Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133+ progenitors into F4/80+ macrophages in experimental autoimmune myocarditis.

AIMS: Experimental autoimmune myocarditis (EAM) model mirrors important mechanisms of inflammatory dilated cardiomyopathy (iDCM). In EAM, inflammatory CD133(+) progenitors are a major cellular source of cardiac myofibroblasts in the post-inflammatory myocardium. We hypothesized that exogenous delivery of macrophage-colony-stimulating factor (M-CSF) can stimulate macrophage lineage differentiation of inflammatory progenitors and, therefore, prevent their naturally occurring myofibroblast fate in EAM. METHODS AND RESULTS: EAM was induced in wild-type (BALB/c) and nitric oxide synthase 2-deficient (Nos2(-/-)) mice and CD133(+) progenitors were isolated from inflamed hearts. In vitro, M-CSF converted inflammatory CD133(+) progenitors into nitric oxide-producing F4/80(+) macrophages and prevented transforming growth factor-β-mediated myofibroblast differentiation. Importantly, only a subset of heart-infiltrating CD133(+) progenitors expresses macrophage-specific antigen F4/80 in EAM. These CD133(+)/F4/80(hi) cells show impaired myofibrogenic potential compared with CD133(+)/F4/80(-) cells. M-CSF treatment of wild-type mice with EAM at the peak of disease markedly increased CD133(+)/F4/80(hi) cells in the myocardium, and CD133(+) progenitors isolated from M-CSF-treated mice failed to differentiate into myofibroblasts. In contrast, M-CSF was not effective in converting CD133(+) progenitors from inflamed hearts of Nos2(-/-) mice into macrophages, and M-CSF treatment did not result in increased CD133(+)/F4/80(hi) cell population in hearts of Nos2(-/-) mice. Accordingly, M-CSF prevented post-inflammatory fibrosis and left ventricular dysfunction in wild-type but not in Nos2(-/-) mice. CONCLUSION: Active and NOS2-dependent induction of macrophage lineage differentiation abrogates the myofibrogenic potential of heart-infiltrating CD133(+) progenitors. Modulating the in vivo differentiation fate of specific progenitors might become a novel approach for the treatment of inflammatory heart diseases.

IDED Quick News, September 2, 2003

Newsletter for Economic Devleopment

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus.

PURPOSE: To determine the relationship between carotid intima-media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM). METHODS: In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with (13)N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation. RESULTS: There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = -0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 +/- 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 +/- 0.24 vs. 0.74 +/- 0.23 and 1.82 +/- 0.50 vs. 1.95 +/- 0.51 ml/g/min; p < or = 0.05, respectively) and also during CPT in DM but less pronounced (0.81 +/- 0.24 vs. 0.83 +/- 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = -0.36, p < or = 0.014; r = -0.46, p < or = 0.007; and r = -0.33, p < or = 0.041, respectively). CONCLUSIONS: The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.

Espécies de cigarrinhas (Hemiptera, Cicadellidae, Cicadellinae) em pomares de citros da região de Bebedouro, SP, com descrição de uma espécie nova de Acrogonia Stål

Sharpshooter leafhoppers (Hemiptera, Cicadellidae, Cicadellinae) in citrus groves of the area of Bebedouro, SP, with description of a new species of Acrogonia Stål. Sixteen species of Cicadellidae, subfamily Cicadellinae, were collected and identified: 11 of the tribe Cicadellini and five of the tribe Proconiini. The ten most common species, together with a new species, are characterized based on external morphology and male genitalia: Acrogonia citrina Marucci & Cavichioli sp. nov.; Bucephalogonia xanthophis (Berg, 1879); Dilobopterus costalimai Young, 1977; Ferrariana trivittata (Signoret, 1854); Hortensia similis (Walker, 1851); Macugonalia cavifrons (Stål, 1862); M. leucomelas (Walker, 1851); Oncometopia facialis (Signoret, 1854); Plesiommata corniculata Young, 1977 and P. mollicella (Fowler, 1900). The leafhopper samples were collected in citrus groves and in adjacent habitats (woods, swamp, cultivable plain, spontaneous vegetation of the grove, coffee crop and sugarcane) at the counties of Bebedouro and Monte Azul Paulista and in the district of Turvínia. The collecting methods were: insect net, yellow sticky cards, portable suction trap and Malaise trap. Identification keys were elaborated for the 16 species. There is a great diversity of Cicadellinae species in the citric groves. In the three areas sampled, it was collected a larger number of species of the tribe Cicadellini than of the tribe Proconiini. In the Bebedouro area, the vector species of Xylella fastidiosa, A. citrina sp. nov., B. xanthophis, D. costalimai and O. facialis, were collected in the citrus groves and in all adjacent habitats.

Nomenclatural notes in Membracidae (Homoptera): new combination and new synonymies in Amastris Stål, 1862

The following nomenclatural changes are made: Amastris convoluta (Fabricius, 1781) comb. nov. (formerly Darnis; Hebetica); Amastris maculata Funkhouser, 1922 = Amastris fasciata Broomfield, 1976 syn. nov. = Amastris pseudomaculata Broomfield, 1976 syn. nov. = Amastris inermis Broomfield, 1976 syn. nov. = Amastris sakakibarai Broomfield, 1976 syn. nov.; Amastris elevata Funkhouser, 1922 = Amastris vismiae Haviland, 1925 syn. nov. = Amastris flavifolia Funkhouser, 1927 syn. nov.

Alternative Flexible Overlays, HR-229, 1988

The objective of this project was to determine if any of several cutback and emulsified asphalt plant mixed and road mixed overlays had the ability to resist thermal cracking at low temperatures without inducing shoving and/or ruttinq at high temperatures. A 2.6 mile section of Osceola County road A-34 and a 7.0 mile section of A-46 were divided into 14 test sections of various lengths. After six years, results show an MC-3000 asphalt cutback cold mix can reduce the amount of reflective cracking when compared to an AC-5 hot mix. This can be done without inducing high temperature related problems. Cold road mixing can be effective in reducing cracking on low volume roads. However, more experience is required if the full benefits of road mixing are to be realized.

Alternative Flexible Overlays, HR-229, Construction Report, 1983

The object of this research project is to construct and evaluate several bituminous concrete base overlays with various high penetration bituminous products which have the potential to reduce future maintenance and construction costs. In September of 1981 nine different bituminous test sections were constructed on Osceola County roads A-34 and A-46 east of Ashton. Asphalt binders used were AC-5 asphalt cement, SC-800 liquid asphalt, MC-3000 cutback asphalt, CSS-1 emulsion and HFMS-2 emulsion. Aggregate for four of the test sections consisted of salvaged bituminous pavement and new aggregate combined. Each section was road mixed using a different binder arid placed 2-1/4" thick with a motor patrol. The other five test sections consisted of an AC-5 Type B asphalt concrete control section and four plant-mixed, cold-laid bituminous concrete overlay sections using new aggregate. The material was mixed in a continuous drum mix plant and laid with a full width paver.

[2 lettres autographes signées de Jules Barbier à Henri Heugel, 1896]

14 février 1896. Lui demande des avances pour tenir ses engagements. - 20 octobre 1896. Remercie "Le Menestrel" pour son compte rendu favorable de "Clarisse Harlowe", mais exprime toute son amertume à l'encontre des compositeurs : "Ils sont encore plus bêtes que les directeurs! Ils ne comprenaient déjà plus rien à la musique. Ils arrivent à ne plus rien comprendre à leur langue maternelle". - Lieu restitué d'après le cachet de la poste : "Paris. Montparnasse. 20 OCT 96"

Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001) after the addition of metformin (1404.4 ± 565.5 mg/day), with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05) of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/dL), BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m²), waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm), and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01%) and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

A single amino acid substitution in the mRNA capping enzyme λ2 of a mammalian orthoreovirus mutant increases interferon sensitivity.

In the last few years, the development of a plasmid-based reverse genetics system for mammalian reovirus has allowed the production and characterization of mutant viruses. This could be especially significant in the optimization of reovirus strains for virotherapeutic applications, either as gene vectors or oncolytic viruses. The genome of a mutant virus exhibiting increased sensitivity to interferon was completely sequenced and compared with its parental virus. Viruses corresponding to either the parental or mutant viruses were then rescued by reverse genetics and shown to exhibit the expected phenotypes. Systematic rescue of different viruses harboring either of the four parental genes in a mutant virus backbone, or reciprocally, indicated that a single amino acid substitution in one of λ2 methyltransferase domains is the major determinant of the difference in interferon sensitivity between these two viruses.

Quadrupole moments of radium isotopes from the 7p^2P_3/2 hyperfine structure in Ra II

The hyperfine structure and isotope shift of ^{221- 226}Ra and ^{212, 214}Ra have been measured in the ionic (Ra 11) transition 7s^2 S_{1/2} - 7p ^2 P_{3/2} (\lamda = 381.4 nm). The method of on-line collinear fast-beam laser spectroscopy has been applied using frequency-doubling of cw dye laser radiation in an external ring cavity. The magnetic hyperfine fields are compared with semi-empirical and ab initio calculations. The analysis of the quadrupole splitting by the same method yields the following, improved values of spectroscopic quadrupole moments: Q_s(^221 Ra)= 1.978(7)b, Q_s (^223 Ra)= 1.254(3)b and the reanalyzed values Q_s(^209 Ra) = 0.40(2)b, Q_s(^211 Ra) = 0.48(2)b, Q_s(^227 Ra)= 1.58(3)b, Q_s (^229 Ra) = 3.09(4)b with an additional scaling uncertainty of ±5%. Furthermore, the J-dependence of the isotope shift is analyzed in both Ra II transitions connecting the 7s^2 S_{1/2} ground state with the first excited doublet 7p^ P_{1/2} and 7p^ P_{3/2}.

Proyecto de jardín para niños de 0-2 años y mejora de jardín para niños de 2-4 años.

Experiencia orientada a mejorar y acondicionar el espacio exterior del centro para lograr que el patio de recreo ayude en la labor educativa de la escuela infantil. Plantea los siguientes objetivos: potenciar las posibilidades de juego; crear un espacio específico para los niños de cero a dos años en el que se tengan en cuanto la seguridad y las necesidades de desarrollo de esta etapa; y conseguir una mejor distribución y aprovechamiento de los espacios dentro del conjunto de la escuela. El espacio se estructura en diferentes zonas: arenero, zona de tierra dura y césped para realizar actividades de acercamiento a la naturaleza y al entorno; zona de intercambio, para juegos en los que interviene la comunicación; zona de movimiento, con diversos elementos como toboganes, balancines, etc., para realizar actividades en las que interviene la acción, el equilibrio, el movimiento, etc.; y, finalmente, una zona para guardar los juguetes. La evaluación de los alumnos es continua mediante la observación directa y la redacción de informes sobre las actividades realizadas en el nuevo espacio, en los que hace se referencia al cumplimiento o no de los objetivos y a la actitud de los alumnos.