Extraction of consensus protein patterns in regions containing non-proline cis peptide bonds and their functional assessment

<p>Abstract</p> <p>Background</p> <p>In peptides and proteins, only a small percentile of peptide bonds adopts the <it>cis </it>configuration. Especially in the case of amide peptide bonds, the amount of <it>cis </it>conformations is quite limited thus hampering systematic studies, until recently. However, lately the emerging population of databases with more 3D structures of proteins has produced a considerable number of sequences containing non-proline <it>cis </it>formations (<it>cis</it>-nonPro).</p> <p>Results</p> <p>In our work, we extract regular expression-type patterns that are descriptive of regions surrounding the <it>cis</it>-nonPro formations. For this purpose, three types of pattern discovery are performed: i) exact pattern discovery, ii) pattern discovery using a chemical equivalency set, and iii) pattern discovery using a structural equivalency set. Afterwards, using each pattern as predicate, we search the Eukaryotic Linear Motif (ELM) resource to identify potential functional implications of regions with <it>cis</it>-nonPro peptide bonds. The patterns extracted from each type of pattern discovery are further employed, in order to formulate a pattern-based classifier, which is used to discriminate between <it>cis</it>-nonPro and <it>trans</it>-nonPro formations.</p> <p>Conclusions</p> <p>In terms of functional implications, we observe a significant association of <it>cis</it>-nonPro peptide bonds towards ligand/binding functionalities. As for the pattern-based classification scheme, the highest results were obtained using the structural equivalency set, which yielded 70% accuracy, 77% sensitivity and 63% specificity.</p

Detection of discriminative sequence patterns in the neighborhood of proline cis peptide bonds and their functional annotation

<p>Abstract</p> <p>Background</p> <p>Polypeptides are composed of amino acids covalently bonded via a peptide bond. The majority of peptide bonds in proteins is found to occur in the <it>trans </it>conformation. In spite of their infrequent occurrence, <it>cis </it>peptide bonds play a key role in the protein structure and function, as well as in many significant biological processes.</p> <p>Results</p> <p>We perform a systematic analysis of regions in protein sequences that contain a proline <it>cis </it>peptide bond in order to discover non-random associations between the primary sequence and the nature of proline <it>cis/trans </it>isomerization. For this purpose an efficient pattern discovery algorithm is employed which discovers regular expression-type patterns that are overrepresented (i.e. appear frequently repeated) in a set of sequences. Four types of pattern discovery are performed: i) exact pattern discovery, ii) pattern discovery using a chemical equivalency set, iii) pattern discovery using a structural equivalency set and iv) pattern discovery using certain amino acids' physicochemical properties. The extracted patterns are carefully validated using a specially implemented scoring function and a significance measure (i.e. log-probability estimate) indicative of their specificity. The score threshold for the first three types of pattern discovery is 0.90 while for the last type of pattern discovery 0.80. Regarding the significance measure, all patterns yielded values in the range [-9, -31] which ensure that the derived patterns are highly unlikely to have emerged by chance. Among the highest scoring patterns, most of them are consistent with previous investigations concerning the neighborhood of <it>cis </it>proline peptide bonds, and many new ones are identified. Finally, the extracted patterns are systematically compared against the PROSITE database, in order to gain insight into the functional implications of <it>cis </it>prolyl bonds.</p> <p>Conclusion</p> <p><it>Cis </it>patterns with matches in the PROSITE database fell mostly into two main functional clusters: family signatures and protein signatures. However considerable propensity was also observed for targeting signals, active and phosphorylation sites as well as domain signatures.</p

Effect of ultrasound on bone fracture healing:A computational bioregulatory model

peer reviewedBone healing is a complex biological procedure in which several cellular actions, directed by biochemical and mechanical signals, take place. Experimental studies have shown that ultrasound accelerates bone ossification and has a multiple influence on angiogenesis. In this study a mathematical model predicting bone healing under the presence of ultrasound is demonstrated. The primary objective is to account for the ultrasound effect on angiogenesis and more specifically on the transport of the Vascular Endothelial Growth Factor (VEGF). Partial differential equations describing the spatiotemporal evolution of cells, growth factors, tissues and ultrasound acoustic pressure and velocity equations determining the development of the blood vessel network constitute the present model. The effect of the ultrasound characteristics on angiogenesis and bone healing is investigated by applying different boundary conditions of acoustic pressure at the periosteal region of the bone model, which correspond to different intensity values. The results made clear that ultrasound enhances angiogenesis mechanisms during bone healing. The proposed model could be regarded as a step towards the monitoring of the effect of ultrasound on bone regeneration. © 2018Action “Supporting Postdoctoral Researchers” of the Operational Program “Education and Lifelong Learning” (Action’s Beneficiary: General Secretariat for Research and Technology); Greek State (PE8-3347

Effect of ultrasound on bone fracture healing:A computational mechanobioregulatory model

Bone healing process is a complicated phenomenon regulated by biochemical and mechanical signals. Experimental studies have shown that ultrasound (US) accelerates bone ossification and has a multiple influence on cell differentiation and angiogenesis. In a recent work of the authors, a bioregulatory model for providing bone-healing predictions was addressed, taking into account for the first time the salutary effect of US on the involved angiogenesis. In the present work, a mechanobioregulatory model of bone solidification under the US presence incorporating also the mechanical environment on the regeneration process, which is known to affect cellular processes, is presented. An iterative procedure is adopted, where the finite element method is employed to compute the mechanical stimuli at the linear elastic phases of the poroelastic callus region and a coupled system of partial differential equations to simulate the enhancement by the US cell angiogenesis process and thus the oxygen concentration in the fractured area. Numerical simulations with and without the presence of US that illustrate the influence of progenitor cells' origin in the healing pattern and the healing rate and simultaneously demonstrate the salutary effect of US on bone repair are presented and discussed

Patient-specific computational modeling of subendothelial LDL accumulation in a stenosed right coronary artery: effect of hemodynamic and biological factors

Patient-specific computational modeling of subendothelial LDL accumulation in a stenosed right coronary artery: effect of hemodynamic and biological factors. Am J Physiol Heart Circ Physiol 304: H1455-H1470, 2013. First published March 15, 2013; doi:10.1152/ajpheart.00539.2012.-Atherosclerosis is a systemic disease with local manifestations. Low-density lipoprotein (LDL) accumulation in the subendothelial layer is one of the hallmarks of atherosclerosis onset and ignites plaque development and progression. Blood flow-induced endothelial shear stress (ESS) is causally related to the heterogenic distribution of atherosclerotic lesions and critically affects LDL deposition in the vessel wall. In this work we modeled blood flow and LDL transport in the coronary arterial wall and investigated the influence of several hemodynamic and biological factors that may regulate LDL accumulation. We used a three-dimensional model of a stenosed right coronary artery reconstructed from angiographic and intravascular ultrasound patient data. We also reconstructed a second model after restoring the patency of the stenosed lumen to its nondiseased state to assess the effect of the stenosis on LDL accumulation

400 Gb/s silicon photonic transmitter and routing WDM technologies for glueless 8-socket chip-to-chip interconnects

Arrayed Waveguide Grating Router (AWGR)-based interconnections for Multi-Socket Server Boards (MSBs) have been identified as a promising solution to replace the electrical interconnects in glueless MSBs towards boosting processing performance. In this article, we present an 8-socket glueless optical flat-topology Wavelength Division Multiplexing (WDM)-based point-to-point (P2P) interconnect pursued within the H2020 ICT project ICT-STREAMS and we report on our latest achievements in the deployment of the constituent silicon (Si)-photonic transmitter and routing building blocks, exploiting experimentally obtained performance metrics for analyzing the 8-socket chip-to-chip (C2C) connectivity in terms of throughput and energy efficiency. We demonstrate an 8-channel WDM Si-photonic microring-based transmitter (Tx) capable of providing 400 (8 x 50) Gb/s non-return-to-zero (NRZ) Tx capacity and an 8 x 8 Coarse-WDM (CWDM) Si-AWGR with verified cyclic data routing capability in O-band. Following an overview of our recently demonstrated crosstalk (XT)-aware wavelength allocation scheme, that enables fully-loaded AWGR-based interconnects even for typical sub-optimal XT values of silicon integrated CWDM AWGRs, we validate the performance of a full-scale 8-socket interconnect architecture through physical layer simulations exploiting experimentally-verified simulation models for the underlying Si-photonic Tx and routing circuits. This analysis reveals a total aggregate capacity of 1.4 Tb/s for an 8-socket interconnect when operating with 25 Gb/s line-rates, which can scale to 2.8 Tb/s at an energy efficiency of just 5.02 pJ/bit by exploiting the experimentally verified building block performance at 50 Gb/s line. This highlights the perspectives for up to 69% energy savings compared to the standard QuickPath Interconnect (QPI) typically employed in electronic glueless MSB interconnects, while scaling the single-hop flat connectivity from 4- to 8-socket interconnection systems

Silicon circuits for chip-to-chip communications in multi-socket server board interconnects

Multi-socket server boards (MSBs) exploit the interconnection of multiple processor chips towards forming powerful cache coherent systems, with the interconnect technology comprising a key element in boosting processing performance. Here, we present an overview of the current electrical interconnects for MSBs, outlining the main challenges currently faced. We propose the use of silicon photonics (SiPho) towards advancing interconnect throughput, socket connectivity and energy efficiency in MSB layouts, enabling a flat-topology wavelength division multiplexing (WDM)-based point-to-point (p2p) optical MSB interconnect scheme. We demonstrate WDM SiPho transceivers (TxRxs) co-assembled with their electronic circuits for up to 50 Gb/s line rate and 400 Gb/s aggregate data transmission and SiPho arrayed waveguide grating routers that can offer collision-less time of flight connectivity for up to 16 nodes. The capacity can scale to 2.8 Gb/s for an eight-socket MSB, when line rate scales to 50 Gb/s, yielding up to 69% energy reduction compared with the QuickPath Interconnect and highlighting the feasibility of single-hop p2p interconnects in MSB systems with >4 sockets