Effect of medium pH onp-aminohippurate accumulation by slices of rat renal cortex

Zusammenfassung Nierenschnitte von verschiedenen Arten akkumulieren PAH mit zunehmendem pH-Wert des Mediums bei einem deutlichen Maximum zwischen pH 7.4 und pH 8.0

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Supported in part by USPHS grant No. AM-10913.

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USPHS predoctoral trainee (GM-01761).

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Predoctoral Fellow of the Canadian Food and Drug Directorate, Ottawa.     

Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response

Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure. The classical short pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are acute-phase proteins produced in the liver in response to inflammatory mediators. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components. In contrast, long pentraxins have an unrelated, long amino-terminal domain coupled to the carboxy-terminal pentraxin domain, and differ, with respect to short pentraxins, in their gene organization, chromosomal localization, cellular source, and in their stimuli-inducing and ligand-recognition ability. To investigate the in vivo function of the long pentraxin PTX3, we generated mice deficient in Ptx3 by homologous recombination. Ptx3-null mice were susceptible to invasive pulmonary aspergillosis. Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response. Thus, the long pentraxin Ptx3 is a secreted pattern-recognition receptor that has a non-redundant role in resistance to selected microbial agents, in particular to the opportunistic fungal pathogen Aspergillus fumigatus.     

Alpha-helical coiled-coil structures of Trypanosoma brucei variable surface glycoproteins

We have used electron microscopy to examine purified intact variable surface glycoproteins (VSGs) from clones derived from two distinct stocks of Trypanosoma brucei. The VSG molecule from MITat 1.2 has a large elongated domain consistent with the shape of the dimeric N-terminal domain determined by X-ray analysis (see preceding paper), and a heretofore unseen short, thin fibrous tail presumed to be the C-terminal domain. Electron microscopy on DiTat 1.3, however, indicates a morphology quite distinct from that of MITat 1.2. Analysis of four VSG amino acid sequences reveals 7-fold periodicities (heptad repeats) which indicate that alpha-helical coiled-coil secondary structure elements occur in all of these VSGs, consistent with the observation of helical bundles in one VSG. These results suggest the possibility that VSG antigenic diversity may be related to a diversity in length and disposition of alpha-helical bundles and coiled-coil domains.     

Effects of lithium chloride on peripheral acetylcholine release and brain acetylcholine levels in the guinea-pig.

Lithium chloride administered acutely or chronically to guinea-pigs had no effect on brain level of acetylcholine or on peripheral release of acetylcholine from longitudinal muscle of the ileum. The results suggest differences between in vitro and in vivo action of lithium.     

Polysaccharide aggregation as a potential sink of marine dissolved organic carbon

The formation and sinking of biogenic particles mediate vertical mass fluxes and drive elemental cycling in the ocean. Whereas marine sciences have focused primarily on particle production by phytoplankton growth, particle formation by the assembly of organic macromolecules has almost been neglected. Here we show, by means of a combined experimental and modelling study, that the formation of polysaccharide particles is an important pathway to convert dissolved into particulate organic carbon during phytoplankton blooms, and can be described in terms of aggregation kinetics. Our findings suggest that aggregation processes in the ocean cascade from the molecular scale up to the size of fast-settling particles, and give new insights into the cycling and export of biogeochemical key elements such as carbon, iron and thorium.     

Bacterial disease resistance in Arabidopsis through flagellin perception

Plants and animals recognize microbial invaders by detecting pathogen-associated molecular patterns (PAMPs) such as flagellin. However, the importance of flagellin perception for disease resistance has, until now, not been demonstrated. Here we show that treatment of plants with flg22, a peptide representing the elicitor-active epitope of flagellin, induces the expression of numerous defence-related genes and triggers resistance to pathogenic bacteria in wild-type plants, but not in plants carrying mutations in the flagellin receptor gene FLS2. This induced resistance seems to be independent of salicylic acid, jasmonic acid and ethylene signalling. Wild-type and fls2 mutants both display enhanced resistance when treated with crude bacterial extracts, even devoid of elicitor-active flagellin, indicating the existence of functional perception systems for PAMPs other than flagellin. Although fls2 mutant plants are as susceptible as the wild type when bacteria are infiltrated into leaves, they are more susceptible to the pathogen Pseudomonas syringae pv. tomato DC3000 when it is sprayed on the leaf surface. Thus, flagellin perception restricts bacterial invasion, probably at an early step, and contributes to the plant's disease resistance.