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https://www.readbyqxmd.com/read/28211491/interference-between-variants-of-peach-latent-mosaic-viroid-reveals-novel-features-of-its-fitness-landscape-implications-for-detection
#1
Pedro Serra, Edson Bertolini, M Carmen Martínez, Mariano Cambra, Ricardo Flores
Natural populations of peach latent mosaic viroid (PLMVd) are complex mixtures of variants. During routine testing, TaqMan rtRT-PCR and RNA gel-blot hybridization produced discordant results with some PLMVd isolates. Analysis of the corresponding populations showed that they were exclusively composed of variants (of class II) with a structural domain different from that of the reference and many other variants (of class I) targeted by the TaqMan rtRT-PCR probe. Bioassays in peach revealed that a representative PLMVd variant of class II replicated without symptoms, generated a progeny with low nucleotide diversity, and, intriguingly, outcompeted a representative symptomatic variant of class I when co-inoculated in equimolecular amounts...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210995/checkpoint-inhibitors-for-the-treatment-of-renal-cell-carcinoma
#2
REVIEW
Pooja Ghatalia, Matthew Zibelman, Daniel M Geynisman, Elizabeth R Plimack
The advent of checkpoint inhibitors has revolutionized systemic therapy for many malignancies, including renal cell carcinoma (RCC) where multiple PD-1, PD-L1, and CTLA-4 inhibitors have demonstrated responses and improved survival for patients in clinical trials. Durable benefit with manageable toxicity can be achieved with these agents-but unfortunately for only a minority of individuals. Efforts are ongoing to understand mechanisms driving the response and resistance to checkpoint inhibitors in order to personalize therapy and extend benefit to more patients...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28209969/solution-of-the-spatial-neutral-model-yields-new-bounds-on-the-amazonian-species-richness
#3
Yahav Shem-Tov, Matan Danino, Nadav M Shnerb
Neutral models, in which individual agents with equal fitness undergo a birth-death-mutation process, are very popular in population genetics and community ecology. Usually these models are applied to populations and communities with spatial structure, but the analytic results presented so far are limited to well-mixed or mainland-island scenarios. Here we combine analytic results and numerics to obtain an approximate solution for the species abundance distribution and the species richness for the neutral model on continuous landscape...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28201879/full-dimensional-ground-and-excited-state-potential-energy-surfaces-and-state-couplings-for-photodissociation-of-thioanisole
#4
Shaohong L Li, Donald G Truhlar
Analytic potential energy surfaces (PESs) and state couplings of the ground and two lowest singlet excited states of thioanisole (C6H5SCH3) are constructed in a diabatic representation based on electronic structure calculations including dynamic correlation. They cover all 42 internal degrees of freedom and a wide range of geometries including the Franck-Condon region and the reaction valley along the breaking S-CH3 bond with the full ranges of the torsion angles. The parameters in the PESs and couplings are fitted to the results of smooth diabatic electronic structure calculations including dynamic electron correlation by the extended multi-configurational quasi-degenerate perturbation theory method for the adiabatic state energies followed by diabatization by the fourfold way...
February 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28198700/towards-a-mechanistic-foundation-of-evolutionary-theory
#5
Michael Doebeli, Yaroslav Ispolatov, Burt Simon
Most evolutionary thinking is based on the notion of fitness and related ideas such as fitness landscapes and evolutionary optima. Nevertheless, it is often unclear what fitness actually is, and its meaning often depends on the context. Here we argue that fitness should not be a basal ingredient in verbal or mathematical descriptions of evolution. Instead, we propose that evolutionary birth-death processes, in which individuals give birth and die at ever-changing rates, should be the basis of evolutionary theory, because such processes capture the fundamental events that generate evolutionary dynamics...
February 15, 2017: ELife
https://www.readbyqxmd.com/read/28196882/trade-offs-between-enzyme-fitness-and-solubility-illuminated-by-deep-mutational-scanning
#6
Justin R Klesmith, John-Paul Bacik, Emily E Wrenbeck, Ryszard Michalczyk, Timothy A Whitehead
Proteins are marginally stable, and an understanding of the sequence determinants for improved protein solubility is highly desired. For enzymes, it is well known that many mutations that increase protein solubility decrease catalytic activity. These competing effects frustrate efforts to design and engineer stable, active enzymes without laborious high-throughput activity screens. To address the trade-off between enzyme solubility and activity, we performed deep mutational scanning using two different screens/selections that purport to gauge protein solubility for two full-length enzymes...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28178827/metabasin-transitions-are-johari-goldstein-relaxation-events
#7
Marcus T Cicerone, Madhusudan Tyagi
We show that by representing quasi-elastic and inelastic neutron scattering from propylene carbonate (PC) with an explicitly heterogeneous model, we recover signatures of two distinct localized modes in addition to diffusive motion. The intermediate scattering function provides access to the time-dependence of these two localized dynamic processes, and they appear to correspond to transitions between inherent states and between metabasins on a potential energy landscape. By fitting the full q-dependence of inelastic scattering, we confirm that the Johari-Goldstein (βJG) relaxation in PC is indistinguishable from metabasin transitions...
February 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28167146/are-males-more-scared-of-predators-differential-change-in-metabolic-rate-between-males-and-females-under-predation-risk
#8
Patricio A Lagos, Marie E Herberstein
The non-consumptive effects of predation contribute to reduce preys' fitness. In this way, predation imposes a cost to animals, not only through direct consumption, but also as an energetic cost. One way used to estimate this cost in the past has been to measure the production of CO2 to estimate the change in metabolic rate because of predation. It has been proposed that this change is mediated by the insect stress neurohormone octopamine. Here we study the change in metabolic rate of the black field cricket (Teleogryllus commodus), and how the production of CO2 varies when a chemical cue from a sympatric predator is added...
February 3, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28167050/changing-mutational-and-adaptive-landscapes-and-the-genesis-of-cancer
#9
L Alexander Liggett, James DeGregori
By the time the process of oncogenesis has produced an advanced cancer, tumor cells have undergone extensive evolution. The cellular phenotypes resulting from this evolution have been well studied, and include accelerated growth rates, apoptosis resistance, immortality, invasiveness, and immune evasion. Yet with all of our current knowledge of tumor biology, the details of early oncogenesis have been difficult to observe and understand. Where different oncogenic mutations may work together to enhance the survival of a tumor cell, in isolation they are often pro-apoptotic, pro-differentiative or pro-senescent, and therefore often, somewhat paradoxically, disadvantageous to a cell...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28165082/microscopic-nucleation-and-propagation-rates-of-an-alanine-based-%C3%AE-helix
#10
Chun-Wei Lin, Feng Gai
An infrared temperature-jump (T-jump) study by Huang et al. (Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 2788-2793) showed that the conformational relaxation kinetics of an alanine-based α-helical peptide depend not only on the final temperature (Tf) but also on the initial temperature (Ti) when Tf is fixed. Their finding indicates that the folding free energy landscape of this peptide is non-two-state like, allowing for the population of conformational ensembles with different helical lengths and relaxation times in the temperature range of the experiment...
February 6, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28159567/probing-the-excitonic-landscape-of-the-chlorobaculum-tepidum-fenna-matthews-olson-fmo-complex-a-mutagenesis-approach
#11
Rafael G Saer, Valentyn Stadnytskyi, Nikki C Magdaong, Carrie Goodson, Sergei Savikhin, Robert E Blankenship
In this paper we report the steady-state optical properties of a series of site-directed mutants in the Fenna-Matthews-Olson (FMO) complex of Chlorobaculum tepidum, a photosynthetic green sulfur bacterium. The FMO antenna complex has historically been used as a model system for energy transfer due to the water-soluble nature of the protein, its stability at room temperature, as well as the availability of high-resolution structural data. Eight FMO mutants were constructed with changes in the environment of each of the bacteriochlorophyll a pigments found within each monomer of the homotrimeric FMO complex...
January 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28153045/visualizing-phylogenetic-tree-landscapes
#12
James C Wilgenbusch, Wen Huang, Kyle A Gallivan
BACKGROUND: Genomic-scale sequence alignments are increasingly used to infer phylogenies in order to better understand the processes and patterns of evolution. Different partitions within these new alignments (e.g., genes, codon positions, and structural features) often favor hundreds if not thousands of competing phylogenies. Summarizing and comparing phylogenies obtained from multi-source data sets using current consensus tree methods discards valuable information and can disguise potential methodological problems...
February 2, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28152601/quantitative-proteomics-charts-the-landscape-of-salmonella-carbon-metabolism-within-host-epithelial-cells
#13
Yanhua Liu, Kaiwen Yu, Fan Zhou, Tao Ding, Yufei Yang, Mo Hu, Xiaoyun Liu
We performed a proteomic survey of Salmonella enterica serovar Typhimurium during infection of host epithelial cells. Our data reveal substantial metabolic reshuffling of Salmonella in the host in addition to severe degeneration of bacterial flagella and chemotaxis systems. The large-scale quantitative data allowed us to chart an overview of intracellular Salmonella carbon metabolism. Notably, we found preferential utilization of glycolysis, the pentose phosphate pathway, mixed acid fermentation, and nucleotide metabolism...
February 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28152456/geomorphology-applied-to-landscape-analysis-for-planning-and-management-of-natural-spaces-case-study-las-batuecas-s-de-francia-and-quilamas-natural-parks-salamanca-spain
#14
A M Martínez-Graña, P G Silva, J L Goy, J Elez, V Valdés, C Zazo
Geomorphology is fundamental to landscape analysis, as it represents the main parameter that determines the land spatial configuration and facilitates reliefs classification. The goal of this article is the elaboration of thematic maps that enable the determination of different landscape units and elaboration of quality and vulnerability synthetic maps for landscape fragility assessment prior to planning human activities. For two natural spaces, the final synthetic maps were created with direct (visual-perceptual features) and indirect (cartographic models and 3D simulations) methods from thematic maps with GIS technique...
January 30, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28120320/culture-and-biology-in-the-origins-of-linguistic-structure
#15
Simon Kirby
Language is systematically structured at all levels of description, arguably setting it apart from all other instances of communication in nature. In this article, I survey work over the last 20 years that emphasises the contributions of individual learning, cultural transmission, and biological evolution to explaining the structural design features of language. These 3 complex adaptive systems exist in a network of interactions: individual learning biases shape the dynamics of cultural evolution; universal features of linguistic structure arise from this cultural process and form the ultimate linguistic phenotype; the nature of this phenotype affects the fitness landscape for the biological evolution of the language faculty; and in turn this determines individuals' learning bias...
January 24, 2017: Psychonomic Bulletin & Review
https://www.readbyqxmd.com/read/28117544/specialist-care-of-older-adults-with-hiv-infection-in-the-uk-a-service-evaluation
#16
F V Cresswell, T Levett
OBJECTIVES: There is a clear trajectory towards cohort ageing in the UK. HIV infection is associated with an increased prevalence of traditionally age-related comorbidities and geriatric syndromes. Some HIV services have been proactive in innovating models that cater for adapting needs. We aimed to describe how widespread this practice is and what form such services take. METHODS: We conducted an evaluation of the perceived need for and current provision of specialist ageing services, and the need for formal guidance on monitoring or treatment of older adults with HIV infection...
January 24, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28116365/exploring-experimental-fitness-landscapes-for-chemical-synthesis-and-property-optimization
#17
Katharine Moore Tibbetts, Xiao-Jiang Feng, Herschel Rabitz
Optimization is a central goal in the chemical sciences, encompassing diverse objectives including synthesis yield, catalytic activity of a material, and binding efficiency of a molecule to a target protein. Considering the enormous size of chemical space and the expected large numbers of experiments necessary to search through it in any particular application, optimization in chemistry is surprisingly efficient. This good fortune has recently been explained by analysis of the fitness landscape, i.e., the functional relationship between a target objective J (e...
January 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28113694/solving-multiobjective-optimization-problems-in-unknown-dynamic-environments-an-inverse-modeling-approach
#18
Sen Bong Gee, Kay Chen Tan, Cesare Alippi
Evolutionary multiobjective optimization in dynamic environments is a challenging task, as it requires the optimization algorithm converging to a time-variant Pareto optimal front. This paper proposes a dynamic multiobjective optimization algorithm which utilizes an inverse model set to guide the search toward promising decision regions. In order to reduce the number of fitness evalutions for change detection purpose, a two-stage change detection test is proposed which uses the inverse model set to check potential changes in the objective function landscape...
September 12, 2016: IEEE Transactions on Cybernetics
https://www.readbyqxmd.com/read/28112740/a-somatic-mutational-process-recurrently-duplicates-germline-susceptibility-loci-and-tissue-specific-super-enhancers-in-breast-cancers
#19
Dominik Glodzik, Sandro Morganella, Helen Davies, Peter T Simpson, Yilong Li, Xueqing Zou, Javier Diez-Perez, Johan Staaf, Ludmil B Alexandrov, Marcel Smid, Arie B Brinkman, Inga Hansine Rye, Hege Russnes, Keiran Raine, Colin A Purdie, Sunil R Lakhani, Alastair M Thompson, Ewan Birney, Hendrik G Stunnenberg, Marc J van de Vijver, John W M Martens, Anne-Lise Børresen-Dale, Andrea L Richardson, Gu Kong, Alain Viari, Douglas Easton, Gerard Evan, Peter J Campbell, Michael R Stratton, Serena Nik-Zainal
Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3...
January 23, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28110273/shifting-balance-on-a-static-mutation-selection-landscape-a-novel-scenario-of-positive-selection
#20
Christopher T Jones, Noor Youssef, Edward Susko, Joseph P Bielawski
A version of the mechanistic mutation-selection (MutSel) model that accounts for temporal dynamics at a site is presented. This is used to show that the rate ratio dN/dS at a site can be transiently >1 even when fitness coefficients are fixed or the fitness landscape is static. This occurs whenever a site drifts away from its fitness peak and is then forced back by selection, a process reminiscent of shifting balance. Shifting balance is strongest when the substitution process is not dominated by selection or drift, but admits interplay between the two...
November 8, 2016: Molecular Biology and Evolution
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