Equilibrium of sinks and sources of sulphate over Europe: comparison between a six-year simulation and EMEP observations

Sulphate distributions were simulated with a global chemistry transport model. A chemical scheme describing the sulphur cycle and the parameterisations of the main sinks for sulphate aerosols were included in the model. A six-year simulation was conducted from the years 2000 to 2005, driven by the ECMWF operational analyses. Emissions come from an inventory representative of the year 2000. This paper focuses on the analysis of the sulphate sinks and sources over Europe for the entire period of simulation. The Sulphate burden shows a marked annual cycle, which is the result of the annual variations of the aqueous and gaseous chemistry. Regionally, the monthly mean aerosol burden can vary by a factor of 2 from one year to another, because of different weather conditions, driving chemistry, transport and wet deposition of sulphate aerosols. Sulphate ground concentrations, scavenging fluxes and precipitation modelled were compared with observations. The model represents quite well sulphate fields over Europe, but has a general tendency to overestimate sulphate ground concentrations, in particular over Northern Europe. We assume that it is linked to the representation of the scavenging fluxes, which are underestimated. We suggest that uncertainties in modelled precipitation explain only partially the underestimation of the scavenging fluxes in the model

Efeito da Gliricidia sepium sobre nutrientes do solo, microclima e produtividade do milho em sistema agroflorestal no Agreste Paraibano.

Gliricidia sepium é uma leguminosa arbórea que tem sido utilizada em sistemas em aléias no semi-árido nordestino por apresentar bom desenvolvimento em condições de estresse hídrico. Entretanto, há pouca informação disponível sobre o efeito da introdução dessa espécie nos agroecossistemas da região. No presente estudo, objetivou-se avaliar a influência da distância de plantas de Gliricidia sepium sobre características da cultura do milho e do solo e microclima no Agreste Paraibano. O estudo foi realizado no município de Esperança (PB), em área de 0,5 ha, onde, em 1996, foram plantadas fileiras de G. sepium espaçadas 6 m entre si e com 1 m entre as árvores. Nesta área, em 2002, foram delimitadas quatro parcelas de 6 x 8 m e, em cada parcela, foi estabelecido um transeto perpendicular às fileiras de árvores com três posições de amostragem: (1) nas fileiras de árvores (0 m); (2) a 1 m das fileiras de árvores, e (3) a 3 m de distância das fileiras de árvores. O delineamento experimental utilizado foi em blocos casualizados com quatro repetições. A massa seca de folhedo caído embaixo da fileira de árvores foi de 1.390 kg ha-1 e diminuiu, gradativamente, para 270 kg ha-1 a 3 m de distância das árvores. As concentrações de P, K e matéria orgânica leve (MOL) embaixo das árvores foram maiores do que a 1 e 3 m de distância das fileiras. As médias mensais das temperaturas mínimas do ar e do solo embaixo e a 3 m das árvores foram similares. Entretanto, as médias mensais das temperaturas máximas do solo e do ar foram de 6 e 2 °C mais altas a 3 m das árvores, respectivamente, ao longo do período de estudo. A umidade do solo foi significativamente menor embaixo das árvores do que a 1 e 3 m de distância. O milho produziu mais grãos e palha e acumulou mais nutrientes nas posições mais próximas das fileiras de G. sepium

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine

High glucose environment inhibits cranial neural crest survival by activating excessive autophagy in the chick embryo

High glucose levels induced by maternal diabetes could lead to defects in neural crest development during embryogenesis, but the cellular mechanism is still not understood. In this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells (CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, apoptotic CNCC increased in the presence of high levels of glucose. In addition, the expression of apoptosis and autophagy relevant genes were elevated by high glucose treatment. Next, the application of beads soaked in either an autophagy stimulator (Tunicamycin) or inhibitor (Hydroxychloroquine) functionally proved that autophagy was involved in regulating the production of CNCC in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the mTOR pathway, most likely participates in mediating the autophagy induced by high glucose. Taken together, our observations indicated that exposure to high levels of glucose could inhibit the survival of CNCC by affecting cell apoptosis, which might result from the dysregulation of the autophagic process

Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease

BACKGROUND: Fabry disease is a lysosomal X-linked enzyme deficiency of α-galactosidase A associated with an increased mortality and morbidity due to renal failure, cardiac disease and early onset stroke. METHODS: We examined the functional blood flow response of the brain after visual stimulation (reversing checkerboard pattern), and cerebral vasoreactivity following acetazolamide (15 mg/kg) with [(15)O]H(2)O and positron emission tomography (PET) in Fabry disease. Twenty-six hemizygous patients (age range 19–47 years) were enrolled in a randomized double-blind placebo-controlled 6-month trial of enzyme replacement therapy administered by intravenous infusion every two weeks. Regional cerebral blood flow (rCBF) was measured with PET at the beginning and end of the trial. RESULTS: Fabry patients had a significantly greater increase in rCBF following visual stimulation and acetazolamide challenge compared to controls. Visual reactivity was normal. The time for recovery of the cerebral vasculature following acetazolamide was prolonged in Fabry patients compared to controls. The abnormal rCBF response induced by visual stimulation and acetazolamide decreased significantly following enzyme replacement therapy, as did the prolonged recovery of the cerebral vasculature. CONCLUSIONS: Enzyme replacement therapy reverses the exaggerated cerebrovascular response in Fabry disease

Pericyte Migration: A Novel Mechanism of Pericyte Loss in Experimental Diabetic Retinopathy

OBJECTIVE— The mechanism underlying pericyte loss during incipient diabetic retinopathy remains controversial. Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary pericyte coverage. In this study, we assessed loss of pericyte subgroups and the contribution of Ang-2 to pericyte migration

Distinct Roles for Neuropilin1 and Neuropilin2 during Mouse Corneal Innervation

Trigeminal sensory innervation of the cornea is critical for protection and synthesis of neuropeptides required for normal vision. Little is known about axon guidance during mammalian corneal innervation. In contrast to the chick where a pericorneal nerve ring forms via Npn/Sema signaling, mouse corneal axons project directly into the presumptive cornea without initial formation of an analogous nerve ring. Here we show that during development of the mouse cornea, Npn1 is strongly expressed by the trigeminal ganglion whereas Npn2 is expressed at low levels. At the same time Sema3A and Sema3F are expressed in distinct patterns in the ocular tissues. Npn1sema−/− mutant corneas become precociously and aberrantly innervated by nerve bundles that project further into the corneal stroma. In contrast, stromal innervation was not affected in Npn2−/− mutants. The corneal epithelium was prematurely innervated in both Npn1sema−/− and Npn2−/− mutants. These defects were exacerbated in Npn1sema−/−;Npn2−/− double mutants, which in addition showed ectopic innervation of the region between the optic cup and lens vesicle. Collectively, our data show that Sema3A/Npn1 and Sema3F/Npn2 signaling play distinct roles and both are required for proper innervation of the mouse cornea

Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly

Apparently balanced chromosomal inversions may lead to disruption of developmentally important genes at the breakpoints of the inversion, causing congenital malformations. Characterization of such inversions may therefore lead to new insights in human development. Here, we report on a de novo inversion of chromosome 7 (p15.2q36.3) in a patient with postaxial polysyndactyly. The breakpoints do not disrupt likely candidate genes for the limb phenotype observed in the patient. However, on the p-arm the breakpoint separates the HOXA cluster from a gene desert containing several conserved noncoding elements, suggesting that a disruption of a cis-regulatory circuit of the HOXA cluster could be the underlying cause of the phenotype in this patient

A subpopulation of smooth muscle cells, derived from melanocyte-competent precursors, prevents patent ductus arteriosus

BACKGROUND: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA), a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2) and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/beta-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes

Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures

Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. Using genetic tracing we show that dbx1-expressing cells and their progeny have a modest contribution to the forebrain and face tissues. However, their genetic ablation triggers extensive and non cell-autonomous apoptosis as well as a decrease in proliferation in surrounding tissues, resulting in the progressive loss of most of the forebrain and frontonasal structures. Targeted ablation of the different subsets reveals that the very first dbx1-expressing progenitors are critically required for the survival of anterior neural tissues, the production and/or migration of cephalic neural crest cells and, ultimately, forebrain formation. In addition, we find that the other subsets, generated at slightly later stages, each play a specific function during head development and that their coordinated activity is required for accurate craniofacial morphogenesis. Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner