chang, C-C [Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu 300, Taiwan (China); Ho, Y-P [Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan (China)], E-mail: chaoji@mail.tcu.edu.tw

2008-05-21

Biological molecules conjugating with nanoparticles are valuable for applications including bio-imaging, bio-detection, and bio-sensing. Nanometer-sized diamond particles have excellent electronic and chemical properties for bio-conjugation. In this study, we manipulated the carboxyl group produced on the surface of nanodiamond (carboxylated nanodiamond, cND) for conjugating with alpha-bungarotoxin ({alpha}-BTX), a neurotoxin derived from Bungarus multicinctus with specific blockade of alpha7-nicotinic acetylcholine receptor ({alpha}7-nAChR). The electrostatic binding of cND-{alpha}-BTX was mediated by the negative charge of the cND and the positive charge of the {alpha}-BTX in physiological pH conditions. Sodium dodecyl sulfate-polyacrylamide gel analysis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF-MS) spectra displayed that {alpha}-BTX proteins were conjugated with cND particles via non-covalent bindings. The green fluorescence of the cND particles combining with the red fluorescence of tetramethylrhodamine-labeled {alpha}-BTX presented a yellow color at the same location, which indicated that {alpha}-BTX proteins were conjugated with cND particles. Xenopus laevis's oocytes expressed the human {alpha}7-nAChR proteins by microinjection with {alpha}7-nAChR mRNA. The cND-{alpha}-BTX complexes were bound to {alpha}7-nAChR locating on the cell membrane of oocytes and human lung A549 cancer cells analyzed by laser scanning confocal microscopy. The choline-evoked {alpha}7-nAChR-mediated inward currents of the oocytes were blocked by cND-{alpha}-BTX complexes in a concentration-dependent manner using two-electrode voltage-clamp recording. Furthermore, the fluorescence intensity of cND-{alpha}-BTX binding on A549 cells could be quantified by flow cytometry. These results indicate that cND-conjugated {alpha}-BTX still preserves its biological activity in blocking the function of {alpha}7-nAChR, and provide a visual

Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

International Nuclear Information System (INIS)

Allen, Barry J.; Abbas Rizvi, Syed M.; Qu, Chang F.; Smith, Ross C.

2011-01-01

Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213 Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro

Single-trial log transformation is optimal in frequency analysis of resting EEG alpha.

Science.gov (United States)

Smulders, Fren T Y; Ten Oever, Sanne; Donkers, Franc C L; Quaedflieg, Conny W E M; van de Ven, Vincent

2018-02-01

The appropriate definition and scaling of the magnitude of electroencephalogram (EEG) oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and nonlinear transformation of alpha power. A family of nonlinear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs within each participant, or across participants. The transformations were performed either at the single epoch level or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in 2 min of eyes-closed and 2 min of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12 Hz) alpha band. The log-transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed conditions when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log-transform on single epochs to achieve appropriate scaling of alpha magnitude. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

Science.gov (United States)

Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

2015-01-01

The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

Long-range alpha detector

International Nuclear Information System (INIS)

MacArthur, D.W.; McAtee, J.L.

1991-01-01

Historically, alpha-particle and alpha-contamination detectors have been limited by the very short range of alpha particles in air and by relatively poor sensitivity even if the particles are intercepted. Alpha detectors have had to be operated in a vacuum or in close proximity to the source if reasonable efficiency is desired. Alpha particles interact with the ambient air, producing ionization in the air at the rate of ∼30,000 ion pairs per mega-electron-volt of alpha energy. These charges can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions. The long-range alpha detector (LRAD) offers several advantages over more traditional alpha detectors. First and foremost, it can operate efficiently even if the contamination is not easily accessible. Second, ions generated by contamination in crevices and other unmonitorable locations can be detected if the airflow penetrates those areas. Third, all of the contamination on a large surface will generate ions that can be detected in a single detector; hence, the detector's sensitivity to distributed sources is not limited by the size of the probe. Finally, a simple ion chamber can detect very small electric currents, making this technique potentially quite sensitive

FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia

International Nuclear Information System (INIS)

Pašaliç, Z; Greif, P A; Jurinoviç, V; Mulaw, M; Kakadia, P M; Tizazu, B; Fröhlich-Archangelo, L; Krause, A; Bohlander, S K

2011-01-01

The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294–335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6

Treatment of alpha bearing wastes

International Nuclear Information System (INIS)

1988-01-01

This report deals with the current state of the art of alpha waste treatment, which is an integral part of the overall nuclear waste management system. The International Atomic Energy Agency (IAEA) defines alpha bearing waste as 'waste containing one or more alpha emitting radionuclides, usually actinides, in quantities above acceptable limits'. The limits are established by national regulatory bodies. The limits above which wastes are considered as alpha contaminated refer to the concentrations of alpha emitters that need special consideration for occupational exposures and/or potential safety, health, or environmental impact during one or more steps from generation through disposal. Owing to the widespread use of waste segregation by source - that is, based upon the 'suspect origin' of the material - significant volumes of waste are being handled as alpha contaminated which, in fact, do not require such consideration by reason of risk or environmental concern. The quantification of de minimis concepts by national regulatory bodies could largely contribute to the safe reduction of waste volumes and associated costs. Other factors which could significantly contribute to the reduction of alpha waste arisings are an increased application of assaying and sorting, instrumentation and the use of feedback mechanisms to control or modify the processes which generate these wastes. Alpha bearing wastes are generated during fabrication and reprocessing of nuclear fuels, decommissioning of alpha contaminated facilities, and other activities. Most alpha wastes are contact handled, but a small portion may require shielding or remote handling because of high levels of neutron (n), beta (β), or gamma (γ) emissions associated with the waste material. This report describes the sources and characteristics of alpha wastes and strategies for alpha waste management. General descriptions of treatment processes for solid and liquid alpha wastes are included. 71 refs, 14 figs, 9 tabs

New ALPHA-2 magnet

CERN Multimedia

Anaïs Schaeffer

2012-01-01

On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

ALPHA-2: the sequel

CERN Multimedia

Katarina Anthony

2012-01-01

While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.   The ALPHA team lower the new superconducting solenoid magnet into place. The ALPHA collaboration is working at full speed to complete the ALPHA-2 set-up for mid-November – this will give them a few weeks of running before the AD shutdown on 17 December. “We really want to get some experience with this device this year so that, if we need to make any changes, we will have time during the long shutdown in which to make them,” says Jeffrey Hangst, ALPHA spokesperson. “Rather than starting the 2014 run in the commissioning stage, we will be up and running from the get go.&...

Technical Basis for the Use of Alpha Absorption Corrections on RCF Gross Alpha Data

International Nuclear Information System (INIS)

Ceffalo, G.M.

1999-01-01

This document provides the supporting data and rationale for making absorption corrections to gross alpha data to correct alpha data for loss due to absorption in the sample matrix. For some time there has been concern that the gross alpha data produced by the Environmental Restoration Contractor Radiological Counting Facility, particularly gross alpha analysis on soils, has been biased toward low results, as no correction for self-absorption was applied to the counting data. The process was investigated, and a new methodology for alpha self-absorption has been developed

Chemical reactivity of {alpha}-isosaccharinic acid in heterogeneous alkaline systems

Energy Technology Data Exchange (ETDEWEB)

Glaus, M. A.; Loon, L. R. Van

2009-05-15

Cellulose degradation under alkaline conditions is of relevance for the mobility of many radionuclides in the near-field of a cementitious repository for radioactive waste, because metal-binding degradation products may be formed. Among these, {alpha}- isosaccharinic acid ({alpha}-ISA) is the strongest complexant. The prediction of the equilibrium concentration of {alpha}-ISA in cement pore water is therefore an important step in the assessment of the influence of cellulose degradation products on the speciation of radionuclides in such environments. The present report focuses on possible chemical transformation reactions of {alpha}-ISA in heterogeneous alkaline model systems containing either Ca(OH){sub 2} or crushed hardened cement paste. The transformation reactions were monitored by measuring the concentration of {alpha}-ISA by high performance anion exchange chromatography and the formation of reaction products by high performance ion exclusion chromatography. The overall loss of organic species from solution was monitored by measuring the concentration of non-purgeable organic carbon. The reactions were examined in diluted and compacted suspensions, at either 25 {sup o}C or 90 {sup o}C, and under anaerobic atmospheres obtained by various methods. It was found that {alpha}-ISA was transformed under all conditions tested to some extent. Reaction products, such as glycolate, formate, lactate and acetate, all compounds with less complexing strength than {alpha}-ISA, were detected. The amount of reaction products identified by the chromatographic technique applied was {approx} 50 % of the amount of {alpha}-ISA reacted. Sorption of {alpha}-ISA to Ca(OH){sub 2} contributed only to a minor extent to the loss of {alpha}-ISA from the solution phase. As the most important conclusion of the present work it was demonstrated that the presence of oxidising agents had a distinctive influence on the turnover of {alpha}-ISA. Under aerobic conditions {alpha}-ISA was

GABA regulates the rat hypothalamic-pituitary-adrenocortical axis via different GABA-A receptor alpha-subtypes

DEFF Research Database (Denmark)

Mikkelsen, Jens D; Bundzikova, Jana; Larsen, Marianne Hald

2008-01-01

dependent on the composition of the GABA-A receptor subunits through which they act. We show here that positive modulators of alpha(1)-subtype containing GABA-A receptors with zolpidem (10 mg/kg) increase HPA activity in terms of increase in plasma corticosterone and induction of Fos in the PVN, whereas...... after positive modulation of GABA-A receptors composed of alpha(1)-subunit(s) affects a selective afferent system than the PVN, which is distinct from another afferent system(s) activated by non alpha(1)-containing GABA-A receptors....

Cloning, expression, and mapping of allergenic determinants of alphaS1-casein, a major cow's milk allergen.

Science.gov (United States)

Schulmeister, Ulrike; Hochwallner, Heidrun; Swoboda, Ines; Focke-Tejkl, Margarete; Geller, Beate; Nystrand, Mats; Härlin, Annika; Thalhamer, Josef; Scheiblhofer, Sandra; Keller, Walter; Niggemann, Bodo; Quirce, Santiago; Ebner, Christoph; Mari, Adriano; Pauli, Gabrielle; Herz, Udo; Valenta, Rudolf; Spitzauer, Susanne

2009-06-01

Milk is one of the first components introduced into human diet. It also represents one of the first allergen sources, which induces IgE-mediated allergies in childhood ranging from gastrointestinal, skin, and respiratory manifestations to severe life-threatening manifestations, such as anaphylaxis. Here we isolated a cDNA coding for a major cow's milk allergen, alphaS1-casein, from a bovine mammary gland cDNA library with allergic patients' IgE Abs. Recombinant alphaS1-casein was expressed in Escherichia coli, purified, and characterized by circular dichroism as a folded protein. IgE epitopes of alphaS1-casein were determined with recombinant fragments and synthetic peptides spanning the alphaS1-casein sequence using microarrayed components and sera from 66 cow's milk-sensitized patients. The allergenic activity of ralphaS1-casein and the alphaS1-casein-derived peptides was determined using rat basophil leukemia cells transfected with human FcepsilonRI, which had been loaded with the patients' serum IgE. Our results demonstrate that ralphaS1-casein as well as alphaS1-casein-derived peptides exhibit IgE reactivity, but mainly the intact ralphaS1-casein induced strong basophil degranulation. These results suggest that primarily intact alphaS1-casein or larger IgE-reactive portions thereof are responsible for IgE-mediated symptoms of food allergy. Recombinant alphaS1-casein as well as alphaS1-casein-derived peptides may be used in clinical studies to further explore pathomechanisms of food allergy as well as for the development of new diagnostic and therapeutic strategies for milk allergy.

Alpha Shapes and Proteins

DEFF Research Database (Denmark)

Winter, Pawel; Sterner, Henrik; Sterner, Peter

2009-01-01

We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

Frontal Alpha Oscillations and Attentional Control: A Virtual Reality Neurofeedback Study.

Science.gov (United States)

Berger, Anna M; Davelaar, Eddy J

2018-05-15

Two competing views about alpha oscillations suggest that cortical alpha reflect either cortical inactivity or cortical processing efficiency. We investigated the role of alpha oscillations in attentional control, as measured with a Stroop task. We used neurofeedback to train 22 participants to increase their level of alpha amplitude. Based on the conflict/control loop theory, we selected to train prefrontal alpha and focus on the Gratton effect as an index of deployment of attentional control. We expected an increase or a decrease in the Gratton effect with increase in neural learning depending on whether frontal alpha oscillations reflect cortical idling or enhanced processing efficiency, respectively. In order to induce variability in neural learning beyond natural occurring individual differences, we provided half of the participants with feedback on alpha amplitude in a 3-dimensional (3D) virtual reality environment and the other half received feedback in a 2D environment. Our results showed variable neural learning rates, with larger rates in the 3D compared to the 2D group, corroborating prior evidence of individual differences in EEG-based learning and the influence of a virtual environment. Regression analyses revealed a significant association between the learning rate and changes on deployment of attentional control, with larger learning rates being associated with larger decreases in the Gratton effect. This association was not modulated by feedback medium. The study supports the view of frontal alpha oscillations being associated with efficient neurocognitive processing and demonstrates the utility of neurofeedback training in addressing theoretical questions in the non-neurofeedback literature. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Suppression of no-longer relevant information in Working Memory: An alpha-power related mechanism?

Science.gov (United States)

Poch, Claudia; Valdivia, María; Capilla, Almudena; Hinojosa, José Antonio; Campo, Pablo

2018-03-27

Selective attention can enhance Working Memory (WM) performance by selecting relevant information, while preventing distracting items from encoding or from further maintenance. Alpha oscillatory modulations are a correlate of visuospatial attention. Specifically, an enhancement of alpha power is observed in the ipsilateral posterior cortex to the locus of attention, along with a suppression in the contralateral hemisphere. An influential model proposes that the alpha enhancement is functionally related to the suppression of information. However, whether ipsilateral alpha power represents a mechanism through which no longer relevant WM representations are inhibited has yet not been explored. Here we examined whether the amount of distractors to be suppressed during WM maintenance is functionally related to alpha power lateralized activity. We measure EEG activity while participants (N = 36) performed a retro-cue task in which the WM load was varied across the relevant/irrelevant post-cue hemifield. We found that alpha activity was lateralized respect to the locus of attention, but did not track post-cue irrelevant load. Additionally, non-lateralized alpha activity increased with post-cue relevant load. We propose that alpha lateralization associated to retro-cuing might be related to a general orienting mechanism toward relevant representation. Copyright © 2018 Elsevier B.V. All rights reserved.

Alpha Momentum and Price Momentum

Directory of Open Access Journals (Sweden)

Hannah Lea Hühn

2018-05-01

Full Text Available We analyze a novel alpha momentum strategy that invests in stocks based on three-factor alphas which we estimate using daily returns. The empirical analysis for the U.S. and for Europe shows that (i past alpha has power in predicting the cross-section of stock returns; (ii alpha momentum exhibits less dynamic factor exposures than price momentum and (iii alpha momentum dominates price momentum only in the U.S. Connecting both strategies to behavioral explanations, alpha momentum is more related to an underreaction to firm-specific news while price momentum is primarily driven by price overshooting due to momentum trading.

/sup 58,60,62/Ni (. cap alpha. ,p) three--nucleon transfer reactions and. cap alpha. optical potential ambiguities

Energy Technology Data Exchange (ETDEWEB)

Yuanda, Wang; Xiuming, Bao; Zhiqiang, Mao; Rongfang, Yuan; Keling, Wen; Binyin, Huang; Zhifu, Wang; Shuming, Li; Jianan, Wang; Zuxun, Sun; others, and

1985-11-01

The differential cross sections are measured using 26.0 MeV ..cap alpha.. particle for /sup 58,62/Ni(..cap alpha.., ..cap alpha..) /sup 58,62/Ni and /sup 58,62/Ni(..cap alpha..,p) /sup 61,65/Cu reactions as well as 25.4 MeV ..cap alpha.. particle for /sup 60/Ni(..cap alpha.., ..cap alpha..)/sup 69/Ni and /sup 60/Ni(..cap alpha.., p)/sup 63/Cu reactions. Consistent calculations with optical model and ZR DWBA are made for (..cap alpha.., ..cap alpha..) and (..cap alpha.., p) reactions by using of single, two, three and four nucleon optical potential parameters. For elastic scattering due to the ..cap alpha.. optical potential ambiguities, all the above optical potential can reproduce the experimental angular distributions. However, the single, two and three nucleon potential, including the Baird's mass systematics and the Chang's energy systematics of ..cap alpha.. potentials, obviously can not provide a reasonable fitting with the (..cap alpha..,p) reaction experimental data. Only the results from the four nucleon potential is in good agreement with the (..cap alpha..,p) reaction experimental data. This reveals that in the ..cap alpha..-particle induced transfer reactions, the real depth of the ..cap alpha..-nucleus optical potential should be rather deep.

Economic analyses of alpha channeling in tokamak power plants

International Nuclear Information System (INIS)

Ehst, D.A.

1998-01-01

The hot-ion-mode of operation [1] has long been thought to offer optimized performance for long-pulse or steady-state magnetic fusion power plants. This concept was revived in recent years when theoretical considerations suggested that nonthermal fusion alpha particles could be made to channel their power density preferentially to the fuel ions [2,3]. This so-called anomalous alpha particle slowing down can create plasmas with fuel ion temperate T i somewhat larger than the electron temperature T e , which puts more of the beta-limited plasma pressure into the useful fuel species (rather than non-reacting electrons). As we show here, this perceived benefit may be negligible or nonexistent for tokamaks with steady state current drive. It has likewise been argued [2,3] that alpha channeling could be arranged such that little or no external power would be needed to generate the steady state toroidal current. Under optimistic assumptions we show that such alpha-channeling current drive would moderately improve the economic performance of a first stability tokamak like ARIES-I [4], however a reversed-shear (advanced equilibrium) tokamak would likely not benefit since traditional radio-wave (rf) electron-heating current drive power would already be quite small

Targeted Alpha Therapy: From Alpha to Omega

International Nuclear Information System (INIS)

Allen, Barry J; Clarke, Raymond; Huang Chenyu

2013-01-01

This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer.

Science.gov (United States)

Uemura, Motohide; Honma, Seijiro; Chung, Suyoun; Takata, Ryo; Furihata, Mutsuo; Nishimura, Kazuo; Nonomura, Norio; Nasu, Yasutomo; Miki, Tsuneharu; Shuin, Taro; Fujioka, Tomoaki; Okuyama, Akihiko; Nakamura, Yusuke; Nakagawa, Hidewaki

2010-08-01

Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

The alpha channeling effect

Science.gov (United States)

Fisch, N. J.

2015-12-01

Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

Calculation of the pulsed Feynman- and Rossi-alpha formulae with delayed neutrons

International Nuclear Information System (INIS)

Kitamura, Y.; Pazsit, I.; Wright, J.; Yamamoto, A.; Yamane, Y.

2005-01-01

In previous works, the authors have developed an effective solution technique for calculating the pulsed Feynman- and Rossi-alpha formulae. Through derivation of these formulae, it was shown that the technique can easily handle various pulse shapes of the pulsed neutron source. Furthermore, it was also shown that both the deterministic (i.e., synchronizing with the pulsing of neutron source) and stochastic (non-synchronizing) Feynman-alpha formulae can be obtained with this solution technique. However, for mathematical simplicity and the sake of insight, the formal derivation was performed in a model without delayed neutrons. In this paper, to demonstrate the robustness of the technique, the pulsed Feynman- and Rossi-alpha formulae were re-derived by taking one group of delayed neutrons into account. The results show that the advantages of this technique are retained even by inclusion of the delayed neutrons. Compact explicit formulae are derived for the Feynman- and Rossi-alpha methods for various pulse shapes and pulsing methods

Direct analysis of the lectin reactivity of alpha-fetoprotein in maternal serum by crossed affinity radio-immunoelectrophoresis

International Nuclear Information System (INIS)

Kerckaert, J.P.; Bayard, B.; Biserte, G.; Puech, F.; Codaccioni, X.

1980-01-01

Affinity experiments with the lentil (Lens culinaris) lectin have revealed the existence of two distinct molecular populations of alpha-fetoprotein: lectin reactive and lectin non-reactive. Using a combination of crossed lectin immunoelectrophoresis and radio-immunoelectrophoresis, it has been possible to obtain directly the lentil lectin affinity patterns of alpha-fetoprotein present in maternal sera. The lentil lectin reactivity of maternal alpha-fetoprotein decreases almost linearly with the gestational age from week 15 to 35. (Auth.)

Unifying Dark Matter and Dark Energy with non-Canonical Scalars

OpenAIRE

Mishra, Swagat S.; Sahni, Varun

2018-01-01

Non-canonical scalar fields with the Lagrangian ${\\cal L} = X^\\alpha - V(\\phi)$, possess the attractive property that the speed of sound, $c_s^{2} = (2\\,\\alpha - 1)^{-1}$, can be exceedingly small for large values of $\\alpha$. This allows a non-canonical field to cluster and behave like warm/cold dark matter on small scales. We demonstrate that simple potentials such as $V = V_0\\coth^2{\\phi}$ and the Starobinsky-type potential $V(\\phi) = V_0 \\left ( 1 - e^{-{\\phi}}\\right )^{2}$ can unify dark...

Prestimulus alpha-band power biases visual discrimination confidence, but not accuracy.

Science.gov (United States)

Samaha, Jason; Iemi, Luca; Postle, Bradley R

2017-09-01

The magnitude of power in the alpha-band (8-13Hz) of the electroencephalogram (EEG) prior to the onset of a near threshold visual stimulus predicts performance. Together with other findings, this has been interpreted as evidence that alpha-band dynamics reflect cortical excitability. We reasoned, however, that non-specific changes in excitability would be expected to influence signal and noise in the same way, leaving actual discriminability unchanged. Indeed, using a two-choice orientation discrimination task, we found that discrimination accuracy was unaffected by fluctuations in prestimulus alpha power. Decision confidence, on the other hand, was strongly negatively correlated with prestimulus alpha power. This finding constitutes a clear dissociation between objective and subjective measures of visual perception as a function of prestimulus cortical excitability. This dissociation is predicted by a model where the balance of evidence supporting each choice drives objective performance but only the magnitude of evidence supporting the selected choice drives subjective reports, suggesting that human perceptual confidence can be suboptimal with respect to tracking objective accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

New production processes for alpha hemihydrate open up new marketing opportunities

International Nuclear Information System (INIS)

Engert, W.; Lehmkaemper, O.; Bunte, H.P.

1991-01-01

New production processes and markets for alpha hemihydrate are discussed. Utility studies concluded that lignite gypsum is harmless in terms of public and occupational health, and is technically comparable to or superior to natural gypsum by virtue of greater purity. Semi-commercial and pilot-scale studies were carried out on the use of flue gas desulfurization (FGD) gypsum for producing alpha hemihydrate, with successful results. The process enabled pure alpha hemihydrate to be produced without dihydrate or dihydrate impurities, and of a constant, uniform quality. The treatment consists of forming pressed mouldings of FGD gypsum followed by steam autoclaving, drying and milling. Agents are used to stabilize the stackable moldings, and to act as growth inhibitors during transformation of dihydrite to alpha-hemihydrate. Markets for the product are found in mining, tunneling and road building, foundation work, floor systems, as hard plaster for dental and moulding applications, for construction industry use, and as structural and non-structural material. Details are presented of the production process and marketing concepts. 12 figs

Compensatory increase in alpha 1-globin gene expression in individuals heterozygous for the alpha-thalassemia-2 deletion.

OpenAIRE

Liebhaber, S A; Cash, F E; Main, D M

1985-01-01

alpha-Globin is encoded by the two adjacent genes, alpha 1 and alpha 2. Although it is clearly established that both alpha-globin genes are expressed, their relative contributions to alpha-globin messenger RNA (mRNA) and protein synthesis are not fully defined. Furthermore, changes that may occur in alpha-globin gene activity secondarily to the loss of function of one or more of these genes (alpha-thalassemia [Thal]) have not been directly investigated. This study further defines the expressi...

Ultraviolet photometry from the orbiting astronomical observatory. XVI - The stellar Lyman-alpha absorption line

Science.gov (United States)

Savage, B. D.; Panek, R. J.

1974-01-01

The stellar Lyman-alpha line at 1216 A was observed in 29 lightly reddened stars of spectral type B2.5 to B9 by a far-UV spectrophotometer on OAO-2. The equivalent widths obtained range from 15 A at type B2.5 to 65 A at type B8; in the late-B stars, the L-alpha line removes 2 to 3% of the total stellar flux. In this sampling, the strength of the L-alpha line correlates well with measures of the Balmer discontinuity and Balmer line strengths; luminosity classification does not seem to affect the line strength. The observed line widths also agree with the predictions of Mihala's grid of non-LTE model atmospheres. In some cases, the L-alpha line influences the interstellar column densities reported in the interstellar OAO-2 L-alpha survey. Hence, these data toward lightly reddened B2 and B1.5 stars should be regarded as upper limits only.

Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume

Science.gov (United States)

Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.

2015-01-01

Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…

Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

DEFF Research Database (Denmark)

Svenson, M; Hansen, M B; Thomsen, Allan Randrup

2000-01-01

with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...

A G {r_arrow} A transition at position IVS-11 +1 of the HEX A {alpha}-chain gene in a non-Ashkenazic Mexican Tay-Sachs infant

Energy Technology Data Exchange (ETDEWEB)

Miranda, S.R.P.; Gwon, S.; DeGasperi, R. [New York Univ. Medical Center, NY (United States)] [and others

1994-09-01

Tay-Sachs disease (TSD) is an autosomal recessive storage disorder caused by a deficiency of the lysosomal enzyme, {beta}-N-acetylhexosaminidase A (Hex A), a heteropolymer composed of two polypeptides, {alpha} and {beta}. Mutations in the {alpha}-chain gene render the enzyme defective, resulting in the accumulation of g{sub m2} ganglioside in the nervous system. Deficiency of Hex A was detected in a non-Ashkenazic girl of Mexican origin indicating infantile onset of TSD. Molecular investigation of the {alpha}-chain gene excluded the typical Ashkenazic 4 bp insertion in the exon 11 and the intron 12 splice-junction mutations by Hae III and Dde I restriction analysis, respectively. Single strand conformation polymorphism (SSCP) analysis showed a different pattern in the sample where exon 11 and flanking regions were amplified in the patient DNA as compared to the migration of control DNA. Sequencing of PCR amplified genomic DNA containing exon 11 and flanking intronic regions showed a single base substitution (G {r_arrow} A) at position IVS-11 +1. This mutation creates a recognition site for the restriction enzyme Mbo II. Digestion of exon 11 and flanking regions with Mbo II demonstrated homozygosity of the patient for this mutation and heterozygosity in the mother. mRNA from cultured fibroblasts obtained from a normal control and from the propositus was reverse transcribed. The cDNAs coding for Hex A {alpha}-chain were amplified in four overlapping fragments. In the patient sample it was not possible to amplify the fragment containing the exon 11/intron 11 junction, indicating that this mutation alters normal RNA processing of the Hex A pre-mRNA resulting in the deficiency of Hex A activity.

Proceedings, High-Precision $\\alpha_s$ Measurements from LHC to FCC-ee

Energy Technology Data Exchange (ETDEWEB)

d' Enterria, David [CERN; Skands, Peter Z. [Monash U.

2015-01-01

This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\\alpha_s(m_Z)$ = 0.1177 $\\pm$ 0.0013, is about 1\\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.

Hydration products and mechanical properties of hydroceramics solidified waste for simulated Non-alpha low and intermediate level radioactive wastes

International Nuclear Information System (INIS)

Wang Jin; Hong Ming; Wang Junxia; Li Yuxiang; Teng Yuancheng; Wu Xiuling

2011-01-01

In this paper, simulated non-alpha low and intermediate level radioactive wastes was handled as curing object and that of 'alkali-slag-coal fly ash-metakaolin' hydroceramics waste forms were prepared by hydrothermal synthesis method. The hydration products were analyzed by X ray diffraction. The composition of hydrates and the compressive strength of waste forms were determined and measured. The results indicate that the main crystalline phase of hydration products were analcite when the temperature was 150 to 180 degree C and the salt content ratio was 0.10 to 0.30. Analcite diffraction peaks in hydration products is increasing when the temperature was raised and the reaction time prolonged. Strength test results show that the solidified waste forms have superior compressive strength. The compressive strength gradually decreased with the increase in salt content ratio in waste forms. (authors)

Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha

NARCIS (Netherlands)

Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P.; Li, Dan L.; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F.; Tschöp, Matthias H.; Clegg, Deborah J.

2014-01-01

High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha

Workshop on Precision Measurements of $\\alpha_s$

Energy Technology Data Exchange (ETDEWEB)

Bethke, Siegfried; /Munich, Max Planck Inst.; Hoang, Andre H.; /Vienna U.; Kluth, Stefan; /Munich, Max Planck Inst.; Schieck, Jochen; /Munich U.; Stewart, Iain W.; Aoki, S.; Beneke, M.; Bethke, S.; Blumlein, J.; Brambilla, N.; Brodsky, S.; /MIT, LNS

2011-10-01

These are the proceedings of the Workshop on Precision Measurements of {alpha}{sub s} held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of {alpha}{sub s}(m{sub Z}) in the {ovr MS} scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, {tau}-decays, electro-weak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

Generation and Characterization of Erythroid Cells from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells: An Overview

Directory of Open Access Journals (Sweden)

Kai-Hsin Chang

2011-01-01

Full Text Available Because of the imbalance in the supply and demand of red blood cells (RBCs, especially for alloimmunized patients or patients with rare blood phenotypes, extensive research has been done to generate therapeutic quantities of mature RBCs from hematopoietic stem cells of various sources, such as bone marrow, peripheral blood, and cord blood. Since human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs can be maintained indefinitely in vitro, they represent potentially inexhaustible sources of donor-free RBCs. In contrast to other ex vivo stem-cell-derived cellular therapeutics, tumorigenesis is not a concern, as RBCs can be irradiated without marked adverse effects on in vivo function. Here, we provide a comprehensive review of the recent publications relevant to the generation and characterization of hESC- and iPSC-derived erythroid cells and discuss challenges to be met before the eventual realization of clinical usage of these cells.

Robust Coefficients Alpha and Omega and Confidence Intervals with Outlying Observations and Missing Data: Methods and Software

Science.gov (United States)

Zhang, Zhiyong; Yuan, Ke-Hai

2016-01-01

Cronbach's coefficient alpha is a widely used reliability measure in social, behavioral, and education sciences. It is reported in nearly every study that involves measuring a construct through multiple items. With non-tau-equivalent items, McDonald's omega has been used as a popular alternative to alpha in the literature. Traditional estimation…

Robust Coefficients Alpha and Omega and Confidence Intervals with Outlying Observations and Missing Data Methods and Software

Science.gov (United States)

Zhang, Zhiyong; Yuan, Ke-Hai

2016-01-01

Cronbach's coefficient alpha is a widely used reliability measure in social, behavioral, and education sciences. It is reported in nearly every study that involves measuring a construct through multiple items. With non-tau-equivalent items, McDonald's omega has been used as a popular alternative to alpha in the literature. Traditional estimation…

Combining Alphas via Bounded Regression

Directory of Open Access Journals (Sweden)

Zura Kakushadze

2015-11-01

Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

Genetics Home Reference: alpha thalassemia

Science.gov (United States)

... Facebook Twitter Home Health Conditions Alpha thalassemia Alpha thalassemia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alpha thalassemia is a blood disorder that reduces the production ...

Coaching the alpha male.

Science.gov (United States)

Ludeman, Kate; Erlandson, Eddie

2004-05-01

Highly intelligent, confident, and successful, alpha males represent about 70% of all senior executives. Natural leaders, they willingly take on levels of responsibility most rational people would find overwhelming. But many of their quintessential strengths can also make alphas difficult to work with. Their self-confidence can appear domineering. Their high expectations can make them excessively critical. Their unemotional style can keep them from inspiring their teams. That's why alphas need coaching to broaden their interpersonal tool kits while preserving their strengths. Drawing from their experience coaching more than 1,000 senior executives, the authors outline an approach tailored specifically for the alpha. Coaches get the alpha's attention by inundating him with data from 360-degree feedback presented in ways he will find compelling--both hard-boiled metrics and vivid verbatim comments from colleagues about his strengths and weaknesses. A 360-degree assessment is a wake-up call for most alphas, providing undeniable proof that their behavior doesn't work nearly as well as they think it does. That paves the way for a genuine commitment to change. In order to change, the alpha must venture into unfamiliar--and often uncomfortable--psychological territory. He must admit vulnerability, accept accountability not just for his own work for others', connect with his underlying emotions, learn to motivate through a balance of criticism and validation, and become aware of unproductive behavior patterns. The goal of executive coaching is not simply to treat the alpha as an individual problem but to improve the entire team dynamic. Initial success creates an incentive to persevere, and the virtuous cycle reverberates throughout the entire organization.

Distribution of the alphaGal- and the non-alphaGal T-antigens in the pig kidney: potential targets for rejection in pig-to-man xenotransplantation

DEFF Research Database (Denmark)

Kirkeby, Svend; Mikkelsen, Hanne B

2008-01-01

Carbohydrate antigens, present on pig vascular endothelial cells, seem to be the prime agents responsible for graft rejection, and although genetically modified animals that express less amounts of carbohydrate antigen are available, it is still useful to decide the localization of the reactive...... xenoantigens in organs contemplated for xenotransplantation. Here we compare the distribution in pig kidney of antigens important in xenograft destruction, namely the Galalpha1-3Gal (alphaGal) glycans, with the localization of the T-antigen (Galbeta1-3GalNAc). The alpha-galactose-specific lectin Griffonia...... simplicifolia isolectin 1B4 was used to detect the Galalpha1-3Gal glycans, whereas Arachis hypogaea (PNA) lectin and a monoclonal antibody (3C9) detected T-antigen. In addition, two vascular markers (anti-caveolin-1 and anti-von Willebrand factor) served to identify vascular structures of the kidney. Both...

Alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells.

Science.gov (United States)

Wells, Shannon R; Jennings, Merilyn H; Rome, Courtney; Hadjivassiliou, Vicky; Papas, Konstantinos A; Alexander, Jonathon S

2010-07-01

Vitamin E, a micronutrient (comprising alpha-, beta-, gamma- and delta-tocopherols, alpha-, beta-, gamma- and delta-tocotrienols), has documented antioxidant and non-antioxidant effects, some of which inhibit inflammation and angiogenesis. We compared the abilities of alpha-, gamma- and delta-tocopherols to regulate human blood cytotoxicity (BEC) and lymphatic endothelial cytotoxicity (LEC), proliferation, invasiveness, permeability, capillary formation and suppression of TNF-alpha-induced VCAM-1 as in vitro models of inflammatory angiogenesis. alpha-, gamma- and delta-tocopherols were not toxic to either cell type up to 40 microM. In BEC, confluent cell density was decreased by all concentrations of delta- and gamma-tocopherol (10-40 microM) but not by alpha-tocopherol. LEC showed no change in cell density in response to tocopherols. delta-Tocopherol (40 microM), but not other isomers, decreased BEC invasiveness. In LEC, all doses of gamma-tocopherol, as well as the highest dose of alpha-tocopherol (40 microM), decreased cell invasiveness. delta-Tocopherol had no effect on LEC invasiveness at any molarity. delta-Tocopherol dose dependently increased cell permeability at 48 h in BEC and LEC; alpha- and gamma-tocopherols showed slight effects. Capillary tube formation was decreased by high dose (40 microM) concentrations of alpha-, gamma- and delta-tocopherol, but showed no effects with smaller doses (10-20 microM) in BEC. gamma-Tocopherol (10-20 microM) and alpha-tocopherol (10 microM), but not delta-tocopherol, increased LEC capillary tube formation. Lastly, in BEC, alpha-, gamma- and delta-tocopherol each dose-dependently reduced TNF-alpha-induced expression of VCAM-1. In LEC, there was no significant change to TNF-alpha-induced VCAM-1 expression with any concentration of alpha-, gamma- or delta-tocopherol. These data demonstrate that physiological levels (0-40 microM) of alpha-, gamma- and delta-tocopherols are nontoxic and dietary tocopherols, especially delta

Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

Science.gov (United States)

Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

2004-01-16

Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

Immunodetection of Thyroid Hormone Receptor (Alpha1/Alpha2) in the Rat Uterus and Oviduct

International Nuclear Information System (INIS)

Öner, Jale; Öner, Hakan

2007-01-01

The aim of this study was to investigate the immunolocalization and the existence of thyroid hormone receptors (THR) (alpha1/alpha2) in rat uterus and oviduct. For this purpose 6 female Wistar albino rats found in estrous period were used. Tissue samples fixed in 10% neutral formalin were examined immunohistochemically. Sections were incubated with primary mouse-monoclonal THR (alpha1/alpha2) antibody. In uterus, THR (alpha1/alpha2) immunoreacted strongly with uterine luminal epithelium, endometrial gland epithelium and endometrial stromal cells and, moderately with myometrial smooth muscle. In oviduct, they were observed moderately in the epithelium of the tube and the smooth muscle cells of the muscular layer. In conclusion, the presence of THR in uterus and oviduct suggests that these organs are an active site of thyroid hormones

Alpha particle emitters in medicine

International Nuclear Information System (INIS)

Fisher, D.R.

1989-09-01

Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ( 211 At) and natural bismuth-212 ( 212 Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ( 223 Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs

Monte Carlo alpha calculation

Energy Technology Data Exchange (ETDEWEB)

Brockway, D.; Soran, P.; Whalen, P.

1985-01-01

A Monte Carlo algorithm to efficiently calculate static alpha eigenvalues, N = ne/sup ..cap alpha..t/, for supercritical systems has been developed and tested. A direct Monte Carlo approach to calculating a static alpha is to simply follow the buildup in time of neutrons in a supercritical system and evaluate the logarithmic derivative of the neutron population with respect to time. This procedure is expensive, and the solution is very noisy and almost useless for a system near critical. The modified approach is to convert the time-dependent problem to a static ..cap alpha../sup -/eigenvalue problem and regress ..cap alpha.. on solutions of a/sup -/ k/sup -/eigenvalue problem. In practice, this procedure is much more efficient than the direct calculation, and produces much more accurate results. Because the Monte Carlo codes are intrinsically three-dimensional and use elaborate continuous-energy cross sections, this technique is now used as a standard for evaluating other calculational techniques in odd geometries or with group cross sections.

Hemopoietic regeneration in murine spleen following transfusion of normal and irradiated marrow: different response of granulocyte/macrophage and erythroid precursors

International Nuclear Information System (INIS)

Wangenheim, K.-H. von; Peterson, H.-P.; Huebner, G.E.; Feinendegen, L.E.

1987-01-01

To investigate cell proliferation in regenerating spleen, bone marrow of normal and gamma-irradiated donor mice (3 weeks after 5 Gy) was transfused into lethally irradiated recipients. In the donors and in the recipient spleens numbers of CFU-S and progenitor cells were determined. In the irradiated donors the progenitors were at control level after 3 weeks of recovery although CFU-S were still at 50% of control. Recipients of the irradiated marrow received therefore an increased proportion of progenitors. CFU-C appeared to be self-renewing and/or increased in number due to enhanced CFU-S differentiation, but not the erythroid progenitors. CFU-S self-renewal was reduced after 5 Gy. The data suggest that cell differentiation and maturation proceed during early splenic regeneration. The quantity of CFU-C does not necessarily mirror the situation in the stem cell compartment. (author)

Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells.

Science.gov (United States)

Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Burak; Tastan, Bora; Genc, Kursad; Genc, Sermin

2018-01-01

Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state.

Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

Energy Technology Data Exchange (ETDEWEB)

Lukas, R.J.; Bennett, E.L.

1979-01-01

The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

Antihydrogen detection in ALPHA

Energy Technology Data Exchange (ETDEWEB)

Hydomako, Richard, E-mail: rhydomako@phas.ucalgary.ca [University of Calgary, Department of Physics and Astronomy (Canada); Bruun Andresen, Gorm [Aarhus University, Department of Physics and Astronomy (Denmark); Ashkezari, Mohammad Dehghani [Simon Fraser University, Department of Physics (Canada); Baquero-Ruiz, Marcelo [University of California, Department of Physics (United States); Bertsche, William [Swansea University, Department of Physics (United Kingdom); Butler, Eoin [CERN, European Laboratory for Particle Physics (Switzerland); Bowe, Paul David [Aarhus University, Department of Physics and Astronomy (Denmark); Cesar, Claudo Lenz [Universidade Federal do Rio de Janeiro, Instituto de Fsica (Brazil); Chapman, Steve [University of California, Department of Physics (United States); Charlton, Michael [Swansea University, Department of Physics (United Kingdom); Fajans, Joel [University of California, Department of Physics (United States); Friesen, Tim; Fujiwara, Makoto C. [University of Calgary, Department of Physics and Astronomy (Canada); Gill, David Russell [TRIUMF (Canada); Hangst, Jeffrey Scott [Aarhus University, Department of Physics and Astronomy (Denmark); Hardy, Walter Newbold [University of British Columbia, Department of Physics and Astronomy (Canada); Hayano, Ryugo S. [University of Tokyo, Department of Physics (Japan); Hayden, Michael Edward [Simon Fraser University, Department of Physics (Canada); Humphries, Andrew James [Swansea University, Department of Physics (United Kingdom); Jonsell, Svante [Stockholm University, Fysikum (Sweden); Collaboration: ALPHA Collaboration; and others

2012-12-15

The ALPHA project is an international collaboration, based at CERN, with the experimental goal of performing precision spectroscopic measurements on antihydrogen. As part of this endeavor, the ALPHA experiment includes a silicon tracking detector. This detector consists of a three-layer array of silicon modules surrounding the antihydrogen trapping region of the ALPHA apparatus. Using this device, the antihydrogen annihilation position can be determined with a spatial resolution of better than 5 mm. Knowledge of the annihilation distribution was a critical component in the recently successful antihydrogen trapping effort. This paper will describe the methods used to reconstruct annihilation events in the ALPHA detector. Particular attention will be given to the description of the background rejection criteria.

Buffett’s Alpha

DEFF Research Database (Denmark)

Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

Energy Technology Data Exchange (ETDEWEB)

Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

1998-06-29

Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

Modeling of the axon membrane skeleton structure and implications for its mechanical properties.

Directory of Open Access Journals (Sweden)

Yihao Zhang

2017-02-01

Full Text Available Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young's modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav, which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration.

Modeling of the axon membrane skeleton structure and implications for its mechanical properties.

Science.gov (United States)

Zhang, Yihao; Abiraman, Krithika; Li, He; Pierce, David M; Tzingounis, Anastasios V; Lykotrafitis, George

2017-02-01

Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM) to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young's modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav), which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration.

Determination of $\\alpha_{s}$ using Jet Rates at LEP with the OPAL detector

CERN Document Server

Abbiendi, G.; Akesson, P.F.; Alexander, G.; Anagnostou, G.; Anderson, K.J.; Asai, S.; Axen, D.; Bailey, I.; Barberio, E.; Barillari, T.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Boeriu, O.; Bock, P.; Boutemeur, M.; Braibant, S.; Brown, Robert M.; Burckhart, H.J.; Campana, S.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, D.G.; Ciocca, C.; Csilling, A.; Cuffiani, M.; Dado, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Etzion, E.; Fabbri, F.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Gagnon, P.; Gary, John William; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harel, A.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hill, J.C.; Horvath, D.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanzaki, J.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kramer, T.; Krasznahorkay, A.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lellouch, D.; Lettso, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, A.; Ludwig, J.; Mader, W.; Marcellini, S.; Martin, A.J.; Mashimo, T.; Mattig, Peter; McKenna, J.; McPherson, R.A.; Meijers, F.; Menges, W.; Merritt, F.S.; Mes, H.; Meyer, Niels T.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Nanjo, H.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Roney, J.M.; Rossi, A.M.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schorner-Sadenius, T.; Schroder, Matthias; Schumacher, M.; Seuster, R.; Shears, T.G.; Shen, B.C.; Sherwood, P.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spano, F.; Stahl, A.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vollmer, C.F.; Vannerem, P.; Vertesi, R.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija

2006-01-01

Hadronic events produced in e+e- collisions by the LEP collider and recorded by the OPAL detector were used to form distributions based on the number of reconstructed jets. The data were collected between 1995 and 2000 and correspond to energies of 91 GeV, 130-136 GeV and 161-209 GeV. The jet rates were determined using four different jet-finding algorithms (Cone, JADE, Durham and Cambridge). The differential two-jet rate and the average jet rate with the Durham and Cambridge algorithms were used to measure alpha(s) in the LEP energy range by fitting an expression in which order alpah_2s calculations were matched to a NLLA prediction and fitted to the data. Combining the measurements at different centre-of-mass energies, the value of alpha_s (Mz) was determined to be alpha(s)(Mz)=0.1177+-0.0006(stat.)+-0.0012$(expt.)+-0.0010(had.)+-0.0032

Development of gas ionization chambers with coplanar electrodes for alpha-ray spectrometry

International Nuclear Information System (INIS)

Iwasaki, Kenta; Tanaka, Naomichi; Murakami, Kohei; Hasebe, Nobuyuki; Kusano, Hiroki; Shibamura, Eido; Miyajima, Mitsuhiro

2016-01-01

A large-area alpha-ray spectrometer is required to measure the low level alpha emitters in environmental samples, which may be distributed in the vicinity of nuclear power plants. A gas ionization chamber with a coplanar electrode has attractive features such as with mechanical ruggedness, easy handling, easy fabrication of large electrode, and relatively well-known performance. We have investigated the performance of a gas ionization chamber with a coplanar electrode for alpha-ray spectrometry, particularly in the energy resolution. The present experiment shows that the energy resolution in the full width at half maximum (FWHM) is 129 keV (= 2.7%) for alpha-rays from Np with an energy of 4.78 MeV, 120 keV (= 2.2%) for those with 5.49 MeV from Am, and 109 keV (= 1.9%) for those with 5.81 MeV from Cm. It is found that the energy resolution obtained at the present experiment is dominated in the electronic noise caused by the large capacitance existed between the collecting anode (CA) and non-collecting anode (NCA) in the coplanar electrode. (author)

Depletion of brain alpha-MSH alters prostaglandin and interleukin fever in rats.

Science.gov (United States)

Martin, S M; Malkinson, T J; Veale, W L; Pittman, Q J

1990-09-03

Alpha-melanocyte stimulating hormone (alpha-MSH), a putative endogenous antipyretic agent, is synthesized largely within neurons in the arcuate nucleus. To test the hypothesis that destruction of this area would increase the febrile response, male Wistar rats, treated as neonates with intraperitoneal injections of monosodium glutamate (MSG) or saline, were given intracerebroventricular (i.c.v.) injections of prostaglandin E1 (20 ng; 200 ng) or purified interleukin-1 (20 U) and body temperature was monitored. The fevers displayed by the MSG-treated animals were significantly greater (P less than 0.05) than those of the controls for the lower dose of PGE1 at 10-30 min and for IL-1 at 3-6 h after the injections. MSG-treated rats showed significant reduction (P less than 0.01) in alpha-MSH content of the medial basal hypothalamus and lateral septum when compared to saline controls. Body temperature response of non-febrile animals to high ambient temperature was not affected by the MSG treatment. These data support the hypothesis that alpha-MSH is an endogenous antipyretic in the rat.

Coincidence study of alpha particle fragmentation at E/sub alpha/ = 140 MeV

International Nuclear Information System (INIS)

Koontz, R.W.

1980-01-01

Results of an experimental study of the interaction of 140 MeV alpha particles with 90 Zr nuclei resulting in fragmentation of the alpha particle are reported. The experimental observations of the study are analyzed and are found to show that alpha particle breakup reactions leading to at least 4-body final states, composed of two charged alpha particle fragments, contribute significantly to the singles yield of charged fragments observed at a fixed forward angle. The conclusions are based on coincidence measurements where one charged fragment is detected at a small forward angle which remains fixed, while the second charged fragment is detected at a series of coplanar secondary angles. The largest coincidence charged particle yield for the multiparticle final state events results from 90 Zr(α,pp)X reactions, where both of the measured protons have energy distributions similar to the proton singles energy distributions. The second largest observed coincidence yield involving two charged fragments arises from 90 Zr(α,pd)X reactions, where the p and d fragments, as in the 90 Zr(α,pp)X reactions also have energy distribution similar to the singles energy distributions. Analysis of additional measurements, where alpha particle fragments at the fixed angle are detected in coincidence with evaporation and nonequilibrium particles at many coplanar angles, show that the alpha particle fragmentation reactions are also generally associated with large energy transfer to the target nucleus. A multiple scattering model of the fragmentation reaction is employed, in conjunction with the experimental observations, to estimate the cross sections for alpha particle fragmentation into multi-particle final states resulting in n, 2n, p, pp, d, dn, dp, t and 3 He fragments. The estimated total cross section for all fragmentation reactions is 755 mb or approximately 38% of the total reaction cross section for 140 MeV alpha particle interactions with 90 Zr

alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages.

Science.gov (United States)

Taherzadeh, S; Sharma, S; Chhajlani, V; Gantz, I; Rajora, N; Demitri, M T; Kelly, L; Zhao, H; Ichiyama, T; Catania, A; Lipton, J M

1999-05-01

The hypothesis that macrophages contain an autocrine circuit based on melanocortin [ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH)] peptides has major implications for neuroimmunomodulation research and inflammation therapy. To test this hypothesis, cells of the THP-1 human monocyte/macrophage line were stimulated with lipopolysaccharide (LPS) in the presence and absence of alpha-MSH. The inflammatory cytokine tumor necrosis factor (TNF)-alpha was inhibited in relation to alpha-MSH concentration. Similar inhibitory effects on TNF-alpha were observed with ACTH peptides that contain the alpha-MSH amino acid sequence and act on melanocortin receptors. Nuclease protection assays indicated that expression of the human melanocortin-1 receptor subtype (hMC-1R) occurs in THP-1 cells; Southern blots of RT-PCR product revealed that additional subtypes, hMC-3R and hMC-5R, also occur. Incubation of resting macrophages with antibody to hMC-1R increased TNF-alpha concentration; the antibody also markedly reduced the inhibitory influence of alpha-MSH on TNF-alpha in macrophages treated with LPS. These results in cells known to produce alpha-MSH at rest and to increase secretion of the peptide when challenged are consistent with an endogenous regulatory circuit based on melanocortin peptides and their receptors. Targeting of this neuroimmunomodulatory circuit in inflammatory diseases in which myelomonocytic cells are prominent should be beneficial.

Unintended changes in protein expression revealed by proteomic analysis of seeds from transgenic pea expressing a bean alpha-amylase inhibitor gene.

Science.gov (United States)

Chen, Hancai; Bodulovic, Greg; Hall, Prudence J; Moore, Andy; Higgins, Thomas J V; Djordjevic, Michael A; Rolfe, Barry G

2009-09-01

Seeds of genetically modified (GM) peas (Pisum sativum L.) expressing the gene for alpha-amylase inhibitor-1 (alphaAI1) from the common bean (Phaseolus vulgaris L. cv. Tendergreen) exhibit resistance to the pea weevil (Bruchus pisorum). A proteomic analysis was carried out to compare seeds from GM pea lines expressing the bean alphaAI1 protein and the corresponding alphaAI1-free segregating lines and non-GM parental line to identify unintended alterations to the proteome of GM peas due to the introduction of the gene for alphaAI1. Proteomic analysis showed that in addition to the presence of alphaAI1, 33 other proteins were differentially accumulated in the alphaAI1-expressing GM lines compared with their non-GM parental line and these were grouped into five expression classes. Among these 33 proteins, only three were found to be associated with the expression of alphaAI1 in the GM pea lines. The accumulation of the remaining 30 proteins appears to be associated with Agrobacterium-mediated transformation events. Sixteen proteins were identified after MALDI-TOF-TOF analysis. About 56% of the identified proteins with altered accumulation in the GM pea were storage proteins including legumin, vicilin or convicilin, phaseolin, cupin and valosin-containing protein. Two proteins were uniquely expressed in the alphaAI1-expressing GM lines and one new protein was present in both the alphaAI1-expressing GM lines and their alphaAI1-free segregating lines, suggesting that both transgenesis and transformation events led to demonstrable changes in the proteomes of the GM lines tested.

The first trimester human placenta is a site for terminal maturation of primitive erythroid cells.

Science.gov (United States)

Van Handel, Ben; Prashad, Sacha L; Hassanzadeh-Kiabi, Nargess; Huang, Andy; Magnusson, Mattias; Atanassova, Boriana; Chen, Angela; Hamalainen, Eija I; Mikkola, Hanna K A

2010-10-28

Embryonic hematopoiesis starts via the generation of primitive red blood cells (RBCs) that satisfy the embryo's immediate oxygen needs. Although primitive RBCs were thought to retain their nuclei, recent studies have shown that primitive RBCs in mice enucleate in the fetal liver. It has been unknown whether human primitive RBCs enucleate, and what hematopoietic site might support this process. Our data indicate that the terminal maturation and enucleation of human primitive RBCs occurs in first trimester placental villi. Extravascular ζ-globin(+) primitive erythroid cells were found in placental villi between 5-7 weeks of development, at which time the frequency of enucleated RBCs was higher in the villous stroma than in circulation. RBC enucleation was further evidenced by the presence of primitive reticulocytes and pyrenocytes (ejected RBC nuclei) in the placenta. Extravascular RBCs were found to associate with placental macrophages, which contained ingested nuclei. Clonogenic macrophage progenitors of fetal origin were present in the chorionic plate of the placenta before the onset of fetoplacental circulation, after which macrophages had migrated to the villi. These findings indicate that placental macrophages may assist the enucleation process of primitive RBCs in placental villi, implying an unexpectedly broad role for the placenta in embryonic hematopoiesis.

Test of the Flavour Independence of $\\alpha_{s}$ using Next-to-Leading Order Calculations for Heavy Quarks

CERN Document Server

Abbiendi, G.; Alexander, G.; Allison, John; Altekamp, N.; Anderson, K.J.; Anderson, S.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Batley, J.R.; Baumann, S.; Bechtluft, J.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bellerive, A.; Bentvelsen, S.; Bethke, S.; Betts, S.; Biebel, O.; Biguzzi, A.; Bloodworth, I.J.; Bock, P.; Bohme, J.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Bright-Thomas, P.; Brigliadori, L.; Brown, Robert M.; Burckhart, H.J.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Ciocca, C.; Clarke, P.E.L.; Clay, E.; Cohen, I.; Conboy, J.E.; Cooke, O.C.; Couchman, J.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Davis, R.; De Jong, S.; de Roeck, A.; Dervan, P.; Desch, K.; Dienes, B.; Dixit, M.S.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Estabrooks, P.G.; Etzion, E.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Fiedler, F.; Fierro, M.; Fleck, I.; Frey, A.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gascon-Shotkin, S.M.; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Gibson, V.; Gibson, W.R.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Gorn, W.; Grandi, C.; Graham, K.; Gross, E.; Grunhaus, J.; Gruwe, M.; Hajdu, C.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Harder, K.; Harel, A.; Hargrove, C.K.; Harin-Dirac, M.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herndon, M.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hobson, P.R.; Hocker, James Andrew; Hoffman, Kara Dion; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jacob, F.R.; Jawahery, A.; Jeremie, H.; Jimack, M.; Jones, C.R.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klier, A.; Kobayashi, T.; Kobel, M.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kyberd, P.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lauber, J.; Lawson, I.; Layter, J.G.; Lellouch, D.; Letts, J.; Levinson, L.; Liebisch, R.; List, B.; Littlewood, C.; Lloyd, A.W.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Lu, J.; Ludwig, J.; Lui, D.; Macchiolo, A.; Macpherson, A.; Mader, W.; Mannelli, M.; Marcellini, S.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; Mckigney, E.A.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Mendez-Lorenzo, P.; Merritt, F.S.; Mes, H.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Petzold, S.; Pfeifenschneider, P.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poffenberger, P.; Poli, B.; Polok, J.; Przybycien, M.; Quadt, A.; Rembser, C.; Rick, H.; Robertson, S.; Robins, S.A.; Rodning, N.; Roney, J.M.; Rosati, S.; Roscoe, K.; Rossi, A.M.; Rozen, Y.; Runge, K.; Runolfsson, O.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schmitt, S.; Schoning, A.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Sittler, A.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Spagnolo, S.; Sproston, M.; Stahl, A.; Stephens, K.; Steuerer, J.; Stoll, K.; Strom, David M.; Strohmer, R.; Surrow, B.; Talbot, S.D.; Taras, P.; Tarem, S.; Teuscher, R.; Thiergen, M.; Thomas, J.; Thomson, M.A.; Torrence, E.; Towers, S.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Voss, H.; Wackerle, F.; Wagner, A.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wermes, N.; Wetterling, D.; White, J.S.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Zacek, V.; Zer-Zion, D.

1999-01-01

We present a test of the flavour independence of the strong coupling constant for charm and bottom quarks with respect to light (uds) quarks, based on a hadronic event sample obtained with the OPAL detector at LEP. Five observables related to global event shapes were used to measure alpha_s in three flavour tagged samples (uds, c and b). The event shape distributions were fitted by Order(alpha_s**2) calculations of jet production taking into account mass effects for the c and b quarks. We find: = 0.997 +- 0.038(stat.) +- 0.030(syst.) +- 0.012(theory) and = 0.993 +- 0.008(stat.) +- 0.006(syst.) +- 0.011(theory) for the ratios alpha_s(charm)/alpha_s(uds) and alpha_s(b)/alpha_s(uds) respectively.

Classification of alpha 1-adrenoceptor subtypes

NARCIS (Netherlands)

Michel, M. C.; Kenny, B.; Schwinn, D. A.

1995-01-01

Two alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) have been detected in various tissues by pharmacological techniques, and three distinct cDNAs encoding alpha 1-adrenoceptor subtypes have been cloned. The profile of an increasing number of subtype-selective compounds at cloned and endogenous

PHYSICAL PROPERTIES OF Ly{alpha} EMITTERS AT z {approx} 0.3 FROM UV-TO-FIR MEASUREMENTS

Energy Technology Data Exchange (ETDEWEB)

Oteo, I.; Bongiovanni, A.; Perez Garcia, A. M.; Cepa, J.; Pintos-Castro, I. [Instituto de Astrofisica de Canarias (IAC), E-38200 La Laguna, Tenerife (Spain); Ederoclite, A. [Centro de Estudios de Fisica del Cosmos de Aragon, Plaza San Juan 1, Planta 2, Teruel, 44001 (Spain); Sanchez-Portal, M.; Altieri, B. [Herschel Science Centre (ESAC), Villafranca del Castillo (Spain); Perez-Martinez, R. [XMM/Newton Science Operations Centre (ESAC), Villafranca del Castillo (Spain); Lutz, D.; Berta, S.; Foerster Schreiber, N.; Genzel, R.; Magnelli, B. [Max-Planck-Institut fuer Extraterrestrische Physik (MPE), Postfach 1312, 85741 Garching (Germany); Andreani, P. [ESO, Karl-Schwarzchild-Str. 2, D-85748 Garching (Germany); Aussel, H.; Daddi, E.; Elbaz, D.; Le Floc' h, E. [Commissariat a l' Energie Atomique (CEA-SAp) Saclay (France); Cimatti, A. [Dipartimento di Astronomia, Universita di Bologna, Via Ranzani 1, 40127 Bologna (Italy); and others

2012-06-01

The analysis of the physical properties of low-redshift Ly{alpha} emitters (LAEs) can provide clues in the study of their high-redshift analogs. At z {approx} 0.3, LAEs are bright enough to be detected over almost the entire electromagnetic spectrum and it is possible to carry out a more precise and complete study than at higher redshifts. In this work, we examine the UV and IR emission, dust attenuation, star formation rate (SFR), and morphology of a sample of 23 GALEX-discovered star-forming LAEs at z {approx} 0.3 with direct UV (GALEX), optical (ACS), and FIR (PACS and MIPS) data. Using the same UV and IR limiting luminosities, we find that LAEs at z {approx} 0.3 tend to be less dusty, have slightly higher total SFRs, have bluer UV continuum slopes, and are much smaller than other galaxies that do not exhibit Ly{alpha} emission in their spectrum (non-LAEs). These results suggest that at z {approx} 0.3, Ly{alpha} photons tend to escape from small galaxies with low dust attenuation. Regarding their morphology, LAEs belong to Irr/merger classes, unlike non-LAEs. Size and morphology represent the most noticeable difference between LAEs and non-LAEs at z {approx} 0.3. Furthermore, the comparison of our results with those obtained at higher redshifts indicates either that the Ly{alpha} technique picks up different kind of galaxies at different redshifts or that the physical properties of LAEs are evolving with redshift.

Microprecipitation of barium sulfate as a suitable source for measurements of 226Ra by alpha spectrometry

International Nuclear Information System (INIS)

Fernandez-Cata, Geyser; Isaac-Olive, Keila : E-mail. geyser@instec.cu

2007-01-01

One of the most hazardous radionuclides released into the environment is the uranium's daughter 226 Ra. This nuclide behaves similar to calcium, therefore is highly toxic for humans. One of the suitable methods for its determination is alpha spectrometry. This technique, however, has as main drawback the source preparation which should be infinitely thin and massless, of regular, known, and reproducible shape, smaller in area than the active area of the detector and new (no sputtering or recoil losses). Among the various ways of preparing an alpha source are the electrodeposition and microprecipitation. Radium electrodeposition is not suitable to carry out because of the high reduction potential of this element, therefore non aqueous media is required and the chemical yield is not good. Radium however can be precipitated with barium sulfate and our previous work has shown that the precipitation is selective to this element in the presence of other alpha emitters such as uranium and polonium but divalent cations are incorporated to it. At the same time, manganese dioxide also precipitates radium free of divalent cations but alpha emitters such as uranium are present as well. The objective of this work was to establish a chemical procedure for the determination of 226 Ra in natural water by alpha spectrometry. The general methodology includes a preconcentration using a non selective coprecipitation via manganese dioxide (where cations are not included but alpha emitters do). Once the manganese dioxide is filtrated, it is re-dissolved and a selective microprecipitation using barium sulphate is carried out (where the only alpha emitter is radium). Details of the procedure, separation methods, source quality and discussion of the results will be given in the paper. (Author)

Dynamical chaos in a linear 3. alpha. system. Dinamicheskij khaos v linejnoj 3. alpha. -sisteme

Energy Technology Data Exchange (ETDEWEB)

Bolotin, Yu L; Gonchar, V Yu; Chekanov, N A [AN Ukrainskoj SSR, Kharkov (Ukrainian SSR). Fiziko-Tekhnicheskij Inst.; Vinitskij, S I [Joint Inst. for Nuclear Research, Dubna (USSR)

1989-01-01

Classical dynamics of the motion of a molecular model of the carbon nucleus, which is a linear 3{alpha} system with realistic {alpha}{alpha} interaction is studied. Transition from a regular to a chaos motion in the nuclear molecule is shown to occur with growing energy more rapidly than in model problems with polynomial potentials. It is found that in a small region of the phase space the motion remains regular at energies higher than the 3{alpha}-system dissociation threshold. This is probably related to the C{sub 3v}-symmetry violation. Formulas for the quasiclassical spectrum of the 3{alpha} system are obtained with the use of the Birkhoff normal form.

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

Directory of Open Access Journals (Sweden)

Debora Lucia Seguro Danilovic

2011-01-01

Full Text Available OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels, which occur despite stable free T4 and TSH levels. A thyroid

Relation of estrogen receptor-alpha gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women.

Science.gov (United States)

Salmén, Timo; Heikkinen, Anna-Mari; Mahonen, Anitta; Kröger, Heikki; Komulainen, Marja; Saarikoski, Seppo; Honkanen, Risto; Partanen, Juhani; Mäenpää, Pekka H

2002-01-01

Several factors may increase fracture risk, among them reduced bone mineral density (BMD), increased bone resorption, microarchitectural deterioration of bone, increased fall risk, and decreased muscle strength. We have previously reported that PvuII polymorphism of the estrogen receptor-alpha (ER alpha) gene is associated with bone loss rate, fracture risk, and response to hormone replacement therapy (HRT) in early postmenopausal Finnish women. We studied the influence of the ER alpha genotype on fall risk and muscle strength in a 5-year randomized HRT trial of 331 early postmenopausal women (subgroup of the population-based OSTPRE study, Kuopio, Finland). A 5-year postal inquiry in May 1994 included questions on falls during the previous 12 months. Grip strength was measured with dynamometer. The ER alpha gene polymorphism was analysed using PCR and PvuII restriction enzyme digestion. RESULTS. In all, 97 out of the 331 women reported falls. Half of those (56%) were slip falls, mostly during the winter season. In the HRT group, the ER alpha genotype was associated with fall risk (P = 0.002, logistic regression). The risk of falls (RR) was higher in women with the PP genotype than in those with the Pp (RR = 5.26, 95% CI 1.98-13.94, P = 0.001) or the pp (RR = 3.84, 95% CI 1.46-10.12, P = 0.007) genotype. When the falls were divided into slip (environment-related) and non-slip (endogenous) falls, the non-slip falls were associated with the genotype (P = 0.004), but the slip falls were not so clearly (P = 0.061). When all falls and non-slip falls were adjusted to the number of chronic health disorders and the variable time-since-menopause, the difference between the genotypes persisted (P = 0.003 and P = 0.010, respectively). In the non-HRT group, the ER alpha genotype was not associated with fall risk. The baseline or the 5-year grip strength values were not influenced by the ER alpha genotype. In conclusion, ER alpha polymorphism is associated with fall risk

Alpha detection on moving surfaces

International Nuclear Information System (INIS)

MacArthur, D.; Orr, C.; Luff, C.

1998-01-01

Both environmental restoration (ER) and decontamination and decommissioning (D and D) require characterization of large surface areas (walls, floors, in situ soil, soil and rubble on a conveyor belt, etc.) for radioactive contamination. Many facilities which have processed alpha active material such as plutonium or uranium require effective and efficient characterization for alpha contamination. Traditional methods for alpha surface characterization are limited by the short range and poor penetration of alpha particles. These probes are only sensitive to contamination located directly under the probe. Furthermore, the probe must be held close to the surface to be monitored in order to avoid excessive losses in the ambient air. The combination of proximity and thin detector windows can easily cause instrument damage unless extreme care is taken. The long-range alpha detection (LRAD) system addresses these problems by detecting the ions generated by alpha particles interacting with ambient air rather than the alpha particle directly. Thus, detectors based on LRAD overcome the limitations due to alpha particle range (the ions can travel many meters as opposed to the several-centimeter alpha particle range) and penetrating ability (an LRAD-based detector has no window). Unfortunately, all LRAD-based detectors described previously are static devices, i.e., these detectors cannot be used over surfaces which are continuously moving. In this paper, the authors report on the first tests of two techniques (the electrostatic ion seal and the gridded electrostatic LRAD detector) which extend the capabilities of LRAD surface monitors to use over moving surfaces. This dynamic surface monitoring system was developed jointly by Los Alamos National Laboratory and at BNFL Instruments. All testing was performed at the BNFL Instruments facility in the UK

Thiols in the alphaIIbbeta3 integrin are necessary for platelet aggregation.

Science.gov (United States)

Manickam, Nagaraj; Sun, Xiuhua; Hakala, Kevin W; Weintraub, Susan T; Essex, David W

2008-07-01

Sulfhydryl groups of platelet surface proteins are important in platelet aggregation. While p-chloromercuribenzene sulphonate (pCMBS) has been used in most studies on platelet surface thiols, the specific thiol-proteins that pCMBS reacts with to inhibit aggregation have not been well defined. Since the thiol-containing P2Y(12) ADP receptor is involved in most types of platelet aggregation, we used the ADP scavenger apyrase and the P2Y(12) receptor antagonist 2-MeSAMP to examine thiol-dependent reactions in the absence of contributions from this receptor. We provide evidence for a non-P2Y(12) thiol-dependent reaction near the final alphaIIbbeta3-dependent events of aggregation. We then used 3-(N-maleimidylpropionyl)biocytin (MPB) and pCMBS to study thiols in alphaIIbbeta3. As previously reported, disruption of the receptor was required to obtain labelling of thiols with MPB. Specificity of labelling for thiols in the alphaIIb and beta3 subunits was confirmed by identification of the purified proteins by mass spectrometry and by inhibition of labelling with 5,5'-dithiobis-(2-nitrobenzoic acid). In contrast to MPB, pCMBS preferentially reacted with thiols in alphaIIbbeta3 and blocked aggregation under physiological conditions. Similarly, pCMBS preferentially inhibited signalling-independent activation of alphaIIbbeta3 by Mn(2+). Our results suggest that the thiols in alphaIIbbeta3 that are blocked by pCMBS are important in the activation of this integrin.

Study of ({alpha}, {sup 3}He) and ({alpha}, t) reactions on {sup 28}Si at 45 MeV

Energy Technology Data Exchange (ETDEWEB)

Darshan, V.P.; Sathyavathiamma, M.P.; Ramaswamy, C.R.; Raja Rao, M.; Puttaswamy, N.G.; Banerjee, S.R.; Chintalapudi, S.N. [Dept. of Phys., Bangalore Univ. (India)

1995-03-01

The {sup 28}Si({alpha}, {sup 3}He){sup 29}Si, {sup 28}Si({alpha}, t){sup 29}P and Si({alpha}, {alpha})Si reactions were studied at E{sub {alpha}} = 45 MeV. Exact finite-range (EFR) DWBA analysis was carried out for the transitions to the ground state and to five excited states in {sup 29}Si and {sup 29}P. Spectroscopic strengths G were extracted for all the states and were compared with the predictions from shell-model and quasi-particle core-coupling calculations. Similar EFR-DWBA analyses were carried out from available (unpublished) data for the {sup 28}Si({alpha}, {sup 3}He){sup 29}Si reaction at E{sub {alpha}} = 64.9 and 120 MeV, and for the {sup 28}Si({alpha}, t){sup 29}P reaction at E{sub {alpha}} = 50 and 64.9 MeV. The comparison of experimental and theoretical values of G are provided. (author)

1H and 15N NMR assignment and solution structure of the SH3 domain of spectrin: Comparison of unrefined and refined structure sets with the crystal structure

International Nuclear Information System (INIS)

Blanco, Francisco J.; Ortiz, Angel R.; Serrano, Luis

1997-01-01

The assignment of the 1 H and 15 Nnuclear magnetic resonance spectra of the Src-homology region 3 domain of chicken brain α-spectrin has been obtained. A set of solution structures has been determined from distance and dihedral angle restraints,which provide a reasonable representation of the protein structure in solution, as evaluated by a principal component analysis of the global pairwise root-mean-square deviation (rmsd) in a large set of structures consisting of the refined and unrefined solution structures and the crystal structure. The solution structure is well defined, with a lower degree of convergence between the structures in the loop regions than in the secondary structure elements. The average pairwise rmsd between the 15 refined solution structures is 0.71 ± 0.13 A for the backbone atoms and 1.43 ± 0.14 A for all heavy atoms. The solution structure is basically the same as the crystal structure. The average rmsd between the 15 refined solution structures and the crystal structure is 0.76 A for the backbone atoms and 1.45 ± 0.09 A for all heavy atoms. There are, however, small differences probably caused by intermolecular contacts in the crystal structure

alpha AD alpha hybrids of Cryptococcus neoformans: evidence of same-sex mating in nature and hybrid fitness.

Directory of Open Access Journals (Sweden)

Xiaorong Lin

2007-10-01

Full Text Available Cryptococcus neoformans is a ubiquitous human fungal pathogen that causes meningoencephalitis in predominantly immunocompromised hosts. The fungus is typically haploid, and sexual reproduction involves two individuals with opposite mating types/sexes, alpha and a. However, the overwhelming predominance of mating type (MAT alpha over a in C. neoformans populations limits alpha-a mating in nature. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions, especially between alpha isolates. Whether same-sex mating occurs in nature and contributes to the current population structure was unknown. In this study, natural alpha AD alpha hybrids that arose by fusion between two alpha cells of different serotypes (A and D were identified and characterized, providing definitive evidence that same-sex mating occurs naturally. A novel truncated allele of the mating-type-specific cell identity determinant SXI1 alpha was also identified as a genetic factor likely involved in this process. In addition, laboratory-constructed alpha AD alpha strains exhibited hybrid vigor both in vitro and in vivo, providing a plausible explanation for their relative abundance in nature despite the fact that AD hybrids are inefficient in meiosis/sporulation and are trapped in the diploid state. These findings provide insights on the origins, genetic mechanisms, and fitness impact of unisexual hybridization in the Cryptococcus population.

Biochemical characterization of CK2alpha and alpha' paralogues and their derived holoenzymes: evidence for the existence of a heterotrimeric CK2alpha'-holoenzyme forming trimeric complexes

DEFF Research Database (Denmark)

Olsen, Birgitte; Rasmussen, Tine; Niefind, Karsten

2008-01-01

Altogether 2 holoenzymes and 4 catalytic CK2 constructs were expressed and characterized i.e. CK2alpha (2) (1-335) beta(2); CK2alpha'-derived holoenzyme; CK2alpha(1-335); MBP-CK2alpha'; His-tagged CK2alpha and His-tagged CK2alpha'. The two His-tagged catalytic subunits were expressed in insect...... cells, all others in Escherichia coli. IC(50) studies involving the established CK2 inhibitors DMAT, TBBt, TBBz, apigenin and emodin were carried out and the K(i) values calculated. Although the differences in the K(i) values found were modest, there was a general tendency showing that the CK2...... holoenzymes were more sensitive towards the inhibitors than the free catalytic subunits. Thermal inactivation experiments involving the individual catalytic subunits showed an almost complete loss of activity after only 2 min at 45 degrees C. In the case of the two holoenzymes, the CK2alpha...

Flavonoids-induced accumulation of hypoxia-inducible factor (HIF)-1alpha/2alpha is mediated through chelation of iron.

Science.gov (United States)

Park, Sung-Soo; Bae, Insoo; Lee, Yong J

2008-04-15

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1 that is the key regulator of cellular response to low oxygen tension. Under normoxic conditions, HIF-1alpha is continuously degraded by the ubiquitin-proteasome pathway through pVHL (von Hippel-Lindau tumor suppressor protein). Under hypoxic conditions, HIF-1alpha is stabilized and induces the transcription of HIF-1 target genes. Quercetin, a flavonoid with anti-oxidant, anti-inflammatory, and kinase modulating properties, has been found to induce HIF-1alpha accumulation and VEGF secretion in normoxia. In this study, the molecular mechanisms of quercetin-mediated HIF-1alpha accumulation were investigated. Previous studies have shown that, in addition to being induced by hypoxia, HIF-1alpha can be induced through the phosphatidylinositol 3-kinase (PI3K)/Akt and p53 signaling pathways. But our study revealed, through p53 mutant-type as well as p53 null cell lines, that neither the PI3K/Akt nor the p53 signaling pathway is required for quercetin-induced HIF-1alpha accumulation. And we observed that HIF-1alpha accumulated by quercetin is not ubiquitinated and the interaction of HIF-1alpha with pVHL is reduced, compared with HIF-1alpha accumulated by the proteasome inhibitor MG132. The use of quercetin's analogues showed that only quercetin and galangin induce HIF-1/2alpha accumulation and this effect is completely reversed by additional iron ions. This is because quercetin and galangin are able to chelate cellular iron ions that are cofactors of HIF-1/2alpha proline hydroxylase (PHD). These data suggest that quercetin inhibits the ubiquitination of HIF-1/2alpha in normoxia by hindering PHD through chelating iron ions.

Alpha/Theta Neurofeedback Increases Mentalization and Default Mode Network Connectivity in a Non-Clinical Sample.

Science.gov (United States)

Imperatori, Claudio; Della Marca, Giacomo; Amoroso, Noemi; Maestoso, Giulia; Valenti, Enrico Maria; Massullo, Chiara; Carbone, Giuseppe Alessio; Contardi, Anna; Farina, Benedetto

2017-11-01

Several studies showed the effectiveness of alpha/theta (A/T) neurofeedback training in treating some psychiatric conditions. Despite the evidence of A/T effectiveness, the psychological and neurobiological bases of its effects is still unclear. The aim of the present study was to explore the usefulness of the A/T training in increasing mentalization in a non-clinical sample. The modifications of electroencephalographic (EEG) functional connectivity in Default Mode Network (DMN) associated with A/T training were also investigated. Forty-four subjects were enrolled in the study and randomly assigned to receive ten sessions of A/T training [neurofeedback group (NFG) = 22], or to act as controls [waiting list group (WLG) = 22]. All participants were administered the mentalization questionnaire (MZQ) and the Symptom Checklist-90-Revised (SCL-90-R). In the post training assessment, compared to WLG, NFG showed a significant increase of MZQ total scores (3.94 ± 0.73 vs. 3.53 ± 0.77; F 1;43 = 8.19; p = 0.007; d = 0.863). Furthermore, A/T training was also associated with a significant increase of EEG functional connectivity in several DMN brain areas (e.g. Posterior Cingulate Cortex). Taken together our results support the usefulness of the A/T training in enhancing mentalization and DMN connectivity.

HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

Directory of Open Access Journals (Sweden)

Freya M Mowat

2010-06-01

Full Text Available Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators.We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF and erythropoietin (Epo by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO.Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation plays a key role in regulating the response of Müller glia to hypoxia.

Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

International Nuclear Information System (INIS)

Andersson, G.; Lundgren, E.; Ekre, H.P.

1991-01-01

Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition of the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity

Alpha and beta detection and spectrometry

International Nuclear Information System (INIS)

Saro, S.

1984-01-01

The theory of alpha and beta radioactive decay, the interaction of alpha and beta particles with matter, and their detection and spectrometry are dealt with in seven chapters: 1. Alpha transformation of atomic nuclei; 2. Basic properties of detectors and statistics of detection; 3. Alpha detectors and spectrometers; 4. Applications of alpha detection and spectrometry; 5. Beta transformation of atomic nuclei; 6. Beta particle detectors and spectrometers; 7. Detection of low energy beta particles. Chapter 8 is devoted to sampling and preparation of samples for radiometry. (E.F.)

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

Science.gov (United States)

Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

2018-03-01

Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians). One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established. There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash. This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

Improvement of non-destructive fissile mass assays in {alpha} low-level waste drums: A matrix correction method based on neutron capture gamma-rays and a neutron generator

Energy Technology Data Exchange (ETDEWEB)

Jallu, F. [Commissariat a l' Energie Atomique, CEA, DEN, Nuclear Measurement Laboratory, Bat. 224, 13108 Saint Paul lez Durance (France)], E-mail: fanny.jallu@cea.fr; Loche, F. [Commissariat a l' Energie Atomique, CEA, DEN, Nuclear Measurement Laboratory, Bat. 224, 13108 Saint Paul lez Durance (France)

2008-08-15

Within the framework of radioactive waste control, non-destructive assay (NDA) methods may be employed. The active neutron interrogation (ANI) method is now well-known and effective in quantifying low {alpha}-activity fissile masses (mainly {sup 235}U, {sup 239}Pu, {sup 241}Pu) with low densities, i.e. less than about 0.4, in radioactive waste drums of volumes up to 200 l. The PROMpt Epithermal and THErmal interrogation Experiment (PROMETHEE [F. Jallu, A. Mariani, C. Passard, A.-C. Raoux, H. Toubon, Alpha low level waste control: improvement of the PROMETHEE 6 assay system performances. Nucl. Technol. 153 (January) (2006); C. Passard, A. Mariani, F. Jallu, J. Romeyer-Dherber, H. Recroix, M. Rodriguez, J. Loridon, C. Denis, PROMETHEE: an alpha low level waste assay system using passive and active neutron measurement methods. Nucl. Technol. 140 (December) (2002) 303-314]) based on ANI has been under development since 1996 to reach the incinerating {alpha} low level waste (LLW) criterion of about 50 Bq[{alpha}] per gram of crude waste ({approx}50 {mu}g Pu) in 118 l drums on the date the drums are conditioned. Difficulties arise when dealing with matrices containing neutron energy moderators such as H and neutron absorbents such as Cl. These components may have a great influence on the fissile mass deduced from the neutron signal measured by ANI. For example, the calibration coefficient measured in a 118 l drum containing a cellulose matrix (density d = 0.144 g cm{sup -3}) may be 50 times higher than that obtained in a poly-vinyl-chloride matrix (d = 0.253 g cm{sup -3}). Without any information on the matrix, the fissile mass is often overestimated due to safety procedures and by considering the most disadvantageous calibration coefficient corresponding to the most absorbing and moderating calibration matrix. The work discussed in this paper was performed at the CEA Nuclear Measurement Laboratory in France. It concerns the development of a matrix effect correction

Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy?

NARCIS (Netherlands)

Bakker, H. D.; de Sonnaville, M. L.; Vreken, P.; Abeling, N. G.; Groener, J. E.; Keulemans, J. L.; van Diggelen, O. P.

2001-01-01

Two new individuals with alpha-NAGA deficiency are presented. The index patient, 3 years old, has congenital cataract, slight motor retardation and secondary demyelinisation. Screening of his sibs revealed an alpha-NAGA deficiency in his 7-year-old healthy brother who had no clinical or neurological

Laser and alpha particle characterization of floating-base BJT detector

Energy Technology Data Exchange (ETDEWEB)

Tyzhnevyi, V., E-mail: tyzhnevyi@disi.unitn.i [Universita di Trento and INFN Trento, Trento (Italy); Batignani, G. [Dipartimento di Fisica, Universita di Pisa and INFN Pisa, Pisa (Italy); Bosisio, L. [Dipartimento di Fisica, Universita di Trieste and INFN Trieste, Trieste (Italy); Dalla Betta, G.-F. [Universita di Trento and INFN Trento, Trento (Italy); Verzellesi, G. [Universita di Modena e Reggio Emilia and INFN Trento, Reggio Emilia (Italy); Zorzi, N. [Fondazione Bruno Kessler (FBK), Trento (Italy)

2010-05-21

In this work, we investigate the detection properties of existing prototypes of BJT detectors operated with floating base. We report about results of two functional tests. The charge-collection properties of BJT detectors were evaluated by means of a pulsed laser setup. The response to {alpha}-particles emitted from radioactive {sup 241}Am source are also presented. Experimental results show that current gains of about 450 with response times in the order of 50 {mu}s are preserved even in this non-standard operation mode, in spite of a non-optimized structure.

Applying alpha-channeling to mirror machines

Energy Technology Data Exchange (ETDEWEB)

Zhmoginov, A. I.; Fisch, N. J. [Department of Astrophysical Sciences, Princeton University, Princeton, New Jersey 08544 (United States)

2012-05-15

The {alpha}-channeling effect entails the use of radio-frequency waves to expel and cool high-energetic {alpha} particles born in a fusion reactor; the device reactivity can then be increased even further by redirecting the extracted energy to fuel ions. Originally proposed for tokamaks, this technique has also been shown to benefit open-ended fusion devices. Here, the fundamental theory and practical aspects of {alpha} channeling in mirror machines are reviewed, including the influence of magnetic field inhomogeneity and the effect of a finite wave region on the {alpha}-channeling mechanism. For practical implementation of the {alpha}-channeling effect in mirror geometry, suitable contained weakly damped modes are identified. In addition, the parameter space of candidate waves for implementing the {alpha}-channeling effect can be significantly extended through the introduction of a suitable minority ion species that has the catalytic effect of moderating the transfer of power from the {alpha}-channeling wave to the fuel ions.

Alpha oscillation neurofeedback modulates amygdala complex connectivity and arousal in posttraumatic stress disorder

Directory of Open Access Journals (Sweden)

Andrew A. Nicholson

2016-01-01

Conclusion: These findings have significant implications for developing targeted non-invasive treatment interventions for PTSD patients that utilize alpha oscillatory neurofeedback, showing evidence of neuronal reconfiguration between areas highly implicated in the disorder, in addition to acute symptom alleviation.

DT results of TFTR's alpha collector

International Nuclear Information System (INIS)

Herrmann, H.W.; Zweben, S.J.; Darrow, D.S.; Timberlake, J.R.; Macaulay-Newcombe, R.G.

1996-01-01

An escaping alpha collector probe has been developed for TFTR's DT phase to complement the results of the lost alpha scintillator detectors which have been operating on TFTR since 1988. Measurements of the energy distribution of escaping alphas have been made by measuring the range of alphas implanted into nickel foils located within the alpha collector. Exposed samples have been analyzed for 4 DT plasma discharges at plasma currents of 1.0 and 1.8 MA. The results at 1.0 MA are in good agreement with predictions for first orbit alpha loss at 3.5 MeV. The 1.8 MA results, however, indicate a large anomalous loss of partially thermalized alphas at an energy ∼30% below the birth energy and at a total fluence nearly an order of magnitude above expected first orbit loss. This anomalous loss is not observed with the lost alpha scintillator detectors in DT plasmas but does resemble the anomalous delayed loss seen in DD plasmas. Several potential explanations for this loss process are examined. None of the candidate explanations proposed thus far are fully consistent with the anomalous loss observations

Functional Cortical Network in Alpha Band Correlates with Social Bargaining

Science.gov (United States)

Billeke, Pablo; Zamorano, Francisco; Chavez, Mario; Cosmelli, Diego; Aboitiz, Francisco

2014-01-01

Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals’ alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts. PMID:25286240

Alpha Thalassemia (For Parents)

Science.gov (United States)

... Safe Videos for Educators Search English Español Alpha Thalassemia KidsHealth / For Parents / Alpha Thalassemia What's in this ... Symptoms Diagnosis Treatment Print en español Alfa talasemia Thalassemias Thalassemias are a group of blood disorders that ...

Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

Science.gov (United States)

Rutault, K; Hazzalin, C A; Mahadevan, L C

2001-03-02

Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

Development of thermal conditioning technology for Alpha-containment wastes: Alpha-contaminated waste incineration technology

Energy Technology Data Exchange (ETDEWEB)

Kim, Joon Hyung; Kim, Jeong Guk; Yang, Hee Chul; Choi, Byung Seon; Jeong, Myeong Soo

1999-03-01

As the first step of a 3-year project named 'development of alpha-contaminated waste incineration technology', the basic information and data were reviewed, while focusing on establishment of R and D direction to develop the final goal, self-supporting treatment of {alpha}- wastes that would be generated from domestic nuclear industries. The status on {alpha} waste incineration technology of advanced states was reviewed. A conceptual design for {alpha} waste incineration process was suggested. Besides, removal characteristics of volatile metals and radionuclides in a low-temperature dry off-gas system were investigated. Radiation dose assessments and some modification for the Demonstration-scale Incineration Plant (DSIP) at Korea Atomic Energy Research Institute (KAERI) were also done.

Tumor necrosis factor-alpha-independent downregulation of hepatic cholesterol 7alpha-hydroxylase gene in mice treated with lead nitrate.

Science.gov (United States)

Kojima, Misaki; Sekikawa, Kenji; Nemoto, Kiyomitsu; Degawa, Masakuni

2005-10-01

We previously reported that lead nitrate (LN), an inducer of hepatic tumor necrosis factor-alpha (TNF-alpha), downregulated gene expression of cholesterol 7alpha-hydroxylase. Herein, to clarify the role of TNF-alpha in LN-induced downregulation of cholesterol 7alpha-hydroxylase, effects of LN on gene expression of hepatic cholesterol 7alpha-hydroxylase (Cyp7a1) in TNF-alpha-knockout (KO) and TNF-alpha-wild-type (WT) mice were comparatively examined. Gene expression of hepatic Cyp7a1 in both WT and KO mice decreased to less than 5% of the corresponding controls at 6-12 h after treatment with LN (100 mumol/kg body weight, iv). Levels of hepatic TNF-alpha protein in either WT or KO mice were below the detection limit, although expression levels of the TNF-alpha gene markedly increased at 6 h in WT mice by LN treatment, but not in KO mice. In contrast, in both WT and KO mice, levels of hepatic IL-1beta protein, which is known to be a suppressor of the cholesterol 7alpha-hydroxylase gene in hamsters, were significantly increased 3-6 h after LN treatment. Furthermore, LN-induced downregulation of the Cyp7a1 gene did not necessarily result from altered gene expression of hepatic transcription factors, including positive regulators (liver X receptor alpha, retinoid X receptor alpha, fetoprotein transcription factor, and hepatocyte nuclear factor 4alpha) and a negative regulator small heterodimer partner responsible for expression of the Cyp7a1 gene. The present findings indicated that LN-induced downregulation of the Cyp7a1 gene in mice did not necessarily occur through a TNF-alpha-dependent pathway and might occur mainly through an IL-1beta-dependent pathway.

Reverse-phase HPLC analysis of human alpha crystallin.

Science.gov (United States)

Swamy, M S; Abraham, E C

1991-03-01

A rapid and highly sensitive reverse-phase HPLC (RP-HPLC) method was used to separate crystallin subunits from human alpha crystallin. Three distinct peaks were separated; by electrophoretic and immunological analyses the first and second peaks were identified as alpha B and alpha A respectively. On the other hand, peak 3 appeared to be a modified form of alpha crystallin. The ratio of alpha A and alpha B proteins was 3:1 in 1 day old lenses which gradually changed to 2:1 in 17 year old lenses and to 1:1 in the 50 and 82 year old whole lenses and 82 year old lens cortex, with a concomitant increase in the modified alpha, suggesting that alpha A subunits are relatively more involved in aggregation. Analysis of the 82 year old lens nucleus also supported this conclusion. The RP-HPLC analysis of the HMW aggregate fraction showed substantial enrichment of the modified alpha. The alpha A and alpha B subunits independently reassociated to form polymeric alpha crystallin whereas the modified alpha reassociated to form HMW aggregates as shown by molecular sieve HPLC. Hence it appears that the HMW aggregate peak was constituted by modified alpha crystallin. Only in the peak 3 material the 280 nm absorbance was about 2-fold higher than what was expected from the actual protein content. The data suggest that the changes induced by post-translational modifications may have some role in the formation of modified alpha. The present RP-HPLC method is useful in separating these modified alpha from the unmodified alpha A and alpha B subunits.

Proteinaceous alpha-araylase inhibitors

DEFF Research Database (Denmark)

Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.

2004-01-01

-amylase inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha...

Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation.

Science.gov (United States)

Matousek, P; Novotný, J; Svoboda, P

2004-01-01

Low-density membrane-domain fractions were prepared from S49 lymphoma cells and clone e2m11 of HEK293 cells expressing a large number of thyrotropin-releasing hormone receptor (TRH-R) and G(11)alpha by flotation on sucrose density gradients. The intact cell structure was broken by detergent-extraction, alkaline-treatment or drastic homogenization. Three types of low-density membranes were resolved by two-dimensional electrophoresis and analyzed for G(s)alpha (S49) or G(q)alpha/G11) (e2m11) content. Four individual immunoblot signals of Gsalpha protein were identified in S49 lymphoma cells indicating complete resolution of the long G(s)alpha L+/-ser and short G(s)alpha S+/-ser variants of G(s)alpha. All these were diminished by prolonged agonist (isoprenaline) stimulation. In e2m11-HEK cells, five different immunoblot signals were detected indicating post-translational modification of G proteins of G(q)alpha/G(11)alpha family. The two major spots corresponding to exogenously (over)expressed G(11)alpha and endogenous G(q)alpha were reduced; the minor spots diminished by hormonal stimulation. Parallel analysis by silver staining of the total protein content indicated that no major changes in protein composition occurred under these conditions. Our data thus indicate that agonist-stimulation of target cells results in down-regulation of all different members of G(s) and G(q)/G(11) families. This agonist-specific effect may be demonstrated in crude membrane as well as domain/raft preparations and it is not accompanied by changes in overall protein composition.

Alpha 1A and alpha 1B-adrenoceptors enhance inositol phosphate generation in rat renal cortex

NARCIS (Netherlands)

Michel, M. C.; Büscher, R.; Philipp, T.; Brodde, O. E.

1993-01-01

We have studied the role of alpha 1A- and alpha 1B-adrenoceptors in noradrenaline- and methoxamine-stimulated inositol phosphate accumulation in rat renal cortical slices. [3H]Prazosin binding studies with and without inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment suggested

Molecular characteristic of alpha thalassaemia among patients diagnosed in UKM Medical Centre.

Science.gov (United States)

Azma, Raja Zahratul; Ainoon, Othman; Hafiza, Alauddin; Azlin, Ithnin; Noor Farisah, Abudul Razak; Nor Hidayati, Sardi; Noor Hamidah, Hussin

2014-04-01

Alpha (Α) thalassaemia is the most common inherited disorder in Malaysia. The clinical severity is dependant on the number of Α genes involved. Full blood count (FBC) and haemoglobin (Hb) analysis using either gel electrophoresis, high performance liquid chromatography (HPLC) or capillary zone electrophoresis (CE) are unable to detect definitively alpha thalassaemia carriers. Definitive diagnosis of Α-thalassaemias requires molecular analysis and methods of detecting both common deletional and non-deletional molecular abnormailities are easily performed in any laboratory involved in molecular diagnostics. We carried out a retrospective analysis of 1623 cases referred to our laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for the diagnosis of Α-thalassaemia during the period October 2001 to December 2012. We examined the frequency of different types of alpha gene abnormalities and their haematologic features. Molecular diagnosis was made using a combination of multiplex polymerase reaction (PCR) and real time PCR to detect deletional and non-deletional alpha genes relevant to southeast Asian population. Genetic analysis confirmed the diagnosis of Α-thalassaemias in 736 cases. Majority of the cases were Chinese (53.1%) followed by Malays (44.2%), and Indians (2.7%). The most common gene abnormality was ΑΑ/--(SEA) (64.0%) followed by ΑΑ/-Α(3.7) (19.8%), -Α(3.7) /--(SEA) (6.9%), ΑΑ/ΑΑCS (3.0%), --(SEA)/--(SEA) (1.2%), -Α(3.7)/-Α(3.7) (1.1%), ΑΑ/-Α(4.2) (0.7%), -Α(4.2)/--(SEA (0.7%), -Α(3.7)/-Α(4.2) (0.5%), ΑΑ(CS)/-- SEA) (0.4%), ΑΑ(CS)/ΑΑ(Cd59) (0.4%), ΑΑ(CS)/ΑΑ(CS) (0.4%), -Α(3.7)/ΑΑ(Cd59) (0.3%), ΑΑ/ΑΑ(Cd59) (0.1%), ΑΑ(Cd59)/ ΑΑ(IVS I-1) (0.1%), -Α(3.7)/ΑΑ(CS) (0.1%) and --(SEA) /ΑΑ(Cd59) (0.1%). This data indicates that the molecular abnormalities of Α-thalassaemia in the Malaysian population is heterogenous. Although Α-gene deletion is the most common cause, non-deletional Α-gene abnormalities

Peak alpha frequency is a neural marker of cognitive function across the autism spectrum.

Science.gov (United States)

Dickinson, Abigail; DiStefano, Charlotte; Senturk, Damla; Jeste, Shafali Spurling

2018-03-01

Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Distinct roles of theta and alpha oscillations in the involuntary capture of goal-directed attention.

Science.gov (United States)

Harris, Anthony M; Dux, Paul E; Jones, Caelyn N; Mattingley, Jason B

2017-05-15

Mechanisms of attention assign priority to sensory inputs on the basis of current task goals. Previous studies have shown that lateralized neural oscillations within the alpha (8-14Hz) range are associated with the voluntary allocation of attention to the contralateral visual field. It is currently unknown, however, whether similar oscillatory signatures instantiate the involuntary capture of spatial attention by goal-relevant stimulus properties. Here we investigated the roles of theta (4-8Hz), alpha, and beta (14-30Hz) oscillations in human goal-directed visual attention. Across two experiments, we had participants respond to a brief target of a particular color among heterogeneously colored distractors. Prior to target onset, we cued one location with a lateralized, non-predictive cue that was either target- or non-target-colored. During the behavioral task, we recorded brain activity using electroencephalography (EEG), with the aim of analyzing cue-elicited oscillatory activity. We found that theta oscillations lateralized in response to all cues, and this lateralization was stronger if the cue matched the target color. Alpha oscillations lateralized relatively later, and only in response to target-colored cues, consistent with the capture of spatial attention. Our findings suggest that stimulus induced changes in theta and alpha amplitude reflect task-based modulation of signals by feature-based and spatial attention, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Alpha-particle emission probabilities of ²³⁶U obtained by alpha spectrometry.

Science.gov (United States)

Marouli, M; Pommé, S; Jobbágy, V; Van Ammel, R; Paepen, J; Stroh, H; Benedik, L

2014-05-01

High-resolution alpha-particle spectrometry was performed with an ion-implanted silicon detector in vacuum on a homogeneously electrodeposited (236)U source. The source was measured at different solid angles subtended by the detector, varying between 0.8% and 2.4% of 4π sr, to assess the influence of coincidental detection of alpha-particles and conversion electrons on the measured alpha-particle emission probabilities. Additional measurements were performed using a bending magnet to eliminate conversion electrons, the results of which coincide with normal measurements extrapolated to an infinitely small solid angle. The measured alpha emission probabilities for the three main peaks - 74.20 (5)%, 25.68 (5)% and 0.123 (5)%, respectively - are consistent with literature data, but their precision has been improved by at least one order of magnitude in this work. © 2013 Published by Elsevier Ltd.

Status of {alpha}{sub s} determinations from the non-perturbatively renormalised three-gluon vertex

Energy Technology Data Exchange (ETDEWEB)

Parrinello, C. [Liverpool Univ. (United Kingdom). Dept. of Math. Sci.; Richards, D.G. [Dept. of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom); Alles, B. [Dept. di Fisica, Sezione Teorica, Universita di Milano, Via Celoria 16, 20133-Milano (Italy); Panagopoulos, H. [Department of Natural Sciences, University of Cyprus, 1678 Nicosia (Cyprus); Pittori, C. [L.P.T.H.E., Universite de Paris Sud, Centre d`Orsay, 91405 Orsay (France)

1998-04-01

We demonstrate the feasibility of computing {alpha}{sub s} from the lattice three-gluon vertex in the Landau gauge. Data from 16{sup 4} and 24{sup 4} quenched lattices at {beta}=6.0 are presented. Our main result is that 2-loop asymptotic scaling is observed for momenta in the range 1.8-2.3 GeV, where lattice artifacts appear to be under control. (orig.). 6 refs.

Therapeutic γ-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms

Science.gov (United States)

Dai, Yan; Sangerman, Jose; Hong, Yuan Luo; Fuchareon, Suthat; Chui, David H.K.; Faller, Douglas V.; Perrine, Susan P.

2015-01-01

Pharmacologic augmentation of γ-globin expression sufficient to reduce anemia and clinical severity in patients with diverse hemoglobinopathies has been challenging. In studies here, representative molecules from four chemical classes, representing several distinct primary mechanisms of action, were investigated for effects on γ-globin transcriptional repressors, including components of the NuRD complex (LSD1 and HDACs 2-3), and the downstream repressor BCL11A, in erythroid progenitors from hemoglobinopathy patients. Two HDAC inhibitors (MS-275 and SB939), a short-chain fatty acid derivative (sodium dimethylbutyrate [SDMB]), and an agent identified in high-throughput screening, Benserazide, were studied. These therapeutics induced γ globin mRNA in progenitors above same subject controls up to 20-fold, and increased F-reticulocytes up to 20%. Cellular protein levels of BCL11A, LSD-1, and KLF1 were suppressed by the compounds. Chromatin immunoprecipitation assays demonstrated a 3.6-fold reduction in LSD1 and HDAC3 occupancy in the γ-globin gene promoter with Benserazide exposure, 3-fold reduction in LSD-1 and HDAC2 occupancy in the γ-globin gene promoter with SDMB exposure, while markers of gene activation (histone H3K9 acetylation and H3K4 demethylation), were enriched 5.7-fold. These findings identify clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. PMID:26603726

Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

DEFF Research Database (Denmark)

Andersen, J T

1995-01-01

During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... of patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... and improvement in objective parameters for bladder outflow obstruction. Approximately 30 to 50% of patients will respond to treatment with 5 alpha-reductase inhibitors. The definitive role of pharmacological treatment in symptomatic BPH remains to be established, although it seems that patients unfit...

Interactions of foot-and-mouth disease virus with soluble bovine alphaVbeta3 and alphaVbeta6 integrins.

Science.gov (United States)

Duque, Hernando; LaRocco, Michael; Golde, William T; Baxt, Barry

2004-09-01

At least four members of the integrin family of receptors, alphaVbeta1, alphaVbeta3, alphaVbeta6, and alphaVbeta8, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. Our investigators have recently shown that the efficiency of receptor usage appears to be related to the viral serotype and may be influenced by structural differences on the viral surface (H. Duque and B. Baxt, J. Virol. 77:2500-2511, 2003). To further examine these differences, we generated soluble alphaVbeta3 and alphaVbeta6 integrins. cDNA plasmids encoding the individual complete integrin alphaV, beta3, and beta6 subunits were used to amplify sequences encoding the subunits' signal peptide and ectodomain, resulting in subunits lacking transmembrane and cytoplasmic domains. COS-1 cells were transfected with plasmids encoding the soluble alphaV subunit and either the soluble beta3 or beta6 subunit and labeled with [35S]methionine-cysteine. Complete subunit heterodimeric integrins were secreted into the medium, as determined by radioimmunoprecipitation with specific monoclonal and polyclonal antibodies. For the examination of the integrins' biological activities, stable cell lines producing the soluble integrins were generated in HEK 293A cells. In the presence of divalent cations, soluble alphaVbeta6 bound to representatives of type A or O viruses, immobilized on plastic dishes, and significantly inhibited viral replication, as determined by plaque reduction assays. In contrast, soluble alphaVbeta3 was unable to bind to immobilized virus of either serotype; however, virus bound to the immobilized integrin, suggesting that FMDV binding to alphaVbeta3 is a low-affinity interaction. In addition, soluble alphaVbeta3 did not neutralize virus infectivity. Incubation of soluble alphaVbeta6 with labeled type A12 or O1 resulted in a significant inhibition of virus adsorption to BHK cells, while soluble alphaVbeta3 caused a low (20 to 30%), but consistent, inhibition of virus

Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis

International Nuclear Information System (INIS)

Fida, Nadia M.; Fadelallah, Mohamed F.; Al-Mughales, Jamil A.

2006-01-01

To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n=28), meningitis (n=7), and healthy controls (n=16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n=6), group 2 = clinical sepsis (n=14), and group 3 = possible-infected (n=8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer: In sepsis and meningitis patients, serum levels of CRP (p<0.01, p<0.05,) and IL-1alpha (p<0.001, p<0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p<0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p<0.05, p<0.001, p<0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis. (author)

Alpha1-antitrypsin deficiency

DEFF Research Database (Denmark)

Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

2006-01-01

The Alpha One International Registry (AIR), a multinational research program focused on alpha1-antitrypsin (AAT) deficiency, was formed in response to a World Health Organization recommendation. Each of the nearly 20 participating countries maintains a national registry of patients with AAT defic...

Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non-hypertrophic and non-failing transgenic mouse hearts expressing N-terminal truncated cardiac troponin I

Directory of Open Access Journals (Sweden)

Stephanie Kern

2014-01-01

Full Text Available We previously reported that a restrictive N-terminal truncation of cardiac troponin I (cTnI-ND is up-regulated in the heart in adaptation to hemodynamic stresses. Over-expression of cTnI-ND in the hearts of transgenic mice revealed functional benefits such as increased relaxation and myocardial compliance. In the present study, we investigated the subsequent effect on myocardial remodeling. The alpha-smooth muscle actin (α-SMA isoform is normally expressed in differentiating cardiomyocytes and is a marker for myocardial hypertrophy in adult hearts. Our results show that in cTnI-ND transgenic mice of between 2 and 3 months of age (young adults, a significant level of α-SMA is expressed in the heart as compared with wild-type animals. Although blood vessel density was increased in the cTnI-ND heart, the mass of smooth muscle tissue did not correlate with the increased level of α-SMA. Instead, immunocytochemical staining and Western blotting of protein extracts from isolated cardiomyocytes identified cardiomyocytes as the source of increased α-SMA in cTnI-ND hearts. We further found that while a portion of the up-regulated α-SMA protein was incorporated into the sarcomeric thin filaments, the majority of SMA protein was found outside of myofibrils. This distribution pattern suggests dual functions for the up-regulated α-SMA as both a contractile component to affect contractility and as possible effector of early remodeling in non-hypertrophic, non-failing cTnI-ND hearts.

15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers.

Science.gov (United States)

Reeder, A Y; Joannou, G E

1995-12-01

In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.

Enzyme replacement therapy for alpha-mannosidosis

DEFF Research Database (Denmark)

Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J

2013-01-01

Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly...

IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

DEFF Research Database (Denmark)

Ross, Christian; Engler, Claus Bødker; Sander, Birgit

2002-01-01

We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2...

IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

DEFF Research Database (Denmark)

Ross, Christian; Engler, Claus Bødker; Sander, Birgit

2002-01-01

We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a...

Alpha-amino acid derivatives and alpha-fluoro ketones by enantioselective decarboxylation

OpenAIRE

Baur, Markus A.

2003-01-01

Die Methode der enantioselektiven Decarboxylierung wurde angewendet, um Enantiomeren-angereicherte alpha-Aminosäurederivate und alpha-Fluorketone zu erhalten. Als Substrate wurden 2-N-Acetylamino-2-alkylmalonsäuremonoethylester beziehungsweise beta-Keto-benzylester verwendet. China-Alkaloide und Derivate davon wurden als Katalysatoren eingesetzt. Die besten erhaltenen Ergebnisse waren N-Acetyl-L-phenylalaninethylester mit 70% Enantiomerenüberschuß unter Verwendung der katalytisch aktiven Base...

Complete primary structure of rainbow trout type I collagen consisting of alpha1(I)alpha2(I)alpha3(I) heterotrimers.

Science.gov (United States)

Saito, M; Takenouchi, Y; Kunisaki, N; Kimura, S

2001-05-01

The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be alpha1(I)alpha2(I)alpha3(I) and [alpha1(I)](2)alpha2(I), respectively. The occurrence of alpha3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 degrees C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proalpha(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proalpha(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific alpha(I) chain, proalpha3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proalpha1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proalpha3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proalpha3(I) had diverged from proalpha1(I). This study is the first report of the complete primary structure of fish type I procollagen.

Alpha radiation and in-pile annealing effects on the fracture properties of a sintered alumino borosilicate glass

International Nuclear Information System (INIS)

Bevilacqua, Arturo M.; Prado, Miguel O.; Messi de Bernasconi, Norma B.; Heredia, Arturo D.; Sanfilippo, Miguel

1999-01-01

The alpha radiation and the in-pile during irradiation effects on the hardness, the crack nucleation and the fracture toughness of the German alumino borosilicate glass SG7 were investigated by using the Vickers indentation. Cold pressed and sintered samples were irradiated with thermal neutrons, in the Argentine nuclear reactors RA-3 and RA-6, to produce alpha particles in the whole volume of the glass by means of the (n, alpha)-reaction with B-10. The Vickers hardness, the crack nucleation, as 50 percent fracture probability load, plotted as the Weibull's fracture probability distribution function and the fracture toughness, as critical stress intensity factor K Ic , were correlated to the four cumulative disintegration values. It was ascertained that: a) the Vickers hardness decreases from 5.6 GPa for the non-irradiated sample up to 4.7 GPa for the sample irradiated 70 h at the lower neutron flux (4.0 x 10 - sup 18 - alpha disintegration per cm - sup 3 -), b) the 50 % fracture probability load increases from 1.4 N for the non-irradiated sample up to 4.7 g for the sample irradiated 22 h at the higher flux (6.8 x 10 - sup 18 - alpha disintegration per cm - sup 3 -), and c) the stress intensity factor increases from 0.80 MPa.m - sup 1/2 - for the non irradiated sample up to 0.86 MPa.m - sup 1/2 - for the sample mentioned in b). The in-pile annealing was analyzed by comparing the crack nucleation after irradiation with data obtained by heavy ion irradiation followed by thermal annealing. Results for the SG7 glass were compared to those for soda-lime and borosilicate glasses. (author)

Photon hormesis deactivates alpha-particle induced bystander effects between zebrafish embryos

International Nuclear Information System (INIS)

Ng, C.Y.P.; Cheng, S.H.; Yu, K.N.

2017-01-01

In the present work, we studied the effects of low-dose X-ray photons on the alpha-particle induced bystander effects between embryos of the zebrafish, Danio rerio. The effects on the naive whole embryos were studied through quantification of apoptotic signals (amounts of cells undergoing apoptosis) at 24 h post fertilization (hpf) using vital dye acridine orange staining, followed by counting the stained cells under a fluorescent microscope. We report data showing that embryos at 5 hpf subjected to a 4.4 mGy alpha-particle irradiation could release a stress signal into the medium, which could induce bystander effect in partnered naive embryos sharing the same medium. We also report that the bystander effect was deactivated when the irradiated embryos were subjected to a concomitant irradiation of 10 or 14 mGy of X-rays, but no such deactivation was achieved if the concomitant X-ray dose dropped to 2.5 or 5 mGy. In the present study, the significant drop in the amount of apoptotic signals on the embryos having received 4.4 mGy alpha particles together X-rays irradiation from 2.5 or 5 mGy to 10 or 14 mGy, together with the deactivation of RIBE with concomitant irradiation of 10 or 14 mGy of X-rays supported the participation of photon hormesis with an onset dose between 5 and 10 mGy, which might lead to removal of aberrant cells through early apoptosis or induction of high-fidelity DNA repair. As we found that photons and alpha particles could have opposite biological effects when these were simultaneously irradiated onto living organisms, these ionizing radiations could be viewed as two different environmental stressors, and the resultant effects could be regarded as multiple stressor effects. The present work presented the first study on a multiple stressor effect which occurred on bystander organisms. In other words, this was a non-targeted multiple stressor effect. The photon hormesis could also explain some failed attempts to observe neutron-induced bystander

TFTR alpha extraction and measurement: Development and testing of advanced alpha detectors: Final report

International Nuclear Information System (INIS)

Wehring, B.W.

1988-01-01

Advanced alpha-particle detectors made of heavy elements were investigated as alternatives to silicon surface-barrier detectors for the ''foil-neutralization technique'' of alpha-particle diagnostics in fusion reactors with high neutron backgrounds. From an extensive literature review, it was decided that HgI 2 would make a more suitable detector for alpha-particle diagnostics than other heavy element detectors such as CdTe. Thus, HgI 2 detectors were designed and fabricated. Experimental tests were performed to determine detector characteristics and detector responses to alpha particles. Radiation noise measurements were also performed using the North Carolina State University PULSTAR nuclear reactor for both the HgI 2 detectors and commercial Si(Au) surface barrier detectors. 15 refs., 1 fig

A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

International Nuclear Information System (INIS)

Kim, Jiyoung; Cha, Young-Nam; Surh, Young-Joon

2010-01-01

Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

On the experience of the management of solid alpha-bearing wastes

International Nuclear Information System (INIS)

Kryuchkov, V.A.; Rakov, N.A.; Romanovskii, V.N.; Yakushev, M.F.

1978-01-01

Spent fuel reprocessing is studied in a pilot plant. Low and high level radioactive wastes handling is described. Liquid wastes are solidified. Combustible solid wastes are incinerated. Non-combustible and ashes are send to disposal site. Volume reduction of alpha-bearing wastes is obtained by optimisation of the reprocessing and development of remote control methods

Two lectin-like receptors for alpha 1-acid glycoprotein in mouse testis

DEFF Research Database (Denmark)

Andersen, U O; Kirkeby, S; Bøg-Hansen, T C

1997-01-01

Three glycoforms of alpha 1-acid glycoprotein (AGP) were biotinylated to examine their binding in mouse testis by light microscopy. The transition from one stage to another in the spermatogenic cycle is marked with an appearance of a receptor for the Concanavalin A (Con A) non-reactive glycoform...

Synthesis and evaluation of phytotoxic activity of {alpha}-Santonin derivatives; Sintese e avaliacao da atividade fitotoxica de derivados da {alpha}-Santonina

Energy Technology Data Exchange (ETDEWEB)

Alvarenga, Elson S.; Barbosa, Luiz C.A.; Saliba, William A.; Arantes, Francisco F.P.; Demuner, Antonio J. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Quimica]. E-mail: elson@ufv.br; Silva, Antonio A. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Fitotecnia

2009-07-01

Mixtures of {alpha}-Santonin and various solvents were irradiated by either high or low pressure mercury lamps. The photochemical reactions afforded lumisantonin (11) (76% in acetonitrile), (3 S,3a S,9{beta}S)-3,6,6-trimethyl-3,3a,4,5-tetrahydronafto[1,2-b]furan-2,7({eta}6,9{beta}{eta}) dione (12) (100% in acetonitrile), 10{alpha}-acetoxy-3-oxo-1,7{alpha}H{eta},6,11{alpha}a{eta}-guaia-4-en-6,12-oli= de (8) (26% in acetic acid), 10{alpha}-hydroxy-3-oxo-1,7{alpha}a{eta},6,11{alpha}{eta}-guaia-4-en-6,12-olid= e (10) (32%) and (E)-3-((3 S,3a S,7{alpha}S)-3-methyl-2-oxo-6-(propan-2-ylidene)hexahydrobenzofuran- 7 - (7{alpha}{eta})-ylidene)propanoic acid (9) (44%) (in water/ acetic acid 1:1, v/v). Lactone 12 was also prepared by irradiation of lumisantonin in diethyl ether. Lactones 8 and 10 were converted, respectively, into the 10 {alpha}-acetoxy-3{alpha}-hydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olid= e (13) (87%) and 3a,10a-dihydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olide (14) (75%) by sodium borohydride reduction. The effects of the compounds on the development of radicle of Sorghum bicolor and Cucumis sativus were evaluated. (author)

Remarks on tilde g_{alpha}-irresolute maps

Directory of Open Access Journals (Sweden)

Nirmala Rebecca Paul

2011-12-01

Full Text Available Only a few of the class of generalized closed sets form a topology. The class of tilde g_{alpha}-closed sets is one among them. The aim of this paper is to introduce the different notions of irresolute function using tilde g_{alpha}-closed sets and study some of their basic properties.We also study the relation between strongly tilde g_{alpha}- continuous and perfectly eg-continuous functions. We also introduce tilde g_{alpha}-compact and ilde g_{alpha}-connectedspaces and study their properties using tilde g_{alpha}-continuous and eg-irresolute functions.

Long-range alpha detector (LRAD)

International Nuclear Information System (INIS)

MacArthur, D.W.; McAtee, J.L.

1991-01-01

Historically, alpha detectors have been limited by the very short range of alpha particles in air and by relatively poor sensitivity, even if the particles are intercepted. Of necessity, these detectors are operated in a vacuum or in close proximity to the source if reasonable efficiency is desired. In our new long-range alpha detector (LRAD), alpha particles interact with the ambient air, producing ionization in the air at the rate of about 30,000 ion pairs per MeV of alpha energy. These charges can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions. The LRAD-based monitor is more sensitive and more thorough than conventional monitors. We present current LRAD sensitivity limits and results, practical monitor designs, and proposed uses for LRAD monitors. 4 refs., 7 figs

Increased humoral immunity by DNA vaccination using an alpha-tocopherol-based adjuvant

DEFF Research Database (Denmark)

Karlsson, Ingrid; Borggren, Marie; Nielsen, Jens

2017-01-01

approaches. We tested whether the emulsion-based and alpha-tocopherol containing adjuvant Diluvac Forte® has the ability to enhance the immunogenicity of a naked DNA vaccine (i.e., plasmid DNA). As a model vaccine, we used plasmids encoding both a surface-exposed viral glycoprotein (hemagglutinin......) and an internal non-glycosylated nucleoprotein in the Th1/Th2 balanced CB6F1 mouse model. The naked DNA (50 µg) was premixed at a 1:1 volume/volume ratio with Diluvac Forte®, an emulsion containing different concentrations of alpha-tocopherol, the emulsion alone or endotoxin-free phosphate-buffered saline (PBS......). The animals received two intracutaneous immunizations spaced 3 weeks apart. When combined with Diluvac Forte® or the emulsion containing alpha-tocopherol, the DNA vaccine induced a more potent and balanced immunoglobulin G (IgG)1 and IgG2c response, and both IgG subclass responses were significantly enhanced...

Microwave-plasma interactions studied via mode diagnostics in ALPHA

Energy Technology Data Exchange (ETDEWEB)

Friesen, T., E-mail: tim.friesen@cern.ch [University of Calgary, Department of Physics and Astronomy (Canada); Andresen, G. B. [Aarhus University, Department of Physics and Astronomy (Denmark); Ashkezari, M. D. [Simon Fraser University, Department of Physics (Canada); Baquero-Ruiz, M. [University of California, Department of Physics (United States); Bertsche, W. [Swansea University, Department of Physics (United Kingdom); Bowe, P. D. [Aarhus University, Department of Physics and Astronomy (Denmark); Butler, E. [CERN, Physics Department (Switzerland); Cesar, C. L. [Universidade Federal do Rio de Janeiro, Instituto de Fisica (Brazil); Chapman, S. [University of California, Department of Physics (United States); Charlton, M.; Eriksson, S. [Swansea University, Department of Physics (United Kingdom); Fajans, J. [University of California, Department of Physics (United States); Fujiwara, M. C. [University of Calgary, Department of Physics and Astronomy (Canada); Gill, D. R. [TRIUMF (Canada); Gutierrez, A. [University of British Columbia, Department of Physics and Astronomy (Canada); Hangst, J. S. [Aarhus University, Department of Physics and Astronomy (Denmark); Hardy, W. N. [University of British Columbia, Department of Physics and Astronomy (Canada); Hayano, R. S. [University of Tokyo, Department of Physics (Japan); Hayden, M. E. [Simon Fraser University, Department of Physics (Canada); Humphries, A. J. [Swansea University, Department of Physics (United Kingdom); Collaboration: ALPHA Collaboration; and others

2012-12-15

The goal of the ALPHA experiment is the production, trapping and spectroscopy of antihydrogen. A direct comparison of the ground state hyperfine spectra in hydrogen and antihydrogen has the potential to be a high-precision test of CPT symmetry. We present a novel method for measuring the strength of a microwave field for hyperfine spectroscopy in a Penning trap. This method incorporates a non-destructive plasma diagnostic system based on electrostatic modes within an electron plasma. We also show how this technique can be used to measure the cyclotron resonance of the electron plasma, which can potentially serve as a non-destructive measurement of plasma temperature.

Beta/alpha continuous air monitor

Science.gov (United States)

Becker, G.K.; Martz, D.E.

1988-06-27

A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinquishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts. 7 figs.

ALPHA experiment facility and Prof. Jeffrey Hangst.

CERN Multimedia

Maximilien Brice

2010-01-01

Picture 01-07: General views of the ALPHA experiment Picture 5: Andrea Gutierrez, a PhD student from UBC, transfers liquid helium from a storage dewar into the cryostat containing the superconducting magnetic trap used by the ALPHA experiment.Picture 08-11: Jeffery Hangst, spokesperson for ALPHA Picture 12: The ALPHA silicon detector, which surrounds the trapping resion and is used for imaging antiproton annihilations (Credit University of Liverpool) Picture 13: Untrapped antihydrogen atoms annihilating on the inner surface of the ALPHA trap. These are measured by the ALPHA annihilation detector. The events are concentrated at the electrode radius of about 22.3 mm. The coordinates are defined in the Nature article, Figure 1b. Picture 14: The electrodes (gold) for the ALPHA Penning trap being inserted into the vacuum chamber and cryostat assembly. This is the trap used to combine or "mix" positrons and antiprotons to make antihydrogen. (Credit: Niels Madsen ALPHA/Swansea.) Picture 15: Top, a diagram of the...

Alpha-Driven MHD and MHD-Induced Alpha Loss in TFTR DT Experiments

Science.gov (United States)

Chang, Zuoyang

1996-11-01

Theoretical calculation and numerical simulation indicate that there can be interesting interactions between alpha particles and MHD activity which can adversely affect the performance of a tokamak reactor (e.g., ITER). These interactions include alpha-driven MHD, like the toroidicity-induced-Alfven-eigenmode (TAE) and MHD induced alpha particle losses or redistribution. Both phenomena have been observed in recent TFTR DT experiments. Weak alpha-driven TAE activity was observed in a NBI-heated DT experiment characterized by high q0 ( >= 2) and low core magnetic shear. The TAE mode appears at ~30-100 ms after the neutral beam turning off approximately as predicted by theory. The mode has an amplitude measured by magnetic coils at the edge tildeB_p ~1 mG, frequency ~150-190 kHz and toroidal mode number ~2-3. It lasts only ~ 30-70 ms and has been seen only in DT discharges with fusion power level about 1.5-2.0 MW. Numerical calculation using NOVA-K code shows that this type of plasma has a big TAE gap. The calculated TAE frequency and mode number are close to the observation. (2) KBM-induced alpha particle loss^1. In some high-β, high fusion power DT experiments, enhanced alpha particle losses were observed to be correlated to the high frequency MHD modes with f ~100-200 kHz (the TAE frequency would be two-times higher) and n ~5-10. These modes are localized around the peak plasma pressure gradient and have ballooning characteristics. Alpha loss increases by 30-100% during the modes. Particle orbit simulations show the added loss results from wave-particle resonance. Linear instability analysis indicates that the plasma is unstable to the kinetic MHD ballooning modes (KBM) driven primarily by strong local pressure gradients. ----------------- ^1Z. Chang, et al, Phys. Rev. Lett. 76 (1996) 1071. In collaberation with R. Nazikian, G.-Y. Fu, S. Batha, R. Budny, L. Chen, D. Darrow, E. Fredrickson, R. Majeski, D. Mansfield, K. McGuire, G. Rewoldt, G. Taylor, R. White, K

Determination of 210Pb in marine sediment core- A comparison between alpha and gamma techniques

International Nuclear Information System (INIS)

Zal Uyun Wan Mahmood; Yii Mei Wo; Zaharudin Ahmad

2010-01-01

The most commonly used techniques of alpha and gamma spectrometry were performed to measure 210 Pb activity in marine sediment core as a comparison. Alpha analytical technique measured the activity of 210 Pb from its in-grow grand-daughter 210 Po after a chemical separation, assuming radioactive equilibrium between the two radionuclides. Meanwhile, gamma analysis technique allows direct measurement, non-destructive and no preliminary chemical separation. Through the comparison, it is found that both alpha and gamma analysis techniques were slightly difference. Overall, the results from alpha analytical technique were basically higher than those from the gamma analytical techniques. Some logical argument had been discussed to explain this situation. In routine analysis, the analytical technique used should be chosen carefully based on advantages and disadvantages of the each technique and analysis requirements. Therefore, it is recommended to determine exactly the needs and purpose of analysis and to know the sample history before decide the appropriate analytical technique. (author)

Alpha decay and various problems related to it

International Nuclear Information System (INIS)

Katori, Kenji

1992-01-01

On the proton-excessive nucleus side of lanthanide and actinide, alpha decay is the main decay mode. In lanthanide region, alpha decay has been measured to the drip line for most even-even nuclei. In the measurement of alpha decay, emitted energy and life are measured, but the measurement of converted alpha width remains in the limited range. In order to obtain the converted alpha width of high accuracy, the nucleus formation in larger quantity on the drip line and the simultaneous measurement with a multiple detector system including gamma ray and beta ray are required. In this paper, three topics related to alpha cluster and alpha decay and the problems that confront at present are discussed. The continuation to exist of alpha cluster structure to heavy nuclei, the analysis of lanthanide nucleus region by the alpha giant resonance model, and the new data on the alpha ray decaying from the mass of 175, 176 and 177 are reported. In lanthanide nucleus region, remarkable interference was not observed between beta-2 and beta-3 modes in the converted alpha width measured between the ground states. The present problems in alpha decay are enumerated. (K.I.)

Cortical Alpha Activity in Schizoaffective Patients.

Science.gov (United States)

Moeini, Mahdi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Zarafshan, Hadi; Fazio, Rachel L; Majidi, Hamid

2017-01-01

Objective: Electrophysiological studies have identified abnormal oscillatory activities in the cerebral cortex in schizophrenia and mood disorders. Biological and pathophysiological evidence suggests specific deficits in serotonin (5-HT) receptor function in schizoaffective disorder (SA), a clinical syndrome with characteristics of both schizophrenia and bipolar disorder. This study investigated alpha oscillations in patients with SA. Method: Electroencephalography was used to measure ongoing and evoked alpha oscillations in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for SA, and in 39 healthy controls. Results: Spontaneous alpha power of the participants with SA was significantly lower than that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025]. Conclusion : A strong reduction of alpha power in the posterior regions may reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and reduced cerebral blood flow is associated with reduced alpha activity among different regions of the brain. Therefore, it can be concluded that greatly decreased alpha activity, particularly in centro-parietal and occipital regions, is related to SA symptoms such as hallucinations.

Alpha 1 B- but not alpha 1 A-adrenoceptors mediate inositol phosphate generation

NARCIS (Netherlands)

Michel, M. C.; Hanft, G.; Gross, G.

1990-01-01

We used novel highly subtype-selective antagonists to study whether alpha 1A- and/or alpha 1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 microM) and prazosin (100 nM) completely abolished the stimulated inositol

Detection of alpha particles using DNA/Al Schottky junctions

Energy Technology Data Exchange (ETDEWEB)

Al-Ta' ii, Hassan Maktuff Jaber, E-mail: hassankirkukly@gmail.com, E-mail: vengadeshp@um.edu.my [Low Dimensional Materials Research Centre (LDMRC), 50603 Kuala Lumpur (Malaysia); Department of Physics, Faculty of Science, University of Al-Muthana, Al-Muthana 66001 (Iraq); Periasamy, Vengadesh, E-mail: hassankirkukly@gmail.com, E-mail: vengadeshp@um.edu.my [Low Dimensional Materials Research Centre (LDMRC), 50603 Kuala Lumpur (Malaysia); Amin, Yusoff Mohd [Department of Physics, Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia)

2015-09-21

Deoxyribonucleic acid or DNA can be utilized in an organic-metallic rectifying structure to detect radiation, especially alpha particles. This has become much more important in recent years due to crucial environmental detection needs in both peace and war. In this work, we fabricated an aluminum (Al)/DNA/Al structure and generated current–voltage characteristics upon exposure to alpha radiation. Two models were utilized to investigate these current profiles; the standard conventional thermionic emission model and Cheung and Cheung's method. Using these models, the barrier height, Richardson constant, ideality factor and series resistance of the metal-DNA-metal structure were analyzed in real time. The barrier height, Φ value calculated using the conventional method for non-radiated structure was 0.7149 eV, increasing to 0.7367 eV after 4 min of radiation. Barrier height values were observed to increase after 20, 30 and 40 min of radiation, except for 6, 8, and 10 min, which registered a decrease of about 0.67 eV. This was in comparison using Cheung and Cheung's method, which registered 0.6983 eV and 0.7528 eV for the non-radiated and 2 min of radiation, respectively. The barrier height values, meanwhile, were observed to decrease after 4 (0.61 eV) to 40 min (0.6945 eV). The study shows that conventional thermionic emission model could be practically utilized for estimating the diode parameters including the effect of series resistance. These changes in the electronic properties of the Al/DNA/Al junctions could therefore be utilized in the manufacture of sensitive alpha particle sensors.

Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

Science.gov (United States)

Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

2007-09-01

Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors.

Science.gov (United States)

Kelley, Joshua B; Talley, Ashley M; Spencer, Adam; Gioeli, Daniel; Paschal, Bryce M

2010-08-11

Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin alpha and importin beta. NLS cargo is recognized by importin alpha, which is bound by importin beta. Importin beta mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin beta triggers disassembly of the complex. To date, six importin alpha family members, encoded by separate genes, have been described in humans. We sequenced and characterized a seventh member of the importin alpha family of transport factors, karyopherin alpha 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin beta (IBB) is divergent, and shows stronger binding to importin beta than the IBB domains from of other importin alpha family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. KPNA7 is a novel importin alpha family member in humans that belongs to the importin alpha2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin alpha family. These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation.

Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments

NARCIS (Netherlands)

Baer, R.; Boehm, T.; Yssel, H.; Spits, H.; Rabbitts, T. H.

1988-01-01

We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one

Non-LTE hydrogen-line formation in moving prominences

Science.gov (United States)

Heinzel, P.; Rompolt, B.

1986-01-01

The behavior of hydrogen-line brightness variations, depending on the prominence-velocity changes were investigated. By solving the NON-Local thermodynamic equilibrium (LTE) problem for hydrogen researchers determine quantitatively the effect of Doppler brightening and/or Doppler dimming (DBE, DDE) in the lines of Lyman and Balmer series. It is demonstrated that in low-density prominence plasmas, DBE in H alpha and H beta lines can reach a factor of three for velocities around 160 km/sec, while the L alpha line exhibits typical DDE. L beta brightness variations follow from a combined DBE in the H alpha and DDE in L alpha and L beta itself, providing that all relevant multilevel interlocking processes are taken into account.

The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes-associated osteoarthritis.

Science.gov (United States)

Vaamonde-Garcia, Carlos; Courties, Alice; Pigenet, Audrey; Laiguillon, Marie-Charlotte; Sautet, Alain; Houard, Xavier; Kerdine-Römer, Saadia; Meijide, Rosa; Berenbaum, Francis; Sellam, Jérémie

2017-09-01

Epidemiological findings support the hypothesis that type 2 diabetes mellitus (T2DM) is a risk factor for osteoarthritis (OA). Moreover, OA cartilage from patients with T2DM exhibits a greater response to inflammatory stress, but the molecular mechanism is unclear. To investigate whether the antioxidant defense system participates in this response, we examined here the expression of nuclear factor-erythroid 2-related factor (Nrf-2), a master antioxidant transcription factor, and of heme oxygenase-1 (HO-1), one of its main target genes, in OA cartilage from T2DM and non-T2DM patients as well as in murine chondrocytes exposed to high glucose (HG). Ex vivo experiments indicated that Nrf-2 and HO-1 expression is reduced in T2DM versus non-T2DM OA cartilage (0.57-fold Nrf-2 and 0.34-fold HO-1), and prostaglandin E 2 (PGE 2 ) release was increased in samples with low HO-1 expression. HG-exposed, IL-1β-stimulated chondrocytes had lower Nrf-2 levels in vitro , particularly in the nuclear fraction, than chondrocytes exposed to normal glucose (NG). Accordingly, HO-1 levels were also decreased (0.49-fold) in these cells. The HO-1 inducer cobalt protoporphyrin IX more efficiently attenuated PGE 2 and IL-6 release in HG+IL-1β-treated cells than in NG+IL-1β-treated cells. Greater reductions in HO-1 expression and increase in PGE 2 /IL-6 production were observed in HG+IL-1β-stimulated chondrocytes from Nrf-2 -/- mice than in chondrocytes from wild-type mice. We conclude that the Nrf-2/HO-1 axis is a critical pathway in the hyperglucidic-mediated dysregulation of chondrocytes. Impairments in this antioxidant system may explain the greater inflammatory responsiveness of OA cartilage from T2DM patients and may inform treatments of such patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Lung cancer after internal alpha-exposure of the lung from incorporated plutonium

International Nuclear Information System (INIS)

Mikhail, S.

2004-01-01

Several epidemiological studies among workers of first Russian nuclear complex Mayak which produced weapon-grade plutonium showed significant increase of lung cancer mortality. The estimated shape of the dose-response was linear with both alpha and gamma dose but risk coefficients for gamma-exposure are on the edge of the significance level. This study was performed in the cohort of male Mayak nuclear workers initially hired in 1948-1958 with known levels of plutonium exposure. Number of observed lung cancer cases available for analyses in this cohort was 217. The relative risk of death from lung cancer among smokers was 10.7 (5.5-25.2) comparatively to non-smokers. This is in good correspondence with results of other studies. The excess relative risk per one Gray was 63. (4.1-9.7) for internal alpha-exposure and 0.18 (0.01-0.5) for external gamma-exposure. According to a model this gives 16:112:60:29 cases of lung cancer attributed to background, smoking, internal alpha-and external gamma-exposure, correspondingly. The relative risks of death from lung cancer were also estimated in a nested case-control study with lung cancer deaths as cases. Controls were selected from the cohort and matched for birth year to account for trend in lung cancer mortality with time. The analyses with nested case-control approach gave relative risks for smoking 14.7 (6.8-38.9). Relative risk of lung cancer among non-smokers after accumulating 0.34 Gy of alpha-exposure to lung was 3.7 (1.7-9.0). It should be emphasized that in fact after accumulation 0.3-0.4 Gy of absorbed dose 3-4 fold increase in lung cancer mortality was observed. This dose is very close to the dose which would be produced after intake of plutonium in quantities which are permissible today. (Author)

Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function

DEFF Research Database (Denmark)

Hansen, Sara K; Párrizas, Marcelina; Jensen, Maria L

2002-01-01

Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. More recent data demonstrates that HNF-4alpha...... in human islets and exocrine cells is primarily mediated by the P2 promoter. Furthermore, we describe a G --> A mutation in a conserved nucleotide position of the HNF-1alpha binding site of the P2 promoter, which cosegregates with MODY. The mutation results in decreased affinity for HNF-1alpha...

The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin

DEFF Research Database (Denmark)

Goldfinger, L E; Hopkinson, S B; deHart, G W

1999-01-01

Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found in epithe......-inhibiting antibodies, we provide evidence that LN5 and its two integrin receptors (alpha6beta4 and alpha3beta1) appear necessary for wound healing to occur in MCF-10A cell culture wounds. We propose a model for healing of wounded epithelial tissues based on these results....... in epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 subunit as a consequence of proteolytic processing. Antibody 12C4 stains throughout the matrix...... the wound site. A similar phenomenon is observed in human skin wounds, since we also detect expression of the unprocessed alpha3 laminin subunit at the leading tip of the sheet of epidermal cells that epithelializes skin wounds in vivo. In addition, using alpha3 laminin subunit and integrin function...

Characterisation of the binding of [{sup 3}H]methyllycaconitine: a new radioligand for labelling {alpha}7-type neuronal nicotinic acetylcholine receptors

Energy Technology Data Exchange (ETDEWEB)

Davies, A.R.L.; Wolstenholme, A.J.; Wonnacott, S. [Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY (United Kingdom); Hardick, D.J.; Blagbrough, I.S.; Potter, B.V.L. [Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY (United Kingdom)

1999-05-15

Methyllycaconitine (MLA), a norditerpenoid alkaloid isolated from Delphinium seeds, is one of the most potent non-proteinacious ligands that is selective for {alpha}bungarotoxin-sensitive neuronal nicotinic acetylcholine receptors (nAChR). [{sup 3}H]MLA bound to rat brain membranes with high affinity (K{sub d}=1.86{+-}0.31 nM) with a good ratio of specific to non-specific binding. The binding of [{sup 3}H]MLA was characterised by rapid association (t{sub 1/2}=2.3 min) and dissociation (t{sub 1/2}=12.6 min) kinetics. The radioligand binding displayed nicotinic pharmacology, consistent with an interaction with {alpha}bungarotoxin-sensitive nAChR. The snake {alpha}-toxins, {alpha}bungarotoxin and {alpha}cobratoxin, displaced [{sup 3}H]MLA with high affinity (K{sub i}=1.8{+-}0.5 and 5.5{+-}0.9 nM, respectively), whereas nicotine was less potent (K{sub i}=6.1{+-}1.1 {mu}M). The distribution of [{sup 3}H]MLA binding sites in crudely dissected rat brain regions was identical to that of [{sup 125}I]{alpha}bungarotoxin binding sites, with a high binding site density in hippocampus and hypothalamus, but low density in striatum and cerebellum. [{sup 3}H]MLA also labelled a sub-population of binding sites which are not sensitive to the snake {alpha}toxins, but which did not differ significantly from the major population with respect to their other pharmacological properties or regional distribution. [{sup 3}H]MLA, therefore, is a novel radiolabel for characterising {alpha}7-type nAChR. A good signal to noise ratio and rapid binding kinetics provide advantages over the use of radiolabelled {alpha}bungarotoxin for rapid and accurate equilibrium binding assays. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Remote Optical Detection of Alpha Radiation

International Nuclear Information System (INIS)

Sand, J.; Hannuksela, V.; Toivonen, J.; Ihantola, S.; Peraejaervi, K.; Toivonen, H.

2010-01-01

Alpha emitting radiation sources are typically hard to detect with conventional detectors due to the short range of alpha particles in the air. However, previous studies have shown that remote detection of alpha radiation is possible by measuring the ionization-induced fluorescence of air molecules. The alpha-induced ultraviolet (UV) light is mainly emitted by molecular nitrogen and its fluorescence properties are well known. The benefit of this method is the long range of UV photons in the air. Secondly, the detection is possible also under a strong beta and gamma radiation backgrounds as they do not cause localized molecular excitation. In this work, the optical detection was studied using two different detection schemes; spectral separation of fluorescence from the background lighting and coincidence detection of UV photons originating from a single radiative decay event. Our spectrally integrated measurements have shown that one alpha decay event yields up to 400 fluorescence photons in the air and all these UV photons are induced in a 5 ns time-window. On the other hand, the probability of a background coincidence event in 5 ns scale is very rare compared to the number of background photons. This information can be applied in fluorescence coincidence filtering to discriminate the alpha radiation initiated fluorescence signal from much more intense background lighting. A device called HAUVA (Handheld Alpha UV Application) was built during this work for demonstration purposes. HAUVA utilizes spectral filtering and it is designed to detect alpha emitters from a distance of about 40 cm. Using specially selected room lighting, the device is able to separate 1 kBq alpha emitter from the background lighting with 1 second integration time. (author)

Monitor for alpha beta contamination of hands; Moniteur de contamination alpha beta des mains

Energy Technology Data Exchange (ETDEWEB)

Guitton, J

1958-07-01

The following specifications of hands alpha beta contamination monitor are presented: the position of the hands, the detection and separation of alpha and beta, the information processing, the programming, the results presentation and general characteristics. (A.L.B.)

Reversal of behavioral depression by infusion of an alpha-2 adrenergic agonist into the locus coeruleus.

Science.gov (United States)

Simson, P G; Weiss, J M; Hoffman, L J; Ambrose, M J

1986-04-01

This experiment demonstrated that behavioral depression produced by exposure of rats to strong uncontrollable shocks could be reversed by infusion of the alpha-2 adrenergic agonist clonidine into the region of the locus coeruleus (LC). A 20-min infusion, through bilateral cannulae, into the locus coeruleus of clonidine, piperoxane (alpha-2 antagonist) or inactive vehicle (0.85% saline), was given beginning 70 min after the animals were removed from the stress situation. The dose and volume of drug given in the infusion (0.16 microgram/microliter, 0.1 microliter/min) had been previously shown to produce effects specific to the locus coeruleus (Weiss, Simson, Hoffman, Ambrose, Cooper and Webster, 1986; Neuropharmacology 25: 367-384). At the conclusion of the infusion, active behavior of animals was measured in a 15-min swim test. Results showed that stressed animals infused with vehicle exhibited significantly less active behavior in the swim test than did non-stressed animals infused with vehicle, thereby showing the usual behavioral depression seen after exposure to an uncontrollable stress. Stressed animals infused with clonidine showed no difference in active behavior in comparison to non-stressed animals infused with vehicle and showed significantly more activity than did the stressed animals infused with vehicle. Stressed animals infused with piperoxane showed no significant difference in activity in comparison to the stressed animals infused with vehicle and were significantly less active than either the non-stressed animals infused with vehicle or the stressed animals infused with clonidine. Thus, infusion into the locus coeruleus of the alpha-2 agonist clonidine, but not the alpha-2 antagonist piperoxane, eliminated behavioral depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of the occipital alpha rhythm and temporal tau rhythm by using magnetoencephalography

Energy Technology Data Exchange (ETDEWEB)

Kim, J. E.; Gohel, Bakul; Kim, K.; Kwon, H.; An, Kyung Min [Center for Biosignals, Korea Research Institute of Standards and Science(KRISS), Daejeon (Korea, Republic of)

2015-12-15

Developing Magnetoencephalography (MEG) based on Superconducting Quantum Interference Device (SQUID) facilitates to observe the human brain functions in non-invasively and high temporal and high spatial resolution. By using this MEG, we studied alpha rhythm (8-13 Hz) that is one of the most predominant spontaneous rhythm in human brain. The 8–13 Hz rhythm is observed in several sensory region in the brain. In visual related region of occipital, we call to alpha rhythm, and auditory related region of temporal call to tau rhythm, sensorimotor related region of parietal call to mu rhythm. These rhythms are decreased in task related region and increased in task irrelevant regions. This means that these rhythms play a pivotal role of inhibition in task irrelevant region. It may be helpful to attention to the task. In several literature about the alpha-band inhibition in multi-sensory modality experiment, they observed this effect in the occipital and somatosensory region. In this study, we hypothesized that we can also observe the alpha-band inhibition in the auditory cortex, mediated by the tau rhythm. Before that, we first investigated the existence of the alpha and tau rhythm in occipital and temporal region, respectively. To see these rhythms, we applied the visual and auditory stimulation, in turns, suppressed in task relevant regions, respectively.

Measurement of the occipital alpha rhythm and temporal tau rhythm by using magnetoencephalography

International Nuclear Information System (INIS)

Kim, J. E.; Gohel, Bakul; Kim, K.; Kwon, H.; An, Kyung Min

2015-01-01

Developing Magnetoencephalography (MEG) based on Superconducting Quantum Interference Device (SQUID) facilitates to observe the human brain functions in non-invasively and high temporal and high spatial resolution. By using this MEG, we studied alpha rhythm (8-13 Hz) that is one of the most predominant spontaneous rhythm in human brain. The 8–13 Hz rhythm is observed in several sensory region in the brain. In visual related region of occipital, we call to alpha rhythm, and auditory related region of temporal call to tau rhythm, sensorimotor related region of parietal call to mu rhythm. These rhythms are decreased in task related region and increased in task irrelevant regions. This means that these rhythms play a pivotal role of inhibition in task irrelevant region. It may be helpful to attention to the task. In several literature about the alpha-band inhibition in multi-sensory modality experiment, they observed this effect in the occipital and somatosensory region. In this study, we hypothesized that we can also observe the alpha-band inhibition in the auditory cortex, mediated by the tau rhythm. Before that, we first investigated the existence of the alpha and tau rhythm in occipital and temporal region, respectively. To see these rhythms, we applied the visual and auditory stimulation, in turns, suppressed in task relevant regions, respectively

[Anti-TNF alpha in dermatology].

Science.gov (United States)

Mahe, E; Descamps, V

2002-12-01

The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.

Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

International Nuclear Information System (INIS)

Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

1989-01-01

This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [ 3 H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

PLE CATALYZED HYDROLYZES OF ALPHA-SUBSTITUTED ALPHA-HYDROXY ESTERS - THE INFLUENCE OF THE SUBSTITUENTS

NARCIS (Netherlands)

MOORLAG, H; KELLOGG, RM

1991-01-01

The enzymatic hydrolyses of a variety of alpha-substituted mandelic and lactic esters using pig liver esterase (PLE) have been investigated. High to moderate enantioselectivity was found for various alpha-substituted mandelic esters, whereas PLE showed low to no enantioselectivity for

Ab initio approach to the non-perturbative scalar Yukawa model

OpenAIRE

Li, YangDepartment of Physics and Astronomy, Iowa State University, Ames, IA, 50011, USA; Karmanov, V.A.(Lebedev Physical Institute, Leninsky Prospekt 53, Moscow, 119991, Russia); Maris, P.(Department of Physics and Astronomy, Iowa State University, Ames, IA, 50011, USA); Vary, J.P.(Department of Physics and Astronomy, Iowa State University, Ames, IA, 50011, USA)

2015-01-01

We report on the first non-perturbative calculation of the scalar Yukawa model in the single-nucleon sector up to four-body Fock sector truncation (one "scalar nucleon" and three "scalar pions"). The light-front Hamiltonian approach with a systematic non-perturbative renormalization is applied. We study the $n$-body norms and the electromagnetic form factor. We find that the one- and two-body contributions dominate up to coupling $\\alpha \\approx 1.7$. As we approach the coupling $\\alpha \\appr...

Alpha particle studies during JET DT experiments

International Nuclear Information System (INIS)

1999-01-01

The 1997 DT experiment (DTE1) at the Joint European Torus included studies of the behaviour of alpha particles in high temperature plasmas. Clear alpha particle heating was observed in a series of otherwise similar 10MW hot-ion H-modes by scanning the DT mixture from 0%T to 93%T. Maxima in central temperature and energy content were obtained which corresponded with the maximum in fusion yield. Alfven Eigenmodes (AEs) have been detected in JET, driven by NBI or ICRH fast ions. However, in agreement with theory, no AE activity was observed in DT plasmas which could be attributed to alpha particle drive, except in the afterglow of some Optimised Shear pulses. Ion Cyclotron Emission (ICE) was detected at harmonics of the alpha particle cyclotron frequency at the outer edge of the plasma. The ICE is interpreted as being close to magnetoacoustic cyclotron instability, driven by inverted alpha distributions at the plasma edge. The high-energy neutral particle spectra showed features, which are ascribed to a mixture of alphas, neutralised by helium-like impurities, and deuterons, born from elastic collisions with alpha particles and neutralised by hydrogen-like impurities. The results of all these studies are consistent with classical alpha particle trapping and slowing-down. Future DT experiments will aim to increase alpha particle pressure, so interactions with plasma instabilities can be studied. The measurement of knock-on neutral triton spectra offers a clean way to determine confined alpha densities in these future experiments. (author)