Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) are a superfamily of integral membrane proteins vital for signaling and are important targets for pharmaceutical intervention in humans. Previously, we identified a group of ten amino acid positions (called key positions), within the seven transmembrane domain (7TM) interhelical region, which had high mutual information with each other and many other positions in the 7TM. Here, we estimated the evolutionary selection pressure at those key positions. We found that the key positions of receptors for small molecule natural ligands were under strong negative selection. Receptors naturally activated by lipids had weaker negative selection in general when compared to small molecule-activated receptors. Selection pressure varied widely in peptide-activated receptors. We used this observation to predict that a subgroup of orphan GPCRs not under strong selection may not possess a natural small-molecule ligand. In the subgroup of MRGX1-type GPCRs, we identified a key position, along with two non-key positions, under statistically significant positive selection

Next Generation Cosmology: Constraints from the Euclid Galaxy Cluster Survey

We study the characteristics of the galaxy cluster samples expected from the European Space Agency's Euclid satellite and forecast constraints on cosmological parameters describing a variety of cosmological models. The method used in this paper, based on the Fisher Matrix approach, is the same one used to provide the constraints presented in the Euclid Red Book (Laureijs et al.2011). We describe the analytical approach to compute the selection function of the photometric and spectroscopic cluster surveys. Based on the photometric selection function, we forecast the constraints on a number of cosmological parameter sets corresponding to different extensions of the standard LambdaCDM model. The dynamical evolution of dark energy will be constrained to Delta w_0=0.03 and Delta w_a=0.2 with free curvature Omega_k, resulting in a (w_0,w_a) Figure of Merit (FoM) of 291. Including the Planck CMB covariance matrix improves the constraints to Delta w_0=0.02, Delta w_a=0.07 and a FoM=802. The amplitude of primordial non-Gaussianity, parametrised by f_NL, will be constrained to \Delta f_NL ~ 6.6 for the local shape scenario, from Euclid clusters alone. Using only Euclid clusters, the growth factor parameter \gamma, which signals deviations from GR, will be constrained to Delta \gamma=0.02, and the neutrino density parameter to Delta Omega_\nu=0.0013 (or Delta \sum m_\nu=0.01). We emphasise that knowledge of the observable--mass scaling relation will be crucial to constrain cosmological parameters from a cluster catalogue. The Euclid mission will have a clear advantage in this respect, thanks to its imaging and spectroscopic capabilities that will enable internal mass calibration from weak lensing and the dynamics of cluster galaxies. This information will be further complemented by wide-area multi-wavelength external cluster surveys that will already be available when Euclid flies. [Abridged]Comment: submitted to MNRA

The palliative-supportive care unit in a comprehensive cancer center as crossroad for patients' oncological pathway

Aim The aim of this study was to assess how an admission to an acute palliative-supportive care unit (APSCU), may influence the therapeutic trajectory of advanced cancer patients. Methods A consecutive sample of advanced cancer patients admitted to APCU was assessed. The following parameters were collected: patients demographics, including age, gender, primary diagnosis, marital status, and educational level, performance status and reasons for and kind of admission, data about care-givers, recent anticancer treatments, being on/off treatment or uncertain, the previous care setting, who proposed the admission to APSCU. Physical and psychological symptoms were evaluated at admission and at time of discharge. The use of opioids was also recorded. Hospital staying was also recorded. At time of discharge the parameters were recorded and a follow-up was performed one month after discharge. Results314 consecutive patients admitted to the APSCU were surveyed. Pain was the most frequent reason for admission. Changes of ESAS were highly significant, as well as the use of opioids and breakthrough pain medications (p lt;0.0005). A significant decrease of the number of [[ampi]]on therapy[[ampi]] patients was reported, and concomitantly a significant number of [[ampi]]offtherapy[[ampi]] patients increased. At one month follow-up, 38.9% patients were at home, 19.7% patients were receiving palliative home care, and 1.6% patients were in hospice. 68.5% of patients were still living. Conclusion Data of this study suggest that the APSCU may have a relevant role for managing the therapeutic trajectory of advanced cancer patients, limiting the risk of futile and aggressive treatment while providing an appropriate care setting

Recent amplification of an alpha satellite DNA in humans.

A repeat sequence 682 base pairs (bp) long produced by cleavage of human DNA with Xba I restriction enzyme is composed of four tandemly arranged subunits with lengths of 171, 170, 171, and 170 bp each. The sequence organization of the 682 bp Xba I repeat bears a striking resemblance to other complex satellite DNAs of primates, including the Eco RI human alpha satellite family which also occurs as a 170 bp repeat. The Eco RI tetramer and the 682 bp Xba I repeat show a sequence divergence of 21%. The 682 bp Xba I repeat sequence is restricted to humans and is only distantly related to the previously reported 340 bp Xba human repeated DNA sequence. These finding are consistent with the concept of occasional amplifications of members or groups of members of alpha satellite DNA during human evolution. Amplifications apparently occurred after humans, apes and gibbons diverged from Old World monkeys (Eco RI satellite), after humans and apes diverged from gibbons (340 bp Xba I satellite) and after humans diverged from the great apes (682 bp Xba I satellite)

Piecewise planar underwater mosaicing

A commonly ignored problem in planar mosaics, yet often present in practice, is the selection of a reference homography reprojection frame where to attach the successive image frames of the mosaic. A bad choice for the reference frame can lead to severe distortions in the mosaic and can degenerate in incorrect configurations after some sequential frame concatenations. This problem is accentuated in uncontrolled underwater acquisition setups as those provided by AUVs or ROVs due to both the noisy trajectory of the acquisition vehicle - with roll and pitch shakes - and to the non-flat nature of the seabed which tends to break the planarity assumption implicit in the mosaic construction. These scenarios can also introduce other undesired effects, such as light variations between successive frames, scattering and attenuation, vignetting, flickering and noise. This paper proposes a novel mosaicing pipeline, also including a strategy to select the best reference homography in planar mosaics from video sequences which minimizes the distortions induced on each image by the mosaic homography itself. Moreover, a new non-linear color correction scheme is incorporated to handle strong color and luminosity variations among the mosaic frames. Experimental evaluation of the proposed method on real, challenging underwater video sequences shows the validity of the approach, providing clear and visually appealing mosaic

Reticulon1-C modulates protein disulphide isomerase function

Endoplasmic reticulum (ER) is the primary site for the synthesis and folding of secreted and membrane-bound proteins. Accumulation of unfolded and misfolded proteins in ER underlies a wide range of human neurodegenerative disorders. Hence, molecules regulating the ER stress response represent potential candidates as drug targets for tackling these diseases. Protein disulphide isomerase (PDI) is a chaperone involved in ER stress pathway, its activity being an important cellular defense against protein misfolding. Here, we demonstrate that human neuroblastoma SH-SY5Y cells overexpressing the reticulon protein 1-C (RTN1-C) reticulon family member show a PDI punctuate subcellular distribution identified as ER vesicles. This represents an event associated with a significant increase of PDI enzymatic activity. We provide evidence that the modulation of PDI localization and activity does not only rely upon ER stress induction or upregulation of its synthesis, but tightly correlates to an alteration in its nitrosylation status. By using different RTN1-C mutants, we demonstrate that the observed effects depend on RTN1-C N-terminal region and on the integrity of the microtubule network. Overall, our results indicate that RTN1-C induces PDI redistribution in ER vesicles, and concomitantly modulates its activity by decreasing the levels of its S-nitrosylated form. Thus RTN1-C represents a promising candidate to modulate PDI function

Development of a navigation algorithm for autonomous underwater vehicles

In this paper, the authors present an underwater navigation system for Autonomous Underwater Vehicles (AUVs) which exploits measurements from an Inertial Measurement Unit (IMU), a Pressure Sensor (PS) for depth and the Global Positioning System (GPS, used during periodic and dedicated resurfacings) and relies on either the Extended Kalman Filter (EKF) or the Unscented Kalman Filter (UKF) for the state estimation. Both (EKF and UKF) navigation algorithms have been validated through experimental navigation data related to some sea tests performed in La Spezia (Italy) with one of Typhoon class vehicles during the NATO CommsNet13 experiment (held in September 2013) and through Ultra-Short BaseLine (USBL) fixes used as a reference (ground truth). Typhoon is an AUV designed by the Department of Industrial Engineering of the Florence University for exploration and surveillance of underwater archaeological sites in the framework of the Italian THESAURUS project and the European ARROWS project. The obtained results have demonstrated the effectiveness of both navigation algorithms and the superiority of the UKF (very suitable for AUV navigation and, up to now, still not used much in this field) without increasing the computational load (affordable for on-line on-board AUV implementation)

Adenosine receptor agonists: Synthesis and binding affinity of 2-(aryl)alkylthioadenosine derivatives

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Response of Foraminifera to Anthropogenic Nicotine Pollution of Cigarette Butts: An Experimental Approach

The most often dispersed environmental pollutants that are released both directly and indirectly into the environment that may eventually reach aquatic ecosystems and contaminate aquatic biomes are cigarette butts (CBs). Toxicants such as nicotine, dangerous metals, total particulate matter, and recognized carcinogens can be introduced and transported via CBs into aquatic ecosystems. The examination of the effects of synthetic nicotine on three different species of cultured benthic foraminifera was the focus of this study. Three foraminiferal species from three distinct biomineralization pathways were specifically examined for viability and cellular ultrastructure, including the calcareous perforate Rosalina globularis, the calcareous imperforate Quinqueloculina spp., and the agglutinated Textularia agglutinans. The survival rate, cellular stress, and decalcification were used to assess the toxicological effects of synthetic nicotine. We were able to analyze the reaction of major macromolecules and calcium carbonate to this pollutant using FTIR (Fourier Transform Infrared) spectroscopy. High Performance Liquid Chromatography (HPLC) study was performed to increase our understanding of nicotine bioavailability in the medium culture. Different acute experiments were performed at different dates, and all indicated that synthetic nicotine is acutely hazardous to all three cultured foraminiferal taxa at lethal and sublethal concentrations. Each species responded differently depending on the type of shell biomineralization. Synthetic nicotine enhances shell decalcification and affects the composition of cytoplasmic macromolecules such as lipids and proteins, according to the FTIR spectroscopy investigations. The lipid content rose at lethal concentrations, possibly due to the creation of vesicles. The proteins signal evidences general cellular dyshomeostasis. The integration among the acute toxicity assay, synchrotron, and chemical HPLC analyses provided a valuable approach for the assessment of nicotine as a biomarker of exposure to the toxicants associated with smoking and the impact of this emerging and hazardous material on calcifying marine species