Data from docking simulations to develop an efficient strategy able to evaluate the interactions between RAGE and MDA-induced albumin adducts

This data article contains the results of docking simulations performed in order to develop a suitable in silico strategy able to assess the stability of the putative complexes between RAGE and MDA induced adducts on human albumin as experimentally determined doi: 10.1016/j.redox.2016.12.017, (Degani et al., 2017) [1]. The docking simulations involved different approaches to give a simplified yet realistic representation of the protein adducts and their environment. With increasing complexity, simulations involved the corresponding albumin tripeptides and pentapeptides with the modified residue in the central position as well as pseudo-structures which were generated by collecting the albumin residues around the adducted residue within a sphere of 7.5 \uc5 and 5 \uc5 radius. The reliability of the tested approaches was assessed by monitoring the score differences between adducted and unmodified residues. The obtained results revealed the greater predictive power of the spherical pseudo-structures compared to the simple tri- or pentapeptidic sequences thus suggesting that RAGE recognition involves residues which are spatially close to the modified residue even though not necessarily adjacent in the primary sequence

On Organization of Information: Approach and Early Work

In this report we describe an approach for organizing information for presentation and display. "e approach stems from the observation that there is a stepwise progression in the way signals (from the environment and the system under consideration) are extracted and transformed into data, and then analyzed and abstracted to form representations (e.g., indications and icons) on the user interface. In physical environments such as aerospace and process control, many system components and their corresponding data and information are interrelated (e.g., an increase in a chamber s temperature results in an increase in its pressure). "ese interrelationships, when presented clearly, allow users to understand linkages among system components and how they may affect one another. Organization of these interrelationships by means of an orderly structure provides for the so-called "big picture" that pilots, astronauts, and operators strive for

Highlights from the 2018 European Respiratory Society International Congress: sleep and clinical physiology.

The 2018 European Respiratory Society (ERS) International Congress held in Paris, France, served as a platform to discover the latest research on respiratory diseases, the improvement in their treatments and patient care. Specifically, the scientific sessions organised by ERS Assembly 4 provided novel insights into sleep disordered breathing and fresh knowledge in respiratory physiology, stressing its importance to understanding and treating respiratory diseases. This article, divided by session, will summarise the most relevant studies presented at the ERS International Congress. Each session has been written by early career members specialised in the different fields of this interdisciplinary assembly

The PHR family : the role of extracellular transglycosylases in shaping Candida albicans cells

Candida albicans is an opportunistic microorganism that can become a pathogen causing mild superficial mycosis or more severe invasive infections that can be life-threatening for debilitated patients. In the etiology of invasive infections, key factors are the adaptability of C. albicans to the different niches of the human body and the transition from a yeast form to hypha. Hyphal morphology confers high adhesiveness to the host cells, as well as the ability to penetrate into organs. The cell wall plays a crucial role in the morphological changes C. albicans undergoes in response to specific environmental cues. Among the different categories of enzymes involved in the formation of the fungal cell wall, the GH72 family of transglycosylases plays an important assembly role. These enzymes cut and religate \u3b2-(1,3)-glucan, the major determinant of cell shape. In C. albicans, the PHR family encodes GH72 enzymes, some of which work in specific environmental conditions. In this review, we will summarize the work from the initial discovery of PHR genes to the study of the pH-dependent expression of PHR1 and PHR2, from the characterization of the gene products to the recent findings concerning the stress response generated by the lack of GH72 activity in C. albicans hyphae

Shape-independent scaling of excitonic confinement in realistic quantum wires

The scaling of exciton binding energy in semiconductor quantum wires is investigated theoretically through a non-variational, fully three-dimensional approach for a wide set of realistic state-of-the-art structures. We find that in the strong confinement limit the same potential-to-kinetic energy ratio holds for quite different wire cross-sections and compositions. As a consequence, a universal (shape- and composition-independent) parameter can be identified that governs the scaling of the binding energy with size. Previous indications that the shape of the wire cross-section may have important effects on exciton binding are discussed in the light of the present results.Comment: To appear in Phys. Rev. Lett. (12 pages + 2 figures in postscript

Polaron effects in electron channels on a helium film

Using the Feynman path-integral formalism we study the polaron effects in quantum wires above a liquid helium film. The electron interacts with two-dimensional (2D) surface phonons, i.e. ripplons, and is confined in one dimension (1D) by an harmonic potential. The obtained results are valid for arbitrary temperature ($T$), electron-phonon coupling strength ($\alpha$), and lateral confinement ($\omega_{0}$). Analytical and numerical results are obtained for limiting cases of $T$, $\alpha$, and $\omega_{0}$. We found the surprising result that reducing the electron motion from 2D to quasi-1D makes the self-trapping transition more continuous.Comment: 6 pages, 7 figures, submitted to Phys. Rev.

Two Novel Fish Paralogs Provide Insights Into the Rid Family of Imine Deaminases Active in Pre-Empting enamine/imine Metabolic Damage

Reactive Intermediate Deaminase (Rid) protein superfamily includes eight families among which the RidA is conserved in all domains of life. RidA proteins accelerate the deamination of the reactive 2-aminoacrylate (2AA), an enamine produced by some pyridoxal phosphate (PLP)-dependent enzymes. 2AA accumulation inhibits target enzymes with a detrimental impact on fitness. As a consequence of whole genome duplication, teleost fish have two ridA paralogs, while other extant vertebrates contain a single-copy gene. We investigated the biochemical properties of the products of two paralogs, identified in Salmo salar. SsRidA-1 and SsRidA-2 complemented the growth defect of a Salmonella enterica ridA mutant, an in vivo model of 2AA stress. In vitro, both proteins hydrolyzed 2-imino acids (IA) to keto-acids and ammonia. SsRidA-1 was active on IA derived from nonpolar amino acids and poorly active or inactive on IA derived from other amino acids tested. In contrast, SsRidA-2 had a generally low catalytic efficiency, but showed a relatively higher activity with IA derived from L-Glu and aromatic amino acids. The crystal structures of SsRidA-1 and SsRidA-2 provided hints of the remarkably different conformational stability and substrate specificity. Overall, SsRidA-1 is similar to the mammalian orthologs whereas SsRidA-2 displays unique properties likely generated by functional specialization of a duplicated ancestral gene

Reducing number entry errors: solving a widespread, serious problem

Number entry is ubiquitous: it is required in many fields including science, healthcare, education, government, mathematics and finance. People entering numbers are to be expected to make errors, but shockingly few systems make any effort to detect, block or otherwise manage errors. Worse, errors may be ignored but processed in arbitrary ways, with unintended results. A standard class of error (defined in the paper) is an ‘out by 10 error’, which is easily made by miskeying a decimal point or a zero. In safety-critical domains, such as drug delivery, out by 10 errors generally have adverse consequences. Here, we expose the extent of the problem of numeric errors in a very wide range of systems. An analysis of better error management is presented: under reasonable assumptions, we show that the probability of out by 10 errors can be halved by better user interface design. We provide a demonstration user interface to show that the approach is practical. To kill an error is as good a service as, and sometimes even better than, the establishing of a new truth or fact.(Charles Darwin 1879 [2008], p. 229

Advanced lipoxidation end products (ALEs) as RAGE binders : Mass spectrometric and computational studies to explain the reasons why

Advanced Lipoxidation End-products (ALEs) are modified proteins that can act as pathogenic factors in several chronic diseases. Several molecular mechanisms have so far been considered to explain the damaging action of ALEs and among these a pathway involving the receptor for advanced glycation end products (RAGE) should be considered. The aim of the present work is to understand if ALEs formed from lipid peroxidation derived reactive carbonyl species (RCS) are able to act as RAGE binders and also to gain a deeper insight into the molecular mechanisms involved in the protein-protein engagement. ALEs were produced in vitro, by incubating human serum albumin (HSA) with 4-hydroxy-trans 12 2-nonenal (HNE), acrolein (ACR) and malondialdehyde (MDA). The identification of ALEs was performed by MS. ALEs were then subjected to the VC1 Pull-Down assay (VC1 is the ligand binding domain of RAGE) and the enrichment factor (the difference between the relative abundance in the enriched sample minus the amount in the untreated one) as an index of affinity, was determined. Computation studies were then carried out to explain the factors governing the affinity of the adducted moieties and the site of interaction on adducted HSA for VC1-binding. The in silico analyses revealed the key role played by those adducts which strongly reduce the basicity of the modified residues and thus occur at their neutral state at physiological conditions (e.g. the MDA adducts, dihydropyridine-Lysine (DHPK) and N-2-pyrimidyl-ornithine (NPO), and acrolein derivatives, N-(3-formyl-3,4-dehydro-piperidinyl) lysine, FDPK). These neutral adducts become unable to stabilize ion-pairs with the surrounding negative residues which thus can contact the RAGE positive residues. In conclusion, ALEs derived from lipid peroxidation-RCS are binders of RAGE and this affinity depends on the effect of the adduct moiety to reduce the basicity of the target amino acid and on the acid moieties surrounding the aminoacidic target