Accelerated Axonal Loss Following Acute CNS Demyelination in Mice Lacking Protein Tyrosine Phosphatase Receptor Type Z

Protein tyrosine phosphatase receptor type Z (Ptprz) is widely expressed in the mammalian central nervous system and has been suggested to regulate oligodendrocyte survival and differentiation. We investigated the role of Ptprz in oligodendrocyte remyelination after acute, toxin-induced demyelination in Ptprz null mice. We found neither obvious impairment in the recruitment of oligodendrocyte precursor cells, astrocytes, or reactive microglia/macrophage to lesions nor a failure for oligodendrocyte precursor cells to differentiate and remyelinate axons at the lesions. However, we observed an unexpected increase in the number of dystrophic axons by 3 days after demyelination, followed by prominent Wallerian degeneration by 21 days in the Ptprz-deficient mice. Moreover, quantitative gait analysis revealed a deficit of locomotor behavior in the mutant mice, suggesting increased vulnerability to axonal injury. We propose that Ptprz is necessary to maintain central nervous system axonal integrity in a demyelinating environment and may be an important target of axonal protection in inflammatory demyelinating diseases, such as multiple sclerosis and periventricular leukomalacia. (Am J Pathol 2012, 181:1518-1523; http://dx.doi.org/10.1016/j.ajpath.2012.07.011)UK Multiple Sclerosis SocietyMultiple Sclerosis International FederationUniv Cambridge, Dept Vet Med, Cambridge CB3 0ES, EnglandUniv Cambridge, Wellcome Trust & MRC Cambridge Stem Cell Inst, Cambridge CB3 0ES, EnglandUniversidade Federal de São Paulo, Dept Biosci, Santos, BrazilMerck Serono Int, Geneva Res Ctr, Geneva, SwitzerlandUniversidade Federal de São Paulo, Dept Biosci, Santos, BrazilWeb of Scienc

Será que a soja aumenta as contagens sanguíneas em síndrome mielodisplásica?

Myelodysplastic syndromes (MDS) are a group of clonal stem cell diseases characterized by ineffective hematopoiesis, bone marrow hyperproliferation, cytopenias in peripheral blood and risk of transformation into acute leukemia. We decided to investigate the effects of a soy concentrate on MDS patients based on the follow-up results of a 61 year-old Japanese female patient who was diagnosed with MDS and refractory cytopenia with multilineage dysplasia in 2003 (hemoglobin = 11g/dL; white blood cells count = 2,500/uL and platelets = 25,000/uL; marrow with mild dysplasia and normal karyotype; paroxysmal nocturnal hemoglobinuria was excluded). She started using soy as a dietary supplementation in May 2004 and presented a gradual increment in blood counts, achieving normalization approximately eight months afterwards. Among the soy components, the main compounds with anti-carcinogenic activity are the isoflavones (genistein and daidzein). Based on these lines of evidence, we proposed to administer daily a standard soy concentrate to 14 MDS out-patients for a minimum period of three months and maximum of 12 months, in an attempt to evaluate prospectively the possible increase in hemoglobin, neutrophils and platelet counts. A historical control group was used to compare results. The use of a soy concentrate in a standardized manner was associated with an increase in neutrophil and/or platelet counts in some cases, but spontaneous increments were also observed in historical controls. This preliminary study does not allow establishing a relation between soy supplementation and blood cell count increase.As síndromes mielodisplásicas (SMD) são um grupo das doenças clonais de células-tronco caracterizado por hematopoese ineficaz, hiperproliferação de medula óssea, citopenias no sangue periférico e risco de transformação para leucemia aguda. Decidimos investigar os efeitos de um concentrado de soja em pacientes com SMD com base no fato de termos o seguimento de uma paciente japonesa, de 61 anos de idade, que foi diagnosticada em 2003 com SMD, citopenia refratária com displasia subtipo multilinhagens (hemoglobina = 11 g/dL; contagem de glóbulos brancos = 2.500/uL e plaquetas = 25.000/uL; medula com displasia leve e cariótipo normal; hemoglobinúria paroxística excluída), e que começou a usar a soja como suplemento alimentar em maio de 2004, apresentando gradual aumento da contagem das células sanguíneas, atingindo a normalização cerca de oito meses depois. Entre os componentes da soja, os principais compostos com propriedades anticarcinogênese são as isoflavonas (Ge nisteína e daidzeína). Com base nessas linhas de evidência, foi proposto oferecer diariamente um concentrado de soja padrão, por um período mínimo de três meses e máximo de doze meses, a 14 pacientes ambulatoriais, na tentativa de avaliar, prospectivamente, o possível aumento de hemoglobina, neutrófilos e plaquetas. Um grupo controle histórico foi utilizado para comparar os resultados. O uso de um concentrado de soja de forma padronizada foi associado ao aumento na contagem de neutrófilos e/ou de plaquetas em alguns casos, mas aumentos espontâneos também foram observados em controles históricos. Este estudo preliminar não permite estabelecer relação entre o uso de soja e o aumento na contagem sanguínea.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Hematologia e HemoterapiaEmpresa Brasileira de Pesquisa Agropecuária Centro Nacional de Pesquisa de SojaInstituto FleuryUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Departamento de MedicinaUNIFESP, EPM, Hematologia e HemoterapiaUNIFESP, EPM, Depto. de MedicinaSciEL

Three-Dimensional Simulations of Jets from Keplerian Disks: Self--Regulatory Stability

We present the extension of previous two-dimensional simulations of the time-dependent evolution of non-relativistic outflows from the surface of Keplerian accretion disks, to three dimensions. The accretion disk itself is taken to provide a set of fixed boundary conditions for the problem. The 3-D results are consistent with the theory of steady, axisymmetric, centrifugally driven disk winds up to the Alfv\'en surface of the outflow. Beyond the Alfv\'en surface however, the jet in 3-D becomes unstable to non-axisymmetric, Kelvin-Helmholtz instabilities. We show that jets maintain their long-term stability through a self-limiting process wherein the average Alfv\'enic Mach number within the jet is maintained to order unity. This is accomplished in at least two ways. First, poloidal magnetic field is concentrated along the central axis of the jet forming a ``backbone'' in which the Alfv\'en speed is sufficiently high to reduce the average jet Alfv\'enic Mach number to unity. Second, the onset of higher order Kelvin-Helmholtz ``flute'' modes (m \ge 2) reduce the efficiency with which the jet material is accelerated, and transfer kinetic energy of the outflow into the stretched, poloidal field lines of the distorted jet. This too has the effect of increasing the Alfv\'en speed, and thus reducing the Alfv\'enic Mach number. The jet is able to survive the onset of the more destructive m=1 mode in this way. Our simulations also show that jets can acquire corkscrew, or wobbling types of geometries in this relatively stable end-state, depending on the nature of the perturbations upon them. Finally, we suggest that jets go into alternating periods of low and high activity as the disappearance of unstable modes in the sub-Alfv\'enic regime enables another cycle of acceleration to super-Alfv\'enic speeds.Comment: 57 pages, 22 figures, submitted to Ap

LonB Protease Is a Novel Regulator of Carotenogenesis Controlling Degradation of Phytoene Synthase in Haloferax volcanii

Cerletti M, Paggi R, Troetschel C, et al. LonB Protease Is a Novel Regulator of Carotenogenesis Controlling Degradation of Phytoene Synthase in Haloferax volcanii. JOURNAL OF PROTEOME RESEARCH. 2018;17(3):1158-1171.The membrane protease LonB is an essential protein in the archaeon Haloferax volcanii and globally impacts its physiology. However, natural substrates of the archaeal Lon protease have not been identified. The whole proteome turnover was examined in a H. volcanii LonB mutant under reduced and physiological protease levels. LC-MS/MS combined with stable isotope labeling was applied for the identification/quantitation of membrane and cytoplasm proteins. Differential synthesis and degradation rates were evidenced for 414 proteins in response to Lon expression. A total of 58 proteins involved in diverse cellular processes showed a degradation pattern (none/very little degradation in the absence of Lon and increased degradation in the presence of Lon) consistent with a LonB substrate, which was further substantiated for several of these candidates by pull-down assays. The most notable was phytoene synthase (PSY), the rate-limiting enzyme in carotenoid biosynthesis. The rapid degradation of PSY upon LonB induction in addition to the remarkable stabilization of this protein and hyperpigmentation phenotype in the Lon mutant strongly suggest that PSY is a LonB substrate. This work identifies for the first time candidate targets of the archaeal Lon protease and establishes proteolysis by Lon as a novel post-translational regulatory mechanism of carotenogenesis

Efficiency and residual effect of alternative potassium sources in grain crops.

ABSTRACT: The objective of this work was to evaluate the efficiency and the residual effects of both molten and ground alkaline potassium-silicate rocks (K1) and of ground phonolite rock (K2), as sources of potassium, compared with the traditional source (KCl), in grain crop successions. Two experiments ? one with the succession soybean-wheat-corn and the other with the succession corn-millet-soybean ? were conducted on a Typic Haplorthox in a randomized complete block design with four replicates. The treatments consisted of three sources (KCl, K1, and K2) and four rates of K (corresponding to 0, 0.5, 1.0, and 2.0 times the recommended rates for soybean and corn). The used sources did not affect leaf K concentration in soybean, but KCl and K2 similarly increased leaf K concentration in corn. Regardless of the source, K application increased the yield of all crops. The K1 and K2 sources present agronomic efficiencies equivalent to that of KCl. K1 and K2 show a more pronounced residual effect than KCl, especially on crops grown approximately one year after their application and under K rates above those recommended for the crops. Index terms: agronomic efficiency, phonolite, potassium fertilization, residual effect, rock dust, silicon. Eficiência e efeito residual de fontes alternativas de potássio em culturas graníferas RESUMO: O objetivo deste trabalho foi avaliar a eficiência e o efeito residual de rochas potássico-silicáticas alcalinas fundidas e moídas (K1) e de rocha de fonolito moída (K2), como fontes alternativas de potássio, em comparação à fonte tradicional (KCl), em sucessões de culturas graníferas. Dois experimentos ? um com sucessão soja-trigo-milho e outro com sucessão milho-milheto-soja ? foram conduzidos em Latossolo Vermelho argiloso, em delineamento de blocos ao acaso, com quatro repetições. Os tratamentos consistiram de três fontes (KCl, K1 e K2) e quatro doses de K (correspondentes a 0, 0,5, 1,0 e 2,0 vezes a dose recomendada para a cultura da soja e do milho). As fontes não afetaram a concentração de K nas folhas da soja, mas KCl e K2 aumentaram de forma semelhante a concentração de K nas folhas do milho. Independentemente da fonte, a aplicação de K aumentou as produtividades de todas as culturas. As fontes alternativas K1 e K2 apresentam eficiências agronômicas equivalentes à do KCl. K1 e K2 têm efeitos residuais mais pronunciados que o do KCl, especialmente em cultivos realizados aproximadamente um ano após suas aplicações e com doses de K acima das recomendadas para as culturas

Potencial de linhagens elite de arroz irrigado para Região Tropical do Brasil.

O objetivo deste trabalho foi avaliar e selecionar linhagens elite de arroz irrigado nos Ensaios Preliminares de rendimento (EP) para as fases subsequentes do programa de melhoramento genético de arroz de irrigado da Embrapa para região tropical do país

Laser-induced etching of few-layer graphene synthesized by Rapid-Chemical Vapour Deposition on Cu thin films

The outstanding electrical and mechanical properties of graphene make it very attractive for several applications, Nanoelectronics above all. However a reproducible and non destructive way to produce high quality, large-scale area, single layer graphene sheets is still lacking. Chemical Vapour Deposition of graphene on Cu catalytic thin films represents a promising method to reach this goal, because of the low temperatures (T < 900 Celsius degrees) involved during the process and of the theoretically expected monolayer self-limiting growth. On the contrary such self-limiting growth is not commonly observed in experiments, thus making the development of techniques allowing for a better control of graphene growth highly desirable. Here we report about the local ablation effect, arising in Raman analysis, due to the heat transfer induced by the laser incident beam onto the graphene sample.Comment: v1:9 pages, 8 figures, submitted to SpringerPlus; v2: 11 pages, PDFLaTeX, 9 figures, revised peer-reviewed version resubmitted to SpringerPlus; 1 figure added, figure 1 and 4 replaced,typos corrected, "Results and discussion" section significantly extended to better explain etching mechanism and features of Raman spectra, references adde

Kinin B(1) receptor deficiency leads to leptin hypersensitivity and resistance to obesity

OBJECTIVE-Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown.RESEARCH DESIGN and METHODS-Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity.RESULTS-Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet.CONCLUSIONS-Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniv Mogi das Cruzes, Mogi Das Cruzes, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilSanofi Aventis, Montpellier, FranceUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, BrazilInst Natl Sante & Rech Med, Dept Renal & Cardiac Remodeling, U858 I2MR, Toulouse, FranceUniv Toulouse 3, Inst Med Mol Rangueil, F-31062 Toulouse, FranceInst Natl Rech Agron AgroParisTech, UMR914 Nutr Physiol & Ingest Behav, Paris, FranceMax Delbruck Ctr Mol Med, Berlin, GermanyUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, BrazilWeb of Scienc

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material