The MoVIN server for the analysis of protein interaction networks

<p>Abstract</p> <p>Background</p> <p>Protein-protein interactions are at the basis of most cellular processes and crucial for many bio-technological applications. During the last few years the development of high-throughput technologies has produced several large-scale protein-protein interaction data sets for various organisms. It is important to develop tools for dissecting their content and analyse the information they embed by data-integration and computational methods.</p> <p>Results</p> <p>Interactions can be mediated by the presence of specific features, such as motifs, surface patches and domains. The co-occurrence of these features on proteins interacting with the same protein can indicate mutually exclusive interactions and, therefore, can be used for inferring the involvement of the proteins in common biological processes.</p> <p>We present here a publicly available server that allows the user to investigate protein interaction data in light of other biological information, such as their sequences, presence of specific domains, process and component ontologies. The server can be effectively used to construct a high-confidence set of mutually exclusive interactions by identifying similar features in groups of proteins sharing a common interaction partner. As an example, we describe here the identification of common motifs, function, cellular localization and domains in different datasets of yeast interactions.</p> <p>Conclusions</p> <p>The server can be used to analyse user-supplied datasets, it contains pre-processed data for four yeast Protein Protein interaction datasets and the results of their statistical analysis. These show that the presence of common motifs in proteins interacting with the same partner is a valuable source of information, it can be used to investigate the properties of the interacting proteins and provides information that can be effectively integrated with other sources. As more experimental interaction data become available, this tool will become more and more useful to gain a more detailed picture of the interactome.</p

Association between Mediterranean diet and hand grip strength in older adult women

BACKGROUND & AIMS: Mediterranean Diet (MD) is an eating pattern associated with multiple healthy benefits, including the conservation of skeletal muscle. Frailty is a major geriatric syndrome characterized by low muscle strength. The Hand Grip Strength (HGS) is the most frequently used indicator of muscle functional capacity for clinical purposes. The association between the adherence to the MD and HGS in elderly has not yet fully investigated. The goal of this study was to examine the association between the adherence to the MD and HGS in a not hospitalized elderly who participated in the project PERsonalised ict Supported Services for Independent Living and Active Ageing (PERSSILAA). METHODS: Eighty-four elderly women were consecutively enrolled (aged 60-85 years) in this cross-sectional observational study. Anthropometric measures were evaluated. A validated 14-item questionnaire PREDIMED (PREvención con DIeta MEDiterránea) was used for the assessment of adherence to the MD. Dietary data were collected by a 7-day food records. Muscle strength was measured by HGS using a grip strength dynamometer (KERN & SOHN GmbH). RESULTS: The majority of participants were overweight (46.4%). An average adherence to the MD was found in 52.4% of participants, while the minority of them showed a low adherence (21.4%). HGS > cut-point of 20 kg were found in 43 subjects (51.2%). According to the adherence to MD, 39% participants with HGS values higher than cut-point presented a high adherence score compared with 14% of those with lower values of HGS (p = 0.018). The participants with HGS > cut-point presented significantly higher PREDIMED score than those with HGS < cut-point (p < 0.001). Based on ROC curves, the most sensitive and specific cut-point for the PREDIMED score to predict HGS categories was ≥8. No evident correlations were observed between HGS and age, while HGS was negatively correlated with hip circumference (r = -0.233, p = 0.033) and BMI (r = -0.219, p = 0.045), and positively correlated with PREDIMED score (r = 0.598, p < 0.001). At binomial logistic regression analysis almost all 14-items of PREDIMED questionnaire were significantly associated with HGS adjusted for BMI. At multinomial logistic regression analysis to assess the association of the three classes of adherence to the MD with the HGS, after adjusting for BMI the lowest adherence to MD was associated with the lowest Odds Ratio of HGS (p < 0.001). CONCLUSIONS: This study evidenced a positive association between the adherence to the MD and muscle strength in a sample of active elderly women, stratified according to the HGS > cut-point of 20 kg. Our study highlights the usefulness of the developing health services to detect and prevent age-associated decline in physical performance in elderly subjects by addressing nutritional and physical intervention

Italian Version of the Pittsburgh Rehabilitation Participation Scale: Psychometric Analysis of Validity and Reliability

Patient’s active participation in therapy is a key component of successful rehabilitation. In fact, low participation has been shown to be a prognostic factor of poor outcome; however, participation is rarely assessed in clinical settings. The Pittsburgh Rehabilitation Participation Scale (PRPS) is a validated, quick, and accurate measure of participation, relying on clinicians’ observation, and not requiring any self-report by patients. The aim of this study was to validate an Italian version of the PRPS. Following forward and back-translation of PRPS into Italian, the translated version was validated in a total of 640 therapy sessions, related to a cohort of 32 patients admitted to an Italian hospital. It was tested for concurrent validity, finding significant correlations with Barthel Index (R &gt; 0.58, p &lt; 0.001) and SF-36 Physical and Mental Health (R &gt; 0.4, p &lt; 0.02), for predictive validity, finding significant correlation with the effectiveness of rehabilitation (R = 0.358, p = 0.045), and for inter-rater and intra-rater reliability, computing an Intra-class correlation coefficient (ICC = 0.926 and 0.756, respectively). These psychometric properties results were similar to those of the original version of this scale. The proposed PRPS can be helpful for Italian clinicians in the assessment of patient’s participation during rehabilitation

Modern Feynman Diagrammatic One-Loop Calculations

In this talk we present techniques for calculating one-loop amplitudes for multi-leg processes using Feynman diagrammatic methods in a semi-algebraic context. Our approach combines the advantages of the different methods allowing for a fast evaluation of the amplitude while monitoring the numerical stability of the calculation. In phase space regions close to singular kinematics we use a method avoiding spurious Gram determinants in the calculation. As an application of our approach we report on the status of the calculation of the amplitude for the process $pp\to b\bar{b}b\bar{b}+X$.Comment: 10 pages, 2 figures; contribution to the proceedings of the CPP2010 Workshop, 23-25 Sep. 2010, KEK, Tsukuba, Japa

Tracing and tracking epiallele families in complex DNA populations

DNA methylation is a stable epigenetic modification, extremely polymorphic and driven by stochastic and deterministic events. Most of the current techniques used to analyse methylated sequences identify methylated cytosines (mCpGs) at a single-nucleotide level and compute the average methylation of CpGs in the population of molecules. Stable epialleles, i.e. CpG strings with the same DNA sequence containing a discrete linear succession of phased methylated/non-methylated CpGs in the same DNA molecule, cannot be identified due to the heterogeneity of the 5′–3′ ends of the molecules. Moreover, these are diluted by random unstable methylated CpGs and escape detection. We present here MethCoresProfiler, an R-based tool that provides a simple method to extract and identify combinations of methylated phased CpGs shared by all components of epiallele families in complex DNA populations. The methylated cores are stable over time, evolve by acquiring or losing new methyl sites and, ultimately, display high information content and low stochasticity. We have validated this method by identifying and tracing rare epialleles and their families in synthetic or in vivo complex cell populations derived from mouse brain areas and cells during postnatal differentiation

Efficacy of overground robotic gait training on balance in stroke survivors: a systematic review and meta-analysis

Strokes often lead to a deficit in motor control that contributes to a reduced balance function. Impairments in the balance function severely limit the activities of daily living (ADL) in stroke survivors. The present systematic review and meta-analysis primarily aims to explore the efficacy of overground robot-assisted gait training (o-RAGT) on balance recovery in individuals with stroke. In addition, the efficacy on ADL is also investigated. This systematic review identified nine articles investigating the effects of o-RAGT on balance, four of which also assessed ADL. The results of the meta-analysis suggest that o-RAGT does not increase balance and ADL outcomes more than conventional therapy in individuals after stroke. The data should not be overestimated due to the low number of studies included in the meta-analysis and the wide confidence intervals. Subgroup analyses to investigate the influence of participant's characteristics and training dosage were not performed due to lack of data availability. Further well-designed randomized controlled trials are needed to investigate the efficacy of o-RAGT on balance in individuals with stroke

High-coverage methylation data of a gene model before and after DNA damage and homologous repair

Genome-wide methylation analysis is limited by its low coverage and the inability to detect single variants below 10%. Quantitative analysis provides accurate information on the extent of methylation of single CpG dinucleotide, but it does not measure the actual polymorphism of the methylation profiles of single molecules. To understand the polymorphism of DNA methylation and to decode the methylation signatures before and after DNA damage and repair, we have deep sequenced in bisulfite-treated DNA a reporter gene undergoing site-specific DNA damage and homologous repair. In this paper, we provide information on the data generation, the rationale for the experiments and the type of assays used, such as cytofluorimetry and immunoblot data derived during a previous work published in Scientific Reports, describing the methylation and expression changes of a model gene (GFP) before and after formation of a double-strand break and repair by homologous-recombination or non-homologous-end-joining. These data provide: 1) a reference for the analysis of methylation polymorphism at selected loci in complex cell populations; 2) a platform and the tools to compare transcription and methylation profiles

Diketo acid inhibitors of nsp13 of SARS-CoV-2 block viral replication

For RNA viruses, RNA helicases have long been recognized to play critical roles during virus replication cycles, facilitating proper folding and replication of viral RNAs, therefore representing an ideal target for drug discovery. SARS-CoV-2 helicase, the non-structural protein 13 (nsp13) is a highly conserved protein among all known coronaviruses, and, at the moment, is one of the most explored viral targets to identify new possible antiviral agents. In the present study, we present six diketo acids (DKAs) as nsp13 inhibitors able to block both SARS-CoV-2 nsp13 enzymatic functions. Among them four compounds were able to inhibit viral replication in the low micromolar range, being active also on other human coronaviruses such as HCoV229E and MERS CoV. The experimental investigation of the binding mode revealed ATP-non-competitive kinetics of inhibition, not affected by substrate-displacement effect, suggesting an allosteric binding mode that was further supported by molecular modelling calculations predicting the binding into an allosteric conserved site located in the RecA2 domain

Targeted DNA oxidation by LSD1–SMAD2/3 primes TGF-β1/ EMT genes for activation or repression

Abstract The epithelial-to-mesenchymal transition (EMT) is a complex transcriptional program induced by transforming growth factor β1 (TGF-β1). Histone lysine-specific demethylase 1 (LSD1) has been recognized as a key mediator of EMT in cancer cells, but the precise mechanism that underlies the activation and repression of EMT genes still remains elusive. Here, we characterized the early events induced by TGF-β1 during EMT initiation and establishment. TGF-β1 triggered, 30–90 min post-treatment, a nuclear oxidative wave throughout the genome, documented by confocal microscopy and mass spectrometry, mediated by LSD1. LSD1 was recruited with phosphorylated SMAD2/3 to the promoters of prototypic genes activated and repressed by TGF-β1. After 90 min, phospho-SMAD2/3 downregulation reduced the complex and LSD1 was then recruited with the newly synthesized SNAI1 and repressors, NCoR1 and HDAC3, to the promoters of TGF-β1-repressed genes such as the Wnt soluble inhibitor factor 1 gene (WIF1), a change that induced a late oxidative burst. However, TGF-β1 early (90 min) repression of transcription also required synchronous signaling by reactive oxygen species and the stress-activated kinase c-Jun N-terminal kinase. These data elucidate the early events elicited by TGF-β1 and the priming role of DNA oxidation that marks TGF-β1-induced and -repressed genes involved in the EMT

Clinical outcomes of a digitally supported approach for self-management of type 2 diabetes mellitus

BackgroundSelf-management of Type 2 diabetes mellitus (T2D) is challenging. Regular self-monitoring of blood glucose and healthy lifestyles are required to improve glycometabolic control, thus delaying diabetes complications, and reducing hospitalizations. Digital technologies can empower patients in their disease management promoting self-management and motivation to change behaviors. We report the results of an exploratory trial aimed at evaluating the metabolic outcomes of using digital solutions for T2D self-management developed in the ProEmpower project, a European Commission funded Pre-Commercial Procurement.MethodsTwo digital solutions, DM4All and DiaWatch, which were codesigned with providers, patients, and caregivers, enabled the collection of clinical parameters by the patient using a smartphone integrated with the medical devices (glucometer, sphygmomanometer, scale, smart watch for heart rate monitoring and step counter). Data were automatically sent to the shared care plan allowing professionals to monitor adherence to treatment, set goals, and communicate more effectively with patients. At baseline and after an average follow-up of 8 months, glycosylated hemoglobin (HbA1c), body weight, blood pressure, and blood lipids were measured in 100 T2D patients using the ProEmpower solutions across different diabetes centers in Campania Region, age 45–79  years, both genders, and compared with a Control cohort of T2D patients (n = 100) with similar clinical characteristics and followed for a comparable period of observation in the same centers.ResultsAt baseline, the ProEmpower participants and the Control subjects were on average overweight, with a similar BMI in the two cohorts, and mean HbA1c was at acceptable levels (around 7.0%). After the 8 month exploratory trial, body weight, HbA1c, systolic and diastolic blood pressure, and plasma and LDL-cholesterol significantly decreased in the ProEmpower participants compared to baseline (p &lt; 0.05 for all). The changes in systolic and diastolic blood pressure, and plasma and LDL-cholesterol were significantly different from those observed in the Control cohort (p &lt; 0.05 for all).ConclusionThis pilot study showed positive effects on metabolic outcomes relevant to cardiovascular risk in T2D of adopting digital telemedicine self-monitoring solutions based on automation of measurements and coaching on healthy lifestyles promotion