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Sample records for hydrogenophaga intermedia s1

  1. The double massa intermedia

    PubMed Central

    Baydin, Serhat; Gungor, Abuzer; Baran, Oguz; Tanriover, Necmettin; Rhoton, Albert L.

    2016-01-01

    Background: To describe the rare finding of a double massa intermedia (MI). Typically, the MI (interthalamic adhesion) is a single bridge of gray matter connecting the medial surfaces of the thalami. Methods: Twelve formalin- and alcohol-fixed human third ventricles were examined from superior to inferior by fiber dissection technique under ×6 to ×40 magnifications and with the endoscope. Results: In all hemispheres, the anterior and posterior commissure were defined. The MI, which bridges the medial surfaces of the thalami, was defined in all hemispheres. In one hemisphere, there was a second bridge between the thalami, located posteroinferior to the common MI. Endoscopic view confirmed that there was a second MI in this specimen. The MI usually traverses the third ventricle posterior to the foramen of Monro and connects the paired thalami. The MI is an important landmark during endoscopic and microscopic surgeries of the third ventricle. Although a double MI is very rare, surgeons should be aware of the possibility in their surgical planning. Conclusion: The surgeon should be aware of the possibility of a double MI to avoid confusion during third ventricle surgery. PMID:27127695

  2. Description of Hydrogenophaga laconesensis sp. nov. isolated from tube well water.

    PubMed

    Mantri, Soniya; Chinthalagiri, Mohan Rao; Gundlapally, Sathyanarayana Reddy

    2016-09-01

    A light cream color colony was isolated, using oligotrophic LB agar medium, from a water sample collected from a tube well and designated as HWB-10(T). Cells of strain HWB-10(T) were Gram-negative, motile rods, non-spore forming, positive for catalase, oxidase, nitrate reduction and esculin. The predominant fatty acids were C16:0, summed feature 4 (C16:1 ω7c/iso-C15:0 2-OH) and summed feature 7 (C18:1 ω7c, C18:1 ω9t and/or C18:1 ω12t), and the major ubiquinone was Q-8. NCBI-BLAST- and EzTaxon-based 16S rRNA gene sequence similarity search identified strain HWB-10(T) as a member of the genus Hydrogenophaga and H. atypica DSM 15342(T), H. defulvi DSM 15341(T), H. palleronii LMG2366(T) and H. taeniospiralis LMG7170(T) being the nearest phylogenetic species with a similarity (%) of 99.3, 99.1, 98.4 and 98.2, respectively, while the similarity was <98.0 % with other species of the genus. However, DNA-DNA similarities between HWB-10(T) and H. atypica DSM 15342(T) and H. defulvi DSM 15341(T) were 37.0 and 43.0 %, respectively, indicating that strain HWB-10(T) is a novel species. Further, the DNA fingerprinting, based on BOX-, ERIC-, (GTG)5- and REP-PCR amplifications, distinguished strain HWB-10(T) from its closest species, H. atypica DSM 15342(T) and H. defulvi DSM 15341(T) with similarity coefficients of 0.45 and 0.37, respectively, a value sufficient to establish the species status within the genus Hydrogenophaga. In addition, strain HWB-10(T) exhibited several phenotypic differences with its closely related species. Based on the above cumulative differentiating characteristics, strain HWB-10(T) was identified as a new species of the genus Hydrogenophaga and proposed as Hydrogenophaga laconesensis sp. nov. with strain HWB-10(T) (KTCC 42478(T) = LMG 28681(T)) as its type strain. PMID:27105873

  3. Hydrogenophaga carboriunda sp. nov., a tertiary butyl alcohol-oxidizing, psychrotolerant aerobe derived from granular-activated carbon (GAC).

    PubMed

    Reinauer, Kimberly M; Popovic, Jovan; Weber, Christopher D; Millerick, Kayleigh A; Kwon, Man Jae; Wei, Na; Zhang, Yang; Finneran, Kevin T

    2014-04-01

    A Gram-negative, rod-shaped bacterium was isolated from a mixed culture that degraded tert-butyl alcohol (TBA) in a granular-activated carbon (GAC) sample from a Biological-GAC reactor. Strain YZ2(T) was assigned to the Betaproteobacteria within the family Comamonadaceae based on 16S rRNA gene similarities. The nearest phylogenetic relative (95.0 % similarity) with a valid name was Hydrogenophaga taeniospiralis. The DNA G+C content was 66.4 mol%. DNA:DNA hybridization indicated that the level of relatedness to members of the genus Hydrogenophaga ranged from 1.1 to 10.8 %. The dominant cellular fatty acids were: 18:1 w7c (75 %), 16:0 (4.9 %), 17:0 (3.85 %), 18:0 (2.93 %), 11 methyl 18:1 w7c (2.69 %), Summed Feature 2 (2.27 %), and 18:0 3OH (1.35 %). The primary substrate used was TBA, which is a fuel oxygenate and groundwater contaminant. YZ2(T) was non-motile, without apparent flagella. It is a psychrotolerant, facultative aerobe that grew between pH 6.5 and 9.5, and 4 and 30 °C. The culture grew on and mineralized TBA at 4 °C, which is the first report of psychrotolerant TBA degradation. Hydrogen was used as an alternative electron donor. The culture also grew well in defined freshwater medium with ethanol, butanol, hydroxy isobutyric acid, acetate, pyruvate, citrate, lactate, isopropanol, and benzoic acid as electron donors. Nitrate was reduced with hydrogen as the sole electron donor. On the basis of morphological, physiological, and chemotaxonomic data, a new species, Hydrogenophaga carboriunda is proposed, with YZ2(T) as the type strain. PMID:24343174

  4. β-Thalassemia Intermedia: A Clinical Perspective

    PubMed Central

    Musallam, Khaled M.; Taher, Ali T.; Rachmilewitz, Eliezer A.

    2012-01-01

    Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with β-thalassemia intermedia has substantially increased over the past decade. Earlier studies observed that patients with β-thalassemia intermedia experience a clinical-complications profile that is different from that in patients with β-thalassemia major. In this article, a variety of clinical morbidities are explored, and their associations with the underlying disease pathophysiology and risk factors are examined. These involve several organs and organ systems including the vasculature, heart, liver, endocrine glands, bone, and the extramedullary hematopoietic system. The effects of some therapeutic interventions on the development of clinical complications are also discussed. PMID:22762026

  5. Legal and institutional aspects of regulating intermedia pollution

    SciTech Connect

    Entman, R.M.

    1980-05-01

    Intermedia pollution is defined here as the creation of new environmental impacts by controlling existing ones. DOE asked four questions: (1) do the major environmental laws address intermedia pollution; (2) does the Environmental Protection Agency (EPA) have rules, regulations, and procedures through which it considers intermedia questions; (3) do the legislative histories of the laws indicate whether Congress intended for the EPA to consider intermedia issues; and (4) in what ways do the existing laws and regulatory procedures exacerbate intermedia pollution. The answer to the first three questions is yes; much of this report is devoted to amplifying and qualifying that response, the rest to answering the fourth question. The report frames these issues by asking how we can control the adverse environmental i.e., intermedia, impacts of EPA itself. A case study of the intermedia implications of recently issued air-pollution standards for coal-fired power plants illustrates the themes concretely. An analysis of policy alternatives for improving intermedia pollution control concludes the study. The major problems impending good intermedia policy decisions are: conflicts among and failures fully to implement environmental laws; political pressures; tendencies of EPA to minimize the adverse environmental consequences of its own actions; uncertainties caused by the rudimentary scientific understanding of intermedia pollution; and limitations on EPA's organizational ability to handle whatever complex intermedia information it does obtain. The final chapter assesses three policy responses to these problems: do nothing new; issue an incremental prod; and a new law and EPA suffice. Evaluation of these alternatives depends on how deficient current practices are thought to be.

  6. Enhancing Transport of Hydrogenophaga flava ENV735 for Bioaugmentation of Aquifers Contaminated with Methyl tert-Butyl Ether

    PubMed Central

    Streger, Sheryl H.; Vainberg, Simon; Dong, Hailiang; Hatzinger, Paul B.

    2002-01-01

    The gasoline oxygenate methyl tert-butyl ether (MTBE) has become a widespread contaminant in groundwater throughout the United States. Bioaugmentation of aquifers with MTBE-degrading cultures may be necessary to enhance degradation of the oxygenate in some locations. However, poor cell transport has sometimes limited bioaugmentation efforts in the past. The objective of this study was to evaluate the transport characteristics of Hydrogenophaga flava ENV735, a pure culture capable of growth on MTBE, and to improve movement of the strain through aquifer solids. The wild-type culture moved only a few centimeters in columns of aquifer sediment. An adhesion-deficient variant (H. flava ENV735:24) of the wild-type strain that moved more readily through sediments was obtained by sequential passage of cells through columns of sterile sediment. Hydrophobic and electrostatic interaction chromatography revealed that the wild-type strain is much more hydrophobic than the adhesion-deficient variant. Electrophoretic mobility assays and transmission electron microscopy showed that the wild-type bacterium contains two distinct subpopulations, whereas the adhesion-deficient strain has only a single, homogeneous population. Both the wild-type strain and adhesion-deficient variant degraded MTBE, and both were identified by 16S rRNA analysis as pure cultures of H. flava. The effectiveness of surfactants for enhancing transport of the wild-type strain was also evaluated. Many of the surfactants tested were toxic to ENV735; however, one nonionic surfactant, Tween 20, enhanced cell transport in sand columns. Improving microbial transport may lead to a more effective bioaugmentation strategy for MTBE-contaminated sites where indigenous oxygenate degraders are absent. PMID:12406751

  7. Use of Hydrogenophaga pseudoflava penetration to quantitatively assess the impact of filtration parameters for 0.2-micrometer-pore-size filters.

    PubMed

    Lee, A; McVey, J; Faustino, P; Lute, S; Sweeney, N; Pawar, V; Khan, M; Brorson, K; Hussong, D

    2010-02-01

    Filters rated as having a 0.2-microm pore size (0.2-microm-rated filters) are used in laboratory and manufacturing settings for diverse applications of bacterial and particle removal from process fluids, analytical test articles, and gasses. Using Hydrogenophaga pseudoflava, a diminutive bacterium with an unusual geometry (i.e., it is very thin), we evaluated passage through 0.2-microm-rated filters and the impact of filtration process parameters and bacterial challenge density. We show that consistent H. pseudoflava passage occurs through 0.2-microm-rated filters. This is in contrast to an absence of significant passage of nutritionally challenged bacteria that are of similar size (i.e., hydrodynamic diameter) but dissimilar geometry. PMID:19966023

  8. Molecular cloning and functional characterization of borneol dehydrogenase from the glandular trichomes of Lavandula x intermedia.

    PubMed

    Sarker, Lukman S; Galata, Mariana; Demissie, Zerihun A; Mahmoud, Soheil S

    2012-12-15

    Several varieties of Lavandula x intermedia (lavandins) are cultivated for their essential oils (EOs) for use in cosmetic, hygiene and personal care products. These EOs are mainly constituted of monoterpenes including camphor, which contributes an off odor reducing the olfactory appeal of the oil. We have recently constructed a cDNA library from the glandular trichomes (the sites of EO synthesis) of L. x intermedia plants. Here, we describe the cloning of a borneol dehydrogenase cDNA (LiBDH) from this library. The 780 bp open reading frame of the cDNA encoded a 259 amino acid short chain alcohol dehydrogenase with a predicted molecular mass of ca. 27.5 kDa. The recombinant LiBDH was expressed in Escherichia coli, purified by Ni-NTA agarose affinity chromatography, and functionally characterized in vitro. The bacterially produced enzyme specifically converted borneol to camphor as the only product with K(m) and k(cat) values of 53 μM and 4.0 × 10(-4) s(-1), respectively. The LiBDH transcripts were specifically expressed in glandular trichomes of mature flowers indicating that like other Lavandula monoterpene synthases the expression of this gene is regulated in a tissue-specific manner. The cloning of LiBDH has far reaching implications in improving the quality of Lavandula EOs through metabolic engineering. PMID:23058847

  9. β-Thalassemia Intermedia: A Bird’s-Eye View

    PubMed Central

    Haddad, Anthony; Tyan, Paul; Radwan, Amr; Mallat, Naji; Taher, Ali

    2014-01-01

    Beta-thalassemia is due to a defect in the synthesis of the beta-globin chains, leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. The spectrum of thalassemias is wide, with one end comprising thalassemia minor, which consists of a mild hypochromic microcytic anemia with no obvious clinical manifestations, while on the other end is thalassemia major, characterized by patients who present in their first years of life with profound anemia and regular transfusion requirements for survival. Along the spectrum lies thalassemia intermedia, a term developed to describe patients with manifestations that are neither mild enough nor severe enough to be classified in the spectrum’s extremes. Over the past decade, our understanding of β-thalassemia intermedia has increased tremendously with regards to molecular information as well as pathophysiology. It is now clear that β-thalassemia intermedia has a clinical presentation as well as complications associated with the disease that are different from those of β-thalassemia major. This review is designed to tackle issues related to β-thalassemia intermedia from the basic definition of the disease to paramedical issues, namely the quality of life in these patients. Genetics and pathophysiology are revisited, as well as the complications specific to this disease. These complications include effects on several organ systems, including the cardiovascular, hepatic, endocrine, renal, brain, and skeletal systems. Extramedullary hematopoiesis is also discussed in this article. Risk factors are highlighted and cutoffs are identified to minimize morbidities in β-thalassemia intermedia. Several treatment modalities are considered by shining a light on the pros and cons of each modality, as well as the role of special pharmacological agents in the progress of the disease and its morbidities. Finally, health-related quality of life is discussed in these patients with a direct comparison to the more severe

  10. CLINICAL APPLICATION OF RECOMBINANT ERYTHROPOIETIN IN BETA-THALASSAEMIA INTERMEDIA.

    PubMed

    Asadov, Ch; Alimirzoyeva, Z; Hasanova, M; Mammadova, T; Shirinova, A

    2016-06-01

    Research objective is to study the efficacy of recombinant erythropoietin (epoetin alfa) as alternative method of treatment beta-thalassemia intermedia. Study involved 58 patients with beta-thalassemia intermedia (23 women and 35 men). In all observed patients was defined levels of hemoglobin (Hb), red blood cells (RBC), erythrocyte indexes (MCV, MCH, MCHC), hemoglobin fractions (HbA, HbA2, HbF), serum ferritin, serum erythropoietin before and after administrated rEPO. All patients received rEPO during 6 month at the dose - 10000 IU subcutaneously. The majority of patients - 39 (67%) had a good response to rEPO (increase in hemoglobin level more than 20 g/l); 16 patients (28%) had a mean response (increase in Hb 10 - 20 g/l); in 3 (5%) patients occurred poor response to rEPO therapy (increase in Hb <10 g/l). After rEPO treatment of beta-thalassemia intermedia patients there was a statistically significant change in the number of RBC, levels of HbF and sEPO. The evaluation of interdependence between the indices of the baseline sEPO and increased Hb values in patients after rEPO treatment revealed the presence of the reverse direct relationship (r=-0.67). Based on the results, it can be concluded that the use of rEPO in complex therapy of beta-thalassemia intermedia leads to increased levels of Hb and consequently reducing the need for blood transfusions, and accordingly expected to prevent severe complications of blood transfusion (alloimmunization, hypersplenism, iron overload, contamination transmissible infections) facilitating normal growth and development, and a better quality of life. PMID:27441542

  11. Development and evaluation of new primers for PCR-based identification of Prevotella intermedia.

    PubMed

    Zhou, Yanbin; Liu, Dali; Wang, Yiwei; Zhu, Cailian; Liang, Jingping; Shu, Rong

    2014-08-01

    The aim of this study was to develop new Prevotella intermedia-specific PCR primers based on the 16S rRNA. The new primer set, Pi-192 and Pi-468, increased the accuracy of PCR-based P. intermedia identification and could be useful in the detection of P. intermedia as well as epidemiological studies on periodontal disease. PMID:24875331

  12. Thalamic Massa Intermedia Duplication in a Dysmorphic 14 month-old Toddler

    PubMed Central

    Whitehead, Matthew T

    2015-01-01

    The massa intermedia is an inconstant parenchymal band connecting the medial thalami. It may be thickened in various disease processes such as Chiari II malformation or absent in other disease states. However, the massa intermedia may also be absent in up to 30% of normal human brains. To the best of my knowledge, detailed imaging findings of massa intermedia duplication have only been described in a single case report. An additional case of thalamic massa intermedia duplication discovered on a routine brain MR performed for dysmorphic facial features is reported herein. PMID:26622932

  13. Spinal epidural extramedullary haematopoiesis in β-thalassaemia intermedia

    PubMed Central

    Wong, Kin Hoi; Li, Allen; Lui, Tun Hing; Sit, Yan Kit

    2014-01-01

    A 22-year-old man known to have β-thalassaemia intermedia since childhood presented with bilateral lower limb weakness after spinal anaesthesia for an elective minor operation of his left leg. MRI and CT scans were performed to rule out acute epidural haematoma; coincidental imaging features of marrow hyperplasia and spinal epidural extramedullary haematopoiesis were found. This article will present and discuss the imaging features, differential diagnosis, management and literature review of the rare occurrence of extramedullary haematopoiesis in the spinal epidural space. PMID:24390965

  14. SYNCHROTRON X-RAY ABSORPTION-EDGE COMPUTED MICROTOMOGRAPHY IMAGING OF THALLIUM COMPARTMENTALIZATION IN IBERIS INTERMEDIA

    EPA Science Inventory

    Thallium (TI) is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants. Thallium is efficiently hyperaccumulated in Iberis intermedia as TI(I). Distribution and compartmentalization of TI in I. intermedia is highes...

  15. Mycelial pellet formation by edible ascomycete filamentous fungi, Neurospora intermedia.

    PubMed

    Nair, Ramkumar B; Lennartsson, Patrik R; Taherzadeh, Mohammad J

    2016-12-01

    Pellet formation of filamentous fungi in submerged culture is an imperative topic of fermentation research. In this study, we report for the first time the growth of filamentous ascomycete fungus, Neurospora intermedia in its mycelial pellet form. In submerged culture, the growth morphology of the fungus was successfully manipulated into growing as pellets by modifying various cultivation conditions. Factors such as pH (2.0-10.0), agitation rate (100-150 rpm), carbon source (glucose, arabinose, sucrose, and galactose), the presence of additive agents (glycerol and calcium chloride) and trace metals were investigated for their effect on the pellet formation. Of the various factors screened, uniform pellets were formed only at pH range 3.0-4.0, signifying it as the most influential factor for N. intermedia pellet formation. The average pellet size ranged from 2.38 ± 0.12 to 2.86 ± 0.38 mm. The pellet formation remained unaffected by the inoculum type used and its size showed an inverse correlation with the agitation rate of the culture. Efficient glucose utilization was observed with fungal pellets, as opposed to the freely suspended mycelium, proving its viability for fast-fermentation processes. Scale up of the pelletization process was also carried out in bench-scale airlift and bubble column reactors (4.5 L). PMID:27103628

  16. Gravi-photomorphogenesis of the moss Pottia intermedia protonemata

    NASA Astrophysics Data System (ADS)

    Demkiv, O. T.; Kyjak, N. Y.; Khorkavtsiv, Y. D.; Kit, N. A.

    The protonemata development proceeds in the process of gradual differentiation of growing apical cells and intercalar cells the shortened lateral branches of the latters being transformed into three-dimensional gametophore buds (Demkiv et al., 1991). Normal course of plant development needs favourable external conditions. Sometimes, however, external environment agents can accelerate the development of organism. So, apical protonema cells of darkgrown gravitropic P. intermedia differentiate gametophore-buds in light of low intensity (Ripetskyj, 1999). We investigate the influence of gravistimulation on bud formation in haploid and diploid P. intermedia protonema. Diploid protonema was found to react on light weaker than haploid one. Under the influence of light the darkgrown apical cells and lateral branches of haploid protonema were directly transformed into buds, while in diploid protonema at first the formation of bundles of rhizoid type filaments takes place on the tips of caulonema and buds appeared in center of such bundles. The participation of gravity in gametophore bud formation was assessed by clinorotating protonema in darkness. Being illuminated such protonema also developed buds quickly the latters being formed along all stolon. It can be suggested that at 1g the growth zone of apical cells actively attract inductors of bud formation. During clinorotation the inductors probably are transferred much more slower than under stationary state and that is why the buds arised not only at the tips of stolons but along all their length. It is known that gametophore bud formation can be stimulated by exogenous phytohormones. As M. Bopp (1980) has shown, that kinetin selectively promotes bud formation on moss protonema. Our observations have shown 0,5 -- 50 μ M of kinetin stimulate the bud formation on diploid aposporic protonema much more effectively that on haploid one. It can be concluded that the amount of endogenous cytokinins in haploid protonemal cells is

  17. Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

    PubMed

    Fteita, Dareen; Könönen, Eija; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2014-06-01

    Alterations in the quantity and quality of biofilms at gingival margin are considered to play a role in the initiation and development of pregnancy-related gingivitis. Prevotella intermedia sensu lato is able to consume estradiol, the major sex hormone secreted during pregnancy, in the absence of vitamin K. The aim of the study was to examine the effect of estradiol on the planktonic growth, coaggregation, polysaccharide production, and biofilm formation of the P. intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens. In all experiments, the type strain (ATCC) and a clinical strain (AHN) of P. intermedia, P. nigrescens, and P. pallens were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol. Planktonic growth was assessed by means of the colony forming unit method, while coaggregation and biofilm formation were assessed by spectrophotometric methods. In the determination of protein and polysaccharide levels, the Bradford and phenol-sulfuric acid methods were used, respectively. P. pallens AHN 9283 and P. nigrescens ATCC 33563 increased their numbers at planktonic stage with increasing estradiol concentrations. In 48-h biofilm tests, elevated protein levels were found for both strains of P. intermedia, and the strains P. nigrescens ATCC 33563 and P. pallens AHN 9283 in the presence of estradiol. The P. intermedia strains also increased the levels of polysaccharide formation in the biofilm. Coaggregation of the P. intermedia group organisms with Fusobacterium nucleatum was enhanced only in P. intermedia AHN 8290. In conclusion, our in vitro experiments indicate that estradiol regulates planktonic growth, coaggregation, polysaccharide production, and biofilm formation characteristics of P. intermedia, P. nigrescens, and P. pallens differently. These results may, at least partly, explain the differences seen in their contribution to the pathogenesis of pregnancy-related gingivitis. PMID

  18. Secondary haemochromatosis in a patient with thalassemia intermedia.

    PubMed

    Rotaru, Ionela; Gaman, Amelia; Gaman, G

    2014-01-01

    Haemochromatosis is due to excessive accumulation of iron in tissues and organs impairing their function. The most common haematologic disorders that are subject to an intensive transfusion regimen bringing excess iron in the body are: thalassemia and myelodysplastic syndrome. The value of serum ferritin in these patients (indicator of iron stores condition) reaches high values. Red cell substitution bringing additional iron intake must be accompanied by administration of chelation therapy in order to prevent haemochromatosis and related complications. We present the case of a patient with thalassemia intermedia, integumentary secondary haemochromatosis, cirrhosis with haemochromatosis, and secondary diabetes, who died at the age of 33 years because of upper gastrointestinal bleeding due to the rupture of oesophageal varices. PMID:24791210

  19. A thalassaemia intermedia case with concomitant left atrial thrombus

    PubMed Central

    Sahin, Cem; Basaran, Ozcan; Topal, Yasar; Akin, Fatih

    2014-01-01

    Although marked improvements have been observed in the life expectancy of patients with thalassaemia by regular blood transfusion and strict iron chelation therapies in recent years, these patients still have to deal with several complications, mainly cardiovascular. One of the life-threatening complications is the chronic hypercoagulable state and thromboembolic events which develop due to haemostatic alterations in patients with thalassaemia, although they are more frequently seen in those with thalassaemia intermedia. Many thromboembolic complications, mainly deep venous thrombosis and cerebral thrombosis, have been reported in thalassaemia. However, intracardiac thrombosis is rarely seen. In this manuscript, we presented a case that underwent splenectomy 6 years ago but not regularly attended the control visits and presented to our clinic with gradually increasing exercise dyspnoea for 2 months. PMID:24951612

  20. Nuevos sistemas de frecuencia intermedia para el IAR

    NASA Astrophysics Data System (ADS)

    Olalde, J. C.; Perilli, D.; Larrarte, J. J.

    Se presenta el diagrama en bloques de los nuevos sistemas de Frecuencia Intermedia para los dos radiómetros instalados en el IAR. Entre las características más importantes del sistema podemos mencionar la posibilidad de conectar cualquiera de las dos antenas a los ``backend" disponibles: analizador espectral de alta resolución (META II) de 0,05 Hz, autocorrelador de 1008 canales y contínuo. Se incorporan al sistema nuevos sintetizadores de frecuencia implementados con PLL y la moderna técnica de síntesis digital directa. Por último, el conjunto del sistema es susceptible de ser configurado por las computadoras de adquisición de datos, supervisadas por otra, que entrega el estado de funcionamiento actual y evita la selección de configuraciones incorrectas por parte del usuario.

  1. Antimicrobial susceptibility pattern of Brachyspira intermedia isolates from European layers.

    PubMed

    Verlinden, Marc; Boyen, Filip; Pasmans, Frank; Garmyn, An; Haesebrouck, Freddy; Martel, An

    2011-09-01

    A broth microdilution method was used to determine the antimicrobial susceptibility of 20 Brachyspira intermedia isolates obtained from different layer flocks in Belgium and The Netherlands between 2008 and 2010. The antimicrobial agents used were tylosin, tilmicosin, tiamulin, valnemulin, doxycycline, and lincomycin. The minimal inhibitory concentration (MIC) distribution patterns of tylosin, tilmicosin, lincomycin, and doxycycline were bimodal, demonstrating acquired resistance against doxycycline in three strains, against the macrolides in two strains, and against lincomycin in one strain. The MICs of tiamulin and valnemulin showed a monomodal distribution, but with tailing toward the higher MIC values, possibly suggesting low-level acquired resistance in six isolates. Sequencing revealed a G1058C mutation in the 16S rRNA gene in all doxycycline-resistant strains. The strain resistant to tylosin, tilmicosin, and lincomycin had an A2058T mutation in the 23S rRNA gene. PMID:21663534

  2. Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia

    PubMed Central

    Mhaidli, Hani; Taher, Ali T.

    2010-01-01

    Ineffective erythropoiesis in patients with thalassemia intermedia drives extramedullary hematopoietic tumor formation in several parts of the body. Paraspinal involvement has received increasing attention due to the associated morbidity secondary to spinal cord compression. Although the history and physical examination may help narrow the differential diagnosis, radiographic imaging remains essential to confirm the existence of hematopoietic tissue. Characteristic appearance has been observed mainly on magnetic resonance imaging. Several treatment options have been described, including transfusion therapy, laminectomy, radiotherapy, and the use of fetal hemoglobin inducing agents that decrease the hematopoietic drive. However, the ideal management scheme remains controversial. Until large prospective trials evaluate the efficacy and safety of the available treatment options, both in single and in combination therapy, an individualized approach should be entertained. PMID:20204423

  3. Pathogenicity of Prevotella intermedia and Prevotella nigrescens isolates in a wound chamber model in rabbits.

    PubMed

    Hafström, C; Dahlén, G

    1997-06-01

    The pathogenicity of 14 isolates identified as Prevotella intermedia or Prevotella nigrescens by serogrouping using monoclonal antibodies was compared in a tissue cage model in rabbits. Seven strains from periodontal abscesses, 5 strains from deep periodontal pockets and 2 strains from gingivitis were tested in the animal model comprising 6 Teflon tissue cages implanted on the back each of 34 rabbits. A total of 10(5)-10(8) cells of P. intermedia or P. nigrescens strains were inoculated alone or together with either Actinobacillus actinomycetemcomitans or Streptococcus mitis. Five strains of Porphyromonas gingivalis were used as a reference. The infectivity was recorded as pus formation and log viable count in aspirated material for 3, 7 and 14 days. None of the Prevotella strains inoculated in monoculture survived more than 3 days, and they had no capacity to produce abscess. P. intermedia or P. nigrescens strains in combination with A. actinomycetemcomitans produced abscesses in 33-100% and with S. mitis in 42-100%. No difference in abscess formation or log viable count in samples after 14 days was recorded between serogroup I (P. intermedia) and serogroup II and III (P. nigrescens). The infectivity of P. intermedia or P. nigresceas strains did not differ whether they were isolated from periodontal abscess, periodontal pocket or gingivitis. P. intermedia and P. nigrescens strains produced abscesses in combination with a facultative anaerobic strain and appears to have a similar pathogenicity in the wound chamber model in rabbits. PMID:9467400

  4. Gravitropism in caulonemata of the moss Pottia intermedia

    NASA Technical Reports Server (NTRS)

    Chaban, C. I.; Kern, V. D.; Ripetskyj, R. T.; Demkiv, O. T.; Sack, F. D.

    1998-01-01

    The gravitropism of caulonemata of Pottia intermedia is described and compared with that of other mosses. Spore germination produces primary protonemata including caulonemata which give rise to buds that form the leafy moss plant, the gametophore. Primary caulonemata are negatively gravitropic but their growth and the number of filaments are limited in the dark. Axenic culture of gametophores results in the production of secondary caulonemata that usually arise near the leaf base. Secondary protonemata that form in the light are agravitropic. Secondary caulonemata that form when gametophores are placed in the dark for several days show strong negative gravitropism and grow well in the dark. When upright caulonemata are reorientated to the horizontal or are inverted, upward bending can be detected after 1 h and caulonemata reach the vertical within 1-2 d. Clear amyloplast sedimentation occurs 10-15 minutes after horizontal placement and before the start of upward curvature. This sedimentation takes place in a sub-apical zone. Amyloplast sedimentation also takes place along the length of upright and inverted Pottia protonemata. These results support the hypothesis that amyloplast sedimentation functions in gravitropic sensing since sedimentation occurs before gravitropism in Pottia and since the location and presence of a unique sedimentation zone is conserved in all four mosses known to gravitropic protonomata.

  5. Genetic determinants of β-thalassemia intermedia in Pakistan.

    PubMed

    Khan, Jabbar; Ahmad, Nafees; Siraj, Sami; Hoti, Naseruddin

    2015-01-01

    This study covers the molecular characterization of clinically diagnosed β-thalassemia intermedia (β-TI) patients in Pakistan. Blood samples of β-TI patients were collected from all four provinces of Pakistan throughout the period of 2011-2013. The study was carried out using allele-specific primers through polymerase chain reaction or sequencing to determine both α- and β-thalassemia (α- and β-thal) mutations, and restriction enzymes for the characterization of β-globin gene arrangements. In a total of 63 patients, the IVS-I-5 (G > C) was the most frequent mutation (33.88%). The codon 30 (G > A) and IVS-II-1 (T > C) mutations were found only in the Punjabi ethnic group, while the codon 30 (G > C) and Hb S (HBB: c.20A > T) mutations were found only in the Pashtoon and Sindhi ethnic groups, respectively. In case of α-globin genotypes, 44 patients were normal (αα/αα), six patients carried the αα/-α(3.7) genotype, 12 patients carried the -α(3.7)/-α(3.7) genotype, while one patient had the αα/ααα(anti 3.7) genotype. We found that haplotype I was the most frequent, mostly associated with the codons 8/9 (+G) mutation, while the Saudi haplotype was found only with Hb S. PMID:25707679

  6. Characterization of Atypical Isolates of Yersinia intermedia and Definition of Two New Biotypes▿ †

    PubMed Central

    Martin, Liliane; Leclercq, Alexandre; Savin, Cyril; Carniel, Elisabeth

    2009-01-01

    The species Yersinia intermedia is a member of the genus Yersinia which belongs to the Enterobacteriaceae family. This species is divided into eight biotypes, according to Brenner's biotyping scheme. This scheme relies on five tests (utilization of Simmons citrate and acid production from d-melibiose, d-raffinose, α-methyl-d-glucoside [αMG], and l-rhamnose). The collection of the French Yersinia Reference Laboratory (Institut Pasteur, Paris, France) contained 44 strains that were originally identified as Y. intermedia but whose characteristics did not fit into the biotyping scheme. These 44 strains were separated into two biochemical groups: variant 1 (positive for acid production from l-rhamnose and αMG and positive for Simmons citrate utlization) and variant 2 (positive for acid production from l-rhamnose and αMG). These atypical strains could correspond to new biotypes of Y. intermedia, to Y. frederiksenii strains having the atypical property of fermenting αMG, or to new Yersinia species. These strains did not exhibit growth or phenotypic properties different from those of Y. intermedia and Y. frederiksenii and did not harbor any of the virulence traits usually found in pathogenic species. DNA-DNA hybridizations performed between one strain each of variants 1 and 2 and the Y. intermedia and Y. frederiksenii type strains demonstrated that these variants do belong to the Y. intermedia species. We thus propose that Brenner's biotyping scheme be updated by adding two new biotypes: 9 (for variant 1) and 10 (for variant 2) to the species Y. intermedia. PMID:19494062

  7. In Vitro Effects of Polyphosphate against Prevotella intermedia in Planktonic Phase and Biofilm.

    PubMed

    Jang, Eun-Young; Kim, Minjung; Noh, Mi Hee; Moon, Ji-Hoi; Lee, Jin-Yong

    2016-02-01

    Polyphosphate (polyP) has gained a wide interest in the food industry due to its potential as a decontaminating agent. In this study, we examined the effect of sodium tripolyphosphate (polyP3; Na5P3O10) against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. The MIC of polyP3 against P. intermedia ATCC 49046 determined by agar dilution method was 0.075%, while 0.05% polyP3 was bactericidal against P. intermedia in time-kill analysis performed using liquid medium. A crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that sub-MICs of polyP3 significantly decreased biofilm formation. Under the scanning electron microscope, decreased numbers of P. intermedia cells forming the biofilms were observed when the bacterial cells were incubated with 0.025% or higher concentrations of polyP3. Assessment of biofilm viability with LIVE/DEAD staining and viable cell count methods showed that 0.05% or higher concentrations of polyP3 significantly decreased the viability of the preformed biofilms in a concentration-dependent manner. The zone sizes of alpha-hemolysis formed on horse blood agar produced by P. intermedia were decreased in the presence of polyP3. The expression of the genes encoding hemolysins and the genes of the hemin uptake (hmu) locus was downregulated by polyP3. Collectively, our results show that polyP is an effective antimicrobial agent against P. intermedia in biofilms as well as planktonic phase, interfering with the process of hemin acquisition by the bacterium. PMID:26596937

  8. Antimicrobial susceptibility testing of Brachyspira intermedia and Brachyspira pilosicoli isolates from Australian chickens.

    PubMed

    Hampson, D J; Stephens, C P; Oxberry, S L

    2006-02-01

    Susceptibilities of predominantly Australian isolates of the pathogenic intestinal spirochaetes Brachyspira intermedia (n = 25) and Brachyspira pilosicoli (n = 17) from chickens were tested in agar dilution against four concentrations each of the antimicrobials tiamulin, lincomycin, tylosin, metronidazole, tetracycline and ampicillin. Based on available minimum inhibitory concentration (MIC) breakpoint values for Brachyspira hyodysenteriae or other Gram-negative enteric veterinary pathogens, isolates of both species generally were susceptible to tiamulin, lincomycin, metronidazole and tetracycline. Although not classed as resistant, four isolates of B. intermedia had an elevated MIC range for tiamulin (1 to 4 mg/l), 11 isolates of B. intermedia and five of B. pilosicoli had an elevated MIC range for lincomycin (10 to 50 mg/l), one isolate of B. pilosicoli had an elevated MIC range for tetracycline (10 to 20 mg/l), and one isolate of B. intermedia and five of B. pilosicoli had an elevated MIC range for ampicillin (10 to 50 mg/l). A clear lack of susceptibility to tylosin (MIC > 4 mg/l) was seen in 11 isolates each of B. intermedia and B. pilosicoli, and to ampicillin (MIC > 32 mg/l) in two isolates of B. pilosicoli. These data suggest that some resistance to common antimicrobials exists among intestinal spirochetes obtained from laying hens and supports the need of MIC data for clinical isolates before any treatment is considered. PMID:16448937

  9. Endocrine and Bone Complications in β-Thalassemia Intermedia: Current Understanding and Treatment

    PubMed Central

    Noureldine, MohammadHassan A.; Abbas, Hussein A.

    2015-01-01

    Thalassemia intermedia (TI), also known as nontransfusion dependent thalassemia (NTDT), is a type of thalassemia where affected patients do not require lifelong regular transfusions for survival but may require occasional or even frequent transfusions in certain clinical settings and for defined periods of time. NTDT encompasses three distinct clinical forms: β-thalassemia intermedia (β-TI), Hb E/β-thalassemia, and α-thalassemia intermedia (Hb H disease). Over the past decade, our understanding of the molecular features, pathophysiology, and complications of NTDT particularly β-TI has increased tremendously but data on optimal treatment of disease and its various complications are still lacking. In this paper, we shall review a group of commonly encountered complications in β-TI, mainly endocrine and bone complications. PMID:25834825

  10. Digital Distribution of Advertising for Publications (DDAP): a graphic arts prototype of electronic intermedia publishing (EIP)

    NASA Astrophysics Data System (ADS)

    Dunn, Patrice M.

    1998-01-01

    The Digital Distribution of Advertising for Publications (DDAP) is a graphic arts industry prototype of Electronic Intermedia Publishing (EIP). EIP is a strategic, multi- industrial concept that seeks to enable the capture and input of volumes of data (i.e., both raster and object oriented data -- as well as the latter's antecedent which is vector data -- color data and black-and-white data) from a multiplicity of devices; then flowing, controlling, manipulating, modifying, storing, retrieving, transmitting, and shipping, that data through an industrial process for output to a multiplicity of output devices (e.g., ink on paper, toner on paper, bits and bytes on CD ROM, Internet, Multimedia, HDTV, etc.). As the technical requirements of the print medium are among the most rigorous in the Intermedia milieu the DDAP prototype addresses some of the most challenging issues faced in Electronic Intermedia Publishing (EIP).

  11. Molecular Characterization of β-Thalassemia Intermedia in Southeast Iran.

    PubMed

    Miri-Moghaddam, Ebrahim; Bahrami, Sara; Naderi, Majid; Bazi, Ali; Karimipoor, Morteza

    2016-06-01

    Inheritance of mild mutations within the β-globin gene and coinheritance of α-thalassemia (α-thal) are known as two important genetic modifiers in β-thalassemia (β-thal) intermedia (β-TI). We aimed to evaluate the spectrum of β- and α-thal mutations in β-TI patients in Southeast Iran. Common β- and α-globin gene mutations were detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and multiplex gap-PCR, respectively. There were 26 male (57.8%) and 19 female (42.2%) patients. HBB: c.92 + 5T > C [IVS-I-5 (G > C)] and HBB: c.-138C + 1G > A [IVS-II-I (G > A)] represented the prevalent alleles with respective frequencies of 60.0 and 10.0%. Other β-globin mutations included HBB: c.-138C > T [-88 (C > T)], HBB: c.27_28insG [frameshift codons (FSC) 8/9 (+G)], HBB: c.46delT [codon 15 (-T)], HBB: c.93-22_95del (IVS-I, 25 del), and the 619 bp deletion (NG_000007.3: g.71609_72227del619). The predominant genotypic combinations were β(0)/β(0) (68.9%), β(0)/β(+ )(8.9%) and β(+)/β(+ )(2.2%). Coinheritance of α-thal was observed in 33.0% of the patients, with the -α(3.7) (rightward) (NG_000006.1: g.34164_37967del3804) as the most common deletion (86.0%). One patient was diagnosed with the -α(4.2) (leftward) (AF221717) and one with the - -(MED) (g.24664_41064del16401) deletions, while no patients carried the -(α)(20.5) (g.15164_37864del22701), α(-5 nt) (HBA2: c.95 + 2_95_6delTGAGG) or codon 19 (-G) (HBA2: c.56delG) mutations. The alleviating molecular mechanism was not explainable by β(+ )or concurrent α-thal in more than half of our β-TI patients. This encourages conducting more studies to identify other contributing factors, especially Hb F-inducing genetic modifiers. PMID:27117567

  12. Issues in Designing a Hypermedia Document System: The Intermedia Case Study.

    ERIC Educational Resources Information Center

    Yankelovich, Nicole; And Others

    1986-01-01

    Intermedia, a hypermedia system developed at Brown University's Institute for Research (Rhode Island) in Information and Scholarship, is first described, and then used as a case study to explore a number of key issues that software designers must consider in the development of hypermedia document systems. A hypermedia document system is defined as…

  13. Identification of a lycopsamine-N-oxide chemotype of Amsinckia intermedia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In February 2012, an apparent poisoning outbreak in cattle occurred on rangeland infested with Amsinckia intermedia near Kingman, Arizona. Plant samples were collected from the location every month from the time of the poisoning outbreak through to when the plant seeded and senesced in May 2012. A...

  14. Composition, Cytotoxic and Antimicrobial Activities of Satureja intermedia C.A.Mey Essential Oil.

    PubMed

    Sharifi-Rad, Javad; Sharifi-Rad, Mehdi; Hoseini-Alfatemi, Seyedeh Mahsan; Iriti, Marcello; Sharifi-Rad, Majid; Sharifi-Rad, Marzieh

    2015-01-01

    In this study, the essential oil (EO) constituents from the aerial parts of Satureja intermedia C.A.Mey were detected by GC and GC/MS. The antimicrobial activity of EO on oral pathogens and its cytotoxicity to human cancer cells were determined by the microbroth dilution method and the crystal violet staining method, respectively. Thirty-nine compounds were identified and the main EO constituents were γ-terpinene (37.1%), thymol (30.2%), p-cymene (16.2%), limonene (3.9%), α-terpinene (3.3%), myrcene (2.5%), germacrene B (1.4%), elemicine (1.1%) and carvacrol (0.5%). The S. intermedia EO showed a concentration-dependent decrease in viability of Hep-G2 (hepatocellular carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines (p < 0.05). Antimicrobial screening of S. intermedia EO demonstrated slight antibacterial and antifungal activities against Streptococcus mutants, S. salivarius, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and C. glabrata. Further preclinical studies are needed to assess the efficacy and safety of S. intermedia EO as a new promising anticancer agent. PMID:26247936

  15. Development and evaluation of the neutralizing capacity of horse antivenom against the Brazilian spider Loxosceles intermedia.

    PubMed

    Braz, A; Minozzo, J; Abreu, J C; Gubert, I C; Chávez-Olórtegui, C

    1999-09-01

    Spider bites due to Loxosceles intermedia are currently a major public health problem in South Brazil. About 3000 cases are reported annually. Specific treatment for spider bites is provided by the polyvalent anti-arachnidic antiserum produced by Butantan Institute, São Paulo, Brazil by immunizing horses with mixtures of venoms from Tityus serrulatus and T. bahiensis scorpions, as well as Phoneutria nigriventer and L. gaucho spiders. Due to the large amounts of the anti-arachnidic antivenom required and since L. intermedia venom has some biochemical and pharmacological variations, we have produced a specific anti-L. intermedia antivenom. This study shows that horses immunized with crude L. intermedia venom produced IgG antibodies that neutralized the dermonecrotic and lethal activities of the venom. The neutralizing potency of the anti-loxoscelic antivenom was compared with that of the anti-arachnidic antivenom. Our results indicate that both antivenoms were effective in terms of neutralization. However, the anti-loxoscelic antivenom was more efficient than the anti-arachnidic. PMID:10400292

  16. Formation of Lignans(-)-Secoisolariciresinol and (-)-Matairesinol with Forsythia intermedia Cell-Free Extracts

    NASA Technical Reports Server (NTRS)

    Umezawa, Toshiaki; Davin, Laurence B.; Lewis, Norman G.

    1991-01-01

    In vivo labeling experiments of Forsythia intermedia plant tissue with [8-(C-14)]- and [9,9-(2)H2,OC(2)H3]coniferyl alcohols revealed that the lignans, (-)-secoisolariciresinol and (-)-matairesinol, were derived from two coniferyl alcohol molecules; no evidence for the formation of the corresponding (+)-enantiomers was found. Administration of (+/-)-[Ar-(H-3)] secoisolariciresinols to excised shoots of F.intermedia resulted in a significant conversion into (-)-matairesinol; again, the (+)-antipode was not detected. Experiments using cell-free extracts of F.intermedia confirmed and extended these findings. In the presence of NAD(P)H and H2O2, the cell-free extracts catalyzed the formation of (-)- secoisolariciresinol, with either [8-(C-14)]- or [9,9-(2)H2,OC(2)H3]coniferyl alcohols as substrates. The (+)- enantiomer was not formed. Finally, when either (-)-[Ar-(H-3)] or (+/-)-[Ar-(H-2)]secoisolariciresinols were used as substrates, in the presence of NAD(P), only (-)- and not (+)-matairesinol formation occurred. The other antipode, (+)-secoisolariciresinol, did not serve as a substrate for the formation of either (+)- or (-)-matairesinol. Thus, in F.intermedia, the formation of the lignan, (-)-secoisolariciresinol, occurs under strict stereochemical control, in a reaction or reactions requiring NAD(P)H and H2O2 as cofactors. This stereoselectivity is retained in the subsequent conversion into (-)-matairesinol, since (+)-secoisolariciresinol is not a substrate. These are the first two enzymes to be discovered in lignan formation.

  17. Ectoparasites of the critically endangered insular cavy, Cavia intermedia (Rodentia: Caviidae), southern Brazil.

    PubMed

    Regolin, André Luis; Furnari, Nina; de Castro Jacinavicius, Fernando; Linardi, Pedro Marcos; de Carvalho-Pinto, Carlos José

    2015-04-01

    Cavia intermedia is a rodent species critically endangered and is found only on a 10 hectare island off the southern Brazilian coast. To identify the ectoparasites of C. intermedia, 27 specimens (14 males and 13 females), representing approximately 65% of the estimated total population, were captured and examined. A total of 1336 chewing lice of two species were collected: Gliricola lindolphoi (Amblycera: Gyropidae) and Trimenopon hispidum (Amblycera: Trimenoponidae). In addition, chiggers Arisocerus hertigi (Acari: Trombiculidae) and Eutrombicula sp. (Acari: Trombiculidae) were collected from the ears of all captured animals. This low species richness compared to those for other Cavia species is expected for island mammals. Although the results presented here are not conclusive about the relationship between C. intermedia and ectoparasites, this low species richness found might be reflected in a low level of investment by the hosts in the basal immune defense, since investments in white blood cell production by mammals are influenced by the diversity of parasites in the environment. Additionally, considering that it might result in host vulnerability to other parasites that might be introduced through exotic or migratory host species, the monitoring of C. intermedia, including parasitological and immunological assessments, is recommended as a key component of conservation efforts. PMID:25830106

  18. Composition, Cytotoxic and Antimicrobial Activities of Satureja intermedia C.A.Mey Essential Oil

    PubMed Central

    Sharifi-Rad, Javad; Sharifi-Rad, Mehdi; Hoseini-Alfatemi, Seyedeh Mahsan; Iriti, Marcello; Sharifi-Rad, Majid; Sharifi-Rad, Marzieh

    2015-01-01

    In this study, the essential oil (EO) constituents from the aerial parts of Satureja intermedia C.A.Mey were detected by GC and GC/MS. The antimicrobial activity of EO on oral pathogens and its cytotoxicity to human cancer cells were determined by the microbroth dilution method and the crystal violet staining method, respectively. Thirty-nine compounds were identified and the main EO constituents were γ-terpinene (37.1%), thymol (30.2%), p-cymene (16.2%), limonene (3.9%), α-terpinene (3.3%), myrcene (2.5%), germacrene B (1.4%), elemicine (1.1%) and carvacrol (0.5%). The S. intermedia EO showed a concentration-dependent decrease in viability of Hep-G2 (hepatocellular carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines (p < 0.05). Antimicrobial screening of S. intermedia EO demonstrated slight antibacterial and antifungal activities against Streptococcus mutants, S. salivarius, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and C. glabrata. Further preclinical studies are needed to assess the efficacy and safety of S. intermedia EO as a new promising anticancer agent. PMID:26247936

  19. Production of poly-3-hydroxybutyrate (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) from synthetic wastewater using Hydrogenophaga palleronii.

    PubMed

    Venkateswar Reddy, M; Mawatari, Yasuteru; Yajima, Yuka; Satoh, Kohki; Venkata Mohan, S; Chang, Young-Cheol

    2016-09-01

    In the present study, synthetic wastewater (SW) was used for production of poly-3-hydroxybutyrate (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) using the bacteria Hydrogenophaga palleronii. SW at various volatile fatty acids concentrations (5-60g/l) was evaluated for the growth and biopolymer production using H. palleronii. Substrate degradation was analyzed using total organic carbon (TOC) analyzer and high pressure liquid chromatography (HPLC). H. palleronii showed highest and lowest removal of TOC at 5g/l (88±4%) and 60g/l (15±6%) respectively. Among all the concentrations evaluated, bacteria showed highest biopolymer production with 20g/l (63±5%), followed by 30g/l (58±3%) and 40g/l (56±2%). Lowest biopolymer production was observed at 5g/l concentration (21±3%). Structure, molecular weight, and thermal properties of the produced biopolymer were analyzed. These results denoted that the strain H. palleronii can be used for degradation of high concentration of volatile fatty acids persistent in wastewaters and their subsequent conversion into useable biopolymers. PMID:26995321

  20. Perianesthetic development of diaphragmatic hernia in a horse with equine pituitary pars intermedia dysfunction (PPID)

    PubMed Central

    Shepard, Molly K.; Lee, Wesley L.; Eggleston, Randy B.

    2015-01-01

    A 21-year-old Thoroughbred gelding with a history of equine pituitary pars intermedia dysfunction (PPID) presented with priapism of 2 days’ duration. The horse received a caudal morphine epidural and then underwent corpus cavernosum lavage and phallectomy under general anesthesia. The patient’s recovery featured multiple unsuccessful attempts to stand and his respiratory distress persisted for several hours until he acutely developed severe colic and was euthanized. Necropsy findings revealed a pituitary adenoma of the pars intermedia, bilateral adrenal cortical hyperplasia, and diaphragmatic herniation. This report suggests that horses with PPID may present a greater risk for diaphragmatic hernia under general anesthesia or during procedures placing stress on the diaphragm, including anesthetic recovery. PMID:25565714

  1. Chemical control of Loxosceles intermedia (Araneae: Sicariidae) with pyrethroids: field and laboratory evaluation.

    PubMed

    Navarro-Silva, M A; Duque, J E L; Ramires, E N; Andrade, C F S; Marques-da-Silva, E; Marques, F A; Delay, C E; Fontana, J D; Silva, A C S; Fraguas, G M

    2010-02-01

    Bites from the recluse or brown spiders (genus Loxosceles) can cause necrotic lesions and systemic effects in humans throughout the world. In the state of Paraná, Brazil, loxoscelism is considered a serious public health problem, and Loxosceles intermedia Mello-Leitão (Araneae: Sicariidae) is associated with the majority of reported accidents. In the present research we evaluated the susceptibility of L. intermedia to pyrethroid insecticides currently used for the control of spiders in both field and laboratory conditions. In laboratory tests, the most active pesticides in descending order were microencapsulated lambda-cyhalothrin (LC50 = 0.023 mg/kg), nonmicroencapsulated lambda-cyhalothrin (LC50 = 0.047 mg/kg), deltamethrin (LC50 = 0.26 mg/kg), and cypermethrin (LC50 = 1.38 mg/kg). Cockroaches, Phoetalia circumvagans (Burmeister) (n = 30), killed with microencapsulated lambdacyalothrin, were offered to the spiders. L. intermedia fed on 63.3% of the dead cockroaches during the first 6 h of experiment; none of the spiders died during the subsequent 15 d. Microencapsulated lambdacyalothrin was chosen for application in two contiguous houses. The mean volume applied was 22.8 mg (AI)/m2. Dead spiders were found during all the inspections up to 60 d after the initial application. In total, 297 dead spiders were collected; 65.7% in the attic shared by the two homes, 10.8% inside the house that had most cracks and crevices sealed and 23.6% in the control house. The use of lambda-cyhalothrin-based products for L. intermedia control is discussed. PMID:20214382

  2. Cleavage of CD14 and LBP by a protease from Prevotella intermedia

    PubMed Central

    Deschner, James; Singhal, Anuradha; Long, Ping; Liu, Chau-Ching; Piesco, Nicholas

    2016-01-01

    Periodontitis is an inflammatory disease caused by subgingival microorganisms and their components, such as lipopolysaccharide (LPS). Responses of the host to LPS are mediated by CD14 and LPS-binding protein (LBP). In this study, it was determined that proteases from a periodontal pathogen, Prevotella intermedia, cleave CD14 and LBP, and thereby modulate the virulence of LPS. Culture supernatants from two strains of P. intermedia (ATCC 25611 and 25261) cleaved CD14 and LBP in a concentration-dependent manner. Zymographic and molecular mass analysis revealed the presence of a membrane-associated, 170-kDa, monomeric protease. Class-specific inhibitors and stimulators demonstrated that this enzyme is a metal-requiring, thiol-activated, cysteine protease. The protease was stable over a wide range of temperatures (4–56 °C) and pH values (4.5–8.5). This enzyme also decreased the expression of interleukin-1β (IL-1β)-specific mRNA in the LPS-activated macrophage-like cell lines U937 and THP-1 in a concentration-dependent manner, indicating that it also cleaves membrane-associated CD14. Furthermore, addition of soluble CD14 abrogated protease-mediated inhibition of IL-1 mRNA expression induced by LPS. The observations suggest that proteolysis of CD14 and LBP by P. intermedia protease might modulate the virulence of LPS at sites of periodontal infections. PMID:12728301

  3. A novel expression profile of the Loxosceles intermedia spider venomous gland revealed by transcriptome analysis.

    PubMed

    Gremski, Luiza Helena; da Silveira, Rafael Bertoni; Chaim, Olga Meiri; Probst, Christian Macagnan; Ferrer, Valéria Pereira; Nowatzki, Jenifer; Weinschutz, Hellen Chris; Madeira, Humberto Maciel; Gremski, Waldemiro; Nader, Helena Bonciani; Senff-Ribeiro, Andrea; Veiga, Silvio Sanches

    2010-12-01

    Spiders of the Loxosceles genus are cosmopolitan, and their venom components possess remarkable biological properties associated with their ability to act upon different molecules and receptors. Accidents with Loxosceles intermedia specimens are recognized as a public health problem in the south of Brazil. To describe the transcriptional profile of the L. intermedia venom gland, we generated a wide cDNA library, and its transcripts were functionally and structurally analyzed. After initial analyses, 1843 expressed sequence tags (ESTs) produced readable sequences that were grouped into 538 clusters, 281 of which were singletons. 985 reads (53% of total ESTs) matched to known proteins. Similarity searches showed that toxin-encoding transcripts account for 43% of the total library and comprise a great number of ESTs. The most frequent toxins were from the LiTx family, which are known for their insecticidal activity. Both phospholipase D and astacin-like metalloproteases toxins account for approximately 9% of total transcripts. Toxins components such as serine proteases, hyaluronidases and venom allergens were also found but with minor representation. Almost 10% of the ESTs encode for proteins involved in cellular processes. These data provide an important overview of the L. intermedia venom gland expression scenario and revealed significant differences from profiles of other spiders from the Loxosceles genus. Furthermore, our results also confirm that this venom constitutes an amazing source of novel compounds with potential agrochemical, industrial and pharmacological applications. PMID:20644878

  4. Method for qualifying microbial removal performance of 0.1 micron rated filters. Part II: preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for use as a standard challenge organism to qualify 0.1 micron rated filters.

    PubMed

    Sundaram, S; Eisenhuth, J; Steves, M; Howard, G; Brandwein, H

    2001-01-01

    In this article, we report on the preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for potential use as a standard challenge organism to qualify 0.1 microm rated filters. Filter-cloned H. pseudoflava (ATCC 700892) was easily cultured in a low nutrient broth (R2A broth) under standard laboratory conditions, reaching high titers of 10(8)-10(9) cfu/mL within 48-65 hours of incubation at 25+/-5 degrees C. Under these conditions, H. pseudoflava is a rod-shaped bacterium, averaging 0.25+/-0.03 microm by 1.65+/-0.35 microm, and appears to be smaller than Brevundimonas diminuta in width (0.31+/-0.03 microm), but somewhat longer in length (0.88+/-0.19 microm), which may partly explain the observed penetration. In total, thirty-five 0.2/0.22 microm rated filter discs, spanning five different "sterilizing grade" filter types from two different filter manufacturers were challenged with H. pseudoflava. In all cases, H. pseudoflava was shown to consistently penetrate every 0.2/0.22 microm rated filter disc tested. These tests also spanned three different challenge durations, including short-term challenges (30-40 minutes), and two different challenge fluids. The use of serial (double) 0.22 mm rated filters, which is a common industry practice to reduce the prefiltration bioburden to the final "sterilizing" filter, was also shown to be inadequate to fully retain H. pseudoflava under the challenge condition used. In contrast, two different 0.1 microm rated filter types functionally qualified with a specified high titer reduction claim for Acholeplasma laidlawii, were shown to consistently and fully retain H. pseudoflava, and retention by these two filter types was shown to be robust and independent of the challenge duration. PMID:11766823

  5. Newly Installed S-1 Truss

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Launched October 7, 2002 aboard the Space Shuttle Orbiter Atlantis, the STS-112 mission lasted 11 days and performed three sessions of Extra Vehicular Activity (EVA). Its primary mission was to install the Starboard (S1) Integrated Truss Structure and Equipment Translation Aid (CETA) Cart to the International Space Station (ISS). The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss, attached to the S0 (S Zero) truss installed by the previous STS-110 mission, flows 637 pounds of anhydrous ammonia through three heat rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA is the first of two human-powered carts that will ride along the International Space Station's railway providing a mobile work platform for future extravehicular activities by astronauts. This is a view of the newly installed S1 Truss as photographed during the mission's first scheduled EVA. The Station's Canadarm2 is in the foreground. Visible are astronauts Piers J. Sellers (lower left) and David A. Wolf (upper right), both STS-112 mission specialists.

  6. Intermedia transfer factors for fifteen toxic pollutants released to air basins in California

    SciTech Connect

    McKone, T.E.; Daniels, J.I.; Chiao, F.F.; Hsieh, D.P.H.

    1993-10-01

    This report provides a summary definition of the intermedia-transfer factors (ITFs). Methods are discussed for estimating these parameters in the absence of measured values, and the estimation errors inherent in these estimation methods are considered. A detailed summary is provided of measured and estimated ITF values for fifteen air contaminants. They include: 1,3 butadiene; cadmium; cellosolve; cellosolve acetate; chloroform; di-2-ethylhexylphthalate; 1,4-dioxame; hexachlorobenzene; inorganic arsenic; inorganic lead; nickel; tetrachloroethylene; toluene; toluene-2,4-diisocyanate; and 1,3-xylene. Recommendations are made regarding the expected value and variance in these values for use in exposure models.

  7. Method for qualifying microbial removal performance of 0.1 micron rated filters. Part III: bacterial challenge tests on 0.2/0.22 and 0.1 micron rated filter cartridges with Hydrogenophaga (formerly Pseudomonas) pseudoflava.

    PubMed

    Sundaram, S; Eisenhuth, J; Lewis, M; Howard, G; Brandwein, H

    2001-01-01

    We have previously reported on the preliminary characterization of Hydrogenophaga (formerly Pseudomonas) pseudoflava for potential use as a standard challenge organism to qualify 0.1 microm rated filters. This article reports on the retention efficiencies of a large panel of 0.2/0.22 microm and 0.1 microm rated filter cartridges for H. pseudoflava (ATCC 700892) versus the retention capabilities of the same filters for Brevundimonas diminuta (ATCC 19146). A total of thirty-two 0.2/0.22 microm rated filter cartridges, spanning nine different "sterilizing grade" filter types from four different filter manufacturers, were challenged with H. pseudoflava at challenge levels exceeding 10(7) cfu/cm2. H. pseudoflava was shown to penetrate every 0.2/0.22 microm rated filter tested, with log titer reduction (LTR) values ranging from 3.5 to 7.7 logs. H. pseudoflava was shown to be more penetrative than B. diminuta under the same challenge conditions. B. diminuta was fully retained by nineteen of the twenty 0.2/0.22 microm rated filters that were challenged with both organisms. In the case of 0.1 microm rated filters, eighteen filter cartridges, spanning five different filter types from three manufacturers were tested. H. pseudoflava was consistently retained by four out of the five filter types tested, with LTR values in excess of 11.5 to 12.2 logs. The 0.1 microm rated filter type that was penetrated by H. pseudoflava has been previously demonstrated to be not fully retentive for naturally occurring bacteria. The data show that H. pseudoflava penetrates 0.2/0.22 microm rated filters just as readily as B. diminuta penetrates 0.45 microm rated filters. In addition, titer reductions provided by 0.2/0.22 microm rated filters for H. pseudoflava are comparable to those reported for A. laidlawii mycoplasma, albeit under different conditions. This study demonstrates that H. pseudoflava meets all criteria for use as a standard organism for qualifying the microbial removal performance

  8. Early changes in the ultrastructure of the pars intermedia of the pituitary of Xenopus laevis after change of background color.

    PubMed

    Volcanes, B D; Weatherhead, B

    1976-01-01

    Stereological analysis of the secretory cells of the pars intermedia of Xenopus laevis over a period of 3 days following the transfer of animals from a white to a black background has revealed that significant alterations in the ultrastructural appearance of these cells can be detected 8 h after the transfer. In particular, changes in the secretory granules and the rough endoplasmic reticulum were found to correlate well with previous reports concerning the melanocyte-stimulating hormone (MSH) content and the capacity for protein synthesis of the pars intermedia. PMID:1028946

  9. Prevalence of Pulmonary Hypertension in Patients with Thalassemia Intermedia in 2009: a single center’s experience

    PubMed Central

    Moghaddam, Hassan Mottaghi; Badiei, Zahra; Eftekhari, Kambiz; Shakeri, Reza; Farhangi, Hamid

    2015-01-01

    Background: There are various clinical symptoms of thalassemia intermedia, and they lie roughly between those of major and minor forms of the disease. Patients with thalassemia intermedia occasionally require blood transfusions. This renders them susceptible to pulmonary arterial hypertension (PAH) syndrome, which is one of the most significant complications in patients with thalassemia intermedia. PAH is more common in in thalassemia intermedia than in thalassemia major, and it may cause cardiac complications in patients who are older than 30. The objective of this study was to estimate the prevalence of PAH in thalassemia intermedia patients so that they can be referred expeditiously for treatment, thereby preventing the complications that occur later. Methods: This cross sectional study was conducted under the supervision of hematology department of Mashhad Medical University. Forty-one patients with thalassemia intermedia were examined at the Sarvar Thalassemia and Hemophilia Clinic of Mashhad. Electrocardiography, chest radiography, and echocardiography tests were performed for all of the patients by the same pediatric cardiologist. The data were processed by SPSS software, version 11.5, and the results were analyzed using chi-squared, Student’s t, and Mann-Whitney tests. Results: The mean age of the patients was 21.93±8.34. They had been under pediatric heart specialists’ constant examination and treatment since their childhood when they were diagnosed with TI, and continue to receive regular follow-up care. The prevalence of pulmonary hypertension was 24% in our study population. In patients with thalassemia intermedia, the left ventricular (LV) mass indices were about 3–5 times higher than would be expected in a normal population. Patients with higher LV mass indices have a greater risk of developing pulmonary hypertension, and those with serum ferritin levels below 1000 ng/ml are less susceptible to diastolic dysfunction. Conclusion: Pulmonary

  10. Evaluation of the antioxidant and antimicrobial properties of in vitro cultured Drosera intermedia extracts.

    PubMed

    Grevenstuk, Tomás; Gonçalves, Sandra; Almeida, Sara; Coelho, Natacha; Quintas, Célia; Gaspar, Maria Nelma; Romano, Anabela

    2009-08-01

    Evaluation of the antioxidant activity of the methanol, water and n-hexane extracts of Drosera intermedia, determined by the Folin-Ciocalteau (F-C), trolox equivalent antioxidant capacity (TEAC) and oxygen radical antioxidant capacity (ORAC) assays showed that the methanol extract had the highest antioxidant activity (F-C: 378.6 +/- 31.5 micromol(GAE)/mg(extract); TEAC: 332.2 +/- 29.1 micromol(TE)/mg(extract); ORAC: 64.7 +/- 7.8 micromol(TE)/mg(extract). Antimicrobial activity was tested against seven bacterial and eight yeast strains using the agar diffusion assay, followed by the determination of minimum inhibitory concentrations (MIC). All tested D. intermedia extracts demonstrated strong antimicrobial properties with a broad spectrum of activity. However, the n-hexane extract exhibited much greater activity than water and methanol extracts. The most susceptible microorganisms to the n-hexane extract were Staphylococcus epidermidis ATCC 12228 and Candida albicans YP0175, for which a MIC value of 13.0 microg/mL was scored. PMID:19768984

  11. Role of cin-miR2118 in drought stress responses in Caragana intermedia and Tobacco.

    PubMed

    Wu, Bi-Fei; Li, Wan-Feng; Xu, Hai-Yan; Qi, Li-Wang; Han, Su-Ying

    2015-12-10

    The miR2118 is highly conserved in leguminous plants. Its function is to regulate the expression of genes encoding the TIR-NBS-LRR resistance protein. In this study, cin-miR2118 from Caragana intermedia was functionally characterized, especially with regard to its role in drought stress resistance. Two target genes of cin-miR2118 were predicted and cloned, the occurrence of miR2118 target sequence in both genes indicated that they might be targets of cin-miR2118. We investigated the expression patterns of cin-miR2118 and its target genes in C. intermedia stems and found diverse changes in expression in response to drought stress. CiDR1 was negatively correlated with corresponding miR2118 expression while CiDR2 was positively correlated with cin-miR2118. For further study, induced tolerance was observed in the transgenic Tobacco with overexpression cin-miR2118 upon 140-min water deficiency. And the expression level of cin-miR2118 was dramatically increased under drought stress. These results reveal that cin-miR2118 exert positive effects on drought stress tolerance. In addition, our study unexpectedly found that overexpression of cin-miR2118 in Tobacco can cause phenotype changes, which suggested that cin-miR2118 may have a novel function as a growth regulator in Tobacco. PMID:26216304

  12. Cumberlandian Mollusk Conservation Program. Activity 8: analysis of macrofauna factors. [Conradilla caelata; quadrula intermedia

    SciTech Connect

    Barr, W.C.; Ahlstedt, S.A.; Hickman, G.D.; Hill, D.M.

    1986-02-01

    This study provides information that may be critical to the continued survival of the mussels Conradilla caelata and Qadrula intermedia in several rivers throughout the region. The biotic components of several river reaches that have populations of these endangered species were examined to determine what biotic attributes were different from those study reaches that did not have these mussels. In all cases the quantity and quality of the benthos would be considered adequate to sustain those consumers, in this case fish, that are necessary to assure continuation of the mussel community. If fish other than Etheostoma zonale (banded darter) are determined to be acceptable hosts for either Conradilla caelata or Qadrula intermedia then there will probably be adequate numbers at each potential transplant site to accomplish reproduction. During this study we have determined that the benthic macrofauna at all sites is adequate, and supports a fish assemblage of considerable diversity and abundance, hence it is probable that adequate fish hosts are available to accommodate a complex mussel fauna.

  13. Cloning of a sesquiterpene synthase from Lavandula x intermedia glandular trichomes.

    PubMed

    Sarker, Lukman S; Demissie, Zerihun A; Mahmoud, Soheil S

    2013-11-01

    The essential oil (EO) of Lavandula is dominated by monoterpenes, but can also contain small amounts of sesquiterpenes, depending on species and environmental conditions. For example, the sesquiterpene 9-epi-caryophyllene can make up to 8 % of the EO in a few species, including those commercially propagated for EO production. Here, we report the cloning and functional characterization of 9-epi-caryophyllene synthase (LiCPS) from the glandular trichomes of Lavandula x intermedia, cv. Grosso. The 1,617 bp open reading frame of LiCPS, which did not encode a transit peptide, was expressed in Escherichia coli and the recombinant protein purified by Ni-NTA agarose affinity chromatography. The ca. 60 kDa recombinant protein specifically converted farnesyl diphosphate to 9-epi-caryophyllene. LiCPS also produced a few monoterpenes when assayed with the monoterpene precursor geranyl diphosphate (GPP), but--unlike most monoterpene synthases--was not able to derive detectable amounts of any products from the cis isomer of GPP, neryl diphosphate. The LiCPS transcripts accumulated in developing L. x intermedia flowers and were highly enriched in glandular trichomes, but were not detected in leaves suggesting that the transcriptional expression of this gene is spatially and developmentally regulated. PMID:23918183

  14. Noninvasive analysis of skin iron and zinc levels in beta-thalassemia major and intermedia

    SciTech Connect

    Gorodetsky, R.; Goldfarb, A.; Dagan, I.; Rachmilewitz, E.A.

    1985-01-01

    Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r . 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent of iron deposition in major parenchymal organs. Repeated DXS examinations of the skin could monitor the clearance of iron from the tissues of patients with iron overload in the course of therapy with chelating agents.

  15. In vitro sensitivity of poultry Brachyspira intermedia isolates to essential oil components and in vivo reduction of Brachyspira intermedia in rearing pullets with cinnamaldehyde feed supplementation.

    PubMed

    Verlinden, M; Pasmans, F; Mahu, M; Vande Maele, L; De Pauw, N; Yang, Z; Haesebrouck, F; Martel, A

    2013-05-01

    Cecal enteritis due to Brachyspira infections tends to be chronic in laying hens. Limited availability of antimicrobial drugs for use in laying hens emphasizes the need for alternative control measures. A broth microdilution method was used to determine the antimicrobial susceptibility of 20 Brachyspira intermedia field isolates from laying hen flocks to components of essential oils (EO). Minimal inhibitory concentration (MIC) distributions, obtained for 8 EO components, were all monomodal. Cinnamaldehyde had the lowest MIC values (40 to 80 mg/L), followed by nerolidol, capsaicin, carvacrol, and thymol (80 to 320 mg/L), eugenol (160 to 640 mg/L), and linalool (320 to 1,280 mg/L). The MIC ranges of piperine were mostly above the test range of 1,280 mg/L. In an in vivo experiment, coated trans-cinnamaldehyde was supplemented to the feed of rearing pullets. A completely randomized experimental design with 4 treatments and 3 replicates each (replicate = group of seven 1-d-old laying hen chickens) was applied. The negative and positive controls received a conventional feed during the whole trial. The positive controls were orally inoculated on 3 consecutive days (d 22, 23, and 24) with 1 mL of 1.0 × 10(8) cfu/mL of a B. intermedia field isolate. Two treatment groups (preventive and curative), identically inoculated, received the coated trans-cinnamaldehyde-supplemented feed (500 mg/kg of trans-cinnamaldehyde), the preventive group from d 1, the curative from d 25. On d 32, ceca were collected for bacteriologic Brachyspira enumeration. The mean enumeration of Brachyspira cells was decreased (P < 0.05) in the curative treated group versus the positive control group. The in vitro results of the present study demonstrate the potential of EO components as antimicrobials against poultry Brachyspira isolates, including isolates with acquired resistance for classic antimicrobial drugs. Reduction of Brachyspira colonization in young pullets was obtained, in a curative way, in

  16. Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

    PubMed

    Fteita, Dareen; Könönen, Eija; Gürsoy, Mervi; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2015-12-01

    Initiation and development of pregnancy-associated gingivitis is seemingly related to the microbial shift towards specific gram-negative anaerobes in subgingival biofilms. It is known that Prevotella intermedia sensu lato is able to use estradiol as an alternative source of growth instead of vitamin K. The aim of the present study was to investigate the impact of estradiol on the bacterial dipeptidyl peptidase IV (DPPIV) enzyme activity in vitro as a virulent factor of the Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, Prevotella pallens, and Prevotella aurantiaca. In all experiments, 2 strains of each Prevotella species were used. Bacteria were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol and were allowed to build biofilms at an air-solid interface. DPPIV activities of biofilms were measured kinetically during 20 min using a fluorometric assay. The enzyme activity was later related to the amount of protein produced by the same biofilm, reflecting the biofilm mass. Estradiol significantly increased DPPIV activities of the 8 Prevotella strains in a strain- and dose-dependent manner. In conclusion, our in vitro experiments indicate that estradiol regulates the DPPIV enzyme activity of P. intermedia, P. nigrescens, P. pallens, and P. aurantiaca strains differently. Our results may, at least partly, explain the role of estradiol to elicit a virulent state which contributes to the pathogenesis of pregnancy-related gingivitis. PMID:26386229

  17. Complete genome sequence of Brachyspira intermedia reveals unique genomic features in Brachyspira species and phage-mediated horizontal gene transfer

    PubMed Central

    2011-01-01

    Background Brachyspira spp. colonize the intestines of some mammalian and avian species and show different degrees of enteropathogenicity. Brachyspira intermedia can cause production losses in chickens and strain PWS/AT now becomes the fourth genome to be completed in the genus Brachyspira. Results 15 classes of unique and shared genes were analyzed in B. intermedia, B. murdochii, B. hyodysenteriae and B. pilosicoli. The largest number of unique genes was found in B. intermedia and B. murdochii. This indicates the presence of larger pan-genomes. In general, hypothetical protein annotations are overrepresented among the unique genes. A 3.2 kb plasmid was found in B. intermedia strain PWS/AT. The plasmid was also present in the B. murdochii strain but not in nine other Brachyspira isolates. Within the Brachyspira genomes, genes had been translocated and also frequently switched between leading and lagging strands, a process that can be followed by different AT-skews in the third positions of synonymous codons. We also found evidence that bacteriophages were being remodeled and genes incorporated into them. Conclusions The accessory gene pool shapes species-specific traits. It is also influenced by reductive genome evolution and horizontal gene transfer. Gene-transfer events can cross both species and genus boundaries and bacteriophages appear to play an important role in this process. A mechanism for horizontal gene transfer appears to be gene translocations leading to remodeling of bacteriophages in combination with broad tropism. PMID:21816042

  18. Desarrollo curricular, conciencia ambiental y tecnologia para estudiantes de intermedia: Una investigacion en accion

    NASA Astrophysics Data System (ADS)

    Rodriguez Ramos, Teresita

    Se llevó a cabo una investigación en acción con los propósitos de 1) documentar las relaciones de las tecnologías de la información y la comunicación en las clases de ciencias de escuela intermedia como elemento de apoyo cuando se aborda el tema ambiental y sus conceptos pertinentes, a partir de las observaciones de la investigadora, así como las entrevistas y diarios reflexivos de los estudiantes de una escuela intermedia en la zona metropolitana, y luego 2) diseñar una unidad instruccional sobre el tema ambiental que integre actividades tecnologías para el curso de ciencias de la escuela intermedia según el modelo PROCIC y las observaciones que hayan iniciado los estudiantes participantes. Finalmente, se plantearon las implicaciones educativas para el currículo del Programa de Ciencias al instrumentar este modelo de unidad mediante PROCIC, e integrado la tecnología y el tema ambiental. Los hallazgos se analizaron y se categorizaron de acuerdo con las preguntas de investigación. El hallazgo principal de la investigación aborda las cuatro relaciones centrales en las que se articula la utilización de las tecnologías y sus aplicaciones en la clase de ciencias. Estas cuatro relaciones que recogen la posición de los estudiantes son: 1) Perspectiva de los estudiantes hacia la tecnología. 2) Participación de los estudiantes en los aspectos docentes. 3) Aprendizaje estudiantil sobre el ambiente, y 4) Conciencia ambiental en relación con la vida diaria. Estas relaciones ponen de manifiesto,cómo se plantea en las implicaciones, la necesidad de más investigación en acción en la sala de clases, la importancia—como tema transversal—de la conciencia ambiental mediante la tecnología al construir conocimientos significativos dentro y fuera de la escuela, asó como, valorar la investigación y la dialogicidad en la sala de clases como actividades que obligan al reexamen de la práctica didáctica en su formas curriculares de objetivos, recursos

  19. Different Water Use Strategies of Juvenile and Adult Caragana intermedia Plantations in the Gonghe Basin, Tibet Plateau

    PubMed Central

    Jia, Zhiqing; Zhu, Yajuan; Liu, Liying

    2012-01-01

    Background In a semi-arid ecosystem, water is one of the most important factors that affect vegetation dynamics, such as shrub plantation. A water use strategy, including the main water source that a plant species utilizes and water use efficiency (WUE), plays an important role in plant survival and growth. The water use strategy of a shrub is one of the key factors in the evaluation of stability and sustainability of a plantation. Methodology/Principal Findings Caragana intermedia is a dominant shrub of sand-binding plantations on sand dunes in the Gonghe Basin in northeastern Tibet Plateau. Understanding the water use strategy of a shrub plantation can be used to evaluate its sustainability and long-term stability. We hypothesized that C. intermedia uses mainly deep soil water and its WUE increases with plantation age. Stable isotopes of hydrogen and oxygen were used to determine the main water source and leaf carbon isotope discrimination was used to estimate long-term WUE. The root system was investigated to determine the depth of the main distribution. The results showed that a 5-year-old C. intermedia plantation used soil water mainly at a depth of 0–30 cm, which was coincident with the distribution of its fine roots. However, 9- or 25-year-old C. intermedia plantations used mainly 0–50 cm soil depth water and the fine root system was distributed primarily at soil depths of 0–50 cm and 0–60 cm, respectively. These sources of soil water are recharged directly by rainfall. Moreover, the long-term WUE of adult plantations was greater than that of juvenile plantations. Conclusions The C. intermedia plantation can change its water use strategy over time as an adaptation to a semi-arid environment, including increasing the depth of soil water used for root growth, and increasing long-term WUE. PMID:23029303

  20. Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors

    PubMed Central

    Barbosa, Graziela Murta; Colombo, Andrea Vieira; Rodrigues, Paulo Henrique; Simionato, Maria Regina Lorenzetti

    2015-01-01

    It is well known that strain and virulence diversity exist within the population structure of Porphyromonas gingivalis. In the present study we investigate intra- and inter-species variability in biofilm formation of Porphyromonas gingivalis and partners Prevotella intermedia and Prevotella nigrescens. All strains tested showed similar hydrophobicity, except for P. gingivalis W83 which has roughly half of the hydrophobicity of P. gingivalis ATCC33277. An intraspecies variability in coaggregation of P. gingivalis with P. intermedia was also found. The association P. gingivalis W83/P. intermedia 17 produced the thickest biofilm and strain 17 was prevalent. In a two-compartment system P. gingivalis W83 stimulates an increase in biomass of strain 17 and the latter did not stimulate the growth of P. gingivalis W83. In addition, P. gingivalis W83 also stimulates the growth of P. intermedia ATCC25611 although strain W83 was prevalent in the association with P. intermedia ATCC25611. P. gingivalis ATCC33277 was prevalent in both associations with P. intermedia and both strains of P. intermedia stimulate the growth of P. gingivalis ATCC33277. FISH images also showed variability in biofilm structure. Thus, the outcome of the association P. gingivalis/P. intermedia seems to be strain-dependent, and both soluble factors and physical contact are relevant. The association P. gingivalis-P. nigrescens ATCC33563 produced larger biomass than each monotypic biofilm, and P. gingivalis was favored in consortia, while no differences were found in the two-compartment system. Therefore, in consortia P. gingivalis-P. nigrescens physical contact seems to favor P. gingivalis growth. The intraspecies variability found in our study suggests strain-dependence in ability of microorganisms to recognize molecules in other bacteria which may further elucidate the dysbiosis event during periodontitis development giving additional explanation for periodontal bacteria, such as P. gingivalis and P

  1. Pituitary pars intermedia dysfunction (equine Cushing’s disease) in a Thoroughbred stallion: a single report

    PubMed Central

    HATAZOE, Takashi; KAWAGUCHI, Hiroaki; HOBO, Seiji; MISUMI, Kazuhiro

    2016-01-01

    ABSTRACT Equine pituitary pars intermedia dysfunction (PPID) generally occurs in older horses showing hirsutism, delayed molting, weight loss, polydipsia, polyuria, laminitis, and reproductive disorders (in broodmares), but there have been no reports on stallions. This report presents a case of a 21-year-old Thoroughbred stallion that developed hirsutism and experienced delayed molting. There were no abnormal findings for semen quality or the stallion’s sexual desire. The horse was diagnosed with PPID based on dexamethasone suppression test and plasma levels of adrenocorticotropic hormone. It was then medicated with pergolide mesylate. Since the horse died due to humerus fracture, an autopsy was conducted, and pituitary adenoma was confirmed. No pathological findings were defined in the testicles; therefore, reproductive activity might not have been impaired. PMID:26858577

  2. Ivy sign in mildly symptomatic β-thalassemia intermedia, with development of moyamoya disease.

    PubMed

    El Beltagi, Ahmed H; El-Sheikh, Ahmed; El-Saif, Reem; Norbash, Alexander

    2014-02-01

    Cerebrovascular occlusive disease with secondary proliferative angiogenesis can be idiopathic as a standalone disease state, known as moyamoya disease, or it may develop secondary to different disease entities, such as chronic hemoglobinopathies, in which case it is known as moyamoya syndrome. Although moyamoya syndrome has been well described with sickle cell anemia, its association with other hemoglobinopathies is rarely reported. We describe a 16-year-old girl with β-thalassemia intermedia who presented with recurrent headaches and focal seizures non-responsive to medical treatment. Magnetic resonance imaging showed diffuse intrasulcal bright signal intensity on fluid-attenuated inversion recovery and leptomeningeal enhancement previously termed the "ivy sign", and her magnetic resonance angiography was consistent with bilateral moyamoya disease. The literature describing and explaining the pathogenesis of the "ivy sign" and its relationship to moyamoya disease was reviewed. PMID:24571831

  3. Purification and partial characterization of an elastolytic serine protease of Prevotella intermedia.

    PubMed Central

    Shibata, Y; Fujimura, S; Nakamura, T

    1993-01-01

    Elastolytic strains of Prevotella intermedia were isolated from pus samples of adult periodontal lesions. Elastase was found to associate with envelope, and it could be solubilized with guanidine-HCl. The enzyme was purified to homogeneity by sequential procedures including ion-exchange chromatography, gel filtration, and hydrophobic interaction chromatography. This elastase was a serine protease, and its mass was 31 kDa. It hydrolyzed elastin powder, but collagen and azodye-conjugated proteins were not degraded by this enzyme. Both synthetic substrates for human pancreatic (glutaryl-L-alanyl-L-alanyl-L-prolyl-L-leucine p-nitroanilide) and leukocyte elastase (methoxy succinyl-L-alanyl-alanyl-L-prolyl-L-valine p-nitroanilide) were hydrolyzed. Images PMID:8357246

  4. Complications of β-thalassemia intermedia in Iran during 1996-2010 (single-center study).

    PubMed

    Rafsanjani, Khadijeh Arjmandi; Mafi, Negar; Tafreshi, R Isa

    2011-09-01

    Patients with thalassemia intermedia (TI) experience many complications, of which the incidence varies greatly among cases. Considering the high prevalence of thalassemia in Iran, the study was carried out to determine the frequency of TI complications in Iranian patients and to find possible risk factors for each of them. Using the sampling method of "census," the authors included 153 patients who were seen in their tertiary hematology clinic with the diagnosis of TI during 1996-2010; an analytical cross-sectional study was performed and the data was analyzed by SPSS software using univariate and regression analyses. Mean age of the patients at the time of the study was 17.4 years and 36.5% were receiving transfusions (regularly or occasionally). Mean hemoglobin was 9.2 g/dL and mean serum ferritin was 858 ng/mL. Splenectomy was performed in 46.9% and it was correlated with age and the age at diagnosis in regression analysis. Cholelithiasis was found in 25.5% and was correlated with age and history of splenectomy. Pulmonary hypertension, detected in 23.5%, was correlated with thrombocytosis and mitral valve regurgitation in univariate analysis. Endocrine disease (hypogonadism, hypothyroidism, and adrenal insufficiency) was detected in 8% of the patients. In univariate analysis, endocrine disease was correlated with age of the patients. Regarding bone density of the spine, 53% of cases had osteoporosis. Thrombocytosis was present in 42% of patients and was correlated with their age. Since the severity of thalassemia intermedia vary greatly among patients, a careful evaluation of clinical, laboratory, and genetic aspects is necessary to differentiate TI in a patient at presentation. Moreover, TI patients should be carefully followed up for early detection and management of newly developed complications. The authors also suggest confirmatory controlled studies with larger sample sizes to assist in developing guidelines for surveillance and treatment of TI. PMID

  5. Characterization of Brown spider (Loxosceles intermedia) hemolymph: cellular and biochemical analyses.

    PubMed

    Bednaski, A V; Trevisan-Silva, D; Matsubara, F H; Boia-Ferreira, M; Olivério, M M; Gremski, L H; Cavalheiro, R P; De Paula, D M B; Paredes-Gamero, E J; Takahashi, H K; Toledo, M S; Nader, H B; Veiga, S S; Chaim, O M; Senff-Ribeiro, A

    2015-05-01

    This is the first study on the hemolymph from a spider of the Loxosceles genus. These animals are responsible for a great number of envenomation cases worldwide. Several studies on Loxosceles venoms have been published, and the knowledge about the venom and its toxins is considerable, not only regarding the biological and biochemical characterization, but also regarding structural, genetic and phylogenetic approaches. However, the literature on Loxosceles hemolymph is nonexistent. The main goal of the present study was to characterize biochemically the hemolymph content, and especially, to identify its different hemocytes. Moreover, many papers have already shown molecules whose source is the hemolymph and their very interesting activities and biomedical applications, for example, antifungal and antibacterial activities. A 2D-SDS-PAGE of brown spider hemolymph showed approximately 111 spots for pH 3-10 and 150 spots for pH 4-7. A lectin-blotting assay showed that hemolymph carbohydrate residues were similar to those found in venom. Several types of TAG and DAG phospholipids were found in the hemolymph and characterized by HPTLC and mass spectrometry. Four different hemocytes were characterized in Loxosceles intermedia hemolymph: prohemocyte, plasmatocyte, granulocyte and adipohemocyte. This paper opens new possibilities on toxinology, studying an unknown biological material, and it characterizes a source of molecules with putative biotechnological applications. PMID:25720299

  6. Old fronds serve as a vernal carbon source in the wintergreen fern Dryopteris intermedia (Aspleniaceae).

    PubMed

    Tessier, Jack T; Bornn, Matthew P

    2007-01-01

    Maintaining green leaves beyond the growing season has been hypothesized to benefit plants by supplying either a nutrient or a carbon source. Understanding such ecophysiological aspects of plants will help us to appreciate how a species functions in its environment and predict how it might be affected by future changes in that environment. The wintergreen fern species Dryopteris intermedia does not retranslocate nitrogen and phosphorus from old fronds in spring, but photosynthesis does take place in the old fronds during this season. To determine if carbon fixed in the old fronds is translocated to other parts of the plant, we labeled old fronds with (13)C via photosynthetic uptake and examined old fronds, new fronds, fine roots, and rhizomes for (13)C content 1 day and 1 month after labeling the old fronds. Vernally fixed carbon was translocated to the new fronds but not significantly to the below ground tissues. Old fronds in this species, therefore, serve as a carbon source for vernal growth of new fronds. This is the first study in which a fern was labeled with (13)C to track vernally fixed carbon from old fronds to the rest of the plant in a wintergreen species. Future research should examine the precise timing of this carbon movement and examine other species for a similar or contrasting strategy. PMID:21642204

  7. A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A

    PubMed Central

    Mallorquí-Fernández, Noemí; Manandhar, Surya P.; Mallorquí-Fernández, Goretti; Usón, Isabel; Wawrzonek, Katarzyna; Kantyka, Tomasz; Solà, Maria; Thøgersen, Ida B.; Enghild, Jan J.; Potempa, Jan; Gomis-Rüth, F.Xavier

    2009-01-01

    Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defences and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and its self-processed mature form. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin and a latency flap in the zymogen. Dramatic rearrangement of up to 20Å of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain. PMID:17993455

  8. Rapid detection of Actinobacillus actinomycetemcomitans, Prevotella intermedia and Porphyromona gingivalis by multiplex PCR.

    PubMed

    García, L; Tercero, J C; Legido, B; Ramos, J A; Alemany, J; Sanz, M

    1998-01-01

    The identification of specific periodontal pathogens by conventional methods, mainly anaerobic cultivation, is difficult, time consuming and even sometimes unreliable. Therefore, a multiplex PCR method for simultaneous detection of Actinobacillus actinomycetemcomitans (A.a.), Porphyromona gingivalis (P.g.) and Prevotella intermedia (P.i.) was developed for rapid and easy identification of these specific bacterial pathogens in subgingival plaque samples. In this paper, there is a detailed description of the oligonucleotide primer selection, DNA extraction and PCR conditions and the sequencing of the amplified products. The locus chosen to be amplified is a highly variable region in the 16S ribosomal DNA. For the development of this technique ATCC cultures and pure cultures from subgingival plaque samples taken from periodontitis patients were used. As an internal positive control a recombinant plasmid was developed. This simple DNA extraction procedure and the DNA amplification and visualization of the amplified product permits the detection of the bacteria in a working day. Thus, this multiplex PCR method is a rapid and effective detection method for specific periodontal pathogens. PMID:9524322

  9. Biosynthesis of silver nanoparticles using Euglena gracilis, Euglena intermedia and their extract.

    PubMed

    Li, Yong; Tang, Xiaoling; Song, Wenshuang; Zhu, Lina; Liu, Xingang; Yan, Xiaomin; Jin, Chengzhi; Ren, Qingguang

    2015-02-01

    Extracellular and intracellular biosynthesis of silver nanoparticles (AgNPs) by Euglena gracilis (EG) strain and Euglena intermedia (EI) strain are reported in this study. The obtained nanoparticles showed an absorption peak approximates 420 nm in the UV-visible spectrum, corresponding to the plasmon resonance of AgNPs. According to the result of inductively coupled plasma-atomic emission spectrometer, the intakes of silver ions by EI and EG are roughly equal. The transmission electron microscope (TEM) analysis of the successful in vivo and in vitro synthesised AgNPs indicated the sizes, ranging from 6 to 24 nm and 15 to 60 nm in diameter, respectively, and a spherical-shaped polydispersal of the particles. The successful formation of AgNPs has been confirmed by energy dispersive X-ray analysis connected to the TEM. The Fourier transform infrared spectroscopy measurements reveal the presence of bioactive functional groups such as amines are found to be the capping and stabilising agents of nanoparticles. To our knowledge, this is the first report where two kinds of Euglena microalga were used as the potential source for in vivo and in vitro biosynthesis of AgNPs. PMID:25650322

  10. CYP2S1: a short review.

    PubMed

    Saarikoski, Sirkku T; Rivera, Steven P; Hankinson, Oliver; Husgafvel-Pursiainen, Kirsti

    2005-09-01

    A new member of the cytochrome P450 superfamily, CYP2S1, has recently been identified in human and mouse. In this paper, we review the data currently available for CYP2S1. The human CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. These genes also show the highest homology to the human CYP2S1. The gene has recently been found to harbor genetic polymorphism. CYP2S1 is inducible by dioxin, the induction being mediated by the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in a manner typical for CYP1 family members. In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene. This points to the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is expressed in epithelial cells of a wide variety of extrahepatic tissues. The highest expression levels have been observed in the epithelial tissues frequently exposed to xenobiotics, e.g., the respiratory, gastrointestinal, and urinary tracts, and in the skin. The observed ubiquitous tissue distribution, as well as the expression of CYP2S1 throughout embryogenesis suggest that CYP2S1 is likely to metabolize important endogenous substrates; thus far, retinoic acid has been identified. In conclusion, CYP2S1 exhibits many features of interest for human health and thus warrants further investigation. PMID:16054184

  11. CYP2S1: A short review

    SciTech Connect

    Saarikoski, Sirkku T. . E-mail: sirkku.saarikoski@ktl.fi; Rivera, Steven P.; Hankinson, Oliver; Husgafvel-Pursiainen, Kirsti

    2005-09-01

    A new member of the cytochrome P450 superfamily, CYP2S1, has recently been identified in human and mouse. In this paper, we review the data currently available for CYP2S1. The human CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. These genes also show the highest homology to the human CYP2S1. The gene has recently been found to harbor genetic polymorphism. CYP2S1 is inducible by dioxin, the induction being mediated by the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in a manner typical for CYP1 family members. In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene. This points to the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is expressed in epithelial cells of a wide variety of extrahepatic tissues. The highest expression levels have been observed in the epithelial tissues frequently exposed to xenobiotics, e.g., the respiratory, gastrointestinal, and urinary tracts, and in the skin. The observed ubiquitous tissue distribution, as well as the expression of CYP2S1 throughout embryogenesis suggest that CYP2S1 is likely to metabolize important endogenous substrates; thus far, retinoic acid has been identified. In conclusion, CYP2S1 exhibits many features of interest for human health and thus warrants further investigation.

  12. Safety assessment for the S-1 Spheromak

    SciTech Connect

    Ellis, R. Jr.; Stencel, J.R.

    1984-02-01

    The S-1 machine is part of the Magnetic Fusion Program. The goal of the Magnetic Fusion Program is to develop and demonstrate the practical application of fusion. S-1 is an experimental device which will provide an essential link in the research effort aiming at the realization of fusion power.

  13. A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich's Hyaluronidase): From Cloning to Functional Characterization

    PubMed Central

    Ferrer, Valéria Pereira; de Mari, Thiago Lopes; Gremski, Luiza Helena; Trevisan Silva, Dilza; da Silveira, Rafael Bertoni; Gremski, Waldemiro; Chaim, Olga Meiri; Senff-Ribeiro, Andrea; Nader, Helena Bonciani; Veiga, Silvio Sanches

    2013-01-01

    Loxoscelism is the designation given to clinical symptoms evoked by Loxosceles spider's bites. Clinical manifestations include skin necrosis with gravitational spreading and systemic disturbs. The venom contains several enzymatic toxins. Herein, we describe the cloning, expression, refolding and biological evaluation of a novel brown spider protein characterized as a hyaluronidase. Employing a venom gland cDNA library, we cloned a hyaluronidase (1200 bp cDNA) that encodes for a signal peptide and a mature protein. Amino acid alignment revealed a structural relationship with members of hyaluronidase family, such as scorpion and snake species. Recombinant hyaluronidase was expressed as N-terminal His-tag fusion protein (∼45 kDa) in inclusion bodies and activity was achieved using refolding. Immunoblot analysis showed that antibodies that recognize the recombinant protein cross-reacted with hyaluronidase from whole venom as well as an anti-venom serum reacted with recombinant protein. Recombinant hyaluronidase was able to degrade purified hyaluronic acid (HA) and chondroitin sulfate (CS), while dermatan sulfate (DS) and heparan sulfate (HS) were not affected. Zymograph experiments resulted in ∼45 kDa lytic zones in hyaluronic acid (HA) and chondroitin sulfate (CS) substrates. Through in vivo experiments of dermonecrosis using rabbit skin, the recombinant hyaluronidase was shown to increase the dermonecrotic effect produced by recombinant dermonecrotic toxin from L. intermedia venom (LiRecDT1). These data support the hypothesis that hyaluronidase is a “spreading factor”. Recombinant hyaluronidase provides a useful tool for biotechnological ends. We propose the name Dietrich's Hyaluronidase for this enzyme, in honor of Professor Carl Peter von Dietrich, who dedicated his life to studying proteoglycans and glycosaminoglycans. PMID:23658852

  14. Ruegeria intermedia sp. nov., a moderately thermophilic bacterium isolated from a coastal hot spring.

    PubMed

    Kämpfer, P; Arun, A B; Rekha, P D; Busse, H-J; Young, C-C; Glaeser, S P

    2013-07-01

    A cream-coloured, Gram-negative, aerobic, non-motile moderately thermophilic, rod-to-irregular-shaped bacterium, CC-GIMAT-2(T), was isolated from a coastal hot spring of Green Island (Lutao), located off Taituang, Taiwan, on marine agar 2216. The 16S rRNA gene sequence analysis and subsequent comparisons showed that it was placed into the genus Ruegeria with 97.4 % similarity to Ruegeria lacuscaerulensis ITI-1157(T), and a lower sequence similarity to all other species of the genus Ruegeria. Reconstruction of phylogenetic trees indicated that strain CC-GIMAT-2(T) clustered within the genus Ruegeria. Robust tree topology for the genus Ruegeria including the new strain was only obtained by including all Rhodobacteraceae type strains but not if the analysis was limited to few selected taxa. The quinone system contained exclusively ubiquinone Q-10 and the fatty acid profile consisted mainly of C18 : 1ω7c, 11-methyl C18 : 1ω7c and C12 : 0 3-OH. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unidentified aminolipid. Other lipids were detected in moderate to minor amounts. The characteristic feature of the polyamine pattern was the predominant triamine spermidine. On the basis of the 16S rRNA gene sequence analysis and of the chemotaxonomic and physiological data, strain CC-GIMAT-2(T) represents a novel species of the genus Ruegeria, for which the name Ruegeria intermedia sp. nov. is proposed. The type strain is CC-GIMAT-2(T) ( = CCUG 59209(T) = LMG 25539(T) = CCM 7758(T)). PMID:23243093

  15. Hypothalamic S1P/S1PR1 axis controls energy homeostasis.

    PubMed

    Silva, Vagner R R; Micheletti, Thayana O; Pimentel, Gustavo D; Katashima, Carlos K; Lenhare, Luciene; Morari, Joseane; Mendes, Maria Carolina S; Razolli, Daniela S; Rocha, Guilherme Z; de Souza, Claudio T; Ryu, Dongryeol; Prada, Patrícia O; Velloso, Lício A; Carvalheira, José B C; Pauli, José Rodrigo; Cintra, Dennys E; Ropelle, Eduardo R

    2014-01-01

    Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats. PMID:25255053

  16. Evolución de estrellas enanas blancas de Helio de masa baja e intermedia

    NASA Astrophysics Data System (ADS)

    Althaus, L. G.; Benvenuto, O. G.

    Numerosas observaciones realizadas particularmente en los últimos dos años parecen confirmar que las enanas blancas (EB) de helio de masa baja e intermedia son el resultado de la evolución de sistemas binarios cercanos. Con el objeto de realizar una adecuada interpretación de estos objetos son necesarios modelos de EBs de helio lo más detallado posibles. En este estudio presentamos cálculos detallados de la evolución de EBs de helio con masas entre M=0.1Msolar y M=0.5Msolar a intervalos de 0.05Msolar . Para ello, hemos tenido en cuenta los efectos de temperatura finita mediante un código de evolución estelar lo más actualizado posible. En particular, el transporte de energía es descripto en el marco del nuevo modelo para la convección turbulenta desarrollado por Canuto - Mazzitelli. Además hemos considerado la nueva ecuación de estado para plasmas de helio de Saumon et al. y nuevas opacidades radiativas OPAL. Las pérdidas por neutrinos fueron asimismo tenidas en cuenta. Excepto para las EBs más masivas, nuestros modelos iniciales están ubicados en las cercanías de la correspondiente línea de Hayashi para configuraciones de helio. Nuestros resultados muestran que existe una región prohibida en el diagrama observacional HR donde ninguna EB de helio puede encontrarse. Dicha región es para log{(L/Lsolar )}>= -0.25 and log{Teff} >= 4.45. Hemos encontrado también que los tracks evolutivos en el diagrama HR en el dominio de alta luminosidad (pre - EB) son fuertemente afectados por la eficiencia convectiva y que las pérdidas por neutrinos son importantes en los modelos más masivos. Finalmente hemos analizado la estructura de la zona convectiva externa encontrando que la teoría de Canuto - Mazzitelli conduce a un perfil convectivo muy diferente del dado por cualquier versión de la popular teoría de la mixing length. Si bién este comportamiento es decisivo en el contexto de las inestabilides pulsacionales, los radios y gravedades superficiales de

  17. A Preliminary Study of the Effects of pH upon Fluorescence in Suspensions of Prevotella intermedia

    PubMed Central

    Hope, Christopher K.; Billingsley, Karen; de Josselin de Jong, Elbert; Higham, Susan M.

    2016-01-01

    The quantification of fluorescence in dental plaque is currently being developed as a diagnostic tool to help inform and improve oral health. The oral anaerobe Prevotella intermedia exhibits red fluorescence due to the accumulation of porphyrins. pH affects the fluorescence of abiotic preparations of porphyrins caused by changes in speciation between monomers, higher aggregates and dimers, but this phenomenon has not been demonstrated in bacteria. Fluorescence spectra were obtained from suspensions of P. intermedia that were adjusted to pHs commensurate with the range found within dental plaque. Two fluorescent motifs were identified; 410 nm excitation / 634 nm emission (peak A) and 398 nm excitation / 622 nm emission (peak B). A transition in the fluorescence spectra was observed from peak A to peak B with increasing pH which was also evident as culture age increased from 24 hours to 96 hours. In addition to these ‘blue-shifts’, the intensity of peak A increased with pH whilst decreasing with culture age from 24 to 96 hours. A bacterium’s relationship with the local physiochemical environment at the time of image capture may therefore affect the quantification of dental plaque fluorescence. PMID:27441707

  18. α:Non-α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea

    PubMed Central

    Najjari, Abbas; Asouri, Mohsen; Gouhari, Ladan Hosseini; Niaki, Haleh Akhavan; Nejad, Amir Sasan Mozaffari; Eslami, Seyyedeh Masoumeh; Abolghasemi, Hassan; Ataee, Ramin; Ebrahimi, Abdol Ali; Moshaei, Masoumeh Rezaei; Ahmadi, Ali Asghar

    2014-01-01

    Objectives To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or β-like) synthesis. Methods A total of 23 thalassemia intermedia patients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg·day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment. Results Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased. Conclusions Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major. PMID:25183077

  19. Simultaneous quantitative analysis of nine triterpenoid saponins for the quality control of Stauntonia obovatifoliola Hayata subsp. intermedia stems.

    PubMed

    Lu, Xuran; Qiu, Feng; Pan, Xueqiang; Li, Jing; Wang, Manyuan; Gong, Muxin

    2014-12-01

    Stauntonia obovatifoliola Hayata subsp. intermedia is used in China to treat rheumatic arthralgia, hernia pain, and traumatic pain. An accurate and reliable method based on high-performance liquid chromatography with diode array detection has been developed and validated for the quantitative determination of nine triterpenoid saponins in this herb. By using a Kromasil 100-5 C18 column (250 mm × 4.6 mm, 5 μm), nine analytes were separated by gradient elution over a running time of 45.0 min. All standard calibration curves demonstrated satisfactory linearity (R(2) ≥ 0.9995) within a relatively wide range. The precision was evaluated by intra- and interday tests, which revealed relative standard deviation values within the ranges of 0.20-2.83 and 0.51-2.79%, respectively. The recoveries for the nine target compounds were between 84.6 and 103% with relative standard deviation values less than 2.67%. The samples were also analyzed on a linear trap quadrupole Orbitrap Velos Pro mass spectrometer equipped with an electrospray ionization source in negative mode to confirm the quantification results. In conclusion, the present high-performance liquid chromatography with diode array detection method could serve as an accurate and reliable method for the quality evaluation of Stauntonia obovatifoliola Hayata subsp. intermedia stems. PMID:25315436

  20. The Global S$_1$ Ocean Tide

    NASA Technical Reports Server (NTRS)

    Ray, Richard D.; Egbert, G. D.

    2003-01-01

    The small S$_1$ ocean tide is caused primarily by diurnal atmospheric pressure loading. Its excitation is therefore unlike any other diurnal tide. The global character of $S-1$ is here determined by numerical modeling and by analysis of Topex/Poseidon satellite altimeter data. The two approaches yield reasonably consistent results, and large ( $ greater than $l\\cm) amplitudes in several regions are further confirmed by comparison with coastal tide gauges. Notwithstanding their excitation differences, S$-1$ and other diurnal tides are found to share several common features, such as relatively large amplitudes in the Arabian Sea, the Sea of Okhotsk, and the Gulf of Alaska. The most noticeable difference is the lack of an S$-1$ Antarctic Kelvin wave. These similarities and differences can be explained in terms of the coherences between near-diurnal oceanic normal modes and the underlying tidal forcings. While gravitational diurnal tidal forces excite primarily a 28-hour Antarctic-Pacific mode, the S$_1$ air tide excites several other near-diurnal modes, none of which has large amplitudes near Antarctica.

  1. Protective antibodies against a sphingomyelinase D from Loxosceles intermedia spider venom elicited in mice with different genetic background.

    PubMed

    Oliveira, Camila Franco Batista; Vilela, Andrea; Coura, Luis Augusto M; Rodrigues, Fernandes Tenório Gomes; Nagem, Ronaldo Alves Pinto; Chávez-Olortegui, Carlos; Maioli, Tatiani U; Felicori, Liza F

    2016-07-19

    In the present investigation we used a recombinant LiD1 toxin, named rLiD1his, from Loxosceles intermedia brown spider to elicit specific antibodies in mice carrying different Human Leukocyte Antigens class II (HLAII) {DRB1.0401 (DR4), DQB1.0601 (DQ6) and DQB1.0302 (DQ8)} as well as in BALB/C and C57BL/6 control mice. All mice strains produced high antibody titers against rLiD1his but DR4 mice antibodies (the lower responder mice) were not able to recognize L. intermedia crude venom. The anti-rLiD1his sera, except from DR4 mice, were able to neutralize dermonecrotic, hemorrhagic and edematogenic effects of rLiD1his in naïve rabbits. Overlapping peptides from the amino acid sequence of LiD1 toxin were prepared by SPOT method and differences in LiD1 epitope recognition were observed using different mice anti-rLiD1his sera. The region (160)DKVGHDFSGNDDISDVGK(177) was recognized by transgenic DQ8 and DQ6 mice sera. Other epitopes were recognized by at least two different animals' sera including (10)MGHMVNAIGQIDEFVNLG(27), (37)FDDNANPEYTYHGIP(51), (70)GLRSATTPGNSKYQEKLV(87) and (259)AAYKKKFRVATYDDN(273). Among these epitopes, the epitopes 37-51 and 160-177 have already been shown in previously studies as good candidates to be used alone or combined with other peptides to induce protective immune response against Loxosceles venoms. The results presented here highlight the importance of HLAII in antibody response and recognition of specific B-cell epitopes of rLiD1his spider toxin according to HLAII type and impact in the epitopic vaccine development against this spider. PMID:27265457

  2. Ethanol and Protein from Ethanol Plant By-Products Using Edible Fungi Neurospora intermedia and Aspergillus oryzae

    PubMed Central

    Bátori, Veronika; Ferreira, Jorge A.; Taherzadeh, Mohammad J.; Lennartsson, Patrik R.

    2015-01-01

    Feasible biorefineries for production of second-generation ethanol are difficult to establish due to the process complexity. An alternative is to partially include the process in the first-generation plants. Whole stillage, a by-product from dry-mill ethanol processes from grains, is mostly composed of undegraded bran and lignocelluloses can be used as a potential substrate for production of ethanol and feed proteins. Ethanol production and the proteins from the stillage were investigated using the edible fungi Neurospora intermedia and Aspergillus oryzae, respectively. N. intermedia produced 4.7 g/L ethanol from the stillage and increased to 8.7 g/L by adding 1 FPU of cellulase/g suspended solids. Saccharomyces cerevisiae produced 0.4 and 5.1 g/L ethanol, respectively. Under a two-stage cultivation with both fungi, up to 7.6 g/L of ethanol and 5.8 g/L of biomass containing 42% (w/w) crude protein were obtained. Both fungi degraded complex substrates including arabinan, glucan, mannan, and xylan where reductions of 91, 73, 38, and 89% (w/v) were achieved, respectively. The inclusion of the current process can lead to the production of 44,000 m3 of ethanol (22% improvement), around 12,000 tons of protein-rich biomass for animal feed, and energy savings considering a typical facility producing 200,000 m3 ethanol/year. PMID:26682213

  3. Immunoglobulin G and A Antibody Responses to Bacteroides forsythus and Prevotella intermedia in Sera and Synovial Fluids of Arthritis Patients

    PubMed Central

    Moen, Ketil; Brun, Johan G.; Madland, Tor Magne; Tynning, Turid; Jonsson, Roland

    2003-01-01

    The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses to Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Candida albicans in the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies against B. forsythus (P < 0.0001) and P. intermedia (P < 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies against B. forsythus (P = 0.003) and P. intermedia (P = 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies against B. forsythus were demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody against B. forsythus were elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P = 0.003) and IgA (P < 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies against B. forsythus were still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P < 0.0001). The levels of antibodies against P. gingivalis and C. albicans in the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies against B. forsythus were elevated in SF from patients with RA and non-RA-SF samples

  4. Spatial Heterogeneity of Soil Nutrients after the Establishment of Caragana intermedia Plantation on Sand Dunes in Alpine Sandy Land of the Tibet Plateau

    PubMed Central

    Li, Qingxue; Jia, Zhiqing; Zhu, Yajuan; Wang, Yongsheng; Li, Hong; Yang, Defu; Zhao, Xuebin

    2015-01-01

    The Gonghe Basin region of the Tibet Plateau is severely affected by desertification. Compared with other desertified land, the main features of this region is windy, cold and short growing season, resulting in relatively difficult for vegetation restoration. In this harsh environment, identification the spatial distribution of soil nutrients and analysis its impact factors after vegetation establishment will be helpful for understanding the ecological relationship between soil and environment. Therefore, in this study, the 12-year-old C. intermedia plantation on sand dunes was selected as the experimental site. Soil samples were collected under and between shrubs on the windward slopes, dune tops and leeward slopes with different soil depth. Then analyzed soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), available nitrogen (AN), available phosphorus (AP) and available potassium (AK). The results showed that the spatial heterogeneity of soil nutrients was existed in C. intermedia plantation on sand dunes. (1) Depth was the most important impact factor, soil nutrients were decreased with greater soil depth. One of the possible reasons is that windblown fine materials and litters were accumulated on surface soil, when they were decomposed, more nutrients were aggregated on surface soil. (2) Topography also affected the distribution of soil nutrients, more soil nutrients distributed on windward slopes. The herbaceous coverage were higher and C. intermedia ground diameter were larger on windward slopes, both of them probably related to the high soil nutrients level for windward slopes. (3) Soil “fertile islands” were formed, and the “fertile islands” were more marked on lower soil nutrients level topography positions, while it decreased towards higher soil nutrients level topography positions. The enrichment ratio (E) for TN and AN were higher than other nutrients, most likely because C. intermedia is a leguminous

  5. Spatial Heterogeneity of Soil Nutrients after the Establishment of Caragana intermedia Plantation on Sand Dunes in Alpine Sandy Land of the Tibet Plateau.

    PubMed

    Li, Qingxue; Jia, Zhiqing; Zhu, Yajuan; Wang, Yongsheng; Li, Hong; Yang, Defu; Zhao, Xuebin

    2015-01-01

    The Gonghe Basin region of the Tibet Plateau is severely affected by desertification. Compared with other desertified land, the main features of this region is windy, cold and short growing season, resulting in relatively difficult for vegetation restoration. In this harsh environment, identification the spatial distribution of soil nutrients and analysis its impact factors after vegetation establishment will be helpful for understanding the ecological relationship between soil and environment. Therefore, in this study, the 12-year-old C. intermedia plantation on sand dunes was selected as the experimental site. Soil samples were collected under and between shrubs on the windward slopes, dune tops and leeward slopes with different soil depth. Then analyzed soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), available nitrogen (AN), available phosphorus (AP) and available potassium (AK). The results showed that the spatial heterogeneity of soil nutrients was existed in C. intermedia plantation on sand dunes. (1) Depth was the most important impact factor, soil nutrients were decreased with greater soil depth. One of the possible reasons is that windblown fine materials and litters were accumulated on surface soil, when they were decomposed, more nutrients were aggregated on surface soil. (2) Topography also affected the distribution of soil nutrients, more soil nutrients distributed on windward slopes. The herbaceous coverage were higher and C. intermedia ground diameter were larger on windward slopes, both of them probably related to the high soil nutrients level for windward slopes. (3) Soil "fertile islands" were formed, and the "fertile islands" were more marked on lower soil nutrients level topography positions, while it decreased towards higher soil nutrients level topography positions. The enrichment ratio (E) for TN and AN were higher than other nutrients, most likely because C. intermedia is a leguminous shrub. PMID

  6. Interaction of Prevotella intermedia Strain 17 Leucine-Rich Repeat Domain Protein AdpF with Eukaryotic Cells Promotes Bacterial Internalization

    PubMed Central

    Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K.; Miyazaki, Hiroshi

    2014-01-01

    Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells. PMID:24711565

  7. Desensitization to hydroxycarbamide following long-term treatment of thalassaemia intermedia as observed in vivo and in primary erythroid cultures from treated patients.

    PubMed

    Rigano, Paolo; Pecoraro, Alice; Calzolari, Roberta; Troia, Antonio; Acuto, Santina; Renda, Disma; Pantalone, Gaetano Restivo; Maggio, Aurelio; Di Marzo, Rosalba

    2010-12-01

    Hydroxycarbamide (HC) is a pharmacological agent capable of stimulating fetal haemoglobin (HbF) production during adult life. High levels of HbF may ameliorate the clinical course of β-thalassaemia and sickle cell disease. The efficacy of HC for the treatment of thalassaemia major and thalassaemia intermedia is variable. Although an increase of HbF has been observed in most patients, only some patients experience significant improvement in total haemoglobin levels. This study aimed to determine the effectiveness and safety of short- (1 year) and long-term (mean follow-up 68 months) HC treatment in 24 thalassaemia intermedia patients. Additionally, we evaluated if primary erythroid progenitor cells cultured from treated patients responded to HC treatment in a manner similar to that observed in vivo. Our results confirm a good response to HC after a short-term follow-up in 70% of thalassaemia intermedia patients and a reduction of clinical response in patients with a long follow-up. Erythroid cultures obtained from patients during treatment reproduced the observed in vivo response. Interestingly, haematopoietic stem cells from long-term treated patients showed reduced ability to develop into primary erythroid cultures some months before the reduction of the 'in vivo' response. The mechanism of this loss of response to HC remains to be determined. PMID:20955403

  8. Growth of rhodococcus S1 on anthracene.

    PubMed

    Tongpim, S; Pickard, M A

    1996-03-01

    Three slow-growing bacteria were isolated from a mixed culture enriched for growth on anthracene, using creosote-contaminated soil as the inoculum. Organisms were shown to use anthracene by the production of a clear zone around the colony after a mineral salts agar plate was sprayed with anthracene. All three bacteria were nonmotile, nonsporulating, gram-positive rods and stained acid-fast. Physiological and biochemical tests, GC content, and cell wall lipid patterns of whole cell methanolysates indicated that they belonged to the Nocardia-Mycobacterium-Rhodococcus group. On the basis of these characteristics and pyrolysis gas chromatography, they were assigned to the genus Rhodococcus. Growth of the isolates was slow on crystalline anthracene, giving a doubling time of 1.5-3 days, and they grew mainly on the crystal surface. When anthracene was supplied by precipitation from a solvent, doubling time was reduced to 1 day. All three isolates mineralized anthracene but not phenanthrene or naphthalene, nor could they grow on naphthalene, phenanthrene, fluorene, fluoranthene, acenaphthene, pyrene, chrysene, or naphthacene as sole carbon source. One isolate, Rhodococcus S1, was able to use 2-methylanthracene or 2-chloroanthracene as carbon source but not 1- or 9-substituted analogs. These results suggest that the initial enzyme attacking anthracene in these isolates has a narrow substrate specificity. PMID:8868237

  9. An Extraordinary Accumulation of (-)-Pinoresinol in Cell-Free Extracts of Forsythia intermedia: Evidence for Enantiospecific Reduction of (+)-Pinoresinol

    NASA Technical Reports Server (NTRS)

    Katayama, Takeshi; Davin, Laurence B.; Lewis, Norman G.

    1992-01-01

    Stereoselective and enantiospecific transformation mechanisms in lignan biogenesis are only now yielding to scientific inquiry: it has been shown that soluble cell-free preparations from Forsythia intermedia catalysis the formation of the enantiomerically pure lignan, (-)-secoisolariciresinol, when incubated with coniferyl alcohol in the presence of NAD(P)H and H2O2. Surprisingly, (-)-pinoresinol also accumulates in this soluble cell-free assay mixture in greater than 96% enantiomeric excess, even though it is not the naturally occurring antipode present in Forsythia sp. But these soluble cell-free preparations do not engender stereoselective coupling; instead, racemic pinoresinols are first formed, catalysed by an H2O2-dependent peroxidase reaction. An enantiospecific NAD(P)H reductase then converts (+)- pinoresinol, and not the (-)-antipode, into (-)-secoisolariciresinol. Stereoselective syntheis of(+)-pinoresinol from E-coniferyl alcohol is, however, catalysed by an insoluble enzyme preparation in F. suspensa, obtained following removal of readily soluble and ionically bound enzymes; no exogenously supplied cofactors were required other than oxygen, although the reaction was stimulated by NAD-malate addition. Thus, the overall biochemical pathway to enantiomerically pure (-)-secoisolariciresinol has been delineated.

  10. Molecular cloning and expression analysis of dihydroflavonol 4-reductase gene in flower organs of Forsythia x intermedia.

    PubMed

    Rosati, C; Cadic, A; Duron, M; Renou, J P; Simoneau, P

    1997-10-01

    The expression, during flower development, of the gene encoding the anthocyanin pathway key enzyme dihydroflavonol 4-reductase (DFR) was investigated in floral organs of Forsythia x intermedia cv. 'Spring Glory'. Full-length DFR and partial chalcone synthase (CHS) cDNAs, the gene of interest and a flavonoid pathway control gene respectively, were obtained from petal RNA by reverse transcription PCR. Whereas for CHS northern blot analysis enabled the study of its expression pattern, competitive PCR assays were necessary to quantify DFR mRNA levels in wild-type plants and in petals of 2 transgenic clones containing a CaMV 35S promoter-driven DFR gene of Antirrhinum majus. Results indicated a peak of CHS and DFR transcript levels in petals at the very early stages of anthesis, and different expression patterns in anthers and sepals. In comparison to wild-type plants, transformants showed a more intense anthocyanin pigmentation of some vegetative organs, and a dramatic increase in DFR transcript concentration and enzymatic activity in petals. However, petals of transformed plants did not accumulate any anthocyanins. These results indicate that other genes and/or regulatory factors should be considered responsible for the lack of anthocyanin production in Forsythia petals. PMID:9349254

  11. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling

    PubMed Central

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain. PMID:26576074

  12. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    SciTech Connect

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  13. Relationship Between Serum Hepcidin and Ferritin Levels in Patients With Thalassemia Major and Intermedia in Southern Iran

    PubMed Central

    Haghpanah, Sezaneh; Esmaeilzadeh, Masoomeh; Honar, Naser; Hassani, Fatemeh; Dehbozorgian, Javad; Rezaei, Narges; Abdollahi, Maryam; Bardestani, Marzieh; Safaei, Sanaz; Karimi, Mehran

    2015-01-01

    Background: Hepcidin is a key regulator of iron absorption in humans. It is mainly affected by hypoxia and iron stores. Objectives: The current study aimed to determine the correlation between serum hepcidin and ferritin levels in patients with Thalassemia Major (TM) and Thalassemia Intermedia (TI). Patients and Methods: The current cross-sectional study investigated 88 randomly selected patients with Thalassemia, 48 TM and 40 TI, registered at the Thalassemia Clinic of Shiraz University of Medical Sciences, a referral center for Thalassemia in Southern Iran in 2013. All patients with TI were receiving Hydroxyurea (HU) 10 - 15 mg/kg/day for at least 10 years. The serum hepcidin, ferritin levels, hemoglobin (Hb) and nucleated Red Blood Cell (RBC) of the two groups were measured. Results: No statistically significant correlation was observed between serum hepcidin and ferritin levels in any of the two groups of patients with TM (rs = 0.02, P = 0.892) or TI (rs = 0.055, P = 0.734). The median Interquartile Range (IQR) for serum hepcidin and ferritin levels were significantly higher in TM compared to TI group, (hepcidin: 87.6 (43.9) vs. 51.8 (23.4), P < 0.001; ferritin: 2208 (3761) vs. 465 (632), P < 0.001). Conclusions: There was insignificant correlation between serum hepcidin and ferritin levels in the two groups of patients with TM and TI. It seems that regulation of hepcidin in patients with Thalassemia is more affected by erythropoeitic activity than iron stores. Also, hepcidin levels were significantly higher in patients with TM than TI, possibly due to higher erythropoeitic activity in TI. In TI, it seems that low dose HU increases Hb levels and leads to transfusion-independence, but it is not high enough to suppress bone marrow activity and ineffective erythropoiesis. Consequently, serum hepcidin level decreases. PMID:26421179

  14. Circumpolar diversity and geographic differentiation of mtDNA in the critically endangered Antarctic blue whale (Balaenoptera musculus intermedia).

    PubMed

    Sremba, Angela L; Hancock-Hanser, Brittany; Branch, Trevor A; LeDuc, Rick L; Baker, C Scott

    2012-01-01

    The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131° longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968±0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F(ST) = 0.032, p<0.005) and microsatellite alleles (F(ST) = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales. PMID:22412889

  15. Role of the cysteine protease interpain A of Prevotella intermedia in breakdown and release of haem from haemoglobin

    PubMed Central

    Byrne, Dominic P; Wawrzonek, Katarzyna; Jaworska, Anna; Birss, Andrew J; Potempa, Jan; Smalley, John W

    2010-01-01

    SUMMARY The Gram-negative oral anaerobe Prevotella intermedia forms an iron(III) protoporphyrin IX pigment from haemoglobin. The microorganism expresses a 90 kDa cysteine protease, Interpain A (InpA), a homologue of Streptococcus pyogenes streptopain (SpeB). The role of InpA in haemoglobin breakdown and haem release was investigated. At pH 7.5, InpA mediated oxidation of oxyhaemoglobin to hydroxymethaemoglobin (in which the haem iron is oxidised to the Fe(III) state and which carries OH− as the sixth co-ordinate ligand) by limited proteolysis of globin chains as indicated by SDS-PAGE and MALDI-TOF analysis. Prolonged incubation at pH 7.5, did not result in further haemoglobin protein breakdown, but in the formation of a haemoglobin haemichrome (where the haem Fe atom is co-ordinated by another amino acid ligand in addition to the proximal histidine) stable to degradation by InpA. InpA-mediated haem release from hydroxymethaemoglobin-agarose was minimal compared with trypsin at pH 7.5. At pH 6.0, InpA increased oxidation at a rate greater than auto-oxidation, producing aquomethaemoglobin (with H2O as sixth co-ordinate ligand), and resulted in its complete breakdown and haem loss. Aquo-methaemoglobin proteolysis and haem release was prevented by blocking haem dissociation by ligation with azide, whilst InpA proteolysis of haem-free globin was rapid even at pH 7.5. Both oxidation of oxyhaemoglobin and breakdown of methaemoglobin by InpA were inhibited by the cysteine-protease inhibitor E64. In summary we conclude that InpA may play a central role in haem acquisition by mediating oxyhaemoglobin oxidation, and by degrading aquomethaemoglobin in which haem-globin affinity is weakened under acidic conditions. PMID:19814715

  16. Conformationally Constrained, Stable, Triplet Ground State (S = 1) Nitroxide Diradicals. Antiferromagnetic Chains of S = 1 Diradicals

    SciTech Connect

    Rajca, Andrzej; Takahashi, Masahiro; Pink, Maren; Spagnol, Gaelle; Rajca, Suchada

    2008-06-30

    Nitroxide diradicals, in which nitroxides are annelated to m-phenylene forming tricyclic benzobisoxazine-like structures, have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and {sup 1}H NMR) spectroscopy, as well as magnetic studies in solution and in solid state. For the octamethyl derivative of benzobisoxazine nitroxide diradical, the conformationally constrained nitroxide moieties are coplanar with the m-phenylene, leading to large values of 2J (2J/k > 200 K in solution and 2J/k >> 300 K in the solid state). For the diradical, in which all ortho and para positions of the m-phenylene are sterically shielded, distortion of the nitroxide moieties from coplanarity is moderate, such that the singlet-triplet gaps remain large in both solution (2J/k > 200 K) and the solid state (2J/k {approx} 400-800 K), though an onset of thermal depopulation of the triplet ground state is detectable near room temperature. These diradicals have robust triplet ground states with strong ferromagnetic coupling and good stability at ambient conditions. Magnetic behavior of the nitroxide diradicals at low temperature is best fit to the model of one-dimensional S = 1 Heisenberg chains with intrachain antiferromagnetic coupling. The antiferromagnetic coupling between the S = 1 diradicals may be associated with the methyl nitroxide C-H {hor_ellipsis} O contacts, including nonclassical hydrogen bonds. These unprecedented organic S = 1 antiferromagnetic chains are highly isotropic, compared to those of the extensively studied Ni(II)-based chains.

  17. Regulation of endothelial nitric oxide synthase activation in endothelial cells by S1P1 and S1P3.

    PubMed

    Tölle, M; Klöckl, L; Wiedon, A; Zidek, W; van der Giet, M; Schuchardt, M

    2016-08-01

    Endothelial nitric oxide synthase (eNOS) plays a crucial role in vascular homeostasis. Lysophospholipid interaction with sphingosine 1-phosphat (S1P) receptors results in eNOS activation in different cells. In endothelial cells, eNOS activation via S1P1 or S1P3 was shown controversially. The aim of this study is to investigate the meaning of both S1P receptors for eNOS activation in human endothelial cells. Therefore, several S1P1 and S1P3 agonists in combination with antagonists and specific RNAi approach were used. eNOS activation was measured in human umbilical vein endothelial cells (HUVEC) via DAF2-DA-based fluorescence microscopy. For investigation of the signaling pathway, agonists/antagonist studies, RNAi approach, Luminex™ multiplex, and Western Blot were used. In HUVEC, both the S1P1 agonist AUY954 as well as the S1P1,3 agonist FTY720P induced eNOS activation in a time- and dose-dependent manner. Other S1P1 agonists activated eNOS to a lesser extent. The AUY954-induced eNOS activation was blocked by the S1P1 antagonist W146, the combination of W146 and the S1P3 antagonist CAY10444 and the S1P1,3 antagonist VPC23019, but not by CAY10444 indicating the meaning of S1P1 for the AUY954-induced eNOS activation. The FTY720P-induced eNOS activation was blocked only by the combination of W146 and CAY10444 and the combined S1P1,3 antagonist VPC23019, but not by W146 or CAY10444 indicating the importance of both S1P1 and S1P3 for FTY720-induced eNOS activation. These results were confirmed using specific siRNA against S1P1 and S1P3. The S1P1,3 activation results in Akt phosphorylation and subsequent activation of eNOS via phosphorylation at serine(1177) and dephosphorylation at threonine(495). Beside former investigations with rather unspecific S1P receptor activation these data show potent selective S1P1 activation by using AUY954 and with selective S1P receptor inhibition evidence was provided that both S1P1 and S1P3 lead to downstream activation of eNOS in

  18. Roles for lysophospholipid S1P receptors in multiple sclerosis.

    PubMed

    Noguchi, Kyoko; Chun, Jerold

    2011-02-01

    Sphingosine 1-phosphate (S1P) signaling in the treatment of multiple sclerosis (MS) has been highlighted by the efficacy of FTY720 (fingolimod), which upon phosphorylation can modulate S1P receptor activities. FTY720 has become the first oral treatment for relapsing MS that was approved by the FDA in September 2010. Phosphorylated FTY720 modulates four of the five known S1P receptors (S1P(1), S1P(3), S1P(4), and S1P(5)) at high affinity. Studies in human MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have revealed that FTY720 exposure alters lymphocyte trafficking via sequestration of auto-aggressive lymphocytes within lymphoid organs, representing the current understanding of its mechanism of action. These effects primarily involve S1P(1), which is thought to attenuate inflammatory insults in the central nervous system (CNS). In addition, FTY720's actions may involve direct effects on S1P receptor-mediated signaling in CNS cells, based upon the known expression of S1P receptors in CNS cell types relevant to MS, access to the CNS through the blood-brain barrier (BBB), and in vitro studies. These data implicate lysophospholipid signaling--via S1P(1) and perhaps other lysophospholipid receptors--in therapeutic approaches to MS and potentially other diseases with immunological and/or neurological components. PMID:20979571

  19. Role of the cysteine protease interpain A of Prevotella intermedia in breakdown and release of haem from haemoglobin.

    PubMed

    Byrne, Dominic P; Wawrzonek, Katarzyna; Jaworska, Anna; Birss, Andrew J; Potempa, Jan; Smalley, John W

    2010-01-01

    The gram-negative oral anaerobe Prevotella intermedia forms an iron(III) protoporphyrin IX pigment from haemoglobin. The bacterium expresses a 90 kDa cysteine protease, InpA (interpain A), a homologue of Streptococcus pyogenes streptopain (SpeB). The role of InpA in haemoglobin breakdown and haem release was investigated. At pH 7.5, InpA mediated oxidation of oxyhaemoglobin to hydroxymethaemoglobin [in which the haem iron is oxidized to the Fe(III) state and which carries OH- as the sixth co-ordinate ligand] by limited proteolysis of globin chains as indicated by SDS/PAGE and MALDI (matrix-assisted laser-desorption ionization)-TOF (time-of-flight) analysis. Prolonged incubation at pH 7.5 did not result in further haemoglobin protein breakdown, but in the formation of a haemoglobin haemichrome (where the haem Fe atom is co-ordinated by another amino acid ligand in addition to the proximal histidine residue) resistant to degradation by InpA. InpA-mediated haem release from hydroxymethaemoglobin-agarose was minimal compared with trypsin at pH 7.5. At pH 6.0, InpA increased oxidation at a rate greater than auto-oxidation, producing aquomethaemoglobin (with water as sixth co-ordinate ligand), and resulted in its complete breakdown and haem loss. Aquomethaemoglobin proteolysis and haem release was prevented by blocking haem dissociation by ligation with azide, whereas InpA proteolysis of haem-free globin was rapid, even at pH 7.5. Both oxidation of oxyhaemoglobin and breakdown of methaemoglobin by InpA were inhibited by the cysteine protease inhibitor E-64 [trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane]. In summary, we conclude that InpA may play a central role in haem acquisition by mediating oxyhaemoglobin oxidation, and by degrading aquomethaemoglobin in which haem-globin affinity is weakened under acidic conditions. PMID:19814715

  20. Description of Trischistoma abharensis n. sp. (Nematoda: Trischistomatidae) and first record of Tripylella intermedia (Bütschli, 1873) Brzeski & Winiszewska-Ślipinska, 1993 (Nematoda: Tripylidae) from Iran.

    PubMed

    Asghari, Ramezan; Eskandari, Ali; Maafi, Zahra Tanha; Zhao, Zeng Qi; Álvarez-Ortega, Sergio; Nadirkhanloo, Majid

    2015-01-01

    Two populations of the genera Trischistoma and Tripylella were recovered from the rhizosphere of grapevines and mosses growing on alder trees in Zanjan and Guilan provinces, respectively, Iran. The nematodes were identified as Trischistoma abharensis n. sp. and Tripylella intermedia, respectively. Trischistoma abharensis n. sp. is characterized by having females with body length 1069-1322 μm, presence of sparse somatic setae on the sublateral body, absence of ventromedian cervical setae, a distinct dorsal tooth directed anteriorly, absence of post-vulval uterine sac, and tail with one pair of subdorsal caudal setae. Males were not found. Tripylella intermedia is characterised by having females with body length 905-990 μm, annulated cuticle, stoma with two chambers: with dorsal tooth lying in posterior buccal chamber, and one large subventral and one small subventral tooth, respectively lying in posterior and anterior buccal chambers, cardiac glands large, composed of six fused cells, and tail 121-155 μm long, ventrally bent, anterior half broad, then suddenly narrowing, with posterior half tapered narrowly and cylindrically. The phylogenetic relationships of both species were analysed using sequences of the partial small subunit (SSU) and D2/D3 expansion segments of large subunit (partial LSU) of ribosomal RNA genes and are discussed. PMID:26250191

  1. Closure of chronic non healing ankle ulcer with low level laser therapy in a patient presenting with thalassemia intermedia: Case report

    PubMed Central

    Dixit, Snehil; Agrawal, Parul Raj; Sharma, Dinesh Kumari; Singh, Ravindra Pratap

    2014-01-01

    In this single case study, the possible effect of low-level laser therapy (LLLT) was explored in the form of light emitting diodes on a chronic non-healing wound of 6 months duration in an 18-year-old male patient suffering from thalassemia intermedia. After irradiation, with LLLT dosage of 17.3 J/cm2 for 8 min for 2 weeks duration followed by proliferative dosage of 8.65-4.33 J/cm2 for 4 min from 3rd week to 6th week for 2 min along with antibiotics vancomycin (15 mg/kg) and a combination of amoxicillin and clavulanic acid (1 g). Proliferation of healthy granulation tissue was observed with decrease in score of pressure ulcer scale with complete re-epithelialization eventually LLLT irradiation could be a novel method of treatment for chronic non-healing wound in a thalassemia intermedia patient and an useful adjunct to standard care of treatment of pressure ulcers. It is postulated that LED irradiation augments wound healing with an early closure and no recurrence at the irradiated site even after follow up of 6 months. PMID:25593435

  2. Closure of chronic non healing ankle ulcer with low level laser therapy in a patient presenting with thalassemia intermedia: Case report.

    PubMed

    Dixit, Snehil; Agrawal, Parul Raj; Sharma, Dinesh Kumari; Singh, Ravindra Pratap

    2014-01-01

    In this single case study, the possible effect of low-level laser therapy (LLLT) was explored in the form of light emitting diodes on a chronic non-healing wound of 6 months duration in an 18-year-old male patient suffering from thalassemia intermedia. After irradiation, with LLLT dosage of 17.3 J/cm(2) for 8 min for 2 weeks duration followed by proliferative dosage of 8.65-4.33 J/cm(2) for 4 min from 3(rd) week to 6(th) week for 2 min along with antibiotics vancomycin (15 mg/kg) and a combination of amoxicillin and clavulanic acid (1 g). Proliferation of healthy granulation tissue was observed with decrease in score of pressure ulcer scale with complete re-epithelialization eventually LLLT irradiation could be a novel method of treatment for chronic non-healing wound in a thalassemia intermedia patient and an useful adjunct to standard care of treatment of pressure ulcers. It is postulated that LED irradiation augments wound healing with an early closure and no recurrence at the irradiated site even after follow up of 6 months. PMID:25593435

  3. Evaluation of anti-microbial activity of spore powder of Ganoderma lucidum on clinical isolates of Prevotella intermedia: A pilot study

    PubMed Central

    Nayak, Ranganath N.; Dixitraj, P. T.; Nayak, Aarati; Bhat, Kishore

    2015-01-01

    Aim: This study aimed at evaluating the anti-microbial activity of spore powder of Ganoderma lucidum on Prevotella intermedia isolated from subgingival plaque from chronic periodontitis patients. Settings and Design: Written informed consent was obtained from each subject enrolled in the study. The Institutional Ethics Committee granted the ethical clearance for the study. Materials and Methods: This study included 20 patients diagnosed with chronic periodontitis. Pooled subgingival plaque samples were collected using sterile curettes from the deepest sites of periodontal pockets. The collected samples were then transported in 1 mL of reduced transport fluid. The organisms were cultured and confirmed. These organisms were then used for minimum inhibitory concentration (MIC) procedure. Statistical Analysis: Mean of the MIC value obtained was calculated. Results: Thirteen out of the 20 clinical samples were tested that showed sensitivity at various concentrations. Five samples showed sensitivity at all concentrations. Twelve samples showed sensitivity at 8 mcg/ml. Eleven samples showed sensitivity at 4 mcg/ml, 8 samples showed sensitivity at 2 mcg/ml, and 5 samples showed sensitivity even at 1 mcg/ml. Mean MIC value of G. lucidum spore powder for P. intermedia obtained was 3.62 mcg/ml. Conclusion: G. lucidum with its multipotential bioactivity could be used as an anti-microbial, in conjunction with conventional therapy in periodontal disease. PMID:26604581

  4. Resonating Valence Bond states for low dimensional S=1 antiferromagnets

    NASA Astrophysics Data System (ADS)

    Liu, Zheng-Xin; Zhou, Yi; Ng, Tai-Kai

    2014-03-01

    We study S = 1 spin liquid states in low dimensions. We show that the resonating-valence-bond (RVB) picture of S = 1 / 2 spin liquid state can be generalized to S = 1 case. For S = 1 system, a many-body singlet (with even site number) can be decomposed into superposition of products of two-body singlets. In other words, the product states of two-body singlets, called the singlet pair states (SPSs), are over complete to span the Hilbert space of many-body singlets. Furthermore, we generalized fermionic representation and the corresponding mean field theory and Gutzwiller projected stats to S = 1 models. We applied our theory to study 1D anti-ferromagnetic bilinear-biquadratic model and show that both the ground states (including the phase transition point) and the excited states can be understood excellently well within the framework. Our method can be applied to 2D S = 1 antiferromagnets.

  5. 26 CFR 1.414(s)-1 - Definition of compensation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... prior regulation provisions of § 1.414(s)-1T. (See § 1.414(s)-1T as contained in the CFR edition revised... to the extent necessary to satisfy the requirements of 29 CFR 2530.204-2(d) (regarding double... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of compensation. 1.414(s)-1 Section...

  6. Precision polarizability measurements of atomic cesium's 8 s 2S1 / 2 and 9 s 2S1 / 2 states

    NASA Astrophysics Data System (ADS)

    Weaver, Hannah; Kortyna, Andrew

    2013-05-01

    We report hyperfine-resolved scalar polarizabilities for cesium's 8 s 2S1 / 2 and 9 s 2S1 / 2 states using resonant two-photon spectroscopy. Two single-mode, external-cavity diode lasers drive the 6 s 2S1 / 2 --> 6 p 2P1 / 2 --> ns 2S1 / 2 transition (n = 8 or 9). Both laser beams are split and counter-propagate through an effusive beam and a vapor cell. An electric field applied across two parallel plates imposes Stark shifts on the ns 2S1 / 2 levels in the effusive beam. Electric-field strengths are measured in situ. The laser frequency is calibrated in the vapor cell using a phase modulation technique, with the modulation frequency referenced to the ground-state hyperfine splitting of atomic rubidium. Our measured 8 s 2S1 / 2 polarizability, 38370 +/- 380 a03, agrees with previous theory and experiments. Our measured 9 s 2S1 / 2 polarizability, 150700 +/- 1100 a03, agrees within two sigma of theory, but we are unaware of previous measurements. We also verify that these polarizabilities are independent of the hyperfine levels, placing upper limits on the differential polarizabilities of 200 +/- 260 a03 for the 8 s 2S1 / 2 state and 490 +/- 450 a03 for the 9 s 2S1 / 2 state. Supported by the National Science Foundation under Grant PHY-0653107.

  7. Cardiac Function and Iron Chelation in Thalassemia Major and Intermedia: a Review of the Underlying Pathophysiology and Approach to Chelation Management

    PubMed Central

    Aessopos, Athanasios; Berdoukas, Vasilios

    2009-01-01

    Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia. The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload. The high output state playing a major role in thalassaemia intermedia and the iron load being more significant in the major form. Arrhythmias, vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness and valvular abnormalities also contribute to the cardiac dysfunction in varying degrees according to the severity of the phenotype. Endocrine abnormalities, infections, renal function and medications can also play a role in the overall cardiac function. For thalassaemia major, regular and adequate blood transfusions and iron chelation therapy are the mainstays of management. The approach to thalassaemia intermedia, today, is aimed at monitoring for complications and initiating, timely, regular transfusions and/or iron chelation therapy. Once the patients are on transfusions, then they should be managed in the same way as the thalassaemia major patients. If cardiac manifestations of dysfunction are present in either form of thalassaemia, high pre transfusion Hb levels need to be maintained in order to reduce cardiac output and appropriate intensive chelation therapy needs to be instituted. In general recommendations on chelation, today, are usually made according to the Cardiac Magnetic Resonance findings, if available. With the advances in the latter technology and the ability to tailor chelation therapy according to the MRI findings as well as the availability of three iron chelators, together with increasing the transfusions as need

  8. Speciation history and widespread introgression in the European short-call tree frogs (Hyla arborea sensu lato, H. intermedia and H. sarda).

    PubMed

    Gvoždík, Václav; Canestrelli, Daniele; García-París, Mario; Moravec, Jiří; Nascetti, Giuseppe; Recuero, Ernesto; Teixeira, José; Kotlík, Petr

    2015-02-01

    European tree frogs (Hyla) characterized by short temporal parameters of the advertisement call form six genetically differentiated but morphologically cryptic taxa, H. arborea sensu stricto, H. orientalis and H. molleri from across Europe to western Asia (together referred to as H. arborea sensu lato), two putative taxa within H. intermedia (Northern and Southern) from the Italian Peninsula and Sicily, and H. sarda from Sardinia and Corsica. Here, we assess species limits and phylogenetic relationships within these 'short-call tree frogs' based on mitochondrial DNA and nuclear protein-coding markers. The mitochondrial and nuclear genes show partly incongruent phylogeographic patterns, which point to a complex history of gene flow across taxa, particularly in the Balkans. To test the species limits in the short-call tree frogs and to infer the species tree, we used coalescent-based approaches. The monophyly of H. arborea sensu lato is supported by the mtDNA as well as by the all-gene species tree. The Northern and Southern lineages of H. intermedia have been connected by nuclear gene flow (despite their deep mtDNA divergence) and should be treated as conspecific. On the contrary, the parapatric taxa within H. arborea sensu lato should be considered distinct species (H. arborea, H. orientalis, H. molleri) based on the coalescent analysis, although signs of hybridization were detected between them (H. arborea×H. orientalis; H. arborea×H. molleri). A mitochondrial capture upon secondary contact appears to explain the close mtDNA relationship between the geographically remote Iberian H. molleri and H. orientalis from around the Black Sea. Introgressive hybridization occurred also between the Balkan H. arborea and northern Italian H. intermedia, and between the Minor Asiatic H. orientalis and Arabian H. felix arabica (the latter belonging to a different acoustic group/clade). Our results shed light on the species limits in the European short-call tree frogs and show

  9. Degenerative Sacrolisthesis of S1-S2: A Case Report

    PubMed Central

    Rajendra, Thakre Kunwar; Issac, Thomas; Swamy, B Mallikarjuna

    2015-01-01

    Introduction: Degenerative spondylolisthesis (DS) is usually seen at L4-L5 level and less frequently at L5-S1 level. This is a rare case report of spondylolisthesis of S1 over S2 with lumbarization of S1. Lumbarization of S1 is seen in just 1-2% of the population and to have spondylolisthesis in this segment is even rarer. The purpose is to report a rare case of DS at S1-S2 level. Case Report: This is a single case report of a 66-year-old gentleman who presented with complains of lower backache for 2 years and acute retention of urine to the emergency department. Detailed clinical and radiological evaluation of the spine was done which revealed lumbarization of S1 with spondylolisthesis at S1-S2 and facetal hypertrophy at L5, S1, and S2. He underwent decompression and stabilization at L5, S1, and S2 along with placement of autologous bone graft. The bladder symptoms disappeared after 3 weeks. At 1-year follow-up, patient’s clinical symptoms were relieved, and he improved clinically. Conclusion: To the best of our knowledge, this is probably the first case of DS of sacral vertebrae to be reported in English literature. The prevalence of complete lumbarization is around 1.8% and to get spondylolisthesis in this segment is even rarer, hence the lack of literature in this regard. Since this is the first of its kind of case, further case series or longitudinal studies of such cases may help understand better the pathomechanics related to spondylolisthesis at this level. PMID:27299082

  10. Determination of antibacterial activity of green coffee bean extract on periodontogenic bacteria like Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans: An in vitro study

    PubMed Central

    Bharath, Nagaraj; Sowmya, Nagur Karibasappa; Mehta, Dhoom Singh

    2015-01-01

    Background: The aim of this study was to evaluate the antibacterial activity of pure green coffee bean extract on periodonto pathogenic bacteria Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa). Materials and Methods: Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were used to assess the antibacterial effect of pure green coffee bean extract against periodonto pathogenic bacteria by micro dilution method and culture method, respectively. Results: MIC values of Pg, Pi and Aa were 0.2 μg/ml whereas Fn showed sensitive at concentration of 3.125 μg/ml. MBC values mirrors the values same as that of MIC. Conclusion: Antimicrobial activity of pure green coffee bean extract against Pg, Pi, Fn and Aa suggests that it could be recommended as an adjunct to mechanical therapy in the management of periodontal disease. PMID:26097349

  11. Molecular cloning and in silico characterization of knottin peptide, U2-SCRTX-Lit2, from brown spider (Loxosceles intermedia) venom glands.

    PubMed

    Meissner, Gabriel Otto; de Resende Lara, Pedro Túlio; Scott, Luis Paulo Barbour; Braz, Antônio Sérgio Kimus; Chaves-Moreira, Daniele; Matsubara, Fernando Hitomi; Soares, Eduardo Mendonça; Trevisan-Silva, Dilza; Gremski, Luiza Helena; Veiga, Silvio Sanches; Chaim, Olga Meiri

    2016-09-01

    Inhibitor cystine knots (ICKs) are a family of structural peptides with a large number of cysteine residues that form intramolecular disulfide bonds, resulting in a knot. These peptides are involved in a variety of biological functions including predation and defense, and are found in various species, such as spiders, scorpions, sea anemones, and plants. The Loxosceles intermedia venom gland transcriptome identified five groups of ICK peptides that represent more than 50 % of toxin-coding transcripts. Here, we describe the molecular cloning of U2-Sicaritoxin-Lit2 (U2-SCRTX-Lit2), bioinformatic characterization, structure prediction, and molecular dynamic analysis. The sequence of U2-SCRTX-Lit2 obtained from the transcriptome is similar to that of μ-Hexatoxin-Mg2, a peptide that inhibits the insect Nav channel. Bioinformatic analysis of sequences classified as ICK family members also showed a conservation of cysteine residues among ICKs from different spiders, with the three dimensional molecular model of U2-SCRTX-Lit2 similar in structure to the hexatoxin from μ-hexatoxin-Mg2a. Molecular docking experiments showed the interaction of U2-SCRTX-Lit2 to its predictable target-the Spodoptera litura voltage-gated sodium channel (SlNaVSC). After 200 ns of molecular dynamic simulation, the final structure of the complex showed stability in agreement with the experimental data. The above analysis corroborates the existence of a peptide toxin with insecticidal activity from a novel ICK family in L. intermedia venom and demonstrates that this peptide targets Nav channels. PMID:27488102

  12. 7S(1/2) ? 9S(1/2) two-photon spectroscopy of trapped francium.

    PubMed

    Simsarian, J E; Shi, W; Orozco, L A; Sprouse, G D; Zhao, W Z

    1996-12-01

    We report on the spectroscopic measurement of the (210)Fr 9S(1/2) energy obtained by two-photon excitation of atoms confined and cooled in a magneto-optic trap. The resonant intermediate level 7P(3/2) is the upper state of the trapping transition. We have measured the energy difference between the 9S(1/2) state and the 7S(1/2) ground state to be 25 671.021 +/- 0.006 cm(-1). PMID:19881852

  13. Structural biology of the S1P1 receptor.

    PubMed

    Hanson, Michael A; Peach, Robert

    2014-01-01

    The sphingosine 1 phosphate receptor family has been studied widely since the initial discovery of its first member, endothelium differentiation gene 1. Since this initial discovery, the family has been renamed and the primary member of the family, the S1P1 receptor, has been targeted for a variety of disease indications and successfully drugged for the treatment of patients with relapsing multiple sclerosis. Recently, the three-dimensional structure of the S1P1 receptor has been determined by X-ray crystallography and the specifics of the sphingosine 1 phosphate ligand binding pocket mapped. Key structural features for the S1P1 receptor will be reviewed and the potential binding modes of additional pharmacologically active agents against the receptor will be analyzed in an effort to better understand the structural basis of important receptor-ligand interactions. PMID:24728592

  14. S1-hypersensitive sites in eukaryotic promoter regions.

    PubMed Central

    Evans, T; Schon, E; Gora-Maslak, G; Patterson, J; Efstratiadis, A

    1984-01-01

    We have examined by fine mapping the S1 nuclease-hypersensitivity of the 5' flanking regions of the human beta-globin and rat preproinsulin II genes and of the SV40 origin/enhancer region. In all cases S1-hypersensitive sites are located in known or presumed promoter/regulatory regions. Though a consensus DNA sequence is not evident, all of these sites reside in predominantly homopurine-homopyrimidine stretches. The alternate (non-B) DNA structure which is revealed by the enzymatic probe is a sequence-dependent feature of a short stretch of DNA, which is retained upon transplantation into a foreign environment. The alternate structure exhibits S1-nicking patterns uniquely different from those associated with the presence of Z-DNA. Images PMID:6095186

  15. S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

    PubMed Central

    Yang, Jian; Zhou, Yan; Min, Ke; Yao, Qiang; Xu, Chun-Ni

    2014-01-01

    AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC). METHODS: We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values. RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens. CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use. PMID:25206296

  16. The S=1 Underscreened Anderson Lattice model for Uranium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Simões, A. S. R.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing coexistence of the Kondo effect and ferromagnetic order are investigated within the degenerate Anderson Lattice Hamiltonian, describing a 5f2 electronic configuration with S = 1 spins. Through the Schrieffer-Wolff transformation, both an exchange Kondo interaction for the S = 1 f-spins and an effective f-band term are obtained, allowing to describe the coexistence of Kondo effect and ferromagnetic ordering and a weak delocalization of the 5f-electrons. We calculate the Kondo and Curie temperatures and we can account for the pressure dependence of the Curie temperature of UTe.

  17. Winding Hopfions on R2×S1

    NASA Astrophysics Data System (ADS)

    Kobayashi, Michikazu; Nitta, Muneto

    2013-11-01

    We study Hopfions in the Faddeev-Skyrme model with potential terms on R2×S1. Apart from the conventional Hopfions, there exist winding Hopfions, that is, the lump (baby Skyrmion) strings with the lump charge Q with the U(1) modulus twisted P times along S1, having the Hopf charge PQ. We consider two kinds of potential terms, that is, the potential linear in the field and the ferromagnetic potential with two easy axes, and present stable solutions numerically. We also point out that a Q-lump carries the unit Hopf charge per the period in d=2+1.

  18. Bacterial versus human sphingosine-1-phosphate lyase (S1PL) in the design of potential S1PL inhibitors.

    PubMed

    Sanllehí, Pol; Abad, José-Luis; Casas, Josefina; Bujons, Jordi; Delgado, Antonio

    2016-09-15

    A series of potential active-site sphingosine-1-phosphate lyase (S1PL) inhibitors have been designed from scaffolds 1 and 2, arising from virtual screening using the X-ray structures of the bacterial (StS1PL) and the human (hS1PL) enzymes. Both enzymes are very similar at the active site, as confirmed by the similar experimental kinetic constants shown by the fluorogenic substrate RBM13 in both cases. However, the docking scoring functions used probably overestimated the weight of electrostatic interactions between the ligands and key active-site residues in the protein environment, which may account for the modest activity found for the designed inhibitors. In addition, the possibility that the inhibitors do not reach the enzyme active site should not be overlooked. Finally, since both enzymes show remarkable structural differences at the access channel and in the proximity to the active site cavity, caution should be taken when designing inhibitors acting around that area, as evidenced by the much lower activity found in StS1PL for the potent hS1PL inhibitor D. PMID:27475537

  19. Effects of long-term exposure to two fungicides, pyrimethanil and tebuconazole, on survival and life history traits of Italian tree frog (Hyla intermedia).

    PubMed

    Bernabò, Ilaria; Guardia, Antonello; Macirella, Rachele; Sesti, Settimio; Crescente, Antonio; Brunelli, Elvira

    2016-03-01

    Over the last few years, the hazards associated with the extensive use of fungicides have become an issue of great concern but, at present, the effects of these substances on amphibians remain poorly understood. The goal of the present study was to assess the effects of two commonly used fungicides, tebuconazole and pyrimethanil, on Italian Tree Frog (Hyla intermedia), a species frequently found in agricultural areas. Tadpoles were exposed to fungicides from developmental Gosner stage 25 (GS 25) to completion of metamorphosis (GS 46) and the whole exposure period lasted 78 days. For both tested fungicides we used two concentrations (5 and 50μg/L) that are comparable to those detected in surface waters, near agricultural fields. A variety of sublethal effects-on growth, development, behavior, and physiology-may be used for evaluating alterations induced by pollutants in amphibians. We estimated whether pyrimethanil and tebuconazole exposure impacted on H. intermedia life history traits. For this purpose, survival, growth, development, initiation of metamorphosis, success and size at metamorphosis, time to metamorphosis, and frequency of morphological abnormalities were evaluated. We showed, for all considered endpoints, that the exposure to tebuconazole exerts more harmful effects on H. intermedia than does exposure to pyrimethanil. Before the onset of metamorphic climax we showed, for both fungicides, that the low concentrations (5μg/L) induced significantly greater effects than the higher ones (50μg/L) on survival and deformity incidence. During the metamorphic climax, a complete reversal of this nonlinear trend takes place, and the percentage of animals initiating metamorphosis was reduced in fungicide-exposed groups in a concentration-dependent manner. Furthermore, a strong correlation emerged between fungicide exposure and the incidence of morphological abnormalities such as tail malformations, scoliosis, edema, mouth and limb deformities. Exposure to tested

  20. Human alpha s1-casein: purification and characterization.

    PubMed

    Rasmussen, L K; Due, H A; Petersen, T E

    1995-05-01

    The human counterpart of alpha s1-casein has been purified by a combination of gel-filtration and ion-exchange chromatography under denaturing conditions. SDS-PAGE analysis revealed the presence of a diffuse ladder with a high molecular mass which upon reduction was replaced by several closely spaced bands of lower molecular masses and a broad diffuse band corresponding to kappa-casein. Amino acid sequence analysis of the closely spaced bands all resulted in the same N-terminal sequence which was found to be homologous with alpha s1-casein from other species. Sequence analysis of a major radiolabelled tryptic peptide from purified 14C-carboxymethylated alpha s1-casein demonstrated that the protein contains at least two cysteine residues. As judged by SDS-PAGE in the presence or absence of a reducing agent, the molecular structure of the polymers constituting the ladder is composed of heteropolymers of alpha s1- and kappa-casein cross-linked by disulfide bonds. PMID:7749638

  1. Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

    PubMed

    Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

    2016-01-15

    Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders. PMID:26687487

  2. Is the addition of cisplatin to S-1 better than S-1 alone for patients with advanced gastroesophageal cancer?

    PubMed

    Ajani, Jaffer A

    2008-09-01

    The investigators of the recent phase III SPIRITS trial found that the addition of cisplatin to S-1 (a fourth generation oral fluoropyrimidine) provided a significant overall survival advantage (P = 0.04) over treatment with S-1 alone among previously untreated patients with advanced gastric cancer. In addition, the combination had an acceptable safety profile. This trial establishes a new first-line standard treatment for patients with advanced gastric cancer in Japan. Level 1 evidence for prolonged survival of patients with advanced gastroesophageal cancer has been established for docetaxel (V-325 trial) and cisplatin (SPIRITS trial) but not for S-1. Fluoropyrimidines (S-1 included) have been considered part of standard front-line therapy without the establishment of level 1 evidence for prolonging survival. The future lies in the rapid incorporation of biologic agents in combination with cytotoxics, with a continued focus on safety and convenience, and efforts to individualize therapy for each patient. Individualized therapy may be defined as the selection of optimum treatment for a specific patient on the basis of knowledge of the cancer's genetic and epigenetic alterations and the patient's genotype. PMID:18628737

  3. Molecular structure of Si_xS_(1-x) glasses

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Boolchand, P.

    2000-03-01

    Bulk Si_xS_1-x glasses in the 0.15S_1/2)4 tetrahedra, S_8-ring and Sn chains. The observed lineshapes change systematically with x, in a manner qualitatively similar to the case of corresponding Selenide glasses( D. Selvanathan, W. J. Bresser, P. Boolchand, B. Goodman Solid State Comm. 111, 619(1999)). Glass transition temperatures established by T-modulated DSC show an increase with x. Results of Raman and MDSC will be correlated, and discussed in relation to the nature of stiffness transitions anticipated in this binary glass system near x ~0.20.

  4. The Global S_1 Tide in Earth's Nutation

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Einšpigel, David; Salstein, David; Böhm, Johannes

    2016-05-01

    Diurnal S_1 tidal oscillations in the coupled atmosphere-ocean system induce small perturbations of Earth's prograde annual nutation, but matching geophysical model estimates of this Sun-synchronous rotation signal with the observed effect in geodetic Very Long Baseline Interferometry (VLBI) data has thus far been elusive. The present study assesses the problem from a geophysical model perspective, using four modern-day atmospheric assimilation systems and a consistently forced barotropic ocean model that dissipates its energy excess in the global abyssal ocean through a parameterized tidal conversion scheme. The use of contemporary meteorological data does, however, not guarantee accurate nutation estimates per se; two of the probed datasets produce atmosphere-ocean-driven S_1 terms that deviate by more than 30 μ as (microarcseconds) from the VLBI-observed harmonic of -16.2+i113.4 μ as. Partial deficiencies of these models in the diurnal band are also borne out by a validation of the air pressure tide against barometric in situ estimates as well as comparisons of simulated sea surface elevations with a global network of S_1 tide gauge determinations. Credence is lent to the global S_1 tide derived from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) and the operational model of the European Centre for Medium-Range Weather Forecasts (ECMWF). When averaged over a temporal range of 2004 to 2013, their nutation contributions are estimated to be -8.0+i106.0 μ as (MERRA) and -9.4+i121.8 μ as (ECMWF operational), thus being virtually equivalent with the VLBI estimate. This remarkably close agreement will likely aid forthcoming nutation theories in their unambiguous a priori account of Earth's prograde annual celestial motion.

  5. Two glucose/xylose transporter genes from the yeast Candida intermedia: first molecular characterization of a yeast xylose–H+ symporter

    PubMed Central

    Leandro, Maria José; Gonçalves, Paula; Spencer-Martins, Isabel

    2006-01-01

    Candida intermedia PYCC 4715 was previously shown to grow well on xylose and to transport this sugar by two different transport systems: high-capacity and low-affinity facilitated diffusion and a high-affinity xylose–proton symporter, both of which accept glucose as a substrate. Here we report the isolation of genes encoding both transporters, designated GXF1 (glucose/xylose facilitator 1) and GXS1 (glucose/xylose symporter 1) respectively. Although GXF1 was isolated by functional complementation of an HXT-null (where Hxt refers to hexose transporters) Saccharomyces cerevisiae strain, isolation of the GXS1 cDNA required partial purification and micro-sequencing of the transporter, identified by its relative abundance in cells grown on low xylose concentrations. Both genes were expressed in S. cerevisiae and the kinetic parameters of glucose and xylose transport were determined. Gxs1 is the first yeast xylose/glucose–H+ symporter to be characterized at the molecular level. Comparison of its amino acid sequence with available sequence data revealed the existence of a family of putative monosaccharide–H+ symporters encompassing proteins from several yeasts and filamentous fungi. PMID:16402921

  6. Fermentation and aerobic metabolism of cellodextrins by yeasts. [Candida wickerhamii; C. guiliermondii; C. molischiana; Debaryomyces polymorphus; Pichia guilliermondii; Clavispora lusitaniae; Kluyveromyces lactis; Brettanomyces claussenii; Rhodotorula minuta; Dekkera intermedia

    SciTech Connect

    Freer, S.N. )

    1991-03-01

    The fermentation and aerobic metabolism of cellodextrins by 14 yeast species or strains was monitored. When grown aerobically, Candida wickerhamii, C. guilliermondii, and C. molischiana metabolized cellodextrins of degree of polymerization 3 to 6. C. wicherhamii and C. molischiana also fermented these substrates, while C. guilliermondii fermented only cellodextrins of degree of polymerization {<=} 3. Debaryomyces polymorphus, Pichia guilliermondii, Clavispora lusitaniae, and one of two strains of Kluyveromyces lactis metabolized glucose, cellobiose, and cellotriose when grown aerobically. These yeasts also fermented these substrates, except for K. lactis, which fermented only glucose and cellobiose. The remaining species/strains tested, K. lactis, Brettanomyces claussenii, Brettanomyces anomalus, Kluyveromyces dobzhanskii, Rhodotorula minuta, and Dekkera intermedia, both fermented and aerobically metabolized glucose and cellobiose. Crude enzyme preparations from all 14 yeast species or strains were tested for ability to hydrolyze cellotriose and cellotretose. Most of the yeasts produced an enzyme(s) capable of hydrolyzing cellotriose. However, with two exceptions, R. minuta and P. guilliermondii, only the yeasts that metabolized cellodextrins of degree of polymerization >3 produced an enzyme(s) that hydrolyzed cellotretose.

  7. Metabolic indicators of oxidative stress correlate with haemichrome attachment to membrane, band 3 aggregation and erythrophagocytosis in beta-thalassaemia intermedia.

    PubMed

    Cappellini, M D; Tavazzi, D; Duca, L; Graziadei, G; Mannu, F; Turrini, F; Arese, P; Fiorelli, G

    1999-03-01

    Haematological data, genotype, transfusion requirements, metabolic indicators of oxidative stress (flux via hexose-monophosphate shunt (HMPS); steady state level of GSH and GSSG, NADPH and NADP; activity of anti-oxidant enzymes), parameters of membrane damage (aggregated band 3; membrane-bound haemichromes, autologous immunoglobulins (Igs) and C3 complement fragments) and erythrophagocytosis were measured in erythrocytes (RBC) of 15 beta-thalassaemia intermedia patients (nine splenectomized) with low, if any, transfusion requirements. Patients presented increased aggregated band 3, bound haemichromes, Igs and C3 complement fragments, and increased erythrophagocytosis. Bound haemichromes strongly correlated with aggregated band 3. Anti-band 3 Igs were predominantly associated with aggregated band 3. Erythrophagocytosis positively correlated with aggregated band 3, haemichromes and Igs, suggesting the involvement of haemichrome-induced band 3 aggregation in phagocytic removal of beta-thalassaemic RBC. Splenectomized patients showed higher degrees of membrane damage and phagocytosis, significantly higher numbers of circulating RBC precursors, and tendentially higher numbers of reticulocytes. Basal flux via HMPS was increased twofold, but HMPS stimulation by methylene blue was decreased, as was the glucose flux via HMPS. GSH was remarkably decreased, whereas NADPH was increased. Except for unchanged catalase and glutathione reductase, anti-oxidant enzymes had increased activity. Negative correlation between HMPS stimulation by methylene blue and bound haemichromes indicated that the ability to enhance HMPS may counteract haemichrome precipitation and limit consequent membrane damage leading to erythrophagocytosis. PMID:10086787

  8. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G. P.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Brucato, J. R.; Bolli, P.; Massi, F.; Tofani, G.

    2015-12-01

    Comets are uniquely pristine bodies providing unique insights about the formation of our Solar System. In this work, we focus on a dynamically new comet as it enters the inner Solar System for the first time after residing for billion of years in the Oort Cloud. Such comets are particularly important because they are thought to be not differentiated by solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH3(1,1) emission at 23.7 GHz towards comet C/2012 S1 (ISON) using a new dual-feed K band receiver mounted on the Medicina 32-m antenna. We observed the comet close to its perihelion, from 25 to 29 November 2013, when its heliocentric distance changed from 0.25 AU to 0.03 AU. We derive an upper limit of Q(NH3) of about 2.5×1029 mol s-1 on 26 November, that is consistent with the last peak of water production rate of ∼2×1030 mol s-1 within the last few days before the perihelion.

  9. Angular momentum budget of the radiational S1 ocean tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Dobslaw, Henryk; Poropat, Lea; Salstein, David; Böhm, Johannes

    2016-04-01

    The balance of diurnal S1 oceanic angular momentum (OAM) variations through torques at the sea surface and the bottom topography is validated using both a barotropic and a baroclinic numerical tide model. This analysis discloses the extent to which atmosphere-driven S1 forward simulations are reliable for use in studies of high-frequency polar motion and changes in length-of-day. Viscous and dissipative torques associated with wind stress, bottom friction, as well as internal tidal energy conversion are shown to be small, and they are overshadowed by gravitational and pressure-related interaction forces. In particular, the zonal OAM variability of S1 is almost completely balanced by the water pressure torque on the local bathymetry, whereas in the prograde equatorial case also the air pressure torque on the seafloor as well as ellipsoidal contributions from the non-spherical atmosphere and solid Earth must be taken into account. Overall, the OAM budget is well closed in both the axial and the equatorial directions, thus allowing for an identification of the main diurnal angular momentum sinks in the ocean. The physical interaction forces are found to be largest at shelf breaks and continental slopes in low latitudes, with the most dominant contribution coming from the Indonesian archipelago.

  10. S1P metabolism in cancer and other pathological conditions

    PubMed Central

    Leong, Weng In

    2010-01-01

    Nearly two decades ago, the sphingolipid metabolite sphingosine 1-phosphate was discovered to function as a lipid mediator and regulator of cell proliferation. Since that time, sphingosine 1-phosphate has been shown to mediate a diverse array of fundamental biological processes including cell proliferation, migration, invasion, angiogenesis, vascular maturation and lymphocyte trafficking. Sphingosine 1-phosphate acts primarily via signaling through five ubiquitously expressed G protein-coupled receptors. Intracellular sphingosine 1-phosphate molecules are transported extracellularly and gain access to its cognate receptors for autocrine and paracrine fashion and for signaling at distant sites reached through blood and lymphatic circulation systems. Intracellular pools of sphingosine 1-phosphate available for signaling are tightly regulated by three enzymes that include sphinosine kinase, S1P lyase and S1P phosphatase. Alterations in S1P levels as well as the enzymes involved in its synthesis and catabolism have been observed in many types of malignancy. These enzymes are being evaluated for their role in mediating cancer formation and progression, as well as their potential to serve as targets of anti-cancer therapeutics. In this review, the impact of sphingosine 1-phosphate, its cognate receptors, and the enzymes of sphingosine 1-phosphate metabolism on cell survival, apoptosis, autophagy, cellular transformation, invasion, angiogenesis and hypoxia in relation to cancer biology and treatment are discussed. PMID:20167244

  11. Argyres-Douglas theories, S 1 reductions, and topological symmetries

    NASA Astrophysics Data System (ADS)

    Buican, Matthew; Nishinaka, Takahiro

    2016-01-01

    In a recent paper, we proposed closed-form expressions for the superconformal indices of the ({A}1,{A}2n-3) and ({A}1,{D}2n) Argyres-Douglas (AD) superconformal field theories (SCFTs) in the Schur limit. Following up on our results, we turn our attention to the small S 1 regime of these indices. As expected on general grounds, our study reproduces the S 3 partition functions of the resulting dimensionally reduced theories. However, we show that in all cases—with the exception of the reduction of the ({A}1,{D}4) SCFT—certain imaginary partners of real mass terms are turned on in the corresponding mirror theories. We interpret these deformations as R symmetry mixing with the topological symmetries of the direct S 1 reductions. Moreover, we argue that these shifts occur in any of our theories whose four-dimensional { N }=2 superconformal U{(1)}R symmetry does not obey an SU(2) quantization condition. We then use our R symmetry map to find the four-dimensional ancestors of certain three-dimensional operators. Somewhat surprisingly, this picture turns out to imply that the scaling dimensions of many of the chiral operators of the four-dimensional theory are encoded in accidental symmetries of the three-dimensional theory. We also comment on the implications of our work on the space of general { N }=2 SCFTs.

  12. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    SciTech Connect

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  13. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors

    PubMed Central

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E.; O’Carroll, Simon J.; Graham, E. Scott

    2016-01-01

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors. PMID:26813587

  14. Effect of anisotropy in the S=1 underscreened Kondo lattice

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Lacroix, Claudine; Iglesias, José Roberto; Coqblin, Bernard

    2014-12-01

    We study the effect of crystal field anisotropy in the underscreened S=1 Kondo lattice model. Starting from the two orbital Anderson lattice model and including a local anisotropy term, we show, through Schrieffer-Wolff transformation, that local anisotropy is equivalent to an anisotropic Kondo interaction (J∥≠J⊥). The competition and coexistence between ferromagnetism and Kondo effect in this effective model is studied within a generalized mean-field approximation. Several regimes are obtained, depending on the parameters, exhibiting or not coexistence of magnetic order and Kondo effect. Particularly, we show that a re-entrant Kondo phase at low temperature can be obtained. We are also able to describe phases where the Kondo temperature is smaller than the Curie temperature (TK

  15. Dynamical instability in the S =1 Bose-Hubbard model

    NASA Astrophysics Data System (ADS)

    Asaoka, Rui; Tsuchiura, Hiroki; Yamashita, Makoto; Toga, Yuta

    2016-01-01

    We study the dynamical instabilities of superfluid flows in the S =1 Bose-Hubbard model. The time evolution of each spin component in a condensate is calculated based on the dynamical Gutzwiller approximation for a wide range of interactions, from a weakly correlated regime to a strongly correlated regime near the Mott-insulator transition. Owing to the spin-dependent interactions, the superfluid flow of the spin-1 condensate decays at a different critical momentum from a spinless case when the interaction strength is the same. We furthermore calculate the dynamical phase diagram of this model and clarify that the obtained phase boundary has very different features depending on whether the average number of particles per site is even or odd. Finally, we analyze the density and spin modulations that appear in association with the dynamical instability. We find that spin modulations are highly sensitive to the presence of a uniform magnetic field.

  16. Confinement and power balance in the S-1 spheromak

    SciTech Connect

    Levinton, F.M.; Meyerhofer, D.D.; Mayo, R.M.; Janos, A.C.; Ono, Y.; Ueda, Y.; Yamada, M.

    1989-07-01

    The confinement and scaling features of the S-1 spheromak have been investigated using magnetic, spectroscopic, and Thomson scattering data in conjunction with numerical modeling. Results from the multipoint Thomson scattering diagnostic shows that the central beta remains constant (/beta//sub to/ /approximately/ 5%) as the plasma current density increases from 0.68--2.1 MA/m/sup 2/. The density is observed to increase slowly over this range, while the central electron temperature increases much more rapidly. Analysis of the global plasma parameters shows a decrease in the volume average beta and energy confinement as the total current is increased. The power balance has been modeled numerically with a 0-D non-equilibrium time-dependent coronal model and is consistent with the experimental observations. 20 refs., 12 figs., 2 tabs.

  17. Ultraviolet spectroscopy of comet ISON (2012 S1)

    NASA Astrophysics Data System (ADS)

    Weaver, H.; A'Hearn, M.; Feldman, P.; Bodewits, D.; Combi, M.; Dello Russo, N.; McCandliss, S.

    2014-07-01

    We performed ultraviolet (UV) spectroscopy of Comet ISON (C/2012 S1) with the Hubble Space Telescope (HST) to monitor the evolution of CO production with heliocentric distance, search for compositional changes associated with the intense heating episode near perihelion, and measure the D/H ratio. We observed C/ISON with Hubble at four different epochs: May 2.5 (r=3.8 au, Δ=4.3 au), Oct 8.8 (r=1.5 au, Δ= 1.9 au), Oct 21.9 (r=1.23 au, Δ = 1.53 au), and Nov 1.5 (r=1.0 au, Δ =1.2 au). No molecular or atomic emissions were detected in May, but a stringent upper limit on the CO production rate was obtained (Q[CO] ≤ 1.0 × 10^{27} molecules s^{-1}, 3 σ). OH emission was detected during all the later observations and showed strong temporal variations on Nov 1. CO was clearly detected on Oct 21.9 and Nov 1.5, from which we derive CO/H_{2}O ˜0.015. Both atomic carbon and sulfur emissions were detected on Nov 1. No atomic deuterium emission was detected during the attempts to measure it on Nov 1, as the comet's gas production rates were significantly smaller than some early predictions suggested. A lightcurve derived from HST optical imaging observations on Nov 1, contemporaneous with the UV spectroscopy, suggests a nucleus rotational period of ˜10.4 hr, but the range of plausible values is fairly broad.

  18. Possible Dust Models for C/2012 S1

    NASA Astrophysics Data System (ADS)

    Yanamandra-Fisher, P. A.

    2014-12-01

    Comet C/2012 S1 (ISON) provided a great opportunity to study a dynamically new Oort-cloud comet on its initial and only passage through the inner solar system. Contrary to expectations, the comet's activity fluctuated from high through a quiescent phase, and a major outburst days before its perihelion passage, ending in a dramatic race to complete disintegration on perihelion day, 28 November 2013. Amateur observations to professional ground-based, sub-orbital telescopes indicate the various changes of visible factors such as Afrho, a proxy for dust activity, and the measured production rates for water, consistent with the disintegration of the nucleus. Hines et al. (2013; ApJ Lett. 780) detected positive polarization in the inner coma and negative polarization in the outer coma, indicative of a jet, independently confirmed by Li et al. (2013, ApJ Lett., 779). Thermal emission observations of the comet pre-perihelion from NAOJ/Subaru/COMICS, a mid-infrared spectrometer, indicated a body with an equivalent brightness temperature of 265K (Ootsubo et al., 2013, ACM, Helsinki,FI); thermal observations acquired at the NASA/Infrared Telescope Facility (IRTF) with The Aerospace Corporation spectrometer (BASS, PI. R. Russell), before and after the November 12, 2013 outburst observed by the CIOC_ISON amateur network, indicates a brightness temperature of 330K and the presence, albeit weak, of the 11.3-micron crystalline silicate feature (Sitko et al., 2014, LPI abstract 1537). A Monte Carlo comet dust tail model, applied to extract the dust environment parameters of comet C/2012 S1 (ISON) from both Earth-based and Solar and Heliospheric Observatory (SOHO) calibrated observations, performed from about 6 AU (inbound), to right after perihelion passage, when just a small portion of the original comet nucleus survived in the form of a cloud of tiny particles, indicates that particles underwent disintegration and fragmentation (Moreno et al., 2014, ApJ Lett., 791). Ongoing work

  19. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human

    PubMed Central

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3–4 compared to those with 0–2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target. PMID:27562371

  20. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    PubMed

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target. PMID:27562371

  1. Photometry of distant active comet C/2010 S1 (LINEAR)

    NASA Astrophysics Data System (ADS)

    Shubina, O.; Kulyk, I.; Korsun, P.; Romanjuk, Ya.

    2014-12-01

    We present the results of photometric observations of a dynamically new comet C/2010 S1 (LINEAR), conducted on June 18, 2012. The comet demonstrated a considerable level of physical activity at a heliocentric distance of 6.3 AU. The brightness, measured under a phase angle of 8.9 degrees, was equal to 14.55^{m}±0.06^{m} and 14.21^{m}±0.04^{m} in V- and R-bands, respectively. The brightness distribution over the coma was found to be inversely proportional to the projected onto the sky plane nucleocentric distance, with a slope of approximately -1. Therefore, the calculated Afρ parameter, approximately 8400 cm and 8200 cm for V and R filters, respectively, was used to estimate the dust production rate. Assuming a steady outflow of dust particles from the nucleus, the dust production rate was estimated to be between 20 and 60 kg/s, depending on the assumed value of the grain's albedo. The V-R colour index obtained from the near-nucleus region of the coma is in agreement with the solar V-R colour index, and does not indicate significant reddening of the reflected solar radiation in the spectral region of 540-683 nm.

  2. Outgassing and chemical evolution of C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Dello Russo, Neil; Vervack, Ronald J.; Kawakita, Hideyo; Cochran, Anita; McKay, Adam J.; Harris, Walter M.; Weaver, Harold A.; Lisse, Carey M.; DiSanti, Michael A.; Kobayashi, Hitomi; Biver, Nicolas; Bockelée-Morvan, Dominique; Crovisier, Jacques; Opitom, Cyrielle; Jehin, Emmanuel

    2015-11-01

    Volatile production rates, relative abundances, rotational temperatures, and spatial distributions in the coma were measured in C/2012 S1 (ISON) using long-slit high-dispersion (λ/Δλ ~ 25,000) infrared spectroscopy as part of a worldwide observing campaign. Spectra were obtained on UT 2013 October 26 and 28 with NIRSPEC at the W. M. Keck Observatory, and UT 2013 November 19 and 20 with CSHELL at the NASA IRTF. H2O was detected on all dates, with production rates increasing by about a factor of 40 between October 26 (Rh = 1.12 AU) and November 20 (Rh = 0.43 AU). Short-term variability of H2O was also seen as the production rate increased by nearly a factor of two during observations obtained over a period of about six hours on November 19. C2H6, CH3OH and CH4 abundances were slightly depleted relative to H2O in ISON compared to mean values for comets measured at infrared wavelengths. On the November dates, C2H2, HCN and OCS abundances relative to H2O appear to be close to the range of mean values, whereas H2CO and NH3 were significantly enhanced. We will compare derived chemical abundances in ISON to other comets measured with infrared spectroscopy.

  3. Sphingosine 1-Phosphate (S1P) Receptor Agonists Mediate Pro-fibrotic Responses in Normal Human Lung Fibroblasts via S1P2 and S1P3 Receptors and Smad-independent Signaling

    PubMed Central

    Sobel, Katrin; Menyhart, Katalin; Killer, Nina; Renault, Bérengère; Bauer, Yasmina; Studer, Rolf; Steiner, Beat; Bolli, Martin H.; Nayler, Oliver; Gatfield, John

    2013-01-01

    Synthetic sphingosine 1-phosphate receptor 1 modulators constitute a new class of drugs for the treatment of autoimmune diseases. Sphingosine 1-phosphate (S1P) signaling, however, is also involved in the development of fibrosis. Using normal human lung fibroblasts, we investigated the induction of fibrotic responses by the S1P receptor (S1PR) agonists S1P, FTY720-P, ponesimod, and SEW2871 and compared them with the responses induced by the known fibrotic mediator TGF-β1. In contrast to TGF-β1, S1PR agonists did not induce expression of the myofibroblast marker α-smooth muscle actin. However, TGF-β1, S1P, and FTY720-P caused robust stimulation of extracellular matrix (ECM) synthesis and increased pro-fibrotic marker gene expression including connective tissue growth factor. Ponesimod showed limited and SEW2871 showed no pro-fibrotic potential in these readouts. Analysis of pro-fibrotic signaling pathways showed that in contrast to TGF-β1, S1PR agonists did not activate Smad2/3 signaling but rather activated PI3K/Akt and ERK1/2 signaling to induce ECM synthesis. The strong induction of ECM synthesis by the nonselective agonists S1P and FTY720-P was due to the stimulation of S1P2 and S1P3 receptors, whereas the weaker induction of ECM synthesis at high concentrations of ponesimod was due to a low potency activation of S1P3 receptors. Finally, in normal human lung fibroblast-derived myofibroblasts that were generated by TGF-β1 pretreatment, S1P and FTY720-P were effective stimulators of ECM synthesis, whereas ponesimod was inactive, because of the down-regulation of S1P3R expression in myofibroblasts. These data demonstrate that S1PR agonists are pro-fibrotic via S1P2R and S1P3R stimulation using Smad-independent pathways. PMID:23589284

  4. WILL COMET ISON (C/2012 S1) SURVIVE PERIHELION?

    SciTech Connect

    Knight, Matthew M.; Walsh, Kevin J.

    2013-10-10

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ∼200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm{sup –3} are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm{sup –3}, with the chances of disruption increasing for lower density, faster prograde rotation, and increasing elongation of the nucleus. Given current constraints on ISON's nucleus properties and the typically determined values for these properties among all comets, we find tidal disruption to be unlikely unless other factors (e.g., spin-up via torquing) affect ISON substantially. Whether or not disruption occurs, the largest remnant must be big enough to survive subsequent mass loss due to sublimation in order for ISON to remain a viable comet well after perihelion.

  5. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Bolli, P.; Brucato, J.; Massi, F.; Tofani, G.

    2014-07-01

    Comets are pristine bodies of the Solar System and their studies can give precious hints on the formation of the Solar System itself. New comets, coming form the Oort Colud at their first passage close to the Sun, are particularly important, because they are not differentiated by the Solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH_3(1,1) emission at 23.7 GHz in comet C/2012 S1 ISON using a new dual-feed K-band receiver mounted on the Medicina 32-m antenna. We observed the comet once close to its perihelion, from 2013 Nov. 25 to Nov. 28, when its heliocentric distance changed from 0.25 au to 0.03 au. We integrated about 6 hrs per day, obtaining high-spectral-resolution (1 km/s) spectra with a typical rms noise of 10 mK. Such sensitivity allowed us to derive an upper limit of Q(NH_3) of about 2.5 ×10^{29} mol/s on November 26. This upper limit would correspond to a Q(H_2O) of about 2.5 ×10^{31} mol/s, assuming the typical Q(H_2O)/Q(NH_3) ratio of 100. These findings confirm that no significant Q(H_2O) enhancement happened near the perihelion, consistent with a definitive decrease of molecules production rate.

  6. Ultraviolet Observations Of C/2012 S1 (ISON) By MAVEN

    NASA Astrophysics Data System (ADS)

    Crismani, Matteo; Schneider, N.; Stewart, I.; Combi, M.; Fougere, N.

    2013-10-01

    On its journey to Mars, MAVEN has been serendipitously positioned to study the anticipated sungrazing comet C/2012 S1(ISON) and offers important scientific observations. The MAVEN mission is the first to attempt to understand the evolution of the Martian atmosphere by determining the effects of atmospheric loss to space. The IUVS instrument has two large field of regard(55x11 and 24x11 degrees) and observes in the mid and far ultraviolet (115-340 nm). It was designed to be able to map the atmosphere in several neutral and some ionized species. These performance characteristics make IUVS ideal to study ISON, as it can take both two dimensional spatial scans as well as spectral data. Tentative plans indicate the comet can be acquired on Dec 8th, assuming that the comet survives the near sun encounter. If observations prove possible, IUVS will be able to study ISON shortly after perihelion, and from a different vantage point from Earth. Science goals include UV observations of D/H, morphology & time evolution of the hydrogen coma and UV spectroscopy of the inner coma. IUVS can potentially make a major contribution to the international community by measuring D/H, thus contributing to our understanding of the origin of Earth’s water. IUVS will also make MUV and FUV observations of molecular species in the inner coma, valuable for understanding the chemical evolution of cometary molecular gases. The poster will present provisional observation plans as well as simulated spectra and spatial profiles. We welcome input from the community on these plans, in the spirit of maximizing the scientific return of the international campaign. The work has been supported by the MAVEN project and NASA Planetary Atmospheres grant NNX09AB59G.

  7. Gravitational dynamics in s+1+1 dimensions

    SciTech Connect

    Gergely, Laszlo A.; Kovacs, Zoltan

    2005-09-15

    We present the concomitant decomposition of an (s+2)-dimensional space-time both with respect to a timelike and a spacelike direction. The formalism we develop is suited for the study of the initial value problem and for canonical gravitational dynamics in braneworld scenarios. The bulk metric is replaced by two sets of variables. The first set consists of one tensorial (the induced metric g{sub ij}), one vectorial (M{sup i}) and one scalar (M) dynamical quantity, all defined on the s space. Their time evolutions are related to the second fundamental form (the extrinsic curvature K{sub ij}), the normal fundamental form (K{sup i}) and normal fundamental scalar (K), respectively. The nondynamical set of variables is given by the lapse function and the shift vector, which however has one component less. The missing component is due to the externally imposed constraint, which states that physical trajectories are confined to the (s+1)-dimensional brane. The pair of dynamical variables (g{sub ij}, K{sub ij}), well known from the Arnowitt-Deser-Misner decomposition is supplemented by the pairs (M{sup i}, K{sup i}) and (M, K) due to the bulk curvature. We give all projections of the junction condition across the brane and prove that for a perfect fluid brane neither of the dynamical variables has jump across the brane. Finally we complete the set of equations needed for gravitational dynamics by deriving the evolution equations of K{sub ij}, K{sup i} and K on a brane with arbitrary matter.

  8. Localization of amylin-like immunoreactivity in melanocyte-stimulating hormone-containing cells of the pars intermedia but not those of the pars distalis in the axolotl (Ambystoma mexicanum) pituitary.

    PubMed

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2016-04-01

    Immunohistochemical techniques were employed to investigate the distribution of amylin-like immunoreactivity in the axolotl (Ambystoma mexicanum) pituitary. Amylin-immunoreactive cells were observed in the pars intermedia, and these cells were found to be immunoreactive for α-melanocyte-stimulating hormone (αMSH) as well. In contrast, αMSH-immunoreactive cells in the pars distalis were immuno-negaitive for amylin. These light microscopic findings were confirmed by immunoelectron microscopy. Amylin-immunoreactive signals were located on the haloes of presumable secretory granules in association with αMSH-immunoreactive signals in the amylin-positive cells. However, in the pars distalis, the αMSH-positive cells did not contain amylin-immunoreactive secretory granules. Western blot analysis of axolotl pituitary extracts revealed the labeling of a protein band at approximately 10.5-kDa by the anti-rat amylin serum, which was not labeled by the anti-αMSH antibody. These findings indicate that amylin secreted from MSH-producing cells in the pars intermedia may modulate MSH secretion in an autocrine fashion and may participate in MSH functions such as fatty homeostasis together with MSH. PMID:26797189

  9. A randomized Phase I/II Trial of HQK-1001, an oral fetal globin gene inducer, in β–thalassaemia intermedia and HbE/β–thalassaemia

    PubMed Central

    Fucharoen, Suthat; Inati, Adlette; Siritanaratku, Noppadol; Thein, Swee Lay; Wargin, William C.; Koussa, Suzanne; Taher, Ali; Chaneim, Nattawara; Boosalis, Michael; Berenson, Ronald; Perrine, Susan P.

    2014-01-01

    β–thalassemia intermedia syndromes (BTI) cause hemolytic anemia, ineffective erythropoiesis, and widespread complications. Higher fetal globin expression within genotypes reduces globin imbalance and ameliorates anemia. Sodium 2,2 dimethylbutyrate (HQK-1001), an orally bioavailable short-chain fatty acid derivative, induces γ-globin expression experimentally and is well-tolerated in normal subjects. Accordingly, a randomized, blinded, placebo-controlled, Phase I/II trial was performed in 21 adult BTI patients (14 with HbE/β0 thalassemia and 7 with β+/β0 thalassemia intermedia, to determine effective doses for fetal globin induction, safety, and tolerability. HQK-1001 or placebo were administered once daily for 8 weeks at four dose levels (10, 20, 30, or 40 mg/kg/day), and subjects were monitored for laboratory and clinical events. Pharmacokinetic profiles demonstrated a t1/2 of 10–12 hours. Adverse events with HQK-1001 treatment were not significantly different from placebo treatment. Median HbF increased with the 20 mg/kg treatment doses above baseline levels by 6.6% and 0.44 g/dL (p <0.01) in 8/9 subjects; total hemoglobin (Hgb) increased by a mean of 1.1 gm/dL in 4/9 subjects. These findings identify a safe oral therapeutic which induces fetal globin in BTI. Further investigation of HQK-1001 with longer dosing to definitively evaluate its hematologic potential appears warranted. PMID:23530969

  10. Lavandin (Lavandula × intermedia Emeric ex Loiseleur) essential oil from Spain: determination of aromatic profile by gas chromatography-mass spectrometry, antioxidant and lipoxygenase inhibitory bioactivities.

    PubMed

    Carrasco, Alejandro; Martinez-Gutierrez, Ramiro; Tomas, Virginia; Tudela, Jose

    2016-01-01

    Lavandin (Lavandula × intermedia Emeric ex Loiseleur) essential oils (EOs), from Abrial, Super and Grosso cultivars, cultivated and extracted in the South East of Spain, were analysed by using GC/MS to determine their composition, in both relative (peak area) and absolute (using standard curves) concentrations. Linalool (34-47%), linalyl acetate (17-34%), camphor (4-9%) and eucalyptol (3-7%) were determined as the main molecules. This characterisation was completed with the enantioselective gas chromatography, where ( - )-linalool, (+)-camphor and ( - )-linalyl acetate were determined as the main components. Antioxidant activity was evaluated positively by several methods: activity against free radicals, chelating and reducing power, probably due to linalool and linalyl acetate. Mild inhibitory activity on lipoxygenase was observed supporting potential anti-inflammatory activity, mainly due to linalool and camphor. These properties support the potential use of L. × intermedia essential oils as natural cosmetic and natural pharmaceutical ingredient to fight several skin diseases. PMID:26106980

  11. A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)

    PubMed Central

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-01-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)–S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. PMID:26631556

  12. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

    PubMed

    Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target. PMID:27160553

  13. Ligand-binding pocket shape differences between S1P1 and S1P3 determine efficiency of chemical probe identification by uHTS

    PubMed Central

    Schürer, Stephan C.; Brown, Steven J.; Cabrera, Pedro Gonzales; Schaeffer, Marie-Therese; Chapman, Jacqueline; Jo, Euijung; Chase, Peter; Spicer, Tim; Hodder, Peter; Rosen, Hugh

    2008-01-01

    We have studied the Sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonists chemotypes for each of the S1P1 and S1P3 receptors. uHTS for S1P1 was more effective than for S1P3, with many selective, low nanomolar hits of proven mechanism emerging for. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for sub-type selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of head-group interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 vs. S1P3 in this closely related receptor family. PMID:18590333

  14. [Stable and efficient expression of hepatitis B virus S antigen and preS1 epitope fusion protein (S/preS1) in CHO cells].

    PubMed

    Yang, Zhenxi; Li, Shichong; Liu, Hong; Zhang, Miao; Ye, Lingling; Wu, Yanzhuo; Xu, Mingbo; Chen, Zhaolie

    2013-12-01

    Hepatitis B surface antigen (HBsAg) carrying preS sequences could be an ideal candidate for a new hepatitis B virus (HBV) vaccine with higher efficacy. Here we report the success in achieving efficient and stable expression of hepatitis B virus S antigen and preS1 epitope fusion protein (S/preS1) in CHO cells. The HMRCHEF53u/Neo-S/preS1 expression vector carrying S/preS1 gene was constructed and transfected into CHO-S cells. A stable and high-expression CHO cell line, named 10G6, was selected by ELISA and limiting dilution analysis. Western blotting analysis showed S/preS1 expressed from 10G6 cells possessed both S and preS1 antigenicity. 10G6 cells displayed characters of favorable growth and stable S/preS1 expression in repeated batch cultures as evaluated by viable cell density, viability and S/preS1 concentration. And cultivation of 10G6 cells in fed-batch mode resulted in S/preS1 production at 17-20 mg/L with viable cell density at 7 x 10(6)-10 x 10(6) cells/mL. PMID:24660628

  15. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2

    PubMed Central

    Patmanathan, Sathya Narayanan; Johnson, Steven P.; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R.; Herr, Deron R.; Murray, Paul G.; Yap, Lee Fah; Paterson, Ian C.

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target. PMID:27160553

  16. Genetic characterization of three qnrS1-harbouring multidrug-resistance plasmids and qnrS1-containing transposons circulating in Ho Chi Minh City, Vietnam

    PubMed Central

    Le, Vien; Nhu, Nguyen Thi Khanh; Cerdeno-Tarraga, Ana; Campbell, James I.; Tuyen, Ha Thanh; Nhu, Tran Do Hoang; Tam, Pham Thi Thanh; Schultsz, Constance; Thwaites, Guy; Thomson, Nicholas R.

    2015-01-01

    Plasmid-mediated quinolone resistance (PMQR) refers to a family of closely related genes that confer decreased susceptibility to fluoroquinolones. PMQR genes are generally associated with integrons and/or plasmids that carry additional antimicrobial resistance genes active against a range of antimicrobials. In Ho Chi Minh City (HCMC), Vietnam, we have previously shown a high frequency of PMQR genes within commensal Enterobacteriaceae. However, there are limited available sequence data detailing the genetic context in which the PMQR genes reside, and a lack of understanding of how these genes spread across the Enterobacteriaceae. Here, we aimed to determine the genetic background facilitating the spread and maintenance of qnrS1, the dominant PMQR gene circulating in HCMC. We sequenced three qnrS1-carrying plasmids in their entirety to understand the genetic context of these qnrS1-embedded plasmids and also the association of qnrS1-mediated quinolone resistance with other antimicrobial resistance phenotypes. Annotation of the three qnrS1-containing plasmids revealed a qnrS1-containing transposon with a closely related structure. We screened 112 qnrS1-positive commensal Enterobacteriaceae isolated in the community and in a hospital in HCMC to detect the common transposon structure. We found the same transposon structure to be present in 71.4 % (45/63) of qnrS1-positive hospital isolates and in 36.7 % (18/49) of qnrS1-positive isolates from the community. The resulting sequence analysis of the qnrS1 environment suggested that qnrS1 genes are widely distributed and are mobilized on elements with a common genetic background. Our data add additional insight into mechanisms that facilitate resistance to multiple antimicrobials in Gram-negative bacteria in Vietnam. PMID:26272054

  17. The S1P/S1PR2 axis regulates early airway T cell infiltration in murine mast cell-dependent acute allergic responses

    PubMed Central

    Oskeritzian, Carole A.; Hait, Nitai C.; Wedman, Piper; Chumanevich, Alena; Kolawole, Elizabeth M.; Price, Megan M.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Ryan, John J.; Milstien, Sheldon; Sabbadini, Roger; Spiegel, Sarah

    2014-01-01

    Background Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid produced by mast cells (MC) upon cross-linking of their high affinity receptors for IgE by antigen (Ag) that can amplify MC responses by binding to its S1P receptors. Acute MC-dependent allergic reaction can lead to systemic shock but the early events of its development in lung tissues have not been investigated, and S1P functions in the onset of allergic processes remain to be examined. Objective We used a highly specific neutralizing anti-S1P antibody (mAb) and an S1P receptor 2 (S1PR2) antagonist, JTE-013, to study S1P and S1PR2 signaling contributions to MC- and IgE-dependent airway allergic responses in mice within minutes after Ag challenge. Methods Allergic reaction was triggered by a single intraperitoneal (i.p.) dose of Ag in sensitized mice pre-treated i.p. with anti-S1P or isotype control mAb, or JTE-013 or vehicle prior to Ag challenge. Results Kinetics experiments revealed early pulmonary infiltration of mostly T cells around blood vessels of sensitized mice 20 minutes post-Ag exposure. Pre-treatment with anti-S1P mAb inhibited in vitro MC activation, as well as in vivo development of airway infiltration and MC activation, reducing serum levels of histamine, cytokines and the chemokines MCP-1/CCL2, MIP-1α/CCL3 and RANTES/CCL5. S1PR2 antagonism or deficiency, or MC deficiency recapitulated these results. Both in vitro and in vivo experiments demonstrated MC S1PR2 dependency for chemokine release and the necessity for signal transducer and activator of transcription 3 (Stat3) activation. Conclusion Activation of S1PR2 by S1P and downstream Stat3 signaling in MC regulate early T cell recruitment to antigen-challenged lungs by chemokine production. PMID:25512083

  18. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications

    PubMed Central

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction. PMID:26539121

  19. 26 CFR 1.6050S-1 - Information reporting for qualified tuition and related expenses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Information reporting for qualified tuition and related expenses. 1.6050S-1 Section 1.6050S-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050S-1 Information reporting for...

  20. 26 CFR 31.3121(s)-1 - Concurrent employment by related corporations with common paymaster.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with common paymaster. 31.3121(s)-1 Section 31.3121(s)-1 Internal Revenue INTERNAL REVENUE SERVICE... Revenue Code of 1954) General Provisions § 31.3121(s)-1 Concurrent employment by related corporations with... this section. Section 3121(s) and this section apply only to remuneration disbursed in the form...

  1. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts

    PubMed Central

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). The conservation of both C/S1 bZIP interactions and SIRT remains poorly characterized in non-model species, leaving their evolutionary origin uncertain and limiting crop research. In this work, we explored recently published plant sequencing data to establish a detailed phylogeny of C and S1 bZIPs, investigating their intertwined role in plant evolution, and the origin of SIRT. Our analyses clarified C and S1 bZIP orthology relationships in angiosperms, and identified S1 sequences in gymnosperms. We experimentally showed that the gymnosperm orthologs are regulated by SIRT, tracing back the origin of this unique regulatory mechanism to the ancestor of seed plants. Additionally, we discovered an earlier S ortholog in the charophyte algae Klebsormidium flaccidum, together with a C ortholog. This suggests that C and S groups originated by duplication from a single algal proto-C/S ancestor. Based on our observations, we propose a model wherein the C/S1 bZIP dimer network evolved in seed plants from pre-existing C/S bZIP interactions. PMID:27457880

  2. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts.

    PubMed

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). The conservation of both C/S1 bZIP interactions and SIRT remains poorly characterized in non-model species, leaving their evolutionary origin uncertain and limiting crop research. In this work, we explored recently published plant sequencing data to establish a detailed phylogeny of C and S1 bZIPs, investigating their intertwined role in plant evolution, and the origin of SIRT. Our analyses clarified C and S1 bZIP orthology relationships in angiosperms, and identified S1 sequences in gymnosperms. We experimentally showed that the gymnosperm orthologs are regulated by SIRT, tracing back the origin of this unique regulatory mechanism to the ancestor of seed plants. Additionally, we discovered an earlier S ortholog in the charophyte algae Klebsormidium flaccidum, together with a C ortholog. This suggests that C and S groups originated by duplication from a single algal proto-C/S ancestor. Based on our observations, we propose a model wherein the C/S1 bZIP dimer network evolved in seed plants from pre-existing C/S bZIP interactions. PMID:27457880

  3. The Clinically-tested S1P Receptor Agonists, FTY720 and BAF312, Demonstrate Subtype-Specific Bradycardia (S1P1) and Hypertension (S1P3) in Rat

    PubMed Central

    Fryer, Ryan M.; Muthukumarana, Akalushi; Harrison, Paul C.; Nodop Mazurek, Suzanne; Chen, Rong Rhonda; Harrington, Kyle E.; Dinallo, Roger M.; Horan, Joshua C.; Patnaude, Lori; Modis, Louise K.; Reinhart, Glenn A.

    2012-01-01

    Sphingosine-1-phospate (S1P) and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1PX receptor agonist) produces modest hypertension in patients (2–3 mmHg in 1-yr trial) as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension), and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P1,5 agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min) or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min) elicited acute bradycardia in anesthetized rats demonstrating an S1P1 mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d) elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls), BAF312 (0.3, 3.0, 30.0 mg/kg/d) had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P3 receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P1 receptors mediate bradycardia while hypertension is mediated by S1P3 receptor activation. PMID:23285242

  4. The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁) and hypertension (S1P₃) in rat.

    PubMed

    Fryer, Ryan M; Muthukumarana, Akalushi; Harrison, Paul C; Nodop Mazurek, Suzanne; Chen, Rong Rhonda; Harrington, Kyle E; Dinallo, Roger M; Horan, Joshua C; Patnaude, Lori; Modis, Louise K; Reinhart, Glenn A

    2012-01-01

    Sphingosine-1-phospate (S1P) and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1P(X) receptor agonist) produces modest hypertension in patients (2-3 mmHg in 1-yr trial) as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension), and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P₁,₅ agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min) or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min) elicited acute bradycardia in anesthetized rats demonstrating an S1P₁ mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d) elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls), BAF312 (0.3, 3.0, 30.0 mg/kg/d) had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P₃ receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P₁ receptors mediate bradycardia while hypertension is mediated by S1P₃ receptor activation. PMID:23285242

  5. A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer†

    PubMed Central

    Ueno, M.; Okusaka, T.; Omuro, Y.; Isayama, H.; Fukutomi, A.; Ikeda, M.; Mizuno, N.; Fukuzawa, K.; Furukawa, M.; Iguchi, H.; Sugimori, K.; Furuse, J.; Shimada, K.; Ioka, T.; Nakamori, S.; Baba, H.; Komatsu, Y.; Takeuchi, M.; Hyodo, I.; Boku, N.

    2016-01-01

    Background We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). Patients and methods Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). Results Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37–0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54–1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47–1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. Conclusion The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. Clinical trials number Japan Pharmaceutical Information Center: JapicCTI-111554. PMID:26681680

  6. S1P lyase in skeletal muscle regeneration and satellite cell activation: Exposing the hidden lyase☆

    PubMed Central

    Saba, Julie D.; de la Garza-Rodea, Anabel S.

    2013-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid whose actions are essential for many physiological processes including angiogenesis, lymphocyte trafficking and development. In addition, S1P serves asamuscle trophic factor that enables efficient muscle regeneration. This is due in part to S1P's ability to activate quiescent muscle stem cells called satellite cells (SCs) that are needed for muscle repair. However, the molecular mechanism by which S1P activates SCs has not been well understood. Further, strategies for harnessing S1P signaling to recruit SCs for therapeutic benefit have been lacking. S1P is irreversibly catabolized by S1P lyase (SPL), a highly conserved enzyme that catalyzes the cleavage of S1P at carbon bond C2–3, resulting in formation of hexadecenal and ethanolamine-phosphate. SPL enhances apoptosis through substrate- and product-dependent events, thereby regulating cellular responses to chemotherapy, radiation and ischemia. SPL is undetectable in resting murine skeletal muscle. However, we recently found that SPL is dynamically upregulated in skeletal muscle after injury. SPL upregulation occurred in the context of a tightly orchestrated genetic program that resulted in a transient S1P signal in response to muscle injury. S1P activated quiescent SCs via a sphingosine-1-phosphate receptor 2 (S1P2)/signal transducer and activator of transcription 3 (STAT3)-dependent pathway, thereby facilitating skeletal muscle regeneration. Mdx mice, which serve as a model for muscular dystrophy (MD), exhibited skeletal muscle SPL upregulation and S1P deficiency. Pharmacological SPL inhibition raised skeletal muscle S1P levels, enhanced SC recruitment and improved mdx skeletal muscle regeneration. These findings reveal how S1P can activate SCs and indicate that SPL suppression may provide a therapeutic strategy for myopathies. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. PMID:22750505

  7. Polyhydroxyalkanoate biosynthesis by Hydrogenophaga pseudoflava DSM1034 from structurally unrelated carbon sources.

    PubMed

    Povolo, Silvana; Romanelli, Maria Giovanna; Basaglia, Marina; Ilieva, Vassilka Ivanova; Corti, Andrea; Morelli, Andrea; Chiellini, Emo; Casella, Sergio

    2013-09-25

    In the present paper we report the exclusive microbial preparation of polyhydroxyalkanoates (PHA) containing 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV) and 4-hydroxybutyrate (4HB) as comonomers through the use of unexpensive carbon sources such as whey from dairy industry. Polymers were produced by growing H. pseudoflava DSM 1034 in minimal medium supplemented with sucrose, lactose or whey without any co-substrate added. The chemical and physical properties of the polymers were fully characterized by GPC, DSC, TGA analyses and the composition by GC and (1)H NMR examinations to especially confirm the content of different monomeric units. The presence of 4HB units into PHA samples is particularly aimed in thermoplastic applications where greater flexibility is required and conventional rigid PHAs tend to fail. Usually the insertion of 4HB into chain backbone consisting of 3-hydroxyalkanoates requires expensive carbon sources mostly of petrochemical origin. According to our study the production of P(3HB-co-3HV-co-4HB) terpolymer can be obtained directly by the use of lactose or waste raw materials such as cheese whey as carbon sources. Although the amount of 4HB in the produced terpolymers was usually low and not exceeding 10% of the total molar composition, a PHA containing 18.4% of 4HB units was produced in 1 step fermentation process from this structurally unrelated carbon sources. The crystallinity of the terpolymer is basically to be markedly affected with respect to that of conventional PHAs, thus obtaining a comparatively less rigid material and easier to be processed. PMID:23201074

  8. Synthesis of new ligands for targeting the S1P1 receptor.

    PubMed

    Schilson, Stefanie S; Keul, Petra; Shaikh, Rizwan S; Schäfers, Michael; Levkau, Bodo; Haufe, Günter

    2015-03-01

    Sphingosine-1-phosphate (S1P) influences various fundamental biological processes by interacting with a family of five G protein-coupled receptors (S1P1-5). FTY720, a sphingosine analogue, which was approved for treatment of relapsing forms of multiple sclerosis, is phosphorylated in vivo and acts as an agonist of four of the five S1P receptor subtypes. Starting from these lead structures we developed new agonists for the S1P1 receptor. The biological activity was tested in vivo and promising ligands were fluorinated at different positions to identify candidates for positron emission tomography (PET) imaging after [(18)F]-labelling. The radioligands shall enable the imaging of S1P1 receptor expression in vivo and thus may serve as novel imaging markers of S1P-related diseases. PMID:25656338

  9. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane lifts the S1 Integrated Truss Structure from its workstand. The S1 will be placed in the payload canister for transport it to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  10. S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-α autoamplification

    PubMed Central

    Teijaro, John R.; Studer, Sean; Leaf, Nora; Kiosses, William B.; Nguyen, Nhan; Matsuki, Kosuke; Negishi, Hideo; Taniguchi, Tadatsugu; Oldstone, Michael B. A.; Rosen, Hugh

    2016-01-01

    Blunting immunopathology without abolishing host defense is the foundation for safe and effective modulation of infectious and autoimmune diseases. Sphingosine 1-phosphate receptor 1 (S1PR1) agonists are effective in treating infectious and multiple autoimmune pathologies; however, mechanisms underlying their clinical efficacy are yet to be fully elucidated. Here, we uncover an unexpected mechanism of convergence between S1PR1 and interferon alpha receptor 1 (IFNAR1) signaling pathways. Activation of S1PR1 signaling by pharmacological tools or endogenous ligand sphingosine-1 phosphate (S1P) inhibits type 1 IFN responses that exacerbate numerous pathogenic conditions. Mechanistically, S1PR1 selectively suppresses the type I IFN autoamplification loop in plasmacytoid dendritic cells (pDCs), a specialized DC subset, for robust type I IFN release. S1PR1 agonist suppression is pertussis toxin-resistant, but inhibited by an S1PR1 C-terminal–derived transactivating transcriptional activator (Tat)-fusion peptide that blocks receptor internalization. S1PR1 agonist treatment accelerates turnover of IFNAR1, suppresses signal transducer and activator of transcription 1 (STAT1) phosphorylation, and down-modulates total STAT1 levels, thereby inactivating the autoamplification loop. Inhibition of S1P-S1PR1 signaling in vivo using the selective antagonist Ex26 significantly elevates IFN-α production in response to CpG-A. Thus, multiple lines of evidence demonstrate that S1PR1 signaling sets the sensitivity of pDC amplification of IFN responses, thereby blunting pathogenic immune responses. These data illustrate a lipid G-protein coupled receptor (GPCR)-IFNAR1 regulatory loop that balances effective and detrimental immune responses and elevated endogenous S1PR1 signaling. This mechanism will likely be advantageous in individuals subject to a range of inflammatory conditions. PMID:26787880

  11. Intersystem crossing rates of S1 state keto-amino cytosine at low excess energy.

    PubMed

    Lobsiger, Simon; Etinski, Mihajlo; Blaser, Susan; Frey, Hans-Martin; Marian, Christel; Leutwyler, Samuel

    2015-12-21

    The amino-keto tautomer of supersonic jet-cooled cytosine undergoes intersystem crossing (ISC) from the v = 0 and low-lying vibronic levels of its S1((1)ππ(∗)) state. We investigate these ISC rates experimentally and theoretically as a function of S1 state vibrational excess energy Eexc. The S1 vibronic levels are pumped with a ∼5 ns UV laser, the S1 and triplet state ion signals are separated by prompt or delayed ionization with a second UV laser pulse. After correcting the raw ISC yields for the relative S1 and T1 ionization cross sections, we obtain energy dependent ISC quantum yields QISC (corr)=1%-5%. These are combined with previously measured vibronic state-specific decay rates, giving ISC rates kISC = 0.4-1.5 ⋅ 10(9) s(-1), the corresponding S1⇝S0 internal conversion (IC) rates are 30-100 times larger. Theoretical ISC rates are computed using SCS-CC2 methods, which predict rapid ISC from the S1; v = 0 state with kISC = 3 ⋅ 10(9) s(-1) to the T1((3)ππ(∗)) triplet state. The surprisingly high rate of this El Sayed-forbidden transition is caused by a substantial admixture of (1)nOπ(∗) character into the S1((1)ππ(∗)) wave function at its non-planar minimum geometry. The combination of experiment and theory implies that (1) below Eexc = 550 cm(-1) in the S1 state, S1⇝S0 internal conversion dominates the nonradiative decay with kIC ≥ 2 ⋅ 10(10) s(-1), (2) the calculated S1⇝T1 ((1)ππ(∗)⇝(3)ππ(∗)) ISC rate is in good agreement with experiment, (3) being El-Sayed forbidden, the S1⇝T1 ISC is moderately fast (kISC = 3 ⋅ 10(9) s(-1)), and not ultrafast, as claimed by other calculations, and (4) at Eexc ∼ 550 cm(-1) the IC rate increases by ∼50 times, probably by accessing the lowest conical intersection (the C5-twist CI) and thereby effectively switching off the ISC decay channels. PMID:26696056

  12. Intersystem crossing rates of S1 state keto-amino cytosine at low excess energy

    NASA Astrophysics Data System (ADS)

    Lobsiger, Simon; Etinski, Mihajlo; Blaser, Susan; Frey, Hans-Martin; Marian, Christel; Leutwyler, Samuel

    2015-12-01

    The amino-keto tautomer of supersonic jet-cooled cytosine undergoes intersystem crossing (ISC) from the v = 0 and low-lying vibronic levels of its S1(1ππ∗) state. We investigate these ISC rates experimentally and theoretically as a function of S1 state vibrational excess energy Eexc. The S1 vibronic levels are pumped with a ˜5 ns UV laser, the S1 and triplet state ion signals are separated by prompt or delayed ionization with a second UV laser pulse. After correcting the raw ISC yields for the relative S1 and T1 ionization cross sections, we obtain energy dependent ISC quantum yields QISC corr = 1 % -5%. These are combined with previously measured vibronic state-specific decay rates, giving ISC rates kISC = 0.4-1.5 ṡ 109 s-1, the corresponding S1⇝S0 internal conversion (IC) rates are 30-100 times larger. Theoretical ISC rates are computed using SCS-CC2 methods, which predict rapid ISC from the S1; v = 0 state with kISC = 3 ṡ 109 s-1 to the T1(3ππ∗) triplet state. The surprisingly high rate of this El Sayed-forbidden transition is caused by a substantial admixture of 1nOπ∗ character into the S1(1ππ∗) wave function at its non-planar minimum geometry. The combination of experiment and theory implies that (1) below Eexc = 550 cm-1 in the S1 state, S1⇝S0 internal conversion dominates the nonradiative decay with kIC ≥ 2 ṡ 1010 s-1, (2) the calculated S1⇝T1 (1ππ∗⇝3ππ∗) ISC rate is in good agreement with experiment, (3) being El-Sayed forbidden, the S1⇝T1 ISC is moderately fast (kISC = 3 ṡ 109 s-1), and not ultrafast, as claimed by other calculations, and (4) at Eexc ˜ 550 cm-1 the IC rate increases by ˜50 times, probably by accessing the lowest conical intersection (the C5-twist CI) and thereby effectively switching off the ISC decay channels.

  13. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    SciTech Connect

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    2011-09-09

    Highlights: {yields} Successfully selected specific PreS1-interacting peptides by using phage displayed library. {yields} Alignment of the positive phage clones revealed a consensus PreS1 binding motif. {yields} A highly enriched peptide named P7 had a strong binding ability for PreS1. {yields} P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX{sub n}HX{sub m}HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  14. VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST END OF QUARRY LOCK, FACING NORTHWEST - U.S. Naval Base, Pearl Harbor, Naval Submarine Base, Berthing Wharf S1, South Waterfront Road along north side of Quarry Loch, Pearl City, Honolulu County, HI

  15. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane moves the S1 Integrated Truss Structure toward the payload canister, which will transport it to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  16. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- The S1 Integrated Truss Structure is lowered into the payload canister for transport to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  17. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane moves the S1 Integrated Truss Structure toward the payload canister below, which will transport it to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  18. Enhanced Raman scattering from cesium suboxides on silver particles and the structure of S-1 photocathodes

    NASA Technical Reports Server (NTRS)

    Bates, C. W., Jr.

    1984-01-01

    An explanation is given for the results of recent enhanced Raman scattering studies of photomultiplier tubes with S-1 photocathode surfaces which indicated the presence of Cs11O3 but not Cs2O. The reason for the discrepancy between the currently accepted model of the S-1 and this recent result is discussed.

  19. Effect of ADP on binding of skeletal S1 to F-actin.

    PubMed

    Andreev, O A; Ushakov, D S; Borejdo, J

    1998-12-22

    The proximity of skeletal myosin subfragment-1 (S1) to actin, and its orientation with respect to thin filaments of single muscle fibers, were compared in the presence and in the absence of ADP. The proximity was assessed by the efficiency of carbodiimide-induced cross-linking and the orientation by polarization of fluorescence of probes attached to the essential light chains. ADP made no difference in proximity or orientation when the molar ratio of S1 to actin was low or high. However, at the intermediate ratios, ADP made a significant difference. Strong dissociating agents, AMP-PNP and PPi, made significant differences at all ratios. To explain this behavior, it is unnecessary to invoke the ADP-induced "swinging" of the tail of S1. Rather, it is simply explained by the "two-state" model which we proposed earlier, in which S1 binds to one or to two actin protomers, depending on the saturation of the filaments with S1s. The dissociation induced by the ADP shifts the equilibrium between the two bound states. At high and low degrees of saturation, ADP is unable to significantly decrease the amount of S1 bound to F-actin. However, at intermediate saturation levels, ADP causes significantly more S1s to bind to two actins. These results suggest that the ADP-induced changes seen at the intermediate molar ratios are due to the dissociation-induced reorientation of S1. PMID:9922150

  20. Calcium alone does not fully activate the thin filament for S1 binding to rigor myofibrils.

    PubMed Central

    Swartz, D R; Moss, R L; Greaser, M L

    1996-01-01

    Skeletal muscle contraction is regulated by calcium via troponin and tropomyosin and appears to involve cooperative activation of cross-bridge binding to actin. We studied the regulation of fluorescent myosin subfragment 1 (fS1) binding to rigor myofibrils over a wide range of fS1 and calcium levels using highly sensitive imaging techniques. At low calcium and low fS1, the fluorescence was restricted to the actin-myosin overlap region. At high calcium and very low fS1, the fluorescence was still predominantly in the overlap region. The ratio of nonoverlap to overlap fluorescence intensity showed that increases in the fS1 level resulted in a shift in maximum fluorescence from the overlap to the nonoverlap region at both low and high calcium; this transition occurred at lower fS1 levels in myofibrils with high calcium. At a fixed fS1 level, increases in calcium also resulted in a shift in maximum fluorescence from the overlap region to the nonoverlap region. These results suggest that calcium alone does not fully activate the thin filament for rigor S1 binding and that, even at high calcium, the thin filament is not activated along its entire length. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 7 FIGURE 9 FIGURE 11 PMID:8889164

  1. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for two years to equalize CSN1S1 and TG genetic marker frequencies to evaluate the epista...

  2. Modulation of membrane phospholipids, the cytosolic calcium influx and cell proliferation following treatment of B16-F10 cells with recombinant phospholipase-D from Loxosceles intermedia (brown spider) venom.

    PubMed

    Wille, Ana Carolina Martins; Chaves-Moreira, Daniele; Trevisan-Silva, Dilza; Magnoni, Mariana Gabriel; Boia-Ferreira, Marianna; Gremski, Luiza Helena; Gremski, Waldemiro; Chaim, Olga Meiri; Senff-Ribeiro, Andrea; Veiga, Silvio Sanches

    2013-06-01

    The mechanism through which brown spiders (Loxosceles genus) cause dermonecrosis, dysregulated inflammatory responses, hemolysis and platelet aggregation, which are effects reported following spider bites, is currently attributed to the presence of phospholipase-D in the venom. In the present investigation, through two-dimensional immunoblotting, we observed immunological cross-reactivity for at least 25 spots in crude Loxosceles intermedia venom, indicating high expression levels for different isoforms of phospholipase-D. Using a recombinant phospholipase-D from the venom gland of L. intermedia (LiRecDT1) in phospholipid-degrading kinetic experiments, we determined that this phospholipase-D mainly hydrolyzes synthetic sphingomyelin in a time-dependent manner, generating ceramide 1-phosphate plus choline, as well as lysophosphatidylcholine, generating lysophosphatidic acid plus choline, but exhibits little activity against phosphatidylcholine. Through immunofluorescence assays with antibodies against LiRecDT1 and using a recombinant GFP-LiRecDT1 fusion protein, we observed direct binding of LiRecDT1 to the membrane of B16-F10 cells. We determined that LiRecDT1 hydrolyzes phospholipids in detergent extracts and from ghosts of B16-F10 cells, generating choline, indicating that the enzyme can access and modulate and has activity against membrane phospholipids. Additionally, using Fluo-4, a calcium-sensitive fluorophore, it was shown that treatment of cells with phospholipase-D induced an increase in the calcium concentration in the cytoplasm, but without altering viability or causing damage to cells. Finally, based on the known endogenous activity of phospholipase-D as an inducer of cell proliferation and the fact that LiRecDT1 binds to the cell surface, hydrolyzing phospholipids to generate bioactive lipids, we employed LiRecDT1 as an exogenous source of phospholipase-D in B16-F10 cells. Treatment of the cells was effective in increasing their proliferation in a

  3. Ribosomal protein S1 induces a conformational change of tmRNA; more than one protein S1 per molecule of tmRNA.

    PubMed

    Bordeau, Valérie; Felden, Brice

    2002-08-01

    tmRNA (10Sa RNA, ssrA) acts to rescue stalled bacterial ribosomes while encoding a peptide tag added trans-translationally to the nascent peptide, targeting it for proteolysis. Ribosomal protein S1 is required for tmRNA binding to isolated and poly U-programmed ribosomes. Mobility assays on native gels indicate that the binding curves of both recombinant and purified proteins S1 from E. coli is biphasic with apparent binding constants of approximately 90 and approximately 300 nM, respectively, suggesting that more than one protein interacts with tmRNA. Structural probing of native tmRNA in the presence and absence of the purified protein suggest that when S1 binds, tmRNA undergoes a significant conformational change. In the presence of the protein, nucleotides from tmRNA with enhanced (H2, H3, PK1, PK2, PK4, in and around the first triplet to be translated), or decreased (H5 and PK2), reactivity towards a probe specific for RNA single-strands are scattered throughout the molecule, with the exception of the tRNA-like domain that may be dispensable for the interaction. Converging experimental evidence suggests that ribosomal protein S1 binds to pseudoknot PK2. Previous structural studies of tmRNA in solution have revealed several discrepancies between the probing data and the phylogeny, and most of these are reconciled when analyzing tmRNA structure in complex with the protein(s). Ribosomal protein(s) S1 is proposed to set tmRNA in the mRNA mode, relieving strains that may develop when translating a looped mRNA. PMID:12457560

  4. Molecular insights into replication initiation by Qβ replicase using ribosomal protein S1

    PubMed Central

    Takeshita, Daijiro; Yamashita, Seisuke; Tomita, Kozo

    2014-01-01

    Ribosomal protein S1, consisting of six contiguous OB-folds, is the largest ribosomal protein and is essential for translation initiation in Escherichia coli. S1 is also one of the three essential host-derived subunits of Qβ replicase, together with EF-Tu and EF-Ts, for Qβ RNA replication in E. coli. We analyzed the crystal structure of Qβ replicase, consisting of the virus-encoded RNA-dependent RNA polymerase (β-subunit), EF-Tu, EF-Ts and the N-terminal half of S1, which is capable of initiating Qβ RNA replication. Structural and biochemical studies revealed that the two N-terminal OB-folds of S1 anchor S1 onto the β-subunit, and the third OB-fold is mobile and protrudes beyond the surface of the β-subunit. The third OB-fold mainly interacts with a specific RNA fragment derived from the internal region of Qβ RNA, and its RNA-binding ability is required for replication initiation of Qβ RNA. Thus, the third mobile OB-fold of S1, which is spatially anchored near the surface of the β-subunit, primarily recruits the Qβ RNA toward the β-subunit, leading to the specific and efficient replication initiation of Qβ RNA, and S1 functions as a replication initiation factor, beyond its established function in protein synthesis. PMID:25122749

  5. The vascular S1P gradient—Cellular sources and biological significance

    PubMed Central

    Hla, Timothy; Venkataraman, Krishnan; Michaud, Jason

    2009-01-01

    Sphingosine 1-phosphate (S1P), a product of sphingomyelin metabolism, is enriched in the circulatory system whereas it is estimated to be much lower in interstitial fluids of tissues. This concentration gradient, termed the vascular S1P gradient appears to form as a result of substrate availability and the action of metabolic enzymes. S1P levels in blood and lymph are estimated to be in the μM range. In the immune system, the S1P gradient is needed as a spatial cue for lymphocyte and hematopoietic cell trafficking. During inflammatory reactions in which enhanced vascular permeability occurs, a burst of S1P becomes available to its receptors in the extravascular compartment, which likely contributes to the tissue reactions. Thus, the presence of the vascular S1P gradient is thought to contribute to physiological and pathological conditions. From an evolutionary perspective, S1P receptors may have co-evolved with the advent of a closed vascular system and the trafficking paradigms for hematopoietic cells to navigate in and out of the vascular system. PMID:18674637

  6. [Combination therapy with S-1 and CDDP for head and neck cancer].

    PubMed

    Fujii, Masato

    2006-06-01

    The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future. PMID:16897992

  7. One-stage surgery through posterior approach-for L5-S1 spondyloptosis

    PubMed Central

    Suslu, Hikmet Turan; Celikoglu, Erhan; Borekcı, Ali; Hıcdonmez, Tufan; Suslu, Hüsnü

    2011-01-01

    Grade 5 spondylolisthesis or spondyloptosis is a rare condition. Generally, the surgical management of spondyloptosis includes multi-staged procedures instead of one-staged procedures. One-stage treatment for spondyloptosis is very rare. A 15-year-old girl with L5-S1 spondyloptosis was admitted with severe low back pain. There was no history of trauma. The patient underwent L5 laminectomy, L5-S1 discectomy, resection of sacral dome, reduction, L3-L4-L5-S1 pedicular screw fixation, and interbody-posterolateral fusion through the posterior approach. The reduction was maintained with bilateral L5-S1 discectomy, resection of the sacral dome, and transpedicular instrumentation from L3 to S1. In this particular case, one-staged approach was adequate for the treatment of L5-S1 spondyloptosis. One-staged surgery using the posterior approach may be adequate for the treatment of L5-S1 spondyloptosis while avoiding the risks inherent in anterior approaches. PMID:23125496

  8. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2.

    PubMed

    Santos-Cortez, Regie Lyn P; Faridi, Rabia; Rehman, Atteeq U; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J; Isaacson, Rivka; Belyantseva, Inna A; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-E-Huma; Smith, Joshua D; Nickerson, Deborah A; Bamshad, Michael J; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B; Leal, Suzanne M

    2016-02-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2(-/-) mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2(-/-) mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  9. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

    PubMed Central

    Santos-Cortez, Regie Lyn P.; Faridi, Rabia; Rehman, Atteeq U.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J.; Isaacson, Rivka; Belyantseva, Inna A.; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A.; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-e-Huma; Smith, Joshua D.; Nickerson, Deborah A.; Bamshad, Michael J.; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B.; Leal, Suzanne M.

    2016-01-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2−/− mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2−/− mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  10. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    SciTech Connect

    Kasamatsu, Atsushi; Uzawa, Katsuhiro; Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki; Endo-Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Takiguchi, Yuichi; Tanzawa, Hideki

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  11. S = 1 Excitations in Heat Capacity of the Haldane Compound TMNIN Doped with a Nonmagnetic Impurity

    NASA Astrophysics Data System (ADS)

    Kawae, Tatsuya; Ito, Masakazu; Mito, Masaki; Takeda, Kazuyoshi

    1999-03-01

    We have studied the field dependence of the heat capacity of a typicalHaldane antiferromagnet (CH3)4NNi(NO)3 (TMNIN) doped with thenonmagnetic impurity Zn2+, as well as of a pure TMNIN. The overallfeatures of the magnetic heat capacity, including the characteristic broadmaximum, are almost reproduced by the theoretical curve with J/k B =-12 K for both systems in zero field. The field dependence in the impuresystems is described well by assuming the Schottky heat capacity with S =1, not S = 1/2 expected from the VBS model. A possible reason why the S= 1 model is suitable is discussed.

  12. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme

    PubMed Central

    Bien-Möller, Sandra; Lange, Sandra; Holm, Tobias; Böhm, Andreas; Paland, Heiko; Küpper, Johannes; Herzog, Susann; Weitmann, Kerstin; Havemann, Christoph; Vogelgesang, Silke; Marx, Sascha; Hoffmann, Wolfgang; Schroeder, Henry W.S.; Rauch, Bernhard H.

    2016-01-01

    A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient's survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient's survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells. In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation. PMID:26887055

  13. Scaling and root planning, and locally delivered minocycline reduces the load of Prevotella intermedia in an interdependent pattern, correlating with symptomatic improvements of chronic periodontitis: a short-term randomized clinical trial

    PubMed Central

    Deng, Shuli; Wang, Ying; Sun, Wei; Chen, Hui; Wu, Gang

    2015-01-01

    Background To evaluate the respective or combinatory efficacy of locally delivered 2% minocycline (MO), and scaling and root planning (SRP) by assessing both clinical parameters and the loads of four main periodontal pathogens in treating chronic periodontitis (CP). Methods Seventy adults with CP were randomly assigned to the three treatment groups: 1) SRP alone; 2) MO alone; and 3) combinatory use of SRP and MO (SRP + MO). Before and 7 days after the treatments, we evaluated both clinical parameters (pocket depth [PD] and sulcus bleeding index [SBI]) and the gene load of four main periodontal pathogens (Aggregatibacter actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Porphyromonas gingivalis [Pg], and Prevotella intermedia [Pi]). Results The bacterial prevalence per patient was: Aa, 31.25%; Fn, 100%; Pg, 95.31%; and Pi, 98.44%. Seven days after treatment, the three treatments significantly reduced both PD and SBI, but not detection frequencies of the four pathogens. For PD, the reduction efficacy of SRP + MO was significantly higher than that of either MO or SRP. Only Pg responded significantly to SRP. Pg and Fn were significantly reduced in the presence of MO. Only SRP + MO showed a significant reduction effect on the gene load of Pi. The reduction of PD significantly correlated with the gene load of Pi (r=0.26; P=0.042) but not of the other bacteria. Conclusion SRP and MO reduced the load of Pi in an interdependent pattern, which correlated with symptomatic improvements of CP. PMID:26676022

  14. Lipochemistry of the progamic stage of a self-incompatible species: Neutral lipids and fatty acids of the secretory stigma during its glandular activity, and of the solid style, the ovary and the anther in Forsythia intermedia Zab. (Heterostylic species).

    PubMed

    Dumas, C

    1977-01-01

    Chromatographic (thin-layer, gas column, column chromatography) analyses of neutral lipids and fatty acids of reproductive tissues of Forsythia intermedia Zab., a self-incompatible species, were performed with two objectives in mind: 1. To determine whether there is a qualitative evolution of the different classes of lipids and fatty acids that could be correlated with the three functional stages observed during previous histochemical and ultrastructural studies. The stigmatic exudate and intracellular accumulations consist mainly of neutral lipids. 2. To compare the lipid composition of the stigma (both "thrum" and "pin" forms) with that of the style, the ovary, and the anther, and to investigate the possible existence of a stigma-specific lipid compound. Stigmatic neutral lipids are found mostly in a glyceridic mixture probably containing hydrocarbons and terpenes. The fatty acids identified are between C:7 and C: 12, with the maximum unsaturated form being a C: 18. During the secretory process there is no great qualitative diference between the neutral lipids and fatty acids found in the stigmas of "thrum" and "pin" forms. Sterols are present in styles, ovaries, and anthers, but not in stigmas. They represent the only difference in the lipid composition of these various floral structures. PMID:24420636

  15. Plastic flow in shock-loaded silver at strain rates from 104 s-1 to 107 s-1 and temperatures from 296 K to 1233 K

    NASA Astrophysics Data System (ADS)

    Zaretsky, E. B.; Kanel, G. I.

    2011-10-01

    The evolution of elastic-plastic shock waves in 99.9% purity silver samples of 0.127 to 2.0 mm thickness has been studied in a series of VISAR-instrumented planar impact experiments with initial sample temperature varied from 296 to 1233 K. The decay of elastic precursor wave at 933, 1173, and 1233 K temperatures is approximately inversely proportional to the square root of the propagation distance. The latter corresponds to the cubic dependence of initial plastic strain rate, ranged from 104 s-1 to 106 s-1, on the shear stress. At fixed strain rates, the flow stress grows linearly with the temperature but the dependence becomes stronger near the silver melting point, 1234 K. An analysis of the rise times of the plastic shock waves shows that for the same level of shear stress the plastic strain rate at the shock front is significantly higher than that at the top of the elastic precursor wave.

  16. Components-dependent optical nonlinearity in a series of CdSexS1-x and CdSexS1-x/ZnS QDs

    NASA Astrophysics Data System (ADS)

    Zhao, Shunlong; Wu, Feng; Zhang, Siwen; Wang, Qian; Li, Songtao; Cheng, Xiaoman

    2016-08-01

    The different compositions of the ternary alloyed CdSexS1-x and CdSexS1-x/ZnS core/shell quantum dots(CSQDs) have been synthesized by the chemical routes. The nonlinear optical properties of these QDs were investigated using Z-scan technique under the excitation of the 1064 nm picosecond laser pulse. The Z-scan results reveal that the nonlinear refractive indices of these QDs can be tuned by changing the ratio of Se and S components. Nonlinear optical (NLO) properties have been shown to be enhanced in CSQDs as compared to their core semiconductor counterparts. These QDs exhibit the components-tuned nonlinear refraction indices, which lead to a wide application in the photonic field.

  17. PMMA Cementoplasty in Symptomatic Metastatic Lesions of the S1 Vertebral Body

    SciTech Connect

    Dehdashti, Amir R.; Martin, Jean-Baptiste; Jean, Beatrix; Ruefenacht, Daniel A.

    2000-03-15

    We describe a lateral transiliac direct puncture approach to the S1 vertebral body for polymethylmethacrylate (PMMA) cementoplasty of painful metastatic lesions. This approach was performed using a 15-cm-long trocar needle with 3-mm outer diameter, introduced under general anesthesia and fluoroscopic control. A lateral projection was used to center the needle just in front of the spinal canal and subjacent to the superior plate of the S1 vertebral body. Needle progression was controlled using anteroposterior and lateral fluoroscopic projections alternately with a needle course parallel to an axial plane, avoiding conflict with the S1 foramen. After needle tip placement in the center of the S1 vertebral body, diluted PMMA with a setting time of 8 min was delivered. Ipsilateral lesions of the lateral sacral compartment were filled with the same needle by stepwise withdrawal and continuous PMMA injection.

  18. The D{sub s1} and its D*K decays

    SciTech Connect

    Segovia, J.; Entem, D. R.; Fernandez, F.

    2010-08-05

    Recently the Belle Collaboration has measured a new decay channel for the charmed strange meson D{sub s1}(2536){sup +{yields}}D{sup +{pi}-}K{sup +} together with an angular analysis of the D{sub s1}(2536){sup +{yields}}D*{sup +}K{sub S}{sup 0} decay. We study this reaction in a constituent quark model which has been able to reproduce the hadronic phenomenology and the baryon-baryon interaction. The reported branching fraction can be explained through a virtual D*{sup 0} and the properties of the D{sub s1}(2536){sup +} state are nicely reproduced. The influence of other intermediate states in the reaction D{sub s1}(2536){sup +{yields}}D{sup +{pi}-}K{sup +} has been analyzed giving negligible contributions.

  19. Intermediate binding of phycocyanobilin to the lyase, CpeS1, and transfer to apoprotein.

    PubMed

    Tu, Jun-Ming; Kupka, Michaela; Böhm, Stephan; Plöscher, Matthias; Eichacker, Lutz; Zhao, Kai-Hong; Scheer, Hugo

    2008-01-01

    The phycobilin: Cysteine-84-phycobiliprotein lyase, CpeS1, catalyzes phycocyanobilin (PCB) and phycoerythrobilin attachment to nearly all cysteine-84 (consensus sequence) binding sites of phycoerythrin, phycoerythrocyanin, phycocyanin and allophycocyanin (Zhao et al. (2007) Proc Natl Acad Sci 104:14300-14305). We now show that CpeS1 can bind PCB, as assayed by Ni(2+) chelating affinity chromatography. Binding is rapid, and the chromophore is bound in an extended conformation similar to that in phycobiliproteins but only poorly fluorescent. Upon addition of apo-biliproteins, the chromophore is transferred to the latter much slower ( approximately 1 h), indicating that chromophorylated CpeS1 is an intermediate in the enzymatic reaction. In addition, imidazole is bound to PCB, as shown by mass spectroscopy of tryptic digests of the intermediate CpeS1-PCB complex. PMID:17912606

  20. Pathway specific modulation of S1P1 receptor signalling in rat and human astrocytes

    PubMed Central

    Healy, Luke M; Sheridan, Graham K; Pritchard, Adam J; Rutkowska, Aleksandra; Mullershausen, Florian; Dev, Kumlesh K

    2013-01-01

    Background and Purpose The sphingosine 1-phosphate receptor subtype 1 (S1P1R) is modulated by phosphorylated FTY720 (pFTY720), which causes S1P1R internalization preventing lymphocyte migration thus limiting autoimmune response. Studies indicate that internalized S1P1Rs continue to signal, maintaining an inhibition of cAMP, thus raising question whether the effects of pFTY720 are due to transient initial agonism, functional antagonism and/or continued signalling. To further investigate this, the current study first determined if continued S1P1R activation is pathway specific. Experimental Approach Using human and rat astrocyte cultures, the effects of S1P1R activation on cAMP, pERK and Ca2+ signalling was investigated. In addition, to examine the role of S1P1R redistribution on these events, a novel biologic (MNP301) that prevented pFTY720-mediated S1P1R redistribution was engineered. Key Results The data showed that pFTY720 induced long-lasting S1P1R redistribution and continued cAMP signalling in rat astrocytes. In contrast, pFTY720 induced a transient increase of Ca2+ in astrocytes and subsequent antagonism of Ca2+ signalling. Notably, while leaving pFTY720-induced cAMP signalling intact, the novel MNP301 peptide attenuated S1P1R-mediated Ca2+ and pERK signalling in cultured rat astrocytes. Conclusions and Implications These findings suggested that pFTY720 causes continued cAMP signalling that is not dependent on S1P1R redistribution and induces functional antagonism of Ca2+ signalling after transient stimulation. To our knowledge, this is the first report demonstrating that pFTY720 causes continued signalling in one pathway (cAMP) versus functional antagonism of another pathway (Ca2+) and which also suggests that redistributed S1P1Rs may have differing signalling properties from those expressed at the surface. PMID:23587004

  1. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. - Workers inside the payload canister watch the S1 Integrated Truss Structure as it is lowered toward them. The canister will transport the truss to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  2. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane moves the S1 Integrated Truss Structure above over other equipment to get to the payload canister for transport to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  3. Characterization of the L4-L5-S1 motion segment using the stepwise reduction method.

    PubMed

    Jaramillo, Héctor Enrique; Puttlitz, Christian M; McGilvray, Kirk; García, José J

    2016-05-01

    The two aims of this study were to generate data for a more accurate calibration of finite element models including the L5-S1 segment, and to find mechanical differences between the L4-L5 and L5-S1 segments. Then, the range of motion (ROM) and facet forces for the L4-S1 segment were measured using the stepwise reduction method. This consists of sequentially testing and reducing each segment in nine stages by cutting the ligaments, facet capsules, and removing the nucleus. Five L4-S1 human segments (median: 65 years, range: 53-84 years, SD=11.0 years) were loaded under a maximum pure moment of 8Nm. The ROM was measured using stereo-photogrammetry via tracking of three markers and the facet contact forces (CF) were measured using a Tekscan system. The ROM for the L4-L5 segment and all stages showed good agreement with published data. The major differences in ROM between the L4-L5 and L5-S1 segments were found for lateral bending and all stages, for which the L4-L5 ROM was about 1.5-3 times higher than that of the L5-S1 segment, consistent with L5-S1 facet CF about 1.3 to 4 times higher than those measured for the L4-L5 segment. For the other movements and few stages, the L4-L5 ROM was significantly lower that of the L5-S1 segment. ROM and CF provide important baseline data for more accurate calibration of FE models and to understand the role that their structures play in lower lumbar spine mechanics. PMID:27017302

  4. STS-112 S1 truss in Payload Changeout Room at Launch Pad 39-B

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- The payload canister is ready to be opened in the Payload Changeout Room at the pad. Inside is the S1 Integrated Truss Structure, primary payload on mission STS-112 aboard Space Shuttle Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during the mission. Atlantis is scheduled to launch no earlier than Oct. 2.

  5. 6S-1 RNA function leads to a delay in sporulation in Bacillus subtilis.

    PubMed

    Cavanagh, Amy T; Wassarman, Karen M

    2013-05-01

    We have discovered that 6S-1 RNA (encoded by bsrA) is important for appropriate timing of sporulation in Bacillus subtilis in that cells lacking 6S-1 RNA sporulate earlier than wild-type cells. The time to generate a mature spore once the decision to sporulate has been made is unaffected by 6S-1 RNA, and, therefore, we propose that it is the timing of onset of sporulation that is altered. Interestingly, the presence of cells lacking 6S-1 RNA in coculture leads to all cell types exhibiting an early-sporulation phenotype. We propose that cells lacking 6S-1 RNA modify their environment in a manner that promotes early sporulation. In support of this model, resuspension of wild-type cells in conditioned medium from ΔbsrA cultures also resulted in early sporulation. Use of Escherichia coli growth as a reporter of the nutritional status of conditioned media suggested that B. subtilis cells lacking 6S-1 RNA reduce the nutrient content of their environment earlier than wild-type cells. Several pathways known to impact the timing of sporulation, such as the skf- and sdp-dependent cannibalism pathways, were eliminated as potential targets of 6S-1 RNA-mediated changes, suggesting that 6S-1 RNA activity defines a novel mechanism for altering the timing of onset of sporulation. In addition, 6S-2 RNA does not influence the timing of sporulation, providing further evidence of the independent influences of these two related RNAs on cell physiology. PMID:23457253

  6. S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart

    PubMed Central

    Bandhuvula, Padmavathi; Honbo, Norman; Wang, Guan-Ying; Jin, Zhu-Qiu; Fyrst, Henrik; Zhang, Meng; Borowsky, Alexander D.; Dillard, Lisa; Karliner, Joel S.

    2011-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes cardiomyocyte survival and contributes to ischemic preconditioning. S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism. We hypothesized that SPL contributes to oxidative stress by depleting S1P pools available for cardioprotective signaling. Accordingly, we evaluated SPL inhibition as a strategy for reducing cardiac ischemia-reperfusion (I/R) injury. We measured SPL expression and enzyme activity in murine hearts. Basal SPL activity was low in wild-type cardiac tissue but was activated in response to 50 min of ischemia (n = 5, P < 0.01). Hearts of heterozygous SPL knockout mice exhibited reduced SPL activity, elevated S1P levels, smaller infarct size, and increased functional recovery after I/R compared with littermate controls (n = 5, P < 0.01). The small molecule tetrahydroxybutylimidazole (THI) is a Federal Drug Administration-approved food additive that inhibits SPL. When given overnight at 25 mg/l in drinking water, THI raised S1P levels and reduced SPL activity (n = 5, P < 0.01). THI reduced infarct size and enhanced hemodynamic recovery in response to 50 min of ischemia and to 40 min of reperfusion in ex vivo hearts (n = 7, P < .01). These data correlated with an increase in MAP kinase-interacting serine/threonine kinase 1, eukaryotic translation initiation factor 4E, and ribosomal protein S6 phosphorylation levels after I/R, suggesting that SPL inhibition enhances protein translation. Pretreatment with an S1P1 and S1P3 receptor antagonist partially reversed the effects of THI. These results reveal, for the first time, that SPL is an ischemia-induced enzyme that can be targeted as a novel strategy for preventing cardiac I/R injury. PMID:21335477

  7. Hyaluroan-regulated lymphatic permeability through S1P receptors is crucial for cancer metastasis.

    PubMed

    Yu, Mengsi; He, Pingqing; Liu, Yiwen; He, Yiqing; Du, Yan; Wu, Man; Zhang, Guoliang; Yang, Cuixia; Gao, Feng

    2015-01-01

    Disruption of cancer lymphatic vessel barrier function occurs has been reported to involve in cancer lymphatic metastasis. Hyaluronan (HA), a major glycosaminoglycan component of the extracellular matrix, is associated with cancer metastasis. We investigated the effect of high/low molecular weight hyaluronan (HMW-HA/LMW-HA) on regulation of barrier function and tight junctions in cancer lymphatic endothelial cell (LEC) monolayer. Results showed that LMW-HA increased the permeability of cancer LEC monolayers and induced disruption of Zonula Occludens-1 (ZO-1)-mediated intercellular tight junction and actin stress fiber formation. HMW-HA treatment decreased permeability in cancer LEC monolayers and cortical actin ring formation. As reported, sphingosine 1-phosphate (S1P) receptors are involved in vascular integrity. After silencing of lymphatic vessel endothelial hyaluronan receptor (LYVE-1), upregulation of S1P receptors (S1P1 and S1P3) induced by HMW-HA/LMW-HA were inhibited, respectively. With S1P3 silenced, the disruption of ZO-1 as well as stress fiber formation and the ROCK1/RhoA signaling pathway induced by LMW-HA was not observed in cancer LEC. These results suggested that S1P receptors may play an important role in HMW-HA-/LMW-HA-mediated regulation of cancer lymphatic vessel integrity, which might be the initial step of cancer lymphatic metastasis and a useful intervention of cancer progression. PMID:25428387

  8. A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

    PubMed Central

    Zhang, Lin; Orban, Martin; Lorenz, Michael; Barocke, Verena; Braun, Daniel; Urtz, Nicole; Schulz, Christian; von Brühl, Marie-Luise; Tirniceriu, Anca; Gaertner, Florian; Proia, Richard L.; Graf, Thomas; Bolz, Steffen-Sebastian; Montanez, Eloi; Prinz, Marco; Müller, Alexandra; von Baumgarten, Louisa; Billich, Andreas; Sixt, Michael; Fässler, Reinhard; von Andrian, Ulrich H.; Junt, Tobias

    2012-01-01

    Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P–S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia. PMID:23148237

  9. Ultrafast S1 to S0 internal conversion dynamics for dimethylnitramine through a conical intersection.

    PubMed

    Guo, Yuanqing; Bhattacharya, Atanu; Bernstein, Elliot R

    2011-09-01

    Electronically nonadiabatic processes such as ultrafast internal conversion (IC) from an upper electronic state (S(1)) to the ground electronic state (S(0)) though a conical intersection (CI), can play an essential role in the initial steps of the decomposition of energetic materials. Such nonradiative processes following electronic excitation can quench emission and store the excitation energy in the vibrational degrees of freedom of the ground electronic state. This excess vibrational energy in the ground electronic state can dissociate most of the chemical bonds of the molecule and can generate stable, small molecule products. The present study determines ultrafast IC dynamics of a model nitramine energetic material, dimethylnitramine (DMNA). Femtosecond (fs) pump-probe spectroscopy, for which a pump pulse at 271 nm and a probe pulse at 405.6 nm are used, is employed to elucidate the IC dynamics of this molecule from its S(1) excited state. A very short lifetime of the S(1) excited state (∼50 ± 16 fs) is determined for DMNA. Complete active space self-consistent field (CASSCF) calculations show that an (S(1)/S(0))(CI) CI is responsible for this ultrafast decay from S(1) to S(0). This decay occurs through a reaction coordinate involving an out-of-plane bending mode of the DMNA NO(2) moiety. The 271 nm excitation of DMNA is not sufficient to dissociate the molecule on the S(1) potential energy surface (PES) through an adiabatic NO(2) elimination pathway. PMID:21351779

  10. Design, Synthesis, and Biological Evaluation of Ganglioside Hp-s1 Analogues Varying at Glucosyl Moiety.

    PubMed

    Hung, Jung-Tung; Yeh, Chun-Hong; Yang, Shih-An; Lin, Chiu-Ya; Tai, Hung-Ju; Shelke, Ganesh B; Reddy, Daggula Mallikarjuna; Yu, Alice L; Luo, Shun-Yuan

    2016-08-17

    Ganglioside Hp-s1 is isolated from the ovary of sea urchin Diadema setosum. It exhibited better neuritogenic activity than GM1 in pheochromocytoma 12 cells. To explore the roles of glucosyl moiety of Hp-s1 in contributing to the neurogenic activity, we developed feasible procedures for synthesis of Hp-s1 analogues (2a-2f). The glucosyl moiety of Hp-s1 was replaced with α-glucose, α-galactose, β-galactose, α-mannose, and β-mannose, and their biological activities on SH-SY5Y cells and natural killer T (NKT) cells were evaluated. We found that the orientation of C-2 hydroxyl group at glucosyl moiety of Hp-s1 plays an important role to induce neurite outgrowth of SH-SY5Y cells. Surprisingly, compound 2d could activate NKT cells to produce interleukin 2, although it did not show great activity on neurite outgrowth of SH-SY5Y cells. In general, the Hp-s1 might be considered as a lead compound for the development of novel drugs aimed at modulating the activity of neuronal cells. PMID:27276519

  11. Photolabelling of mutant forms of the S1 subunit of pertussis toxin with NAD+.

    PubMed Central

    Cieplak, W; Locht, C; Mar, V L; Burnette, W N; Keith, J M

    1990-01-01

    The S1 subunit of pertussis toxin catalyses the hydrolysis of NAD+ (NAD+ glycohydrolysis) and the NAD(+)-dependent ADP-ribosylation of guanine-nucleotide-binding proteins. Recently, the S1 subunit of pertussis toxin was shown to be photolabelled by using radiolabelled NAD+ and u.v.; the primary labelled residue was Glu-129, thereby implicating this residue in the binding of NAD+. Studies from various laboratories have shown that the N-terminal portion of the S1 subunit, which shows sequence similarity to cholera toxin and Escherichia coli heat-labile toxin, is important to the maintenance of both glycohydrolase and transferase activity. In the present study the photolabelling technique was applied to the analysis of a series of recombinant-derived S1 molecules that possessed deletions or substitutions near the N-terminus of the S1 molecule. The results revealed a positive correlation between the extent of photolabelling with NAD+ and the magnitude of specific NAD+ glycohydrolase activity exhibited by the mutants. Enzyme kinetic analyses of the N-terminal mutants also identified a mutant with substantially reduced activity, a depressed photolabelling efficiency and a markedly increased Km for NAD+. The results support a direct role for the N-terminal region of the S1 subunit in the binding of NAD+, thereby providing a rationale for the effect of mutations in this region on enzymic activity. Images Fig. 1. PMID:2363691

  12. The Effects of Spinopelvic Parameters and Paraspinal Muscle Degeneration on S1 Screw Loosening

    PubMed Central

    Kim, Jin-Bum; Lee, Young-Seok; Nam, Taek-Kyun; Park, Yong-Sook; Kim, Young-Baeg

    2015-01-01

    Objective To investigate risk factors for S1 screw loosening after lumbosacral fusion, including spinopelvic parameters and paraspinal muscles. Methods We studied with 156 patients with degenerative lumbar disease who underwent lumbosacral interbody fusion and pedicle screw fixation including the level of L5-S1 between 2005 and 2012. The patients were divided into loosening and non-loosening groups. Screw loosening was defined as a halo sign larger than 1 mm around a screw. We checked cross sectional area of paraspinal muscles, mean signal intensity of the muscles on T2 weight MRI as a degree of fatty degeneration, spinopelvic parameters, bone mineral density, number of fusion level, and the characteristic of S1 screw. Results Twenty seven patients showed S1 screw loosening, which is 24.4% of total. The mean duration for S1 screw loosening was 7.3±4.1 months after surgery. Statistically significant risk factors were increased age, poor BMD, 3 or more fusion levels (p<0.05). Among spinopelvic parameters, a high pelvic incidence (p<0.01), a greater difference between pelvic incidence and lumbar lordotic angle preoperatively (p<0.01) and postoperatively (p<0.05). Smaller cross-sectional area and high T2 signal intensity in both multifidus and erector spinae muscles were also significant muscular risk factors (p<0.05). Small converging angle (p<0.001) and short intraosseous length (p<0.05) of S1 screw were significant screw related risk factors (p<0.05). Conclusion In addition to well known risk factors, spinopelvic parameters and the degeneration of paraspinal muscles also showed significant effects on the S1 screw loosening. PMID:26587190

  13. Identification of genetic polymorphisms of CYP2S1 in a Finnish Caucasian population.

    PubMed

    Saarikoski, Sirkku T; Suitiala, Tuula; Holmila, Reetta; Impivaara, Olli; Järvisalo, Jorma; Hirvonen, Ari; Husgafvel-Pursiainen, Kirsti

    2004-10-01

    CYP2S1 is a recently discovered member of the cytochrome P450 (CYP) gene superfamily. Interestingly, even though the DNA sequence identifies it as the sole member of the new CYP2S family, CYP2S1 exhibits many features typical to CYP1 family members, e.g. dioxin-inducibility mediated by the aryl hydrocarbon receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, CYP2S1 metabolises some aromatic hydrocarbons as well as cellular substances. These characteristics, together with a wide extrahepatic tissue distribution, suggest that CYP2S1 may have an important role in both exogenous and endogenous metabolism. This is the first study characterising CYP2S1 alleles and naming them with the recommended CYP allele nomenclature. We used denaturing gradient gel electrophoresis (DGGE) and direct sequencing to investigate genetic variation of CYP2S1 in 100 male Finnish Caucasians. Those exons in which variation was found were examined in subsequent 100 subjects. The coding region of all of the nine exons, as well as a 449 bp fragment of the proximal promoter region, was analysed. This systematic investigation revealed eight single nucleotide polymorphisms (SNPs), which comprise nine different variant alleles (haplotypes), in addition to the wild-type allele. Seven of the SNPs occurred in the protein-coding areas and one in the proximal 3' untranslated region (3'UTR). Two of these sequence variations (10347C > T and 13106C > T) result in non-conservative amino acid substitutions, i.e. Arg380Cys and Pro466Leu, respectively. The respective allelic variants, CYP2S1*2 ([10347C > T]) and CYP2S1*3 (13106C > T; 13255A > G]), occurred in our study population at frequencies of 0.50 and 3.75%, respectively. The most common of the variant alleles was CYP2S1*1H (23.8%), harbouring a 13255A > G substitution located in the 3'UTR. PMID:15450424

  14. Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer.

    PubMed

    Qiu, Meng; Peng, Xing-chen; Bi, Feng; Wang, Xin; Li, Qiu; Xu, Feng; Li, Zhi-ping; Shen, Ya-li; Liu, Ji-yan; Zhao, Ya-qing; Cao, Dan; Gou, Hong-feng; Yang, Yu; Chen, Ye; Yi, Cheng

    2015-07-01

    Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1

  15. Novel S1P(1) receptor agonists--part 3: from thiophenes to pyridines.

    PubMed

    Bolli, Martin H; Abele, Stefan; Birker, Magdalena; Bravo, Roberto; Bur, Daniel; de Kanter, Ruben; Kohl, Christopher; Grimont, Julien; Hess, Patrick; Lescop, Cyrille; Mathys, Boris; Müller, Claus; Nayler, Oliver; Rey, Markus; Scherz, Michael; Schmidt, Gunther; Seifert, Jürgen; Steiner, Beat; Velker, Jörg; Weller, Thomas

    2014-01-01

    In preceding communications we summarized our medicinal chemistry efforts leading to the identification of potent, selective, and orally active S1P1 agonists such as the thiophene derivative 1. As a continuation of these efforts, we replaced the thiophene in 1 by a 2-, 3-, or 4-pyridine and obtained less lipophilic, potent, and selective S1P1 agonists (e.g., 2) efficiently reducing blood lymphocyte count in the rat. Structural features influencing the compounds' receptor affinity profile and pharmacokinetics are discussed. In addition, the ability to penetrate brain tissue has been studied for several compounds. As a typical example for these pyridine based S1P1 agonists, compound 53 showed EC50 values of 0.6 and 352 nM for the S1P1 and S1P3 receptor, respectively, displayed favorable PK properties, and penetrated well into brain tissue. In the rat, compound 53 maximally reduced the blood lymphocyte count for at least 24 h after oral dosing of 3 mg/kg. PMID:24367923

  16. Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide.

    PubMed

    Ye, Xiaoli; Zhou, Ming; He, Yonggang; Wan, Yanmin; Bai, Weiya; Tao, Shuai; Ren, Yanqin; Zhang, Xinxin; Xu, Jianqing; Liu, Jing; Zhang, Junqi; Hu, Kanghong; Xie, Youhua

    2016-01-01

    Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1-binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors. PMID:27384014

  17. S1 pocket of glutamate carboxypeptidase II: a new binding site for amyloid-β degradation.

    PubMed

    Lee, Suk Kyung; Kim, Hyunyoung; Cheong, You-Hoon; Kim, Min-Ju; Jo, Sangmee Ahn; Youn, Hyung-Seop; Park, Sang Ick

    2013-09-01

    We recently reported that glutamate carboxypeptidase II (GCPII) has a new physiological function degrading amyloid-β (Aβ), distinct from its own hydrolysis activity in N-acetyl-L-aspartyl-L-glutamate (NAAG); however, its underlying mechanism remains undiscovered. Using site-directed mutagenesis and S1 pocket-specific chemical inhibitor (compound 2), which was developed for the present study based on in sillico computational modeling, we discovered that the Aβ degradation occurs through S1 pocket but not through S1' pocket responsible for NAAG hydrolysis. Treatment with compound 2 prevented GCPII from Aβ degradation without any impairment in NAAG hydrolysis. Likewise, 2-PMPA (specific GCPII inhibitor developed targeting S1' pocket) completely blocked the NAAG hydrolysis without any effect on Aβ degradation. Pre-incubation with NAAG and Aβ did not affect Aβ degradation and NAAG hydrolysis, respectively. These data suggest that GCPII has two distinctive binding sites for two different substrates and that Aβ degradation occurs through binding to S1 pocket of GCPII. PMID:23891752

  18. Short-range correlations and the 3 s1 /2 wave function in 206Pb

    NASA Astrophysics Data System (ADS)

    Anders, M. R.; Shlomo, S.; Talmi, I.

    2015-09-01

    The charge-density difference between 206Pb and 205Tl , measured by elastic electron scattering, offers a unique opportunity to look for effects of short-range correlations on a shell-model wave function of a single proton. The measured difference is very similar to the charge density due to a proton in a 3 s1 /2 orbit. If there is a potential whose 3 s1 /2 wave function yields the measured difference between the charge distributions, no effect of short-range correlations is evident. To check this point, we look for a potential whose 3 s1 /2 wave function yields the measured data. We developed a novel method to obtain the potential directly from the density and its first and second derivatives. Fits to parametrized potentials were also carried out. The 3 s1 /2 wave functions of the potentials determined here reproduce fairly well the experimental data within the quoted errors. To detect possible effects of two-body correlations on the 3 s1 /2 shell-model wave function, more accurate measurements are required.

  19. Renormalized Traces and Cocycles on the Algebra of S 1-Pseudo-differential Operators

    NASA Astrophysics Data System (ADS)

    Magnot, Jean-Pierre

    2006-02-01

    Using renormalized (or weighted) traces of classical pseudo-differential operators and calculus on formal symbols. We exhibit three cocycles on the Lie algebra of classical pseudo-differential operators Cl(S^1,mathbb{C}^n) acting on L^2(S^1,mathbb{C}^n). We first show that the Schwinger functional c_S^D associated to the Dirac operator is a cocycle on Cl(S^1,mathbb{C}^n), and not only on a restricted algebra Cl(S^1,mathbb{C}^n)^D_res. Then, we investigate two bilinear functionals c+^D and c_{++}^D, which satisfies {1 over 2}c_S^D = c_+^D - c_{++}^D. We show that c+^D and c_{++}^D are two cocycles in Cl(S^1,mathbb{C}^n), and {1 over 2}c_S^D and c_+^D have the same nonvanishing cohomology class. We finaly calculate c+^D on classical pseudo-differential operators of order 1 and on differential operators of order 1, in terms of partial symbols. By this last computation, we recover the Virasoro cocyle and the Kähler form of the loop group.

  20. Novel S1P1 receptor agonists - Part 5: From amino-to alkoxy-pyridines.

    PubMed

    Bolli, Martin H; Lescop, Cyrille; Birker, Magdalena; de Kanter, Ruben; Hess, Patrick; Kohl, Christopher; Nayler, Oliver; Rey, Markus; Sieber, Patrick; Velker, Jörg; Weller, Thomas; Steiner, Beat

    2016-06-10

    In a previous communication we reported on the discovery of aminopyridine 1 as a potent, selective and orally active S1P1 receptor agonist. More detailed studies revealed that this compound is phototoxic in vitro. As a result of efforts aiming at eliminating this undesired property, a series of alkoxy substituted pyridine derivatives was discovered. The photo irritancy factor (PIF) of these alkoxy pyridines was significantly lower than the one of aminopyridine 1 and most compounds were not phototoxic. Focused SAR studies showed, that 2-, 3-, and 4-pyridine derivatives delivered highly potent S1P1 receptor agonists. While the 2-pyridines were clearly more selective against S1PR3, the corresponding 3- or 4-pyridine analogues showed significantly longer oral half-lives and as a consequence longer pharmacological duration of action after oral administration. One of the best compounds, cyclopentoxy-pyridine 45b lacked phototoxicity, showed EC50 values of 0.7 and 140 nM on S1PR1 and S1PR3, respectively, and maximally reduced the blood lymphocyte count for at least 24 h after oral administration of 10 mg/kg to Wistar rats. PMID:27027817

  1. An oral fluoropyrimidine agent S-1 induced interstitial lung disease: A case report

    PubMed Central

    Yamane, Hiromichi; Kinugawa, Masahide; Umemura, Shigeki; Shiote, Yasuhiro; Kudo, Kenichiro; Suwaki, Toshimitsu; Kamei, Haruhito; Takigawa, Nagio; Kiura, Katsuyuki

    2011-01-01

    A 66-year-old Japanese man with pancreatic cancer received eleven courses of gemcitabine monotherapy. The tumor responded to gemcitabine until metastatic liver tumors progressed. Subsequently, he was treated with S-1, an oral fluoropyrimidine anticancer agent, as salvage chemotherapy. Forty-two days after initiating S-1, he presented with dyspnea and fever. Chest computed tomography showed diffuse interstitial lesions with thickening of the alveolar septa and ground glass opacity. Serum KL-6 level was elevated to 1,230 U/mL and he did not use any other drugs except insulin. Thus, the development of interstitial lung disease (ILD) was considered to be due to S-1. Arterial blood oxygen pressure was 49.6 Torr in spite of oxygen administration (5 L/min). Steroid therapy improved his symptoms and the interstitial shadows on chest radiograph. Although S-1-induced ILD has mostly been reported to be mild, clinicians should be aware that S-1 has the potential to cause fatal ILD. PMID:21773080

  2. Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide

    PubMed Central

    Ye, Xiaoli; Zhou, Ming; He, Yonggang; Wan, Yanmin; Bai, Weiya; Tao, Shuai; Ren, Yanqin; Zhang, Xinxin; Xu, Jianqing; Liu, Jing; Zhang, Junqi; Hu, Kanghong; Xie, Youhua

    2016-01-01

    Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1-binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors. PMID:27384014

  3. Novel S1P1 receptor agonists - Part 4: Alkylaminomethyl substituted aryl head groups.

    PubMed

    Lescop, Cyrille; Müller, Claus; Mathys, Boris; Birker, Magdalena; de Kanter, Ruben; Kohl, Christopher; Hess, Patrick; Nayler, Oliver; Rey, Markus; Sieber, Patrick; Steiner, Beat; Weller, Thomas; Bolli, Martin H

    2016-06-30

    In a previous communication we reported on the discovery of alkylamino pyridine derivatives (e.g. 1) as a new class of potent, selective and efficacious S1P1 receptor (S1PR1) agonists. However, more detailed profiling revealed that this compound class is phototoxic in vitro. Here we describe a new class of potent S1PR1 agonists wherein the exocyclic nitrogen was moved away from the pyridine ring (e.g. 11c). Further structural modifications led to the identification of novel alkylaminomethyl substituted phenyl and thienyl derivatives as potent S1PR1 agonists. These new alkylaminomethyl aryl compounds showed no phototoxic potential. Based on their in vivo efficacy and ability to penetrate the brain, the 5-alkyl-aminomethyl thiophenes appeared to be the most interesting class. Potent and selective S1PR1 agonist 20e, for instance, maximally reduced the blood lymphocyte count (LC) for 24 h after oral administration of 10 mg/kg to rat and its brain concentrations reached >500 ng/g over 24 h. PMID:27061986

  4. Combination chemotherapy with S-1 and docetaxel for cutaneous angiosarcoma resistant to paclitaxel.

    PubMed

    Kajihara, Ikko; Kanemaru, Hisashi; Miyake, Taiga; Aoi, Jun; Masuguchi, Shinichi; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu

    2015-02-01

    The prognosis of cutaneous angiosarcoma is very poor compared with that of other skin malignancies. The main reason for this is the limited regimens of chemotherapy available for angiosarcoma, because it is resistant to most common chemotherapeutic agents. Therefore, there is an urgent need to identify new treatment options. Recently, S-1 and docetaxel therapy was reported to be effective for advanced gastric cancer and metastatic extramammary Paget's disease. Therefore, we treated paclitaxel-resistant angiosarcoma patient with S-1/docetaxel chemotherapy. The progression-free survival was 5.0 months although grade 3 adverse events such as diarrhea and neutropenia developed. Our data need to be confirmed in a large number of patients, but S-1/docetaxel chemotherapy as an additional regimen seems to be an effective treatment option for paclitaxel-resistant angiosarcoma. PMID:25788055

  5. A search for the H2 /3, 0/ S1 line in the spectrum of Titan

    NASA Technical Reports Server (NTRS)

    Muench, G.; Trauger, J. T.; Roesler, F. L.

    1977-01-01

    Results are reported for measurements of the quadrupole S1 line of the (3, 0) absorption band of H2 in spectra of Titan, which were performed at an effective resolution of 0.09 A by scanning with a PEPSIOS spectrometer over a range of 0.85 A centered at the expected position of the investigated line and sampling in 80 contiguous channels. No statistically significant H2 (3, 0) S1 feature is found in the spectra, but a three-sigma upper limit of 3 mA is set for the equivalent width of the S1 line that might be present in a co-added spectrum. It is concluded that these measurements do not provide any evidence for the presence of H2 in the atmosphere of Titan.

  6. The 2(2S + 1)-formalism and its connection with other descriptions

    NASA Astrophysics Data System (ADS)

    Dvoeglazov, Valeriy V.

    2016-02-01

    In the framework of the Joos-Weinberg 2(2S + 1)-theory for massless particles, the dynamical invariants have been derived from the Lagrangian density which is considered to be a 4-vector. A la Majorana interpretation of the 6-component “spinors”, the field operators of S = 1 particles, as the left- and right-circularly polarized radiation, leads us to the conserved quantities which are analogous to those obtained by Lipkin and Sudbery. The scalar Lagrangian of the Joos-Weinberg theory is shown to be equivalent to the Lagrangian of a free massless field, introduced by Hayashi. As a consequence of a new “gauge” invariance this skew-symmetric field describes physical particles with the longitudinal components only. The interaction of the spinor field with the Weinberg’s 2(2S + 1)-component massless field is considered. New interpretation of the Weinberg field function is proposed.

  7. Use of S1 nuclease in deep sequencing for detection of double-stranded RNA viruses.

    PubMed

    Shimada, Saya; Nagai, Makoto; Moriyama, Hiromitsu; Fukuhara, Toshiyuki; Koyama, Satoshi; Omatsu, Tsutomu; Furuya, Tetsuya; Shirai, Junsuke; Mizutani, Tetsuya

    2015-09-01

    Metagenomic approach using next-generation DNA sequencing has facilitated the detection of many pathogenic viruses from fecal samples. However, in many cases, majority of the detected sequences originate from the host genome and bacterial flora in the gut. Here, to improve efficiency of the detection of double-stranded (ds) RNA viruses from samples, we evaluated the applicability of S1 nuclease on deep sequencing. Treating total RNA with S1 nuclease resulted in 1.5-28.4- and 10.1-208.9-fold increases in sequence reads of group A rotavirus in fecal and viral culture samples, respectively. Moreover, increasing coverage of mapping to reference sequences allowed for sufficient genotyping using analytical software. These results suggest that library construction using S1 nuclease is useful for deep sequencing in the detection of dsRNA viruses. PMID:25843154

  8. Radiationless deactivation of 6-aminocoumarin from the S1-ICT state in nonspecifically interacting solvents.

    PubMed

    Krystkowiak, Ewa; Dobek, Krzysztof; Burdziński, Gotard; Maciejewski, Andrzej

    2012-08-01

    This paper presents the results of a spectral (absorption and emission) and photophysical study of 6-aminocoumarin (6AC) in the solvents with which this molecule interacts only nonspecifically (n-alkanes, tetrachloromethane and 1-chloro-n-alkanes) and in nitriles. The strong effects of the solvents on the emission spectra, fluorescence quantum yield and lifetime of 6AC were observed. The results of the steady-state and time-resolved photophysical study suggest the presence of very fast nonradiative deactivation processes. It is concluded that besides fluorescence, the efficient S(1)-ICT → S(0) internal conversion in nonpolar aprotic solvents arises from vibronic interactions between close-lying S(1)-ICT(π,π*) and S(2)(n,π*) states. Moreover, unexpectedly efficient triplet state formation occurs. In nitriles the intermolecular hydrogen-bonding interactions with solvent molecules also facilitate the nonradiative decay process involving the S(1)-exciplex. PMID:22622372

  9. Molecular and immunological characterization of the glycosylated orange allergen Cit s 1.

    PubMed

    Pöltl, Gerald; Ahrazem, Oussama; Paschinger, Katharina; Ibañez, M Dolores; Salcedo, Gabriel; Wilson, Iain B H

    2007-02-01

    The IgE of sera from patients with a history of allergy to oranges (Citrus sinensis) binds a number of proteins in orange extract, including Cit s 1, a germin-like protein. In the present study, we have analyzed its immunological cross-reactivity and its molecular nature. Sera from many of the patients examined recognize a range of glycoproteins and neoglycoconjugates containing beta1,2-xylose and core alpha1,3-fucose on their N-glycans. These reagents also inhibited the interaction of Cit s 1 with patients' sera, thus underlining the critical role of glycosylation in the recognition of this protein by patients' IgE and extending previous data showing that deglycosylated Cit s 1 does not possess IgE epitopes. In parallel, we examined the peptide sequence and glycan structure of Cit s 1, using mass spectrometric techniques. Indeed, we achieved complete sequence coverage of the mature protein compared with the translation of an expressed sequence tag cDNA clone and demonstrated that the single N-glycosylation site of this protein carries oligosaccharides with xylose and fucose residues. Owing to the presumed requirement for multivalency for in vivo allergenicity, our molecular data showing that Cit s 1 is monovalent as regards glycosylation and that the single N-glycan is the target of the IgE response to this protein explain the immunological cross-reactive properties of Cit s 1 as well as its equivocal nature as a clinically relevant allergen. PMID:17095532

  10. Optimization of a Potent, Orally Active S1P1 Agonist Containing a Quinolinone Core

    PubMed Central

    2011-01-01

    The optimization of a series of S1P1 agonists with limited activity against S1P3 is reported. A polar headgroup was used to improve the physicochemical and pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22 was dosed orally at 2 and 100 mg/kg. PMID:24900374

  11. STS-112 S1 truss in Payload Changeout Room at Launch Pad 39-B

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- In the Payload Changeout Room at the pad, the payload is moved out of the payload canister for transfer to Space Shuttle Atlantis' payload bay for mission STS-112. The primary payload on the mission is the S1 Integrated Truss Structure. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during the mission. Atlantis is scheduled to launch no earlier than Oct. 2.

  12. Negative infrared photoconductivity in CdS1-xSex films

    NASA Astrophysics Data System (ADS)

    Abdinov, A. S.; Jafarov, M. A.; Mamedov, H. M.; Nasirov, E. F.

    2003-09-01

    The negative infrared photoconductivity (NPH) has been observed for the first time in CdS1-xSex films, in the wavelength region of 0.700 - 1.23 μm. at values of stimulating light intensity Φ = 100 - 400 Lk. electrical field E = 0.5 - 130 V/cm and temperature T = 265 - 310 Κ. It is established, that basic laws of NPH explains on the basis of two-barrier model and in the considered conditions a charge carriers, overcome a barrier by tunneling. A films of CdS1-xSex can be used in IR engineering and negatronics.

  13. Observation of an exotic S = +1 baryon in exclusive photoproduction from the deuteron.

    PubMed

    Stepanyan, S; Hicks, K; Carman, D S; Pasyuk, E; Schumacher, R A; Smith, E S; Tedeschi, D J; Todor, L; Adams, G; Ambrozewicz, P; Anciant, E; Anghinolfi, M; Asavapibhop, B; Audit, G; Avakian, H; Bagdasaryan, H; Ball, J P; Barrow, S P; Battaglieri, M; Beard, K; Bektasoglu, M; Bellis, M; Berman, B L; Bianchi, N; Biselli, A S; Boiarinov, S; Bouchigny, S; Bradford, R; Branford, D; Briscoe, W J; Brooks, W K; Burkert, V D; Butuceanu, C; Calarco, J R; Carnahan, B; Chen, S; Ciciani, L; Cole, P L; Coleman, A; Cords, D; Corvisiero, P; Crabb, D; Crannell, H; Cummings, J P; De Sanctis, E; Degtyarenko, P V; Denizli, H; Dennis, L; De Vita, R; Dharmawardane, K V; Dhuga, K S; Djalali, C; Dodge, G E; Doughty, D; Dragovitsch, P; Dugger, M; Dytman, S; Dzyubak, O P; Egiyan, H; Egiyan, K S; Elouadrhiri, L; Empl, A; Eugenio, P; Fatemi, R; Feuerbach, R J; Ficenec, J; Forest, T A; Funsten, H; Garçon, M; Gavalian, G; Gilfoyle, G P; Giovanetti, K L; Gordon, C I O; Gothe, R; Griffioen, K; Guidal, M; Guillo, M; Guo, L; Gyurjyan, V; Hadjidakis, C; Hakobyan, R S; Hardie, J; Heddle, D; Heimberg, P; Hersman, F W; Hicks, R S; Holtrop, M; Hu, J; Hyde-Wright, C E; Ito, M M; Jenkins, D; Joo, K; Juengst, H G; Kellie, J D; Khandaker, M; Kim, K Y; Kim, K; Kim, W; Klein, A; Klein, F J; Klimenko, A V; Klusman, M; Kossov, M; Kramer, L H; Kuang, Y; Kubarovsky, V; Kuhn, S E; Kuhn, J; Lachniet, J; Lawrence, D; Li, J; Lima, A; Livingston, K; Lukashin, K; Manak, J J; McAleer, S; McNabb, J W C; Mecking, B A; Mehrabyan, S; Melone, J J; Mestayer, M D; Meyer, C A; Mikhailov, K; Minehart, R; Mirazita, M; Miskimen, R; Mokeev, V; Morand, L; Morrow, S; Muccifora, V; Mueller, J; Murphy, L Y; Mutchler, G S; Napolitano, J; Nasseripour, R; Niccolai, S; Niculescu, G; Niculescu, I; Niczyporuk, B B; Niyazov, R A; Nozar, M; O'Brien, J; O'Rielly, G V; Opper, A K; Osipenko, M; Park, K; Peterson, G; Philips, S A; Pivnyuk, N; Pocanic, D; Pogorelko, O; Polli, E; Pozdniakov, S; Preedom, B M; Price, J W; Prok, Y; Protopopescu, D; Qin, L M; Raue, B A; Riccardi, G; Ricco, G; Ripani, M; Ritchie, B G; Ronchetti, F; Rossi, P; Rowntree, D; Rubin, P; Sabatié, F; Salgado, C; Santoro, J; Sapunenko, V; Serov, V S; Sharabian, Y G; Shaw, J; Simionatto, S; Skabelin, A V; Smith, L C; Sober, D I; Strakovsky, I I; Stavinsky, A; Stoler, P; Suleiman, R; Taiuti, M; Taylor, S; Thoma, U; Thompson, R; Tur, C; Ungaro, M; Vineyard, M F; Vlassov, A V; Wang, K; Weinstein, L B; Weller, H; Weygand, D P; Whisnant, C S; Wolin, E; Wood, M H; Yegneswaran, A; Yun, J

    2003-12-19

    In an exclusive measurement of the reaction gammad-->K(+)K(-)pn, a narrow peak that can be attributed to an exotic baryon with strangeness S=+1 is seen in the K(+)n invariant mass spectrum. The peak is at 1.542+/-0.005 GeV/c(2) with a measured width of 0.021 GeV/c(2) FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is (5.2+/-0.6)sigma. The mass and width of the observed peak are consistent with recent reports of a narrow S=+1 baryon by other experimental groups. PMID:14754107

  14. 11-cis retinal torsion: A QTAIM and stress tensor analysis of the S1 excited state

    NASA Astrophysics Data System (ADS)

    Maza, Julio R.; Jenkins, Samantha; Kirk, Steven R.

    2016-05-01

    We investigate torsion about the C11-C12 bond mid-point for the S1 state of 11-cis retinal, using a QTAIM and stress tensor analysis. The QTAIM and stress tensor responses to a torsion ±α increase at a faster rate for the preferred direction of torsion though the CI seam. A QTAIM and stress tensor vector-based analysis provides an alternative way of characterising the asymmetry of the S1 potential energy surface. In the vicinity of the CI seam the ellipticity ε attained minimum values. The application of this analysis to molecular rotary motors is briefly discussed.

  15. S1P3 receptor influences key physiological properties of fast-twitch extensor digitorum longus muscle.

    PubMed

    Germinario, Elena; Bondì, Michela; Cencetti, Francesca; Donati, Chiara; Nocella, Marta; Colombini, Barbara; Betto, Romeo; Bruni, Paola; Bagni, Maria Angela; Danieli-Betto, Daniela

    2016-06-01

    To examine the role of sphingosine 1-phosphate (S1P) receptor 3 (S1P3) in modulating muscle properties, we utilized transgenic mice depleted of the receptor. Morphological analyses of extensor digitorum longus (EDL) muscle did not show evident differences between wild-type and S1P3-null mice. The body weight of 3-mo-old S1P3-null mice and the mean cross-sectional area of transgenic EDL muscle fibers were similar to those of wild-type. S1P3 deficiency enhanced the expression level of S1P1 and S1P2 receptors mRNA in S1P3-null EDL muscle. The contractile properties of S1P3-null EDL diverge from those of wild-type, largely more fatigable and less able to recover. The absence of S1P3 appears responsible for a lower availability of calcium during fatigue. S1P supplementation, expected to stimulate residual S1P receptors and signaling, reduced fatigue development of S1P3-null muscle. Moreover, in the absence of S1P3, denervated EDL atrophies less than wild-type. The analysis of atrophy-related proteins in S1P3-null EDL evidences high levels of the endogenous regulator of mitochondria biogenesis peroxisome proliferative-activated receptor-γ coactivator 1α (PGC-1α); preserving mitochondria could protect the muscle from disuse atrophy. In conclusion, the absence of S1P3 makes the muscle more sensitive to fatigue and slows down atrophy development after denervation, indicating that S1P3 is involved in the modulation of key physiological properties of the fast-twitch EDL muscle. PMID:26718782

  16. Effect of Self-Regulated Learning and Motivation to Achieve against Teacher Professional Capability for Student S1 PGSD of Science Field Compared with Regular Student S1 PGSD at UPBJJ Serang

    ERIC Educational Resources Information Center

    Prayekti

    2015-01-01

    This study is to know effect of self-regulated learning and motivation to achieve against teacher professional capability for student S1 PGSD of science field compared with regular student S1 PGSD. The student uses grades of Classroom Action Research (CAR) and Stabilization of Professional Capability (SPC) on curriculum of S1 PGSD to see…

  17. The 3P0-VERSUS 3S1-MODELS for Quark-Antiquark Annihilation

    NASA Astrophysics Data System (ADS)

    Green, A. M.; Niskanen, J. A.

    A comparison is made between the 3S1- and 3P0-models for quark-antiquark annihilation or creation. Even though the former appears, at first sight, to be superior for Nbar {N} annihilation into two mesons, it is argued from their effects in meson decays that this conclusion is premature.

  18. Installation of the S1 Truss to the International Space Station

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Astronauts Piers J. Sellers (left ) and David A. Wolf work on the newly installed Starboard One (S1) truss to the International Space Station (ISS) during the STS-112 mission. The primary payloads of this mission, ISS Assembly Mission 9A, were the Integrated Truss Assembly S1 (S One), the starboard side thermal radiator truss, and the Crew Equipment Translation Aid (CETA) cart to the ISS. The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss was attached to the S0 (S Zero) truss, which was launched on April 8, 2002 aboard the STS-110, and flows 637 pounds of anhydrous ammonia through three heat-rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA cart was attached to the Mobil Transporter and will be used by assembly crews on later missions. Manufactured by the Boeing Company in Huntington Beach, California, the truss primary structure was transferred to the Marshall Space Flight Center in February 1999 for hardware installations and manufacturing acceptance testing. The launch of the STS-112 mission occurred on October 7, 2002, and its 11-day mission ended on October 18, 2002.

  19. 26 CFR 1.6050S-1 - Information reporting for qualified tuition and related expenses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050S-1... relating to substitute forms (see § 601.601(d)(2) of this chapter). (ii) Information included on return. An... form complies with applicable revenue procedures relating to substitute forms (see § 601.601(d)(2)...

  20. 26 CFR 1.6050S-1 - Information reporting for qualified tuition and related expenses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050S-1... relating to substitute forms (see § 601.601(d)(2) of this chapter). (ii) Information included on return. An... form complies with applicable revenue procedures relating to substitute forms (see § 601.601(d)(2)...

  1. Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1.

    PubMed

    He, Chang-Liang; Bian, Yang-Yang; Xue, Yu; Liu, Ze-Xian; Zhou, Kai-Qiang; Yao, Cui-Fang; Lin, Yan; Zou, Han-Fa; Luo, Fang-Xiu; Qu, Yuan-Yuan; Zhao, Jian-Yuan; Ye, Ming-Liang; Zhao, Shi-Min; Xu, Wei

    2016-01-01

    In cancer cells, the mammalian target of rapamycin complex 1 (mTORC1) that requires hormonal and nutrient signals for its activation, is constitutively activated. We found that overexpression of pyruvate kinase M2 (PKM2) activates mTORC1 signaling through phosphorylating mTORC1 inhibitor AKT1 substrate 1 (AKT1S1). An unbiased quantitative phosphoproteomic survey identified 974 PKM2 substrates, including serine202 and serine203 (S202/203) of AKT1S1, in the proteome of renal cell carcinoma (RCC). Phosphorylation of S202/203 of AKT1S1 by PKM2 released AKT1S1 from raptor and facilitated its binding to 14-3-3, resulted in hormonal- and nutrient-signals independent activation of mTORC1 signaling and led accelerated oncogenic growth and autophagy inhibition in cancer cells. Decreasing S202/203 phosphorylation by TEPP-46 treatment reversed these effects. In RCCs and breast cancers, PKM2 overexpression was correlated with elevated S202/203 phosphorylation, activated mTORC1 and inhibited autophagy. Our results provided the first phosphorylome of PKM2 and revealed a constitutive mTORC1 activating mechanism in cancer cells. PMID:26876154

  2. Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1

    PubMed Central

    He, Chang-Liang; Bian, Yang-Yang; Xue, Yu; Liu, Ze-Xian; Zhou, Kai-Qiang; Yao, Cui-Fang; Lin, Yan; Zou, Han-Fa; Luo, Fang-Xiu; Qu, Yuan-Yuan; Zhao, Jian-Yuan; Ye, Ming-Liang; Zhao, Shi-Min; Xu, Wei

    2016-01-01

    In cancer cells, the mammalian target of rapamycin complex 1 (mTORC1) that requires hormonal and nutrient signals for its activation, is constitutively activated. We found that overexpression of pyruvate kinase M2 (PKM2) activates mTORC1 signaling through phosphorylating mTORC1 inhibitor AKT1 substrate 1 (AKT1S1). An unbiased quantitative phosphoproteomic survey identified 974 PKM2 substrates, including serine202 and serine203 (S202/203) of AKT1S1, in the proteome of renal cell carcinoma (RCC). Phosphorylation of S202/203 of AKT1S1 by PKM2 released AKT1S1 from raptor and facilitated its binding to 14-3-3, resulted in hormonal- and nutrient-signals independent activation of mTORC1 signaling and led accelerated oncogenic growth and autophagy inhibition in cancer cells. Decreasing S202/203 phosphorylation by TEPP-46 treatment reversed these effects. In RCCs and breast cancers, PKM2 overexpression was correlated with elevated S202/203 phosphorylation, activated mTORC1 and inhibited autophagy. Our results provided the first phosphorylome of PKM2 and revealed a constitutive mTORC1 activating mechanism in cancer cells. PMID:26876154

  3. Study of the Vibrational Spectra of the Mixed Crystal ZnS1-xSex

    NASA Astrophysics Data System (ADS)

    Basak, Tista; Rao, Mala N.; Chaplot, S. L.

    2011-07-01

    A simple transferable potential model has been employed to study the vibrational mode behavior of the mixed system ZnS1-xSex as a function of concentration and pressure. Further, the existence of a localized resonance mode has also been confirmed, in agreement with experimental data from Raman scattering.

  4. B cell-specific S1PR1 deficiency blocks prion dissemination between secondary lymphoid organs.

    PubMed

    Mok, Simon W F; Proia, Richard L; Brinkmann, Volker; Mabbott, Neil A

    2012-05-15

    Many prion diseases are peripherally acquired (e.g., orally or via lesions to skin or mucous membranes). After peripheral exposure, prions replicate first upon follicular dendritic cells (FDC) in the draining lymphoid tissue before infecting the brain. However, after replication upon FDC within the draining lymphoid tissue, prions are subsequently propagated to most nondraining secondary lymphoid organs (SLO), including the spleen, by a previously underdetermined mechanism. The germinal centers in which FDC are situated produce a population of B cells that can recirculate between SLO. Therefore, we reasoned that B cells were ideal candidates by which prion dissemination between SLO may occur. Sphingosine 1-phosphate receptor (S1PR)1 stimulation controls the egress of T and B cells from SLO. S1PR1 signaling blockade sequesters lymphocytes within SLO, resulting in lymphopenia in the blood and lymph. We show that, in mice treated with the S1PR modulator FTY720 or with S1PR1 deficiency restricted to B cells, the dissemination of prions from the draining lymph node to nondraining SLO is blocked. These data suggest that B cells interacting with and acquiring surface proteins from FDC and recirculating between SLO via the blood and lymph mediate the initial propagation of prions from the draining lymphoid tissue to peripheral tissues. PMID:22504650

  5. Wavelength-tunable lasing in single-crystal CdS1-XSeX nanoribbons

    NASA Astrophysics Data System (ADS)

    Liu, Y. K.; Zapien, J. A.; Shan, Y. Y.; Tang, H.; Lee, C. S.; Lee, S. T.

    2007-09-01

    Alloyed ternary CdS1-XSeX nanoribbons of variable composition X were synthesized by the combination of thermal evaporation and laser ablation. High-resolution transmission electron microscopy and x-ray diffraction showed that the ternary CdS1-XSeX nanoribbons were single phase and highly crystalline. Room-temperature optical measurements showed that band-gap engineering could be realized in CdS1-XSeX nanoribbons via modulation in composition X. Lasing emission between the band-gap energy of CdS (512 nm) and that of CdSe (710 nm) was observed for composition 0S1-XSeX nanoribbons reveal the uniform optical properties of the nanoribbons, which supports the absence of phase segregation within the nanoribbon. Fine tuning of the lasing wavelength via composition changes is shown to be smaller than 0.1 nm, and is capable of overlapping thermally induced tuning, demonstrating the possibility of continuous tuning in the lasing wavelength. The broad and fine tunable lasing properties of ternary nanoribbons have potential applications in color-tuned nanolasers, biological labels, and nano-optoelectronics.

  6. Sacrum fracture following L5-S1 stand-alone interbody fusion for isthmic spondylolisthesis.

    PubMed

    Phan, Kevin; Mobbs, Ralph J

    2015-11-01

    We report a 72-year-old man with a rare sacral fracture following stand-alone L5-S1 anterior lumbar interbody fusion for isthmic spondylolisthesis. The man underwent a minimally invasive management strategy using posterior percutaneous pedicle fixation and partial reduction of the deformity. We also discuss the current literature on fusion procedures for isthmic spondylolisthesis. PMID:26100158

  7. SKI-1/S1P inhibitor PF-429242 impairs the onset of HCV infection.

    PubMed

    Blanchet, Matthieu; Sureau, Camille; Guévin, Carl; Seidah, Nabil G; Labonté, Patrick

    2015-03-01

    Worldwide, approximately 170 million individuals are afflicted with chronic hepatitis C virus (HCV) infection. To prevent the development of inherent diseases such as cirrhosis and hepatocellular carcinoma, tremendous efforts have been made, leading to the development of promising new treatments. However, their efficiency is still dependent on the viral genotype. Additionally, these treatments that target the virus directly can trigger the emergence of resistant variants. In a previous study, we have demonstrated that a long-term (72h) inhibition of SKI-1/S1P, a master lipogenic pathway regulator through activation of SREBP, resulted in impaired HCV genome replication and infectious virion secretion. In the present study, we sought to investigate the antiviral effect of the SKI-1/S1P small molecule inhibitor PF-429242 at the early steps of the HCV lifecycle. Our results indicate a very potent antiviral effect of the inhibitor early in the viral lifecycle and that the overall action of the compound relies on two different contributions. The first one is SREBP/SKI-1/S1P dependent and involves LDLR and NPC1L1 proteins, while the second one is SREBP independent. Overall, our study confirms that SKI-1/S1P is a relevant target to impair HCV infection and that PF-429242 could be a promising candidate in the field of HCV infection treatment. PMID:25573299

  8. Structure of the S1S2 Glutamate Binding Domain of GluR3

    PubMed Central

    Ahmed, Ahmed H.; Wang, Qi; Sondermann, Holger; Oswald, Robert E.

    2009-01-01

    Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. Determining the structural differences between the binding sites of different subtypes is crucial to our understanding of neuronal circuits and to the development of subtype specific drugs. The structures of the binding domain (S1S2) of the GluR3 (flip) AMPA receptor subunit bound to glutamate and AMPA and the GluR2 (flop) subunit bound to glutamate were determined by X-ray crystallography to 1.9, 2.1, and 1.55 Å, respectively. Overall, the structure of GluR3 (flip) S1S2 is very similar to GluR2 (flop) S1S2 (backbone RMSD of 0.30 ± 0.05 for glutamate-bound and 0.26 ± 0.01 for AMPA-bound). The differences in the flip and flop isoforms are subtle and largely arise from one hydrogen bond across the dimer interface and associated water molecules. Comparison of the binding affinity for various agonists and partial agonists suggest that the S1S2 domains of GluR2 and GluR3 show only small differences in affinity, unlike what is found for the intact receptors (with the exception of one ligand, Cl-HIBO, which has a ten-fold difference in affinity for GluR2 vs GluR3). PMID:19003990

  9. High-Dispersion Spectroscopic Observations of Comet C/2012 S1 (ISON) with the Subaru Telescope

    NASA Astrophysics Data System (ADS)

    Shinnaka, Yoshiharu; Kawakita, Hideyo; Nagashima, Masayoshi; Hitomi, Kobayashi; Decock, Alice; Jehin, Emmanuel; Boice, Daniel C.

    2014-11-01

    Comet C/2012 S1 (ISON) was one of the Oort cloud comets and dynamically new. This comet was broken at its perihelion passage on UT 2013 November 28.1 (at Rh ~ 17 solar radius). We observed the comet C/2012 S1 (ISON) on UT 2013 November 15 with the High Dispersion Spectrograph (HDS) mounted on the Subaru Telescope atop Mauna Kea, Hawaii. Its heliocentric and geocentric distances were 0.601 and 0.898 AU, respectively. We selected the slit size of 0”.5 x 9”.0 on the sky to achieve the spectral resolution of R = 72,000 from 550 to 830 nm. The total exposure time of comet C/2012 S1 (ISON) was 1200 seconds. We detected many emission lines caused from radicals (e.g., CN, C2, NH2), ions (H2O+), atoms ([OI] and Na I) and also many unidentified lines in the spectra. We report the (1) the ortho-to-para abundance ratios (OPRs) of water and ammonia estimated from the high-dispersion spectra of H2O+ and NH2, (2) the green-to-red line ratio of forbidden oxygen emissions, (3) the isotopic ratios of C2 (the carbon isotopic ratio from Swan band) and CN (the carbon and nitrogen isotopic ratios from red band), (4) the sodium-to-continuum ratio of comet C/2012 S1 (ISON).

  10. Determination of the hyperfine coupling constant of the cesium 7S1/2 state

    NASA Astrophysics Data System (ADS)

    Yang, Guang; Wang, Jie; Yang, Baodong; Wang, Junmin

    2016-08-01

    We report the hyperfine splitting (HFS) measurement of the cesium (Cs) 7S1/2 state by optical–optical double-resonance spectroscopy with the Cs 6S1/2–6P3/2–7S1/2 (852 nm  +  1470 nm) ladder-type system. The HFS frequency calibration is performed by employing a phase-type waveguide electro-optic modulator together with a stable confocal Fabry–Perot cavity. From the measured HFS between the F″  =  3 and F″  =  4 manifolds of the Cs 7S1/2 state (HFS  =  2183.273  ±  0.062 MHz), we have determined the magnetic dipole hyperfine coupling constant (A  =  545.818  ±  0.016 MHz), which is in good agreement with the previous work but much more precise.