A natural CCL5/RANTES variant antagonist for CCR1 and CCR3

The N-terminal domain of the chemokine CCL5/regulated upon activation normal T cell expressed and secreted (RANTES) has been shown to be critical for its biological activity on leukocytes. Several N-terminus-modified CCL5/RANTES derivatives, such as N-Terminal truncated CCL5/RANTES, Met-RANTES, and amino-oxypentane (AOP)-RANTES exhibited antagonist or partial agonist functions when investigated on the properties of their receptors CCR1, CCR3, and CCR5. Studying 95 African samples from Cameroon, we found a naturally occurring variant of CCL5/RANTES containing a missense mutation located in the first amino acid of the secreted form (S24F). S24F binds CCR1, CCR3, and CCR5 and triggers receptor down-modulation comparable to CCL5/RANTES. Moreover, in CCR5 positive cells, S24F elicits cellular calcium mobilization equivalent to that obtained with CCL5/RANTES. By contrast, S24F does not provoke any response in CCR1 and CCR3 positive cells. As CCL5/RANTES is able to attract different subtypes of leukocytes into inflamed tissue and intervenes in a wide range of allergic and autoimmune diseases, the discovery of this natural N-terminus-modified CCL5/RANTES analogue exhibiting differential effects on CCL5/RANTES receptors, opens up additional perspectives for therapeutic intervention.Nucleotide sequence data reported is available in the DDBJ/EMBL/GenBank databases under the accession number: DQ230537.     

Coexistence and Spread of Competitors in Heterogeneous Landscapes

Competition between species is ubiquitous in nature and therefore widely studied in ecology through experiment and theory. One of the central questions is under which conditions a (rare) invader can establish itself in a landscape dominated by a resident species at carrying capacity. Applying the same question with the roles of the invader and resident reversed leads to the principle that “mutual invasibility implies coexistence.” A related but different question is how fast a locally introduced invader spreads into a landscape (with or without competing resident), provided it can invade. We explore some aspects of these questions in a deterministic, spatially explicit model for two competing species with discrete non-overlapping generations in a patchy periodic environment. We obtain threshold values for fragmentation levels and dispersal distances that allow for mutual invasion and coexistence even if the non-spatial competition model predicts competitive exclusion. We obtain exact results when dispersal is governed by a Laplace kernel. Using the average dispersal success, we develop a mathematical framework to obtain approximate results that are independent of the exact dispersal patterns, and we show numerically that these approximations are very accurate.     

Biological roles of specific peptides in enzymes

It has recently been shown (Kunik et al., PLOS Comput Biol 2007;3(8):e167) that the occurrence of specific peptides (SPs) on sequences of enzymes allows for accurate EC classification of enzymes. We inquire whether these SPs play important roles in bringing about the enzymatic function. This is assessed by cross-checking the occurrence of SPs on enzymes with Swiss-Prot annotations and PDB spatial structures of enzymes. Analyzing the coverage of functional annotations of enzymes, we demonstrate that SPs contain major fractions of all annotated features. This result is statistically highly significant and associates over 10% of all SPs with important biological markers. Concentrating on DNA binding regions, relevant to LexA repressor enzymes, we find interesting coverage patterns. Moreover, for the same data, we demonstrate that SPs allow for subclassification of the relevant bacteria into phylogenetic classes. An analysis of mutagen annotations on SPs appearing on all enzymes leads to the conclusion that mutations on SPs tend to damage the enzymatic function much more than expected from a background model, hence SPs are of high importance to enzymatic functions. SPs that lie in 3D pockets that are shared by active and binding sites, are shown to be significantly enriched by glycine, leading to the hypothesis that they are responsible for conformational plasticity. Finally we show that SPs can partially resolve outstanding difficult problems of convergent evolution by representing correctly enzyme functions in spite of remote homologies in sequence and in structure.     

Phlebotomine sandflies in Parque Nacional Cavernas do Peruaçu, Minas Gerais state, Brazil

We surveyed the phlebotomine fauna in the Parque Nacional Cavernas do Perua?u, Minas Gerais, Brazil, aiming to associate the presence of vector with the risk of leishmaniasis transmission. Field captures were performed with CDC light traps between February and March 2003. A total of 436 sand flies were captured, belonging to 14 species. The predominant species (28.7%) was Lutzomyia ischnacantha Martins, Souza e Falc?o, followed by L. renei (27,06%) and L. cavernicola (13,07%). The finding of L. intermedia, a species that is incriminated as vector of cutaneous leishmaniasis, has to be taken into account.     

Molecular cloning of glutathione reductase cDNAs and analysis of GR gene expression in cowpea and common bean leaves during recovery from moderate drought stress

Two cDNAs of the enzyme glutathione reductase (GR; EC 1.6.4.2) encoding a dual-targeted isoform (dtGR) and a cytosolic isoform (cGR), were cloned from leaves of common bean (Phaseolus vulgaris L.). Moderate drought stress (Psi w=-1.5MPa) followed by re-watering was applied to common bean cultivars, one tolerant to drought (IPA), the other susceptible (Carioca) and to cowpea (Vigna unguiculata L. Walp) cultivars, one tolerant to drought (EPACE-1), and the other susceptible (1183). mRNA levels were much higher for PvcGR than for PvdtGR in all cases. Moderate drought stress induced an up-regulation of the expression of PvcGR in the susceptible cultivars. On the contrary, PvdtGR expression decreased. In the tolerant cowpea EPACE-1, GR gene expression remained stable under drought. During recovery from drought, an up-regulation of the two GR isoforms occurred, with a peak at 6-10h after re-hydration. This suggests that moderate drought stress may lead to a hardening process and acclimation tolerance. The role of GR isoforms in plant tolerance and capacity to recover from drought stress is discussed.     

Downstream flow and upstream movement determine the value of a stream reach for potadromous fish populations

Given that human activities often have negative impacts on biological populations, a common question is to find the location of greatest positive or least negative impact. Local habitat suitability is frequently used to evaluate viability of fish populations in river networks. Upper stream reaches are often undervalued, in particular when they are not navigable or do not contain commercially interesting fish. Since water flow transports certain local conditions downstream and individuals navigate river networks upstream and downstream, impacts of local perturbations can manifest elsewhere in the system, and overall effects of disturbances should be assessed on a network level. We study a model for a potadromous fish population in a system of connected stream reaches. We consider different geometries to evaluate how downstream transport and individual movement interact to determine the location of greatest and least impact of a single or two concurrent disturbances. Our results show how upper stream reaches can be highly significant for population persistence if downstream transport of abiotic conditions or upstream movement of individuals is strong.