Functional Information, Biomolecular Messages and Complexity of BioSequences and Structures

In the quest for a mathematical measure able to capture and shed light on the dual notions of information and complexity in biosequences, Hazen et al. have introduced the notion of Functional Information (FI for short). It is also the result of earlier considerations and findings by Szostak and Carothers et al. Based on the experiments by Charoters et al., regarding FI in RNA binding activities, we decided to study the relation existing between FI and classic measures of complexity applied on protein-DNA interactions on a genome-wide scale. Using classic complexity measures, i.e, Shannon entropy and Kolmogorov Complexity as both estimated by data compression, we found that FI applied to protein-DNA interactions is genuinely different from them. Such a fact, together with the non-triviality of the biological function considered, contributes to the establishment of FI as a novel and useful measure of biocomplexity. Remarkably, we also found a relationship, on a genome-wide scale, between the redundancy of a genomic region and its ability to interact with a protein. This latter finding justifies even more some principles for the design of motif discovery algorithms. Finally, our experiments bring to light methodological limitations of Linguistic Complexity measures, i.e., a class of measures that is a function of the vocabulary richness of a sequence. Indeed, due to the technology and associated statistical preprocessing procedures used to conduct our studies, i.e., genome-wide ChIP-chip experiments, that class of measures cannot give any statistically significant indication about complexity and function. A serious limitation due to the widespread use of the technology. References J.M. Carothers, S.C. Oestreich, J.H. Davis, and J.W. Szostack. Informational complexity and functional activity of RNA structures. J. AM. CHEM. SOC., 126 (2004), pp. 5130-5137. R.M. Hazen, P.L. Griffin, J.M. Carothers, and J.W. Szostak. Functional Information and the emergence of biocomplexity. Proc. of Nat. Acad. Sci, 104 (2007), pp. 8574-8581. J.W. Szostak. Functional Information: molecular messages, Nature, 423 (2003)

Road tunnel risk-based safety design methodology by GU@LARP Quantum risk model

The ALARP concept is used in different countries for different sectors of activity where a risk assessment or measure is requested. In this paper a model is developed based upon ALARP principle for tunnel risk-based design in case of fire accident scenarios. In Italy, ALARP risk acceptability and tolerability criteria have been adopted then the compliance with them has to be verified in order to guarantee a minimum-sufficient level of safety. The quantum of risk coupled with any design scenario is defined and modelled and the consequent individual quantum of risk coupled with the single exposed unit in the scenario is defined too. The methodologies for the identification of the requested design scenario, in number and type, are outlined. The scenarios are described in a shape suitable as INPUTS in the thermo-dynamical numerical simulations for fire generation and exposed units evacuation. The expected OUTPUTS of the numerical simulation are the estimations of the number of the fatalities (N) coupled with the single specific scenarios. In parallel with the above physical deterministic scenario simulations, a conceptual and operational procedure has been also established for the scenarios probabilities assessment. Merging the resulting data of both the above separate models, the risk quanta Gu@larp model is finally established. A case study is developed considering scenarios related to a virtual limit tunnel to support the description of the model itself, properties, advantages and perspectives

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments

Fusing Acoustic Ranges and Inertial Measurements in AUV Navigation: the Typhoon AUV at CommsNet13 Sea Trial

The paper presents some experimental results of autonomous underwater navigation, based on the fusion of acoustic and inertial measurements. The work is in the framework of the Thesaurus project, funded by the Tuscany Region, aiming at developing techniques for systematic exploration of marine areas of archaeological interest through a team of Autonomous Underwater Vehicles (AUVs). The test was carried out with one Typhoon vehicle, a 300m depth rated AUV with acoustic communication capabilities, during the CommsNet13 experiment, organized and scientifically coordinated by the NATO S&T Org. Ctr. for Maritime Research and Experimentation (CMRE, formerly NURC), with the participation of several research institutions. The fusion algorithm is formally casted into an optimal stochastic filtering problem, where the rough estimation of the vehicle position, velocity and attitude, are refined by using the depth measurement, the relative measurements available on the acoustic channel and the vehicle surge speed

YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation

The Yes-associated protein YAP, one of the major effectors of the Hippo pathway together with its related protein TAZ, mediates a range of cellular processes from proliferation and death to morphogenesis. YAP and TAZ regulate a large number of target genes, acting as co-activators of DNA-binding transcription factors or as negative regulators of transcription by interacting with the nucleosome remodeling and histone deacetylase complexes. YAP is expressed in self-renewing embryonic stem cells (ESCs), although it is still debated whether it plays any crucial roles in the control of either stemness or differentiation. Here we show that the transient downregulation of YAP in mouse ESCs perturbs cellular homeostasis, leading to the inability to differentiate properly. Bisulfite genomic sequencing revealed that this transient knockdown caused a genome-wide alteration of the DNA methylation remodeling that takes place during the early steps of differentiation, suggesting that the phenotype we observed might be due to the dysregulation of some of the mechanisms involved in regulation of ESC exit from pluripotency. By gene expression analysis we identified two molecules which could have a role in the altered genome-wide methylation profile: the long non-coding RNA Ephemeron, whose rapid upregulation is crucial for ESCs transition into epiblast, and the methyltransferase-like protein Dnmt3l, which, during the embryo development, cooperates with Dnmt3a and Dnmt3b to contribute to the de novo DNA methylation that governs early steps of ESC differentiation. These data suggest a new role for YAP in the governance of the epigenetic dynamics of exit from pluripotency

First report of Stephanostomum cesticillus (Molin, 1858) Looss, 1899 in Merluccius merluccius (Linnaeus, 1758) from the Tyrrhenian Sea (Southern Italy)

The genus Stephanostomum consists of digenean trematodes found in many marine teleosts. In this study, Stephanostomum cesticillus (Molin, 1858) Looss, 1899 metacercariae were identified in European hake (Merluccius merluccius, Linnaeus, 1758) caught in the Tyrrhenian Sea. The metacercariae were found encapsulated in the muscle, close to the spine and gills. Out of 131 specimens, 111 (P = 84.7%, mI = 25.1 mA = 21.3) were infected by digenean trematode metacercariae. Morphological and histological evaluations were carried out. The members of this genus are characterised by a double crown of spines close to the oral sucker. For identification of the parasite, molecular analysis was performed via 28S and 18S ribosomal DNA (rDNA) genes. Partial rDNA sequences of Stephanostomum highly matched to S. cesticillus for the percentage of similar identity from the nucleotide database of BLAST. The present survey reports the presence of S. cesticillus metacercariae in M. merluccius for the first time. Our results improve current knowledge on hake parasites to better understand the distribution of S. cesticillus in M. merluccius caught in the Mediterranean Sea and shed light on the life cycle of the parasite adding other possible hosts