The surface accessibility of α-bungarotoxin monitored by a novel paramagnetic probe

The surface accessibility of {alpha}-bungarotoxin has been investigated by using Gd2L7, a newly designed paramagnetic NMR probe. Signal attenuations induced by Gd2L7 on {alpha}-bungarotoxin C{alpha}H peaks of 1H-13C HSQC spectra have been analyzed and compared with the ones previously obtained in the presence of GdDTPA-BMA. In spite of the different molecular size and shape, for the two probes a common pathway of approach to the {alpha}-bungarotoxin surface can be observed with an equally enhanced access of both GdDTPA-BMA and Gd2L7 towards the protein surface side where the binding site is located. Molecular dynamics simulations suggest that protein backbone flexibility and surface hydration contribute to the observed preferential approach of both gadolinium complexes specifically to the part of the {alpha}-bungarotoxin surface which is involved in the interaction with its physiological target, the nicotinic acetylcholine receptor

Thermodynamic scaling of vibrational dynamics and relaxation

We investigate by thorough molecular dynamics simulations the thermodynamic scaling (TS) of a polymer melt. Two distinct models, with strong and weak virial-energy correlations, are considered. Both evidence the joint TS with the same characteristic exponent γts of the fast mobility - the mean square amplitude of the picosecond rattling motion inside the cage - and the much slower structural relaxation and chain reorientation. If the cage effect is appreciable, the TS master curves of the fast mobility are nearly linear, grouping in a bundle of approximately concurrent lines for different fragilities. An expression of the TS master curve of the structural relaxation with one adjustable parameter less than the available three-parameter alternatives is derived. The novel expression fits well with the experimental TS master curves of thirty-four glassformers and, in particular, their slope at the glass transition, i.e., the isochoric fragility. For the glassformer OTP, the isochoric fragility allows to satisfactorily predict the TS master curve of the fast mobility with no adjustments

Filosofia di Berlusconi: l'essere e il nulla nell'Italia del Cavaliere

La filosofia, diceva Hegel, \ue8 come la nottola di Minerva, che "spicca il volo sul far della sera", ossia inizia a prendere la parola sugli eventi solo quando sono compiuti e si avviano verso il declino. Lo scenario da basso impero del crepuscolo del berlusconismo \ue8 quindi il momento giusto per fare i conti con un fenomeno che \ue8 stato la cifra dominante dell'ultimo ventennio di storia italiana, ma la cui rilevanza va ben oltre il ristretto panorama delle vicende nostrane. Per comprendere ci\uf2 che all'apparenza risulta incomprensibile non bastano le analisi di tipo sociologico, semiologico o politologico, che pure in queste anni non sono mancate, ma sono necessari altri strumenti per individuare la logica, la narrativa, la fisica e la metafisica che hanno reso possibile la drammatica trasformazione della nostra quotidianit\ue0 in un perverso intreccio di menzogne, barzellette, millanterie e volgarit\ue0, sullo sfondo di una sistematica, sprezzante opera di demolizione e privatizzazione delle istituzioni

“A long-term mortality analysis of subsidized firms in rural areas: an empirical study in the Portuguese Alentejo region”

Studies have demonstrated that public policies to support private firms’ investment have the ability to promote entrepreneurship, but the sustainability of subsidized firms has not often been analysed. This paper aims to examine this dimension specifically through evaluating the mortality of subsidized firms in the long-term. The analysis focuses on a case study of the LEADER+ Programme in the Alentejo region of Portugal. With this purpose, the paper examines the activity status (active or not active) of 154 private, rural, for-profit firms in Alentejo that had received a subsidy to support investment between 2002 and 2008 under the LEADER+ Programme. The methodology is based on binary choice models in order to study the probability of these firms still being active. The explanatory variables used are the following: (1) the characteristics of entrepreneurs and managers’ strategic decisions, (2) firm profile and characteristics, (3) regional economic environment. Data assessment showed that the cumulative mortality rate of firms on 31st December 2013 is over 20 %. Interpretation of the regression model revealed that he probability of firms’ survival increases with higher investment, firm age and regional business concentration, whereas the number of applications made by firms has a negative impact on their survival. So it seems that for subsidized firms the amount of investment is as important as its frequency

The CHOLEGAS study: multicentric randomized, blinded, controlled trial of gastrectomy plus prophylactic cholecystectomy versus gastrectomy only, in adults submitted to Gastric cancer surgery with curative intent

<p>Abstract</p> <p>Background</p> <p>The incidence of gallstones and gallbladder sludge is known to be higher in patients after gastrectomy than in general population. This higher incidence is probably related to surgical dissection of the vagus nerve branches and the anatomical gastrointestinal reconstruction. Therefore, some surgeons perform routine concomitant cholecystectomy during standard surgery for gastric malignancies. However, not all the patients who are diagnosed to have cholelithiasis after gastric cancer surgery will develop symptoms or require additional surgical treatments and a standard laparoscopic cholecystectomy is feasible even in those patients who underwent previous gastric surgery. At the present, no randomized study has been published and the decision of gallbladder management is left to each surgeon preference.</p> <p>Design</p> <p>The study is a randomized controlled investigation. The study will be performed in the General and Oncologic Surgery, Department of Oncology – Azienda Ospedaliero-Universitaria Careggi – Florence – Italy, a large teaching institution, with the participation of all surgeons who accept to be involved in, together with other Italian Surgical Centers, on behalf of the GIRCG (Italian Research Group for Gastric Cancer).</p> <p>The patients will be randomized into two groups: in the first group the patient will be submitted to prophylactic cholecystectomy during standard surgery for curable gastric cancer (subtotal or total gastrectomy), while in the second group he/she will be submitted to standard gastric surgery only.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID. NCT00757640</p

Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic changes associated with dietary amino acid supplementation in dairy calves

The effects of different amino acid (AA) supplementations of milk protein-based milk replacers in pre-ruminant calves from 3 days to 7 weeks of age were studied. Animals were divided into 4 groups: Ctrl) Control group fed with milk protein-based milk replacer without supplementation; GP) supplementation with 0.1% glycine and 0.3% proline; FY) supplementation with 0.2% phenylalanine and 0.2% tyrosine; MKT) supplementation with 0.62% lysine, 0.22% methionine and 0.61% threonine. For statistical analysis, t-test was used to compare AA-supplemented animals to the Ctrl group. At week 7, body weight and average daily gain (ADG) were measured and blood samples and skeletal muscle biopsies were taken. Blood biochemistry analytes related to energy metabolism were determined and it was shown that MKT group had higher serum creatinine and higher plasma concentration of three supplemented AAs as well as arginine compared with the Ctrl group. GP group had similar glycine/proline plasma concentration compared with the other groups while in FY group only plasma phenylalanine concentration was higher compared with Control. Although the AA supplementations in the GP and FY groups did not affect average daily gain and metabolic health profile from serum, the metabolome analysis from skeletal muscle biopsy revealed several differences between the GP-FY groups and the Ctrl-MKT groups, suggesting a metabolic adaptation especially in GP and FY groupsinfo:eu-repo/semantics/publishedVersio

Double-check: validation of diagnostic statistics for PLS-DA models in metabolomics studies

Partial Least Squares-Discriminant Analysis (PLS-DA) is a PLS regression method with a special binary ‘dummy’ y-variable and it is commonly used for classification purposes and biomarker selection in metabolomics studies. Several statistical approaches are currently in use to validate outcomes of PLS-DA analyses e.g. double cross validation procedures or permutation testing. However, there is a great inconsistency in the optimization and the assessment of performance of PLS-DA models due to many different diagnostic statistics currently employed in metabolomics data analyses. In this paper, properties of four diagnostic statistics of PLS-DA, namely the number of misclassifications (NMC), the Area Under the Receiver Operating Characteristic (AUROC), Q2 and Discriminant Q2 (DQ2) are discussed. All four diagnostic statistics are used in the optimization and the performance assessment of PLS-DA models of three different-size metabolomics data sets obtained with two different types of analytical platforms and with different levels of known differences between two groups: control and case groups. Statistical significance of obtained PLS-DA models was evaluated with permutation testing. PLS-DA models obtained with NMC and AUROC are more powerful in detecting very small differences between groups than models obtained with Q2 and Discriminant Q2 (DQ2). Reproducibility of obtained PLS-DA models outcomes, models complexity and permutation test distributions are also investigated to explain this phenomenon. DQ2 and Q2 (in contrary to NMC and AUROC) prefer PLS-DA models with lower complexity and require higher number of permutation tests and submodels to accurately estimate statistical significance of the model performance. NMC and AUROC seem more efficient and more reliable diagnostic statistics and should be recommended in two group discrimination metabolomic studies

Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies

The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in ‘omics’ technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the “Nutritional Phenotype database” (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different—omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed—omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and—omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance) will be directed towards a sustainable and federated infrastructure