Scoring predictive models using a reduced representation of proteins: model and energy definition

Background  

Reduced representations of proteins have been playing a keyrole in the study of protein folding. Many such models are available, with different representation detail. Although the usefulness of many such models for structural bioinformatics applications has been demonstrated in recent years, there are few intermediate resolution models endowed with an energy model capable, for instance, of detecting native or native-like structures among decoy sets. The aim of the present work is to provide a discrete empirical potential for a reduced protein model termed here PC2CA, because it employs a PseudoCovalent structure with only 2 Centers of interactions per Amino acid, suitable for protein model quality assessment.     

Putative role of heparan sulfate proteoglycan expression and shedding on the proliferation and survival of cells after photodynamic therapy

INTRODUCTION: Photodynamic therapy is based on the selective retention of a photosensitizer by highly proliferating cells and its activation with light at the appropriate wavelength. This combination generates reactive oxygen species that ultimately kill the cells. Some cells, however, may survive photodynamic therapy and the interaction of these cells with the extracellular matrix has profound effect in tumor biology. The knowledge of photodynamic therapy action on the extracellular matrix has not been fully explored. It has been focused mainly on integrins, matrix metalloproteinases and on growth factors and immunological mediators. Other important molecules involved in the regulation of many cell processes are the glycosaminoglycans, polymers of disaccharide units, present on the cell surface and in the extracellular matrix. In most cases, the glycosaminoglycans occur as proteoglycans. AIMS: The purpose of the present investigation is to evaluate heparan sulfate proteoglycan expression and shedding, and its relation to the survival of the remaining cells, after a liposomal-AlClPc based photodynamic treatment. MATERIALS: A wild-type endothelial cell derived from rabbit aorta and its counterpart transfected with EJ-ras oncogene were used. RESULTS: Both cell lines presented augmented heparan sulfate proteoglycan syndecan-4 mRNA expression, augmented synthesis of heparan sulfate chains and increased shedding. Also, the formation of stress fibers on the border of the cells and the arrest in G(1) phase of the cell cycle was observed. CONCLUSIONS: These results show that surviving cells after photodynamic therapy exhibit changes in their morphology and cell processes that differ from that of non-treated cells, and these changes are probably hindering the cells from resuming normal proliferation.     

Sanio's laws revisited. Size-dependent changes in the xylem architecture of trees

Early observations led Sanio [ Wissen. Bot. , 8 , (1872) 401] to state that xylem conduit diameters and lengths in a coniferous tree increase from the apex down to a height below which they begin to decrease towards the tree base. Sanio's law of vertical tapering has been repeatedly tested with contradictory results and the debate over the scaling of conduit diameters with distance from the apex has not been settled. The debate has recently acquired new vigour, as an accurate knowledge of the vertical changes in wood anatomy has been shown to be crucial to scaling metabolic properties to plant and ecosystem levels. Contrary to Sanio's hypothesis, a well known model (MST, metabolic scaling theory) assumes that xylem conduits monotonically increase in diameter with distance from the apex following a power law. This has been proposed to explain the three-fourth power scaling between size and metabolism seen across plants. Here, we (i) summarized available data on conduit tapering in trees and (ii) propose a new numerical model that could explain the observed patterns. Data from 101 datasets grouped into 48 independent profiles supported the notions that phylogenetic group (angiosperms versus gymnosperms) and tree size strongly affected the vertical tapering of conduit diameter. For both angiosperms and gymnosperms, within-tree tapering also varied with distance from the apex. The model (based on the concept that optimal conduit tapering occurs when the difference between photosynthetic gains and wall construction costs is maximal) successfully predicted all three major empirical patterns. Our results are consistent with Sanio's law only for large trees and reject the MST assumptions that vertical tapering in conduit diameter is universal and independent of rank number.     

The bacterial aetiology of rosy discoloration of ancient wall paintings

The inventory of microorganisms responsible for biological deterioration of ancient paintings has become an integral part of restoration activities. Here, the microbial agent of rosy discoloration on medieval frescoes in the Crypt of the Original Sin (Matera, Italy) was investigated by a combination of microscopic, molecular and spectroscopic approaches. The bacterial community from three rosy-discoloured painting sites was characterized by 16S rRNA gene-based techniques. The eubacterial population was prevalently composed of Actinobacteria, among which Rubrobacter radiotolerans-related bacteria accounted for 63-87% of the 16S rRNA gene pool per sampled site. Archaea, with prevalence of Haloarchaea-related species, were detected in one of the three sites where they accounted for < 0.1% of the total 16S rRNA gene pool. Raman spectroscopy confirmed the identity between R. radiotolerans carotenoids (bacterioruberins) and pigments responsible for colour alteration of frescoes. This investigation provides the first evidence of a causal relationship between heavy contamination by Rubrobacter-related bacterioruberin-producing bacteria and rosy discoloration of ancient wall paintings.     

Transgenic Fatal Familial Insomnia Mice Indicate Prion Infectivity-Independent Mechanisms of Pathogenesis and Phenotypic Expression of Disease

Fatal familial insomnia (FFI) and a genetic form of Creutzfeldt-Jakob disease (CJD¹⁷⁸) are clinically different prion disorders linked to the D178N prion protein (PrP) mutation. The disease phenotype is determined by the 129 M/V polymorphism on the mutant allele, which is thought to influence D178N PrP misfolding, leading to the formation of distinctive prion strains with specific neurotoxic properties. However, the mechanism by which misfolded variants of mutant PrP cause different diseases is not known. We generated transgenic (Tg) mice expressing the mouse PrP homolog of the FFI mutation. These mice synthesize a misfolded form of mutant PrP in their brains and develop a neurological illness with severe sleep disruption, highly reminiscent of FFI and different from that of analogously generated Tg(CJD) mice modeling CJD¹⁷⁸. No prion infectivity was detectable in Tg(FFI) and Tg(CJD) brains by bioassay or protein misfolding cyclic amplification, indicating that mutant PrP has disease-encoding properties that do not depend on its ability to propagate its misfolded conformation. Tg(FFI) and Tg(CJD) neurons have different patterns of intracellular PrP accumulation associated with distinct morphological abnormalities of the endoplasmic reticulum and Golgi, suggesting that mutation-specific alterations of secretory transport may contribute to the disease phenotype.     

Reproducibility in urine peptidome profiling using MALDI‐TOF

MALDI‐TOF profiling of low molecular weight peptides (peptidome) usage is limited due to the lack of reproducibility from the confounding inferences of sample preparation, data acquisition, and processing. We applied MALDI‐TOF analysis to profile urine peptidome with the aims to: (i) compare centrifugal ultrafiltration and dialysis pretreatments, (ii) determine whether using signal LOD (sLOD), together with data normalization, may reduce MALDI‐TOF variability. We also investigated the influence of peaks detection on reproducibility. Dialysis allowed to obtain better MALDI‐TOF spectra than ultrafiltration. Within the 1000–4000 m/z range, we identified 120 and 129 peaks in intra‐ and interassay studies, respectively. To estimate the sLOD, serial dilution of pooled urines up to 1/256 were analyzed in triplicate. Six data normalization strategies were investigated–the mean, median, internal standard, relative intensity, TIC, and linear rescaling normalization. Normalization methods alone performed poorly in reducing features variability while when combined to sLOD adjustment showed an overall reduction in features CVs. Applying a feedback signal processing approach, after median normalization and sLOD adjustment, CVs were reduced from 103 to 26% and 113 to 25% for the intra‐ and interassay, respectively, and spectra became more comparable in terms of data dispersion.     

Cell aging-induced methionine oxidation causes an autocrine to paracrine shift of the pheromone activity in the protozoan ciliate, Euplotes raikovi

Ciliates of the genus Euplotes rely on the autocrine (self) and paracrine (non-self) activities of their water-borne protein pheromones to control the two fundamental phenomena of their life cycle, i.e. vegetative (mitotic) growth and sex manifested as cell union in mating pairs. We observed that cell aging determines the synthesis of increasing concentrations of pheromones that are oxidized at the level of methionine residues which are more exposed on the molecular surface. The oxidized form of the E. raikovi pheromone Er-1 was purified and its interactions with its source cells were shown no longer to be of autocrine type directed to promote cell growth, but changed to interactions of the paracrine type directed to induce cell unions in mating pairs of the selfing type (i.e. involving genetically identical cells). These pairs generate viable offspring, like pairs formed between genetically different cells. It was therefore concluded that aging cells may paradoxically gain beneficial effects from the synthesis of oxidized forms of their pheromones. By undergoing mating in response to the interactions with these forms, they can re-initiate a new life cycle and, in fact, rejuvenate.