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https://www.readbyqxmd.com/read/28530655/a-quantitative-and-multiplexed-approach-to-uncover-the-fitness-landscape-of-tumor-suppression-in-vivo
#1
Zoë N Rogers, Christopher D McFarland, Ian P Winters, Santiago Naranjo, Chen-Hua Chuang, Dmitri Petrov, Monte M Winslow
Cancer growth is a multistage, stochastic evolutionary process. While cancer genome sequencing has been instrumental in identifying the genomic alterations that occur in human tumors, the consequences of these alterations on tumor growth remain largely unexplored. Conventional genetically engineered mouse models enable the study of tumor growth in vivo, but they are neither readily scalable nor sufficiently quantitative to unravel the magnitude and mode of action of many tumor-suppressor genes. Here, we present a method that integrates tumor barcoding with ultradeep barcode sequencing (Tuba-seq) to interrogate tumor-suppressor function in mouse models of human cancer...
May 22, 2017: Nature Methods
https://www.readbyqxmd.com/read/28522360/sex-with-no-regrets-how-sexual-reproduction-uses-a-no-regret-learning-algorithm-for-evolutionary-advantage
#2
Omer Edhan, Ziv Hellman, Dana Sherill-Rofe
The question of 'why sex' has long been a puzzle. The randomness of recombination, which potentially produces low fitness progeny, contradicts notions of fitness landscape hill climbing. We use the concept of evolution as an algorithm for learning unpredictable environments to provide a possible answer. While sex and asex both implement similar machine learning no-regret algorithms in the context of random samples that are small relative to a vast genotype space, the algorithm of sex constitutes a more efficient goal-directed walk through this space...
May 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28507232/energy-landscape-analysis-of-neuroimaging-data
#3
Takahiro Ezaki, Takamitsu Watanabe, Masayuki Ohzeki, Naoki Masuda
Computational neuroscience models have been used for understanding neural dynamics in the brain and how they may be altered when physiological or other conditions change. We review and develop a data-driven approach to neuroimaging data called the energy landscape analysis. The methods are rooted in statistical physics theory, in particular the Ising model, also known as the (pairwise) maximum entropy model and Boltzmann machine. The methods have been applied to fitting electrophysiological data in neuroscience for a decade, but their use in neuroimaging data is still in its infancy...
June 28, 2017: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/28493816/sample-types-applied-for-molecular-diagnosis-of-therapeutic-management-of-advanced-non-small-cell-lung-cancer-in-the-precision-medicine
#4
Yanxi Han, Jinming Li
In this era of precision medicine, molecular biology is becoming increasingly significant for the diagnosis and therapeutic management of non-small cell lung cancer. The specimen as the primary element of the whole testing flow is particularly important for maintaining the accuracy of gene alteration testing. Presently, the main sample types applied in routine diagnosis are tissue and cytology biopsies. Liquid biopsies are considered as the most promising alternatives when tissue and cytology samples are not available...
May 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28486496/phenotypic-heterogeneity-promotes-adaptive-evolution
#5
Zoltán Bódi, Zoltán Farkas, Dmitry Nevozhay, Dorottya Kalapis, Viktória Lázár, Bálint Csörgő, Ákos Nyerges, Béla Szamecz, Gergely Fekete, Balázs Papp, Hugo Araújo, José L Oliveira, Gabriela Moura, Manuel A S Santos, Tamás Székely, Gábor Balázsi, Csaba Pál
Genetically identical cells frequently display substantial heterogeneity in gene expression, cellular morphology and physiology. It has been suggested that by rapidly generating a subpopulation with novel phenotypic traits, phenotypic heterogeneity (or plasticity) accelerates the rate of adaptive evolution in populations facing extreme environmental challenges. This issue is important as cell-to-cell phenotypic heterogeneity may initiate key steps in microbial evolution of drug resistance and cancer progression...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28484629/multiple-phase-transitions-in-an-agent-based-evolutionary-model-with-neutral-fitness
#6
Dawn M King, Adam D Scott, Sonya Bahar
Null models are crucial for understanding evolutionary processes such as speciation and adaptive radiation. We analyse an agent-based null model, considering a case without selection-neutral evolution-in which organisms are defined only by phenotype. Universal dynamics has previously been demonstrated in a related model on a neutral fitness landscape, showing that this system belongs to the directed percolation (DP) universality class. The traditional null condition of neutral fitness (where fitness is defined as the number of offspring each organism produces) is extended here to include equal probability of death among organisms...
April 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28483864/multiple-extreme-climatic-events-strengthen-selection-for-earlier-breeding-in-a-wild-passerine
#7
Pascal Marrot, Dany Garant, Anne Charmantier
Global climate warming results in an increase in mean temperatures and in the frequency of extreme climatic events (ECEs), which could both strongly impact ecosystems and populations. Most studies assessing the impact of global warming on ecosystems have focused on warming trends while neglecting ECEs. In particular, the effects of multiple ECEs on fitness, and their consequences for selection, are still missing. Here we explored the effects of daily extreme rainfalls, as well as the occurrence of extremely hot and cold days, on clutch size and laying date in a wild blue tit population (Cyanistes caeruleus) monitored over 25 years...
June 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28464395/specificity-effects-of-amino-acid-substitutions-in-promiscuous-hydrolases-context-dependence-of-catalytic-residue-contributions-to-local-fitness-landscapes-in-nearby-sequence-space
#8
Christopher D Bayer, Bert van Loo, Florian Hollfelder
Catalytic promiscuity can facilitate evolution of enzyme functions-a multifunctional catalyst may act as a springboard for efficient functional adaptation. We test the effect of single mutations on multiple activities in two groups of promiscuous AP superfamily members to probe this hypothesis. We quantify the effect of site-saturating mutagenesis of an analogous, nucleophile-flanking residue in two superfamily members: an arylsulfatase (AS) and a phosphonate monoester hydrolase (PMH). Statistical analysis suggests that no one physicochemical characteristic alone explains the mutational effects...
May 2, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28462019/the-importance-of-scale-dependent-ravine-characteristics-on-breeding-site-selection-by-the-burrowing-parrot-cyanoliseus-patagonus
#9
Myriam Ramirez-Herranz, Rodrigo S Rios, Renzo Vargas-Rodriguez, Jose-Enrique Novoa-Jerez, Francisco A Squeo
In birds, the environmental variables and intrinsic characteristics of the nest have important fitness consequences through its influence on the selection of nesting sites. However, the extent to which these variables interact with variables that operate at the landscape scale, and whether there is a hierarchy among the different scales that influences nest-site selection, is unknown. This interaction could be crucial in burrowing birds, which depend heavily on the availability of suitable nesting locations...
2017: PeerJ
https://www.readbyqxmd.com/read/28461506/molecular-mechanism-of-multispecific-recognition-of-calmodulin-through-conformational-changes
#10
Fei Liu, Xiakun Chu, H Peter Lu, Jin Wang
Calmodulin (CaM) is found to have the capability to bind multiple targets. Investigations on the association mechanism of CaM to its targets are crucial for understanding protein-protein binding and recognition. Here, we developed a structure-based model to explore the binding process between CaM and skMLCK binding peptide. We found the cooperation between nonnative electrostatic interaction and nonnative hydrophobic interaction plays an important role in nonspecific recognition between CaM and its target. We also found that the conserved hydrophobic anchors of skMLCK and binding patches of CaM are crucial for the transition from high affinity to high specificity...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28458914/in-vivo-mutation-rates-and-the-landscape-of-fitness-costs-of-hiv-1
#11
Fabio Zanini, Vadim Puller, Johanna Brodin, Jan Albert, Richard A Neher
Mutation rates and fitness costs of deleterious mutations are difficult to measure in vivo but essential for a quantitative understanding of evolution. Using whole genome deep sequencing data from longitudinal samples during untreated HIV-1 infection, we estimated mutation rates and fitness costs in HIV-1 from the dynamics of genetic variation. At approximately neutral sites, mutations accumulate with a rate of 1.2 × 10(-5) per site per day, in agreement with the rate measured in cell cultures. We estimated the rate from G to A to be the largest, followed by the other transitions C to T, T to C, and A to G, while transversions are less frequent...
January 2017: Virus Evolution
https://www.readbyqxmd.com/read/28455145/managing-expense-and-expectation-in-a-treatment-revolution-problematizing-prioritisation-through-an-exploration-of-hepatitis-c-treatment-benefit
#12
Magdalena Harris
BACKGROUND: Direct-acting antivirals (DAAs) have transformed the hepatitis C (HCV) treatment landscape. These highly effective drugs are, however, not available to all. In a context of DAA rationing, clinicians are advised to "manage patient expectations" about the benefits of a HCV cure. This directive particularly pertains to people with minimal liver damage and those who have ceased injecting: populations negated in contemporary prioritisation debates. METHODS: This paper engages with the assumptions underpinning HCV treatment prioritisation discourses to explore the concept of treatment 'benefit' from patient perspectives...
April 25, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28450460/genotypic-complexity-of-fisher-s-geometric-model
#13
Sungmin Hwang, Su-Chan Park, Joachim Krug
Fisher's geometric model was originally introduced to argue that complex adaptations must occur in small steps because of pleiotropic constraints. When supplemented with the assumption of additivity of mutational effects on phenotypic traits, it provides a simple mechanism for the emergence of genotypic epistasis from the nonlinear mapping of phenotypes to fitness. Of particular interest is the occurrence of reciprocal sign epistasis, which is a necessary condition for multipeaked genotypic fitness landscapes...
April 26, 2017: Genetics
https://www.readbyqxmd.com/read/28442429/woodland-features-determining-home-range-size-of-roe-deer
#14
Sandro Lovari, Giulia Serrao, Emiliano Mori
Use of ecotones by ungulates may be mediated by their movements between main feeding areas and woodland, where they locate their shelter. The roe deer Capreolus capreolus has been termed as a woodland species, although we suggest that it did not evolve as a forest ungulate, but depending on forest glades. Roe deer feed on a wide range of vegetal species, although their diet is mainly dominated by woody plants. Our study was carried out in a fragmented area covered with small forest patches of Mediterranean "macchia" scrubwood, interspersed in an agricultural matrix...
April 23, 2017: Behavioural Processes
https://www.readbyqxmd.com/read/28425825/reviewing-treatments-and-outcomes-in-the-evolving-landscape-of-ulcerative-colitis
#15
Marla C Dubinsky
Ulcerative colitis (UC) is a chronic inflammatory disease extending proximally from the rectum to varying lengths of the colon that is characterized by alternating cycles of relapse and remission. Therapeutic goals for patients with active UC include induction and maintenance of remission and improvement in quality of life, as well as mucosal healing, a clinical outcome recently recognized in treatment guidance as being equally important. Mucosal healing is associated with favorable long-term patient outcomes related to remission, surgery, hospitalization, and quality of life...
May 2, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28423062/filamentous-fungal-carbon-catabolite-repression-supports-metabolic-plasticity-and-stress-responses-essential-for-disease-progression
#16
Sarah R Beattie, Kenneth M K Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna K Caffrey-Carr, Chao Cheng, Candice C Black, Paul Bowyer, Michael J Bromley, Joshua J Obar, Gustavo H Goldman, Robert A Cramer
Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28419782/natural-resource-landscapes-of-a-marine-bacterium-reveal-distinct-fitness-determining-genes-across-the-genome
#17
Alison F Takemura, Christopher H Corzett, Fatima Hussain, Philip Arevalo, Manoshi Datta, Xiaoqian Yu, Frederique Le Roux, Martin F Polz
Heterotrophic bacteria exploit diverse microhabitats in the ocean, from particles to transient gradients. Yet the degree to which genes and pathways can contribute to an organism's fitness on such complex and variable natural resource landscapes remains poorly understood. Here, we determine the gene-by-gene fitness of a generalist saprophytic marine bacterium (Vibrio sp. F13 9CS106) on complex resources derived from its natural habitats - copepods (Apocyclops royi) and brown algae (Fucus vesiculosus) - and as reference substrates, glucose and the polysaccharide alginate, derived from brown algal cell walls...
April 17, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28410373/parallel-reorganization-of-protein-function-in-the-spindle-checkpoint-pathway-through-evolutionary-paths-in-the-fitness-landscape-that-appear-neutral-in-laboratory-experiments
#18
Alex N Nguyen Ba, Bob Strome, Selma Osman, Elizabeth-Ann Legere, Taraneh Zarin, Alan M Moses
Regulatory networks often increase in complexity during evolution through gene duplication and divergence of component proteins. Two models that explain this increase in complexity are: 1) adaptive changes after gene duplication, such as resolution of adaptive conflicts, and 2) non-adaptive processes such as duplication, degeneration and complementation. Both of these models predict complementary changes in the retained duplicates, but they can be distinguished by direct fitness measurements in organisms with short generation times...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28408285/from-epigenetic-landscape-to-phenotypic-fitness-landscape-evolutionary-effect-of-pathogens-on-host-traits
#19
Mark Jayson V Cortez, Jomar F Rabajante, Jerrold M Tubay, Ariel L Babierra
The epigenetic landscape illustrates how cells differentiate through the control of gene regulatory networks. Numerous studies have investigated epigenetic gene regulation but there are limited studies on how the epigenetic landscape and the presence of pathogens influence the evolution of host traits. Here, we formulate a multistable decision-switch model involving several phenotypes with the antagonistic influence of parasitism. As expected, pathogens can drive dominant (common) phenotypes to become inferior through negative frequency-dependent selection...
April 10, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28404780/environmental-modification-via-a-quorum-sensing-molecule-influences-the-social-landscape-of-siderophore-production
#20
Roman Popat, Freya Harrison, Ana C da Silva, Scott A S Easton, Luke McNally, Paul Williams, Stephen P Diggle
Bacteria produce a wide variety of exoproducts that favourably modify their environment and increase their fitness. These are often termed 'public goods' because they are costly for individuals to produce and can be exploited by non-producers (cheats). The outcome of conflict over public goods is dependent upon the prevailing environment and the phenotype of the individuals in competition. Many bacterial species use quorum sensing (QS) signalling molecules to regulate the production of public goods. QS, therefore, determines the cooperative phenotype of individuals, and influences conflict over public goods...
April 12, 2017: Proceedings. Biological Sciences
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