MoDEL (Molecular Dynamics Extended Library): a database of atomistic molecular dynamics trajectories

More than 1700 trajectories of proteins representative of monomeric soluble structures in the protein data bank (PDB) have been obtained by means of state-of-the-art atomistic molecular dynamics simulations in near-physiological conditions. The trajectories and analyses are stored in a large data warehouse, which can be queried for dynamic information on proteins, including interactions. Here, we describe the project and the structure and contents of our database, and provide examples of how it can be used to describe the global flexibility properties of proteins. Basic analyses and trajectories stripped of solvent molecules at a reduced resolution level are available from our web server.     

Migration pattern suggested by terrestrial proximity as possible origin of wild annual <Emphasis Type="Italic">Helianthus</Emphasis> populations in central Argentina

There is a high interest to understand and recreate the invasive process of successful non-native plant invaders. The genetic tools provide scanty information when the invasion is recent and there is gene flow among the invader and its crop relative. The concern about the government and private companies’ responsibilities in the diffusion process and the risk of occupancy of new areas motivated the interest in two wild annual Helianthus species naturalized in the central agricultural lands of Argentina. We used multivariate techniques and random tests to estimate the successive steps accomplished by the plant invaders across transportation routes, following an environmental and ecological gradient. A minimum connection tree through road distances was created considering dispersal from a unique dispersal point for each species. The proposed tree minimized, at the same time, the environmental and the ecological distances calculated by Euclidean and Gower indexes with abiotic and biotic habitat variables, being significantly different from random (P ≤ 0.05). Our methodology allowed the development of an approach for the best estimation of the invasion route. This could be used to clarify the role of different agents involved in the diffusion process and to develop management strategies to prevent the plant invasion. The migration pattern suggests that after their historical introduction, both wild species moved in successive steps across a biotic and abiotic gradient, aided by anthropogenic activity along the road connection infrastructure. There were no evidences of escapes from sunflower breeding stations.     

Cot/tpl2 (MAP3K8) Mediates Myeloperoxidase Activity and Hypernociception following Peripheral Inflammation

Cot/tpl2 (also known as MAP3K8) has emerged as a new and potentially interesting therapeutic anti-inflammatory target. Here, we report the first study of Cot/tpl2 involvement in acute peripheral inflammation in vivo. Six hours after an intraplantar injection of zymosan, Cot/tpl2^−/− mice showed a 47% reduction in myeloperoxidase activity, concomitant with a 46% lower neutrophil recruitment and a 40% decreased luminol-mediated bioluminescence imaging in vivo. Accordingly, Cot/tpl2 deficiency provoked a 25–30% reduction in luminol-mediated bioluminescence and neutrophil recruitment together with a 65% lower macrophage recruitment 4 h following zymosan-induced peritonitis. Significantly impaired levels of G-CSF and GM-CSF and of other cytokines such as TNFα, IL-1β, and IL-6, as well as some chemokines such as MCP-1, MIP-1β, and keratinocyte-derived chemokine, were detected during the acute zymosan-induced intraplantar inflammatory response in Cot/tpl2^−/− mice. Moreover, Cot/tpl2 deficiency dramatically decreased the production of the hypernociceptive ligand NGF at the inflammatory site during the course of inflammation. Most importantly, Cot/tpl2 deficiency significantly reduced zymosan-induced inflammatory hypernociception in mice, with a most pronounced effect of a 50% decrease compared with wild type (WT) at 24 h following intraplantar injection of zymosan. At this time, Cot/tpl2^−/− mice showed significantly reduced NGF, TNFα, and prostaglandin E₂ levels compared with WT littermates. In conclusion, our study demonstrates an important role of Cot/tpl2 in the NGF, G-CSF, and GM-CSF production and myeloperoxidase activity in the acute inflammatory response process and its implication in inflammatory hypernociception.     

Allosteric modulation of dopamine D2 receptors by homocysteine

It has been suggested that L-DOPA-induced hyperhomocysteinemia can increase the risk of stroke, heart disease, and dementia and is an additional pathogenetic factor involved in the progression of Parkinson's disease. In Chinese hamster ovary (CHO) cells stably cotransfected with adenosine A(2A) and dopamine D2 receptors, homocysteine selectively decreased the ability of D2 receptor stimulation to internalize adenosine A(2A)-dopamine D2 receptor complexes. Radioligand-binding experiments in the same cell line demonstrated that homocysteine acts as an allosteric D2 receptor antagonist, by selectively reducing the affinity of D2 receptors for agonists but not for antagonists. Mass spectrometric analysis showed that, by means of an arginine (Arg)-thiol electrostatic interaction, homocysteine forms noncovalent complexes with the two Arg-rich epitopes of the third intracellular loop of the D2 receptor, one of them involved in A(2A)-D2 receptor heteromerization. However, homocysteine was unable to prevent or disrupt A(2A)-D2 receptor heteromerization, as demonstrated with Fluorescence Resonance Energy Transfer (FRET) experiments in stably cotransfected HEK cells. The present results could have implications for Parkinson's disease.     

Molecular biology in the diagnosis of deep-seated candidiasis in the critically ill non-neutropenic patient

Candida infections are an important cause of morbidity and mortality in critically ill patients. Rapid detection of the yeast in blood and other tissues by molecular biology methods has been the goal of some recent studies. An analysis of the sensitivity and specificity of these methods assayed in clinical specimens from critically ill and other patients is carried out. PCR amplification of ribosomal genes and their internal spacers showed a higher sensitivity than culture based methods. A standardization of most of the methodological steps in molecular methods is needed. Real time PCR with fluorescent probes seems to be the most interesting proposal. It has the advantage of the possible quantification of fungal presence in tissues and minimizes the samples' contamination risk.