LMProt: an efficient algorithm for Monte Carlo sampling of protein conformational space

A new and efficient Monte Carlo algorithm for sampling protein configurations in the continuous space is presented; the efficiency of this algorithm, named Local Moves for Proteins (LMProt), was compared to other alternative algorithms. For this purpose, we used an intrachain interaction energy function that is proportional to the root mean square deviation (rmsd) with respect to alpha-carbons from native structures of real proteins. For phantom chains, the LMProt method is approximately 10(4) and 20 times faster than the algorithms Thrashing (no local moves) and Sevenfold Way (local moves), respectively. Additionally, the LMProt was tested for real chains (excluded-volume all-atoms model); proteins 5NLL (138 residues) and 1BFF (129 residues) were used to determine the folding success xi as a function of the number eta of residues involved in the chain movements, and as a function of the maximum amplitude of atomic displacement delta r(max). Our results indicate that multiple local moves associated with relative chain flexibility, controlled by appropriate adjustments for eta and delta r(max), are essential for configurational search efficiency.     

Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-term-nonprogressing child

The emergence of cytotoxic T-lymphocyte (CTL) escape mutations in human immunodeficiency virus type 1 (HIV-1) proteins has been anecdotally associated with progression to AIDS, but it has been difficult to determine whether viral mutation is the cause or the result of increased viral replication. Here we describe a perinatally HIV-infected child who maintained a plasma viral load of <400 copies/ml for almost a decade until a nonbinding escape mutation emerged within the immunodominant CTL epitope. The child subsequently experienced a reemergence of HIV-1 viremia accompanied by a marked increase in the number of CTL epitopes targeted. This temporal pattern suggests that CD8 escape can play a causal role in the loss of immune control.     

Tree Community Change across 700 km of Lowland Amazonian Forest from the Andean Foothills to Brazil

We describe patterns of tree community change along a 700-km transect through terra firme forests of western Amazonia, running from the base of the Andes in Ecuador to the Peru–Brazil border. Our primary question is whether floristic variation at large scales arises from many gradual changes or a few abrupt ones. Data from 54 1-ha tree plots along the transect support the latter model, showing two sharp discontinuities in community structure at the genus level. One is located near the Ecuador–Peru border, where the suite of species that dominates large areas of Ecuadorean forest declines abruptly in importance to the east. This discontinuity is underlain by a subterranean paleoarch and congruent with a change in soil texture. A second discontinuity is associated with the shift from clay to white sand soils near Iquitos. We hypothesize that the first discontinuity is part of an edaphic boundary that runs along the Andean piedmont and causes a transition from tree communities preferring richer, younger soils near the base of the Andes to those preferring poorer, older soils farther east. Because the floristic changes observed at this discontinuity are conserved for large distances to the east and west of it, the discontinuity is potentially key for understanding floristic variation in western Amazonia. The significant floristic turnover at the Ecuador–Peru border suggests that the only large protected area in the region—Ecuador's Yasuní National Park—is not adequate protection for the very diverse tree communities that cover vast areas of northern Peru.     

Inhibition of Paracoccidioides lutzii Pb01 Isocitrate Lyase by the Natural Compound Argentilactone and Its Semi-Synthetic Derivatives

The dimorphic fungus Paracoccidioides spp. is responsible for paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America, causing serious public health problems. Adequate treatment of mycotic infections is difficult, since fungi are eukaryotic organisms with a structure and metabolism similar to those of eukaryotic hosts. In this way, specific fungus targets have become important to search of new antifungal compound. The role of the glyoxylate cycle and its enzymes in microbial virulence has been reported in many fungal pathogens, including Paracoccidioides spp. Here, we show the action of argentilactone and its semi-synthetic derivative reduced argentilactone on recombinant and native isocitrate lyase from Paracoccidioides lutzii Pb01 (PbICL) in the presence of different carbon sources, acetate and glucose. Additionally, argentilactone and its semi-synthetic derivative reduced argentilactone exhibited relevant inhibitory activity against P. lutzii Pb01 yeast cells and dose-dependently influenced the transition from the mycelium to yeast phase. The other oxygenated derivatives tested, epoxy argentilactone and diol argentilactone-, did not show inhibitory action on the fungus. The results were supported by in silico experiments.     

Are all species necessary to reveal ecologically important patterns?

While studying ecological patterns at large scales, ecologists are often unable to identify all collections, forcing them to either omit these unidentified records entirely, without knowing the effect of this, or pursue very costly and time‐consuming efforts for identifying them. These “indets” may be of critical importance, but as yet, their impact on the reliability of ecological analyses is poorly known. We investigated the consequence of omitting the unidentified records and provide an explanation for the results. We used three large‐scale independent datasets, (Guyana/ Suriname, French Guiana, Ecuador) each consisting of records having been identified to a valid species name (identified morpho‐species – IMS) and a number of unidentified records (unidentified morpho‐species – UMS). A subset was created for each dataset containing only the IMS, which was compared with the complete dataset containing all morpho‐species (AMS: = IMS + UMS) for the following analyses: species diversity (Fisher's alpha), similarity of species composition, Mantel test and ordination (NMDS). In addition, we also simulated an even larger number of unidentified records for all three datasets and analyzed the agreement between similarities again with these simulated datasets. For all analyses, results were extremely similar when using the complete datasets or the truncated subsets. IMS predicted ≥91% of the variation in AMS in all tests/analyses. Even when simulating a larger fraction of UMS, IMS predicted the results for AMS rather well. Using only IMS also out‐performed using higher taxon data (genus‐level identification) for similarity analyses. Finding a high congruence for all analyses when using IMS rather than AMS suggests that patterns of similarity and composition are very robust. In other words, having a large number of unidentified species in a dataset may not affect our conclusions as much as is often thought.     

Reversal of haloperidol-induced orofacial dyskinesia and neuroinflammation by isoflavones

Molecular Biology Reports - Schizophrenia is a mental illness and its pharmacological treatment consists in the administration of antipsychotics like haloperidol. However, haloperidol often causes...     

Estimating and interpreting migration of Amazonian forests using spatially implicit and semi‐explicit neutral models

With many sophisticated methods available for estimating migration, ecologists face the difficult decision of choosing for their specific line of work. Here we test and compare several methods, performing sanity and robustness tests, applying to large‐scale data and discussing the results and interpretation. Five methods were selected to compare for their ability to estimate migration from spatially implicit and semi‐explicit simulations based on three large‐scale field datasets from South America (Guyana, Suriname, French Guiana and Ecuador). Space was incorporated semi‐explicitly by a discrete probability mass function for local recruitment, migration from adjacent plots or from a metacommunity. Most methods were able to accurately estimate migration from spatially implicit simulations. For spatially semi‐explicit simulations, estimation was shown to be the additive effect of migration from adjacent plots and the metacommunity. It was only accurate when migration from the metacommunity outweighed that of adjacent plots, discrimination, however, proved to be impossible. We show that migration should be considered more an approximation of the resemblance between communities and the summed regional species pool. Application of migration estimates to simulate field datasets did show reasonably good fits and indicated consistent differences between sets in comparison with earlier studies. We conclude that estimates of migration using these methods are more an approximation of the homogenization among local communities over time rather than a direct measurement of migration and hence have a direct relationship with beta diversity. As betadiversity is the result of many (non)‐neutral processes, we have to admit that migration as estimated in a spatial explicit world encompasses not only direct migration but is an ecological aggregate of these processes. The parameter m of neutral models then appears more as an emerging property revealed by neutral theory instead of being an effective mechanistic parameter and spatially implicit models should be rejected as an approximation of forest dynamics.     

Myxospore Formation in Myxococcus xanthus: Chemical Changes in the Cell Wall During Cellular Morphogenesis

Vegetative cells of Myxococcus xanthus (strain FB) were induced to form myxospores by the glycerol induction technique. Several structural changes took place in the peptidoglycan during myxospore formation. The percent of the peptidoglycan comprised of monomer (disaccharide peptide) decreased from about 20% to approximately 7%. The proportion of the total diaminopimelic acid possessing a free amino group decreased about 11%. A carbohydrate containing only glucose was found to be bound, possibly covalently, to the vegetative cell and myxospore peptidoglycan. The amount of carbohydrate relative to peptidoglycan decreased by two-thirds during myxospore formation. None of the above changes in the peptidoglycan were observed in a mutant (strain GNI) of M. xanthus which was unable to convert to myxospores when incubated in the glycerol induction medium, or in the parental wild type (FB) when it was incubated in induction medium lacking the myxospore inducer, glycerol.