CCR5 is involved in controlling the early stage of Cryptosporidium parvum infection in neonates but is dispensable for parasite elimination

Chemokines play a critical role in immune cell trafficking and the transition from an innate to an acquired immune response. We analyzed host response in neonatal mice deficient in chemokine receptor CCR5 following infection with the intracellular protozoan parasite Cryptosporidium parvum. CCR5 neonatal mice had a higher parasite burden at the early stage of infection but eliminated the parasite as efficiently as their wild-type counterparts. The higher sensitivity of neonates at the beginning of infection was not due to an altered IFNgamma response. An increased CCR2-attracting chemokine response associated with the recruitment of CCR2-positive cells in the infected mucosa may have compensated for the absence of CCR5. A lack of CCR5 thus has an impact in the early stage of C. parvum infection in neonates, but this receptor is dispensable for subsequent parasite elimination.     

Investigation of the functional relevance of the catalytically important Glu(28) in family 51 arabinosidases

The alpha-L-arabinofuranosidase (AbfD3) from Thermobacillus xylanilyticus is a family 51 glycosyl hydrolase. According to classification hierarchy, family 51 belongs to clan GH-A. While the major GH-A motifs, the catalytic acid-base and nucleophile, are conserved in AbfD3, a third catalytically important residue (Glu(28)) does not appear to be analogous to any known GH-A motif. To evaluate the importance of Glu(28), bioinformatics analyses and site-saturation mutagenesis were performed. The results indicate that Glu(28) forms part of a family 51 arabinosidase motif which might be functionally homologous to a conserved N-terminal motif found in exo-acting enzymes from families 1 and 5. Importantly, the data reveal that Glu(28) is a key determinant of substrate recognition in the -1 subsite, where it may also play an important role in water-mediated deglycosylation of the glycosyl-enzyme covalent intermediate.     

Overexpression of the nucleolar protein nucleophosmin/B23 in collagen lattice-cultured fibroblasts: Potential role in the control of protein synthesis

Fibroblasts cultivated in tridimensional collagen lattices exhibit a downregulation of protein synthesis, related to decreased ribosomal RNA (rRNA) content and half life, when compared to monolayer cultivated cells. The involvement in this process of nucleophosmin/B23, a nucleolar phosphoprotein with ribonuclease properties, was checked. We compared production of nucleophosmin/B23 in monolayer and collagen lattice cultured fibroblasts. A significant increase of nucleophosmin/B23 mRNA levels was noticed in lattice-cultured fibroblasts vs monolayers (+154%, p < 0.05). A concomitant enhancement of nucleolar nucleophosmin/B23 content was found (+112%, p < 0.001). Simultaneously, ribonuclease activity contained in nucleolar extracts from collagen lattice-cultured fibroblasts was significantly increased (+54%, p < 0.01). These data demonstrate that extracellular collagen matrix induces the overexpression of nucleophosmin/B23, and suggest that the regulation of protein syntheses in collagen lattice cultures may be explained, at least partly, by an increased degradation of neosynthesized rRNAs dependent on nucleophosmin.     

Synthesis of aza and oxaglutamyl-p-nitroanilide derivatives and their kinetic studies with gamma-glutamyltranspeptidase

A new series of L-glutamic acid p-nitroanilide analogues has been synthesized and tested as substrates and inhibitors of rat kidney gamma-glutamyltranspeptidase (GGT). Kinetic parameters (K(m) and k(cat)) were determined for each analogue and provide insight into the scope and limits of GGT catalytic efficiency.     

Fitness costs associated with unnecessary virulence factors and life history traits: evolutionary insights from the potato late blight pathogen <Emphasis Type="Italic">Phytophthora infestans</Emphasis>

Background  

In gene-for-gene models of plant-pathogen interactions, the existence of fitness costs associated with unnecessary virulence factors still represents an issue, both in evolutionary biology and agricultural sciences. Measuring such costs experimentally has proven difficult, especially in pathogens not readily amenable to genetic transformation, since the creation of isogenic lines differing only by the presence or absence of avirulence genes cannot be achieved in many organisms. Here, we circumvented this difficulty by comparing fitness traits in groups of Phytophthora infestans isolates sharing the same multilocus fingerprint, but differing by their virulence/avirulence spectrum.     

A Michaelis–Menten type equation for describing methylmercury dependence on inorganic mercury in aquatic sediments

Methylation of mercury (Hg) is the crucial process that controls Hg biomagnification along the aquatic food chains. Aquatic sediments are of particular interest because they constitute an essential reservoir where inorganic divalent Hg (Hg^II) is methylated. Methylmercury (MeHg) concentrations in sediments mainly result from the balance between methylation and demethylation reactions, two opposite natural processes primarily mediated by aquatic microorganisms. Thus, Hg availability and the activity of methylating microbial communities control the MeHg abundance in sediments. Consistently, some studies have reported a significant positive correlation between MeHg and Hg^II or total Hg (Hg_T), taken as a proxy for Hg^II, in aquatic sediments using enzyme-catalyzed methylation/demethylation mechanisms. By compiling 1,442 published and unpublished Hg_T–MeHg couples from lacustrine, riverine, estuarine and marine sediments covering various environmental conditions, from deep pristine abyssal to heavily contaminated riverine sediments, we show that a Michaelis–Menten type relationship is an appropriate model to relate the two parameters: MeHg = aHg_T/(K _m  + Hg_T), with a = 0.277 ± 0.011 and K _m  = 188 ± 15 (R ² = 0.70, p < 0.001). From K _m variations, which depend on the various encountered environmental conditions, it appears that MeHg formation and accumulation are favoured in marine sediments compared to freshwater ones, and under oxic/suboxic conditions compared to anoxic ones, with redox potential and organic matter lability being the governing factors.     

Molecular mapping of a Yq deletion in a patient with normal stature

The proximal long arm of the Y chromosome probably contains a gene (GCY) involved in stature determination. Recent reports have proposed the critical region extends from interval 4B to interval 5G (or 5E). In the present study, the deletion breakpoint in a male adult patient of normal height with a 46,X,del(Yq) karyotype was defined by the use of sequence-tagged site markers. The breakpoint was found between sY78 (interval 4B) and sY79 (interval 5A). The existence of a normal stature in this patient suggests that the growth determinant is proximal to sY79, therefore probably located in interval 4B or in proximal interval 5A of the Y chromosome. Received: 22 March 1996