Suppression of Arabidopsis protophloem differentiation and root meristem growth by CLE45 requires the receptor-like kinase BAM3.

Peptide signaling presumably occupies a central role in plant development, yet only few concrete examples of receptor-ligand pairs that act in the context of specific differentiation processes have been described. Here we report that second-site null mutations in the Arabidopsis leucine-rich repeat receptor-like kinase gene barely any meristem 3 (BAM3) perfectly suppress the postembryonic root meristem growth defect and the associated perturbed protophloem development of the brevis radix (brx) mutant. The roots of bam3 mutants specifically resist growth inhibition by the CLAVATA3/ENDOSPERM SURROUNDING REGION 45 (CLE45) peptide ligand. WT plants transformed with a construct for ectopic overexpression of CLE45 could not be recovered, with the exception of a single severely dwarfed and sterile plant that eventually died. By contrast, we obtained numerous transgenic bam3 mutants transformed with the same construct. These transgenic plants displayed a WT phenotype, however, supporting the notion that CLE45 is the likely BAM3 ligand. The results correlate with the observation that external CLE45 application represses protophloem differentiation in WT, but not in bam3 mutants. BAM3, BRX, and CLE45 are expressed in a similar spatiotemporal trend along the developing protophloem, up to the end of the transition zone. Induction of BAM3 expression upon CLE45 application, ectopic overexpression of BAM3 in brx root meristems, and laser ablation experiments suggest that intertwined regulatory activity of BRX, BAM3, and CLE45 could be involved in the proper transition of protophloem cells from proliferation to differentiation, thereby impinging on postembryonic growth capacity of the root meristem.

Immunological tolerance to pig-serum partially inhibits the formation of septal fibrosis of the liver in Capillaria hepatica-infected rats

Systhematized septal fibrosis of the liver can be induced in rats either by repeated intraperitoneal injections of pig-serum or by Capillaria hepatica infection. The relationship between these two etiological factors, as far as hepatic fibrosis is concerned, is not known, and present investigation attempts to investigate it. C. hepatica-induced septal fibrosis of the liver was considerably inhibited in rats previously rendered tolerant to pig-serum. Pig-serum-tolerant rats developed antibodies against pig-serum when infected with C. hepatica, but this did not happen when the infection occurred in normal rats. On the other hand, anti-C. hepatica antibodies failed to recognize any epitope in pig-serum, by Western blot. However, no evidence of an immunological cross reactivity was found, at least at the humoral level. Alternatively, cell-mediated mechanisms may be involved, and further investigations are warranted.

The transventricular-transseptal access to the aortic root: a new route for extrapleural trans-catheter aortic stent-valve implantation.

Objective: The aim of this study was to investigate the feasibility of transventricular-transseptal approach (TVSA) for extrapleural transcatheter aortic valved stent implantation via a subxyphoidian access. Methods: In five porcine experiments (52.3 +/- 10.9 kg) the right ventricle was exposed via subxyphoidian access. Under the guidance of intracardiac echocardiography (ICE) and fluoroscopy, the transseptal access from right ventricle to left ventricle was created progressively by puncture and dilation with dilators (8F-26F). Valved stents built in-house from commercial tanned pericardium and self-expandable Nitinol stents were loaded into a cartridge. A delivery sheath was then introduced from the right ventricle into the left ventricle and then into the ascending aorta. The cartridge was connected and the valved stent was deployed in the aortic position. Then, the ventricular septal access was sealed with an Amplatzer septal occluder device and the right ventricular access was closed by tying prepared purse-string suture directly. Thirty minutes after the whole procedure, the animals were sacrificed for macroscopic evaluation of the position of valved stent and septal closure device. Result: Procedural success of TVSA was 100% at the first attempt. Mean procedure time was 49 +/- 4 min. Progressive dilatation of the transseptal access resulted in a measurable ventricular septal defect (VSD) after dilator sizes 18F and more. All valved stents were delivered at the target site over the native aortic valve with good acute valve function and no paravalvular leaks. During the procedure, premature beats (5/5) and supraventriclar tachycardias (5/5) were observed, but no atrial-ventricular block (0/5) occurred. Heart rate before (after) was 90 +/- 3 beats min(-1) (100 +/- 2 beats min(-1): p < 0.05), whereas blood pressure was 60 + 1 mm Hg (55 + 2 mm Hg (p < 0.05)). Total blood loss was 280 + 10 ml. The Amplatzer septal occluder devices were fully deployed and the ventricular septal accesses were sealed successfully, without detectable residual shunt. Conclusion: Trans-catheter implantation of aortic valved stent via extrapleural transventricular-transseptal access is technically feasible and has the potential for a simplified procedure under local anaesthesia. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B. V. All rights reserved.

Angiogenesis and schistosomal granuloma formation

An increasing amount of evidences points to angiogenesis as playing a paramount role in fibrosis development. However, granulomas in general, and periovular schistosomal granulomas in particular, are considered avascular structures, although they usually result in dense areas of focal fibrosis. In order to clarify this apparent paradox, the presence of blood vessels was systematically searched in hepatic schistosomal granulomas of mice, during different stages of the infection, and at different stages of granuloma evolution, by means of vascular injections of colored masses, demonstration of laminin in vascular basement membranes and by ultra structural analysis. Vascular proliferation appeared evident at the early stages of granuloma formation, gradually decreasing thereafter, older granulomas becoming almost avascular structures, sometimes delimited at the periphery by a rich vascular network.

La prise en charge de l'hypertension artérielle par des médecins en formation suit-elle les recommandations actuelles?

Résumé De nombreuses recommandations nationales et internationales sont publiées régulièrement qui définissent la manière dont les patients hypertendus devraient être pris en charge. Ces recommandations sont-elles suivies et applicables ? Dans cette étude transverse effectuée à la PMU à Lausanne, nous avons évalué la qualité de la prise en charge de 225 patients hypertendus suivis par des assistants en formation de médecine de premier recours. Ces 225 patients ont été retenus après une sélection de 1044 dossiers de la consultation générale de la PMU. Les résultats montrent que la moyenne des 3 dernières pressions artérielles était contrôlée dans 32,4% des cas à moins de 140/90 mmHg (TA systolique contrôlée à 42% et TA diastolique à 58%). 60% des patients ont eu une mesure de pression à chacune des 3 dernières consultations. 79% des mesures se terminaient par 0 ou par 5(théoriquement 20%). Le contrôle de la pression artérielle n'était pas statistiquement différent quelles que soient les comorbidités connues (diabète, insuffisance rénale ou insuffisance cardiaque). En conclusion, la qualité de la mesure et de la prise en charge de la TA par les médecins de premier recours en formation est comparable à celle retrouvée en pratique ambulatoire et pourrait être améliorée. Les recommandations basées sur la stratification des FRCV se heurtent à des problèmes dans leur application pratique. Le contrôle de la TA n'est pas meilleur chez les patients à haut risque cardio-vasculaire.

Mechanisms of leukocyte lipid body formation and function in inflammation

An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation.

Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis.

BACKGROUND: Activation of innate pattern-recognition receptors promotes CD4+ T-cell-mediated autoimmune myocarditis and subsequent inflammatory cardiomyopathy. Mechanisms that counterregulate exaggerated heart-specific autoimmunity are poorly understood. METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with α-myosin heavy chain peptide and complete Freund's adjuvant. Together with interferon-γ, heat-killed Mycobacterium tuberculosis, an essential component of complete Freund's adjuvant, converted CD11b(hi)CD11c(-) monocytes into tumor necrosis factor-α- and nitric oxide synthase 2-producing dendritic cells (TipDCs). Heat-killed M. tuberculosis stimulated production of nitric oxide synthase 2 via Toll-like receptor 2-mediated nuclear factor-κB activation. TipDCs limited antigen-specific T-cell expansion through nitric oxide synthase 2-dependent nitric oxide production. Moreover, they promoted nitric oxide synthase 2 production in hematopoietic and stromal cells in a paracrine manner. Consequently, nitric oxide synthase 2 production by both radiosensitive hematopoietic and radioresistant stromal cells prevented exacerbation of autoimmune myocarditis in vivo. CONCLUSIONS: Innate Toll-like receptor 2 stimulation promotes formation of regulatory TipDCs, which confine autoreactive T-cell responses in experimental autoimmune myocarditis via nitric oxide. Therefore, activation of innate pattern-recognition receptors is critical not only for disease induction but also for counterregulatory mechanisms, protecting the heart from exaggerated autoimmunity.

Extracellular protease of Pseudomonas fluorescens CHA0, a biocontrol factor with activity against the root-knot nematode Meloidogyne incognita.

In Pseudomonas fluorescens CHA0, mutation of the GacA-controlled aprA gene (encoding the major extracellular protease) or the gacA regulatory gene resulted in reduced biocontrol activity against the root-knot nematode Meloidogyne incognita during tomato and soybean infection. Culture supernatants of strain CHA0 inhibited egg hatching and induced mortality of M. incognita juveniles more strongly than did supernatants of aprA and gacA mutants, suggesting that AprA protease contributes to biocontrol.

Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.

Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.

Calbindin-immunoreactive sensory neurons in dissociated dorsal root ganglion cell cultures of chick embryo: role of culture conditions.

Immunoreactivity to calbindin D-28k, a vitamin D-dependent calcium-binding protein, is expressed by neuronal subpopulations of dorsal root ganglia (DRG) in the chick embryo. To determine whether the expression of this phenotypic characteristic is maintained in vitro and controlled by environmental factors, dissociated DRG cell cultures were performed under various conditions. Subpopulations of DRG cells cultured at embryonic day 10 displayed calbindin-immunoreactive cell bodies and neurites in both neuron-enriched or mixed DRG cell cultures. The number of calbindin-immunoreactive ganglion cells increased up to 7-10 days of culture independently of the changes occurring in the whole neuronal population. The presence of non-neuronal cells, which promotes the maturation of the sensory neurons, tended to reduce the percentage of calbindin-immunoreactive cell bodies. Addition of horse serum enhanced both the number of calbindin-positive neurons and the intensity of the immunostaining, but does not prevent the decline of the subpopulation of calbindin-immunoreactive neurons during the second week of culture; on the contrary, the addition of muscular extract to cultures at 10 days maintained the number of calbindin-expressing neurons. While calbindin-immunoreactive cell bodies grown in culture were small- or medium-sized, no correlation was found between cell size and immunostaining density. At the ultrastructural level, the calbindin immunoreaction was distributed throughout the neuroplasm. These results indicate that the expression of calbindin by sensory neurons grown in vitro may be modulated by horse serum-contained factors or interaction with non-neuronal cells. As distinct from horse serum, muscular extract is able to maintain the expression of calbindin by a subpopulation of DRG cells.

Le canon du Nouveau Testament. Regards nouveaux sur l'histoire de sa formation

Comment, dans les premiers siècles de l'histoire du christianisme, se sont formés les livres du Nouveau Testament ? Une dizaine de spécialistes européens et américains abordent ce problème majeur avec un double souci : présenter au public francophone un état de la recherche et faire progresser les études par le recours à l'histoire sociale et à l'histoire des controverses. Une attention particulière est portée à des sources habituellement négligées parce qu'elles sont d'un accès difficile| il s'agit en particulier de textes orientaux (coptes, syriaques, arméniens) qui montrent que le Nouveau Testament est loin de s'être constitué de manière strictement uniforme au cours des cinq premiers siècles.