Dissecting the Specificity of Protein-Protein Interaction in Bacterial Two-Component Signaling: Orphans and Crosstalks

Predictive understanding of the myriads of signal transduction pathways in a cell is an outstanding challenge of systems biology. Such pathways are primarily mediated by specific but transient protein-protein interactions, which are difficult to study experimentally. In this study, we dissect the specificity of protein-protein interactions governing two-component signaling (TCS) systems ubiquitously used in bacteria. Exploiting the large number of sequenced bacterial genomes and an operon structure which packages many pairs of interacting TCS proteins together, we developed a computational approach to extract a molecular interaction code capturing the preferences of a small but critical number of directly interacting residue pairs. This code is found to reflect physical interaction mechanisms, with the strongest signal coming from charged amino acids. It is used to predict the specificity of TCS interaction: Our results compare favorably to most available experimental results, including the prediction of 7 (out of 8 known) interaction partners of orphan signaling proteins in Caulobacter crescentus. Surveying among the available bacterial genomes, our results suggest 15~25% of the TCS proteins could participate in out-of-operon "crosstalks". Additionally, we predict clusters of crosstalking candidates, expanding from the anecdotally known examples in model organisms. The tools and results presented here can be used to guide experimental studies towards a system-level understanding of two-component signaling.Comment: Supplementary information available on http://www.plosone.org/article/info:doi/10.1371/journal.pone.001972

A glimpse at the flat-spacetime limit of quantum gravity using the Bekenstein argument in reverse

An insightful argument for a linear relation between the entropy and the area of a black hole was given by Bekenstein using only the energy-momentum dispersion relation, the uncertainty principle, and some properties of classical black holes. Recent analyses within String Theory and Loop Quantum Gravity describe black-hole entropy in terms of a dominant contribution, which indeed depends linearly on the area, and a leading log-area correction. We argue that, by reversing the Bekenstein argument, the log-area correction can provide insight on the energy-momentum dispersion relation and the uncertainty principle of a quantum-gravity theory. As examples we consider the energy-momentum dispersion relations that recently emerged in the Loop Quantum Gravity literature and the Generalized Uncertainty Principle that is expected to hold in String Theory.Comment: 7 pages, LaTex; this essay received an "honorable mention" in the 2004 Essay Competition of the Gravity Research Foundation; submitted to IJMPD on 23 June 2004; published as Int.J.Mod.Phys.D13:2337-2343,200

Epoxy-silica/clay nanocomposite for silver-based antibacterial thin coatings: Synthesis and structural characterization

Development of new functional coatings in the field of health care, as antibacterial applications, deals with a straight control of the diffusive properties that rules the releasing of the active component. In this work, the development of a silver-rich nanocomposite thin coating, loaded with organically modified clay nanoparticles, is presented. The synthesis process included an environment-friendly silanization process of clay nanoparticles (Laponite® S482) with (3-glycidoxypropyl)trimethoxysilane (GPTMS) and the further hydrolytic condensation with tetraethoxysilane (TEOS). Silanization process and the obtained coatings were analysed by Fourier transformed infrared spectroscopy, UV–visible spectroscopy, X-ray diffraction, thermogravimetric curves and scanning electron microscopy. The silanization process of clay nanoparticles with the organically reactive alkyl alkoxysilane, allowed to stabilize and exfoliate the clay nanosheets within a hybrid organic-inorganic sol-gel material. Ring opening of grafted epoxy groups carried to an increasing of the basal spacing, of intercalated clay nanosheets, from 1.3 to 1.8 nm. Moreover, incorporation of organically modified clay nanosheets introduced a significant stabilization on the development of silver nanoparticles inside the structure of the nanocomposite coating, retaining the silver inside the coating material and restricting the growing of silver nanoparticles on the surface of the coating. Antibacterial behaviour, against E. coli cultures, performed through agar diffusion tests, provided promising results that allow assuming that the studied nanocomposite coating serves as a reservoir of ionic silver, permitting the antibacterial effect.Fil: Giraldo Mejía, Hugo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Yohai del Cerro, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Pedetta, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Herrera Seitz, Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Procaccini, Raul Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Pellice, Sergio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin

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

Connected Insurance Reshaping the Health Insurance Industry

The role of today’s insurer is changing toward a more preventive and digital or connected approach. In this context, connected health insurance has the potential to contribute toward the health and the general well-being of the population. New technologies like e-health and wearables employed by the insurance industry might even help deal with major issues related to the rising number of people, of chronic disease patients, and of elders while keeping them healthier and at the same time protected by insurance. The aim of this chapter is to briefly illustrate the concept of “connected insurance” with specific focus on “connected health” and “wearables” and to present two case studies: Discovery’s Vitality program which aims to create healthier lifestyles for its customers through the use of wearables and rewards and ICS Maugeri’s MOSAIC project based on AI and predictive models aimed at helping with the management of treatment and quality of life in type 2 diabetes patients

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

An Overview on Current Non-invasive Diagnostic Devices in Oral Oncology

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, and despite advances in cancer therapies, the overall 5-year survival rate has remained below 50% over the past decades. OSCC is typically preceded by potentially malignant disorders (PMD), but distinguishing high-risk from low-risk PMD is challenging. In the last years, several diagnostic methods as light-based detection systems (LBDS) have been proposed to facilitate the detection of OSCC and PMD. Furthermore, the recent evolution of nanotechnology may provide new opportunities to detect PMD and OSCC at an early stage. Indeed, several preclinical studies showed the potential of nanotechnology to enhance diagnostic accuracy. For these reasons, it is fundamental to conduct studies to evaluate the efficacy of nanotechnology implementation in LBDS. The aim of this article is to review the current literature on LBDS and to provide a summary of the sensitivity and specificity of each technique, and possible future applications of nanotechnologies. The LBDS showed great potential for screening and monitoring oral lesions, but there are several factors that hinder an extensive use of these devices. These devices seem to be useful in assessing lesion margins that must be biopsied. However, to date, conventional oral examination, and tissue biopsy remain the gold standard for OSCC diagnosis. The use of nanotechnologies could be the next step in the evolution of LBDS, thus providing devices that can help clinicians to detect and better monitor oral lesions

Severe constraints on the loop-quantum-gravity energy-momentum dispersion relation from the black-hole area-entropy law

We explore a possible connection between two aspects of Loop Quantum Gravity which have been extensively studied in the recent literature: the black-hole area-entropy law and the energy-momentum dispersion relation. We observe that the original Bekenstein argument for the area-entropy law implicitly requires information on the energy-momentum dispersion relation. Recent results show that in first approximation black-hole entropy in Loop Quantum Gravity depends linearly on the area, with small correction terms which have logarithmic or inverse-power dependence on the area. Preliminary studies of the Loop-Quantum-Gravity dispersion relation reported some evidence of the presence of terms that depend linearly on the Planck length, but we observe that this possibility is excluded since it would require, for consistency, a contribution to black-hole entropy going like the square root of the area