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Articles 61 - 84 of 84
Full-Text Articles in Physical Sciences and Mathematics
Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman
Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman
Publications and Research
Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …
Two Distinct Modes Of Metal Ion Binding In The Nuclease Active Site Of A Viral Dna-Packaging Terminase: Insight Into The Two-Metal-Ion Catalytic Mechanism, Haiyan Zhao, Zihan Lin, Anna Y. Lynn, Brittany Varnado, John A. Beutler, Ryan P. Murelli, Stuart F.J. Le Grice, Liang Tang
Two Distinct Modes Of Metal Ion Binding In The Nuclease Active Site Of A Viral Dna-Packaging Terminase: Insight Into The Two-Metal-Ion Catalytic Mechanism, Haiyan Zhao, Zihan Lin, Anna Y. Lynn, Brittany Varnado, John A. Beutler, Ryan P. Murelli, Stuart F.J. Le Grice, Liang Tang
Publications and Research
Many dsDNA viruses encode DNA-packaging terminases, each containing a nuclease domain that resolves concatemeric DNA into genome-length units. Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, and share a two-metal-ion catalytic mechanism. Here we show that residue K428 of a bacteriophage terminase gp2 nuclease domain mediates binding of the metal cofactor Mg2+. A K428A mutation allows visualization, at high resolution, of a metal ion binding mode with a coupled-octahedral configuration at the active site, exhibiting an unusually short metal-metal distance of 2.42 A° . Such proximity of the two metal ions may play an essential role in catalysis by …
An Evolutionary Vaccination Game In The Modified Activity Driven Network By Considering The Closeness, Dun Han, Mei Sun
An Evolutionary Vaccination Game In The Modified Activity Driven Network By Considering The Closeness, Dun Han, Mei Sun
Publications and Research
In this paper, we explore an evolutionary vaccination game in the modified activity driven network by considering the closeness. We set a closeness parameter p which is used to describe the way of connection between two individuals. The simulation results show that the closeness p may have an active role in weakening both the spreading of epidemic and the vaccination. Besides, when vaccination is not allowed, the final recovered density increases with the value of the ratio of the infection rate to the recovery rate λ/μ. However, when vaccination is allowed the final density of recovered individual first increases and …
Geospatial Resolution Of Human And Bacterial Diversity With City-Scale Metagenomics, Ebrahim Afshinnekoo, Cem Meydan, Shanin Chowdhury, Dyala Jaroudi, Collin Boyer, Nick Bernstein, Julia M. Maritz, Darryl Reeves, Jorge Gandara, Sagar Chhangawala, Sofia Ahsanuddin, Amber Simmons, Timothy Nessel, Bharathi Sundaresh, Elizabeth Pereira, Ellen Jorgensen, Sergios-Orestis Kolokotronis, Nell Kirchberger, Isaac Garcia, David Gandara, Sean Dhanraj, Tanzina Nawrin, Yogesh Saletore, Noah Alexander, Priyanka Vijay, Elizabeth M. Hénaff, Paul Zumbo, Michael Walsh, Gregory D. O'Mullan, Scott Tighe, Joel T. Dudley, Anya Dunaif, Sean Ennis, Eoghan O'Halloran, Tiago R. Magalhaes, Braden Boone, Angela L. Jones, Theodore R. Muth, Katie Schneider Paolantonio, Elizabeth Alter, Eric E. Schadt, Jeanne Garbarino, Robert J. Prill, Jane M. Carlton, Shawn Levy, Christopher E. Mason
Geospatial Resolution Of Human And Bacterial Diversity With City-Scale Metagenomics, Ebrahim Afshinnekoo, Cem Meydan, Shanin Chowdhury, Dyala Jaroudi, Collin Boyer, Nick Bernstein, Julia M. Maritz, Darryl Reeves, Jorge Gandara, Sagar Chhangawala, Sofia Ahsanuddin, Amber Simmons, Timothy Nessel, Bharathi Sundaresh, Elizabeth Pereira, Ellen Jorgensen, Sergios-Orestis Kolokotronis, Nell Kirchberger, Isaac Garcia, David Gandara, Sean Dhanraj, Tanzina Nawrin, Yogesh Saletore, Noah Alexander, Priyanka Vijay, Elizabeth M. Hénaff, Paul Zumbo, Michael Walsh, Gregory D. O'Mullan, Scott Tighe, Joel T. Dudley, Anya Dunaif, Sean Ennis, Eoghan O'Halloran, Tiago R. Magalhaes, Braden Boone, Angela L. Jones, Theodore R. Muth, Katie Schneider Paolantonio, Elizabeth Alter, Eric E. Schadt, Jeanne Garbarino, Robert J. Prill, Jane M. Carlton, Shawn Levy, Christopher E. Mason
Publications and Research
The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial …
Population Genetic Structure Of The Dwarf Seahorse (Hippocampus Zosterae) In Florida, Nathan Fedrizzi, Melanie L. J. Stiassny, J. T. Boehm, Eric R. Dougherty, George Amato, Martin Mendez
Population Genetic Structure Of The Dwarf Seahorse (Hippocampus Zosterae) In Florida, Nathan Fedrizzi, Melanie L. J. Stiassny, J. T. Boehm, Eric R. Dougherty, George Amato, Martin Mendez
Publications and Research
The dwarf seahorse (Hippocampus zosterae) is widely distributed throughout near-shore habitats of the Gulf of Mexico and is of commercial significance in Florida, where it is harvested for the aquarium and curio trades. Despite its regional importance, the genetic structure of dwarf seahorse populations remains largely unknown. As an aid to ongoing conservation efforts, we employed three commonly applied mtDNA markers (ND4, DLoop and CO1) to investigate the genetic structuring of H. zosterae in Florida using samples collected throughout its range in the state. A total of 1450 bp provided sufficient resolution to delineate four populations of dwarf seahorses, as …
Stably Stratified Canopy Flow In Complex Terrain, Xiyan Xu, Chuixiang Yi, Eric Kutter
Stably Stratified Canopy Flow In Complex Terrain, Xiyan Xu, Chuixiang Yi, Eric Kutter
Publications and Research
Stably stratified canopy flow in complex terrain has been considered a difficult condition for measuring net ecosystem–atmosphere exchanges of carbon, water vapor, and energy. A long-standing advection error in eddy-flux measurements is caused by stably stratified canopy flow. Such a condition with strong thermal gradient and less turbulent air is also difficult for modeling. To understand the challenging atmospheric condition for eddy-flux measurements, we use the renormalized group (RNG) k–ε turbulence model to investigate the main characteristics of stably stratified canopy flows in complex terrain. In this two-dimensional simulation, we imposed persistent constant heat flux at ground surface and linearly …
The Energetic Value Of Land-Based Foods In Western Hudson Bayand Their Potential To Alleviate Energy Deficits Of Starving Adult Male Polar Bears, Linda J. Gormezano, Robert F. Rockwell
The Energetic Value Of Land-Based Foods In Western Hudson Bayand Their Potential To Alleviate Energy Deficits Of Starving Adult Male Polar Bears, Linda J. Gormezano, Robert F. Rockwell
Publications and Research
Climate change is predicted to expand the ice-free season in western Hudson Bay and when it grows to 180 days, 28–48% of adult male polar bears are projected to starve unless nutritional deficits can be offset by foods consumed on land. We updated a dynamic energy budget model developed by Molnar et al. to allow influx of additional energy from novel terrestrial foods (lesser snow geese, eggs, caribou) that polar bears currently consume as part of a mixed diet while on land. We calculated the units of each prey, alone and in combination, needed to alleviate these lethal energy deficits …
Estimates Of Micro-, Nano-, And Picoplankton Contributions To Particle Export In The Northeast Pacific, B. L. Mackinson, S. B. Moran, M. W. Lomas, Gillian M. Stewart, R. P. Kelly
Estimates Of Micro-, Nano-, And Picoplankton Contributions To Particle Export In The Northeast Pacific, B. L. Mackinson, S. B. Moran, M. W. Lomas, Gillian M. Stewart, R. P. Kelly
Publications and Research
The contributions of micro-, nano-, and picoplankton to particle export were estimated from measurements of size-fractionated particulate 234Th, organic carbon, and phytoplankton indicator pigments obtained during five cruises between 2010 and 2012 along Line P in the subarctic northeast Pacific Ocean. Sinking fluxes of particulate organic carbon (POC) and indicator pigments were calculated from 234Th;238U disequilibria and, during two cruises, measured by a sediment trap at Ocean Station Papa. POC fluxes at 100m ranged from 0.65 to 7.95 mmolm2 d1, similar in magnitude to previous results at Line P. Microplankton pigments dominate indicator pigment fluxes (averaging 6919% of total pigment …
Mapping Regional Inundation With Spaceborne L-Band Sar, Bruce Chapman, Kyle Macdonald, Masanobu Shimada, Ake Rosenqvist, Ronny Schroeder, Laura Hess
Mapping Regional Inundation With Spaceborne L-Band Sar, Bruce Chapman, Kyle Macdonald, Masanobu Shimada, Ake Rosenqvist, Ronny Schroeder, Laura Hess
Publications and Research
Shortly after the launch of ALOS PALSAR L-band SAR by the Japan Space Exploration Agency (JAXA), a program to develop an Earth Science Data Record (ESDR) for inundated wetlands was funded by NASA. Using established methodologies, extensive multi-temporal L-band ALOS ScanSAR data acquired bi-monthly by the PALSAR instrument onboard ALOS were used to classify the inundation state for South America for delivery as a component of this Inundated Wetlands ESDR (IW-ESDR) and in collaboration with JAXA’s ALOS Kyoto and Carbon Initiative science programme. We describe these methodologies and the final classification of the inundation state, then compared this with results …
The Hosoya Entropy Of A Graph, Abbe Mowshowitz, Matthias Dehmer
The Hosoya Entropy Of A Graph, Abbe Mowshowitz, Matthias Dehmer
Publications and Research
This paper demonstrates properties of Hosoya entropy, a quantitative measure of graph complexity based on a decomposition of the vertices linked to partial Hosoya polynomials. Connections between the information content of a graph and Hosoya entropy are established, and the special case of Hosoya entropy of trees is investigated.
Protein Sectors: Statistical Coupling Analysis Versus Conservation, Tiberiu Teşileanu, Lucy J. Colwell, Stanislas Leibler
Protein Sectors: Statistical Coupling Analysis Versus Conservation, Tiberiu Teşileanu, Lucy J. Colwell, Stanislas Leibler
Publications and Research
Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed “sectors”. The method applies spectral analysis to a matrix obtained by combining correlation information with sequence conservation. It has been asserted that the protein sectors identified by SCA are functionally significant, with different sectors controlling different biochemical properties of the protein. Here we reconsider the available experimental data and note that it involves almost exclusively proteins with a single sector. We show that in this case sequence conservation is the dominating factor in SCA, and can alone be …
A Principle Of Economy Predicts The Functional Architecture Of Grid Cells, Xue-Xin Wei, Jason Prentice, Vijay Balasubramanian
A Principle Of Economy Predicts The Functional Architecture Of Grid Cells, Xue-Xin Wei, Jason Prentice, Vijay Balasubramanian
Publications and Research
Grid cells in the brain respond when an animal occupies a periodic lattice of ‘grid fields’ during navigation. Grids are organized in modules with different periodicity. We propose that the grid system implements a hierarchical code for space that economizes the number of neurons required to encode location with a given resolution across a range equal to the largest period. This theory predicts that (i) grid fields should lie on a triangular lattice, (ii) grid scales should follow a geometric progression, (iii) the ratio between adjacent grid scales should be √e for idealized neurons, and lie between 1.4 and 1.7 …
Tipping Point Of A Conifer-Based Ecosystem Under Severe Drought, Kaicheng Huang, Chuixiang Yi, Donghai Wu, Tao Zhou, Xiang Zhao, William J. Blanford, Suhua Wei, Hao Wu, Du Ling, Zheng Li
Tipping Point Of A Conifer-Based Ecosystem Under Severe Drought, Kaicheng Huang, Chuixiang Yi, Donghai Wu, Tao Zhou, Xiang Zhao, William J. Blanford, Suhua Wei, Hao Wu, Du Ling, Zheng Li
Publications and Research
Drought-induced tree mortality has recently received considerable attention. Questions have arisen over the necessary intensity and duration thresholds of droughts that are sufficient to trigger rapid forest declines. The values of such tipping points leading to forest declines due to drought are presently unknown. In this study, we have evaluated the potential relationship between the level of tree growth and concurrent drought conditions with data of the tree growth-related ring width index (RWI) of the two dominant conifer species (Pinus edulis and Pinus ponderosa) in the Southwestern United States (SWUS) and the meteorological drought-related standardized precipitation evapotranspiration index …
Effects Of Extreme Climate Events On Tea (Camellia Sinensis) Functional Quality Validate Indigenous Farmer Knowledge And Sensory Preferences In Tropical China, Selena Ahmed, John Richard Stepp, Colin M. Orians, Timothy S. Griffin, Corene Matyas, Albert Robbat, Sean Cash, Dayuan Xue, Chunlin Long, Uchenna Unachukwu, Sarabeth Buckley, Edward J. Kennelly
Effects Of Extreme Climate Events On Tea (Camellia Sinensis) Functional Quality Validate Indigenous Farmer Knowledge And Sensory Preferences In Tropical China, Selena Ahmed, John Richard Stepp, Colin M. Orians, Timothy S. Griffin, Corene Matyas, Albert Robbat, Sean Cash, Dayuan Xue, Chunlin Long, Uchenna Unachukwu, Sarabeth Buckley, Edward J. Kennelly
Publications and Research
Climate change is impacting agro-ecosystems, crops, and farmer livelihoods in communities worldwide. While it is well understood that more frequent and intense climate events in many areas are resulting in a decline in crop yields, the impact on crop quality is less acknowledged, yet it is critical for food systems that benefit both farmers and consumers through high-quality products. This study examines tea (Camellia sinensis; Theaceae), the world’s most widely consumed beverage after water, as a study system to measure effects of seasonal precipitation variability on crop functional quality and associated farmer knowledge, preferences, and livelihoods. Sampling was conducted in …
Deconstructing A Plant Macromolecular Assembly: Chemical Architecture, Molecular Flexibility, And Mechanical Performance Of Natural And Engineered Potato Suberins, Olga Serra, Subhasish Chatterjee, Merce Figueras, Marisa Molinas, Ruth E. Stark
Deconstructing A Plant Macromolecular Assembly: Chemical Architecture, Molecular Flexibility, And Mechanical Performance Of Natural And Engineered Potato Suberins, Olga Serra, Subhasish Chatterjee, Merce Figueras, Marisa Molinas, Ruth E. Stark
Publications and Research
Periderms present in plant barks are essential protective barriers to water diffusion, mechanical breakdown, and pathogenic invasion. They consist of densely packed layers of dead cells with cell walls that are embedded with suberin. Understanding the interplay of molecular structure, dynamics, and biomechanics in these cell wall-associated insoluble amorphous polymeric assemblies presents substantial investigative challenges. We report solid-state NMR coordinated with FT-IR and tensile strength measurements for periderms from native and wound-healing potatoes and from potatoes with genetically modified suberins. The analyses include the intact suberin aromatic; aliphatic polymer and cell-wall polysaccharides, previously reported soluble depolymerized transmethylation products, and undegraded …
Remote Sensing Of Soil Moisture In Vineyards Using Airborne And Ground-Based Thermal Inertia Data, Aiman Soliman, Richard J. Heck, Alexander Brenning, Ralph Brown, Stephen Miller
Remote Sensing Of Soil Moisture In Vineyards Using Airborne And Ground-Based Thermal Inertia Data, Aiman Soliman, Richard J. Heck, Alexander Brenning, Ralph Brown, Stephen Miller
Publications and Research
Thermal remote sensing of soil moisture in vineyards is a challenge. The grass-covered soil, in addition to a standing grape canopy, create complex patterns of heating and cooling and increase the surface temperature variability between vine rows. In this study, we evaluate the strength of relationships between soil moisture, mechanical resistance and thermal inertia calculated from the drop of surface temperature during a clear sky night over a vineyard in the Niagara region. We utilized data from two sensors, an airborne thermal camera (height ≈ 500 m a.g.l.) and a handheld thermal gun (height ≈ 1 m a.g.l.), to explore …
Allometric Scaling And Resource Limitations Model Of Tree Heights: Part 1. Model Optimization And Testing Over Continental Usa, Yuli Shi, Sungho Choi, Xiliang Ni, Sangram Ganguly, Gong Zhang, Hieu V. Duong, Michael A. Lefsky, Marc Simard, Sassan S. Saatchi, Shihyan Lee, Wenge Ni-Meister, Shilong Piao, Chunxiang Cao, Ramakrishna R. Nemani, Ranga B. Myneni
Allometric Scaling And Resource Limitations Model Of Tree Heights: Part 1. Model Optimization And Testing Over Continental Usa, Yuli Shi, Sungho Choi, Xiliang Ni, Sangram Ganguly, Gong Zhang, Hieu V. Duong, Michael A. Lefsky, Marc Simard, Sassan S. Saatchi, Shihyan Lee, Wenge Ni-Meister, Shilong Piao, Chunxiang Cao, Ramakrishna R. Nemani, Ranga B. Myneni
Publications and Research
A methodology to generate spatially continuous fields of tree heights with an optimized Allometric Scaling and Resource Limitations (ASRL) model is reported in this first of a multi-part series of articles. Model optimization is performed with the Geoscience Laser Altimeter System (GLAS) waveform data. This methodology is demonstrated by mapping tree heights over forested lands in the continental USA (CONUS) at 1 km spatial resolution. The study area is divided into 841 eco-climatic zones based on three forest types, annual total precipitation classes (30 mm intervals) and annual average temperature classes (2 °C intervals). Three model parameters (area of single …
Entropy And The Complexity Of Graphs Revisited, Abbe Mowshowitz, Matthias Dehmer
Entropy And The Complexity Of Graphs Revisited, Abbe Mowshowitz, Matthias Dehmer
Publications and Research
This paper presents a taxonomy and overview of approaches to the measurement of graph and network complexity. The taxonomy distinguishes between deterministic (e.g., Kolmogorov complexity) and probabilistic approaches with a view to placing entropy-based probabilistic measurement in context. Entropy-based measurement is the main focus of the paper. Relationships between the different entropy functions used to measure complexity are examined; and intrinsic (e.g., classical measures) and extrinsic (e.g., Körner entropy) variants of entropy-based models are discussed in some detail.
Group 11 Metal Compounds With Tripodal Bis(Imidazole) Thioether Ligands. Applications As Catalysts In The Oxidation Of Alkenes And As Antimicrobial Agents, Fangwei Liu, Reema Anis, Eunmi Hwang, Rafael Ovalle, Armando Varela-Ramírez, Renato J. Aguilera, María Contel
Group 11 Metal Compounds With Tripodal Bis(Imidazole) Thioether Ligands. Applications As Catalysts In The Oxidation Of Alkenes And As Antimicrobial Agents, Fangwei Liu, Reema Anis, Eunmi Hwang, Rafael Ovalle, Armando Varela-Ramírez, Renato J. Aguilera, María Contel
Publications and Research
New group 11 metal complexes have been prepared using the previously described tripodal bis(imidazole) thioether ligand (N-methyl-4,5-diphenyl-2- imidazolyl)2C(OMe)C(CH3)2S(tert-Bu) ({BITOMe,StBu}, 2). The pincer ligand offers a N2S donor atom set that can be used to coordinate the group 11 metals in different oxidation states [AuI , AuIII, AgI , CuI and CuII]. Thus the new compounds [Au{BITOMe,StBu}Cl][AuCl4]2 (3), [Au{BITOMe,StBu}Cl] (4), [Ag{BITOMe,StBu}X] (X = OSO2CF3 - 5, PF6 - 6) and [Cu{BITOMe,StBu}Cl2] (7) have been synthesized from reaction of 2 with the appropriate metal precursors, and characterized in solution. While attempting characterization in the solid state of 3, single crystals of the …
Polycationic Glycosides, Robert Engel, Ishrat Ghani, Diego Montenegro, Marie Thomas, Barbara Klaritch-Vrana, Alejandra Castaño, Laura Friedman, Jay Leb, Leah Rothman, Heidi Lee, Craig Capodiferro, Daniel Ambinder, Eve Cere, Christopher Awad, Faiza Sheikh, Jaimelee Rizzo, Lisa-Marie Nisbett, Erika Testani, Karin Melkonian
Polycationic Glycosides, Robert Engel, Ishrat Ghani, Diego Montenegro, Marie Thomas, Barbara Klaritch-Vrana, Alejandra Castaño, Laura Friedman, Jay Leb, Leah Rothman, Heidi Lee, Craig Capodiferro, Daniel Ambinder, Eve Cere, Christopher Awad, Faiza Sheikh, Jaimelee Rizzo, Lisa-Marie Nisbett, Erika Testani, Karin Melkonian
Publications and Research
Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial …
The Mycobacterium Tuberculosis Drugome And Its Polypharmacological Implications, Sarah L. Kinnings, Li Xie, Kingston H. Fung, Richard M. Jackson, Lei Xie, Phillip E. Bourne
The Mycobacterium Tuberculosis Drugome And Its Polypharmacological Implications, Sarah L. Kinnings, Li Xie, Kingston H. Fung, Richard M. Jackson, Lei Xie, Phillip E. Bourne
Publications and Research
We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today’s most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the ‘TB-drugome’. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable …
Drug Off-Target Effects Predicted Using Structural Analysis In The Context Of A Metabolic Network Model, Roger L. Chang, Lei Xie, Philip E. Bourne, Bernhard O. Palsson
Drug Off-Target Effects Predicted Using Structural Analysis In The Context Of A Metabolic Network Model, Roger L. Chang, Lei Xie, Philip E. Bourne, Bernhard O. Palsson
Publications and Research
Recent advances in structural bioinformatics have enabled the prediction of protein-drug off-targets based on their ligand binding sites. Concurrent developments in systems biology allow for prediction of the functional effects of system perturbations using large-scale network models. Integration of these two capabilities provides a framework for evaluating metabolic drug response phenotypes in silico. This combined approach was applied to investigate the hypertensive side effect of the cholesteryl ester transfer protein inhibitor torcetrapib in the context of human renal function. A metabolic kidney model was generated in which to simulate drug treatment. Causal drug off-targets were predicted that have previously been …
A Multidimensional Strategy To Detect Polypharmacological Targets In The Absence Of Structural And Sequence Homology, Jacob D. Durrant, Rommie E. Amaro, Lei Xie, Michael D. Urbaniak, Michael A. J. Ferguson, Antti Haapalainen, Zhijun Chen, Anne Marie Di Guilmi, Frank Wunder, Philip E. Bourne, J. Andrew Mccammon
A Multidimensional Strategy To Detect Polypharmacological Targets In The Absence Of Structural And Sequence Homology, Jacob D. Durrant, Rommie E. Amaro, Lei Xie, Michael D. Urbaniak, Michael A. J. Ferguson, Antti Haapalainen, Zhijun Chen, Anne Marie Di Guilmi, Frank Wunder, Philip E. Bourne, J. Andrew Mccammon
Publications and Research
Conventional drug design embraces the ‘‘one gene, one drug, one disease’’ philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional …
Correlating Molecular Phylogeny With Venom Apparatus Occurrence In Panamic Auger Snails (Terebridae), Mandë Holford, Nicolas Puillandre, Maria Vittoria Modica, Maren Watkins, Rachel Collin, Eldredge Bermingham, Baldomero M. Olivera
Correlating Molecular Phylogeny With Venom Apparatus Occurrence In Panamic Auger Snails (Terebridae), Mandë Holford, Nicolas Puillandre, Maria Vittoria Modica, Maren Watkins, Rachel Collin, Eldredge Bermingham, Baldomero M. Olivera
Publications and Research
Central to the discovery of neuroactive compounds produced by predatory marine snails of the superfamily Conoidea (cone snails, terebrids, and turrids) is identifying those species with a venom apparatus. Previous analyses of western Pacific terebrid specimens has shown that some Terebridae groups have secondarily lost their venom apparatus. In order to efficiently characterize terebrid toxins, it is essential to devise a key for identifying which species have a venom apparatus. The findings presented here integrate molecular phylogeny and the evolution of character traits to infer the presence or absence of the venom apparatus in the Terebridae. Using a combined dataset …