Activation of aldosterone and renin secretion by thermal stress

Résumé Un stress thermique aigu est un activateur rapide et puissant de la sécrétion du système rénineangiotensine et de l'aldosterone au cours d'une alimentation normo ou hyposodée, et peut être utilisé pour mesurer l'intégrité des systèmes de production de ces hormones.     

Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes

Copper is a cofactor for many cellular enzymes and transporters. It can be loaded onto secreted and endomembrane cuproproteins by translocation from the cytosol into membrane-bound organelles by ATP7A or ATP7B transporters, the genes for which are mutated in the copper imbalance syndromes Menkes disease and Wilson disease, respectively. Endomembrane cuproproteins are thought to incorporate copper stably on transit through the trans-Golgi network, in which ATP7A accumulates by dynamic cycling through early endocytic compartments. Here we show that the pigment-cell-specific cuproenzyme tyrosinase acquires copper only transiently and inefficiently within the trans-Golgi network of mouse melanocytes. To catalyse melanin synthesis, tyrosinase is subsequently reloaded with copper within specialized organelles called melanosomes. Copper is supplied to melanosomes by ATP7A, a cohort of which localizes to melanosomes in a biogenesis of lysosome-related organelles complex-1 (BLOC-1)-dependent manner. These results indicate that cell-type-specific localization of a metal transporter is required to sustain metallation of an endomembrane cuproenzyme, providing a mechanism for exquisite spatial control of metalloenzyme activity. Moreover, because BLOC-1 subunits are mutated in subtypes of the genetic disease Hermansky-Pudlak syndrome, these results also show that defects in copper transporter localization contribute to hypopigmentation, and hence perhaps other systemic defects, in Hermansky-Pudlak syndrome.     

Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta

A recessive form of severe osteogenesis imperfecta that is not caused by mutations in type I collagen has long been suspected. Mutations in human CRTAP (cartilage-associated protein) causing recessive bone disease have been reported. CRTAP forms a complex with cyclophilin B and prolyl 3-hydroxylase 1, which is encoded by LEPRE1 and hydroxylates one residue in type I collagen, alpha1(I)Pro986. We present the first five cases of a new recessive bone disorder resulting from null LEPRE1 alleles; its phenotype overlaps with lethal/severe osteogenesis imperfecta but has distinctive features. Furthermore, a mutant allele from West Africa, also found in African Americans, occurs in four of five cases. All proband LEPRE1 mutations led to premature termination codons and minimal mRNA and protein. Proband collagen had minimal 3-hydroxylation of alpha1(I)Pro986 but excess lysyl hydroxylation and glycosylation along the collagen helix. Proband collagen secretion was moderately delayed, but total collagen secretion was increased. Prolyl 3-hydroxylase 1 is therefore crucial for bone development and collagen helix formation.     

Detection of antibody and antigen in the milkweed bug,Oncopeltus fasciatus

Zusammenfassung Mit Hilfe der Fluoreszenzmarkierung von Proteinen und Ouchterlonys Methode wurde festgestellt, dass Insekten keine Immunität besitzen; Blutserum des Kaninchens blieb während 197 h im Hämolymph der Insekten.

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This research was supported in part by St. Louis University CRIC grants Nos. 64-03 and 65-03.     

In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment

The organization of cellular niches is known to have a key role in regulating normal stem cell differentiation and regeneration, but relatively little is known about the architecture of microenvironments that support malignant metastasis. Using dynamic in vivo confocal imaging, here we show that murine bone marrow contains unique anatomic regions defined by specialized endothelium. This vasculature expresses the adhesion molecule E-selectin and the chemoattractant stromal-cell-derived factor 1 (SDF-1) in discrete, discontinuous areas that influence the homing of a variety of tumour cell lines. Disruption of the interactions between SDF-1 and its receptor CXCR4 inhibits the homing of Nalm-6 cells (an acute lymphoblastic leukaemia cell line) to these vessels. Further studies revealed that circulating leukaemic cells can engraft around these vessels, suggesting that this molecularly distinct vasculature demarcates a microenvironment for early metastatic tumour spread in bone marrow. Finally, purified haematopoietic stem/progenitor cells and lymphocytes also localize to the same microdomains, indicating that this vasculature might also function in benign states to demarcate specific portals for the entry of cells into the marrow space. Specialized vascular structures therefore appear to delineate a microenvironment with unique physiology that can be exploited by circulating malignant cells.     

Exploring Community Collaborations: Social Network Analysis as a Reflective Tool for Public Health

Social network analysis is a potentially useful reflective tool that could be used by public health practitioners to assess the overall composition of their networks, strengthen collaborations with other community partners, and evaluate network function. The purpose of this paper is to report on public health practitioners’ experiences with social network analysis. Thirteen public health practitioners, each associated with their own advocacy-oriented community collaboration, participated in the study. Specifically, the intervention consisted of social network analysis output (social network analysis measures and sociograms) and a facilitated discussion to stimulate reflection on the respondents’ professional networks. Semi-structured interviews were conducted two weeks later to solicit participants’ reactions to the sociograms and the accompanying measures, and elicit thoughts about how social network analysis might have an impact on their work. Participants commented on ways in which social network analysis could be applied in practice, such as using sociograms to raise awareness of the nature of current networks, as a planning and evaluation tool, to identify gaps, and to assess the degree of sustainability of current networks.