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https://www.readbyqxmd.com/read/28319179/biophysical-comparison-of-atp-driven-proton-pumping-mechanisms-suggests-a-kinetic-advantage-for-the-rotary-process-depending-on-coupling-ratio
#1
Ramu Anandakrishnan, Daniel M Zuckerman
ATP-driven proton pumps, which are critical to the operation of a cell, maintain cytosolic and organellar pH levels within a narrow functional range. These pumps employ two very different mechanisms: an elaborate rotary mechanism used by V-ATPase H+ pumps, and a simpler alternating access mechanism used by P-ATPase H+ pumps. Why are two different mechanisms used to perform the same function? Systematic analysis, without parameter fitting, of kinetic models of the rotary, alternating access and other possible mechanisms suggest that, when the ratio of protons transported per ATP hydrolyzed exceeds one, the one-at-a-time proton transport by the rotary mechanism is faster than other possible mechanisms across a wide range of driving conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28298007/impact-of-centrality-on-cooperative-processes
#2
Sandro M Reia, Sebastian Herrmann, José F Fontanari
The solution of today's complex problems requires the grouping of task forces whose members are usually connected remotely over long physical distances and different time zones. Hence, understanding the effects of imposed communication patterns (i.e., who can communicate with whom) on group performance is important. Here we use an agent-based model to explore the influence of the betweenness centrality of the nodes on the time the group requires to find the global maxima of NK-fitness landscapes. The agents cooperate by broadcasting messages, informing on their fitness to their neighbors, and use this information to copy the more successful agents in their neighborhood...
February 2017: Physical Review. E
https://www.readbyqxmd.com/read/28297440/evaluation-of-the-uncertainty-in-an-ebt3-film-dosimetry-system-utilizing-net-optical-density
#3
Elsa Y León Marroquin, José A Herrera González, Miguel A Camacho López, José E Villarreal Barajas, Olivia A García-Garduño
Radiochromic film has become an important tool to verify dose distributions for intensity-modulated radiotherapy (IMRT) and quality assurance (QA) procedures. A new radiochromic film model, EBT3, has recently become available, whose composition and thickness of the sensitive layer are the same as those of previous EBT2 films. However, a matte polyester layer was added to EBT3 to prevent the formation of Newton's rings. Furthermore, the symmetrical design of EBT3 allows the user to eliminate side-orientation dependence...
September 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28289190/ampk-blocks-starvation-inducible-transgenerational-defects-in-caenorhabditis-elegans
#4
Emilie Demoinet, Shaolin Li, Richard Roy
Life history events, such as traumatic stress, illness, or starvation, can influence us through molecular changes that are recorded in a pattern of characteristic chromatin modifications. These modifications are often associated with adaptive adjustments in gene expression that can persist throughout the lifetime of the organism, or even span multiple generations. Although these adaptations may confer some selective advantage, if they are not appropriately regulated they can also be maladaptive in a context-dependent manner...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28287430/targeted-drugs-as-maintenance-therapy-after-autologous-stem-cell-transplantation-in-patients-with-mantle-cell-lymphoma
#5
REVIEW
Fengting Yan, Ajay K Gopal, Solomon A Graf
The treatment landscape for mantle cell lymphoma (MCL) is rapidly evolving toward the incorporation of novel and biologically targeted pharmaceuticals with improved disease activity and gentler toxicity profiles compared with conventional chemotherapeutics. Upfront intensive treatment of MCL includes autologous stem cell transplantation (SCT) consolidation aimed at deepening and lengthening disease remission, but subsequent relapse occurs. Maintenance therapy after autologous SCT in patients with MCL in remission features lower-intensity treatments given over extended periods to improve disease outcomes...
March 10, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28286924/treatment-of-relapsed-refractory-acute-myeloid-leukemia
#6
REVIEW
Prithviraj Bose, Pankit Vachhani, Jorge E Cortes
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28271105/optimal-parameter-values-for-the-control-of-gene-regulation
#7
R G Brajesh, Nikhil Raj, Supreet Saini
How does a transcription network arrive at the particular values of biochemical interactions defining it? These interactions define DNA-transcription factor interaction, degradation rates of proteins, promoter strengths, and communication of the environmental signal with the network. What is the structure of the fitness landscape that is defined by the space that these parameters can take on? To answer these questions, we simulate the simplest regulatory network: a transcription factor, R, and a target protein, T...
March 8, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28267748/inferring-fitness-landscapes-and-selection-on-phenotypic-states-from-single-cell-genealogical-data
#8
Takashi Nozoe, Edo Kussell, Yuichi Wakamoto
Recent advances in single-cell time-lapse microscopy have revealed non-genetic heterogeneity and temporal fluctuations of cellular phenotypes. While different phenotypic traits such as abundance of growth-related proteins in single cells may have differential effects on the reproductive success of cells, rigorous experimental quantification of this process has remained elusive due to the complexity of single cell physiology within the context of a proliferating population. We introduce and apply a practical empirical method to quantify the fitness landscapes of arbitrary phenotypic traits, using genealogical data in the form of population lineage trees which can include phenotypic data of various kinds...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28267242/arctic-shrub-growth-trajectories-differ-across-soil-moisture-levels
#9
Daniel Ackerman, Daniel Griffin, Sarah E Hobbie, Jacques C Finlay
The circumpolar expansion of woody deciduous shrubs in arctic tundra alters key ecosystem properties including carbon balance and hydrology. However, landscape-scale patterns and drivers of shrub expansion remain poorly understood, inhibiting accurate incorporation of shrub effects into climate models. Here, we use dendroecology to elucidate the role of soil moisture in modifying the relationship between climate and growth for a dominant deciduous shrub, Salix pulchra, on the North Slope of Alaska, USA. We improve upon previous modeling approaches by using ecological theory to guide model selection for the relationship between climate and shrub growth...
March 7, 2017: Global Change Biology
https://www.readbyqxmd.com/read/28262665/correlation-of-fitness-landscapes-from-three-orthologous-tim-barrels-originates-from-sequence-and-structure-constraints
#10
Yvonne H Chan, Sergey V Venev, Konstantin B Zeldovich, C Robert Matthews
Sequence divergence of orthologous proteins enables adaptation to environmental stresses and promotes evolution of novel functions. Limits on evolution imposed by constraints on sequence and structure were explored using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Analysis of beneficial mutations pointed to an unexpected, long-range allosteric pathway towards the active site of the protein...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28261445/evaluating-the-consequences-of-salmon-nutrients-for-riparian-organisms-linking-condition-metrics-to-stable-isotopes
#11
Carmella Vizza, Beth L Sanderson, Holly J Coe, Dominic T Chaloner
Stable isotope ratios (δ(13)C and δ(15)N) have been used extensively to trace nutrients from Pacific salmon, but salmon transfer more than carbon and nitrogen to stream ecosystems, such as phosphorus, minerals, proteins, and lipids. To examine the importance of these nutrients, metrics other than isotopes need to be considered, particularly when so few studies have made direct links between these nutrients and how they affect riparian organisms. Our study specifically examined δ(13)C and δ(15)N of riparian organisms from salmon and non-salmon streams in Idaho, USA, at different distances from the streams, and examined whether the quality of riparian plants and the body condition of invertebrates varied with access to these nutrients...
March 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28259431/the-impact-of-land-use-intensity-and-associated-pesticide-applications-on-fitness-and-enzymatic-activity-in-reptiles-a-field-study
#12
Valentin Mingo, Stefan Lötters, Norman Wagner
Environmental pollution and habitat loss are described as underlying causes for population declines in reptiles and especially affect species in agricultural landscapes. Studies dealing with effects of pesticide exposure on reptiles are limited, mainly addressing the orders Testudines and Crocodylia, but largely neglecting the most diverse reptile order Squamata (lizards and snakes). As a consequence, information regarding effects on their organisms, as well as exposure probability and pesticide uptake in the Reptilia has to be considered rather uncharted...
March 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28250184/pedigree-based-inbreeding-coefficient-explains-more-variation-in-fitness-than-heterozygosity-at-160-microsatellites-in-a-wild-bird-population
#13
Pirmin Nietlisbach, Lukas F Keller, Glauco Camenisch, Frédéric Guillaume, Peter Arcese, Jane M Reid, Erik Postma
Although the pedigree-based inbreeding coefficient F predicts the expected proportion of an individual's genome that is identical-by-descent (IBD), heterozygosity at genetic markers captures Mendelian sampling variation and thereby provides an estimate of realized IBD. Realized IBD should hence explain more variation in fitness than their pedigree-based expectations, but how many markers are required to achieve this in practice remains poorly understood. We use extensive pedigree and life-history data from an island population of song sparrows (Melospiza melodia) to show that the number of genetic markers and pedigree depth affected the explanatory power of heterozygosity and F, respectively, but that heterozygosity measured at 160 microsatellites did not explain more variation in fitness than F This is in contrast with other studies that found heterozygosity based on far fewer markers to explain more variation in fitness than F Thus, the relative performance of marker- and pedigree-based estimates of IBD depends on the quality of the pedigree, the number, variability and location of the markers employed, and the species-specific recombination landscape, and expectations based on detailed and deep pedigrees remain valuable until we can routinely afford genotyping hundreds of phenotyped wild individuals of genetic non-model species for thousands of genetic markers...
March 15, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28246638/evolutionary-fine-tuning-of-conformational-ensembles-in-fimh-during-host-pathogen-interactions
#14
Vasilios Kalas, Jerome S Pinkner, Thomas J Hannan, Michael E Hibbing, Karen W Dodson, Alex S Holehouse, Hao Zhang, Niraj H Tolia, Michael L Gross, Rohit V Pappu, James Janetka, Scott J Hultgren
Positive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro...
February 2017: Science Advances
https://www.readbyqxmd.com/read/28245845/adaptive-multiscapes-an-up-to-date-metaphor-to-visualize-molecular-adaptation
#15
EDITORIAL
Pablo Catalán, Clemente F Arias, Jose A Cuesta, Susanna Manrubia
BACKGROUND: Wright's metaphor of the fitness landscape has shaped and conditioned our view of the adaptation of populations for almost a century. Since its inception, and including criticism raised by Wright himself, the concept has been surrounded by controversy. Among others, the debate stems from the intrinsic difficulty to capture important features of the space of genotypes, such as its high dimensionality or the existence of abundant ridges, in a visually appealing two-dimensional picture...
February 28, 2017: Biology Direct
https://www.readbyqxmd.com/read/28238940/dynamic-landscape-models-of-coevolutionary-games
#16
Hendrik Richter
Players of coevolutionary games may update not only their strategies but also their networks of interaction. Based on interpreting the payoff of players as fitness, dynamic landscape models are proposed. The modeling procedure is carried out for Prisoner's Dilemma (PD) and Snowdrift (SD) games that both use either birth-death (BD) or death-birth (DB) strategy updating. The main focus is on using dynamic fitness landscapes as a mathematical model of coevolutionary game dynamics. Hence, an alternative tool for analyzing coevolutionary games becomes available, and landscape measures such as modality, ruggedness and information content can be computed and analyzed...
February 24, 2017: Bio Systems
https://www.readbyqxmd.com/read/28236707/effect-of-landscape-tree-cover-sex-and-season-on-the-bioaccumulation-of-persistent-organochlorine-pesticides-in-fruit-bats-of-riparian-corridors-in-eastern-mexico
#17
Carolina Valdespino, Vinicio J Sosa
Riparian forests are recognized as important ecosystems for biodiversity conservation in transformed landscapes. Many animal species that use this type of vegetation facilitate its recovery through pollination and seed dispersal. In landscapes dominated by agrosystems and cattle ranching, persistent organochlorine pesticides (OCPs) in the riparian system may have an effect on the physiology and fitness of animals. In this study, we measured bioaccumulation of OCPs in the most abundant frugivorous bat, Sturnira hondurensis, from the upper part of La Antigua basin, Veracruz, Mexico and, from these data, estimated accumulation by the frugivorous bat community of riparian forests in contrasting, transformed (TL) and forested (FL) landscapes...
May 2017: Chemosphere
https://www.readbyqxmd.com/read/28211491/interference-between-variants-of-peach-latent-mosaic-viroid-reveals-novel-features-of-its-fitness-landscape-implications-for-detection
#18
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
#19
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
#20
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
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