Fast and Accurate Multivariate Gaussian Modeling of Protein Families: Predicting Residue Contacts and Protein-Interaction Partners

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/cod

Comparison of relativity theories with observer-independent scales of both velocity and length/mass

We consider the two most studied proposals of relativity theories with observer-independent scales of both velocity and length/mass: the one discussed by Amelino-Camelia as illustrative example for the original proposal (gr-qc/0012051) of theories with two relativistic invariants, and an alternative more recently proposed by Magueijo and Smolin (hep-th/0112090). We show that these two relativistic theories are much more closely connected than it would appear on the basis of a naive analysis of their original formulations. In particular, in spite of adopting a rather different formal description of the deformed boost generators, they end up assigning the same dependence of momentum on rapidity, which can be described as the core feature of these relativistic theories. We show that this observation can be used to clarify the concepts of particle mass, particle velocity, and energy-momentum-conservation rules in these theories with two relativistic invariants.Comment: 21 pages, LaTex. v2: Andrea Procaccini (contributing some results from hia Laurea thesis) is added to the list of authors and the paper provides further elements of comparison between DSR1 and DSR2, including the observation that both lead to the same formula for the dependence of momentum on rapidit

High-Order Corrections to the Entropy and Area of Quantum Black Holes

The celebrated area-entropy formula for black holes has provided the most important clue in the search for the elusive theory of quantum gravity. We explore the possibility that the (linear) area-entropy relation acquires some smaller corrections. Using the Boltzmann-Einstein formula, we rule out the possibility for a power-law correction, and provide severe constraints on the coefficient of a possible log-area correction. We argue that a non-zero logarithmic correction to the area-entropy relation, would also imply a modification of the area-mass relation for quantum black holes.Comment: 3 page

Depth-specific fluctuations of gene expression and protein abundance modulate the photophysiology in the seagrass <i>Posidonia oceanica</i>

Here we present the results of a multiple organizational level analysis conceived to identify acclimative/adaptive strategies exhibited by the seagrass Posidonia oceanica to the daily fluctuations in the light environment, at contrasting depths. We assessed changes in photophysiological parameters, leaf respiration, pigments, and protein and mRNA expression levels. The results show that the diel oscillations of P. oceanica photophysiological and respiratory responses were related to transcripts and proteins expression of the genes involved in those processes and that there was a response asynchrony between shallow and deep plants probably caused by the strong differences in the light environment. The photochemical pathway of energy use was more effective in shallow plants due to higher light availability, but these plants needed more investment in photoprotection and photorepair, requiring higher translation and protein synthesis than deep plants. The genetic differentiation between deep and shallow stands suggests the existence of locally adapted genotypes to contrasting light environments. The depth-specific diel rhythms of photosynthetic and respiratory processes, from molecular to physiological levels, must be considered in the management and conservation of these key coastal ecosystems

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe

Assessment of circadian rhythm in pain and stiffness in rheumatic diseases according the EMA (Ecologic Momentary Assessment) method: patient compliance with an electronic diary

Background: Many researchers have used paper diaries in an attempt to capture patient experience. However, patient non-compliance with written diary protocols is a serious problem for researchers. Electronic patient experience diaries (eDiary) facilitate Ecologic Momentary Assessment (EMA) study designs by allowing the researcher to administer flexible, programmable assessments and mark each record with a time and date stamp. Objectives: The objectives of the current study were to evaluate methodological issues associated with real-time pain reports (EMA) using electronic patient experience diaries, to quantify compliance (percentage of the total number of diary reports scheduled that were actually completed), and to examine the circadian rhythm in pain and stiffness of patients with rheumatic diseases in an ecologically valid manner. Methods: In this cross-sectional study we examined 49 patients with rheumatic diseases (14 patients with rheumatoid arthritis, 18 with fibromyalgia and 17 with osteoarthritis of the knee), attending the care facilities of the Department of Rheumatology of Universita Politecnica delle Marche. All patients fulfilling the American College of Rheumatology (ACR) criteria. The assessment of pain and stiffness in all patients were repeated seven times a day (8 A.M., 10 A.M., 12 A.M., 2 P.M., 4 P.M., 6 P.M. and 8 P.M.) on seven consecutive days using an electronic diary (DataLoggerO - Pain Level Recorder). A datalogger is newly developed electronic instrument that records measurements of pain and stiffness over time. Dataloggers are small, battery-powered devices that are equipped with a microprocessor. Specific software is then used to select logging parameters (sampling intervals, start time, etc.) and view/analyse the collected data. Compliance is based on the time and date record that was automatically recorded by the devices. Results: Using the data from the electronic diary, we determined that the average verified compliance rate for pain and stiffness were 93.8 and 93.6%, respectively. The two highest compliance rates were observed in patients with rheumatoid arthritis (95.6 and 95.2%, respectively). There were no statistically significant difference in compliance between females and males or patients above or below 60 years old. Significant circadian rhytms in patients with RA and OA of the knee were detected in pain and stiffness. No rhythm in pain or stiffness was observed in subjects with fibromyalgia. Conclusions: We conclude that collection of subjective data using electronic diary in rheumatologic setting is a feasible method than can be adopted with high compliance rates across a range of patient demographic subgroups. The identification of diurnal cycles of self-reported pain and stiffness, using EMA method, has important implications for patients with respect to planning their daily activities and in developing individual therapeutic programs with respect to diurnal variability, which therefore may be more effective

The influence of soft acidic drinks in exposing dentinal tubules after non-surgical periodontal treatment: : a SEM investigation on the protective effects of oxalate-containing phytocomplex

Objective: The aim of this study was to investigate the different smear layer morphologies produced by instrumentation with a hand curette and a periodontal sonic scaler for potential removal by soft acidic solution. The effect of a new oxalate-containing phytocomplex spray in preventing tubules exposure after citric acid solution application was also evaluated. Methods: Thirty recently extracted human teeth were used to obtain root dentinal fragments and divided in two groups: Curette treatment (CRT) root planed applying 30 working strokes to each surface using a Gracey?s curette 5-6 and Ultrasonic scaler (USC) treated using a periodontal scaler mounted on an ultrasonic hand-piece for 30 seconds. Each principal group was further divided in three sub-groups (Control, Acid challenge and Acid/Phyto-oxalate). The control group samples were immersed in distilled water buffered to pH 7.4 using NH4 OH solution. The samples of the acid challenge group were immersed in a solution of citric acid 0,02M; [pH 2.5] for 3 minutes. The samples of the Acid/Phyto-oxalate group were sprayed for 15 sec with a 1.5% phytocomplex spray prior to immersion. Samples were examined using SEM. Results: Ultrasonic instrumentation created a very thin smear layer whereas curettes produced a multilayered smear layer. The acidic solution was able to remove the smear layer from root surfaces treated with ultrasonic instrumentation exposing the dentinal tubules. The smear layer on the root surfaces treated with hand instruments was not completely removed. The phytocomplex solution was able to prevent dentinal tubule exposure. Conclusions: Acidic soft drinks are able to remove the smear layer created on root surfaces during different non-surgical periodontally treatments. The smear plugs created by hand instrumentation appeared to be more resistant to acid attack. The tested phytocomplex solution protected the dentine from demineralization and it might prevent post-treatment dentinal hypersensitivity induced by acidic soft drinks

Assessment of Genetic Diversity of Seagrass Populations Using DNA Fingerprinting: Implications for Population Stability and Management

Populations of the temperate seagrass, Zostera marina L. (eelgrass), often exist as discontinuous beds in estuaries, harbors, and bays where they can reproduce sexually or vegetatively through clonal propagation. We examined the genetic structure of three geographically and morphologically distinct populations from central California (Elkhorn Slough, Tomales Bay, and Del Monte Beach), using multilocus restriction fragment length polymorphisms (DNA fingerprints). Within-population genetic similarity (Sw) values for the three eelgrass populations ranged from 0.44 to 0.68. The Tomales Bay population located in an undisturbed, littoral site possessed a within-population genetic similarity (Sw = 0.44) that was significantly lower than those of the other two populations. Cluster analysis identified genetic substructure in only the undisturbed subtidal population (Del Monte Beach). Between-population similarity values Sb for all pairwise comparisons ranged from 0.47 to 0.51. The three eelgrass populations show significantly less between locale genetic similarity than found within populations, indicating that gene flow is restricted between locales even though two of the populations are separated by only 30 km. The study demonstrates that (i) natural populations of Z. marina from both disturbed and undisturbed habitats possess high genetic diversity and are not primarily clonal, (ii) gene flow is restricted even between populations in dose proximity, (iii) an intertidal population from a highly disturbed habitat shows much lower genetic diversity than an intertidal population from an undisturbed site, and (iv) DNA fingerprinting techniques can be exploited to understand gene flow and population genetic structure in Z. marina, a widespread and ecologically important species, and as such are relevant to the management of this coastal resource

The genome of the seagrass <i>Zostera marina</i> reveals angiosperm adaptation to the sea

Seagrasses colonized the sea on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet. Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes, genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae and that is important for ion homoeostasis, nutrient uptake and O2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming, to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants