A leucine-rich repeat motif of Leishmania parasite surface antigen 2 binds to macrophages through the complement receptor 3

Membrane glycoconjugates on the Leishmania parasites, notably leishmanolysin and lipophosphoglycan, have been implicated in attachment and invasion of host macrophages. However, the function of parasite surface Ag 2 (PSA-2) and membrane proteophosphoglycan (PPG) has not been elucidated. In this study we demonstrate that native and recombinant Leishmania infantum PSA-2, which consists predominantly of 15 leucine-rich repeats (LRR) and a recombinant LRR domain derived from L. major PPG, bind to macrophages. The interaction is restricted to macrophages and appears to be calcium independent. We have investigated the PSA-2-macrophage interaction to identify the host receptor involved in binding and we show that binding of PSA-2 to macrophages can be blocked by Abs to the complement receptor 3 (CR3, Mac-1). Data derived from mouse macrophage studies were further confirmed using cell lines expressing human CR3, and showed that PSA-2 also binds to the human receptor. This is the first demonstration of a functional role for PSA-2. Our data indicate that in addition to leishmanolysin and lipophosphoglycan, parasite attachment and invasion of macrophages involve a third ligand comprising the LRRs shared by PSA-2 and PPG and that these interactions occur via the CR3.     

Ecophysiology of Fe-cycling bacteria in acidic sediments

Using a combination of cultivation-dependent and -independent methods, this study aimed to elucidate the diversity of microorganisms involved in iron cycling and to resolve their in situ functional links in sediments of an acidic lignite mine lake. Using six different media with pH values ranging from 2.5 to 4.3, 117 isolates were obtained that grouped into 38 different strains, including 27 putative new species with respect to the closest characterized strains. Among the isolated strains, 22 strains were able to oxidize Fe(II), 34 were able to reduce Fe(III) in schwertmannite, the dominant iron oxide in this lake, and 21 could do both. All isolates falling into the Gammaproteobacteria (an unknown Dyella-like genus and Acidithiobacillus-related strains) were obtained from the top acidic sediment zones (pH 2.8). Firmicutes strains (related to Bacillus and Alicyclobacillus) were only isolated from deep, moderately acidic sediment zones (pH 4 to 5). Of the Alphaproteobacteria, Acidocella-related strains were only isolated from acidic zones, whereas Acidiphilium-related strains were isolated from all sediment depths. Bacterial clone libraries generally supported and complemented these patterns. Geobacter-related clone sequences were only obtained from deep sediment zones, and Geobacter-specific quantitative PCR yielded 8 × 10(5) gene copy numbers. Isolates related to the Acidobacterium, Acidocella, and Alicyclobacillus genera and to the unknown Dyella-like genus showed a broad pH tolerance, ranging from 2.5 to 5.0, and preferred schwertmannite to goethite for Fe(III) reduction. This study highlighted the variety of acidophilic microorganisms that are responsible for iron cycling in acidic environments, extending the results of recent laboratory-based studies that showed this trait to be widespread among acidophiles.     

Exercise training normalizes impaired NOS-dependent responses of cerebral arterioles in type 1 diabetic rats

Our goal was to examine whether exercise training (ExT) could normalize impaired nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during type 1 diabetes (T1D). We measured the in vivo diameter of pial arterioles in sedentary and exercised nondiabetic and diabetic rats in response to an endothelial NOS (eNOS)-dependent (ADP), an neuronal NOS (nNOS)-dependent [N-methyl-D-aspartate (NMDA)], and a NOS-independent (nitroglycerin) agonist. In addition, we measured superoxide anion levels in brain tissue under basal conditions in sedentary and exercised nondiabetic and diabetic rats. Furthermore, we used Western blot analysis to determine eNOS and nNOS protein levels in cerebral vessels/brain tissue in sedentary and exercised nondiabetic and diabetic rats. We found that ADP and NMDA produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic rats. In contrast, ADP and NMDA produced only minimal vasodilation in sedentary diabetic rats. ExT restored impaired ADP- and NMDA-induced vasodilation observed in diabetic rats to that observed in nondiabetics. Nitroglycerin produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic and diabetic rats. Superoxide levels in cortex tissue were similar in sedentary and exercised nondiabetic rats, were increased in sedentary diabetic rats, and were normalized by ExT in diabetic rats. Finally, we found that eNOS protein was increased in diabetic rats and further increased by ExT and that nNOS protein was not influenced by T1D but was increased by ExT. We conclude that ExT can alleviate impaired eNOS- and nNOS-dependent responses of pial arterioles during T1D.     

Exposure and Multiple Lines of Evidence Assessment of Risk for PCBs Found in the Diets of Passerine Birds at the Kalamazoo River Superfund Site,Michigan

Dietary exposures of passerine birds at the Kalamazoo River, Michigan, were examined due to the presence of polychlorinated biphenyls (PCBs) in the terrestrial and aquatic food webs. Average potential daily doses in diets were 6- to 29-fold and 16- to 35-fold greater at a contaminated location than at a reference location for PCB exposures quantified as total PCBs and 2,3,7,8–tetrachlorodibenzo-p-dioxin equivalents (TEQs), respectively. Birds with diets comprised of primarily aquatic insects had greater dietary exposure than birds with diets of primarily terrestrial insects. Risk associated with dietary exposure varied with the selection of the threshold for effects including hazard quotients, which exceeded 1 in instances where the most conservative toxicity reference values were utilized. Risk based on concentrations of PCBs in the tissues indicated little risk to avian species, and co-located studies evaluating reproductive health did not suggest that observed incidences of diminished reproductive success were related to PCB exposure. Measures of risk based on comparison to toxicity reference values (TRVs) were consistent with direct measures of ecologically relevant endpoints of reproductive fitness, but uncertainty exists in the selection of threshold values for effects in these species especially based on TEQs. This is largely due to the absence of species-specific, dose-response relationships. Therefore, the best estimate of risk is through the application of multiple lines of evidence.     

Norfloxacin Zn(II)-based complexes: acid base ionization constant determination, DNA and albumin binding properties and the biological effect against Trypanosoma cruzi

Zn(II) complexes with norfloxacin (NOR) in the absence or in the presence of 1,10-phenanthroline (phen) were obtained and characterized. In both complexes, the ligand NOR was coordinated through a keto and a carboxyl oxygen. Tetrahedral and octahedral geometries were proposed for [ZnCl₂(NOR)]·H₂O (1) and [ZnCl₂(NOR)(phen)]·2H₂O (2), respectively. Since the biological activity of the chemicals depends on the pH value, pH titrations of the Zn(II) complexes were performed. UV spectroscopic studies of the interaction of the complexes with calf-thymus DNA (CT DNA) have suggested that they can bind to CT DNA with moderate affinity in an intercalative mode. The interactions between the Zn(II) complexes and bovine serum albumin (BSA) were investigated by steady-state and time-resolved fluorescence spectroscopy at pH 7.4. The experimental data showed static quenching of BSA fluorescence, indicating that both complexes bind to BSA. A modified Stern–Volmer plot for the quenching by complex 2 demonstrated preferential binding near one of the two tryptophan residues of BSA. The binding constants obtained (K _b ) showed that BSA had a two orders of magnitude higher affinity for complex 2 than for 1. The results also showed that the affinity of both complexes for BSA was much higher than for DNA. This preferential interaction with protein sites could be important to their biological mechanisms of action. The analysis in vitro of the Zn(II) complexes and corresponding ligand were assayed against Trypanosoma cruzi, the causative agent of Chagas disease and the data showed that complex 2 was the most active against bloodstream trypomastigotes.     

Copy-number variant analysis of classic heterotaxy highlights the importance of body patterning pathways

Classic heterotaxy consists of congenital heart defects with abnormally positioned thoracic and abdominal organs. We aimed to uncover novel, genomic copy-number variants (CNVs) in classic heterotaxy cases. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 infants (cases) with classic heterotaxy identified from California live births from 1998 to 2009. CNVs were identified using the PennCNV software. We identified 56 rare CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, not previously linked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and near MIR302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axes determination. FGF12, RBFOX1, and MIR302F could be important in human heterotaxy, because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIR302F is warranted.     

Sulfoglucuronyl Neolactoglycolipids in Adult Cerebellum: Specific Absence in Murine Mutants with Purkinje Cell Abnormality

It is shown here that glycolipids of the sulfoglucuronyl neolacto series (SGGLs) are present in the adult rodent cerebellum. SGGLs were not detected in the cerebellar murine mutants lurcher, Purkinje cell degeneration, and staggerer, in which Purkinje cell loss is the primary defect. SGGLs were present, however, in normal amounts in weaver and reeler mutants, in which there is a major and relatively specific loss of granule cells without obvious deficiency in Purkinje cells. In the myelin-deficient quaking mutant, the expression of SGGLs also was nearly normal. The loss of SGGLs in Purkinje cell-deficient mutants was specific, since most of the major lipids were not affected significantly and only the percentage composition of other lipids, such as sulfatides and gangliosides, was altered in the mutants. These and other results strongly suggest that SGGLs and other glycolipids of the paragloboside family are localized specifically in Purkinje cells and their arbors in the adult cerebellum. This is the first demonstration of the localization of a specific glycolipid and its analogs in a specific cell type in the nervous system.     

Are ABA,ethylene or their interaction involved in the response of leaf growth to soil water deficit? An analysis using naturally occurring variation or genetic transformation of ABA production in maize

The role of abscisic acid (ABA) and its possible interaction with ethylene in mediating leaf elongation response to soil water deficit are a matter of controversy. To address this question, we used a set of maize genotypes with various levels of ABA either due to natural variability or to genetic transformation targeted on NCED/VP14, a key enzyme of ABA synthesis. The transgenic lines yielded less strong phenotypes than available mutants, making it possible to use them under normal growing conditions. We focused on leaf elongation during night periods in order to avoid the confounding effect of ABA on leaf water status. Our results suggest that over a wide range, internal ABA level (measured in both leaf extracts or xylem sap) has no clear effect on leaf elongation response to soil water deficit, except in the case of an antisense line presenting the strongest reduction in ABA accumulation that showed a slight maintenance of leaf elongation during water deficit. Leaf ethylene production rate was variable and not related to water deficit except in the ABA-deficient transgenic lines where it was increased by water deficit on average but not systematically. Moreover, variability in ethylene production rate was not linked to variability in elongation rate. Our results thus suggest that neither ABA nor ethylene seems to play a major role in the control of leaf elongation response to soil water deficit.     

Signification des caractères partagés entre Bennettitales et Cycadales. Implications de la découverte d''une Cycadale nouvelle du Cénomanien de l''Anjou (France)

The lagoonal Cenomanian formation (Lower Cretaceous) of clays of the region of Baugeois (north of Angers) has supplied an exceptionally well-preserved fossil flora: leaves, woody structures or/and reproductive organs of pteridophyta, gymnosperms and angiosperms. A well-preserved fossil plant found in a quarry “Le Brouillard” (8 km from Angers), has allowed a detailed morphological and structural study of this species. A comparative study with extant plants has confirmed an undoubted link between the contemporary genus Dioon (an endemic cycad from Mexico) and the fossil species. However, features observed on the lower epidermis of the leaflets, present a similarity with some Jurassic Bennettitales. This discovery, added to other common features shared by these two orders, raises questions about their relationships, thought to be different from a phylogenetic viewpoint.

Résumé

La formation lagunaire cénomanienne (Crétacé inférieur) des Argiles du Baugeois, au nord d'Angers, a fourni une flore fossile riche et exceptionnellement bien conservée: feuilles, structures ligneuses ou/et organes reproducteurs de ptéridophytes, de gymnospermes et d'angiospermes. L'excellent état de conservation d'un fragment de plante fossile, récolté dans la carrière Le Brouillard à 8 km d'Angers, a permis une étude détaillée de la morphologie et de la structure foliaire de cette plante. L'étude comparative avec des plantes actuelles a démontré l'existence d'un lien de parenté entre le genre Dioon (cycadale endémique du Mexique) et le fossile, mais des caractères originaux observés sur l'épiderme inférieur des folioles, présentent des similitudes avec certains genres de Bennettitales du Jurassique. Une telle découverte, ajoutée aux autres caractères communs préalablement décrits par d'autres auteurs, soulèvent à nouveau quelques questions sur les relations de parentés entre ces deux groupes supposés phylogénétiquement éloignés actuellement.