CTQ 414: A New Gravitational Lens

We report the discovery and ground based observations of the new gravitational lens CTQ 414. The source quasar lies at a redshift of z = 1.29 with a B magnitude of 17.6. Ground based optical imaging reveals two point sources separated by 1.2 arcsec with a magnitude difference of roughly 1 mag. Subtraction of two stellar point spread functions from images obtained in subarcsecond seeing consistently leaves behind a faint, residual object. Fits for two point sources plus an extended object places the fainter object collinear with the two brighter components. Subsequent HST/NICMOS observations have confirmed the identification of the fainter object as the lensing galaxy. VLA observations at 8.46 GHz reveal that all components of the lensing system are radio quiet down to the 0.2 mJy flux level.Comment: Latex, 18 pages including 2 ps figures; accepted for publication in A

Globin gene expression in correlation with G protein-related genes during erythroid differentiation

Background: The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation. By analyzing erythroid progenitors, derived from hematopoietic cells through in vitro ontogeny, our study intends to determine early markers and signaling pathways of globin gene regulation and their relation to GPCR expression. Results: Human hematopoietic CD34(+) progenitors are isolated from fetal liver (FL), cord blood (CB), adult bone marrow (BM), peripheral blood (PB) and G-CSF stimulated mobilized PB (mPB), and then differentiated in vitro into erythroid progenitors. We find that growth capacity is most abundant in FL- and CB-derived erythroid cells. The erythroid progenitor cells are sorted as 100% CD71(+), but we did not find statistical significance in the variations of CD34, CD36 and GlyA antigens and that confirms similarity in maturation of studied ontogenic periods. During ontogeny, beta-globin gene expression reaches maximum levels in cells of adult blood origin (176 fmol/mu g), while gamma-globin gene expression is consistently up-regulated in CB-derived cells (60 fmol/mu g). During gamma-globin induction by hydroxycarbamide, we identify stimulated GPCRs (PTGDR, PTGER1) and GPCRs-coupled genes known to be activated via the cAMP/PKA (ADIPOQ), MAPK pathway (JUN) and NO/cGMP (PRPF18) signaling pathways. During ontogeny, GPR45 and ARRDC1 genes have the most prominent expression in FL-derived erythroid progenitor cells, GNL3 and GRP65 genes in CB-derived cells (high gamma-globin gene expression), GPR110 and GNG10 in BM-derived cells, GPR89C and GPR172A in PB-derived cells, and GPR44 and GNAQ genes in mPB-derived cells (high beta-globin gene expression). Conclusions: These results demonstrate the concomitant activity of GPCR-coupled genes and related signaling pathways during erythropoietic stimulation of globin genes. In accordance with previous reports, the stimulation of GPCRs supports the postulated connection between cAMP/PKA and NO/cGMP pathways in activation of.-globin expression, via JUN and p38 MAPK signaling

Erythropoietin and hypoxia increase erythropoietin receptor and nitric oxide levels in lung microvascular endothelial cells

Acute lung exposure to low oxygen results in pulmonary vasoconstriction and redistribution of blood flow. We used human microvascular endothelial cells from lung (HMVEC-L) to study the acute response to oxygen stress. We observed that hypoxia and erythropoietin (EPO) increased erythropoietin receptor (EPOR) gene expression and protein level in HMVEC-L In addition, EPO dose- and time-dependently stimulated nitric oxide (NO) production. This NO stimulation was evident despite hypoxia induced reduction of endothelial NO synthase (eNOS) gene expression. Western blot of phospho-eNOS (serine1177) and eNOS and was significantly induced by hypoxia but not after EPO treatment. However, iNOS increased at hypoxia and with EPO stimulation compared to normal oxygen tension. In accordance with our previous results of NO induction by EPO at low oxygen tension in human umbilical vein endothelial cells and bone marrow endothelial cells, these results provide further evidence in HMVEC-L for EPO regulation of NO production to modify the effects of hypoxia and cause compensatory vasoconstriction

Increased reticulocytosis during infancy is associated with increased hospitalizations in sickle cell anemia patients during the first three years of life

Objective Among older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60–180 days. Study Design Data from fifty-nine subjects who were followed at Children’s National Medical Center’s Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60–180 days and the clinical course of sickle cell anemia during infancy and childhood. Results A majority of subjects had demonstrable anemia with increased reticulocytosis. Only increased absolute reticulocyte levels during early infancy were associated with a significant increase in hospitalization during the first three years of life. Higher absolute reticulocyte counts were also associated with a markedly shorter time to first hospitalizations and a four-fold higher cumulative frequency of clinical manifestations over the first three years of life. No significant increase in white blood cell counts was identified among the infant subjects. Conclusions These data suggest that during early infancy, increased reticulocytosis among asymptomatic SCA subjects is associated with increased severity of disease in childhood

Французский язык. Практический курс по развитию навыков устной речи

<div><p>Nitrite is recognized as a bioactive nitric oxide (NO) metabolite. We have shown that nitrite inhibits platelet activation and increases platelet cGMP levels in the presence of partially deoxygenated erythrocytes. In this study, we investigated the effect of nitrite on phosphorylation of vasodilator-stimulated phosphoprotein on residue serine 239 (P-VASP^Ser239), a marker of protein kinase G (PKG) activation, in human platelets. In platelet-rich plasma (PRP), nitrite itself had no effect on levels of P-VASP^Ser239 while DEANONOate increased P-VASP^Ser239. Deoxygenation of PRP + erythrocytes (20% hematocrit) raised baseline P-VASP^Ser239 in platelets. At 20% hematocrit, nitrite (10 μM) increased P-VASP^Ser239 in platelets about 31% at 10–20 minutes of incubation while the levels of P-VASP^Ser157, a marker of protein kinase A (PKA) activation, were not changed. Nitrite increased P-VASP^Ser239 in platelets in the presence of deoxygenated erythrocytes at 20–40% hematocrit, but the effects were slightly greater at 20% hematocrit. In conclusion, our data confirm that nitrite increases P-VASP^Ser239 in platelets in the presence of deoxygenated erythrocytes. They also further support the idea that partially deoxygenated erythrocytes may modulate platelet activity, at least in part, via the NO/sGC/PKG pathway from NO formed by reduction of circulating nitrite ions.</p></div

PMN J1838-3427: A new gravitationally lensed quasar

We report the discovery of a new double-image quasar that was found during a search for gravitational lenses in the southern sky. Radio source PMN J1838-3427 is composed of two flat-spectrum components with separation 1", flux density ratio 14:1 and matching spectral indices, in VLA and VLBA images. Ground-based BRI images show the optical counterpart (total I=18.6) is also double with the same separation and position angle as the radio components. An HST/WFPC2 image reveals the lens galaxy. The optical flux ratio (27:1) is higher than the radio value probably due to differential extinction of the components by the lens galaxy. An optical spectrum of the bright component contains quasar emission lines at z=2.78 and several absorption features, including prominent Ly-alpha absorption. The lens galaxy redshift could not be measured but is estimated to be z=0.36 +/- 0.08. The image configuration is consistent with the simplest plausible models for the lens potential. The flat radio spectrum and observed variability of PMN J1838-3427 suggest the time delay between flux variations of the components is measurable, and could thus provide an independent measurement of H_0.Comment: 23 pages, incl. 6 figures, to appear in A.J.; replaced with accepted version; minor changes to text, improved figure

Construction of effective disposable biosensors for point of care testing of nitrite

© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/"In this paper we aim to demonstrate, as a proof-of-concept, the feasibility of the mass production of effective point of care tests for nitrite quantification in environmental, food and clinical samples. Following our previous work on the development of third generation electrochemical biosensors based on the ammonia forming nitrite reductase (ccNiR), herein we reduced the size of the electrodes’ system to a miniaturized format, solved the problem of oxygen interference and performed simple quantification assays in real samples. In particular, carbon paste screen printed electrodes (SPE) were coated with a ccNiR/carbon ink composite homogenized in organic solvents and cured at low temperatures. The biocompatibility of these chemical and thermal treatments was evaluated by cyclic voltammetry showing that the catalytic performance was higher with the combination acetone and a 40 °C curing temperature. The successful incorporation of the protein in the carbon ink/solvent composite, while remaining catalytically competent, attests for ccNiR’s robustness and suitability for application in screen printed based biosensors. Because the direct electrochemical reduction of molecular oxygen occurs when electroanalytical measurements are performed at the negative potentials required to activate ccNiR (ca. -0.4 V vs Ag/AgCl), an oxygen scavenging system based on the coupling of glucose oxidase and catalase activities was successfully used. This enabled the quantification of nitrite in different samples (milk, water, plasma and urine) in a straightforward way and with small error (1 – 6%). The sensitivity of the biosensor towards nitrite reduction under optimized conditions was 0.55 A M-1 cm-2 with a linear response range 0.7 – 370 μM.

Human skeletal muscle nitrate and nitrite in individuals with peripheral arterial disease: effect of inorganic nitrate supplementation and exercise

Skeletal muscle may act as a reservoir for N-oxides following inorganic nitrate supplementation. This idea is most intriguing in individuals with peripheral artery disease (PAD) who are unable to endogenously upregulate nitric oxide. This study analyzed plasma and skeletal muscle nitrate and nitrite concentrations along with exercise performance, prior to and following 12-weeks of exercise training combined with oral inorganic nitrate supplementation (EX+BR) or placebo (EX+PL) in participants with PAD. Non-supplemented, at baseline, there were no differences in plasma and muscle nitrate. For nitrite, muscle concentration was higher than plasma (+0.10 nmol.g−1). After 12 -weeks, acute oral nitrate increased both plasma and muscle nitrate (455.04 and 121.14 nmol.g−1, p < 0.01), which were correlated (r = 0.63, p < 0.01), plasma nitrate increase was greater than in muscle (p < 0.01). Nitrite increased in the plasma (1.01 nmol.g−1, p < 0.05) but not in the muscle (0.22 nmol.g−1) (p < 0.05 between compartments). Peak walk time (PWT) increased in both groups (PL + 257.6 s;BR + 315.0 s). Six-minute walk (6 MW) distance increased only in the (EX+BR) group (BR + 75.4 m). We report no substantial gradient of nitrate (or nitrite) from skeletal muscle to plasma, suggesting a lack of reservoir-like function in participants with PAD. Oral nitrate supplementation produced increases in skeletal muscle nitrate, but not skeletal muscle nitrite. The related changes in nitrate concentration between plasma and muscle suggests a potential for inter-compartmental nitrate “communication”. Skeletal muscle did not appear to play a role in within compartment nitrate reduction. Muscle nitrate and nitrite concentrations did not appear to contribute to exercise performance in patients with PAD