The Burmese python genome reveals the molecular basis for extreme adaptation in snakes

PubMed Central

Castoe, Todd A.; de Koning, A. P. Jason; Hall, Kathryn T.; Card, Daren C.; Schield, Drew R.; Fujita, Matthew K.; Ruggiero, Robert P.; Degner, Jack F.; Daza, Juan M.; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J.; Castoe, Jill M.; Fox, Samuel E.; Poole, Alex W.; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W.; Li, Qing; Schott, Ryan K.; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A.; Hoffmann, Federico G.; Bogden, Robert; Smith, Eric N.; Chang, Belinda S. W.; Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Richardson, Michael K.; Mackessy, Stephen P.; Bronikowski, Anne M.; Yandell, Mark; Warren, Wesley C.; Secor, Stephen M.; Pollock, David D.

2013-01-01

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome. PMID:24297902

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes.

PubMed

Castoe, Todd A; de Koning, A P Jason; Hall, Kathryn T; Card, Daren C; Schield, Drew R; Fujita, Matthew K; Ruggiero, Robert P; Degner, Jack F; Daza, Juan M; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J; Castoe, Jill M; Fox, Samuel E; Poole, Alex W; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W; Li, Qing; Schott, Ryan K; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A; Hoffmann, Federico G; Bogden, Robert; Smith, Eric N; Chang, Belinda S W; Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Richardson, Michael K; Mackessy, Stephen P; Bronikowski, Anne M; Bronikowsi, Anne M; Yandell, Mark; Warren, Wesley C; Secor, Stephen M; Pollock, David D

2013-12-17

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.

Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation.

PubMed

Amato, Roberto; Pinelli, Michele; Monticelli, Antonella; Miele, Gennaro; Cocozza, Sergio

2010-11-11

Many natural phenomena are directly or indirectly related to latitude. Living at different latitudes, indeed, has its consequences with being exposed to different climates, diets, light/dark cycles, etc. In humans, one of the best known examples of genetic traits following a latitudinal gradient is skin pigmentation. Nevertheless, also several diseases show latitudinal clinals such as hypertension, cancer, dismetabolic conditions, schizophrenia, Parkinson's disease and many more. We investigated, for the first time on a wide genomic scale, the latitude-driven adaptation phenomena. In particular, we selected a set of genes showing signs of latitude-dependent population differentiation. The biological characterization of these genes showed enrichment for neural-related processes. In light of this, we investigated whether genes associated to neuropsychiatric diseases were enriched by Latitude-Related Genes (LRGs). We found a strong enrichment of LRGs in the set of genes associated to schizophrenia. In an attempt to try to explain this possible link between latitude and schizophrenia, we investigated their associations with vitamin D. We found in a set of vitamin D related genes a significant enrichment of both LRGs and of genes involved in schizophrenia. Our results suggest a latitude-driven adaptation for both schizophrenia and vitamin D related genes. In addition we confirm, at a molecular level, the link between schizophrenia and vitamin D. Finally, we discuss a model in which schizophrenia is, at least partly, a maladaptive by-product of latitude dependent adaptive changes in vitamin D metabolism.

Targeting the adaptive molecular landscape of castration-resistant prostate cancer

PubMed Central

Wyatt, Alexander W; Gleave, Martin E

2015-01-01

Castration and androgen receptor (AR) pathway inhibitors induce profound and sustained responses in advanced prostate cancer. However, the inevitable recurrence is associated with reactivation of the AR and progression to a more aggressive phenotype termed castration-resistant prostate cancer (CRPC). AR reactivation can occur directly through genomic modification of the AR gene, or indirectly via co-factor and co-chaperone deregulation. This mechanistic heterogeneity is further complicated by the stress-driven induction of a myriad of overlapping cellular survival pathways. In this review, we describe the heterogeneous and evolvable molecular landscape of CRPC and explore recent successes and failures of therapeutic strategies designed to target AR reactivation and adaptive survival pathways. We also discuss exciting areas of burgeoning anti-tumour research, and their potential to improve the survival and management of patients with CRPC. PMID:25896606

Molecular-channel driven actuator with considerations for multiple configurations and color switching.

PubMed

Mu, Jiuke; Wang, Gang; Yan, Hongping; Li, Huayu; Wang, Xuemin; Gao, Enlai; Hou, Chengyi; Pham, Anh Thi Cam; Wu, Lianjun; Zhang, Qinghong; Li, Yaogang; Xu, Zhiping; Guo, Yang; Reichmanis, Elsa; Wang, Hongzhi; Zhu, Meifang

2018-02-09

The ability to achieve simultaneous intrinsic deformation with fast response in commercially available materials that can safely contact skin continues to be an unresolved challenge for artificial actuating materials. Rather than using a microporous structure, here we show an ambient-driven actuator that takes advantage of inherent nanoscale molecular channels within a commercial perfluorosulfonic acid ionomer (PFSA) film, fabricated by simple solution processing to realize a rapid response, self-adaptive, and exceptionally stable actuation. Selective patterning of PFSA films on an inert soft substrate (polyethylene terephthalate film) facilitates the formation of a range of different geometries, including a 2D (two-dimensional) roll or 3D (three-dimensional) helical structure in response to vapor stimuli. Chemical modification of the surface allowed the development of a kirigami-inspired single-layer actuator for personal humidity and heat management through macroscale geometric design features, to afford a bilayer stimuli-responsive actuator with multicolor switching capability.

Application of Bounded Linear Stability Analysis Method for Metrics-Driven Adaptive Control

NASA Technical Reports Server (NTRS)

Bakhtiari-Nejad, Maryam; Nguyen, Nhan T.; Krishnakumar, Kalmanje

2009-01-01

This paper presents the application of Bounded Linear Stability Analysis (BLSA) method for metrics-driven adaptive control. The bounded linear stability analysis method is used for analyzing stability of adaptive control models, without linearizing the adaptive laws. Metrics-driven adaptive control introduces a notion that adaptation should be driven by some stability metrics to achieve robustness. By the application of bounded linear stability analysis method the adaptive gain is adjusted during the adaptation in order to meet certain phase margin requirements. Analysis of metrics-driven adaptive control is evaluated for a second order system that represents a pitch attitude control of a generic transport aircraft. The analysis shows that the system with the metrics-conforming variable adaptive gain becomes more robust to unmodeled dynamics or time delay. The effect of analysis time-window for BLSA is also evaluated in order to meet the stability margin criteria.

Electrostatic stiffening and induced persistence length for coassembled molecular bottlebrushes

NASA Astrophysics Data System (ADS)

Storm, Ingeborg M.; Stuart, Martien A. Cohen; de Vries, Renko; Leermakers, Frans A. M.

2018-03-01

A self-consistent field analysis for tunable contributions to the persistence length of isolated semiflexible polymer chains including electrostatically driven coassembled deoxyribonucleic acid (DNA) bottlebrushes is presented. When a chain is charged, i.e., for polyelectrolytes, there is, in addition to an intrinsic rigidity, an electrostatic stiffening effect, because the electric double layer resists bending. For molecular bottlebrushes, there is an induced contribution due to the grafts. We explore cases beyond the classical phantom main-chain approximation and elaborate molecularly more realistic models where the backbone has a finite volume, which is necessary for treating coassembled bottlebrushes. We find that the way in which the linear charge density or the grafting density is regulated is important. Typically, the stiffening effect is reduced when there is freedom for these quantities to adapt to the curvature stresses. Electrostatically driven coassembled bottlebrushes, however, are relatively stiff because the chains have a low tendency to escape from the compressed regions and the electrostatic binding force is largest in the convex part. For coassembled bottlebrushes, the induced persistence length is a nonmonotonic function of the polymer concentration: For low polymer concentrations, the stiffening grows quadratically with coverage; for semidilute polymer concentrations, the brush chains retract and regain their Gaussian size. When doing so, they lose their induced persistence length contribution. Our results correlate well with observed physical characteristics of electrostatically driven coassembled DNA-bioengineered protein-polymer bottlebrushes.

Rotaxane liquid crystals with variable length: The effect of switching efficiency on the isotropic-nematic transition

NASA Astrophysics Data System (ADS)

He, Hao; Sevick, Edith M.; Williams, David R. M.

2018-04-01

We examine a solution of non-adaptive two-state rotaxane molecules which can switch from a short state of length L to a long state of length qL, using statistical thermodynamics. This molecular switching is externally driven and can result in an isotropic-nematic phase transition without altering temperature and concentration. Here we concentrate on the limitation imposed by switching inefficiency, i.e., on the case where molecular switching is not quantitative, leading to a solution of rotaxanes in different states. We present switching diagrams that can guide in the design of rotaxanes which affect a macroscopic phase change.

High-Resolution Structure and Mechanism of an F/V-Hybrid Rotor Ring in a Na+-coupled ATP Synthase

PubMed Central

Matthies, Doreen; Zhou, Wenchang; Klyszejko, Adriana L.; Anselmi, Claudio; Yildiz, Özkan; Brandt, Karsten; Müller, Volker; Faraldo-Gómez, José D.; Meier, Thomas

2014-01-01

All rotary ATPases catalyze the interconversion of ATP and ADP-Pi through a mechanism that is coupled to the transmembrane flow of H+ or Na+. Physiologically, however, F/A-type enzymes specialize in ATP synthesis driven by downhill ion diffusion, while eukaryotic V-type ATPases function as ion pumps. To begin to rationalize the molecular basis for this functional differentiation, we solved the crystal structure of the Na+-driven membrane rotor of the Acetobacterium woodii ATP synthase, at 2.1 Å resolution. Unlike known structures, this rotor ring is a 9:1 heteromer of F- and V-type c-subunits, and therefore features a hybrid configuration of ion-binding sites along its circumference. Molecular and kinetic simulations are used to dissect the mechanisms of Na+ recognition and rotation of this c-ring, and to explain the functional implications of the V-type c-subunit. These structural and mechanistic insights indicate an evolutionary path between synthases and pumps involving adaptations in the rotor ring. PMID:25381992

On Mixed Data and Event Driven Design for Adaptive-Critic-Based Nonlinear $H_{\\infty}$ Control.

PubMed

Wang, Ding; Mu, Chaoxu; Liu, Derong; Ma, Hongwen

2018-04-01

In this paper, based on the adaptive critic learning technique, the control for a class of unknown nonlinear dynamic systems is investigated by adopting a mixed data and event driven design approach. The nonlinear control problem is formulated as a two-player zero-sum differential game and the adaptive critic method is employed to cope with the data-based optimization. The novelty lies in that the data driven learning identifier is combined with the event driven design formulation, in order to develop the adaptive critic controller, thereby accomplishing the nonlinear control. The event driven optimal control law and the time driven worst case disturbance law are approximated by constructing and tuning a critic neural network. Applying the event driven feedback control, the closed-loop system is built with stability analysis. Simulation studies are conducted to verify the theoretical results and illustrate the control performance. It is significant to observe that the present research provides a new avenue of integrating data-based control and event-triggering mechanism into establishing advanced adaptive critic systems.

Emergence of robust growth laws from optimal regulation of ribosome synthesis.

PubMed

Scott, Matthew; Klumpp, Stefan; Mateescu, Eduard M; Hwa, Terence

2014-08-22

Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large-scale changes in protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple growth laws connect the ribosome abundance and the growth rate. Here, we investigate the origin of these growth laws by analyzing the features of ribosomal regulation that coordinate proteome-wide expression changes with cell growth in a variety of nutrient conditions in the model organism Escherichia coli. We identify supply-driven feedforward activation of ribosomal protein synthesis as the key regulatory motif maximizing amino acid flux, and autonomously guiding a cell to achieve optimal growth in different environments. The growth laws emerge naturally from the robust regulatory strategy underlying growth rate control, irrespective of the details of the molecular implementation. The study highlights the interplay between phenomenological modeling and molecular mechanisms in uncovering fundamental operating constraints, with implications for endogenous and synthetic design of microorganisms. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Role of Endoplasmic Reticulum Stress in Metabolic Disease and Other Disorders

PubMed Central

Ozcan, Lale; Tabas, Ira

2012-01-01

Perturbations in the normal functions of the endoplasmic reticulum (ER) trigger a signaling network that coordinates adaptive and apoptotic responses. There is accumulating evidence implicating prolonged ER stress in the development and progression of many diseases, including neurodegeneration, atherosclerosis, type 2 diabetes, liver disease, and cancer. With the improved understanding of the underlying molecular mechanisms, therapeutic interventions that target the ER stress response would be potential strategies to treat various diseases driven by prolonged ER stress. PMID:22248326

Light-Driven Chiral Molecular Motors for Passive Agile Filters

DTIC Science & Technology

2014-05-20

liquid crystal , we fabricated the self-organized, phototubable 3D photonic superstructure, i.e. photoresponsive monodisperse cholesteric liquid...systems for applications. Here the new light-driven chiral molecular switch and upconversion nanoparticles, doped in a liquid crystal media, were...the bottom-up nanofabrication of intelligent molecular devices. Light-driven chiral molecular switches or motors in liquid crystal (LC) media that

DeDaL: Cytoscape 3 app for producing and morphing data-driven and structure-driven network layouts.

PubMed

Czerwinska, Urszula; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

2015-08-14

Visualization and analysis of molecular profiling data together with biological networks are able to provide new mechanistic insights into biological functions. Currently, it is possible to visualize high-throughput data on top of pre-defined network layouts, but they are not always adapted to a given data analysis task. A network layout based simultaneously on the network structure and the associated multidimensional data might be advantageous for data visualization and analysis in some cases. We developed a Cytoscape app, which allows constructing biological network layouts based on the data from molecular profiles imported as values of node attributes. DeDaL is a Cytoscape 3 app, which uses linear and non-linear algorithms of dimension reduction to produce data-driven network layouts based on multidimensional data (typically gene expression). DeDaL implements several data pre-processing and layout post-processing steps such as continuous morphing between two arbitrary network layouts and aligning one network layout with respect to another one by rotating and mirroring. The combination of all these functionalities facilitates the creation of insightful network layouts representing both structural network features and correlation patterns in multivariate data. We demonstrate the added value of applying DeDaL in several practical applications, including an example of a large protein-protein interaction network. DeDaL is a convenient tool for applying data dimensionality reduction methods and for designing insightful data displays based on data-driven layouts of biological networks, built within Cytoscape environment. DeDaL is freely available for downloading at http://bioinfo-out.curie.fr/projects/dedal/.

The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis

PubMed Central

Desai, Omkar; Winkler, Julia; Minasyan, Maksym; Herzog, Erica L.

2018-01-01

The contribution of the immune system to idiopathic pulmonary fibrosis (IPF) remains poorly understood. While most sources agree that IPF does not result from a primary immunopathogenic mechanism, evidence gleaned from animal modeling and human studies suggests that innate and adaptive immune processes can orchestrate existing fibrotic responses. This review will synthesize the available data regarding the complex role of professional immune cells in IPF. The role of innate immune populations such as monocytes, macrophages, myeloid suppressor cells, and innate lymphoid cells will be discussed, as will the activation of these cells via pathogen-associated molecular patterns derived from invading or commensural microbes, and danger-associated molecular patterns derived from injured cells and tissues. The contribution of adaptive immune responses driven by T-helper cells and B cells will be reviewed as well. Each form of immune activation will be discussed in the context of its relationship to environmental and genetic factors, disease outcomes, and potential therapies. We conclude with discussion of unanswered questions and opportunities for future study in this area. PMID:29616220

Size-dependent single electron transfer and semi-metal-to-insulator transitions in molecular metal oxide electronics

NASA Astrophysics Data System (ADS)

Balliou, Angelika; Bouroushian, Mirtat; Douvas, Antonios M.; Skoulatakis, George; Kennou, Stella; Glezos, Nikos

2018-07-01

All-inorganic self-arranged molecular transition metal oxide hyperstructures based on polyoxometalate molecules (POMs) are fabricated and tested as electronically tunable components in emerging electronic devices. POM hyperstructures reveal great potential as charging nodes of tunable charging level for molecular memories and as enhancers of interfacial electron/hole injection for photovoltaic stacks. STM, UPS, UV–vis spectroscopy and AFM measurements show that this functionality stems from the films’ ability to structurally tune their HOMO–LUMO levels and electron localization length at room temperature. By adapting POM nanocluster size in solution, self-doping and current modulation of four orders of magnitude is monitored on a single nanocluster on SiO2 at voltages as low as 3 Volt. Structurally driven insulator-to-semi-metal transitions and size-dependent current regulation through single electron tunneling are demonstrated and examined with respect to the stereochemical and electronic structure of the molecular entities. This extends the value of self-assembly as a tool for correlation length and electronic properties tuning and demonstrate POM hyperstructures’ plausibility for on-chip molecular electronics operative at room temperature.

Size-dependent single electron transfer and semi-metal-to-insulator transitions in molecular metal oxide electronics.

PubMed

Balliou, Angelika; Bouroushian, Mirtat; Douvas, Antonios M; Skoulatakis, George; Kennou, Stella; Glezos, Nikos

2018-07-06

All-inorganic self-arranged molecular transition metal oxide hyperstructures based on polyoxometalate molecules (POMs) are fabricated and tested as electronically tunable components in emerging electronic devices. POM hyperstructures reveal great potential as charging nodes of tunable charging level for molecular memories and as enhancers of interfacial electron/hole injection for photovoltaic stacks. STM, UPS, UV-vis spectroscopy and AFM measurements show that this functionality stems from the films' ability to structurally tune their HOMO-LUMO levels and electron localization length at room temperature. By adapting POM nanocluster size in solution, self-doping and current modulation of four orders of magnitude is monitored on a single nanocluster on SiO 2 at voltages as low as 3 Volt. Structurally driven insulator-to-semi-metal transitions and size-dependent current regulation through single electron tunneling are demonstrated and examined with respect to the stereochemical and electronic structure of the molecular entities. This extends the value of self-assembly as a tool for correlation length and electronic properties tuning and demonstrate POM hyperstructures' plausibility for on-chip molecular electronics operative at room temperature.

Molecular proxies for climate maladaptation in a long-lived tree (Pinus pinaster Aiton, Pinaceae).

PubMed

Jaramillo-Correa, Juan-Pablo; Rodríguez-Quilón, Isabel; Grivet, Delphine; Lepoittevin, Camille; Sebastiani, Federico; Heuertz, Myriam; Garnier-Géré, Pauline H; Alía, Ricardo; Plomion, Christophe; Vendramin, Giovanni G; González-Martínez, Santiago C

2015-03-01

Understanding adaptive genetic responses to climate change is a main challenge for preserving biological diversity. Successful predictive models for climate-driven range shifts of species depend on the integration of information on adaptation, including that derived from genomic studies. Long-lived forest trees can experience substantial environmental change across generations, which results in a much more prominent adaptation lag than in annual species. Here, we show that candidate-gene SNPs (single nucleotide polymorphisms) can be used as predictors of maladaptation to climate in maritime pine (Pinus pinaster Aiton), an outcrossing long-lived keystone tree. A set of 18 SNPs potentially associated with climate, 5 of them involving amino acid-changing variants, were retained after performing logistic regression, latent factor mixed models, and Bayesian analyses of SNP-climate correlations. These relationships identified temperature as an important adaptive driver in maritime pine and highlighted that selective forces are operating differentially in geographically discrete gene pools. The frequency of the locally advantageous alleles at these selected loci was strongly correlated with survival in a common garden under extreme (hot and dry) climate conditions, which suggests that candidate-gene SNPs can be used to forecast the likely destiny of natural forest ecosystems under climate change scenarios. Differential levels of forest decline are anticipated for distinct maritime pine gene pools. Geographically defined molecular proxies for climate adaptation will thus critically enhance the predictive power of range-shift models and help establish mitigation measures for long-lived keystone forest trees in the face of impending climate change. Copyright © 2015 by the Genetics Society of America.

Molecular Proxies for Climate Maladaptation in a Long-Lived Tree (Pinus pinaster Aiton, Pinaceae)

PubMed Central

Jaramillo-Correa, Juan-Pablo; Rodríguez-Quilón, Isabel; Grivet, Delphine; Lepoittevin, Camille; Sebastiani, Federico; Heuertz, Myriam; Garnier-Géré, Pauline H.; Alía, Ricardo; Plomion, Christophe; Vendramin, Giovanni G.; González-Martínez, Santiago C.

2015-01-01

Understanding adaptive genetic responses to climate change is a main challenge for preserving biological diversity. Successful predictive models for climate-driven range shifts of species depend on the integration of information on adaptation, including that derived from genomic studies. Long-lived forest trees can experience substantial environmental change across generations, which results in a much more prominent adaptation lag than in annual species. Here, we show that candidate-gene SNPs (single nucleotide polymorphisms) can be used as predictors of maladaptation to climate in maritime pine (Pinus pinaster Aiton), an outcrossing long-lived keystone tree. A set of 18 SNPs potentially associated with climate, 5 of them involving amino acid-changing variants, were retained after performing logistic regression, latent factor mixed models, and Bayesian analyses of SNP–climate correlations. These relationships identified temperature as an important adaptive driver in maritime pine and highlighted that selective forces are operating differentially in geographically discrete gene pools. The frequency of the locally advantageous alleles at these selected loci was strongly correlated with survival in a common garden under extreme (hot and dry) climate conditions, which suggests that candidate-gene SNPs can be used to forecast the likely destiny of natural forest ecosystems under climate change scenarios. Differential levels of forest decline are anticipated for distinct maritime pine gene pools. Geographically defined molecular proxies for climate adaptation will thus critically enhance the predictive power of range-shift models and help establish mitigation measures for long-lived keystone forest trees in the face of impending climate change. PMID:25549630

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels.

PubMed

Cooper, Jacob C; Phadnis, Nitin

2017-07-01

Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Flight Validation of a Metrics Driven L(sub 1) Adaptive Control

NASA Technical Reports Server (NTRS)

Dobrokhodov, Vladimir; Kitsios, Ioannis; Kaminer, Isaac; Jones, Kevin D.; Xargay, Enric; Hovakimyan, Naira; Cao, Chengyu; Lizarraga, Mariano I.; Gregory, Irene M.

2008-01-01

The paper addresses initial steps involved in the development and flight implementation of new metrics driven L1 adaptive flight control system. The work concentrates on (i) definition of appropriate control driven metrics that account for the control surface failures; (ii) tailoring recently developed L1 adaptive controller to the design of adaptive flight control systems that explicitly address these metrics in the presence of control surface failures and dynamic changes under adverse flight conditions; (iii) development of a flight control system for implementation of the resulting algorithms onboard of small UAV; and (iv) conducting a comprehensive flight test program that demonstrates performance of the developed adaptive control algorithms in the presence of failures. As the initial milestone the paper concentrates on the adaptive flight system setup and initial efforts addressing the ability of a commercial off-the-shelf AP with and without adaptive augmentation to recover from control surface failures.

Stress inoculation training supported by physiology-driven adaptive virtual reality stimulation.

PubMed

Popović, Sinisa; Horvat, Marko; Kukolja, Davor; Dropuljić, Branimir; Cosić, Kresimir

2009-01-01

Significant proportion of psychological problems related to combat stress in recent large peacekeeping operations underscores importance of effective methods for strengthening the stress resistance of military personnel. Adaptive control of virtual reality (VR) stimulation, based on estimation of the subject's emotional state from physiological signals, may enhance existing stress inoculation training (SIT). Physiology-driven adaptive VR stimulation can tailor the progress of stressful stimuli delivery to the physiological characteristics of each individual, which is indicated for improvement in stress resistance. Therefore, following an overview of SIT and its applications in the military setting, generic concept of physiology-driven adaptive VR stimulation is presented in the paper. Toward the end of the paper, closed-loop adaptive control strategy applicable to SIT is outlined.

Broken detailed balance and non-equilibrium dynamics in living systems: a review

NASA Astrophysics Data System (ADS)

Gnesotto, F. S.; Mura, F.; Gladrow, J.; Broedersz, C. P.

2018-06-01

Living systems operate far from thermodynamic equilibrium. Enzymatic activity can induce broken detailed balance at the molecular scale. This molecular scale breaking of detailed balance is crucial to achieve biological functions such as high-fidelity transcription and translation, sensing, adaptation, biochemical patterning, and force generation. While biological systems such as motor enzymes violate detailed balance at the molecular scale, it remains unclear how non-equilibrium dynamics manifests at the mesoscale in systems that are driven through the collective activity of many motors. Indeed, in several cellular systems the presence of non-equilibrium dynamics is not always evident at large scales. For example, in the cytoskeleton or in chromosomes one can observe stationary stochastic processes that appear at first glance thermally driven. This raises the question how non-equilibrium fluctuations can be discerned from thermal noise. We discuss approaches that have recently been developed to address this question, including methods based on measuring the extent to which the system violates the fluctuation-dissipation theorem. We also review applications of this approach to reconstituted cytoskeletal networks, the cytoplasm of living cells, and cell membranes. Furthermore, we discuss a more recent approach to detect actively driven dynamics, which is based on inferring broken detailed balance. This constitutes a non-invasive method that uses time-lapse microscopy data, and can be applied to a broad range of systems in cells and tissue. We discuss the ideas underlying this method and its application to several examples including flagella, primary cilia, and cytoskeletal networks. Finally, we briefly discuss recent developments in stochastic thermodynamics and non-equilibrium statistical mechanics, which offer new perspectives to understand the physics of living systems.

Broken detailed balance and non-equilibrium dynamics in living systems: a review.

PubMed

Gnesotto, F S; Mura, F; Gladrow, J; Broedersz, C P

2018-06-01

Living systems operate far from thermodynamic equilibrium. Enzymatic activity can induce broken detailed balance at the molecular scale. This molecular scale breaking of detailed balance is crucial to achieve biological functions such as high-fidelity transcription and translation, sensing, adaptation, biochemical patterning, and force generation. While biological systems such as motor enzymes violate detailed balance at the molecular scale, it remains unclear how non-equilibrium dynamics manifests at the mesoscale in systems that are driven through the collective activity of many motors. Indeed, in several cellular systems the presence of non-equilibrium dynamics is not always evident at large scales. For example, in the cytoskeleton or in chromosomes one can observe stationary stochastic processes that appear at first glance thermally driven. This raises the question how non-equilibrium fluctuations can be discerned from thermal noise. We discuss approaches that have recently been developed to address this question, including methods based on measuring the extent to which the system violates the fluctuation-dissipation theorem. We also review applications of this approach to reconstituted cytoskeletal networks, the cytoplasm of living cells, and cell membranes. Furthermore, we discuss a more recent approach to detect actively driven dynamics, which is based on inferring broken detailed balance. This constitutes a non-invasive method that uses time-lapse microscopy data, and can be applied to a broad range of systems in cells and tissue. We discuss the ideas underlying this method and its application to several examples including flagella, primary cilia, and cytoskeletal networks. Finally, we briefly discuss recent developments in stochastic thermodynamics and non-equilibrium statistical mechanics, which offer new perspectives to understand the physics of living systems.

Dopamine drives Drosophila sechellia adaptation to its toxic host

PubMed Central

Lavista-Llanos, Sofía; Svatoš, Aleš; Kai, Marco; Riemensperger, Thomas; Birman, Serge; Stensmyr, Marcus C; Hansson, Bill S

2014-01-01

Many insect species are host-obligate specialists. The evolutionary mechanism driving the adaptation of a species to a toxic host is, however, intriguing. We analyzed the tight association of Drosophila sechellia to its sole host, the fruit of Morinda citrifolia, which is toxic to other members of the melanogaster species group. Molecular polymorphisms in the dopamine regulatory protein Catsup cause infertility in D. sechellia due to maternal arrest of oogenesis. In its natural host, the fruit compensates for the impaired maternal dopamine metabolism with the precursor l-DOPA, resuming oogenesis and stimulating egg production. l-DOPA present in morinda additionally increases the size of D. sechellia eggs, what in turn enhances early fitness. We argue that the need of l-DOPA for successful reproduction has driven D. sechellia to become an M. citrifolia obligate specialist. This study illustrates how an insect's dopaminergic system can sustain ecological adaptations by modulating ontogenesis and development. DOI: http://dx.doi.org/10.7554/eLife.03785.001 PMID:25487989

Molecular investigation of genetic assimilation during the rapid adaptive radiations of East African cichlid fishes.

PubMed

Gunter, Helen M; Schneider, Ralf F; Karner, Immanuel; Sturmbauer, Christian; Meyer, Axel

2017-12-01

Adaptive radiations are characterized by adaptive diversification intertwined with rapid speciation within a lineage resulting in many ecologically specialized, phenotypically diverse species. It has been proposed that adaptive radiations can originate from ancestral lineages with pronounced phenotypic plasticity in adaptive traits, facilitating ecologically driven phenotypic diversification that is ultimately fixed through genetic assimilation of gene regulatory regions. This study aimed to investigate how phenotypic plasticity is reflected in gene expression patterns in the trophic apparatus of several lineages of East African cichlid fishes, and whether the observed patterns support genetic assimilation. This investigation used a split brood experimental design to compare adaptive plasticity in species from within and outside of adaptive radiations. The plastic response was induced in the crushing pharyngeal jaws through feeding individuals either a hard or soft diet. We find that nonradiating, basal lineages show higher levels of adaptive morphological plasticity than the derived, radiated lineages, suggesting that these differences have become partially genetically fixed during the formation of the adaptive radiations. Two candidate genes that may have undergone genetic assimilation, gif and alas1, were identified, in addition to alterations in the wiring of LPJ patterning networks. Taken together, our results suggest that genetic assimilation may have dampened the inducibility of plasticity related genes during the adaptive radiations of East African cichlids, flattening the reaction norms and canalizing their feeding phenotypes, driving adaptation to progressively more narrow ecological niches. © 2017 John Wiley & Sons Ltd.

Quantum dynamics of light-driven chiral molecular motors.

PubMed

Yamaki, Masahiro; Nakayama, Shin-ichiro; Hoki, Kunihito; Kono, Hirohiko; Fujimura, Yuichi

2009-03-21

The results of theoretical studies on quantum dynamics of light-driven molecular motors with internal rotation are presented. Characteristic features of chiral motors driven by a non-helical, linearly polarized electric field of light are explained on the basis of symmetry argument. The rotational potential of the chiral motor is characterized by a ratchet form. The asymmetric potential determines the directional motion: the rotational direction is toward the gentle slope of the asymmetric potential. This direction is called the intuitive direction. To confirm the unidirectional rotational motion, results of quantum dynamical calculations of randomly-oriented molecular motors are presented. A theoretical design of the smallest light-driven molecular machine is presented. The smallest chiral molecular machine has an optically driven engine and a running propeller on its body. The mechanisms of transmission of driving forces from the engine to the propeller are elucidated by using a quantum dynamical treatment. The results provide a principle for control of optically-driven molecular bevel gears. Temperature effects are discussed using the density operator formalism. An effective method for ultrafast control of rotational motions in any desired direction is presented with the help of a quantum control theory. In this method, visible or UV light pulses are applied to drive the motor via an electronic excited state. A method for driving a large molecular motor consisting of an aromatic hydrocarbon is presented. The molecular motor is operated by interactions between the induced dipole of the molecular motor and the electric field of light pulses.

From precision polymers to complex materials and systems

NASA Astrophysics Data System (ADS)

Lutz, Jean-François; Lehn, Jean-Marie; Meijer, E. W.; Matyjaszewski, Krzysztof

2016-05-01

Complex chemical systems, such as living biological matter, are highly organized structures based on discrete molecules in constant dynamic interactions. These natural materials can evolve and adapt to their environment. By contrast, man-made materials exhibit simpler properties. In this Review, we highlight that most of the necessary elements for the development of more complex synthetic matter are available today. Using modern strategies, such as controlled radical polymerizations, supramolecular polymerizations or stepwise synthesis, polymers with precisely controlled molecular structures can be synthesized. Moreover, such tailored polymers can be folded or self-assembled into defined nanoscale morphologies. These self-organized macromolecular objects can be at thermal equilibrium or can be driven out of equilibrium. Recently, in the latter case, interesting dynamic materials have been developed. However, this is just a start, and more complex adaptive materials are anticipated.

An Item-Driven Adaptive Design for Calibrating Pretest Items. Research Report. ETS RR-14-38

ERIC Educational Resources Information Center

Ali, Usama S.; Chang, Hua-Hua

2014-01-01

Adaptive testing is advantageous in that it provides more efficient ability estimates with fewer items than linear testing does. Item-driven adaptive pretesting may also offer similar advantages, and verification of such a hypothesis about item calibration was the main objective of this study. A suitability index (SI) was introduced to adaptively…

Course-based undergraduate research experiences in molecular biosciences-patterns, trends, and faculty support.

PubMed

Wang, Jack T H

2017-08-15

Inquiry-driven learning, research internships and course-based undergraduate research experiences all represent mechanisms through which educators can engage undergraduate students in scientific research. In life sciences education, the benefits of undergraduate research have been thoroughly evaluated, but limitations in infrastructure and training can prevent widespread uptake of these practices. It is not clear how faculty members can integrate complex laboratory techniques and equipment into their unique context, while finding the time and resources to implement undergraduate research according to best practice guidelines. This review will go through the trends and patterns in inquiry-based undergraduate life science projects with particular emphasis on molecular biosciences-the research-aligned disciplines of biochemistry, molecular cell biology, microbiology, and genomics and bioinformatics. This will provide instructors with an overview of the model organisms, laboratory techniques and research questions that are adaptable for semester-long projects, and serve as starting guidelines for course-based undergraduate research. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modeling light-induced charge transfer dynamics across a metal-molecule-metal junction: Bridging classical electrodynamics and quantum dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Zixuan; Ratner, Mark A.; Seideman, Tamar, E-mail: t-seideman@northwestern.edu

2014-12-14

We develop a numerical approach for simulating light-induced charge transport dynamics across a metal-molecule-metal conductance junction. The finite-difference time-domain method is used to simulate the plasmonic response of the metal structures. The Huygens subgridding technique, as adapted to Lorentz media, is used to bridge the vastly disparate length scales of the plasmonic metal electrodes and the molecular system, maintaining accuracy. The charge and current densities calculated with classical electrodynamics are transformed to an electronic wavefunction, which is then propagated through the molecular linker via the Heisenberg equations of motion. We focus mainly on development of the theory and exemplify ourmore » approach by a numerical illustration of a simple system consisting of two silver cylinders bridged by a three-site molecular linker. The electronic subsystem exhibits fascinating light driven dynamics, wherein the charge density oscillates at the driving optical frequency, exhibiting also the natural system timescales, and a resonance phenomenon leads to strong conductance enhancement.« less

Physiology-driven adaptive virtual reality stimulation for prevention and treatment of stress related disorders.

PubMed

Cosić, Kresimir; Popović, Sinisa; Kukolja, Davor; Horvat, Marko; Dropuljić, Branimir

2010-02-01

The significant proportion of severe psychological problems related to intensive stress in recent large peacekeeping operations underscores the importance of effective methods for strengthening the prevention and treatment of stress-related disorders. Adaptive control of virtual reality (VR) stimulation presented in this work, based on estimation of the person's emotional state from physiological signals, may enhance existing stress inoculation training (SIT). Physiology-driven adaptive VR stimulation can tailor the progress of stressful stimuli delivery to the physiological characteristics of each individual, which is indicated for improvement in stress resistance. Following an overview of physiology-driven adaptive VR stimulation, its major functional subsystems are described in more detail. A specific algorithm of stimuli delivery applicable to SIT is outlined.

Emerging Trends in Epigenetic Regulation of Nutrient Deficiency Response in Plants.

PubMed

Sirohi, Gunjan; Pandey, Bipin K; Deveshwar, Priyanka; Giri, Jitender

2016-03-01

Diverse environmental stimuli largely affect the ionic balance of soil, which have a direct effect on growth and crop yield. Details are fast emerging on the genetic/molecular regulators, at whole-genome levels, of plant responses to mineral deficiencies in model and crop plants. These genetic regulators determine the root architecture and physiological adaptations for better uptake and utilization of minerals from soil. Recent evidence also shows the potential roles of epigenetic mechanisms in gene regulation, driven by minerals imbalance. Mineral deficiency or sufficiency leads to developmental plasticity in plants for adaptation, which is preceded by a change in the pattern of gene expression. Notably, such changes at molecular levels are also influenced by altered chromatin structure and methylation patterns, or involvement of other epigenetic components. Interestingly, many of the changes induced by mineral deficiency are also inheritable in the form of epigenetic memory. Unravelling these mechanisms in response to mineral deficiency would further advance our understanding of this complex plant response. Further studies on such approaches may serve as an exciting interaction model of epigenetic and genetic regulations of mineral homeostasis in plants and designing strategies for crop improvement.

Rod-driven OFF pathway responses in the distal retina: dark-adapted flicker electroretinogram in mouse.

PubMed

Lei, Bo

2012-01-01

The rodent retina does not exhibit a positive OFF-response in the electroretinogram (ERG), which makes it difficult to evaluate its OFF-pathway functions in vivo. We studied the rod-driven OFF pathway responses by using a dark-adapted 10-Hz flicker ERG procedure in mouse. Conventional ERGs and 10-Hz dark-adapted flicker ERGs were obtained in wild-type mice (C57BL/6), in mice with pure rod (cpfl1) or pure cone (rho(-/-)) function, and in nob1 mice which have a selective ON-pathway defect. To isolate the response from ON or OFF pathway, glutamate analogs 2-amino-4-phosphobutyric acid (APB, an ON pathway blocker) and cis-2, 3-piperidine-dicarboxylic acid (PDA, an OFF pathway blocker), were injected intravitreally. The amplitude-intensity profile of the dark-adapted 10-Hz flicker ERG in the wild-type mice exhibits two peaks at middle and high light intensities. The two peaks represent rod- and cone-driven responses respectively. In APB-treated C57BL/6 mice and in nob1 mice, the dark-adapted ERG b-waves were absent. However, both rod- and cone-driven OFF pathway responses were evident with flicker ERG recording. At middle light intensities that activate only rod system, the flicker ERG responses in saline-injected nob1 mice were similar to those in APB-injected cpfl1 mice and wild-type mice. These responses are sensitive to PDA. The amplitudes of these rod-driven OFF pathway responses were approximately 20% of the total rod-driven flicker ERG responses. We demonstrate that the rod-OFF bipolar cell pathway is functional in the outer retina. The dark-adapted flicker ERG is practical for the evaluation of rod- and cone-driven responses, and the residual OFF pathway signals in subjects with ON pathway defects.

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks

PubMed Central

Fortunato, Angelo; Boddy, Amy; Mallo, Diego; Aktipis, Athena; Maley, Carlo C.; Pepper, John W.

2017-01-01

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of “cancer” and for why this convergent condition becomes life-threatening. PMID:28148564

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks.

PubMed

Fortunato, Angelo; Boddy, Amy; Mallo, Diego; Aktipis, Athena; Maley, Carlo C; Pepper, John W

2017-02-01

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of "cancer" and for why this convergent condition becomes life-threatening. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Opposing influences on conflict-driven adaptation in the Eriksen flanker task

PubMed Central

Bugg, Julie M.

2009-01-01

Compatibility effects in conflict paradigms are reduced following incompatible trials, and this effect is referred to as conflict adaptation. A perplexing pattern exists, however, with conflict-driven adaptation emerging in several paradigms (e.g., Stroop, Simon) but not consistently in the Eriksen and Eriksen (1974) flanker task. The present experiments address the seemingly elusive presence of conflict adaptation in this task. Experiment 1 shows that a negative-priming-like slowing may be masking conflict adaptation in the flanker task. In Experiment 2, conflict adaptation was revealed when a larger stimulus set designed to reduce negative priming was implemented. Taken together, the findings indicate that a consideration of processes opposing conflict adaptation in the flanker task may help reconcile prior findings. PMID:18927038

Keys to success for data-driven decision making: Lessons from participatory monitoring and collaborative adaptive management

USDA-ARS?s Scientific Manuscript database

Recent years have witnessed a call for evidence-based decisions in conservation and natural resource management, including data-driven decision-making. Adaptive management (AM) is one prevalent model for integrating scientific data into decision-making, yet AM has faced numerous challenges and limit...

Integrating Model-Driven and Data-Driven Techniques for Analyzing Learning Behaviors in Open-Ended Learning Environments

ERIC Educational Resources Information Center

Kinnebrew, John S.; Segedy, James R.; Biswas, Gautam

2017-01-01

Research in computer-based learning environments has long recognized the vital role of adaptivity in promoting effective, individualized learning among students. Adaptive scaffolding capabilities are particularly important in open-ended learning environments, which provide students with opportunities for solving authentic and complex problems, and…

Mammalian phospholipid homeostasis: evidence that membrane curvature elastic stress drives homeoviscous adaptation in vivo

PubMed Central

2016-01-01

Several theories of phospholipid homeostasis have postulated that cells regulate the molecular composition of their bilayer membranes, such that a common biophysical membrane parameter is under homeostatic control. Two commonly cited theories are the intrinsic curvature hypothesis, which states that cells control membrane curvature elastic stress, and the theory of homeoviscous adaptation, which postulates cells control acyl chain packing order (membrane order). In this paper, we present evidence from data-driven modelling studies that these two theories correlate in vivo. We estimate the curvature elastic stress of mammalian cells to be 4–7 × 10−12 N, a value high enough to suggest that in mammalian cells the preservation of membrane order arises through a mechanism where membrane curvature elastic stress is controlled. These results emerge from analysing the molecular contribution of individual phospholipids to both membrane order and curvature elastic stress in nearly 500 cellular compositionally diverse lipidomes. Our model suggests that the de novo synthesis of lipids is the dominant mechanism by which cells control curvature elastic stress and hence membrane order in vivo. These results also suggest that cells can increase membrane curvature elastic stress disproportionately to membrane order by incorporating polyunsaturated fatty acids into lipids. PMID:27534697

Mammalian phospholipid homeostasis: evidence that membrane curvature elastic stress drives homeoviscous adaptation in vivo.

PubMed

Dymond, Marcus K

2016-08-01

Several theories of phospholipid homeostasis have postulated that cells regulate the molecular composition of their bilayer membranes, such that a common biophysical membrane parameter is under homeostatic control. Two commonly cited theories are the intrinsic curvature hypothesis, which states that cells control membrane curvature elastic stress, and the theory of homeoviscous adaptation, which postulates cells control acyl chain packing order (membrane order). In this paper, we present evidence from data-driven modelling studies that these two theories correlate in vivo. We estimate the curvature elastic stress of mammalian cells to be 4-7 × 10(-12) N, a value high enough to suggest that in mammalian cells the preservation of membrane order arises through a mechanism where membrane curvature elastic stress is controlled. These results emerge from analysing the molecular contribution of individual phospholipids to both membrane order and curvature elastic stress in nearly 500 cellular compositionally diverse lipidomes. Our model suggests that the de novo synthesis of lipids is the dominant mechanism by which cells control curvature elastic stress and hence membrane order in vivo These results also suggest that cells can increase membrane curvature elastic stress disproportionately to membrane order by incorporating polyunsaturated fatty acids into lipids. © 2016 The Author(s).

Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies

PubMed Central

Fritzsch, Bernd; Straka, Hans

2014-01-01

Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation, were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. PMID:24281353

Adaptive processes drive ecomorphological convergent evolution in antwrens (Thamnophilidae).

PubMed

Bravo, Gustavo A; Remsen, J V; Brumfield, Robb T

2014-10-01

Phylogenetic niche conservatism (PNC) and convergence are contrasting evolutionary patterns that describe phenotypic similarity across independent lineages. Assessing whether and how adaptive processes give origin to these patterns represent a fundamental step toward understanding phenotypic evolution. Phylogenetic model-based approaches offer the opportunity not only to distinguish between PNC and convergence, but also to determine the extent that adaptive processes explain phenotypic similarity. The Myrmotherula complex in the Neotropical family Thamnophilidae is a polyphyletic group of sexually dimorphic small insectivorous forest birds that are relatively homogeneous in size and shape. Here, we integrate a comprehensive species-level molecular phylogeny of the Myrmotherula complex with morphometric and ecological data within a comparative framework to test whether phenotypic similarity is described by a pattern of PNC or convergence, and to identify evolutionary mechanisms underlying body size and shape evolution. We show that antwrens in the Myrmotherula complex represent distantly related clades that exhibit adaptive convergent evolution in body size and divergent evolution in body shape. Phenotypic similarity in the group is primarily driven by their tendency to converge toward smaller body sizes. Differences in body size and shape across lineages are associated to ecological and behavioral factors. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Loss of Heterozygosity Drives Adaptation in Hybrid Yeast.

PubMed

Smukowski Heil, Caiti S; DeSevo, Christopher G; Pai, Dave A; Tucker, Cheryl M; Hoang, Margaret L; Dunham, Maitreya J

2017-07-01

Hybridization is often considered maladaptive, but sometimes hybrids can invade new ecological niches and adapt to novel or stressful environments better than their parents. The genomic changes that occur following hybridization that facilitate genome resolution and/or adaptation are not well understood. Here, we examine hybrid genome evolution using experimental evolution of de novo interspecific hybrid yeast Saccharomyces cerevisiae × Saccharomyces uvarum and their parentals. We evolved these strains in nutrient-limited conditions for hundreds of generations and sequenced the resulting cultures identifying numerous point mutations, copy number changes, and loss of heterozygosity (LOH) events, including species-biased amplification of nutrient transporters. We focused on a particularly interesting example, in which we saw repeated LOH at the high-affinity phosphate transporter gene PHO84 in both intra- and interspecific hybrids. Using allele replacement methods, we tested the fitness of different alleles in hybrid and S. cerevisiae strain backgrounds and found that the LOH is indeed the result of selection on one allele over the other in both S. cerevisiae and the hybrids. This is an example where hybrid genome resolution is driven by positive selection on existing heterozygosity and demonstrates that even infrequent outcrossing may have lasting impacts on adaptation. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Radiating on oceanic islands: patterns and processes of speciation in the land snail genus Theba (Risso 1826).

PubMed

Greve, Carola; Gimnich, France; Hutterer, Rainer; Misof, Bernhard; Haase, Martin

2012-01-01

Island radiations have played a major role in shaping our current understanding of allopatric, sympatric and parapatric speciation. However, the fact that species divergence correlates with island size emphasizes the importance of geographic isolation (allopatry) in speciation. Based on molecular and morphological data, we investigated the diversification of the land snail genus Theba on the two Canary Islands of Lanzarote and Fuerteventura. Due to the geological history of both islands, this study system provides ideal conditions to investigate the interplay of biogeography, dispersal ability and differentiation in generating species diversity. Our analyses demonstrated extensive cryptic diversification of Theba on these islands, probably driven mainly by non-adaptive allopatric differentiation and secondary gene flow. In a few cases, we observed a complete absence of gene flow among sympatrically distributed forms suggesting an advanced stage of speciation. On the Jandía peninsula genome scans suggested genotype-environment associations and potentially adaptive diversification of two closely related Theba species to different ecological environments. We found support for the idea that genetic differentiation was enhanced by divergent selection in different environments. The diversification of Theba on both islands is therefore best explained by a mixture of non-adaptive and adaptive speciation, promoted by ecological and geomorphological factors.

Radiating on Oceanic Islands: Patterns and Processes of Speciation in the Land Snail Genus Theba (Risso 1826)

PubMed Central

Greve, Carola; Gimnich, France; Hutterer, Rainer; Misof, Bernhard; Haase, Martin

2012-01-01

Island radiations have played a major role in shaping our current understanding of allopatric, sympatric and parapatric speciation. However, the fact that species divergence correlates with island size emphasizes the importance of geographic isolation (allopatry) in speciation. Based on molecular and morphological data, we investigated the diversification of the land snail genus Theba on the two Canary Islands of Lanzarote and Fuerteventura. Due to the geological history of both islands, this study system provides ideal conditions to investigate the interplay of biogeography, dispersal ability and differentiation in generating species diversity. Our analyses demonstrated extensive cryptic diversification of Theba on these islands, probably driven mainly by non-adaptive allopatric differentiation and secondary gene flow. In a few cases, we observed a complete absence of gene flow among sympatrically distributed forms suggesting an advanced stage of speciation. On the Jandía peninsula genome scans suggested genotype-environment associations and potentially adaptive diversification of two closely related Theba species to different ecological environments. We found support for the idea that genetic differentiation was enhanced by divergent selection in different environments. The diversification of Theba on both islands is therefore best explained by a mixture of non-adaptive and adaptive speciation, promoted by ecological and geomorphological factors. PMID:22493687

Footprints of Directional Selection in Wild Atlantic Salmon Populations: Evidence for Parasite-Driven Evolution?

PubMed Central

Zueva, Ksenia J.; Lumme, Jaakko; Veselov, Alexey E.; Kent, Matthew P.; Lien, Sigbjørn; Primmer, Craig R.

2014-01-01

Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved. PMID:24670947

Footprints of directional selection in wild Atlantic salmon populations: evidence for parasite-driven evolution?

PubMed

Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Lien, Sigbjørn; Primmer, Craig R

2014-01-01

Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved.

Genomic Analyses Reveal Demographic History and Temperate Adaptation of the Newly Discovered Honey Bee Subspecies Apis mellifera sinisxinyuan n. ssp.

PubMed

Chen, Chao; Liu, Zhiguang; Pan, Qi; Chen, Xiao; Wang, Huihua; Guo, Haikun; Liu, Shidong; Lu, Hongfeng; Tian, Shilin; Li, Ruiqiang; Shi, Wei

2016-05-01

Studying the genetic signatures of climate-driven selection can produce insights into local adaptation and the potential impacts of climate change on populations. The honey bee (Apis mellifera) is an interesting species to study local adaptation because it originated in tropical/subtropical climatic regions and subsequently spread into temperate regions. However, little is known about the genetic basis of its adaptation to temperate climates. Here, we resequenced the whole genomes of ten individual bees from a newly discovered population in temperate China and downloaded resequenced data from 35 individuals from other populations. We found that the new population is an undescribed subspecies in the M-lineage of A. mellifera (Apis mellifera sinisxinyuan). Analyses of population history show that long-term global temperature has strongly influenced the demographic history of A. m. sinisxinyuan and its divergence from other subspecies. Further analyses comparing temperate and tropical populations identified several candidate genes related to fat body and the Hippo signaling pathway that are potentially involved in adaptation to temperate climates. Our results provide insights into the demographic history of the newly discovered A. m. sinisxinyuan, as well as the genetic basis of adaptation of A. mellifera to temperate climates at the genomic level. These findings will facilitate the selective breeding of A. mellifera to improve the survival of overwintering colonies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Biochemistry of Mitosis

PubMed Central

Wieser, Samuel; Pines, Jonathon

2015-01-01

In this article, we will discuss the biochemistry of mitosis in eukaryotic cells. We will focus on conserved principles that, importantly, are adapted to the biology of the organism. It is vital to bear in mind that the structural requirements for division in a rapidly dividing syncytial Drosophila embryo, for example, are markedly different from those in a unicellular yeast cell. Nevertheless, division in both systems is driven by conserved modules of antagonistic protein kinases and phosphatases, underpinned by ubiquitin-mediated proteolysis, which create molecular switches to drive each stage of division forward. These conserved control modules combine with the self-organizing properties of the subcellular architecture to meet the specific needs of the cell. Our discussion will draw on discoveries in several model systems that have been important in the long history of research on mitosis, and we will try to point out those principles that appear to apply to all cells, compared with those in which the biochemistry has been specifically adapted in a particular organism. PMID:25663668

Die Fledermaus: Regarding Optokinetic Contrast Sensitivity and Light-Adaptation, Chicks Are Mice with Wings

PubMed Central

Shi, Qing; Stell, William K.

2013-01-01

Background Through adaptation, animals can function visually under an extremely broad range of light intensities. Light adaptation starts in the retina, through shifts in photoreceptor sensitivity and kinetics plus modulation of visual processing in retinal circuits. Although considerable research has been conducted on retinal adaptation in nocturnal species with rod-dominated retinas, such as the mouse, little is known about how cone-dominated avian retinas adapt to changes in mean light intensity. Methodology/Principal Findings We used the optokinetic response to characterize contrast sensitivity (CS) in the chick retina as a function of spatial frequency and temporal frequency at different mean light intensities. We found that: 1) daytime, cone-driven CS was tuned to spatial frequency; 2) nighttime, presumably rod-driven CS was tuned to temporal frequency and spatial frequency; 3) daytime, presumably cone-driven CS at threshold intensity was invariant with temporal and spatial frequency; and 4) daytime photopic CS was invariant with clock time. Conclusion/Significance Light- and dark-adaptational changes in CS were investigated comprehensively for the first time in the cone-dominated retina of an avian, diurnal species. The chick retina, like the mouse retina, adapts by using a “day/night” or “cone/rod” switch in tuning preference during changes in lighting conditions. The chick optokinetic response is an attractive model for noninvasive, behavioral studies of adaptation in retinal circuitry in health and disease. PMID:24098693

Irrelevance of the Power Stroke for the Directionality, Stopping Force, and Optimal Efficiency of Chemically Driven Molecular Machines

PubMed Central

Astumian, R. Dean

2015-01-01

A simple model for a chemically driven molecular walker shows that the elastic energy stored by the molecule and released during the conformational change known as the power-stroke (i.e., the free-energy difference between the pre- and post-power-stroke states) is irrelevant for determining the directionality, stopping force, and efficiency of the motor. Further, the apportionment of the dependence on the externally applied force between the forward and reverse rate constants of the power-stroke (or indeed among all rate constants) is irrelevant for determining the directionality, stopping force, and efficiency of the motor. Arguments based on the principle of microscopic reversibility demonstrate that this result is general for all chemically driven molecular machines, and even more broadly that the relative energies of the states of the motor have no role in determining the directionality, stopping force, or optimal efficiency of the machine. Instead, the directionality, stopping force, and optimal efficiency are determined solely by the relative heights of the energy barriers between the states. Molecular recognition—the ability of a molecular machine to discriminate between substrate and product depending on the state of the machine—is far more important for determining the intrinsic directionality and thermodynamics of chemo-mechanical coupling than are the details of the internal mechanical conformational motions of the machine. In contrast to the conclusions for chemical driving, a power-stroke is very important for the directionality and efficiency of light-driven molecular machines and for molecular machines driven by external modulation of thermodynamic parameters. PMID:25606678

[Relevance of big data for molecular diagnostics].

PubMed

Bonin-Andresen, M; Smiljanovic, B; Stuhlmüller, B; Sörensen, T; Grützkau, A; Häupl, T

2018-04-01

Big data analysis raises the expectation that computerized algorithms may extract new knowledge from otherwise unmanageable vast data sets. What are the algorithms behind the big data discussion? In principle, high throughput technologies in molecular research already introduced big data and the development and application of analysis tools into the field of rheumatology some 15 years ago. This includes especially omics technologies, such as genomics, transcriptomics and cytomics. Some basic methods of data analysis are provided along with the technology, however, functional analysis and interpretation requires adaptation of existing or development of new software tools. For these steps, structuring and evaluating according to the biological context is extremely important and not only a mathematical problem. This aspect has to be considered much more for molecular big data than for those analyzed in health economy or epidemiology. Molecular data are structured in a first order determined by the applied technology and present quantitative characteristics that follow the principles of their biological nature. These biological dependencies have to be integrated into software solutions, which may require networks of molecular big data of the same or even different technologies in order to achieve cross-technology confirmation. More and more extensive recording of molecular processes also in individual patients are generating personal big data and require new strategies for management in order to develop data-driven individualized interpretation concepts. With this perspective in mind, translation of information derived from molecular big data will also require new specifications for education and professional competence.

Genetic component of flammability variation in a Mediterranean shrub.

PubMed

Moreira, B; Castellanos, M C; Pausas, J G

2014-03-01

Recurrent fires impose a strong selection pressure in many ecosystems worldwide. In such ecosystems, plant flammability is of paramount importance because it enhances population persistence, particularly in non-resprouting species. Indeed, there is evidence of phenotypic divergence of flammability under different fire regimes. Our general hypothesis is that flammability-enhancing traits are adaptive; here, we test whether they have a genetic component. To test this hypothesis, we used the postfire obligate seeder Ulex parviflorus from sites historically exposed to different fire recurrence. We associated molecular variation in potentially adaptive loci detected with a genomic scan (using AFLP markers) with individual phenotypic variability in flammability across fire regimes. We found that at least 42% of the phenotypic variation in flammability was explained by the genetic divergence in a subset of AFLP loci. In spite of generalized gene flow, the genetic variability was structured by differences in fire recurrence. Our results provide the first field evidence supporting that traits enhancing plant flammability have a genetic component and thus can be responding to natural selection driven by fire. These results highlight the importance of flammability as an adaptive trait in fire-prone ecosystems. © 2014 John Wiley & Sons Ltd.

En route to surface-bound electric field-driven molecular motors.

PubMed

Jian, Huahua; Tour, James M

2003-06-27

Four caltrop-shaped molecules that might be useful as surface-bound electric field-driven molecular motors have been synthesized. The caltrops are comprised of a pair of electron donor-acceptor arms and a tripod base. The molecular arms are based on a carbazole or oligo(phenylene ethynylene) core with a strong net dipole. The tripod base uses a silicon atom as its core. The legs of the tripod bear sulfur-tipped bonding units, as acetyl-protected benzylic thiols, for bonding to a gold surface. The geometry of the tripod base allows the caltrop to project upward from a metallic surface after self-assembly. Ellipsometric studies show that self-assembled monolayers of the caltrops are formed on Au surfaces with molecular thicknesses consistent with the desired upright-shaft arrangement. As a result, the zwitterionic molecular arms might be controllable when electric fields are applied around the caltrops, thereby constituting field-driven motors.

Adaptive Formation Control of Electrically Driven Nonholonomic Mobile Robots With Limited Information.

PubMed

Bong Seok Park; Jin Bae Park; Yoon Ho Choi

2011-08-01

We present a leader-follower-based adaptive formation control method for electrically driven nonholonomic mobile robots with limited information. First, an adaptive observer is developed under the condition that the velocity measurement is not available. With the proposed adaptive observer, the formation control part is designed to achieve the desired formation and guarantee the collision avoidance. In addition, neural network is employed to compensate the actuator saturation, and the projection algorithm is used to estimate the velocity information of the leader. It is shown, by using the Lyapunov theory, that all errors of the closed-loop system are uniformly ultimately bounded. Simulation results are presented to illustrate the performance of the proposed control system.

Learning-Based Adaptive Optimal Tracking Control of Strict-Feedback Nonlinear Systems.

PubMed

Gao, Weinan; Jiang, Zhong-Ping; Weinan Gao; Zhong-Ping Jiang; Gao, Weinan; Jiang, Zhong-Ping

2018-06-01

This paper proposes a novel data-driven control approach to address the problem of adaptive optimal tracking for a class of nonlinear systems taking the strict-feedback form. Adaptive dynamic programming (ADP) and nonlinear output regulation theories are integrated for the first time to compute an adaptive near-optimal tracker without any a priori knowledge of the system dynamics. Fundamentally different from adaptive optimal stabilization problems, the solution to a Hamilton-Jacobi-Bellman (HJB) equation, not necessarily a positive definite function, cannot be approximated through the existing iterative methods. This paper proposes a novel policy iteration technique for solving positive semidefinite HJB equations with rigorous convergence analysis. A two-phase data-driven learning method is developed and implemented online by ADP. The efficacy of the proposed adaptive optimal tracking control methodology is demonstrated via a Van der Pol oscillator with time-varying exogenous signals.

Retrospective cost adaptive Reynolds-averaged Navier-Stokes k-ω model for data-driven unsteady turbulent simulations

NASA Astrophysics Data System (ADS)

Li, Zhiyong; Hoagg, Jesse B.; Martin, Alexandre; Bailey, Sean C. C.

2018-03-01

This paper presents a data-driven computational model for simulating unsteady turbulent flows, where sparse measurement data is available. The model uses the retrospective cost adaptation (RCA) algorithm to automatically adjust the closure coefficients of the Reynolds-averaged Navier-Stokes (RANS) k- ω turbulence equations to improve agreement between the simulated flow and the measurements. The RCA-RANS k- ω model is verified for steady flow using a pipe-flow test case and for unsteady flow using a surface-mounted-cube test case. Measurements used for adaptation of the verification cases are obtained from baseline simulations with known closure coefficients. These verification test cases demonstrate that the RCA-RANS k- ω model can successfully adapt the closure coefficients to improve agreement between the simulated flow field and a set of sparse flow-field measurements. Furthermore, the RCA-RANS k- ω model improves agreement between the simulated flow and the baseline flow at locations at which measurements do not exist. The RCA-RANS k- ω model is also validated with experimental data from 2 test cases: steady pipe flow, and unsteady flow past a square cylinder. In both test cases, the adaptation improves agreement with experimental data in comparison to the results from a non-adaptive RANS k- ω model that uses the standard values of the k- ω closure coefficients. For the steady pipe flow, adaptation is driven by mean stream-wise velocity measurements at 24 locations along the pipe radius. The RCA-RANS k- ω model reduces the average velocity error at these locations by over 35%. For the unsteady flow over a square cylinder, adaptation is driven by time-varying surface pressure measurements at 2 locations on the square cylinder. The RCA-RANS k- ω model reduces the average surface-pressure error at these locations by 88.8%.

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels

PubMed Central

Phadnis, Nitin

2017-01-01

Abstract Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. PMID:28810709

Evolvability of flower geometry: Convergence in pollinator-driven morphological evolution of flowers.

PubMed

Woźniak, Natalia Joanna; Sicard, Adrien

2018-07-01

Flowers represent a key innovation during plant evolution. Driven by reproductive optimization, evolution of flower morphology has been central in boosting species diversification. In most cases, this has happened through specialized interactions with animal pollinators and subsequent reduction of gene flow between specialized morphs. While radiation has led to an enormous variability in flower forms and sizes, recurrent evolutionary patterns can be observed. Here, we discuss the targets of selection involved in major trends of pollinator-driven flower evolution. We review recent findings on their adaptive values, developmental grounds and genetic bases, in an attempt to better understand the repeated nature of pollinator-driven flower evolution. This analysis highlights how structural innovation can provide flexibility in phenotypic evolution, adaptation and speciation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Linking conceptual mechanisms and transcriptomic evidence of plasticity-driven diversification.

PubMed

Young, Rebecca L

2013-09-01

The East African cichlid fishes provide text book examples of adaptive radiation. Diversification and speciation of cichlids associate with variation in diet and trophic morphologies among other ecological, behavioural and morphological phenotypes (Kocher 2004). Numerous case studies in cichlids reveal a role of developmental plasticity in generating jaw ecomorphs in response to variation in feeding ecology that can facilitate niche exploitation and subsequent diversification (e.g. Meyer 1987). Specifically, genetic divergence among such environmentally induced morphs can occur via reproductive isolation due to divergence in habitat and resource use in combination with genetic assimilation of environmentally induced phenotypes (West-Eberhard 2003; Pfennig et al. 2010). Expansion of this conceptual model has been hampered in part by the limited knowledge of the molecular mechanisms of plasticity in nonstandard model systems and the associated lack of evidence linking the molecular mechanisms of plasticity to those that generate phenotypic divergence among populations and taxa. In this issue of Molecular Ecology, Gunter et al. (2013) identify the transcriptional mechanisms of diet-induced lower pharyngeal jaw (LPJ) plasticity in the cichlid fish Astatoreochromis alluaudi. Natural populations of A. alluaudi exhibit variation in jaw morphology in relation to diet hardness. Among the plastic responses to diet are adjustments to the LPJ ranging from a robust molariform morph in response to a hard diet to a more gracile papilliform morph in response to a soft diet (Fig. 1). Gunter and colleagues induced developmental plasticity of the A. alluaudi jaw using diet manipulations and compared LPJ transcriptomic profiles of the resulting morphs. In this foundational work, the authors identify 187 differentially expressed genes that underlie the development and maintenance of diet-induced LPJ morphologies. This list includes a wide range of genes spanning from broad-acting transcription factors to signalling molecules and structural genes. Here, I examine the ontogeny of the molecular response to mechanical strain imposed by diet hardness and discuss the role of the stages of this response in the evolution of plasticity and plasticity-driven diversification.

A 3D visualization system for molecular structures

NASA Technical Reports Server (NTRS)

Green, Terry J.

1989-01-01

The properties of molecules derive in part from their structures. Because of the importance of understanding molecular structures various methodologies, ranging from first principles to empirical technique, were developed for computing the structure of molecules. For large molecules such as polymer model compounds, the structural information is difficult to comprehend by examining tabulated data. Therefore, a molecular graphics display system, called MOLDS, was developed to help interpret the data. MOLDS is a menu-driven program developed to run on the LADC SNS computer systems. This program can read a data file generated by the modeling programs or data can be entered using the keyboard. MOLDS has the following capabilities: draws the 3-D representation of a molecule using stick, ball and ball, or space filled model from Cartesian coordinates, draws different perspective views of the molecule; rotates the molecule on the X, Y, Z axis or about some arbitrary line in space, zooms in on a small area of the molecule in order to obtain a better view of a specific region; and makes hard copy representation of molecules on a graphic printer. In addition, MOLDS can be easily updated and readily adapted to run on most computer systems.

Mechanical-Kinetic Modeling of a Molecular Walker from a Modular Design Principle

NASA Astrophysics Data System (ADS)

Hou, Ruizheng; Loh, Iong Ying; Li, Hongrong; Wang, Zhisong

2017-02-01

Artificial molecular walkers beyond burnt-bridge designs are complex nanomachines that potentially replicate biological walkers in mechanisms and functionalities. Improving the man-made walkers up to performance for widespread applications remains difficult, largely because their biomimetic design principles involve entangled kinetic and mechanical effects to complicate the link between a walker's construction and ultimate performance. Here, a synergic mechanical-kinetic model is developed for a recently reported DNA bipedal walker, which is based on a modular design principle, potentially enabling many directional walkers driven by a length-switching engine. The model reproduces the experimental data of the walker, and identifies its performance-limiting factors. The model also captures features common to the underlying design principle, including counterintuitive performance-construction relations that are explained by detailed balance, entropy production, and bias cancellation. While indicating a low directional fidelity for the present walker, the model suggests the possibility of improving the fidelity above 90% by a more powerful engine, which may be an improved version of the present engine or an entirely new engine motif, thanks to the flexible design principle. The model is readily adaptable to aid these experimental developments towards high-performance molecular walkers.

A modular DNA signal translator for the controlled release of a protein by an aptamer.

PubMed

Beyer, Stefan; Simmel, Friedrich C

2006-01-01

Owing to the intimate linkage of sequence and structure in nucleic acids, DNA is an extremely attractive molecule for the development of molecular devices, in particular when a combination of information processing and chemomechanical tasks is desired. Many of the previously demonstrated devices are driven by hybridization between DNA 'effector' strands and specific recognition sequences on the device. For applications it is of great interest to link several of such molecular devices together within artificial reaction cascades. Often it will not be possible to choose DNA sequences freely, e.g. when functional nucleic acids such as aptamers are used. In such cases translation of an arbitrary 'input' sequence into a desired effector sequence may be required. Here we demonstrate a molecular 'translator' for information encoded in DNA and show how it can be used to control the release of a protein by an aptamer using an arbitrarily chosen DNA input strand. The function of the translator is based on branch migration and the action of the endonuclease FokI. The modular design of the translator facilitates the adaptation of the device to various input or output sequences.

A modular DNA signal translator for the controlled release of a protein by an aptamer

PubMed Central

Beyer, Stefan; Simmel, Friedrich C.

2006-01-01

Owing to the intimate linkage of sequence and structure in nucleic acids, DNA is an extremely attractive molecule for the development of molecular devices, in particular when a combination of information processing and chemomechanical tasks is desired. Many of the previously demonstrated devices are driven by hybridization between DNA ‘effector’ strands and specific recognition sequences on the device. For applications it is of great interest to link several of such molecular devices together within artificial reaction cascades. Often it will not be possible to choose DNA sequences freely, e.g. when functional nucleic acids such as aptamers are used. In such cases translation of an arbitrary ‘input’ sequence into a desired effector sequence may be required. Here we demonstrate a molecular ‘translator’ for information encoded in DNA and show how it can be used to control the release of a protein by an aptamer using an arbitrarily chosen DNA input strand. The function of the translator is based on branch migration and the action of the endonuclease FokI. The modular design of the translator facilitates the adaptation of the device to various input or output sequences. PMID:16547201

Does External Funding Help Adaptation? Evidence from Community-Based Water Management in the Colombian Andes

NASA Astrophysics Data System (ADS)

Murtinho, Felipe; Eakin, Hallie; López-Carr, David; Hayes, Tanya M.

2013-11-01

Despite debate regarding whether, and in what form, communities need external support for adaptation to environmental change, few studies have examined how external funding impacts adaptation decisions in rural resource-dependent communities. In this article, we use quantitative and qualitative methods to assess how different funding sources influence the initiative to adapt to water scarcity in the Colombian Andes. We compare efforts to adapt to water scarcity in 111 rural Andean communities with varied dependence on external funding for water management activities. Findings suggest that despite efforts to use their own internal resources, communities often need external support to finance adaptation strategies. However, not all external financial support positively impacts a community’s abilities to adapt. Results show the importance of community-driven requests for external support. In cases where external support was unsolicited, the results show a decline, or “crowding-out,” in community efforts to adapt. In contrast, in cases where communities initiated the request for external support to fund their own projects, findings show that external intervention is more likely to enhance or “crowds-in” community-driven adaptation.

Cytoskeletal motor-driven active self-assembly in in vitro systems

DOE PAGES

Lam, A. T.; VanDelinder, V.; Kabir, A. M. R.; ...

2015-11-11

Molecular motor-driven self-assembly has been an active area of soft matter research for the past decade. Because molecular motors transform chemical energy into mechanical work, systems which employ molecular motors to drive self-assembly processes are able to overcome kinetic and thermodynamic limits on assembly time, size, complexity, and structure. Here, we review the progress in elucidating and demonstrating the rules and capabilities of motor-driven active self-assembly. Lastly, we focus on the types of structures created and the degree of control realized over these structures, and discuss the next steps necessary to achieve the full potential of this assembly mode whichmore » complements robotic manipulation and passive self-assembly.« less

Adaptive Statistical Iterative Reconstruction-Applied Ultra-Low-Dose CT with Radiography-Comparable Radiation Dose: Usefulness for Lung Nodule Detection.

PubMed

Yoon, Hyun Jung; Chung, Myung Jin; Hwang, Hye Sun; Moon, Jung Won; Lee, Kyung Soo

2015-01-01

To assess the performance of adaptive statistical iterative reconstruction (ASIR)-applied ultra-low-dose CT (ULDCT) in detecting small lung nodules. Thirty patients underwent both ULDCT and standard dose CT (SCT). After determining the reference standard nodules, five observers, blinded to the reference standard reading results, independently evaluated SCT and both subsets of ASIR- and filtered back projection (FBP)-driven ULDCT images. Data assessed by observers were compared statistically. Converted effective doses in SCT and ULDCT were 2.81 ± 0.92 and 0.17 ± 0.02 mSv, respectively. A total of 114 lung nodules were detected on SCT as a standard reference. There was no statistically significant difference in sensitivity between ASIR-driven ULDCT and SCT for three out of the five observers (p = 0.678, 0.735, < 0.01, 0.038, and < 0.868 for observers 1, 2, 3, 4, and 5, respectively). The sensitivity of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT in three out of the five observers (p < 0.01 for three observers, and p = 0.064 and 0.146 for two observers). In jackknife alternative free-response receiver operating characteristic analysis, the mean values of figure-of-merit (FOM) for FBP, ASIR-driven ULDCT, and SCT were 0.682, 0.772, and 0.821, respectively, and there were no significant differences in FOM values between ASIR-driven ULDCT and SCT (p = 0.11), but the FOM value of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT and SCT (p = 0.01 and 0.00). Adaptive statistical iterative reconstruction-driven ULDCT delivering a radiation dose of only 0.17 mSv offers acceptable sensitivity in nodule detection compared with SCT and has better performance than FBP-driven ULDCT.

Adaptive Statistical Iterative Reconstruction-Applied Ultra-Low-Dose CT with Radiography-Comparable Radiation Dose: Usefulness for Lung Nodule Detection

PubMed Central

Yoon, Hyun Jung; Hwang, Hye Sun; Moon, Jung Won; Lee, Kyung Soo

2015-01-01

Objective To assess the performance of adaptive statistical iterative reconstruction (ASIR)-applied ultra-low-dose CT (ULDCT) in detecting small lung nodules. Materials and Methods Thirty patients underwent both ULDCT and standard dose CT (SCT). After determining the reference standard nodules, five observers, blinded to the reference standard reading results, independently evaluated SCT and both subsets of ASIR- and filtered back projection (FBP)-driven ULDCT images. Data assessed by observers were compared statistically. Results Converted effective doses in SCT and ULDCT were 2.81 ± 0.92 and 0.17 ± 0.02 mSv, respectively. A total of 114 lung nodules were detected on SCT as a standard reference. There was no statistically significant difference in sensitivity between ASIR-driven ULDCT and SCT for three out of the five observers (p = 0.678, 0.735, < 0.01, 0.038, and < 0.868 for observers 1, 2, 3, 4, and 5, respectively). The sensitivity of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT in three out of the five observers (p < 0.01 for three observers, and p = 0.064 and 0.146 for two observers). In jackknife alternative free-response receiver operating characteristic analysis, the mean values of figure-of-merit (FOM) for FBP, ASIR-driven ULDCT, and SCT were 0.682, 0.772, and 0.821, respectively, and there were no significant differences in FOM values between ASIR-driven ULDCT and SCT (p = 0.11), but the FOM value of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT and SCT (p = 0.01 and 0.00). Conclusion Adaptive statistical iterative reconstruction-driven ULDCT delivering a radiation dose of only 0.17 mSv offers acceptable sensitivity in nodule detection compared with SCT and has better performance than FBP-driven ULDCT. PMID:26357505

Hydrogen exchange mass spectrometry of bacteriorhodopsin reveals light-induced changes in the structural dynamics of a biomolecular machine.

PubMed

Pan, Yan; Brown, Leonid; Konermann, Lars

2011-12-21

Many proteins act as molecular machines that are fuelled by a nonthermal energy source. Examples include transmembrane pumps and stator-rotor complexes. These systems undergo cyclic motions (CMs) that are being driven along a well-defined conformational trajectory. Superimposed on these CMs are thermal fluctuations (TFs) that are coupled to stochastic motions of the solvent. Here we explore whether the TFs of a molecular machine are affected by the occurrence of CMs. Bacteriorhodopsin (BR) is a light-driven proton pump that serves as a model system in this study. The function of BR is based on a photocycle that involves trans/cis isomerization of a retinal chromophore, as well as motions of transmembrane helices. Hydrogen/deuterium exchange (HDX) mass spectrometry was used to monitor the TFs of BR, focusing on the monomeric form of the protein. Comparative HDX studies were conducted under illumination and in the dark. The HDX kinetics of BR are dramatically accelerated in the presence of light. The isotope exchange rates and the number of backbone amides involved in EX2 opening transitions increase roughly 2-fold upon illumination. In contrast, light/dark control experiments on retinal-free protein produced no discernible differences. It can be concluded that the extent of TFs in BR strongly depends on photon-driven CMs. The light-induced differences in HDX behavior are ascribed to protein destabilization. Specifically, the thermodynamic stability of the dark-adapted protein is estimated to be 5.5 kJ mol(-1) under the conditions of our work. This value represents the free energy difference between the folded state F and a significantly unfolded conformer U. Illumination reduces the stability of F by 2.2 kJ mol(-1). Mechanical agitation caused by isomerization of the chromophore is transferred to the surrounding protein scaffold, and subsequently, the energy dissipates into the solvent. Light-induced retinal motions therefore act analogously to an internal heat source that promotes the occurrence of TFs. Overall, our data highlight the potential of HDX methods for probing the structural dynamics of molecular machines under "engine on" and "engine off" conditions. © 2011 American Chemical Society

A multi-band environment-adaptive approach to noise suppression for cochlear implants.

PubMed

Saki, Fatemeh; Mirzahasanloo, Taher; Kehtarnavaz, Nasser

2014-01-01

This paper presents an improved environment-adaptive noise suppression solution for the cochlear implants speech processing pipeline. This improvement is achieved by using a multi-band data-driven approach in place of a previously developed single-band data-driven approach. Seven commonly encountered noisy environments of street, car, restaurant, mall, bus, pub and train are considered to quantify the improvement. The results obtained indicate about 10% improvement in speech quality measures.

Natural selection in avian protein-coding genes expressed in brain.

PubMed

Axelsson, Erik; Hultin-Rosenberg, Lina; Brandström, Mikael; Zwahlén, Martin; Clayton, David F; Ellegren, Hans

2008-06-01

The evolution of birds from theropod dinosaurs took place approximately 150 million years ago, and was associated with a number of specific adaptations that are still evident among extant birds, including feathers, song and extravagant secondary sexual characteristics. Knowledge about the molecular evolutionary background to such adaptations is lacking. Here, we analyse the evolution of > 5000 protein-coding gene sequences expressed in zebra finch brain by comparison to orthologous sequences in chicken. Mean d(N)/d(S) is 0.085 and genes with their maximal expression in the eye and central nervous system have the lowest mean d(N)/d(S) value, while those expressed in digestive and reproductive tissues exhibit the highest. We find that fast-evolving genes (those which have higher than expected rate of nonsynonymous substitution, indicative of adaptive evolution) are enriched for biological functions such as fertilization, muscle contraction, defence response, response to stress, wounding and endogenous stimulus, and cell death. After alignment to mammalian orthologues, we identify a catalogue of 228 genes that show a significantly higher rate of protein evolution in the two bird lineages than in mammals. These accelerated bird genes, representing candidates for avian-specific adaptations, include genes implicated in vocal learning and other cognitive processes. Moreover, colouration genes evolve faster in birds than in mammals, which may have been driven by sexual selection for extravagant plumage characteristics.

Adaptive time steps in trajectory surface hopping simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spörkel, Lasse, E-mail: spoerkel@kofo.mpg.de; Thiel, Walter, E-mail: thiel@kofo.mpg.de

2016-05-21

Trajectory surface hopping (TSH) simulations are often performed in combination with active-space multi-reference configuration interaction (MRCI) treatments. Technical problems may arise in such simulations if active and inactive orbitals strongly mix and switch in some particular regions. We propose to use adaptive time steps when such regions are encountered in TSH simulations. For this purpose, we present a computational protocol that is easy to implement and increases the computational effort only in the critical regions. We test this procedure through TSH simulations of a GFP chromophore model (OHBI) and a light-driven rotary molecular motor (F-NAIBP) on semiempirical MRCI potential energymore » surfaces, by comparing the results from simulations with adaptive time steps to analogous ones with constant time steps. For both test molecules, the number of successful trajectories without technical failures rises significantly, from 53% to 95% for OHBI and from 25% to 96% for F-NAIBP. The computed excited-state lifetime remains essentially the same for OHBI and increases somewhat for F-NAIBP, and there is almost no change in the computed quantum efficiency for internal rotation in F-NAIBP. We recommend the general use of adaptive time steps in TSH simulations with active-space CI methods because this will help to avoid technical problems, increase the overall efficiency and robustness of the simulations, and allow for a more complete sampling.« less

Adaptive time steps in trajectory surface hopping simulations

NASA Astrophysics Data System (ADS)

Spörkel, Lasse; Thiel, Walter

2016-05-01

Trajectory surface hopping (TSH) simulations are often performed in combination with active-space multi-reference configuration interaction (MRCI) treatments. Technical problems may arise in such simulations if active and inactive orbitals strongly mix and switch in some particular regions. We propose to use adaptive time steps when such regions are encountered in TSH simulations. For this purpose, we present a computational protocol that is easy to implement and increases the computational effort only in the critical regions. We test this procedure through TSH simulations of a GFP chromophore model (OHBI) and a light-driven rotary molecular motor (F-NAIBP) on semiempirical MRCI potential energy surfaces, by comparing the results from simulations with adaptive time steps to analogous ones with constant time steps. For both test molecules, the number of successful trajectories without technical failures rises significantly, from 53% to 95% for OHBI and from 25% to 96% for F-NAIBP. The computed excited-state lifetime remains essentially the same for OHBI and increases somewhat for F-NAIBP, and there is almost no change in the computed quantum efficiency for internal rotation in F-NAIBP. We recommend the general use of adaptive time steps in TSH simulations with active-space CI methods because this will help to avoid technical problems, increase the overall efficiency and robustness of the simulations, and allow for a more complete sampling.

A charge-driven molecular water pump.

PubMed

Gong, Xiaojing; Li, Jingyuan; Lu, Hangjun; Wan, Rongzheng; Li, Jichen; Hu, Jun; Fang, Haiping

2007-11-01

Understanding and controlling the transport of water across nanochannels is of great importance for designing novel molecular devices, machines and sensors and has wide applications, including the desalination of seawater. Nanopumps driven by electric or magnetic fields can transport ions and magnetic quanta, but water is charge-neutral and has no magnetic moment. On the basis of molecular dynamics simulations, we propose a design for a molecular water pump. The design uses a combination of charges positioned adjacent to a nanopore and is inspired by the structure of channels in the cellular membrane that conduct water in and out of the cell (aquaporins). The remarkable pumping ability is attributed to the charge dipole-induced ordering of water confined in the nanochannels, where water can be easily driven by external fields in a concerted fashion. These findings may provide possibilities for developing water transport devices that function without osmotic pressure or a hydrostatic pressure gradient.

Non-Hemagglutinating Flaviviruses: Molecular Mechanisms for the Emergence of New Strains via Adaptation to European Ticks

PubMed Central

Khasnatinov, Maxim A.; Ustanikova, Katarina; Frolova, Tatiana V.; Pogodina, Vanda V.; Bochkova, Nadezshda G.; Levina, Ludmila S.; Slovak, Mirko; Kazimirova, Maria; Labuda, Milan; Klempa, Boris; Eleckova, Elena; Gould, Ernest A.; Gritsun, Tamara S.

2009-01-01

Tick-borne encephalitis virus (TBEV) causes human epidemics across Eurasia. Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. TBEV is characteristically a hemagglutinating (HA) virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus. By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A) in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface. Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency. Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains. Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution. Retrospectively, the mutation D67G was identified in viruses isolated from patients with encephalitis. We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks. This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species. As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis. Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards across Europe by adaptation to the indigenous tick species and if they are associated with severe forms of TBE. PMID:19802385

Bounded Linear Stability Margin Analysis of Nonlinear Hybrid Adaptive Control

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Boskovic, Jovan D.

2008-01-01

This paper presents a bounded linear stability analysis for a hybrid adaptive control that blends both direct and indirect adaptive control. Stability and convergence of nonlinear adaptive control are analyzed using an approximate linear equivalent system. A stability margin analysis shows that a large adaptive gain can lead to a reduced phase margin. This method can enable metrics-driven adaptive control whereby the adaptive gain is adjusted to meet stability margin requirements.

Molecular Dynamics Simulations of an Idealized Shock Tube: N2 in Ar Bath Driven by He

NASA Astrophysics Data System (ADS)

Piskulich, Ezekiel Ashe; Sewell, Thomas D.; Thompson, Donald L.

2015-06-01

The dynamics of 10% N2 in Ar initially at 298 K in an idealized shock tube driven by He was studied using molecular dynamics. The simulations were performed using the Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) code. Nitrogen was modeled as a Morse oscillator and non-covalent interactions were approximated by the Buckingham exponential-6 pair potential. The initial pressures in the He driver gas and the driven N2/Ar gas were 1000 atm and 20 atm, respectively. Microcanonical trajectories were followed for 2 ns following release of the driver gas. Results for excitation and subsequent relaxation of the N2, as well as properties of the gas during the simulations, will be reported.

Advances on molecular mechanism of the adaptive evolution of Chiroptera (bats).

PubMed

Yunpeng, Liang; Li, Yu

2015-01-01

As the second biggest animal group in mammals, Chiroptera (bats) demonstrates many unique adaptive features in terms of flight, echolocation, auditory acuity, feeding habit, hibernation and immune defense, providing an excellent system for understanding the molecular basis of how organisms adapt to the living environments encountered. In this review, we summarize the researches on the molecular mechanism of the adaptive evolution of Chiroptera, especially the recent researches at the genome levels, suggesting a far more complex evolutionary pattern and functional diversity than previously thought. In the future, along with the increasing numbers of Chiroptera species genomes available, new evolutionary patterns and functional divergence will be revealed, which can promote the further understanding of this animal group and the molecular mechanism of adaptive evolution.

Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

PubMed Central

2017-01-01

Conspectus Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular biodynamers are commonly produced in aqueous media under mild or even physiological conditions to suit their biorelated applications. In contrast to static biopolymers emphasizing structural stability and unity by using irreversible covalent bonds, molecular biodynamers are seeking relative structural adaptability and diversity through the formation of reversible covalent bonds. Based on these considerations, molecular biodynamers are capable of reorganizing their monomers, generating, identifying, and amplifying the fittest structures in response to environmental factors. Hence, molecular biodynamers have received considerable research attention over the past decades. Accordingly, the construction of molecular biodynamers through equilibrium polymerization of nucleobase-, carbohydrate- or amino-acid-based monomers can lead to the fabrication of dynamic analogues of nucleic acids (DyNAs), polysaccharides (glycodynamers), or proteins (dynamic proteoids), respectively. In this Account, we summarize recent advances in developing different types of molecular biodynamers as structural or functional biomimetics of biopolymers, including DyNAs, glycodynamers, and dynamic proteoids. We introduce how chemists utilize various reversible reactions to generate molecular biodynamers with specific sequences and well-ordered structures in aqueous medium. We also discuss and list their potential applications in various research fields, such as drug delivery, drug discovery, gene sensing, cancer diagnosis, and treatment. PMID:28169527

Spin Seebeck effect in a metal-single-molecule-magnet-metal junction

NASA Astrophysics Data System (ADS)

Niu, Pengbin; Liu, Lixiang; Su, Xiaoqiang; Dong, Lijuan; Luo, Hong-Gang

2018-01-01

We investigate the nonlinear regime of temperature-driven spin-related currents through a single molecular magnet (SMM), which is connected with two metal electrodes. Under a large spin approximation, the SMM is simplified to a natural two-channel model possessing spin-opposite configuration and Coulomb interaction. We find that in temperature-driven case the system can generate spin-polarized currents. More interestingly, at electron-hole symmetry point, the competition of the two channels induces a temperature-driven pure spin current. This device demonstrates that temperature-driven SMM junction shows some results different from the usual quantum dot model, which may be useful in the future design of thermal-based molecular spintronic devices.

Evolution of complex adaptations in molecular systems

PubMed Central

Pál, Csaba; Papp, Balázs

2017-01-01

A central challenge in evolutionary biology concerns the mechanisms by which complex adaptations arise. Such adaptations depend on the fixation of multiple, highly specific mutations, where intermediate stages of evolution seemingly provide little or no benefit. It is generally assumed that the establishment of complex adaptations is very slow in nature, as evolution of such traits demands special population genetic or environmental circumstances. However, blueprints of complex adaptations in molecular systems are pervasive, indicating that they can readily evolve. We discuss the prospects and limitations of non-adaptive scenarios, which assume multiple neutral or deleterious steps in the evolution of complex adaptations. Next, we examine how complex adaptations can evolve by natural selection in changing environment. Finally, we argue that molecular ’springboards’, such as phenotypic heterogeneity and promiscuous interactions facilitate this process by providing access to new adaptive paths. PMID:28782044

Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

PubMed

Kwon, Ronald Y; Meays, Diana R; Meilan, Alexander S; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A

2012-01-01

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF.

The protein level of hypoxia-inducible factor-1alpha is increased in the plateau pika (Ochotona curzoniae) inhabiting high altitudes.

PubMed

Li, Hong-Ge; Ren, Yong-Ming; Guo, Song-Chang; Cheng, Long; Wang, De-Peng; Yang, Jie; Chang, Zhi-Jie; Zhao, Xin-Quan

2009-02-01

The plateau pika (Ochotona curzoniae) is a high hypoxia-tolerant species living only at 3,000-5,000 m above sea-level on the Qinghai-Tibetan plateau. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates a variety of cellular and systemic adaptations to hypoxia. To investigate how the plateau pika adapts to a high-altitude hypoxic environment at the molecular level, we examined the expression pattern of the HIF-1alpha protein in the pika by Western blot and immunohistochemical analysis. We found that HIF-1alpha protein is expressed at a significantly high level in the pika, which is higher in most tissues (particularly in the lung, liver, spleen and kidney) of the plateau pika than that of mice living at sea-level. Importantly, we found that the protein levels of HIF-1alpha in the lung, liver, spleen and kidney of the pika were increased with increased habitat altitudes. We observed that the plateau pika HIF-1alpha localized to the nucleus of cells by an immunostaining analysis, and enhanced HRE-driven gene expression by luciferase reporter assays. Our study suggests that the HIF-1alpha protein levels are related to the adaptation of the plateau pika to the high-altitude hypoxic environment.

Bioengineered 'golden' indica rice cultivars with beta-carotene metabolism in the endosperm with hygromycin and mannose selection systems.

PubMed

Datta, Karabi; Baisakh, Niranjan; Oliva, Norman; Torrizo, Lina; Abrigo, Editha; Tan, Jing; Rai, Mayank; Rehana, Sayda; Al-Babili, Salim; Beyer, Peter; Potrykus, Ingo; Datta, Swapan K

2003-03-01

Vitamin-A deficiency (VAD) is a major malnutrition problem in South Asia, where indica rice is the staple food. Indica-type rice varieties feed more than 2 billion people. Hence, we introduced a combination of transgenes using the biolistic system of transformation enabling biosynthesis of provitamin A in the endosperm of several indica rice cultivars adapted to diverse ecosystems of different countries. The rice seed-specific glutelin promoter (Gt-1 P) was used to drive the expression of phytoene synthase (psy), while lycopene beta-cyclase (lcy) and phytoene desaturase (crtI), fused to the transit peptide sequence of the pea-Rubisco small subunit, were driven by the constitutive cauliflower mosaic virus promoter (CaMV35S P). Transgenic plants were recovered through selection with either CaMV35S P driven hph (hygromycin phosphotransferase) gene or cestrum yellow leaf curling virus promoter (CMP) driven pmi (phophomannose isomerase) gene. Molecular and biochemical analyses demonstrated stable integration and expression of the transgenes. The yellow colour of the polished rice grain evidenced the carotenoid accumulation in the endosperm. The colour intensity correlated with the estimated carotenoid content by spectrophotometric and HPLC analysis. Carotenoid level in cooked polished seeds was comparable (with minor loss of xanthophylls) to that in non-cooked seeds of the same transgenic line. The variable segregation pattern in T1 selfing generation indicated single to multiple loci insertion of the transgenes in the genome. This is the first report of using nonantibiotic pmi driven by a novel promoter in generating transgenic indica rice for possible future use in human nutrition.

Object-Driven and Temporal Action Rules Mining

ERIC Educational Resources Information Center

Hajja, Ayman

2013-01-01

In this thesis, I present my complete research work in the field of action rules, more precisely object-driven and temporal action rules. The drive behind the introduction of object-driven and temporally based action rules is to bring forth an adapted approach to extract action rules from a subclass of systems that have a specific nature, in which…

Single shot ultrafast dynamic ellipsometry (UDE) of laser-driven shocks in single crystal explosives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitley, Von H; Mcgrane, Shawn D; Moore, David S

2009-01-01

We report on the first experiments to measure states in shocked energetic single crystals with dynamic ellipsometry. We demonstrate that these ellipsometric techniques can produce reasonable Hugoniot values using small amounts of crystalline RDX and PETN. Pressures, particle velocities and shock velocities obtained using shocked ellipsometry are comparable to those found using gas-gun flyer plates and molecular dynamics calculations. The adaptation of the technique from uniform thin films of polymers to thick non-perfect crystalline materials was a significant achievement. Correct sample preparation proved to be a crucial component. Through trial and error, we were able to resolve polishing issues, samplemore » quality problems, birefringence effects and mounting difficulties that were not encountered using thin polymer films.« less

How molecular motors work – insights from the molecular machinist's toolbox: the Nobel prize in Chemistry 2016

PubMed Central

Astumian, R. D.

2017-01-01

The Nobel prize in Chemistry for 2016 was awarded to Jean Pierre Sauvage, Sir James Fraser Stoddart, and Bernard (Ben) Feringa for their contributions to the design and synthesis of molecular machines. While this field is still in its infancy, and at present there are no commercial applications, many observers have stressed the tremendous potential of molecular machines to revolutionize technology. However, perhaps the most important result so far accruing from the synthesis of molecular machines is the insight provided into the fundamental mechanisms by which molecular motors, including biological motors such as kinesin, myosin, FoF1 ATPase, and the flagellar motor, function. The ability to “tinker” with separate components of molecular motors allows asking, and answering, specific questions about mechanism, particularly with regard to light driven vs. chemistry driven molecular motors. PMID:28572896

Real-time divergent evolution in plants driven by pollinators

PubMed Central

Gervasi, Daniel D. L.; Schiestl, Florian P

2017-01-01

Pollinator-driven diversification is thought to be a major source of floral variation in plants. Our knowledge of this process is, however, limited to indirect assessments of evolutionary changes. Here, we employ experimental evolution with fast cycling Brassica rapa plants to demonstrate adaptive evolution driven by different pollinators. Our study shows pollinator-driven divergent selection as well as divergent evolution in plant traits. Plants pollinated by bumblebees evolved taller size and more fragrant flowers with increased ultraviolet reflection. Bumblebees preferred bumblebee-pollinated plants over hoverfly-pollinated plants at the end of the experiment, showing that plants had adapted to the bumblebees' preferences. Plants with hoverfly pollination became shorter, had reduced emission of some floral volatiles, but increased fitness through augmented autonomous self-pollination. Our study demonstrates that changes in pollinator communities can have rapid consequences on the evolution of plant traits and mating system. PMID:28291771

Molecular and cellular bases of adaptation to a changing environment in microorganisms.

PubMed

Bleuven, Clara; Landry, Christian R

2016-10-26

Environmental heterogeneity constitutes an evolutionary challenge for organisms. While evolutionary dynamics under variable conditions has been explored for decades, we still know relatively little about the cellular and molecular mechanisms involved. It is of paramount importance to examine these molecular bases because they may play an important role in shaping the course of evolution. In this review, we examine the diversity of adaptive mechanisms in the face of environmental changes. We exploit the recent literature on microbial systems because those have benefited the most from the recent emergence of genetic engineering and experimental evolution followed by genome sequencing. We identify four emerging trends: (i) an adaptive molecular change in a pathway often results in fitness trade-off in alternative environments but the effects are dependent on a mutation's genetic background; (ii) adaptive changes often modify transcriptional and signalling pathways; (iii) several adaptive changes may occur within the same molecular pathway but be associated with pleiotropy of different signs across environments; (iv) because of their large associated costs, macromolecular changes such as gene amplification and aneuploidy may be a rapid mechanism of adaptation in the short-term only. The course of adaptation in a variable environment, therefore, depends on the complexity of the environment but also on the molecular relationships among the genes involved and between the genes and the phenotypes under selection. © 2016 The Author(s).

Functionally dissociable influences on learning rate in a dynamic environment

PubMed Central

McGuire, Joseph T.; Nassar, Matthew R.; Gold, Joshua I.; Kable, Joseph W.

2015-01-01

Summary Maintaining accurate beliefs in a changing environment requires dynamically adapting the rate at which one learns from new experiences. Beliefs should be stable in the face of noisy data, but malleable in periods of change or uncertainty. Here we used computational modeling, psychophysics and fMRI to show that adaptive learning is not a unitary phenomenon in the brain. Rather, it can be decomposed into three computationally and neuroanatomically distinct factors that were evident in human subjects performing a spatial-prediction task: (1) surprise-driven belief updating, related to BOLD activity in visual cortex; (2) uncertainty-driven belief updating, related to anterior prefrontal and parietal activity; and (3) reward-driven belief updating, a context-inappropriate behavioral tendency related to activity in ventral striatum. These distinct factors converged in a core system governing adaptive learning. This system, which included dorsomedial frontal cortex, responded to all three factors and predicted belief updating both across trials and across individuals. PMID:25459409

Optimizing Likelihood Models for Particle Trajectory Segmentation in Multi-State Systems.

PubMed

Young, Dylan Christopher; Scrimgeour, Jan

2018-06-19

Particle tracking offers significant insight into the molecular mechanics that govern the behav- ior of living cells. The analysis of molecular trajectories that transition between different motive states, such as diffusive, driven and tethered modes, is of considerable importance, with even single trajectories containing significant amounts of information about a molecule's environment and its interactions with cellular structures. Hidden Markov models (HMM) have been widely adopted to perform the segmentation of such complex tracks. In this paper, we show that extensive analysis of hidden Markov model outputs using data derived from multi-state Brownian dynamics simulations can be used both for the optimization of the likelihood models used to describe the states of the system and for characterization of the technique's failure mechanisms. This analysis was made pos- sible by the implementation of parallelized adaptive direct search algorithm on a Nvidia graphics processing unit. This approach provides critical information for the visualization of HMM failure and successful design of particle tracking experiments where trajectories contain multiple mobile states. © 2018 IOP Publishing Ltd.

Recovery from retinal lesions: molecular plasticity mechanisms in visual cortex far beyond the deprived zone.

PubMed

Hu, Tjing-Tjing; Van den Bergh, Gert; Thorrez, Lieven; Heylen, Kevin; Eysel, Ulf T; Arckens, Lutgarde

2011-12-01

In cats with central retinal lesions, deprivation of the lesion projection zone (LPZ) in primary visual cortex (area 17) induces remapping of the cortical topography. Recovery of visually driven cortical activity in the LPZ involves distinct changes in protein expression. Recent observations, about molecular activity changes throughout area 17, challenge the view that its remote nondeprived parts would not be involved in this recovery process. We here investigated the dynamics of the protein expression pattern of remote nondeprived area 17 triggered by central retinal lesions to explore to what extent far peripheral area 17 would contribute to the topographic map reorganization inside the visual cortex. Using functional proteomics, we identified 40 proteins specifically differentially expressed between far peripheral area 17 of control and experimental animals 14 days to 8 months postlesion. Our results demonstrate that far peripheral area 17 is implicated in the functional adaptation to the visual deprivation, involving a meshwork of interacting proteins, operating in diverse pathways. In particular, endocytosis/exocytosis processes appeared to be essential via their intimate correlation with long-term potentiation and neurite outgrowth mechanisms.

Temporal switching of an amphiphilic self-assembly by a chemical fuel-driven conformational response† †Electronic supplementary information (ESI) available: Experimental section, synthetic procedures and supporting figures. See DOI: 10.1039/c7sc01730h Click here for additional data file.

PubMed Central

Jalani, Krishnendu; Dhiman, Shikha

2017-01-01

The spatial and temporal control of self-assemblies is the latest scientific hurdle in supramolecular chemistry which is inspired by the functioning of biological systems fueled by chemical signals. In this study, we work towards alleviating this scenario by employing a unique amphiphilic foldamer that operates under the effect of a chemical fuel. The conformational changes in the foldamer amplify into observable morphological changes in its amphiphilic assembly that are controlled by external molecular cues (fuel). We take advantage of this redox responsive foldamer to affect its conformation in a temporal manner by an enzymatic pathway. The temporal characteristics of the transient conformation/assembly can be modulated by varying the concentrations of the fuel and enzyme. We believe that such a design strategy can have positive consequences in designing molecular and supramolecular systems for future active, adaptive and autonomous materials. PMID:28989632

Comparative study of adaptive radiations with an example using parasitic flatworms (Platyhelminthes): Cercomeria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brooks, D.R.; McLennan, D.A.

1993-11-01

Studies of adaptive radiations require robust phylogenies, estimates of species numbers for monophyletic groups within clades, assessments of the adaptive value of putative key innovations, and estimates of the frequency of speciation modes. Four criteria are necessary to identify an adaptive radiation within the parasitic platyhelminths: (1) a group contains significantly more species than its sister group, (2) species richness is apomorphic, (3) apomorphic traits enhance the potential for adaptively driven modes of speciation (sympatric speciation and speciation by peripheral isolation via host switching), and (4) the frequency of adaptively driven speciation modes is high within the group when comparedmore » with data from free-living groups. Only the species-rich Monogenea fulfill all four criteria. The Digenea and Eucestoda also are more species rich than their sister groups, their species richness is derived, and they possess unique characters that increase the potential for host switching to occur. However, because there is not enough information to determine whether the frequency of adaptive modes of speciation is high for those groups, we cannot yet assert that their radiations have been adaptive. 102 refs., 3 figs., 1 tab.« less

Solar Radiation-Associated Adaptive SNP Genetic Differentiation in Wild Emmer Wheat, Triticum dicoccoides.

PubMed

Ren, Jing; Chen, Liang; Jin, Xiaoli; Zhang, Miaomiao; You, Frank M; Wang, Jirui; Frenkel, Vladimir; Yin, Xuegui; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

2017-01-01

Whole-genome scans with large number of genetic markers provide the opportunity to investigate local adaptation in natural populations and identify candidate genes under positive selection. In the present study, adaptation genetic differentiation associated with solar radiation was investigated using 695 polymorphic SNP markers in wild emmer wheat originated in a micro-site at Yehudiyya, Israel. The test involved two solar radiation niches: (1) sun, in-between trees; and (2) shade, under tree canopy, separated apart by a distance of 2-4 m. Analysis of molecular variance showed a small (0.53%) but significant portion of overall variation between the sun and shade micro-niches, indicating a non-ignorable genetic differentiation between sun and shade habitats. Fifty SNP markers showed a medium (0.05 ≤ F ST ≤ 0.15) or high genetic differentiation ( F ST > 0.15). A total of 21 outlier loci under positive selection were identified by using four different F ST -outlier testing algorithms. The markers and genome locations under positive selection are consistent with the known patterns of selection. These results suggested that genetic differentiation between sun and shade habitats is substantial, radiation-associated, and therefore ecologically determined. Hence, the results of this study reflected effects of natural selection through solar radiation on EST-related SNP genetic diversity, resulting presumably in different adaptive complexes at a micro-scale divergence. The present work highlights the evolutionary theory and application significance of solar radiation-driven natural selection in wheat improvement.

Metal-centred azaphosphatriptycene gear with a photo- and thermally driven mechanical switching function based on coordination isomerism.

PubMed

Ube, Hitoshi; Yasuda, Yoshihiro; Sato, Hiroyasu; Shionoya, Mitsuhiko

2017-02-08

Metal ions can serve as a centre of molecular motions due to their coordination geometry, reversible bonding nature and external stimuli responsiveness. Such essential features of metal ions have been utilized for metal-mediated molecular machines with the ability to motion switch via metallation/demetallation or coordination number variation at the metal centre; however, motion switching based on the change in coordination geometry remain largely unexplored. Herein, we report a Pt II -centred molecular gear that demonstrates control of rotor engagement and disengagement based on photo- and thermally driven cis-trans isomerization at the Pt II centre. This molecular rotary motion transmitter has been constructed from two coordinating azaphosphatriptycene rotators and one Pt II ion as a stator. Isomerization between an engaged cis-form and a disengaged trans-form is reversibly driven by ultraviolet irradiation and heating. Such a photo- and thermally triggered motional interconversion between engaged/disengaged states on a metal ion would provide a selector switch for more complex interlocking systems.

Time-resolved photoelectron spectroscopy of IR-driven electron dynamics in a charge transfer model system.

PubMed

Falge, Mirjam; Fröbel, Friedrich Georg; Engel, Volker; Gräfe, Stefanie

2017-08-02

If the adiabatic approximation is valid, electrons smoothly adapt to molecular geometry changes. In contrast, as a characteristic of diabatic dynamics, the electron density does not follow the nuclear motion. Recently, we have shown that the asymmetry in time-resolved photoelectron spectra serves as a tool to distinguish between these dynamics [Falge et al., J. Phys. Chem. Lett., 2012, 3, 2617]. Here, we investigate the influence of an additional, moderately intense infrared (IR) laser field, as often applied in attosecond time-resolved experiments, on such asymmetries. This is done using a simple model for coupled electronic-nuclear motion. We calculate time-resolved photoelectron spectra and their asymmetries and demonstrate that the spectra directly map the bound electron-nuclear dynamics. From the asymmetries, we can trace the IR field-induced population transfer and both the field-driven and intrinsic (non-)adiabatic dynamics. This holds true when considering superposition states accompanied by electronic coherences. The latter are observable in the asymmetries for sufficiently short XUV pulses to coherently probe the coupled states. It is thus documented that the asymmetry is a measure for phases in bound electron wave packets and non-adiabatic dynamics.

Adaptive Detection and ISI Mitigation for Mobile Molecular Communication.

PubMed

Chang, Ge; Lin, Lin; Yan, Hao

2018-03-01

Current studies on modulation and detection schemes in molecular communication mainly focus on the scenarios with static transmitters and receivers. However, mobile molecular communication is needed in many envisioned applications, such as target tracking and drug delivery. Until now, investigations about mobile molecular communication have been limited. In this paper, a static transmitter and a mobile bacterium-based receiver performing random walk are considered. In this mobile scenario, the channel impulse response changes due to the dynamic change of the distance between the transmitter and the receiver. Detection schemes based on fixed distance fail in signal detection in such a scenario. Furthermore, the intersymbol interference (ISI) effect becomes more complex due to the dynamic character of the signal which makes the estimation and mitigation of the ISI even more difficult. In this paper, an adaptive ISI mitigation method and two adaptive detection schemes are proposed for this mobile scenario. In the proposed scheme, adaptive ISI mitigation, estimation of dynamic distance, and the corresponding impulse response reconstruction are performed in each symbol interval. Based on the dynamic channel impulse response in each interval, two adaptive detection schemes, concentration-based adaptive threshold detection and peak-time-based adaptive detection, are proposed for signal detection. Simulations demonstrate that the ISI effect is significantly reduced and the adaptive detection schemes are reliable and robust for mobile molecular communication.

Dense CO in Mrk 71-A: Superwind Suppressed in a Young Super Star Cluster

NASA Astrophysics Data System (ADS)

Oey, M. S.; Herrera, C. N.; Silich, Sergiy; Reiter, Megan; James, Bethan L.; Jaskot, A. E.; Micheva, Genoveva

2017-11-01

We report the detection of CO(J=2-1) coincident with the super star cluster (SSC) Mrk 71-A in the nearby Green Pea analog galaxy, NGC 2366. Our observations with the Northern Extended Millimeter Array reveal a compact, ˜7 pc, molecular cloud whose mass ({10}5 {M}⊙ ) is similar to that of the SSC, consistent with a high star formation efficiency, on the order of 0.5. There are two spatially distinct components separated by 11 {km} {{{s}}}-1. If expanding, these could be due to momentum-driven stellar wind feedback. Alternatively, we may be seeing remnants of the infalling, colliding clouds responsible for triggering the SSC formation. The kinematics are also consistent with a virialized system. These extreme, high-density, star-forming conditions inhibit energy-driven feedback; the co-spatial existence of a massive, molecular cloud with the SSC supports this scenario, and we quantitatively confirm that any wind-driven feedback in Mrk 71-A is momentum-driven, rather than energy-driven. Since Mrk 71-A is a candidate Lyman continuum emitter, this implies that energy-driven superwinds may not be a necessary condition for the escape of ionizing radiation. In addition, the detection of nebular continuum emission yields an accurate astrometric position for the Mrk 71-A. We also detect four other massive molecular clouds in this giant star-forming complex.

Test Platform for Advanced Digital Control of Brushless DC Motors (MSFC Center Director's Discretionary Fund)

NASA Technical Reports Server (NTRS)

Gwaltney, D. A.

2002-01-01

A FY 2001 Center Director's Discretionary Fund task to develop a test platform for the development, implementation. and evaluation of adaptive and other advanced control techniques for brushless DC (BLDC) motor-driven mechanisms is described. Important applications for BLDC motor-driven mechanisms are the translation of specimens in microgravity experiments and electromechanical actuation of nozzle and fuel valves in propulsion systems. Motor-driven aerocontrol surfaces are also being utilized in developmental X vehicles. The experimental test platform employs a linear translation stage that is mounted vertically and driven by a BLDC motor. Control approaches are implemented on a digital signal processor-based controller for real-time, closed-loop control of the stage carriage position. The goal of the effort is to explore the application of advanced control approaches that can enhance the performance of a motor-driven actuator over the performance obtained using linear control approaches with fixed gains. Adaptive controllers utilizing an exact model knowledge controller and a self-tuning controller are implemented and the control system performance is illustrated through the presentation of experimental results.

Adaptation to conflict via context-driven anticipatory signals in the dorsomedial prefrontal cortex.

PubMed

Horga, Guillermo; Maia, Tiago V; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S

2011-11-09

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict.

Adaptation to Conflict via Context-Driven Anticipatory Signals in the Dorsomedial Prefrontal Cortex

PubMed Central

Horga, Guillermo; Maia, Tiago V.; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S.

2011-01-01

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging (fMRI), we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict. PMID:22072672

How Complex, Probable, and Predictable is Genetically Driven Red Queen Chaos?

PubMed

Duarte, Jorge; Rodrigues, Carla; Januário, Cristina; Martins, Nuno; Sardanyés, Josep

2015-12-01

Coevolution between two antagonistic species has been widely studied theoretically for both ecologically- and genetically-driven Red Queen dynamics. A typical outcome of these systems is an oscillatory behavior causing an endless series of one species adaptation and others counter-adaptation. More recently, a mathematical model combining a three-species food chain system with an adaptive dynamics approach revealed genetically driven chaotic Red Queen coevolution. In the present article, we analyze this mathematical model mainly focusing on the impact of species rates of evolution (mutation rates) in the dynamics. Firstly, we analytically proof the boundedness of the trajectories of the chaotic attractor. The complexity of the coupling between the dynamical variables is quantified using observability indices. By using symbolic dynamics theory, we quantify the complexity of genetically driven Red Queen chaos computing the topological entropy of existing one-dimensional iterated maps using Markov partitions. Co-dimensional two bifurcation diagrams are also built from the period ordering of the orbits of the maps. Then, we study the predictability of the Red Queen chaos, found in narrow regions of mutation rates. To extend the previous analyses, we also computed the likeliness of finding chaos in a given region of the parameter space varying other model parameters simultaneously. Such analyses allowed us to compute a mean predictability measure for the system in the explored region of the parameter space. We found that genetically driven Red Queen chaos, although being restricted to small regions of the analyzed parameter space, might be highly unpredictable.

Communication: Adaptive boundaries in multiscale simulations

NASA Astrophysics Data System (ADS)

Wagoner, Jason A.; Pande, Vijay S.

2018-04-01

Combined-resolution simulations are an effective way to study molecular properties across a range of length and time scales. These simulations can benefit from adaptive boundaries that allow the high-resolution region to adapt (change size and/or shape) as the simulation progresses. The number of degrees of freedom required to accurately represent even a simple molecular process can vary by several orders of magnitude throughout the course of a simulation, and adaptive boundaries react to these changes to include an appropriate but not excessive amount of detail. Here, we derive the Hamiltonian and distribution function for such a molecular simulation. We also design an algorithm that can efficiently sample the boundary as a new coordinate of the system. We apply this framework to a mixed explicit/continuum simulation of a peptide in solvent. We use this example to discuss the conditions necessary for a successful implementation of adaptive boundaries that is both efficient and accurate in reproducing molecular properties.

Materials learning from life: concepts for active, adaptive and autonomous molecular systems.

PubMed

Merindol, Rémi; Walther, Andreas

2017-09-18

Bioinspired out-of-equilibrium systems will set the scene for the next generation of molecular materials with active, adaptive, autonomous, emergent and intelligent behavior. Indeed life provides the best demonstrations of complex and functional out-of-equilibrium systems: cells keep track of time, communicate, move, adapt, evolve and replicate continuously. Stirred by the understanding of biological principles, artificial out-of-equilibrium systems are emerging in many fields of soft matter science. Here we put in perspective the molecular mechanisms driving biological functions with the ones driving synthetic molecular systems. Focusing on principles that enable new levels of functionalities (temporal control, autonomous structures, motion and work generation, information processing) rather than on specific material classes, we outline key cross-disciplinary concepts that emerge in this challenging field. Ultimately, the goal is to inspire and support new generations of autonomous and adaptive molecular devices fueled by self-regulating chemistry.

Tilt aftereffect following adaptation to translational Glass patterns

PubMed Central

Pavan, Andrea; Hocketstaller, Johanna; Contillo, Adriano; Greenlee, Mark W.

2016-01-01

Glass patterns (GPs) consist of randomly distributed dot pairs (dipoles) whose orientations are determined by specific geometric transforms. We assessed whether adaptation to stationary oriented translational GPs suppresses the activity of orientation selective detectors producing a tilt aftereffect (TAE). The results showed that adaptation to GPs produces a TAE similar to that reported in previous studies, though reduced in amplitude. This suggests the involvement of orientation selective mechanisms. We also measured the interocular transfer (IOT) of the GP-induced TAE and found an almost complete IOT, indicating the involvement of orientation selective and binocularly driven units. In additional experiments, we assessed the role of attention in TAE from GPs. The results showed that distraction during adaptation similarly modulates the TAE after adapting to both GPs and gratings. Moreover, in the case of GPs, distraction is likely to interfere with the adaptation process rather than with the spatial summation of local dipoles. We conclude that TAE from GPs possibly relies on visual processing levels in which the global orientation of GPs has been encoded by neurons that are mostly binocularly driven, orientation selective and whose adaptation-related neural activity is strongly modulated by attention. PMID:27005949

The Physics and Physical Chemistry of Molecular Machines.

PubMed

Astumian, R Dean; Mukherjee, Shayantani; Warshel, Arieh

2016-06-17

The concept of a "power stroke"-a free-energy releasing conformational change-appears in almost every textbook that deals with the molecular details of muscle, the flagellar rotor, and many other biomolecular machines. Here, it is shown by using the constraints of microscopic reversibility that the power stroke model is incorrect as an explanation of how chemical energy is used by a molecular machine to do mechanical work. Instead, chemically driven molecular machines operating under thermodynamic constraints imposed by the reactant and product concentrations in the bulk function as information ratchets in which the directionality and stopping torque or stopping force are controlled entirely by the gating of the chemical reaction that provides the fuel for the machine. The gating of the chemical free energy occurs through chemical state dependent conformational changes of the molecular machine that, in turn, are capable of generating directional mechanical motions. In strong contrast to this general conclusion for molecular machines driven by catalysis of a chemical reaction, a power stroke may be (and often is) an essential component for a molecular machine driven by external modulation of pH or redox potential or by light. This difference between optical and chemical driving properties arises from the fundamental symmetry difference between the physics of optical processes, governed by the Bose-Einstein relations, and the constraints of microscopic reversibility for thermally activated processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

PubMed Central

Kwon, Ronald Y.; Meays, Diana R.; Meilan, Alexander S.; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A.

2012-01-01

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF. PMID:22413015

Neuroendocrine control of seasonal plasticity in the auditory and vocal systems of fish

PubMed Central

Forlano, Paul M.; Sisneros, Joseph A.; Rohmann, Kevin N.; Bass, Andrew H.

2014-01-01

Seasonal changes in reproductive-related vocal behavior are widespread among fishes. This review highlights recent studies of the vocal plainfin midshipman fish, Porichthys notatus, a neuroethological model system used for the past two decades to explore neural and endocrine mechanisms of vocal-acoustic social behaviors shared with tetrapods. Integrative approaches combining behavior, neurophysiology, neuropharmacology, neuroanatomy, and gene expression methodologies have taken advantage of simple, stereotyped and easily quantifiable behaviors controlled by discrete neural networks in this model system to enable discoveries such as the first demonstration of adaptive seasonal plasticity in the auditory periphery of a vertebrate as well as rapid steroid and neuropeptide effects on vocal physiology and behavior. This simple model system has now revealed cellular and molecular mechanisms underlying seasonal and steroid-driven auditory and vocal plasticity in the vertebrate brain. PMID:25168757

The butterfly plant arms-race escalated by gene and genome duplications

PubMed Central

Edger, Patrick P.; Heidel-Fischer, Hanna M.; Bekaert, Michaël; Rota, Jadranka; Glöckner, Gernot; Platts, Adrian E.; Heckel, David G.; Der, Joshua P.; Wafula, Eric K.; Tang, Michelle; Hofberger, Johannes A.; Smithson, Ann; Hall, Jocelyn C.; Blanchette, Matthieu; Bureau, Thomas E.; Wright, Stephen I.; dePamphilis, Claude W.; Eric Schranz, M.; Barker, Michael S.; Conant, Gavin C.; Wahlberg, Niklas; Vogel, Heiko; Pires, J. Chris; Wheat, Christopher W.

2015-01-01

Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits. PMID:26100883

Timing and Targeting of Treatment in Left Ventricular Hypertrophy.

PubMed

Nam, Deokhwa; Reineke, Erin L

2017-01-01

In most clinical cases, left ventricular hypertrophy (LVH) occurs over time from persistent cardiac stress. At the molecular level, this results in both transient and long-term changes to metabolic, sarcomeric, ion handling, and stress signaling pathways. Although this is initially an adaptive change, the mechanisms underlying LVH eventually lead to maladaptive changes including fibrosis, decreased cardiac function, and failure. Understanding the regulators of long-term changes, which are largely driven by transcriptional remodeling, is a crucial step in identifying novel therapeutic targets for preventing the downstream negative effects of LVH and treatments that could reverse or prevent it. The development of effective therapeutics, however, will require a critical understanding of what to target, how to modify important pathways, and how to identify the stage of pathology in which a specific treatment should be used.

The butterfly plant arms-race escalated by gene and genome duplications.

PubMed

Edger, Patrick P; Heidel-Fischer, Hanna M; Bekaert, Michaël; Rota, Jadranka; Glöckner, Gernot; Platts, Adrian E; Heckel, David G; Der, Joshua P; Wafula, Eric K; Tang, Michelle; Hofberger, Johannes A; Smithson, Ann; Hall, Jocelyn C; Blanchette, Matthieu; Bureau, Thomas E; Wright, Stephen I; dePamphilis, Claude W; Eric Schranz, M; Barker, Michael S; Conant, Gavin C; Wahlberg, Niklas; Vogel, Heiko; Pires, J Chris; Wheat, Christopher W

2015-07-07

Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.

PD-1/PD-L1 pathway: an adaptive immune resistance mechanism to immunogenic chemotherapy in colorectal cancer.

PubMed

Dosset, Magalie; Vargas, Thaiz Rivera; Lagrange, Anaïs; Boidot, Romain; Végran, Frédérique; Roussey, Aurélie; Chalmin, Fanny; Dondaine, Lucile; Paul, Catherine; Marie-Joseph, Elodie Lauret; Martin, François; Ryffel, Bernhard; Borg, Christophe; Adotévi, Olivier; Ghiringhelli, François; Apetoh, Lionel

2018-01-01

Chemotherapy is currently evaluated in order to enhance the efficacy of immune checkpoint blockade (ICB) therapy in colorectal cancer. However, the mechanisms by which these drugs could synergize with ICB remains unclear. The impact of chemotherapy on the PD-1/PD-L1 pathway and the resulting anticancer immune responses was assessed in two mouse models of colorectal cancer and validated in tumor samples from metastatic colorectal cancer patients that received neoadjuvant treatment. We demonstrated that 5-Fluorouracil plus Oxaliplatin (Folfox) drove complete tumor cure in mice when combined to anti-PD-1 treatment, while each monotherapy failed. This synergistic effect relies on the ability of Folfox to induce tumor infiltration by activated PD-1 + CD8 T cells in a T-bet dependent manner. This effect was concomitantly associated to the expression of PD-L1 on tumor cells driven by IFN-γ secreted by PD-1+ CD8 T cells, indicating that Folfox triggers tumor adaptive immune resistance. Finally, we observed an induction of PD-L1 expression and high CD8 T cell infiltration in the tumor microenvironment of colorectal cancer patients treated by Folfox regimen. Our study delineates a molecular pathway involved in Folfox-induced adaptive immune resistance in colorectal cancer. The results strongly support the use of immune checkpoint blockade therapy in combination with chemotherapies like Folfox.

Role of selection and gene flow in population differentiation at the edge vs. interior of the species range differing in climatic conditions.

PubMed

Volis, S; Ormanbekova, D; Shulgina, I

2016-04-01

Evaluating the relative importance of neutral and adaptive processes as determinants of population differentiation across environments is a central theme of evolutionary biology. We applied the QST-FST comparison flanked by a direct test for local adaptation to infer the role of climate-driven selection and gene flow in population differentiation of an annual grass Avena sterilis in two distinct parts of the species range, edge and interior, which represent two globally different climates, desert and Mediterranean. In a multiyear reciprocal transplant experiment, the plants of desert and Mediterranean origin demonstrated home advantage, and population differentiation in several phenotypic traits related to reproduction exceeded neutral predictions, as determined by comparisons of QST values with theoretical FST distributions. Thus, variation in these traits likely resulted from local adaptation to desert and Mediterranean environments. The two separate common garden experiments conducted with different experimental design revealed that two population comparisons, in contrast to multi-population comparisons, are likely to detect population differences in virtually every trait, but many of these differences reflect effects of local rather than regional environment. We detected a general reduction in neutral (SSR) genetic variation but not in adaptive quantitative trait variation in peripheral desert as compared with Mediterranean core populations. On the other hand, the molecular data indicated intensive gene flow from the Mediterranean core towards desert periphery. Although species range position in our study (edge vs. interior) was confounded with climate (desert vs. Mediterranean), the results suggest that the gene flow from the species core does not have negative consequences for either performance of the peripheral plants or their adaptive potential. © 2016 John Wiley & Sons Ltd.

Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators.

PubMed

Luján, Adela M; Maciá, María D; Yang, Liang; Molin, Søren; Oliver, Antonio; Smania, Andrea M

2011-01-01

Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF) patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS)], play important roles in P. aeruginosa chronic infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition experiments we demonstrate for the first time that P. aeruginosa MRS-deficient mutators had enhanced adaptability over wild-type strains when grown in structured biofilms but not as planktonic cells. This advantage was associated with enhanced micro-colony development and increased rates of phenotypic diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution in the biofilm mode of growth. This work helps to understand the basis for the specific high proportion and role of mutators in chronic infections, where P. aeruginosa develops in biofilm communities.

Evolution and Adaptation in Pseudomonas aeruginosa Biofilms Driven by Mismatch Repair System-Deficient Mutators

PubMed Central

Yang, Liang; Molin, Søren; Oliver, Antonio; Smania, Andrea M.

2011-01-01

Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF) patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS)], play important roles in P. aeruginosa chronic infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition experiments we demonstrate for the first time that P. aeruginosa MRS-deficient mutators had enhanced adaptability over wild-type strains when grown in structured biofilms but not as planktonic cells. This advantage was associated with enhanced micro-colony development and increased rates of phenotypic diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution in the biofilm mode of growth. This work helps to understand the basis for the specific high proportion and role of mutators in chronic infections, where P. aeruginosa develops in biofilm communities. PMID:22114708

Defocused Imaging of UV-Driven Surface-Bound Molecular Motors.

PubMed

Krajnik, Bartosz; Chen, Jiawen; Watson, Matthew A; Cockroft, Scott L; Feringa, Ben L; Hofkens, Johan

2017-05-31

Synthetic molecular motors continue to attract great interest due to their ability to transduce energy into nanomechanical motion, the potential to do work and drive systems out-of-equilibrium. Of particular interest are unidirectional rotary molecular motors driven by chemical fuel or light. Probing the mechanistic details of their operation at the single-molecule level is hampered by the diffraction limit, which prevents the collection of dynamic positional information by traditional optical methods. Here, we use defocused wide-field imaging to examine the unidirectional rotation of individual molecular rotary motors on a quartz surface in unprecedented detail. The sequential occupation of nanomechanical states during the UV and heat-induced cycle of rotation are directly imaged in real-time. The approach will undoubtedly prove important in elucidating the mechanistic details and assessing the utility of novel synthetic molecular motors in the future.

Molecular determinants of enzyme cold adaptation: comparative structural and computational studies of cold- and warm-adapted enzymes.

PubMed

Papaleo, Elena; Tiberti, Matteo; Invernizzi, Gaetano; Pasi, Marco; Ranzani, Valeria

2011-11-01

The identification of molecular mechanisms underlying enzyme cold adaptation is a hot-topic both for fundamental research and industrial applications. In the present contribution, we review the last decades of structural computational investigations on cold-adapted enzymes in comparison to their warm-adapted counterparts. Comparative sequence and structural studies allow the definition of a multitude of adaptation strategies. Different enzymes carried out diverse mechanisms to adapt to low temperatures, so that a general theory for enzyme cold adaptation cannot be formulated. However, some common features can be traced in dynamic and flexibility properties of these enzymes, as well as in their intra- and inter-molecular interaction networks. Interestingly, the current data suggest that a family-centered point of view is necessary in the comparative analyses of cold- and warm-adapted enzymes. In fact, enzymes belonging to the same family or superfamily, thus sharing at least the three-dimensional fold and common features of the functional sites, have evolved similar structural and dynamic patterns to overcome the detrimental effects of low temperatures.

Adaptive control of a Stewart platform-based manipulator

NASA Technical Reports Server (NTRS)

Nguyen, Charles C.; Antrazi, Sami S.; Zhou, Zhen-Lei; Campbell, Charles E., Jr.

1993-01-01

A joint-space adaptive control scheme for controlling noncompliant motion of a Stewart platform-based manipulator (SPBM) was implemented in the Hardware Real-Time Emulator at Goddard Space Flight Center. The six-degrees of freedom SPBM uses two platforms and six linear actuators driven by dc motors. The adaptive control scheme is based on proportional-derivative controllers whose gains are adjusted by an adaptation law based on model reference adaptive control and Liapunov direct method. It is concluded that the adaptive control scheme provides superior tracking capability as compared to fixed-gain controllers.

A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host–Pathogen Interaction Networks

PubMed Central

Wu, Chia-Chou; Chen, Bor-Sen

2016-01-01

Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host–pathogen dynamic interaction networks. The consideration of host–pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host–pathogen molecular interaction networks, and consequent inferences of the host–pathogen relationship could be translated into biomedical applications. PMID:26881892

A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

PubMed

Wu, Chia-Chou; Chen, Bor-Sen

2016-01-01

Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications.

Evolution of animal and plant dicers: early parallel duplications and recurrent adaptation of antiviral RNA binding in plants.

PubMed

Mukherjee, Krishanu; Campos, Henry; Kolaczkowski, Bryan

2013-03-01

RNA interference (RNAi) is a eukaryotic molecular system that serves two primary functions: 1) gene regulation and 2) protection against selfish elements such as viruses and transposable DNA. Although the biochemistry of RNAi has been detailed in model organisms, very little is known about the broad-scale patterns and forces that have shaped RNAi evolution. Here, we provide a comprehensive evolutionary analysis of the Dicer protein family, which carries out the initial RNA recognition and processing steps in the RNAi pathway. We show that Dicer genes duplicated and diversified independently in early animal and plant evolution, coincident with the origins of multicellularity. We identify a strong signature of long-term protein-coding adaptation that has continually reshaped the RNA-binding pocket of the plant Dicer responsible for antiviral immunity, suggesting an evolutionary arms race with viral factors. We also identify key changes in Dicer domain architecture and sequence leading to specialization in either gene-regulatory or protective functions in animal and plant paralogs. As a whole, these results reveal a dynamic picture in which the evolution of Dicer function has driven elaboration of parallel RNAi functional pathways in animals and plants.

Fast convergence of learning requires plasticity between inferior olive and deep cerebellar nuclei in a manipulation task: a closed-loop robotic simulation

PubMed Central

Luque, Niceto R.; Garrido, Jesús A.; Carrillo, Richard R.; D'Angelo, Egidio; Ros, Eduardo

2014-01-01

The cerebellum is known to play a critical role in learning relevant patterns of activity for adaptive motor control, but the underlying network mechanisms are only partly understood. The classical long-term synaptic plasticity between parallel fibers (PFs) and Purkinje cells (PCs), which is driven by the inferior olive (IO), can only account for limited aspects of learning. Recently, the role of additional forms of plasticity in the granular layer, molecular layer and deep cerebellar nuclei (DCN) has been considered. In particular, learning at DCN synapses allows for generalization, but convergence to a stable state requires hundreds of repetitions. In this paper we have explored the putative role of the IO-DCN connection by endowing it with adaptable weights and exploring its implications in a closed-loop robotic manipulation task. Our results show that IO-DCN plasticity accelerates convergence of learning by up to two orders of magnitude without conflicting with the generalization properties conferred by DCN plasticity. Thus, this model suggests that multiple distributed learning mechanisms provide a key for explaining the complex properties of procedural learning and open up new experimental questions for synaptic plasticity in the cerebellar network. PMID:25177290

Basket Studies: Redefining Clinical Trials in the Era of Genome-Driven Oncology.

PubMed

Tao, Jessica J; Schram, Alison M; Hyman, David M

2018-01-29

Understanding a tumor's detailed molecular profile has become increasingly necessary to deliver the standard of care for patients with advanced cancer. Innovations in both tumor genomic sequencing technology and the development of drugs that target molecular alterations have fueled recent gains in genome-driven oncology care. "Basket studies," or histology-agnostic clinical trials in genomically selected patients, represent one important research tool to continue making progress in this field. We review key aspects of genome-driven oncology care, including the purpose and utility of basket studies, biostatistical considerations in trial design, genomic knowledgebase development, and patient matching and enrollment models, which are critical for translating our genomic knowledge into clinically meaningful outcomes.

Enhanced conflict-driven cognitive control by emotional arousal, not by valence.

PubMed

Zeng, Qinghong; Qi, Senqing; Li, Miaoyun; Yao, Shuxia; Ding, Cody; Yang, Dong

2017-09-01

Emotion is widely agreed to have two dimensions, valence and arousal. Few studies have explored the effect of emotion on conflict adaptation by considering both of these, which could have dissociate influence. The present study aimed to fill the gap as to whether emotional valence and arousal would exert dissociable influence on conflict adaptation. In the experiments, we included positive, neutral, and negative conditions, with comparable arousal between positive and negative conditions. Both positive and negative conditions have higher arousal than neutral ones. In Experiment 1, by using a two-colour-word Flanker task, we found that conflict adaptation was enhanced in both positive and negative contexts compared to a neutral context. Furthermore, this effect still existed when controlling stimulus-response repetitions in Experiment 2, which used a four-colour-word Flanker task. The findings suggest emotional arousal enhances conflict adaptation, regardless of emotional valence. Thus, future studies should consider emotional arousal when studying the effect of emotion on conflict adaptation. Moreover, the unique role of the emotional context in conflict-driven cognitive control is emphasised.

Combining environment-driven adaptation and task-driven optimisation in evolutionary robotics.

PubMed

Haasdijk, Evert; Bredeche, Nicolas; Eiben, A E

2014-01-01

Embodied evolutionary robotics is a sub-field of evolutionary robotics that employs evolutionary algorithms on the robotic hardware itself, during the operational period, i.e., in an on-line fashion. This enables robotic systems that continuously adapt, and are therefore capable of (re-)adjusting themselves to previously unknown or dynamically changing conditions autonomously, without human oversight. This paper addresses one of the major challenges that such systems face, viz. that the robots must satisfy two sets of requirements. Firstly, they must continue to operate reliably in their environment (viability), and secondly they must competently perform user-specified tasks (usefulness). The solution we propose exploits the fact that evolutionary methods have two basic selection mechanisms-survivor selection and parent selection. This allows evolution to tackle the two sets of requirements separately: survivor selection is driven by the environment and parent selection is based on task-performance. This idea is elaborated in the Multi-Objective aNd open-Ended Evolution (monee) framework, which we experimentally validate. Experiments with robotic swarms of 100 simulated e-pucks show that monee does indeed promote task-driven behaviour without compromising environmental adaptation. We also investigate an extension of the parent selection process with a 'market mechanism' that can ensure equitable distribution of effort over multiple tasks, a particularly pressing issue if the environment promotes specialisation in single tasks.

The Birth of a Galaxy: Primordial Metal Enrichment and Stellar Populations

NASA Astrophysics Data System (ADS)

Wise, John H.; Turk, Matthew J.; Norman, Michael L.; Abel, Tom

2012-01-01

By definition, Population III stars are metal-free, and their protostellar collapse is driven by molecular hydrogen cooling in the gas phase, leading to large characteristic masses. Population II stars with lower characteristic masses form when the star-forming gas reaches a critical metallicity of 10-6-10-3.5 Z ⊙. We present an adaptive mesh refinement radiation hydrodynamics simulation that follows the transition from Population III to Population II star formation. The maximum spatial resolution of 1 comoving parsec allows for individual molecular clouds to be well resolved and their stellar associations to be studied in detail. We model stellar radiative feedback with adaptive ray tracing. A top-heavy initial mass function for the Population III stars is considered, resulting in a plausible distribution of pair-instability supernovae and associated metal enrichment. We find that the gas fraction recovers from 5% to nearly the cosmic fraction in halos with merger histories rich in halos above 107 M ⊙. A single pair-instability supernova is sufficient to enrich the host halo to a metallicity floor of 10-3 Z ⊙ and to transition to Population II star formation. This provides a natural explanation for the observed floor on damped Lyα systems metallicities reported in the literature, which is of this order. We find that stellar metallicities do not necessarily trace stellar ages, as mergers of halos with established stellar populations can create superpositions of t-Z evolutionary tracks. A bimodal metallicity distribution is created after a starburst occurs when the halo can cool efficiently through atomic line cooling.

Future Technology-Driven Revolutions in Military Operations. Results of a Workshop

DTIC Science & Technology

1994-01-01

sensor missions. "• Biomolecular Electronics - The use of techniques from molecular biology and biotechnology to develop new molecular electronic materials...34* Biomolecular electronics - The use of techniques from molecular biology and biotechnology to develop new molecular electronic materials, components, and...occurring in molecular biology . 42 Biotechnology Molecular Biologists Arm Develoni "Magical" Caoabilitles "• To mynthsieh genm (frm satch) with conboi

Compiler-Driven Performance Optimization and Tuning for Multicore Architectures

DTIC Science & Technology

2015-04-10

develop a powerful system for auto-tuning of library routines and compute-intensive kernels, driven by the Pluto system for multicores that we are...kernels, driven by the Pluto system for multicores that we are developing. The work here is motivated by recent advances in two major areas of...automatic C-to-CUDA code generator using a polyhedral compiler transformation framework. We have used and adapted PLUTO (our state-of-the-art tool

Development of an electrically driven molecular motor.

PubMed

Murphy, Colin J; Sykes, E Charles H

2014-10-01

For molecules to be used as components in molecular machinery, methods are required that couple individual molecules to external energy sources in order to selectively excite motion in a given direction. While significant progress has been made in the construction of synthetic molecular motors powered by light and by chemical reactions, there are few experimental examples of electrically driven molecular motors. To this end, we pioneered the use of a new, stable and tunable molecular rotor system based on surface-bound thioethers to comprehensively study many aspects of molecular rotation. As biological molecular motors often operate at interfaces, our synthetic system is especially amenable to microscopic interrogation as compared to solution-based systems. Using scanning tunneling microscopy (STM) and density functional theory, we studied the rotation of surface-bound thioethers, which can be induced either thermally or by electrons from the STM tip in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. This work culminated in the first experimental demonstration of a single-molecule electric motor, where the electrically driven rotation of a butyl methyl sulfide molecule adsorbed on a copper surface could be directionally biased. The direction and rate of the rotation are related to the chirality of both the molecule and the STM tip (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adopting best practices: "Agility" moves from software development to healthcare project management.

PubMed

Kitzmiller, Rebecca; Hunt, Eleanor; Sproat, Sara Breckenridge

2006-01-01

It is time for a change in mindset in how nurses operationalize system implementations and manage projects. Computers and systems have evolved over time from unwieldy mysterious machines of the past to ubiquitous computer use in every aspect of daily lives and work sites. Yet, disconcertingly, the process used to implement these systems has not evolved. Technology implementation does not need to be a struggle. It is time to adapt traditional plan-driven implementation methods to incorporate agile techniques. Agility is a concept borrowed from software development and is presented here because it encourages flexibility, adaptation, and continuous learning as part of the implementation process. Agility values communication and harnesses change to an advantage, which facilitates the natural evolution of an adaptable implementation process. Specific examples of agility in an implementation are described, and plan-driven implementation stages are adapted to incorporate relevant agile techniques. This comparison demonstrates how an agile approach enhances traditional implementation techniques to meet the demands of today's complex healthcare environments.

Electron Driven Processes in Atmospheric Behaviour

NASA Astrophysics Data System (ADS)

Campbell, L.; Brunger, M. J.; Teubner, P. J. O.

2006-11-01

Electron impact plays an important role in many atmospheric processes. Calculation of these is important for basic understanding, atmospheric modeling and remote sensing. Accurate atomic and molecular data, including electron impact cross sections, are required for such calculations. Five electron-driven processes are considered: auroral and dayglow emissions, the reduction of atmospheric electron density by vibrationally excited N2, NO production and infrared emission from NO. In most cases the predictions are compared with measurements. The dependence on experimental atomic and molecular data is also investigated.

A nanojet: propulsion of a molecular machine by an asymmetric distribution of reaction--products

NASA Astrophysics Data System (ADS)

Liverpool, Tanniemola; Golestanian, Ramin; Ajdari, Armand

2006-03-01

A simple model for the reaction-driven propulsion of a small device is proposed as a model for (part of) a molecular machine in aqueous media. Motion of the device is driven by an asymmetric distribution of reaction products. We calculate the propulsive velocity of the device as well as the scale of the velocity fluctuations. We also consider the effects of hydrodynamic flow as well as a number of different scenarios for the kinetics of the reaction.

Propulsion of a Molecular Machine by Asymmetric Distribution of Reaction Products

NASA Astrophysics Data System (ADS)

Golestanian, Ramin; Liverpool, Tanniemola B.; Ajdari, Armand

2005-06-01

A simple model for the reaction-driven propulsion of a small device is proposed as a model for (part of) a molecular machine in aqueous media. The motion of the device is driven by an asymmetric distribution of reaction products. The propulsive velocity of the device is calculated as well as the scale of the velocity fluctuations. The effects of hydrodynamic flow as well as a number of different scenarios for the kinetics of the reaction are addressed.

Propulsion of a molecular machine by asymmetric distribution of reaction products.

PubMed

Golestanian, Ramin; Liverpool, Tanniemola B; Ajdari, Armand

2005-06-10

A simple model for the reaction-driven propulsion of a small device is proposed as a model for (part of) a molecular machine in aqueous media. The motion of the device is driven by an asymmetric distribution of reaction products. The propulsive velocity of the device is calculated as well as the scale of the velocity fluctuations. The effects of hydrodynamic flow as well as a number of different scenarios for the kinetics of the reaction are addressed.

Molecular signatures of plastic phenotypes in two eusocial insect species with simple societies.

PubMed

Patalano, Solenn; Vlasova, Anna; Wyatt, Chris; Ewels, Philip; Camara, Francisco; Ferreira, Pedro G; Asher, Claire L; Jurkowski, Tomasz P; Segonds-Pichon, Anne; Bachman, Martin; González-Navarrete, Irene; Minoche, André E; Krueger, Felix; Lowy, Ernesto; Marcet-Houben, Marina; Rodriguez-Ales, Jose Luis; Nascimento, Fabio S; Balasubramanian, Shankar; Gabaldon, Toni; Tarver, James E; Andrews, Simon; Himmelbauer, Heinz; Hughes, William O H; Guigó, Roderic; Reik, Wolf; Sumner, Seirian

2015-11-10

Phenotypic plasticity is important in adaptation and shapes the evolution of organisms. However, we understand little about what aspects of the genome are important in facilitating plasticity. Eusocial insect societies produce plastic phenotypes from the same genome, as reproductives (queens) and nonreproductives (workers). The greatest plasticity is found in the simple eusocial insect societies in which individuals retain the ability to switch between reproductive and nonreproductive phenotypes as adults. We lack comprehensive data on the molecular basis of plastic phenotypes. Here, we sequenced genomes, microRNAs (miRNAs), and multiple transcriptomes and methylomes from individual brains in a wasp (Polistes canadensis) and an ant (Dinoponera quadriceps) that live in simple eusocial societies. In both species, we found few differences between phenotypes at the transcriptional level, with little functional specialization, and no evidence that phenotype-specific gene expression is driven by DNA methylation or miRNAs. Instead, phenotypic differentiation was defined more subtly by nonrandom transcriptional network organization, with roles in these networks for both conserved and taxon-restricted genes. The general lack of highly methylated regions or methylome patterning in both species may be an important mechanism for achieving plasticity among phenotypes during adulthood. These findings define previously unidentified hypotheses on the genomic processes that facilitate plasticity and suggest that the molecular hallmarks of social behavior are likely to differ with the level of social complexity.

Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms

PubMed Central

Tsave, Olga; Petanidis, Savvas; Kioseoglou, Efrosini; Yavropoulou, Maria P.; Yovos, John G.; Anestakis, Doxakis; Tsepa, Androniki; Salifoglou, Athanasios

2016-01-01

Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs. PMID:27190573

The impact of Staphylococcus aureus-associated molecular patterns on staphylococcal superantigen-induced toxic shock syndrome and pneumonia.

PubMed

Tilahun, Ashenafi Y; Karau, Melissa; Ballard, Alessandro; Gunaratna, Miluka P; Thapa, Anusa; David, Chella S; Patel, Robin; Rajagopalan, Govindarajan

2014-01-01

Staphylococcus aureus is capable of causing a spectrum of human illnesses. During serious S. aureus infections, the staphylococcal pathogen-associated molecular patterns (PAMPs) such as peptidoglycan, lipoteichoic acid, and lipoproteins and even intact S. aureus, are believed to act in conjunction with the staphylococcal superantigens (SSAg) to activate the innate and adaptive immune system, respectively, and cause immunopathology. However, recent studies have shown that staphylococcal PAMPs could suppress inflammation by several mechanisms and protect from staphylococcal toxic shock syndrome, a life-threatening systemic disease caused by toxigenic S. aureus. Given the contradictory pro- and anti-inflammatory roles of staphylococcal PAMPs, we examined the effects of S. aureus-derived molecular patterns on immune responses driven by SSAg in vivo using HLA-DR3 and HLA-DQ8 transgenic mice. Our study showed that neither S. aureus-derived peptidoglycans (PGN), lipoteichoic acid (LTA), nor heat-killed Staphylococcus aureus (HKSA) inhibited SSAg-induced T cell proliferation in vitro. They failed to antagonize the immunostimulatory effects of SSAg in vivo as determined by their inability to attenuate systemic cytokine/chemokine response and reduce SSAg-induced T cell expansion. These staphylococcal PAMPs also failed to protect HLA-DR3 as well as HLA-DQ8 transgenic mice from either SSAg-induced toxic shock or pneumonia induced by a SSAg-producing strain of S. aureus.

Molecular signatures of plastic phenotypes in two eusocial insect species with simple societies

PubMed Central

Patalano, Solenn; Vlasova, Anna; Wyatt, Chris; Ewels, Philip; Camara, Francisco; Ferreira, Pedro G.; Asher, Claire L.; Jurkowski, Tomasz P.; Segonds-Pichon, Anne; Bachman, Martin; González-Navarrete, Irene; Minoche, André E.; Krueger, Felix; Lowy, Ernesto; Marcet-Houben, Marina; Rodriguez-Ales, Jose Luis; Nascimento, Fabio S.; Balasubramanian, Shankar; Gabaldon, Toni; Tarver, James E.; Andrews, Simon; Himmelbauer, Heinz; Hughes, William O. H.; Guigó, Roderic; Reik, Wolf; Sumner, Seirian

2015-01-01

Phenotypic plasticity is important in adaptation and shapes the evolution of organisms. However, we understand little about what aspects of the genome are important in facilitating plasticity. Eusocial insect societies produce plastic phenotypes from the same genome, as reproductives (queens) and nonreproductives (workers). The greatest plasticity is found in the simple eusocial insect societies in which individuals retain the ability to switch between reproductive and nonreproductive phenotypes as adults. We lack comprehensive data on the molecular basis of plastic phenotypes. Here, we sequenced genomes, microRNAs (miRNAs), and multiple transcriptomes and methylomes from individual brains in a wasp (Polistes canadensis) and an ant (Dinoponera quadriceps) that live in simple eusocial societies. In both species, we found few differences between phenotypes at the transcriptional level, with little functional specialization, and no evidence that phenotype-specific gene expression is driven by DNA methylation or miRNAs. Instead, phenotypic differentiation was defined more subtly by nonrandom transcriptional network organization, with roles in these networks for both conserved and taxon-restricted genes. The general lack of highly methylated regions or methylome patterning in both species may be an important mechanism for achieving plasticity among phenotypes during adulthood. These findings define previously unidentified hypotheses on the genomic processes that facilitate plasticity and suggest that the molecular hallmarks of social behavior are likely to differ with the level of social complexity. PMID:26483466

Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

PubMed

Rooney, Claire; Sethi, Tariq

2015-10-01

Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health.

PubMed

Fuhrmeister, Jessica; Zota, Annika; Sijmonsma, Tjeerd P; Seibert, Oksana; Cıngır, Şahika; Schmidt, Kathrin; Vallon, Nicola; de Guia, Roldan M; Niopek, Katharina; Berriel Diaz, Mauricio; Maida, Adriano; Blüher, Matthias; Okun, Jürgen G; Herzig, Stephan; Rose, Adam J

2016-06-01

Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered "growth arrest and DNA damage-inducible" GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Molecular-Simulation-Driven Fragment Screening for the Discovery of New CXCL12 Inhibitors.

PubMed

Martinez-Rosell, Gerard; Harvey, Matt J; De Fabritiis, Gianni

2018-03-26

Fragment-based drug discovery (FBDD) has become a mainstream approach in drug design because it allows the reduction of the chemical space and screening libraries while identifying fragments with high protein-ligand efficiency interactions that can later be grown into drug-like leads. In this work, we leverage high-throughput molecular dynamics (MD) simulations to screen a library of 129 fragments for a total of 5.85 ms against the CXCL12 monomer, a chemokine involved in inflammation and diseases such as cancer. Our in silico binding assay was able to recover binding poses, affinities, and kinetics for the selected library and was able to predict 8 mM-affinity fragments with ligand efficiencies higher than 0.3. All of the fragment hits present a similar chemical structure, with a hydrophobic core and a positively charged group, and bind to either sY7 or H1S68 pockets, where they share pharmacophoric properties with experimentally resolved natural binders. This work presents a large-scale screening assay using an exclusive combination of thousands of short MD adaptive simulations analyzed with a Markov state model (MSM) framework.

Sustained IFN-I Expression during Established Persistent Viral Infection: A “Bad Seed” for Protective Immunity

PubMed Central

Murira, Armstrong; Laulhé, Xavier; Stäger, Simona; Lamarre, Alain; van Grevenynghe, Julien

2017-01-01

Type I interferons (IFN-I) are one of the primary immune defenses against viruses. Similar to all other molecular mechanisms that are central to eliciting protective immune responses, IFN-I expression is subject to homeostatic controls that regulate cytokine levels upon clearing the infection. However, in the case of established persistent viral infection, sustained elevation of IFN-I expression bears deleterious effects to the host and is today considered as the major driver of inflammation and immunosuppression. In fact, numerous emerging studies place sustained IFN-I expression as a common nexus in the pathogenesis of multiple chronic diseases including persistent infections with the human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), as well as the rodent-borne lymphocytic choriomeningitis virus clone 13 (LCMV clone 13). In this review, we highlight recent studies illustrating the molecular dysregulation and resultant cellular dysfunction in both innate and adaptive immune responses driven by sustained IFN-I expression. Here, we place particular emphasis on the efficacy of IFN-I receptor (IFNR) blockade towards improving immune responses against viral infections given the emerging therapeutic approach of blocking IFNR using neutralizing antibodies (Abs) in chronically infected patients. PMID:29301196

Virtual Institute of Microbial Stress and Survival: Deduction of Stress Response Pathways in Metal and Radionuclide Reducing Microorganisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2004-04-17

The projects application goals are to: (1) To understand bacterial stress-response to the unique stressors in metal/radionuclide contamination sites; (2) To turn this understanding into a quantitative, data-driven model for exploring policies for natural and biostimulatory bioremediation; (3) To implement proposed policies in the field and compare results to model predictions; and (4) Close the experimental/computation cycle by using discrepancies between models and predictions to drive new measurements and construction of new models. The projects science goals are to: (1) Compare physiological and molecular response of three target microorganisms to environmental perturbation; (2) Deduce the underlying regulatory pathways that controlmore » these responses through analysis of phenotype, functional genomic, and molecular interaction data; (3) Use differences in the cellular responses among the target organisms to understand niche specific adaptations of the stress and metal reduction pathways; (4) From this analysis derive an understanding of the mechanisms of pathway evolution in the environment; and (5) Ultimately, derive dynamical models for the control of these pathways to predict how natural stimulation can optimize growth and metal reduction efficiency at field sites.« less

Different conical intersections control nonadiabatic photochemistry of fluorene light-driven molecular rotary motor: A CASSCF and spin-flip DFT study

NASA Astrophysics Data System (ADS)

Li, Yuanying; Liu, Fengyi; Wang, Bin; Su, Qingqing; Wang, Wenliang; Morokuma, Keiji

2016-12-01

We report the light-driven isomerization mechanism of a fluorene-based light-driven rotary motor (corresponding to Feringa's 2nd generation rotary motor, [M. M. Pollard et al., Org. Biomol. Chem. 6, 507-512 (2008)]) at the complete active space self-consistent field (CASSCF) and spin-flip time-dependent density functional theory (TDDFT) (SFDFT) levels, combined with the complete active space second-order perturbation theory (CASPT2) single-point energy corrections. The good consistence between the SFDFT and CASSCF results confirms the capability of SFDFT in investigating the photoisomerization step of the light-driven molecular rotary motor, and proposes the CASPT2//SFDFT as a promising and effective approach in exploring photochemical processes. At the mechanistic aspect, for the fluorene-based motor, the S1/S0 minimum-energy conical intersection (MECIs) caused by pyramidalization of a fluorene carbon have relatively low energies and are easily accessible by the reactive molecule evolution along the rotary reaction path; therefore, the fluorene-type MECIs play the dominant role in nonadiabatic decay, as supported by previous experimental and theoretical works. Comparably, the other type of MECIs that results from pyramidalization of an indene carbon, which has been acting as the dominant nonadiabatic decay channel in the stilbene motor, is energetically inaccessible, thus the indene-type MECIs are "missing" in previous mechanistic studies including molecular dynamic simulations. A correlation between the geometric and electronic factors of MECIs and that of the S1 energy profile along the C═C rotary coordinate was found. The findings in current study are expected to deepen the understanding of nonadiabatic transition in the light-driven molecular rotary motor and provide insights into mechanistic tuning of their performance.

A phylogenomic analysis of the role and timing of molecular adaptation in the aquatic transition of cetartiodactyl mammals.

PubMed

Tsagkogeorga, Georgia; McGowen, Michael R; Davies, Kalina T J; Jarman, Simon; Polanowski, Andrea; Bertelsen, Mads F; Rossiter, Stephen J

2015-09-01

Recent studies have reported multiple cases of molecular adaptation in cetaceans related to their aquatic abilities. However, none of these has included the hippopotamus, precluding an understanding of whether molecular adaptations in cetaceans occurred before or after they split from their semi-aquatic sister taxa. Here, we obtained new transcriptomes from the hippopotamus and humpback whale, and analysed these together with available data from eight other cetaceans. We identified more than 11 000 orthologous genes and compiled a genome-wide dataset of 6845 coding DNA sequences among 23 mammals, to our knowledge the largest phylogenomic dataset to date for cetaceans. We found positive selection in nine genes on the branch leading to the common ancestor of hippopotamus and whales, and 461 genes in cetaceans compared to 64 in hippopotamus. Functional annotation revealed adaptations in diverse processes, including lipid metabolism, hypoxia, muscle and brain function. By combining these findings with data on protein-protein interactions, we found evidence suggesting clustering among gene products relating to nervous and muscular systems in cetaceans. We found little support for shared ancestral adaptations in the two taxa; most molecular adaptations in extant cetaceans occurred after their split with hippopotamids.

A phylogenomic analysis of the role and timing of molecular adaptation in the aquatic transition of cetartiodactyl mammals

PubMed Central

Tsagkogeorga, Georgia; McGowen, Michael R.; Davies, Kalina T. J.; Jarman, Simon; Polanowski, Andrea; Bertelsen, Mads F.; Rossiter, Stephen J.

2015-01-01

Recent studies have reported multiple cases of molecular adaptation in cetaceans related to their aquatic abilities. However, none of these has included the hippopotamus, precluding an understanding of whether molecular adaptations in cetaceans occurred before or after they split from their semi-aquatic sister taxa. Here, we obtained new transcriptomes from the hippopotamus and humpback whale, and analysed these together with available data from eight other cetaceans. We identified more than 11 000 orthologous genes and compiled a genome-wide dataset of 6845 coding DNA sequences among 23 mammals, to our knowledge the largest phylogenomic dataset to date for cetaceans. We found positive selection in nine genes on the branch leading to the common ancestor of hippopotamus and whales, and 461 genes in cetaceans compared to 64 in hippopotamus. Functional annotation revealed adaptations in diverse processes, including lipid metabolism, hypoxia, muscle and brain function. By combining these findings with data on protein–protein interactions, we found evidence suggesting clustering among gene products relating to nervous and muscular systems in cetaceans. We found little support for shared ancestral adaptations in the two taxa; most molecular adaptations in extant cetaceans occurred after their split with hippopotamids. PMID:26473040

Two dimensional molecular electronics spectroscopy for molecular fingerprinting, DNA sequencing, and cancerous DNA recognition.

PubMed

Rajan, Arunkumar Chitteth; Rezapour, Mohammad Reza; Yun, Jeonghun; Cho, Yeonchoo; Cho, Woo Jong; Min, Seung Kyu; Lee, Geunsik; Kim, Kwang S

2014-02-25

Laser-driven molecular spectroscopy of low spatial resolution is widely used, while electronic current-driven molecular spectroscopy of atomic scale resolution has been limited because currents provide only minimal information. However, electron transmission of a graphene nanoribbon on which a molecule is adsorbed shows molecular fingerprints of Fano resonances, i.e., characteristic features of frontier orbitals and conformations of physisorbed molecules. Utilizing these resonance profiles, here we demonstrate two-dimensional molecular electronics spectroscopy (2D MES). The differential conductance with respect to bias and gate voltages not only distinguishes different types of nucleobases for DNA sequencing but also recognizes methylated nucleobases which could be related to cancerous cell growth. This 2D MES could open an exciting field to recognize single molecule signatures at atomic resolution. The advantages of the 2D MES over the one-dimensional (1D) current analysis can be comparable to those of 2D NMR over 1D NMR analysis.

Trial-to-trial adaptation in control of arm reaching and standing posture

PubMed Central

Pienciak-Siewert, Alison; Horan, Dylan P.

2016-01-01

Classical theories of motor learning hypothesize that adaptation is driven by sensorimotor error; this is supported by studies of arm and eye movements that have shown that trial-to-trial adaptation increases with error. Studies of postural control have shown that anticipatory postural adjustments increase with the magnitude of a perturbation. However, differences in adaptation have been observed between the two modalities, possibly due to either the inherent instability or sensory uncertainty in standing posture. Therefore, we hypothesized that trial-to-trial adaptation in posture should be driven by error, similar to what is observed in arm reaching, but the nature of the relationship between error and adaptation may differ. Here we investigated trial-to-trial adaptation of arm reaching and postural control concurrently; subjects made reaching movements in a novel dynamic environment of varying strengths, while standing and holding the handle of a force-generating robotic arm. We found that error and adaptation increased with perturbation strength in both arm and posture. Furthermore, in both modalities, adaptation showed a significant correlation with error magnitude. Our results indicate that adaptation scales proportionally with error in the arm and near proportionally in posture. In posture only, adaptation was not sensitive to small error sizes, which were similar in size to errors experienced in unperturbed baseline movements due to inherent variability. This finding may be explained as an effect of uncertainty about the source of small errors. Our findings suggest that in rehabilitation, postural error size should be considered relative to the magnitude of inherent movement variability. PMID:27683888

Trial-to-trial adaptation in control of arm reaching and standing posture.

PubMed

Pienciak-Siewert, Alison; Horan, Dylan P; Ahmed, Alaa A

2016-12-01

Classical theories of motor learning hypothesize that adaptation is driven by sensorimotor error; this is supported by studies of arm and eye movements that have shown that trial-to-trial adaptation increases with error. Studies of postural control have shown that anticipatory postural adjustments increase with the magnitude of a perturbation. However, differences in adaptation have been observed between the two modalities, possibly due to either the inherent instability or sensory uncertainty in standing posture. Therefore, we hypothesized that trial-to-trial adaptation in posture should be driven by error, similar to what is observed in arm reaching, but the nature of the relationship between error and adaptation may differ. Here we investigated trial-to-trial adaptation of arm reaching and postural control concurrently; subjects made reaching movements in a novel dynamic environment of varying strengths, while standing and holding the handle of a force-generating robotic arm. We found that error and adaptation increased with perturbation strength in both arm and posture. Furthermore, in both modalities, adaptation showed a significant correlation with error magnitude. Our results indicate that adaptation scales proportionally with error in the arm and near proportionally in posture. In posture only, adaptation was not sensitive to small error sizes, which were similar in size to errors experienced in unperturbed baseline movements due to inherent variability. This finding may be explained as an effect of uncertainty about the source of small errors. Our findings suggest that in rehabilitation, postural error size should be considered relative to the magnitude of inherent movement variability. Copyright © 2016 the American Physiological Society.

Motor-driven intracellular transport powers bacterial gliding motility.

PubMed

Sun, Mingzhai; Wartel, Morgane; Cascales, Eric; Shaevitz, Joshua W; Mignot, Tâm

2011-05-03

Protein-directed intracellular transport has not been observed in bacteria despite the existence of dynamic protein localization and a complex cytoskeleton. However, protein trafficking has clear potential uses for important cellular processes such as growth, development, chromosome segregation, and motility. Conflicting models have been proposed to explain Myxococcus xanthus motility on solid surfaces, some favoring secretion engines at the rear of cells and others evoking an unknown class of molecular motors distributed along the cell body. Through a combination of fluorescence imaging, force microscopy, and genetic manipulation, we show that membrane-bound cytoplasmic complexes consisting of motor and regulatory proteins are directionally transported down the axis of a cell at constant velocity. This intracellular motion is transmitted to the exterior of the cell and converted to traction forces on the substrate. Thus, this study demonstrates the existence of a conserved class of processive intracellular motors in bacteria and shows how these motors have been adapted to produce cell motility.

NEAMS Update. Quarterly Report for January - March 2014

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stan, Marius

2014-08-01

This quarterly report covers the following points: A fully three-dimensional smeared cracking model has been implemented and tested in BISON; DAKOTA-BISON was used to study the parameters that govern heat transfer across the fuel-cladding; Calculations of grain boundary mobility in UO 2 have been extended to high temperatures; Mesh adaptivity is being employed in MARMOT simulations to increase computational efficiency; Molecular dynamics simulations have shown correlation between atomic displacements and the anisotropic thermal conductivity in UO 2; The SHARP team continues to address the application of the toolkit to assembly deformations driven by reactivity feedback; The Nek5000 team has extendedmore » the low-Machnumber capability to mixtures with multiple species; The generalized cross section library has been tested for various fuel assemblies and reactor types; and The subgroup cross-section interface was successfully implemented in PROTEUS-SN (page 6).« less

Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids

PubMed Central

He, Susu; Chandler, Michael; Varani, Alessandro M.; Hickman, Alison B.; Dekker, John P.

2016-01-01

ABSTRACT The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content) of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE) from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance. PMID:27923922

Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

PubMed

Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

2017-09-11

In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

Cultivating Inquiry-Driven Learners: A College Education for the Twenty-First Century

ERIC Educational Resources Information Center

Conrad, Clifton; Dunek, Laura

2012-01-01

Inquiry-driven learners anticipate, embrace, and adapt to disruptive change. Clifton Conrad and Laura Dunek advance a transformative purpose of a college education. They invite stakeholders from across higher education to engage in vigorous dialogue about the aims of a college education--and how to realize those aims. Increasingly influenced by…

Sensor modeling and demonstration of a multi-object spectrometer for performance-driven sensing

NASA Astrophysics Data System (ADS)

Kerekes, John P.; Presnar, Michael D.; Fourspring, Kenneth D.; Ninkov, Zoran; Pogorzala, David R.; Raisanen, Alan D.; Rice, Andrew C.; Vasquez, Juan R.; Patel, Jeffrey P.; MacIntyre, Robert T.; Brown, Scott D.

2009-05-01

A novel multi-object spectrometer (MOS) is being explored for use as an adaptive performance-driven sensor that tracks moving targets. Developed originally for astronomical applications, the instrument utilizes an array of micromirrors to reflect light to a panchromatic imaging array. When an object of interest is detected the individual micromirrors imaging the object are tilted to reflect the light to a spectrometer to collect a full spectrum. This paper will present example sensor performance from empirical data collected in laboratory experiments, as well as our approach in designing optical and radiometric models of the MOS channels and the micromirror array. Simulation of moving vehicles in a highfidelity, hyperspectral scene is used to generate a dynamic video input for the adaptive sensor. Performance-driven algorithms for feature-aided target tracking and modality selection exploit multiple electromagnetic observables to track moving vehicle targets.

Coestimation of recombination, substitution and molecular adaptation rates by approximate Bayesian computation.

PubMed

Lopes, J S; Arenas, M; Posada, D; Beaumont, M A

2014-03-01

The estimation of parameters in molecular evolution may be biased when some processes are not considered. For example, the estimation of selection at the molecular level using codon-substitution models can have an upward bias when recombination is ignored. Here we address the joint estimation of recombination, molecular adaptation and substitution rates from coding sequences using approximate Bayesian computation (ABC). We describe the implementation of a regression-based strategy for choosing subsets of summary statistics for coding data, and show that this approach can accurately infer recombination allowing for intracodon recombination breakpoints, molecular adaptation and codon substitution rates. We demonstrate that our ABC approach can outperform other analytical methods under a variety of evolutionary scenarios. We also show that although the choice of the codon-substitution model is important, our inferences are robust to a moderate degree of model misspecification. In addition, we demonstrate that our approach can accurately choose the evolutionary model that best fits the data, providing an alternative for when the use of full-likelihood methods is impracticable. Finally, we applied our ABC method to co-estimate recombination, substitution and molecular adaptation rates from 24 published human immunodeficiency virus 1 coding data sets.

Dynamically adaptive data-driven simulation of extreme hydrological flows

NASA Astrophysics Data System (ADS)

Kumar Jain, Pushkar; Mandli, Kyle; Hoteit, Ibrahim; Knio, Omar; Dawson, Clint

2018-02-01

Hydrological hazards such as storm surges, tsunamis, and rainfall-induced flooding are physically complex events that are costly in loss of human life and economic productivity. Many such disasters could be mitigated through improved emergency evacuation in real-time and through the development of resilient infrastructure based on knowledge of how systems respond to extreme events. Data-driven computational modeling is a critical technology underpinning these efforts. This investigation focuses on the novel combination of methodologies in forward simulation and data assimilation. The forward geophysical model utilizes adaptive mesh refinement (AMR), a process by which a computational mesh can adapt in time and space based on the current state of a simulation. The forward solution is combined with ensemble based data assimilation methods, whereby observations from an event are assimilated into the forward simulation to improve the veracity of the solution, or used to invert for uncertain physical parameters. The novelty in our approach is the tight two-way coupling of AMR and ensemble filtering techniques. The technology is tested using actual data from the Chile tsunami event of February 27, 2010. These advances offer the promise of significantly transforming data-driven, real-time modeling of hydrological hazards, with potentially broader applications in other science domains.

Remote Photoregulated Ring Gliding in a [2]Rotaxane via a Molecular Effector.

PubMed

Tron, Arnaud; Pianet, Isabelle; Martinez-Cuezva, Alberto; Tucker, James H R; Pisciottani, Luca; Alajarin, Mateo; Berna, Jose; McClenaghan, Nathan D

2017-01-06

A molecular barbiturate messenger, which is reversibly released/captured by a photoswitchable artificial molecular receptor, is shown to act as an effector to control ring gliding on a distant hydrogen-bonding [2]rotaxane. Thus, light-driven chemical communication governing the operation of a remote molecular machine is demonstrated using an information-rich neutral molecule.

CRISPR-Cas adaptation: insights into the mechanism of action.

PubMed

Amitai, Gil; Sorek, Rotem

2016-02-01

Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

Accelerated model of lupus autoimmunity and vasculopathy driven by toll-like receptor 7/9 imbalance

PubMed Central

Liu, Yudong; Seto, Nickie L; Carmona-Rivera, Carmelo; Kaplan, Mariana J

2018-01-01

Objectives Activation of endosomal toll-like receptor (TLR)7 or TLR9 has been proposed as a critical step for the initiation and development of SLE. Traditional spontaneous lupus models normally introduce multiple risk alleles, thereby adding additional confounding factors. In the induced lupus models, the role of TLR9 remains unclear. In the present study, we explored the role of an imbalance between TLR7 and TLR9 pathways in the pathogenesis of lupus and its associated vasculopathy using the imiquimod model in TLR9 KO/B6 background. Methods Wild type (WT) and Tlr9-/- mice were epicutaneously treated with imiquimod cream 5% on both ears three times per week for indicated times. At euthanasia, mice were analysed for organ involvement, endothelium-dependent vasorelaxation, serum autoantibodies, and innate and adaptive immune responses. Results Compared with the lupus-like phenotype that develops in imiquimod-treated WT mice, Tlr9-/- mice exposed to imiquimod have increased severity of autoimmunity features and inflammatory phenotype that develops at earlier stages. These abnormalities are characterised by enhanced TLR7 expression and immune activation, increased immune complex deposition, Th1 T cells and dendritic cell kidney infiltration and significant impairments in endothelial function. Modulation of TLR7 expression was observed in the Tlr9-/- mice. Conclusions These findings further underscore the protective role of TLR9 in TLR7-driven autoimmunity and also in the development of vasculopathy, further strengthening the importance of tightly manipulating TLRs in putative therapeutic strategies. This study provides a new model of accelerated lupus phenotype driven by danger-associated molecular patterns. PMID:29765617

Accelerated model of lupus autoimmunity and vasculopathy driven by toll-like receptor 7/9 imbalance.

PubMed

Liu, Yudong; Seto, Nickie L; Carmona-Rivera, Carmelo; Kaplan, Mariana J

2018-01-01

Activation of endosomal toll-like receptor (TLR)7 or TLR9 has been proposed as a critical step for the initiation and development of SLE. Traditional spontaneous lupus models normally introduce multiple risk alleles, thereby adding additional confounding factors. In the induced lupus models, the role of TLR9 remains unclear. In the present study, we explored the role of an imbalance between TLR7 and TLR9 pathways in the pathogenesis of lupus and its associated vasculopathy using the imiquimod model in TLR9 KO/B6 background. Wild type (WT) and Tlr9 -/- mice were epicutaneously treated with imiquimod cream 5% on both ears three times per week for indicated times. At euthanasia, mice were analysed for organ involvement, endothelium-dependent vasorelaxation, serum autoantibodies, and innate and adaptive immune responses. Compared with the lupus-like phenotype that develops in imiquimod-treated WT mice, Tlr9 -/- mice exposed to imiquimod have increased severity of autoimmunity features and inflammatory phenotype that develops at earlier stages. These abnormalities are characterised by enhanced TLR7 expression and immune activation, increased immune complex deposition, Th1 T cells and dendritic cell kidney infiltration and significant impairments in endothelial function. Modulation of TLR7 expression was observed in the Tlr9 -/- mice. These findings further underscore the protective role of TLR9 in TLR7-driven autoimmunity and also in the development of vasculopathy, further strengthening the importance of tightly manipulating TLRs in putative therapeutic strategies. This study provides a new model of accelerated lupus phenotype driven by danger-associated molecular patterns.

Divergent oviposition preferences of sister species are not driven by nest survival: The evidence for neutrality

EPA Science Inventory

Both adaptive and neutral trait evolution can contribute to divergence, but the relative contributions of the two remain unclear. Oviposition preference, a trait that has been demonstrated to contribute to divergence among populations, is often presumed to be an adaptive trait. F...

Development of simulation approach for two-dimensional chiral molecular self-assembly driven by hydrogen bond at the liquid/solid interface

NASA Astrophysics Data System (ADS)

Qin, Yuan; Yao, Man; Hao, Ce; Wan, Lijun; Wang, Yunhe; Chen, Ting; Wang, Dong; Wang, Xudong; Chen, Yonggang

2017-09-01

Two-dimensional (2D) chiral self-assembly system of 5-(benzyloxy)-isophthalic acid derivative/(S)-(+)-2-octanol/highly oriented pyrolytic graphite was studied. A combined density functional theory/molecular mechanics/molecular dynamics (DFT/MM/MD) approach for system of 2D chiral molecular self-assembly driven by hydrogen bond at the liquid/solid interface was thus proposed. Structural models of the chiral assembly were built on the basis of scanning tunneling microscopy (STM) images and simplified for DFT geometry optimization. Merck Molecular Force Field (MMFF) was singled out as the suitable force field by comparing the optimized configurations of MM and DFT. MM and MD simulations for hexagonal unit model which better represented the 2D assemble network were then preformed with MMFF. The adhesion energy, evolution of self-assembly process and characteristic parameters of hydrogen bond were obtained and analyzed. According to the above simulation, the stabilities of the clockwise and counterclockwise enantiomorphous networks were evaluated. The calculational results were supported by STM observations and the feasibility of the simulation method was confirmed by two other systems in the presence of chiral co-absorbers (R)-(-)-2-octanol and achiral co-absorbers 1-octanol. This theoretical simulation method assesses the stability trend of 2D enantiomorphous assemblies with atomic scale and can be applied to the similar hydrogen bond driven 2D chirality of molecular self-assembly system.

Does Integration Help Adapt to Climate Change? Case of Increased US Corn Yield Volatility

NASA Astrophysics Data System (ADS)

Verma, M.; Diffenbaugh, N. S.; Hertel, T. W.

2012-12-01

In absence of of new crop varieties or significant shifts in the geography of corn production, US national corn yields variation could double by the year 2040 as a result of climate change and without adaptation this could lead the variability in US corn prices to quadruple (Diffenbaugh et al. 2012). In addition to climate induced price changes, analysis of recent commodity price spikes suggests that interventionist trade policies are partly to blame. Assuming we cannot much influence the future climate outcome, what policies can we undertake to adapt better? Can we use markets to blunt this edge? Diffenbaugh et al. find that sale of corn- ethanol for use in liquid fuel, when governed by quotas such as US Renewable Fuel Standard (RFS), could make US corn prices even more variable; in contrast the same food-fuel market link (we refer to it as intersectoral link) may well dampen price volatility when the sale of corn to ethanol industry is driven by higher future oil prices. The latter however comes at the cost of exposing corn prices to the greater volatility in oil markets. Similarly intervention in corn trade can make US corn prices less or more volatile by distorting international corn price transmission. A negative US corn yield shock shows that domestic corn supply falls and domestic prices to go up irrespective of whether or not markets are integrated. How much the prices go up depends on how much demand adjusts to accommodate the supply shock. Based on the forgoing analysis, one should expect that demand would adjust more readily when markets are integrated and therefore reduce the resulting price fluctuation. Simulation results confirm this response of corn markets. In terms of relative comparisons however a policy driven intersectoral integration is least effective and prices rise much more. Similarly, a positive world oil price shock makes the US oil imports expensive and with oil being used to produce gasoline blends, it increases the price of gasoline and reduces its demand. In the presence of domestic integration, ethanol production rises to substitute oil in the gasoline blend and thereby increases the corn demand and prices. However if one takes into account increase in corn price due to increased production costs (increase in oil price increases fertilizer prices - a major input into corn production) and reduced corn prices due to reduced fuel demand and therefore reduced ethanol additive demand; the prices can go either way. Our initial simulations show that they do in fact go down with mandate driven integration. This raises some more general questions: Whether integration (intersectoral and international) can be an effective strategy for adapting to climate change? And which of the four adaptation options - RFS or oil price driven domestic integration, full corn tariff liberalization or restricting tariff manipulation by partners - would be more effective in comparison to other adaptation (including no adaptation) scenarios? We implement the alternative adaptation strategies, while sampling from the same corn yield and oil price distributions and compare the resulting corn price variations to the base case where no such adaptation has been undertaken. Our initial results suggest that intersectoral integration is more effective form of adaptation than international one, but only if driven by market forces and not mandates.

Data-based virtual unmodeled dynamics driven multivariable nonlinear adaptive switching control.

PubMed

Chai, Tianyou; Zhang, Yajun; Wang, Hong; Su, Chun-Yi; Sun, Jing

2011-12-01

For a complex industrial system, its multivariable and nonlinear nature generally make it very difficult, if not impossible, to obtain an accurate model, especially when the model structure is unknown. The control of this class of complex systems is difficult to handle by the traditional controller designs around their operating points. This paper, however, explores the concepts of controller-driven model and virtual unmodeled dynamics to propose a new design framework. The design consists of two controllers with distinct functions. First, using input and output data, a self-tuning controller is constructed based on a linear controller-driven model. Then the output signals of the controller-driven model are compared with the true outputs of the system to produce so-called virtual unmodeled dynamics. Based on the compensator of the virtual unmodeled dynamics, the second controller based on a nonlinear controller-driven model is proposed. Those two controllers are integrated by an adaptive switching control algorithm to take advantage of their complementary features: one offers stabilization function and another provides improved performance. The conditions on the stability and convergence of the closed-loop system are analyzed. Both simulation and experimental tests on a heavily coupled nonlinear twin-tank system are carried out to confirm the effectiveness of the proposed method.

The control of the controller: molecular mechanisms for robust perfect adaptation and temperature compensation.

PubMed

Ni, Xiao Yu; Drengstig, Tormod; Ruoff, Peter

2009-09-02

Organisms have the property to adapt to a changing environment and keep certain components within a cell regulated at the same level (homeostasis). "Perfect adaptation" describes an organism's response to an external stepwise perturbation by regulating some of its variables/components precisely to their original preperturbation values. Numerous examples of perfect adaptation/homeostasis have been found, as for example, in bacterial chemotaxis, photoreceptor responses, MAP kinase activities, or in metal-ion homeostasis. Two concepts have evolved to explain how perfect adaptation may be understood: In one approach (robust perfect adaptation), the adaptation is a network property, which is mostly, but not entirely, independent of rate constant values; in the other approach (nonrobust perfect adaptation), a fine-tuning of rate constant values is needed. Here we identify two classes of robust molecular homeostatic mechanisms, which compensate for environmental variations in a controlled variable's inflow or outflow fluxes, and allow for the presence of robust temperature compensation. These two classes of homeostatic mechanisms arise due to the fact that concentrations must have positive values. We show that the concept of integral control (or integral feedback), which leads to robust homeostasis, is associated with a control species that has to work under zero-order flux conditions and does not necessarily require the presence of a physico-chemical feedback structure. There are interesting links between the two identified classes of homeostatic mechanisms and molecular mechanisms found in mammalian iron and calcium homeostasis, indicating that homeostatic mechanisms may underlie similar molecular control structures.

Efficient GIS-based model-driven method for flood risk management and its application in central China

NASA Astrophysics Data System (ADS)

Liu, Y.; Zhou, J.; Song, L.; Zou, Q.; Guo, J.; Wang, Y.

2014-02-01

In recent years, an important development in flood management has been the focal shift from flood protection towards flood risk management. This change greatly promoted the progress of flood control research in a multidisciplinary way. Moreover, given the growing complexity and uncertainty in many decision situations of flood risk management, traditional methods, e.g., tight-coupling integration of one or more quantitative models, are not enough to provide decision support for managers. Within this context, this paper presents a beneficial methodological framework to enhance the effectiveness of decision support systems, through the dynamic adaptation of support regarding the needs of the decision-maker. In addition, we illustrate a loose-coupling technical prototype for integrating heterogeneous elements, such as multi-source data, multidisciplinary models, GIS tools and existing systems. The main innovation is the application of model-driven concepts, which put the system in a state of continuous iterative optimization. We define the new system as a model-driven decision support system (MDSS ). Two characteristics that differentiate the MDSS are as follows: (1) it is made accessible to non-technical specialists; and (2) it has a higher level of adaptability and compatibility. Furthermore, the MDSS was employed to manage the flood risk in the Jingjiang flood diversion area, located in central China near the Yangtze River. Compared with traditional solutions, we believe that this model-driven method is efficient, adaptable and flexible, and thus has bright prospects of application for comprehensive flood risk management.

Design of fuzzy system by NNs and realization of adaptability

NASA Technical Reports Server (NTRS)

Takagi, Hideyuki

1993-01-01

The issue of designing and tuning fuzzy membership functions by neural networks (NN's) was started by NN-driven Fuzzy Reasoning in 1988. NN-driven fuzzy reasoning involves a NN embedded in the fuzzy system which generates membership values. In conventional fuzzy system design, the membership functions are hand-crafted by trial and error for each input variable. In contrast, NN-driven fuzzy reasoning considers several variables simultaneously and can design a multidimensional, nonlinear membership function for the entire subspace.

Conflict-driven adaptive control is enhanced by integral negative emotion on a short time scale.

PubMed

Yang, Qian; Pourtois, Gilles

2018-02-05

Negative emotion influences cognitive control, and more specifically conflict adaptation. However, discrepant results have often been reported in the literature. In this study, we broke down negative emotion into integral and incidental components using a modern motivation-based framework, and assessed whether the former could change conflict adaptation. In the first experiment, we manipulated the duration of the inter-trial-interval (ITI) to assess the actual time-scale of this effect. Integral negative emotion was induced by using loss-related feedback contingent on task performance, and measured at the subjective and physiological levels. Results showed that conflict-driven adaptive control was enhanced when integral negative emotion was elicited, compared to a control condition without changes in defensive motivation. Importantly, this effect was only found when a short, as opposed to long ITI was used, suggesting that it had a short time scale. In the second experiment, we controlled for effects of feature repetition and contingency learning, and replicated an enhanced conflict adaptation effect when integral negative emotion was elicited and a short ITI was used. We interpret these new results against a standard cognitive control framework assuming that integral negative emotion amplifies specific control signals transiently, and in turn enhances conflict adaptation.

Optimized molecular design of ADAPT-based HER2-imaging probes labelled with 111In and 68Ga.

PubMed

Lindbo, Sarah; Garousi, Javad; Mitran, Bogdan; Vorobyeva, Anzhelika; Oroujeni, Maryam; Orlova, Anna; Hober, Sophia; Tolmachev, Vladimir

2018-06-04

Radionuclide molecular imaging is a promising tool for visualization of cancer associated molecular abnormalities in vivo and stratification of patients for specific therapies. ADAPT is a new type of small engineered proteins based on the scaffold of an albumin binding domain of protein G. ADAPTs have been utilized to select and develop high affinity binders to different proteinaceous targets. ADAPT6 binds to human epidermal growth factor 2 (HER2) with low nanomolar affinity and can be used for its in vivo visualization. Molecular design of 111 In-labeled anti-HER2 ADAPT has been optimized in several earlier studies. In this study, we made a direct comparison of two of the most promising variants, having either a DEAVDANS or a (HE) 3 DANS sequence at the N-terminus, conjugated with a maleimido derivative of DOTA to a GSSC amino acids sequence at the C-terminus. The variants (designated DOTA-C 59 - DEAVDANS-ADAPT6-GSSC and DOTA-C 61 -(HE) 3 DANS-ADAPT6-GSSC) were stably labeled with 111 In for SPECT and 68 Ga for PET. Biodistribution of labeled ADAPT variants was evaluated in nude mice bearing human tumor xenografts with different levels of HER2 expression. Both variants enabled clear discrimination between tumors with high and low levels of HER2 expression. 111 In-labeled ADAPT6 derivatives provided higher tumor-to-organ ratios compared to 68 Ga-labeled counterparts. The best performing variant was DOTA-C 61 -(HE) 3 DANS-ADAPT6-GSSC, providing tumor-to-blood ratios of 208±36 and 109±17 at 3 h for 111 In and 68 Ga labels, respectively.

The Evolutionary Dynamics of the Odorant Receptor Gene Family in Corbiculate Bees.

PubMed

Brand, Philipp; Ramírez, Santiago R

2017-08-01

Insects rely on chemical information to locate food, choose mates, and detect potential predators. It has been hypothesized that adaptive changes in the olfactory system facilitated the diversification of numerous insect lineages. For instance, evolutionary changes of Odorant Receptor (OR) genes often occur in parallel with modifications in life history strategies. Corbiculate bees display a diverse array of behaviors that are controlled through olfaction, including varying degrees of social organization, and manifold associations with floral resources. Here we investigated the molecular mechanisms driving the evolution of the OR gene family in corbiculate bees in comparison to other chemosensory gene families. Our results indicate that the genomic organization of the OR gene family has remained highly conserved for ∼80 Myr, despite exhibiting major changes in repertoire size among bee lineages. Moreover, the evolution of OR genes appears to be driven mostly by lineage-specific gene duplications in few genomic regions that harbor large numbers of OR genes. A selection analysis revealed that OR genes evolve under positive selection, with the strongest signals detected in recently duplicated copies. Our results indicate that chromosomal translocations had a minimal impact on OR evolution, and instead local molecular mechanisms appear to be main drivers of OR repertoire size. Our results provide empirical support to the longstanding hypothesis that positive selection shaped the diversification of the OR gene family. Together, our results shed new light on the molecular mechanisms underlying the evolution of olfaction in insects. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Air-Breathing Hypersonic Vehicle Tracking Control Based on Adaptive Dynamic Programming.

PubMed

Mu, Chaoxu; Ni, Zhen; Sun, Changyin; He, Haibo

2017-03-01

In this paper, we propose a data-driven supplementary control approach with adaptive learning capability for air-breathing hypersonic vehicle tracking control based on action-dependent heuristic dynamic programming (ADHDP). The control action is generated by the combination of sliding mode control (SMC) and the ADHDP controller to track the desired velocity and the desired altitude. In particular, the ADHDP controller observes the differences between the actual velocity/altitude and the desired velocity/altitude, and then provides a supplementary control action accordingly. The ADHDP controller does not rely on the accurate mathematical model function and is data driven. Meanwhile, it is capable to adjust its parameters online over time under various working conditions, which is very suitable for hypersonic vehicle system with parameter uncertainties and disturbances. We verify the adaptive supplementary control approach versus the traditional SMC in the cruising flight, and provide three simulation studies to illustrate the improved performance with the proposed approach.

Reliable Adaptive Video Streaming Driven by Perceptual Semantics for Situational Awareness

PubMed Central

Pimentel-Niño, M. A.; Saxena, Paresh; Vazquez-Castro, M. A.

2015-01-01

A novel cross-layer optimized video adaptation driven by perceptual semantics is presented. The design target is streamed live video to enhance situational awareness in challenging communications conditions. Conventional solutions for recreational applications are inadequate and novel quality of experience (QoE) framework is proposed which allows fully controlled adaptation and enables perceptual semantic feedback. The framework relies on temporal/spatial abstraction for video applications serving beyond recreational purposes. An underlying cross-layer optimization technique takes into account feedback on network congestion (time) and erasures (space) to best distribute available (scarce) bandwidth. Systematic random linear network coding (SRNC) adds reliability while preserving perceptual semantics. Objective metrics of the perceptual features in QoE show homogeneous high performance when using the proposed scheme. Finally, the proposed scheme is in line with content-aware trends, by complying with information-centric-networking philosophy and architecture. PMID:26247057

A Hybrid Adaptive Routing Algorithm for Event-Driven Wireless Sensor Networks

PubMed Central

Figueiredo, Carlos M. S.; Nakamura, Eduardo F.; Loureiro, Antonio A. F.

2009-01-01

Routing is a basic function in wireless sensor networks (WSNs). For these networks, routing algorithms depend on the characteristics of the applications and, consequently, there is no self-contained algorithm suitable for every case. In some scenarios, the network behavior (traffic load) may vary a lot, such as an event-driven application, favoring different algorithms at different instants. This work presents a hybrid and adaptive algorithm for routing in WSNs, called Multi-MAF, that adapts its behavior autonomously in response to the variation of network conditions. In particular, the proposed algorithm applies both reactive and proactive strategies for routing infrastructure creation, and uses an event-detection estimation model to change between the strategies and save energy. To show the advantages of the proposed approach, it is evaluated through simulations. Comparisons with independent reactive and proactive algorithms show improvements on energy consumption. PMID:22423207

A hybrid adaptive routing algorithm for event-driven wireless sensor networks.

PubMed

Figueiredo, Carlos M S; Nakamura, Eduardo F; Loureiro, Antonio A F

2009-01-01

Routing is a basic function in wireless sensor networks (WSNs). For these networks, routing algorithms depend on the characteristics of the applications and, consequently, there is no self-contained algorithm suitable for every case. In some scenarios, the network behavior (traffic load) may vary a lot, such as an event-driven application, favoring different algorithms at different instants. This work presents a hybrid and adaptive algorithm for routing in WSNs, called Multi-MAF, that adapts its behavior autonomously in response to the variation of network conditions. In particular, the proposed algorithm applies both reactive and proactive strategies for routing infrastructure creation, and uses an event-detection estimation model to change between the strategies and save energy. To show the advantages of the proposed approach, it is evaluated through simulations. Comparisons with independent reactive and proactive algorithms show improvements on energy consumption.

Nutrient-induced intestinal adaption and its effect in obesity.

PubMed

Dailey, Megan J

2014-09-01

Obese and lean individuals respond differently to nutrients with changes in digestion, absorption and hormone release. This may be a result of differences in intestinal epithelial morphology and function driven by the hyperphagia or the type of diet associated with obesity. It is well known that the maintenance and growth of the intestine is driven by the amount of luminal nutrients, with high nutrient content resulting in increases in cell number, villi length and crypt depth. In addition, the type of nutrient appears to contribute to alterations in the morphology and function of the epithelial cells. This intestinal adaptation may be what is driving the differences in nutrient processing in lean versus obese individuals. This review describes how nutrients may be able to induce changes in intestinal epithelial cell proliferation, differentiation and function and the link between intestinal adaptation and obesity. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessing Satisfaction with Selected Student Services Using SERVQUAL, a Market-Driven Model of Service Quality.

ERIC Educational Resources Information Center

Ruby, Carl A.

1998-01-01

Demonstrates how the use of SERVQUAL, a market-driven assessment model adapted from business, can be used to study student satisfaction with four areas of support services hypothetically related to enrollment management. The sample included 748 students enrolled in general education courses at ten different private institutions. (Contains 27…

Molecular Mechanisms That Underlie the Dynamic Adaptation of Innate Monocyte Memory to Varying Stimulant Strength of TLR Ligands.

PubMed

Yuan, Ruoxi; Geng, Shuo; Li, Liwu

2016-01-01

In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by super-low dose LPS exhibited higher levels of transcription factor, interferon regulatory factor 5 (IRF5), and reduced levels of transcriptional modulator B lymphocyte-induced maturation protein-1 (Blimp-1). Intriguingly, the inflammatory monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp contrast, rising doses of TLR3 agonist preferentially caused inflammatory adaptation without inducing tolerance. At the molecular level, the differential regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the understanding of monocyte adaptation and memory toward distinct TLR ligands.

Calibration of visually guided reaching is driven by error-corrective learning and internal dynamics.

PubMed

Cheng, Sen; Sabes, Philip N

2007-04-01

The sensorimotor calibration of visually guided reaching changes on a trial-to-trial basis in response to random shifts in the visual feedback of the hand. We show that a simple linear dynamical system is sufficient to model the dynamics of this adaptive process. In this model, an internal variable represents the current state of sensorimotor calibration. Changes in this state are driven by error feedback signals, which consist of the visually perceived reach error, the artificial shift in visual feedback, or both. Subjects correct for > or =20% of the error observed on each movement, despite being unaware of the visual shift. The state of adaptation is also driven by internal dynamics, consisting of a decay back to a baseline state and a "state noise" process. State noise includes any source of variability that directly affects the state of adaptation, such as variability in sensory feedback processing, the computations that drive learning, or the maintenance of the state. This noise is accumulated in the state across trials, creating temporal correlations in the sequence of reach errors. These correlations allow us to distinguish state noise from sensorimotor performance noise, which arises independently on each trial from random fluctuations in the sensorimotor pathway. We show that these two noise sources contribute comparably to the overall magnitude of movement variability. Finally, the dynamics of adaptation measured with random feedback shifts generalizes to the case of constant feedback shifts, allowing for a direct comparison of our results with more traditional blocked-exposure experiments.

AGN feedback through UFO and galaxy-wide winds in the early Universe

NASA Astrophysics Data System (ADS)

Feruglio, C.; Piconcelli, E.; Bischetti, M.; Zappacosta, L.; Fiore, F.

2017-10-01

AGN feedback through massive molecular winds is today routinely observed in local AGN host galaxies, but not as such in the early universe. I will present the first evidence for a massive, AGN-driven molecular wind in the z 4 QSO APM08279, which also hosts the most well studied and persistent nuclear semi-raltivistic wind (UFO). This observation directly probes the expansion mechanism of a nuclear wind into the ISM on galaxy wide scales, that so far was constrained by a couple of other objects only (Feruglio et al. 2015, Tombesi et al. 2015). This result also opens the path toward the exploration of molecular AGN-driven winds at early epochs, close after the end of the Epoch of Reionisation (EoR).

Design, Synthesis, and Isomerization Studies of Light-Driven Molecular Motors for Single Molecular Imaging

PubMed Central

2018-01-01

The design of a multicomponent system that aims at the direct visualization of a synthetic rotary motor at the single molecule level on surfaces is presented. The synthesis of two functional motors enabling photochemical rotation and fluorescent detection is described. The light-driven molecular motor is found to operate in the presence of a fluorescent tag if a rigid long rod (32 Å) is installed between both photoactive moieties. The photochemical isomerization and subsequent thermal helix inversion steps are confirmed by 1H NMR and UV–vis absorption spectroscopies. In addition, the tetra-acid functioned motor can be successfully grafted onto amine-coated quartz and it is shown that the light responsive rotary motion on surfaces is preserved. PMID:29741383

Photochemically and Thermally Driven Full-Color Reflection in a Self-Organized Helical Superstructure Enabled by a Halogen-Bonded Chiral Molecular Switch.

PubMed

Wang, Hao; Bisoyi, Hari Krishna; Wang, Ling; Urbas, Augustine M; Bunning, Timothy J; Li, Quan

2018-02-05

Supramolecular approaches toward the fabrication of functional materials and systems have been an enabling endeavor. Recently, halogen bonding has been harnessed as a promising supramolecular tool. Herein we report the synthesis and characterization of a novel halogen-bonded light-driven axially chiral molecular switch. The photoactive halogen-bonded chiral switch is able to induce a self-organized, tunable helical superstructure, that is, cholesteric liquid crystal (CLC), when doped into an achiral liquid crystal (LC) host. The halogen-bonded switch as a chiral dopant has a high helical twisting power (HTP) and shows a large change of its HTP upon photoisomerization. This light-driven dynamic modulation enables reversible selective reflection color tuning across the entire visible spectrum. The chiral switch also displays a temperature-dependent HTP change that enables thermally driven red, green, and blue (RGB) reflection colors in the self-organized helical superstructure. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid and Parallel Adaptive Evolution of the Visual System of Neotropical Midas Cichlid Fishes.

PubMed

Torres-Dowdall, Julián; Pierotti, Michele E R; Härer, Andreas; Karagic, Nidal; Woltering, Joost M; Henning, Frederico; Elmer, Kathryn R; Meyer, Axel

2017-10-01

Midas cichlid fish are a Central American species flock containing 13 described species that has been dated to only a few thousand years old, a historical timescale infrequently associated with speciation. Their radiation involved the colonization of several clear water crater lakes from two turbid great lakes. Therefore, Midas cichlids have been subjected to widely varying photic conditions during their radiation. Being a primary signal relay for information from the environment to the organism, the visual system is under continuing selective pressure and a prime organ system for accumulating adaptive changes during speciation, particularly in the case of dramatic shifts in photic conditions. Here, we characterize the full visual system of Midas cichlids at organismal and genetic levels, to determine what types of adaptive changes evolved within the short time span of their radiation. We show that Midas cichlids have a diverse visual system with unexpectedly high intra- and interspecific variation in color vision sensitivity and lens transmittance. Midas cichlid populations in the clear crater lakes have convergently evolved visual sensitivities shifted toward shorter wavelengths compared with the ancestral populations from the turbid great lakes. This divergence in sensitivity is driven by changes in chromophore usage, differential opsin expression, opsin coexpression, and to a lesser degree by opsin coding sequence variation. The visual system of Midas cichlids has the evolutionary capacity to rapidly integrate multiple adaptations to changing light environments. Our data may indicate that, in early stages of divergence, changes in opsin regulation could precede changes in opsin coding sequence evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Interference and Shaping in Sensorimotor Adaptations with Rewards

PubMed Central

Darshan, Ran; Leblois, Arthur; Hansel, David

2014-01-01

When a perturbation is applied in a sensorimotor transformation task, subjects can adapt and maintain performance by either relying on sensory feedback, or, in the absence of such feedback, on information provided by rewards. For example, in a classical rotation task where movement endpoints must be rotated to reach a fixed target, human subjects can successfully adapt their reaching movements solely on the basis of binary rewards, although this proves much more difficult than with visual feedback. Here, we investigate such a reward-driven sensorimotor adaptation process in a minimal computational model of the task. The key assumption of the model is that synaptic plasticity is gated by the reward. We study how the learning dynamics depend on the target size, the movement variability, the rotation angle and the number of targets. We show that when the movement is perturbed for multiple targets, the adaptation process for the different targets can interfere destructively or constructively depending on the similarities between the sensory stimuli (the targets) and the overlap in their neuronal representations. Destructive interferences can result in a drastic slowdown of the adaptation. As a result of interference, the time to adapt varies non-linearly with the number of targets. Our analysis shows that these interferences are weaker if the reward varies smoothly with the subject's performance instead of being binary. We demonstrate how shaping the reward or shaping the task can accelerate the adaptation dramatically by reducing the destructive interferences. We argue that experimentally investigating the dynamics of reward-driven sensorimotor adaptation for more than one sensory stimulus can shed light on the underlying learning rules. PMID:24415925

Adaptation to Externally Driven Change: The Impact of Political Change on Job Satisfaction in the Public Sector

PubMed Central

Tabvuma, Vurain; Bui, Hong T M; Homberg, Fabian

2014-01-01

This article uses a quasi-natural experiment to investigate the adaptation of job satisfaction to externally driven political change in the public sector. This is important because democratic government bureaucracies often experience changes in leadership after elections. The analyses are based on data drawn from a large longitudinal data set, the British Household Panel Survey. Findings indicate that the impact of political elections is largely weak and temporary and is only present for men. For women, the internal processes of the organization tend to be more important. These findings suggest that changes in political leadership may not be associated with fundamental changes in policy. PMID:25598554

EXTRACTION APPARATUS

DOEpatents

Ballard, A.E.; Brigham, H.R.

1958-10-28

An apparatus whereby relatlvely volatile solvents may be contacted with volatile or non-volatile material without certaln attendant hazards is described. A suitable apparatus for handling relatively volatlle liqulds may be constructed comprising a tank, and a closure covering the tank and adapted to be securely attached to an external suppont. The closure is provided with a rigidly mounted motor-driven agitator. This agitator is connected from the driving motor lnto the lnterlor of the tank through a gland adapted to be cooled witb inert gas thereby eliminating possible hazard due to frictional heat. The closure is arranged so that the tank may be removed from it without materially dlsturbing the closure which, as described, carrles the motor driven agitator and other parts.

From Local Adaptation to Ecological Speciation in Copepod Populations from Neighboring Lakes

PubMed Central

Barrera-Moreno, Omar Alfredo; Ciros-Pérez, Jorge; Ortega-Mayagoitia, Elizabeth; Alcántara-Rodríguez, José Arturo; Piedra-Ibarra, Elías

2015-01-01

Continental copepods have been derived from several independent invasive events from the sea, but the subsequent evolutionary processes that account for the current diversity in lacustrine environments are virtually unknown. Salinity is highly variable among lakes and constitutes a source of divergent selection driving potential reproductive isolation. We studied four populations of the calanoid copepod Leptodiaptomus cf. sicilis inhabiting four neighboring lakes with a common history (since the Late Pleistocene) located in the Oriental Basin, Mexico; one lake is shallow and varies in salinity periodically (1.4–10 g L-1), while three are deep and permanent, with constant salinity (0.5, 1.1 and 6.5 g L-1, respectively). We hypothesized that (1) these populations belong to a different species than L. sicilis sensu stricto and (2) are experiencing ecologically based divergence due to salinity differences. We assessed morphological and molecular (mtDNA) COI variation, as well as fitness differences and tests of reproductive isolation. Although relationships of the Mexican populations with L. sicilis s.s. could not be elucidated, we identified a clear pattern of divergent selection driven by salinity conditions. The four populations can still be considered a single biological species (sexual recognition and hybridization are still possible in laboratory conditions), but they have diverged into at least three different phenotypes: two locally adapted, specialized in the lakes of constant salinity (saline vs. freshwater), and an intermediate generalist phenotype inhabiting the temporary lake with fluctuating salinity. The specialized phenotypes are poorly suited as migrants, so prezygotic isolation due to immigrant inviability is highly probable. This implication was supported by molecular evidence that showed restricted gene flow, persistence of founder events, and a pattern of allopatric fragmentation. This study showed how ecologically based divergent selection may explain diversification patterns in lacustrine copepods. PMID:25915059

Elemental economy: microbial strategies for optimizing growth in the face of nutrient limitation.

PubMed

Merchant, Sabeeha S; Helmann, John D

2012-01-01

Microorganisms play a dominant role in the biogeochemical cycling of nutrients. They are rightly praised for their facility for fixing both carbon and nitrogen into organic matter, and microbial driven processes have tangibly altered the chemical composition of the biosphere and its surrounding atmosphere. Despite their prodigious capacity for molecular transformations, microorganisms are powerless in the face of the immutability of the elements. Limitations for specific elements, either fleeting or persisting over eons, have left an indelible trace on microbial genomes, physiology, and their very atomic composition. We here review the impact of elemental limitation on microbes, with a focus on selected genetic model systems and representative microbes from the ocean ecosystem. Evolutionary adaptations that enhance growth in the face of persistent or recurrent elemental limitations are evident from genome and proteome analyses. These range from the extreme (such as dispensing with a requirement for a hard to obtain element) to the extremely subtle (changes in protein amino acid sequences that slightly, but significantly, reduce cellular carbon, nitrogen, or sulfur demand). One near-universal adaptation is the development of sophisticated acclimation programs by which cells adjust their chemical composition in response to a changing environment. When specific elements become limiting, acclimation typically begins with an increased commitment to acquisition and a concomitant mobilization of stored resources. If elemental limitation persists, the cell implements austerity measures including elemental sparing and elemental recycling. Insights into these fundamental cellular properties have emerged from studies at many different levels, including ecology, biological oceanography, biogeochemistry, molecular genetics, genomics, and microbial physiology. Here, we present a synthesis of these diverse studies and attempt to discern some overarching themes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparative Genomics Identifies Epidermal Proteins Associated with the Evolution of the Turtle Shell.

PubMed

Holthaus, Karin Brigit; Strasser, Bettina; Sipos, Wolfgang; Schmidt, Heiko A; Mlitz, Veronika; Sukseree, Supawadee; Weissenbacher, Anton; Tschachler, Erwin; Alibardi, Lorenzo; Eckhart, Leopold

2016-03-01

The evolution of reptiles, birds, and mammals was associated with the origin of unique integumentary structures. Studies on lizards, chicken, and humans have suggested that the evolution of major structural proteins of the outermost, cornified layers of the epidermis was driven by the diversification of a gene cluster called Epidermal Differentiation Complex (EDC). Turtles have evolved unique defense mechanisms that depend on mechanically resilient modifications of the epidermis. To investigate whether the evolution of the integument in these reptiles was associated with specific adaptations of the sequences and expression patterns of EDC-related genes, we utilized newly available genome sequences to determine the epidermal differentiation gene complement of turtles. The EDC of the western painted turtle (Chrysemys picta bellii) comprises more than 100 genes, including at least 48 genes that encode proteins referred to as beta-keratins or corneous beta-proteins. Several EDC proteins have evolved cysteine/proline contents beyond 50% of total amino acid residues. Comparative genomics suggests that distinct subfamilies of EDC genes have been expanded and partly translocated to loci outside of the EDC in turtles. Gene expression analysis in the European pond turtle (Emys orbicularis) showed that EDC genes are differentially expressed in the skin of the various body sites and that a subset of beta-keratin genes within the EDC as well as those located outside of the EDC are expressed predominantly in the shell. Our findings give strong support to the hypothesis that the evolutionary innovation of the turtle shell involved specific molecular adaptations of epidermal differentiation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Elemental Economy: microbial strategies for optimizing growth in the face of nutrient limitation

PubMed Central

Merchant, Sabeeha S.; Helmann, John D.

2014-01-01

Microorganisms play a dominant role in the biogeochemical cycling of nutrients. They are rightly praised for their facility at fixing both carbon and nitrogen into organic matter, and microbial driven processes have tangibly altered the chemical composition of the biosphere and its surrounding atmosphere. Despite their prodigious capacity for molecular transformations, microorganisms are powerless in the face of the immutability of the elements. Limitations for specific elements, either fleeting or persisting over eons, have left an indelible trace on microbial genomes, physiology, and their very atomic composition. We here review the impact of elemental limitation on microbes, with a focus on selected genetic model systems and representative microbes from the ocean ecosystem. Evolutionary adaptations that enhance growth in the face of persistent or recurrent elemental limitations are evident from genome and proteome analyses. These range from the extreme (such as dispensing with a requirement for a hard to obtain element) to the extremely subtle (changes in protein amino acid sequences that slightly, but significantly, reduce cellular carbon, nitrogen, or sulfur demand). One near universal adaptation is the development of sophisticated acclimation programs by which cells adjust their chemical composition in response to a changing environment. When specific elements become limiting, acclimation typically begins with an increased commitment to acquisition and a concomitant mobilization of stored resources. If elemental limitation persists, the cell implements austerity measures including elemental-sparing and elemental-recycling. Insights into these fundamental cellular properties have emerged from studies at many different levels; including ecology, biological oceanography, biogeochemistry, molecular genetics, genomics, and microbial physiology. Here, we present a synthesis of these diverse studies and attempt to discern some overarching themes. PMID:22633059

Identification of coeliac disease triggering glutenin peptides in adults.

PubMed

Donnelly, Suzanne C; Šuligoj, Tanja; Ellis, H Julia; Ciclitira, Paul J

2016-07-01

Coeliac disease affects approximately 1% of Northern American and European populations. It is caused by an inappropriate immune response to dietary gluten. Gluten comprises of two major protein fractions: gliadins and glutenins. Glutenins have recently been found to be toxic to coeliac individuals. Proliferation assays suggest in some but not all paediatric coeliac individuals there may be immunological stimulation with high molecular weight (HMW) glutenins. Less evidence pertains to low molecular weight (LMW) glutenins. The aim is to assess adaptive, T-cell driven, and innate immune response in adult coeliac individuals towards HMW glutenin peptide, glut04, and LMW glutenin peptide, glt156. Coeliac patients were recruited attending endoscopy for routine monitoring. Adaptive immune response towards glut04 and glt156 was measured by proliferation assays and measurement of interferon-γ secretion in 28 T-cell lines. The innate immune response was assessed by measurement of enterocyte cell height (ECH) in coeliac small intestinal biopsies following overnight incubation in organ culture chambers in a further nine individuals. There were 3/28 and 2/28 positive proliferation results using gluten-sensitive T-cells with glut04 and glt156, respectively. All coeliac biopsies tested in organ culture chambers demonstrated clear reduction in ECH with peptic-tryptic digest of whole industrial gluten, glut04 and glt156 when compared to negative control ovalbumin (p < 0.005). Three individuals had both T-cell and organ culture study data. Their proliferation assays showed no stimulation of the T-cells. This study demonstrates glutenin epitopes glut04 and glt156, while minor T-cell epitopes, are important in their ability to trigger the innate immune response.

Southwest regional climate hub and California subsidiary hub assessment of climate change vulnerability and adaptation and mitigation strategies

USDA-ARS?s Scientific Manuscript database

This report describes the potential vulnerability of specialty crops, field crops, forests, and animal agriculture to climate-driven environmental changes. Here, vulnerability is defined as a function of exposure to climate change effects, sensitivity to these effects, and adaptive capacity. The exp...

Evaluating an Adaptive Equity-Oriented Pedagogy: A Study of Its Impacts in Higher Education

ERIC Educational Resources Information Center

Phuong, Andrew Estrada; Nguyen, Judy; Marie, Dena

2017-01-01

This study examines whether and how an adaptive equity-oriented pedagogy can address diverse college students' needs and preferred modes of learning. Using a mixed-methods approach, we evaluated this pedagogical intervention that synthesizes democratic, assessment-driven, strengths-based, multimodal, and game-based instructional strategies. This…

Cognitive Processing Therapy for Spanish-speaking Latinos: A Formative Study of a Model-Driven Cultural Adaptation of the Manual to Enhance Implementation in a Usual Care Setting.

PubMed

Valentine, Sarah E; Borba, Christina P C; Dixon, Louise; Vaewsorn, Adin S; Guajardo, Julia Gallegos; Resick, Patricia A; Wiltsey Stirman, Shannon; Marques, Luana

2017-03-01

As part of a larger implementation trial for cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) in a community health center, we used formative evaluation to assess relations between iterative cultural adaption (for Spanish-speaking clients) and implementation outcomes (appropriateness and acceptability) for CPT. Qualitative data for the current study were gathered through multiple sources (providers: N = 6; clients: N = 22), including CPT therapy sessions, provider fieldnotes, weekly consultation team meetings, and researcher fieldnotes. Findings from conventional and directed content analysis of the data informed refinements to the CPT manual. Data-driven refinements included adaptations related to cultural context (i.e., language, regional variation in wording), urban context (e.g., crime/violence), and literacy level. Qualitative findings suggest improved appropriateness and acceptability of CPT for Spanish-speaking clients. Our study reinforces the need for dual application of cultural adaptation and implementation science to address the PTSD treatment needs of Spanish-speaking clients. © 2016 Wiley Periodicals, Inc.

Cognitive Processing Therapy for Spanish-speaking Latinos: A formative study of a model-driven cultural adaptation of the manual to enhance implementation in a usual care setting

PubMed Central

Valentine, Sarah E.; Borba, Christina P. C.; Dixon, Louise; Vaewsorn, Adin S.; Guajardo, Julia Gallegos; Resick, Patricia A.; Wiltsey-Stirman, Shannon; Marques, Luana

2016-01-01

Objective As part of a larger implementation trial for Cognitive Processing Therapy (CPT) for posttraumatic stress disorder (PTSD) in a community health center, we used formative evaluation to assess relations between iterative cultural adaption (for Spanish-speaking clients) and implementation outcomes (appropriateness & acceptability) for CPT. Method Qualitative data for the current study were gathered through multiple sources (providers: N=6; clients: N=22), including CPT therapy sessions, provider field notes, weekly consultation team meetings, and researcher field notes. Findings from conventional and directed content analysis of the data informed refinements to the CPT manual. Results Data-driven refinements included adaptations related to cultural context (i.e., language, regional variation in wording), urban context (e.g., crime/violence), and literacy level. Qualitative findings suggest improved appropriateness and acceptability of CPT for Spanish-speaking clients. Conclusion Our study reinforces the need for dual application of cultural adaptation and implementation science to address the PTSD treatment needs of Spanish-speaking clients. PMID:27378013

Inactivation of Semicircular Canals Causes Adaptive Increases in Otolith-driven Tilt Responses

NASA Technical Reports Server (NTRS)

Angelaki, Dora E.; Newlands, Shawn D.; Dickman, J. David

2002-01-01

Growing experimental and theoretical evidence suggests a functional synergy in the processing of otolith and semicircular canal signals for the generation of the vestibulo-ocular reflexes (VORs). In this study we have further tested this functional interaction by quantifying the adaptive changes in the otolith-ocular system during both rotational and translational movements after surgical inactivation of the semicircular canals. For 0.1- 0.5 Hz (stimuli for which there is no recovery of responses from the plugged canals), pitch and roll VOR gains recovered during earth- horizontal (but not earth-vertical) axis rotations. Corresponding changes were also observed in eye movements elicited by translational motion (0.1 - 5 Hz). Specifically, torsional eye movements increased during lateral motion, whereas vertical eye movements increased during fore-aft motion. The findings indicate that otolith signals can be adapted according to compromised strategy that leads to improved gaze stabilization during motion. Because canal-plugged animals permanently lose the ability to discriminate gravitoinertial accelerations, adapted animals can use the presence of gravity through otolith-driven tilt responses to assist gaze stabilization during earth-horizontal axis rotations.

Recognition-driven chemical labeling of endogenous proteins in multi-molecular crowding in live cells.

PubMed

Amaike, Kazuma; Tamura, Tomonori; Hamachi, Itaru

2017-11-14

Endogenous protein labeling is one of the most invaluable methods for studying the bona fide functions of proteins in live cells. However, multi-molecular crowding conditions, such as those that occur in live cells, hamper the highly selective chemical labeling of a protein of interest (POI). We herein describe how the efficient coupling of molecular recognition with a chemical reaction is crucial for selective protein labeling. Recognition-driven protein labeling is carried out by a synthetic labeling reagent containing a protein (recognition) ligand, a reporter tag, and a reactive moiety. The molecular recognition of a POI can be used to greatly enhance the reaction kinetics and protein selectivity, even under live cell conditions. In this review, we also briefly discuss how such selective chemical labeling of an endogenous protein can have a variety of applications at the interface of chemistry and biology.

Molecular propulsion: chemical sensing and chemotaxis of DNA driven by RNA polymerase.

PubMed

Yu, Hua; Jo, Kyubong; Kounovsky, Kristy L; de Pablo, Juan J; Schwartz, David C

2009-04-29

Living cells sense extracellular signals and direct their movements in response to stimuli in environment. Such autonomous movement allows these machines to sample chemical change over a distance, leading to chemotaxis. Synthetic catalytic rods have been reported to chemotax toward hydrogen peroxide fuel. Nevertheless individualized autonomous control of movement of a population of biomolecules under physiological conditions has not been demonstrated. Here we show the first experimental evidence that a molecular complex consisting of a DNA template and associating RNA polymerases (RNAPs) displays chemokinetic motion driven by transcription substrates nucleoside triphosphates (NTPs). Furthermore this molecular complex exhibits a biased migration into a concentration gradient of NTPs, resembling chemotaxis. We describe this behavior as "Molecular Propulsion", in which RNAP transcriptional actions deform DNA template conformation engendering measurable enhancement of motility. Our results provide new opportunities for designing and directing nanomachines by imposing external triggers within an experimental system.

Ancient Origins of Vertebrate-Specific Innate Antiviral Immunity

PubMed Central

Mukherjee, Krishanu; Korithoski, Bryan; Kolaczkowski, Bryan

2014-01-01

Animals deploy various molecular sensors to detect pathogen infections. RIG-like receptor (RLR) proteins identify viral RNAs and initiate innate immune responses. The three human RLRs recognize different types of RNA molecules and protect against different viral pathogens. The RLR protein family is widely thought to have originated shortly before the emergence of vertebrates and rapidly diversified through a complex process of domain grafting. Contrary to these findings, here we show that full-length RLRs and their downstream signaling molecules were present in the earliest animals, suggesting that the RLR-based immune system arose with the emergence of multicellularity. Functional differentiation of RLRs occurred early in animal evolution via simple gene duplication followed by modifications of the RNA-binding pocket, many of which may have been adaptively driven. Functional analysis of human and ancestral RLRs revealed that the ancestral RLR displayed RIG-1-like RNA-binding. MDA5-like binding arose through changes in the RNA-binding pocket following the duplication of the ancestral RLR, which may have occurred either early in Bilateria or later, after deuterostomes split from protostomes. The sensitivity and specificity with which RLRs bind different RNA structures has repeatedly adapted throughout mammalian evolution, suggesting a long-term evolutionary arms race with viral RNA or other molecules. PMID:24109602

The Validity and Value of Peer Assessment Using Adaptive Comparative Judgement in Design Driven Practical Education

ERIC Educational Resources Information Center

Seery, Niall; Canty, Donal; Phelan, Pat

2012-01-01

This paper presents the response of the technology teacher education programmes at the University of Limerick to the assessment challenge created by the shift in philosophy of the Irish national curriculum from a craft-based focus to design-driven education. This study observes two first year modules of the undergraduate programmes that focused on…

Sensor Web Dynamic Measurement Techniques and Adaptive Observing Strategies

NASA Technical Reports Server (NTRS)

Talabac, Stephen J.

2004-01-01

Sensor Web observing systems may have the potential to significantly improve our ability to monitor, understand, and predict the evolution of rapidly evolving, transient, or variable environmental features and events. This improvement will come about by integrating novel data collection techniques, new or improved instruments, emerging communications technologies and protocols, sensor mark-up languages, and interoperable planning and scheduling systems. In contrast to today's observing systems, "event-driven" sensor webs will synthesize real- or near-real time measurements and information from other platforms and then react by reconfiguring the platforms and instruments to invoke new measurement modes and adaptive observation strategies. Similarly, "model-driven" sensor webs will utilize environmental prediction models to initiate targeted sensor measurements or to use a new observing strategy. The sensor web concept contrasts with today's data collection techniques and observing system operations concepts where independent measurements are made by remote sensing and in situ platforms that do not share, and therefore cannot act upon, potentially useful complementary sensor measurement data and platform state information. This presentation describes NASA's view of event-driven and model-driven Sensor Webs and highlights several research and development activities at the Goddard Space Flight Center.

Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process

PubMed Central

Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

2015-01-01

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution. PMID:26177190

Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.

PubMed

Kishimoto, Toshihiko; Ying, Bei-Wen; Tsuru, Saburo; Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

2015-07-01

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.

Molecular Gas in Obscured and Extremely Red Quasars at z ˜ 2.5

NASA Astrophysics Data System (ADS)

Alexandroff, Rachael; Zakamska, Nadia; Hamann, Fred; Greene, Jenny; Rahman, Mubdi

2018-01-01

Quasar feedback is a key element of modern galaxy evolution theory. During powerful episodes of feedback, quasar-driven winds are suspected of removing large amounts of molecular gas from the host galaxy, thus limiting supplies for star formation and ultimately curtailing the maximum mass of galaxies. Here we present Karl A. Jansky Very Large Array (VLA) observations of the CO(1-0) transition in 11 powerful obscured and extremely red quasars (ERQs) at z~2.5. Previous observations have shown that several of these targets display signatures of powerful quasar-driven winds in their ionized gas. Molecular emission is not detected in a single object, whether kinematically disturbed due to a quasar wind or in equilibrium with the host galaxy and neither is molecular gas detected in a combined stack of all objects (equivalent to an exposure time of over 10 hours with the VLA). This observation is in contrast with the previous suggestions that such objects should occupy gas-rich, extremely star-forming galaxies. Possible explanations include a paucity of molecular gas or an excess of high- excitation molecular gas, both of which could be the results of quasar feedback. In the radio continuum, we detect an average point-like (< 5 kpc) emission with luminosity νLν[33 GHz]=2.2 x 1042 erg s-1, consistent with optically-thin (α ≈ -1.0) synchrotron with some possible contribution from thermal free-free emission. The continuum radio emission of these radio-intermediate objects may be a bi-product of radiatively driven winds or may be due to weak jets confined to the host galaxy.

Comparison of genetic diversity and population structure of Pacific Coast whitebark pine across multiple markers

Treesearch

Andrew D. Bower; Bryce A. Richardson; Valerie Hipkins; Regina Rochefort; Carol Aubry

2011-01-01

Analysis of "neutral" molecular markers and "adaptive" quantitative traits are common methods of assessing genetic diversity and population structure. Molecular markers typically reflect the effects of demographic and stochastic processes but are generally assumed to not reflect natural selection. Conversely, quantitative (or "adaptive")...

Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase

PubMed Central

Mukherjee, Shayantani; Warshel, Arieh

2012-01-01

The molecular origin of the action of the F0 proton gradient-driven rotor presents a major puzzle despite significant structural advances. Although important conceptual models have provided guidelines of how such systems should work, it has been challenging to generate a structure-based molecular model using physical principles that will consistently lead to the unidirectional proton-driven rotational motion during ATP synthesis. This work uses a coarse-grained (CG) model to simulate the energetics of the F0-ATPase system in the combined space defined by the rotational coordinate and the proton transport (PTR) from the periplasmic side (P) to the cytoplasmic side (N). The model establishes the molecular origin of the rotation, showing that this effect is due to asymmetry in the energetics of the proton path rather than only the asymmetry of the interaction of the Asp on the c-ring helices and Arg on the subunit-a. The simulation provides a clear conceptual background for further exploration of the electrostatic basis of proton-driven mechanochemical systems. PMID:22927379

Perspective: THz-driven nuclear dynamics from solids to molecules

PubMed Central

Hamm, Peter; Meuwly, Markus; Johnson, Steve L.; Beaud, Paul; Staub, Urs

2017-01-01

Recent years have seen dramatic developments in the technology of intense pulsed light sources in the THz frequency range. Since many dipole-active excitations in solids and molecules also lie in this range, there is now a tremendous potential to use these light sources to study linear and nonlinear dynamics in such systems. While several experimental investigations of THz-driven dynamics in solid-state systems have demonstrated a variety of interesting linear and nonlinear phenomena, comparatively few efforts have been made to drive analogous dynamics in molecular systems. In the present Perspective article, we discuss the similarities and differences between THz-driven dynamics in solid-state and molecular systems on both conceptual and practical levels. We also discuss the experimental parameters needed for these types of experiments and thereby provide design criteria for a further development of this new research branch. Finally, we present a few recent examples to illustrate the rich physics that may be learned from nonlinear THz excitations of phonons in solids as well as inter-molecular vibrations in liquid and gas-phase systems. PMID:29308420

Perspective: THz-driven nuclear dynamics from solids to molecules.

PubMed

Hamm, Peter; Meuwly, Markus; Johnson, Steve L; Beaud, Paul; Staub, Urs

2017-11-01

Recent years have seen dramatic developments in the technology of intense pulsed light sources in the THz frequency range. Since many dipole-active excitations in solids and molecules also lie in this range, there is now a tremendous potential to use these light sources to study linear and nonlinear dynamics in such systems. While several experimental investigations of THz-driven dynamics in solid-state systems have demonstrated a variety of interesting linear and nonlinear phenomena, comparatively few efforts have been made to drive analogous dynamics in molecular systems. In the present Perspective article, we discuss the similarities and differences between THz-driven dynamics in solid-state and molecular systems on both conceptual and practical levels. We also discuss the experimental parameters needed for these types of experiments and thereby provide design criteria for a further development of this new research branch. Finally, we present a few recent examples to illustrate the rich physics that may be learned from nonlinear THz excitations of phonons in solids as well as inter-molecular vibrations in liquid and gas-phase systems.

Multi-channel dynamics in high harmonic generation of aligned CO2: ab initio analysis with time-dependent B-spline algebraic diagrammatic construction.

PubMed

Ruberti, M; Decleva, P; Averbukh, V

2018-03-28

Here we present a fully ab initio study of the high-order harmonic generation (HHG) spectrum of aligned CO 2 molecules. The calculations have been performed by using the molecular time-dependent (TD) B-spline algebraic diagrammatic construction (ADC) method. We quantitatively study how the sub-cycle laser-driven multi-channel dynamics, as reflected in the position of the dynamical minimum in the HHG spectrum, is affected by the full inclusion of both correlation-driven and laser-driven dipole interchannel couplings. We calculate channel-resolved spectral intensities as well as the phase differences between contributions of the different ionization-recombination channels to the total HHG spectrum. Our results show that electron correlation effectively controls the relative contributions of the different channels to the total HHG spectrum, leading to the opening of the new ones (1 2 Π u , 1 2 Σ), previously disregarded for the aligned molecular setup. We conclude that inclusion of many-electron effects into the theoretical interpretation of molecular HHG spectra is essential in order to correctly extract ultrafast electron dynamics using HHG spectroscopy.

Segmentation-driven compound document coding based on H.264/AVC-INTRA.

PubMed

Zaghetto, Alexandre; de Queiroz, Ricardo L

2007-07-01

In this paper, we explore H.264/AVC operating in intraframe mode to compress a mixed image, i.e., composed of text, graphics, and pictures. Even though mixed contents (compound) documents usually require the use of multiple compressors, we apply a single compressor for both text and pictures. For that, distortion is taken into account differently between text and picture regions. Our approach is to use a segmentation-driven adaptation strategy to change the H.264/AVC quantization parameter on a macroblock by macroblock basis, i.e., we deviate bits from pictorial regions to text in order to keep text edges sharp. We show results of a segmentation driven quantizer adaptation method applied to compress documents. Our reconstructed images have better text sharpness compared to straight unadapted coding, at negligible visual losses on pictorial regions. Our results also highlight the fact that H.264/AVC-INTRA outperforms coders such as JPEG-2000 as a single coder for compound images.

Phylodynamics of H1N1/2009 influenza reveals the transition from host adaptation to immune-driven selection

PubMed Central

Su, Yvonne C. F.; Bahl, Justin; Joseph, Udayan; Butt, Ka Man; Peck, Heidi A.; Koay, Evelyn S. C.; Oon, Lynette L. E.; Barr, Ian G.; Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.

2015-01-01

Influenza A H1N1/2009 virus that emerged from swine rapidly replaced the previous seasonal H1N1 virus. Although the early emergence and diversification of H1N1/2009 is well characterized, the ongoing evolutionary and global transmission dynamics of the virus remain poorly investigated. To address this we analyse >3,000 H1N1/2009 genomes, including 214 full genomes generated from our surveillance in Singapore, in conjunction with antigenic data. Here we show that natural selection acting on H1N1/2009 directly after introduction into humans was driven by adaptation to the new host. Since then, selection has been driven by immunological escape, with these changes corresponding to restricted antigenic diversity in the virus population. We also show that H1N1/2009 viruses have been subject to regular seasonal bottlenecks and a global reduction in antigenic and genetic diversity in 2014. PMID:26245473

Molecular and physiological evidence of genetic assimilation to high CO2 in the marine nitrogen fixer Trichodesmium.

PubMed

Walworth, Nathan G; Lee, Michael D; Fu, Fei-Xue; Hutchins, David A; Webb, Eric A

2016-11-22

Most investigations of biogeochemically important microbes have focused on plastic (short-term) phenotypic responses in the absence of genetic change, whereas few have investigated adaptive (long-term) responses. However, no studies to date have investigated the molecular progression underlying the transition from plasticity to adaptation under elevated CO 2 for a marine nitrogen-fixer. To address this gap, we cultured the globally important cyanobacterium Trichodesmium at both low and high CO 2 for 4.5 y, followed by reciprocal transplantation experiments to test for adaptation. Intriguingly, fitness actually increased in all high-CO 2 adapted cell lines in the ancestral environment upon reciprocal transplantation. By leveraging coordinated phenotypic and transcriptomic profiles, we identified expression changes and pathway enrichments that rapidly responded to elevated CO 2 and were maintained upon adaptation, providing strong evidence for genetic assimilation. These candidate genes and pathways included those involved in photosystems, transcriptional regulation, cell signaling, carbon/nitrogen storage, and energy metabolism. Conversely, significant changes in specific sigma factor expression were only observed upon adaptation. These data reveal genetic assimilation as a potentially adaptive response of Trichodesmium and importantly elucidate underlying metabolic pathways paralleling the fixation of the plastic phenotype upon adaptation, thereby contributing to the few available data demonstrating genetic assimilation in microbial photoautotrophs. These molecular insights are thus critical for identifying pathways under selection as drivers in plasticity and adaptation.

The Evolutionary Dynamics of the Odorant Receptor Gene Family in Corbiculate Bees

PubMed Central

Ramírez, Santiago R.

2017-01-01

Abstract Insects rely on chemical information to locate food, choose mates, and detect potential predators. It has been hypothesized that adaptive changes in the olfactory system facilitated the diversification of numerous insect lineages. For instance, evolutionary changes of Odorant Receptor (OR) genes often occur in parallel with modifications in life history strategies. Corbiculate bees display a diverse array of behaviors that are controlled through olfaction, including varying degrees of social organization, and manifold associations with floral resources. Here we investigated the molecular mechanisms driving the evolution of the OR gene family in corbiculate bees in comparison to other chemosensory gene families. Our results indicate that the genomic organization of the OR gene family has remained highly conserved for ∼80 Myr, despite exhibiting major changes in repertoire size among bee lineages. Moreover, the evolution of OR genes appears to be driven mostly by lineage-specific gene duplications in few genomic regions that harbor large numbers of OR genes. A selection analysis revealed that OR genes evolve under positive selection, with the strongest signals detected in recently duplicated copies. Our results indicate that chromosomal translocations had a minimal impact on OR evolution, and instead local molecular mechanisms appear to be main drivers of OR repertoire size. Our results provide empirical support to the longstanding hypothesis that positive selection shaped the diversification of the OR gene family. Together, our results shed new light on the molecular mechanisms underlying the evolution of olfaction in insects. PMID:28854688

An Hypothesis-Driven, Molecular Phylogenetics Exercise for College Biology Students

ERIC Educational Resources Information Center

Parker, Joel D.; Ziemba, Robert E.; Cahan, Sara Helms; Rissing, Steven W.

2004-01-01

This hypothesis-driven laboratory exercise teaches how DNA evidence can be used to investigate an organism's evolutionary history while providing practical modeling of the fundamental processes of gene transcription and translation. We used an inquiry-based approach to construct a laboratory around a nontrivial, open-ended evolutionary question…

ATP synthase--a marvellous rotary engine of the cell.

PubMed

Yoshida, M; Muneyuki, E; Hisabori, T

2001-09-01

ATP synthase can be thought of as a complex of two motors--the ATP-driven F1 motor and the proton-driven Fo motor--that rotate in opposite directions. The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale.

Switches of stimulus tagging frequencies interact with the conflict-driven control of selective attention, but not with inhibitory control.

PubMed

Scherbaum, Stefan; Frisch, Simon; Dshemuchadse, Maja

2016-01-01

Selective attention and its adaptation by cognitive control processes are considered a core aspect of goal-directed action. Often, selective attention is studied behaviorally with conflict tasks, but an emerging neuroscientific method for the study of selective attention is EEG frequency tagging. It applies different flicker frequencies to the stimuli of interest eliciting steady state visual evoked potentials (SSVEPs) in the EEG. These oscillating SSVEPs in the EEG allow tracing the allocation of selective attention to each tagged stimulus continuously over time. The present behavioral investigation points to an important caveat of using tagging frequencies: The flicker of stimuli not only produces a useful neuroscientific marker of selective attention, but interacts with the adaptation of selective attention itself. Our results indicate that RT patterns of adaptation after response conflict (so-called conflict adaptation) are reversed when flicker frequencies switch at once. However, this effect of frequency switches is specific to the adaptation by conflict-driven control processes, since we find no effects of frequency switches on inhibitory control processes after no-go trials. We discuss the theoretical implications of this finding and propose precautions that should be taken into account when studying conflict adaptation using frequency tagging in order to control for the described confounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating

PubMed Central

Böcking, Till; Aguet, François; Harrison, Stephen C.; Kirchhausen, Tomas

2010-01-01

Heat shock cognate protein 70 (Hsc70) supports remodeling of protein complexes -- for example, disassembly of clathrin coats on endocytic coated vesicles. To understand how a simple ATP driven molecular clamp catalyzes a large-scale disassembly reaction, we have used single-particle fluorescence imaging to track the dynamics of Hsc70 and its clathrin substrate in real time. Hsc70 accumulates to a critical level, determined by kinetic modeling to be one Hsc70 for every two functional attachment sites; rapid, all-or-none uncoating then ensues. We propose that Hsc70 traps conformational distortions, seen previously by electron cryomicroscopy, in the vicinity of each occupied site and that accumulation of local strains destabilises the clathrin lattice. Capture of conformational fluctuations may be a general mechanism for chaperone-driven disassembly of protein complexes. PMID:21278753

Traffic Flow of Interacting Self-Driven Particles: Rails and Trails, Vehicles and Vesicles

NASA Astrophysics Data System (ADS)

Chowdhury, Debashish

One common feature of a vehicle, an ant and a kinesin motor is that they all convert chemical energy, derived from fuel or food, into mechanical energy required for their forward movement; such objects have been modelled in recent years as self-driven particles. Cytoskeletal filaments, e.g., microtubules, form a rail network for intra-cellular transport of vesicular cargo by molecular motors like, for example, kinesins. Similarly, ants move along trails while vehicles move along lanes. Therefore, the traffic of vehicles and organisms as well as that of molecular motors can be modelled as systems of interacting self-driven particles; these are of current interest in non-equilibrium statistical mechanics. In this paper we point out the common features of these model systems and emphasize the crucial differences in their physical properties.

Impact of Parkinson's Disease and Dopaminergic Medication on Adaptation to Explicit and Implicit Visuomotor Perturbations

ERIC Educational Resources Information Center

Mongeon, David; Blanchet, Pierre; Messier, Julie

2013-01-01

The capacity to learn new visuomotor associations is fundamental to adaptive motor behavior. Evidence suggests visuomotor learning deficits in Parkinson's disease (PD). However, the exact nature of these deficits and the ability of dopamine medication to improve them are under-explored. Previous studies suggested that learning driven by large and…

Evidence for Site-Specific, Systematic Adaptation of Substance Prevention Curriculum with High-Risk Youths in Community and Alternative School Settings

ERIC Educational Resources Information Center

Holleran Steiker, Lori K.; Hopson, Laura M.; Goldbach, Jeremy T.; Robinson, Charletta

2014-01-01

The problem of substance use among older youths is often disregarded in prevention research. The prevailing perception has been that prevention programming is developmentally inappropriate for those who are actively experimenting with substances. This project examines the differential effectiveness of youth-driven adaptations of the evidence-based…

Hard Sphere Simulation by Event-Driven Molecular Dynamics: Breakthrough, Numerical Difficulty, and Overcoming the issues

NASA Astrophysics Data System (ADS)

Isobe, Masaharu

Hard sphere/disk systems are among the simplest models and have been used to address numerous fundamental problems in the field of statistical physics. The pioneering numerical works on the solid-fluid phase transition based on Monte Carlo (MC) and molecular dynamics (MD) methods published in 1957 represent historical milestones, which have had a significant influence on the development of computer algorithms and novel tools to obtain physical insights. This chapter addresses the works of Alder's breakthrough regarding hard sphere/disk simulation: (i) event-driven molecular dynamics, (ii) long-time tail, (iii) molasses tail, and (iv) two-dimensional melting/crystallization. From a numerical viewpoint, there are serious issues that must be overcome for further breakthrough. Here, we present a brief review of recent progress in this area.

Electric-field-driven electron-transfer in mixed-valence molecules.

PubMed

Blair, Enrique P; Corcelli, Steven A; Lent, Craig S

2016-07-07

Molecular quantum-dot cellular automata is a computing paradigm in which digital information is encoded by the charge configuration of a mixed-valence molecule. General-purpose computing can be achieved by arranging these compounds on a substrate and exploiting intermolecular Coulombic coupling. The operation of such a device relies on nonequilibrium electron transfer (ET), whereby the time-varying electric field of one molecule induces an ET event in a neighboring molecule. The magnitude of the electric fields can be quite large because of close spatial proximity, and the induced ET rate is a measure of the nonequilibrium response of the molecule. We calculate the electric-field-driven ET rate for a model mixed-valence compound. The mixed-valence molecule is regarded as a two-state electronic system coupled to a molecular vibrational mode, which is, in turn, coupled to a thermal environment. Both the electronic and vibrational degrees-of-freedom are treated quantum mechanically, and the dissipative vibrational-bath interaction is modeled with the Lindblad equation. This approach captures both tunneling and nonadiabatic dynamics. Relationships between microscopic molecular properties and the driven ET rate are explored for two time-dependent applied fields: an abruptly switched field and a linearly ramped field. In both cases, the driven ET rate is only weakly temperature dependent. When the model is applied using parameters appropriate to a specific mixed-valence molecule, diferrocenylacetylene, terahertz-range ET transfer rates are predicted.

Paradigm shift in bacteriophage-mediated delivery of anticancer drugs: from targeted 'magic bullets' to self-navigated 'magic missiles'.

PubMed

Petrenko, Valery A; Gillespie, James W

2017-03-01

New phage-directed nanomedicines have emerged recently as a result of the in-depth study of the genetics and structure of filamentous phage and evolution of phage display and phage nanobiotechnology. This review focuses on the progress made in the development of the cancer-targeted nanomaterials and discusses the trends in using phage as a bioselectable molecular navigation system. Areas covered: The merging of phage display technologies with nanotechnology in recent years has proved promising in different areas of medicine and technology, such as medical diagnostics, molecular imaging, vaccine development and targeted drug/gene delivery, which is the focus of this review. The authors used data obtained from their research group and sourced using Science Citation Index (Web of Science) and NCBI PubMed search resources. Expert opinion: First attempts of adapting traditional concepts of direct targeting of tumor using phage-targeted nanomedicines has shown minimal improvements. With discovery and study of biological and technical barriers that prevent anti-tumor drug delivery, a paradigm shift from traditional drug targeting to nanomedicine navigation systems is required. The advanced bacteriophage-driven self-navigation systems are thought to overcome those barriers using more precise, localized phage selection methods, multi-targeting 'promiscuous' ligands and advanced multifunctional nanomedicine platforms.

A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast

PubMed Central

Chang, Shang-Lin; Leu, Jun-Yi

2011-01-01

Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance. PMID:21483812

Molecular Cloning and Optimization for High Level Expression of Cold-Adapted Serine Protease from Antarctic Yeast Glaciozyma antarctica PI12

PubMed Central

Ahmad Mazian, Mu'adz; Salleh, Abu Bakar; Basri, Mahiran; Rahman, Raja Noor Zaliha Raja Abd.

2014-01-01

Psychrophilic basidiomycete yeast, Glaciozyma antarctica strain PI12, was shown to be a protease-producer. Isolation of the PI12 protease gene from genomic and mRNA sequences allowed determination of 19 exons and 18 introns. Full-length cDNA of PI12 protease gene was amplified by rapid amplification of cDNA ends (RACE) strategy with an open reading frame (ORF) of 2892 bp, coded for 963 amino acids. PI12 protease showed low homology with the subtilisin-like protease from fungus Rhodosporidium toruloides (42% identity) and no homology to other psychrophilic proteases. The gene encoding mature PI12 protease was cloned into Pichia pastoris expression vector, pPIC9, and positioned under the induction of methanol-alcohol oxidase (AOX) promoter. The recombinant PI12 protease was efficiently secreted into the culture medium driven by the Saccharomyces cerevisiae α-factor signal sequence. The highest protease production (28.3 U/ml) was obtained from P. pastoris GS115 host (GpPro2) at 20°C after 72 hours of postinduction time with 0.5% (v/v) of methanol inducer. The expressed protein was detected by SDS-PAGE and activity staining with a molecular weight of 99 kDa. PMID:25093119

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

PubMed

Curtis, Christina; Shah, Sohrab P; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M; Dunning, Mark J; Speed, Doug; Lynch, Andy G; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-04-18

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome.

Genomic signatures of parasite-driven natural selection in north European Atlantic salmon (Salmo salar).

PubMed

Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Primmer, Craig R

2018-06-01

Understanding the genomic basis of host-parasite adaptation is important for predicting the long-term viability of species and developing successful management practices. However, in wild populations, identifying specific signatures of parasite-driven selection often presents a challenge, as it is difficult to unravel the molecular signatures of selection driven by different, but correlated, environmental factors. Furthermore, separating parasite-mediated selection from similar signatures due to genetic drift and population history can also be difficult. Populations of Atlantic salmon (Salmo salar L.) from northern Europe have pronounced differences in their reactions to the parasitic flatworm Gyrodactylus salaris Malmberg 1957 and are therefore a good model to search for specific genomic regions underlying inter-population differences in pathogen response. We used a dense Atlantic salmon SNP array, along with extensive sampling of 43 salmon populations representing the two G. salaris response extremes (extreme susceptibility vs resistant), to screen the salmon genome for signatures of directional selection while attempting to separate the parasite effect from other factors. After combining the results from two independent genome scan analyses, 57 candidate genes potentially under positive selection were identified, out of which 50 were functionally annotated. This candidate gene set was shown to be functionally enriched for lymph node development, focal adhesion genes and anti-viral response, which suggests that the regulation of both innate and acquired immunity might be an important mechanism for salmon response to G. salaris. Overall, our results offer insights into the apparently complex genetic basis of pathogen susceptibility in salmon and highlight methodological challenges for separating the effects of various environmental factors. Copyright © 2018 Elsevier B.V. All rights reserved.

A perspective on bridging scales and design of models using low-dimensional manifolds and data-driven model inference

PubMed Central

Zenil, Hector; Kiani, Narsis A.; Ball, Gordon; Gomez-Cabrero, David

2016-01-01

Systems in nature capable of collective behaviour are nonlinear, operating across several scales. Yet our ability to account for their collective dynamics differs in physics, chemistry and biology. Here, we briefly review the similarities and differences between mathematical modelling of adaptive living systems versus physico-chemical systems. We find that physics-based chemistry modelling and computational neuroscience have a shared interest in developing techniques for model reductions aiming at the identification of a reduced subsystem or slow manifold, capturing the effective dynamics. By contrast, as relations and kinetics between biological molecules are less characterized, current quantitative analysis under the umbrella of bioinformatics focuses on signal extraction, correlation, regression and machine-learning analysis. We argue that model reduction analysis and the ensuing identification of manifolds bridges physics and biology. Furthermore, modelling living systems presents deep challenges as how to reconcile rich molecular data with inherent modelling uncertainties (formalism, variables selection and model parameters). We anticipate a new generative data-driven modelling paradigm constrained by identified governing principles extracted from low-dimensional manifold analysis. The rise of a new generation of models will ultimately connect biology to quantitative mechanistic descriptions, thereby setting the stage for investigating the character of the model language and principles driving living systems. This article is part of the themed issue ‘Multiscale modelling at the physics–chemistry–biology interface’. PMID:27698038

What actually confers adaptive capacity? Insights from agro-climatic vulnerability of Australian wheat.

PubMed

Bryan, Brett A; Huai, Jianjun; Connor, Jeff; Gao, Lei; King, Darran; Kandulu, John; Zhao, Gang

2015-01-01

Vulnerability assessments have often invoked sustainable livelihoods theory to support the quantification of adaptive capacity based on the availability of capital--social, human, physical, natural, and financial. However, the assumption that increased availability of these capitals confers greater adaptive capacity remains largely untested. We quantified the relationship between commonly used capital indicators and an empirical index of adaptive capacity (ACI) in the context of vulnerability of Australian wheat production to climate variability and change. We calculated ACI by comparing actual yields from farm survey data to climate-driven expected yields estimated by a crop model for 12 regions in Australia's wheat-sheep zone from 1991-2010. We then compiled data for 24 typical indicators used in vulnerability analyses, spanning the five capitals. We analyzed the ACI and used regression techniques to identify related capital indicators. Between regions, mean ACI was not significantly different but variance over time was. ACI was higher in dry years and lower in wet years suggesting that farm adaptive strategies are geared towards mitigating losses rather than capitalizing on opportunity. Only six of the 24 capital indicators were significantly related to adaptive capacity in a way predicted by theory. Another four indicators were significantly related to adaptive capacity but of the opposite sign, countering our theory-driven expectation. We conclude that the deductive, theory-based use of capitals to define adaptive capacity and vulnerability should be more circumspect. Assessments need to be more evidence-based, first testing the relevance and influence of capital metrics on adaptive capacity for the specific system of interest. This will more effectively direct policy and targeting of investment to mitigate agro-climatic vulnerability.

What Actually Confers Adaptive Capacity? Insights from Agro-Climatic Vulnerability of Australian Wheat

PubMed Central

Bryan, Brett A.; Huai, Jianjun; Connor, Jeff; Gao, Lei; King, Darran; Kandulu, John; Zhao, Gang

2015-01-01

Vulnerability assessments have often invoked sustainable livelihoods theory to support the quantification of adaptive capacity based on the availability of capital—social, human, physical, natural, and financial. However, the assumption that increased availability of these capitals confers greater adaptive capacity remains largely untested. We quantified the relationship between commonly used capital indicators and an empirical index of adaptive capacity (ACI) in the context of vulnerability of Australian wheat production to climate variability and change. We calculated ACI by comparing actual yields from farm survey data to climate-driven expected yields estimated by a crop model for 12 regions in Australia’s wheat-sheep zone from 1991–2010. We then compiled data for 24 typical indicators used in vulnerability analyses, spanning the five capitals. We analyzed the ACI and used regression techniques to identify related capital indicators. Between regions, mean ACI was not significantly different but variance over time was. ACI was higher in dry years and lower in wet years suggesting that farm adaptive strategies are geared towards mitigating losses rather than capitalizing on opportunity. Only six of the 24 capital indicators were significantly related to adaptive capacity in a way predicted by theory. Another four indicators were significantly related to adaptive capacity but of the opposite sign, countering our theory-driven expectation. We conclude that the deductive, theory-based use of capitals to define adaptive capacity and vulnerability should be more circumspect. Assessments need to be more evidence-based, first testing the relevance and influence of capital metrics on adaptive capacity for the specific system of interest. This will more effectively direct policy and targeting of investment to mitigate agro-climatic vulnerability. PMID:25668192

Right ventrolateral prefrontal cortex mediates individual differences in conflict-driven cognitive control

PubMed Central

Egner, Tobias

2013-01-01

Conflict adaptation – a conflict-triggered improvement in the resolution of conflicting stimulus or response representations – has become a widely used probe of cognitive control processes in both healthy and clinical populations. Previous functional magnetic resonance imaging (fMRI) studies have localized activation foci associated with conflict resolution to dorsolateral prefrontal cortex (dlPFC). The traditional group-analysis approach employed in these studies highlights regions that are, on average, activated during conflict resolution, but does not necessarily reveal areas mediating individual differences in conflict resolution, because between-subject variance is treated as noise. Here, we employed a complementary approach in order to elucidate the neural bases of variability in the proficiency of conflict-driven cognitive control. We analyzed two independent fMRI data sets of face-word Stroop tasks by using individual variability in the behavioral expression of conflict adaptation as the metric against which brain activation was regressed, while controlling for individual differences in mean reaction time and Stroop interference. Across the two experiments, a replicable neural substrate of individual variation in conflict adaptation was found in ventrolateral prefrontal cortex (vlPFC), specifically, in the right inferior frontal gyrus, pars orbitalis (BA 47). Unbiased regression estimates showed that variability in activity in this region accounted for ~40% of the variance in behavioral expression of conflict adaptation across subjects, thus documenting a heretofore unsuspected key role for vlPFC in mediating conflict-driven adjustments in cognitive control. We speculate that vlPFC plays a primary role in conflict control that is supplemented by dlPFC recruitment under conditions of suboptimal performance. PMID:21568631

Right ventrolateral prefrontal cortex mediates individual differences in conflict-driven cognitive control.

PubMed

Egner, Tobias

2011-12-01

Conflict adaptation--a conflict-triggered improvement in the resolution of conflicting stimulus or response representations--has become a widely used probe of cognitive control processes in both healthy and clinical populations. Previous fMRI studies have localized activation foci associated with conflict resolution to dorsolateral PFC (dlPFC). The traditional group analysis approach employed in these studies highlights regions that are, on average, activated during conflict resolution, but does not necessarily reveal areas mediating individual differences in conflict resolution, because between-subject variance is treated as noise. Here, we employed a complementary approach to elucidate the neural bases of variability in the proficiency of conflict-driven cognitive control. We analyzed two independent fMRI data sets of face-word Stroop tasks by using individual variability in the behavioral expression of conflict adaptation as the metric against which brain activation was regressed while controlling for individual differences in mean RT and Stroop interference. Across the two experiments, a replicable neural substrate of individual variation in conflict adaptation was found in ventrolateral PFC (vlPFC), specifically, in the right inferior frontal gyrus, pars orbitalis (BA 47). Unbiased regression estimates showed that variability in activity in this region accounted for ∼ 40% of the variance in behavioral expression of conflict adaptation across subjects, thus documenting a heretofore unsuspected key role for vlPFC in mediating conflict-driven adjustments in cognitive control. We speculate that vlPFC plays a primary role in conflict control that is supplemented by dlPFC recruitment under conditions of suboptimal performance.

Biomimetic molecular design tools that learn, evolve, and adapt.

PubMed

Winkler, David A

2017-01-01

A dominant hallmark of living systems is their ability to adapt to changes in the environment by learning and evolving. Nature does this so superbly that intensive research efforts are now attempting to mimic biological processes. Initially this biomimicry involved developing synthetic methods to generate complex bioactive natural products. Recent work is attempting to understand how molecular machines operate so their principles can be copied, and learning how to employ biomimetic evolution and learning methods to solve complex problems in science, medicine and engineering. Automation, robotics, artificial intelligence, and evolutionary algorithms are now converging to generate what might broadly be called in silico-based adaptive evolution of materials. These methods are being applied to organic chemistry to systematize reactions, create synthesis robots to carry out unit operations, and to devise closed loop flow self-optimizing chemical synthesis systems. Most scientific innovations and technologies pass through the well-known "S curve", with slow beginning, an almost exponential growth in capability, and a stable applications period. Adaptive, evolving, machine learning-based molecular design and optimization methods are approaching the period of very rapid growth and their impact is already being described as potentially disruptive. This paper describes new developments in biomimetic adaptive, evolving, learning computational molecular design methods and their potential impacts in chemistry, engineering, and medicine.

Biomimetic molecular design tools that learn, evolve, and adapt

PubMed Central

2017-01-01

A dominant hallmark of living systems is their ability to adapt to changes in the environment by learning and evolving. Nature does this so superbly that intensive research efforts are now attempting to mimic biological processes. Initially this biomimicry involved developing synthetic methods to generate complex bioactive natural products. Recent work is attempting to understand how molecular machines operate so their principles can be copied, and learning how to employ biomimetic evolution and learning methods to solve complex problems in science, medicine and engineering. Automation, robotics, artificial intelligence, and evolutionary algorithms are now converging to generate what might broadly be called in silico-based adaptive evolution of materials. These methods are being applied to organic chemistry to systematize reactions, create synthesis robots to carry out unit operations, and to devise closed loop flow self-optimizing chemical synthesis systems. Most scientific innovations and technologies pass through the well-known “S curve”, with slow beginning, an almost exponential growth in capability, and a stable applications period. Adaptive, evolving, machine learning-based molecular design and optimization methods are approaching the period of very rapid growth and their impact is already being described as potentially disruptive. This paper describes new developments in biomimetic adaptive, evolving, learning computational molecular design methods and their potential impacts in chemistry, engineering, and medicine. PMID:28694872

Glacial history affected phenotypic differentiation in the alpine plant, Campanula thyrsoides.

PubMed

Scheepens, J F; Frei, Eva S; Stöcklin, Jürg

2013-01-01

Numerous widespread Alpine plant species show molecular differentiation among populations from distinct regions. This has been explained as the result of genetic drift during glacial survival in isolated refugia along the border of the European Alps. Since genetic drift may affect molecular markers and phenotypic traits alike, we asked whether phenotypic differentiation mirrors molecular patterns among Alpine plant populations from different regions. Phenotypic traits can be under selection, so we additionally investigated whether part of the phenotypic differentiation can be explained by past selection and/or current adaptation. Using the monocarpic Campanula thyrsoides as our study species, a common garden experiment with plants from 21 populations from four phylogeographic groups located in regions across the Alps and the Jura Mountains was performed to test for differentiation in morphological and phenological traits. Past selection was investigated by comparing phenotypic differentiation among and within regions with molecular differentiation among and within regions. The common garden results indicated regional differentiation among populations for all investigated phenotypic traits, particularly in phenology. Delayed flowering in plants from the South-eastern Alps suggested adaptation to long sub-mediterranean summers and contrasted with earlier flowering of plants experiencing shorter growing seasons in regions with higher elevation to the West. Comparisons between molecular and phenotypic differentiation revealed diversifying selection among regions in height and biomass, which is consistent with adaptation to environmental conditions in glacial refugia. Within regions, past selection acted against strong diversification for most phenotypic traits, causing restricted postglacial adaptation. Evidence consistent with post-glacial adaptation was also given by negative correlation coefficients between several phenotypic traits and elevation of the population's origin. In conclusion, our study suggests that, irrespective of adaptation of plants to their current environment, glacial history can have a strong and long-lasting influence on the phenotypic evolution of Alpine plants.

Evolutionary layering and the limits to cellular perfection

PubMed Central

Lynch, Michael

2012-01-01

Although observations from biochemistry and cell biology seemingly illustrate hundreds of examples of exquisite molecular adaptations, the fact that experimental manipulation can often result in improvements in cellular infrastructure raises the question as to what ultimately limits the level of molecular perfection achievable by natural selection. Here, it is argued that random genetic drift can impose a strong barrier to the advancement of molecular refinements by adaptive processes. Moreover, although substantial improvements in fitness may sometimes be accomplished via the emergence of novel cellular features that improve on previously established mechanisms, such advances are expected to often be transient, with overall fitness eventually returning to the level before incorporation of the genetic novelty. As a consequence of such changes, increased molecular/cellular complexity can arise by Darwinian processes, while yielding no long-term increase in adaptation and imposing increased energetic and mutational costs. PMID:23115338

An adaptive liquid microlens driven by a ferrofluidic transducer

NASA Astrophysics Data System (ADS)

Xiao, Wenjia; Hardt, Steffen

2010-05-01

Ferrofluids behave superparamagnetically and can be manipulated by external magnetic fields, providing numerous applications in microfluidic systems. In this paper, an adaptive liquid microlens driven by a ferrofluidic actuator is presented. The microlens consists of a cylindrical well filled with a lens liquid connected to a microchannel containing a ferrofluid plug. When the ferrofluid plug is moved back and forth by an external magnetic field, the lens liquid is displaced, forming a liquid lens with an adaptive focus in the cylindrical well. The focal length of the lens can be changed from infinity to the scale of the radius of the cylindrical well, leading to a high optical power compared to conventional liquid lenses utilizing liquid crystals or electrowetting. The lens curvature is reversibly tunable without hysteresis when the ferrofluid plug moves with a speed below a specific threshold value. The lens can be acted on by a magnetic field of about 100 mT which can be generated by microcoils requiring much lower voltages than the electrowetting principle.

Mixture-based gatekeeping procedures in adaptive clinical trials.

PubMed

Kordzakhia, George; Dmitrienko, Alex; Ishida, Eiji

2018-01-01

Clinical trials with data-driven decision rules often pursue multiple clinical objectives such as the evaluation of several endpoints or several doses of an experimental treatment. These complex analysis strategies give rise to "multivariate" multiplicity problems with several components or sources of multiplicity. A general framework for defining gatekeeping procedures in clinical trials with adaptive multistage designs is proposed in this paper. The mixture method is applied to build a gatekeeping procedure at each stage and inferences at each decision point (interim or final analysis) are performed using the combination function approach. An advantage of utilizing the mixture method is that it enables powerful gatekeeping procedures applicable to a broad class of settings with complex logical relationships among the hypotheses of interest. Further, the combination function approach supports flexible data-driven decisions such as a decision to increase the sample size or remove a treatment arm. The paper concludes with a clinical trial example that illustrates the methodology by applying it to develop an adaptive two-stage design with a mixture-based gatekeeping procedure.

Molecular adaptation in Rubisco: Discriminating between convergent evolution and positive selection using mechanistic and classical codon models.

PubMed

Parto, Sahar; Lartillot, Nicolas

2018-01-01

Rubisco (Ribulose-1, 5-biphosphate carboxylase/oxygenase) is the most important enzyme on earth, catalyzing the first step of photosynthetic CO2 fixation. So, without it, there would be no storing of the sun's energy in plants. Molecular adaptation of Rubisco to C4 photosynthetic pathway has attracted a lot of attention. C4 plants, which comprise less than 5% of land plants, have evolved more efficient photosynthesis compared to C3 plants. Interestingly, a large number of independent transitions from C3 to C4 phenotype have occurred. Each time, the Rubisco enzyme has been subject to similar changes in selective pressure, thus providing an excellent model for convergent evolution at the molecular level. Molecular adaptation is often identified with positive selection and is typically characterized by an elevated ratio of non-synonymous to synonymous substitution rate (dN/dS). However, convergent adaptation is expected to leave a different molecular signature, taking the form of repeated transitions toward identical or similar amino acids. Here, we used a previously introduced codon-based differential-selection model to detect and quantify consistent patterns of convergent adaptation in Rubisco in eudicots. We further contrasted our results with those obtained by classical codon models based on the estimation of dN/dS. We found that the two classes of models tend to select distinct, although overlapping, sets of positions. This discrepancy in the results illustrates the conceptual difference between these models while emphasizing the need to better discriminate between qualitatively different selective regimes, by using a broader class of codon models than those currently considered in molecular evolutionary studies.

Adaptive mesh strategies for the spectral element method

NASA Technical Reports Server (NTRS)

Mavriplis, Catherine

1992-01-01

An adaptive spectral method was developed for the efficient solution of time dependent partial differential equations. Adaptive mesh strategies that include resolution refinement and coarsening by three different methods are illustrated on solutions to the 1-D viscous Burger equation and the 2-D Navier-Stokes equations for driven flow in a cavity. Sharp gradients, singularities, and regions of poor resolution are resolved optimally as they develop in time using error estimators which indicate the choice of refinement to be used. The adaptive formulation presents significant increases in efficiency, flexibility, and general capabilities for high order spectral methods.

Digest: Local adaptation at close quarters.

PubMed

Schmidt, Chloé; Garroway, Colin

2018-06-19

Although the theory of how gene flow and genetic drift interact with local adaptation is well understood, few empirical studies have examined this process. Hämälä et al. (2018) present evidence that adaptive divergence between populations of Arabidopsis lyrata can persist in the face of relatively high levels of gene flow and drift. Maintaining divergence despite gene flow and drift has important implications for understanding adaptive responses of populations in response to human-driven environmental change. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Outcomes of a Research-Driven Laboratory and Literature Course Designed to Enhance Undergraduate Contributions to Original Research

ERIC Educational Resources Information Center

Rasche, Madeline E.

2004-01-01

This work describes outcomes of a research-driven advanced microbiology laboratory and literature research course intended to enhance undergraduate preparation for and contributions to original research. The laboratory section was designed to teach fundamental biochemistry and molecular biology techniques in the context of an original research…

A Conceptual Systems Model to Facilitate Hypothesis-driven Ecotoxicogenomics Research on the Teleost Brain-pituitary-gonadal Axis

EPA Science Inventory

This provides an overview of a novel open-source conceptuial model of molecular and biochemical pathways involved in the regulation of fish reproduction. Further, it provides concrete examples of how such models can be used to design and conduct hypothesis-driven "omics" experim...

DynamO: a free O(N) general event-driven molecular dynamics simulator.

PubMed

Bannerman, M N; Sargant, R; Lue, L

2011-11-30

Molecular dynamics algorithms for systems of particles interacting through discrete or "hard" potentials are fundamentally different to the methods for continuous or "soft" potential systems. Although many software packages have been developed for continuous potential systems, software for discrete potential systems based on event-driven algorithms are relatively scarce and specialized. We present DynamO, a general event-driven simulation package, which displays the optimal O(N) asymptotic scaling of the computational cost with the number of particles N, rather than the O(N) scaling found in most standard algorithms. DynamO provides reference implementations of the best available event-driven algorithms. These techniques allow the rapid simulation of both complex and large (>10(6) particles) systems for long times. The performance of the program is benchmarked for elastic hard sphere systems, homogeneous cooling and sheared inelastic hard spheres, and equilibrium Lennard-Jones fluids. This software and its documentation are distributed under the GNU General Public license and can be freely downloaded from http://marcusbannerman.co.uk/dynamo. Copyright © 2011 Wiley Periodicals, Inc.

Faster-X evolution of gene expression is driven by recessive adaptive cis-regulatory variation in Drosophila.

PubMed

Llopart, Ana

2018-05-01

The hemizygosity of the X (Z) chromosome fully exposes the fitness effects of mutations on that chromosome and has evolutionary consequences on the relative rates of evolution of X and autosomes. Specifically, several population genetics models predict increased rates of evolution in X-linked loci relative to autosomal loci. This prediction of faster-X evolution has been evaluated and confirmed for both protein coding sequences and gene expression. In the case of faster-X evolution for gene expression divergence, it is often assumed that variation in 5' noncoding sequences is associated with variation in transcript abundance between species but a formal, genomewide test of this hypothesis is still missing. Here, I use whole genome sequence data in Drosophila yakuba and D. santomea to evaluate this hypothesis and report positive correlations between sequence divergence at 5' noncoding sequences and gene expression divergence. I also examine polymorphism and divergence in 9,279 noncoding sequences located at the 5' end of annotated genes and detected multiple signals of positive selection. Notably, I used the traditional synonymous sites as neutral reference to test for adaptive evolution, but I also used bases 8-30 of introns <65 bp, which have been proposed to be a better neutral choice. X-linked genes with high degree of male-biased expression show the most extreme adaptive pattern at 5' noncoding regions, in agreement with faster-X evolution for gene expression divergence and a higher incidence of positively selected recessive mutations. © 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Data-driven robust approximate optimal tracking control for unknown general nonlinear systems using adaptive dynamic programming method.

PubMed

Zhang, Huaguang; Cui, Lili; Zhang, Xin; Luo, Yanhong

2011-12-01

In this paper, a novel data-driven robust approximate optimal tracking control scheme is proposed for unknown general nonlinear systems by using the adaptive dynamic programming (ADP) method. In the design of the controller, only available input-output data is required instead of known system dynamics. A data-driven model is established by a recurrent neural network (NN) to reconstruct the unknown system dynamics using available input-output data. By adding a novel adjustable term related to the modeling error, the resultant modeling error is first guaranteed to converge to zero. Then, based on the obtained data-driven model, the ADP method is utilized to design the approximate optimal tracking controller, which consists of the steady-state controller and the optimal feedback controller. Further, a robustifying term is developed to compensate for the NN approximation errors introduced by implementing the ADP method. Based on Lyapunov approach, stability analysis of the closed-loop system is performed to show that the proposed controller guarantees the system state asymptotically tracking the desired trajectory. Additionally, the obtained control input is proven to be close to the optimal control input within a small bound. Finally, two numerical examples are used to demonstrate the effectiveness of the proposed control scheme.

Linking high harmonics from gases and solids.

PubMed

Vampa, G; Hammond, T J; Thiré, N; Schmidt, B E; Légaré, F; McDonald, C R; Brabec, T; Corkum, P B

2015-06-25

When intense light interacts with an atomic gas, recollision between an ionizing electron and its parent ion creates high-order harmonics of the fundamental laser frequency. This sub-cycle effect generates coherent soft X-rays and attosecond pulses, and provides a means to image molecular orbitals. Recently, high harmonics have been generated from bulk crystals, but what mechanism dominates the emission remains uncertain. To resolve this issue, we adapt measurement methods from gas-phase research to solid zinc oxide driven by mid-infrared laser fields of 0.25 volts per ångström. We find that when we alter the generation process with a second-harmonic beam, the modified harmonic spectrum bears the signature of a generalized recollision between an electron and its associated hole. In addition, we find that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology. Future experiments will permit the band structure of a solid to be tomographically reconstructed.

Species-specific temperature sensitivity of TRPA1

PubMed Central

Laursen, Willem J; Anderson, Evan O; Hoffstaetter, Lydia J; Bagriantsev, Sviatoslav N; Gracheva, Elena O

2015-01-01

Abstract Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel sensitive to temperature and chemical stimuli. The importance of temperature and aversive chemical detection for survival has driven the evolutionary diversity of TRPA1 sensitivity. This diversity can be observed in the various roles of TRPA1 in different species, where it is proposed to act as a temperature-insensitive chemosensor, a heat transducer, a noxious cold transducer, or a detector of low-intensity heat for prey localization. Exploring the variation of TRPA1 functions among species provides evolutionary insight into molecular mechanisms that fine-tune thermal and chemical sensitivity, and offers an opportunity to address basic principles of temperature gating in ion channels. A decade of research has yielded a number of hypotheses describing physiological roles of TRPA1, modulators of its activity, and biophysical principles of gating. This review surveys the diversity of TRPA1 adaptations across evolutionary taxa and explores possible mechanisms of TRPA1 activation. PMID:27227025

Motor-driven intracellular transport powers bacterial gliding motility

PubMed Central

Sun, Mingzhai; Wartel, Morgane; Cascales, Eric; Shaevitz, Joshua W.; Mignot, Tâm

2011-01-01

Protein-directed intracellular transport has not been observed in bacteria despite the existence of dynamic protein localization and a complex cytoskeleton. However, protein trafficking has clear potential uses for important cellular processes such as growth, development, chromosome segregation, and motility. Conflicting models have been proposed to explain Myxococcus xanthus motility on solid surfaces, some favoring secretion engines at the rear of cells and others evoking an unknown class of molecular motors distributed along the cell body. Through a combination of fluorescence imaging, force microscopy, and genetic manipulation, we show that membrane-bound cytoplasmic complexes consisting of motor and regulatory proteins are directionally transported down the axis of a cell at constant velocity. This intracellular motion is transmitted to the exterior of the cell and converted to traction forces on the substrate. Thus, this study demonstrates the existence of a conserved class of processive intracellular motors in bacteria and shows how these motors have been adapted to produce cell motility. PMID:21482768

Light-driven transformable optical agent with adaptive functions for boosting cancer surgery outcomes.

PubMed

Qi, Ji; Chen, Chao; Zhang, Xiaoyan; Hu, Xianglong; Ji, Shenglu; Kwok, Ryan T K; Lam, Jacky W Y; Ding, Dan; Tang, Ben Zhong

2018-05-10

Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; however, combining effects in one agent normally requires a trade-off as the mechanisms interfere. Here, based on rational molecular design, we introduce a smart organic nanoparticle whose absorbed excitation energy can be photo-switched to the pathway of thermal deactivation for photoacoustic imaging, or to allow opposed routes for fluorescence imaging and photodynamic therapy. The molecule is made of a dithienylethene (DTE) core with two surrounding 2-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) units (DTE-TPECM). The photosensitive molecule changes from a ring-closed, for photoacoustic imaging, to a ring-opened state for fluorescence and photodynamic effects upon an external light trigger. The nanoparticles' photoacoustic and fluorescence imaging properties demonstrate the advantage of the switch. The use of the nanoparticles improves the outcomes of in vivo cancer surgery using preoperative photoacoustic imaging and intraoperative fluorescent visualization/photodynamic therapy of residual tumours to ensure total tumour removal.

Highly efficient and robust molecular ruthenium catalysts for water oxidation.

PubMed

Duan, Lele; Araujo, Carlos Moyses; Ahlquist, Mårten S G; Sun, Licheng

2012-09-25

Water oxidation catalysts are essential components of light-driven water splitting systems, which could convert water to H(2) driven by solar radiation (H(2)O + hν → 1/2O(2) + H(2)). The oxidation of water (H(2)O → 1/2O(2) + 2H(+) + 2e(-)) provides protons and electrons for the production of dihydrogen (2H(+) + 2e(-) → H(2)), a clean-burning and high-capacity energy carrier. One of the obstacles now is the lack of effective and robust water oxidation catalysts. Aiming at developing robust molecular Ru-bda (H(2)bda = 2,2'-bipyridine-6,6'-dicarboxylic acid) water oxidation catalysts, we carried out density functional theory studies, correlated the robustness of catalysts against hydration with the highest occupied molecular orbital levels of a set of ligands, and successfully directed the synthesis of robust Ru-bda water oxidation catalysts. A series of mononuclear ruthenium complexes [Ru(bda)L(2)] (L = pyridazine, pyrimidine, and phthalazine) were subsequently synthesized and shown to effectively catalyze Ce(IV)-driven [Ce(IV) = Ce(NH(4))(2)(NO(3))(6)] water oxidation with high oxygen production rates up to 286 s(-1) and high turnover numbers up to 55,400.

Temperature-driven decoupling of key phases of organic matter degradation in marine sediments.

PubMed

Weston, Nathaniel B; Joye, Samantha B

2005-11-22

The long-term burial of organic carbon in sediments results in the net accumulation of oxygen in the atmosphere, thereby mediating the redox state of the Earth's biosphere and atmosphere. Sediment microbial activity plays a major role in determining whether particulate organic carbon is recycled or buried. A diverse consortium of microorganisms that hydrolyze, ferment, and terminally oxidize organic compounds mediates anaerobic organic matter mineralization in anoxic sediments. Variable temperature regulation of the sequential processes, leading from the breakdown of complex particulate organic carbon to the production and subsequent consumption of labile, low-molecular weight, dissolved intermediates, could play a key role in controlling rates of overall organic carbon mineralization. We examined sediment organic carbon cycling in a sediment slurry and in flow through bioreactor experiments. The data show a variable temperature response of the microbial functional groups mediating organic matter mineralization in anoxic marine sediments, resulting in the temperature-driven decoupling of the production and consumption of organic intermediates. This temperature-driven decoupling leads to the accumulation of labile, low-molecular weight, dissolved organic carbon at low temperatures and low-molecular weight dissolved organic carbon limitation of terminal metabolism at higher temperatures.

Characterization of the transcriptome of an ecologically important avian species, the Vinous-throated Parrotbill Paradoxornis webbianus bulomachus (Paradoxornithidae; Aves)

PubMed Central

2012-01-01

Background Adaptive divergence driven by environmental heterogeneity has long been a fascinating topic in ecology and evolutionary biology. The study of the genetic basis of adaptive divergence has, however, been greatly hampered by a lack of genomic information. The recent development of transcriptome sequencing provides an unprecedented opportunity to generate large amounts of genomic data for detailed investigations of the genetics of adaptive divergence in non-model organisms. Herein, we used the Illumina sequencing platform to sequence the transcriptome of brain and liver tissues from a single individual of the Vinous-throated Parrotbill, Paradoxornis webbianus bulomachus, an ecologically important avian species in Taiwan with a wide elevational range of sea level to 3100 m. Results Our 10.1 Gbp of sequences were first assembled based on Zebra Finch (Taeniopygia guttata) and chicken (Gallus gallus) RNA references. The remaining reads were then de novo assembled. After filtering out contigs with low coverage (<10X), we retained 67,791 of 487,336 contigs, which covered approximately 5.3% of the P. w. bulomachus genome. Of 7,779 contigs retained for a top-hit species distribution analysis, the majority (about 86%) were matched to known Zebra Finch and chicken transcripts. We also annotated 6,365 contigs to gene ontology (GO) terms: in total, 122 GO-slim terms were assigned, including biological process (41%), molecular function (32%), and cellular component (27%). Many potential genetic markers for future adaptive genomic studies were also identified: 8,589 single nucleotide polymorphisms, 1,344 simple sequence repeats and 109 candidate genes that might be involved in elevational or climate adaptation. Conclusions Our study shows that transcriptome data can serve as a rich genetic resource, even for a single run of short-read sequencing from a single individual of a non-model species. This is the first study providing transcriptomic information for species in the avian superfamily Sylvioidea, which comprises more than 1,000 species. Our data can be used to study adaptive divergence in heterogeneous environments and investigate other important ecological and evolutionary questions in parrotbills from different populations and even in other species in the Sylvioidea. PMID:22530590

Computational efficiency and Amdahl’s law for the adaptive resolution simulation technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Junghans, Christoph; Agarwal, Animesh; Delle Site, Luigi

Here, we discuss the computational performance of the adaptive resolution technique in molecular simulation when it is compared with equivalent full coarse-grained and full atomistic simulations. We show that an estimate of its efficiency, within 10%–15% accuracy, is given by the Amdahl’s Law adapted to the specific quantities involved in the problem. The derivation of the predictive formula is general enough that it may be applied to the general case of molecular dynamics approaches where a reduction of degrees of freedom in a multi scale fashion occurs.

Computational efficiency and Amdahl’s law for the adaptive resolution simulation technique

DOE PAGES

Junghans, Christoph; Agarwal, Animesh; Delle Site, Luigi

2017-06-01

Here, we discuss the computational performance of the adaptive resolution technique in molecular simulation when it is compared with equivalent full coarse-grained and full atomistic simulations. We show that an estimate of its efficiency, within 10%–15% accuracy, is given by the Amdahl’s Law adapted to the specific quantities involved in the problem. The derivation of the predictive formula is general enough that it may be applied to the general case of molecular dynamics approaches where a reduction of degrees of freedom in a multi scale fashion occurs.

Natural language processing and visualization in the molecular imaging domain.

PubMed

Tulipano, P Karina; Tao, Ying; Millar, William S; Zanzonico, Pat; Kolbert, Katherine; Xu, Hua; Yu, Hong; Chen, Lifeng; Lussier, Yves A; Friedman, Carol

2007-06-01

Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

Electric-field-driven electron-transfer in mixed-valence molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blair, Enrique P., E-mail: enrique-blair@baylor.edu; Corcelli, Steven A., E-mail: scorcell@nd.edu; Lent, Craig S., E-mail: lent@nd.edu

2016-07-07

Molecular quantum-dot cellular automata is a computing paradigm in which digital information is encoded by the charge configuration of a mixed-valence molecule. General-purpose computing can be achieved by arranging these compounds on a substrate and exploiting intermolecular Coulombic coupling. The operation of such a device relies on nonequilibrium electron transfer (ET), whereby the time-varying electric field of one molecule induces an ET event in a neighboring molecule. The magnitude of the electric fields can be quite large because of close spatial proximity, and the induced ET rate is a measure of the nonequilibrium response of the molecule. We calculate themore » electric-field-driven ET rate for a model mixed-valence compound. The mixed-valence molecule is regarded as a two-state electronic system coupled to a molecular vibrational mode, which is, in turn, coupled to a thermal environment. Both the electronic and vibrational degrees-of-freedom are treated quantum mechanically, and the dissipative vibrational-bath interaction is modeled with the Lindblad equation. This approach captures both tunneling and nonadiabatic dynamics. Relationships between microscopic molecular properties and the driven ET rate are explored for two time-dependent applied fields: an abruptly switched field and a linearly ramped field. In both cases, the driven ET rate is only weakly temperature dependent. When the model is applied using parameters appropriate to a specific mixed-valence molecule, diferrocenylacetylene, terahertz-range ET transfer rates are predicted.« less

Light-directing chiral liquid crystal nanostructures: from 1D to 3D.

PubMed

Bisoyi, Hari Krishna; Li, Quan

2014-10-21

Endowing external, remote, and dynamic control to self-organized superstructures with desired functionalities is a principal driving force in the bottom-up nanofabrication of molecular devices. Light-driven chiral molecular switches or motors in liquid crystal (LC) media capable of self-organizing into optically tunable one-dimensional (1D) and three-dimensional (3D) superstructures represent such an elegant system. As a consequence, photoresponsive cholesteric LCs (CLCs), i.e., self-organized 1D helical superstructures, and LC blue phases (BPs), i.e., self-organized 3D periodic cubic lattices, are emerging as a new generation of multifunctional supramolecular 1D and 3D photonic materials in their own right because of their fundamental academic interest and technological significance. These smart stimuli-responsive materials can be facilely fabricated from achiral LC hosts by the addition of a small amount of a light-driven chiral molecular switch or motor. The photoresponsiveness of these materials is a result of both molecular interaction and geometry changes in the chiral molecular switch upon light irradiation. The doped photoresponsive CLCs undergo light-driven pitch modulation and/or helix inversion, which has many applications in color filters, polarizers, all-optical displays, optical lasers, sensors, energy-saving smart devices, and so on. Recently, we have conceptualized and rationally synthesized different light-driven chiral molecular switches that have very high helical twisting powers (HTPs) and exhibit large changes in HTP in different states, thereby enabling wide phototunability of the systems by the addition of very small amounts of the molecular switches into commercially available achiral LCs. The light-driven chiral molecular switches are based on well-recognized azobenzene, dithienylcyclopentene, and spirooxazine derivatives. We have demonstrated high-resolution and lightweight photoaddressable displays without patterned electronics on flexible substrates. The wide tunability of the HTP furnishes reflection colors encompassing the whole visible spectrum and beyond in a reversible manner. Photomodulation of the helical pitch of the CLCs has been achieved by UV, visible, and near-infrared (NIR) light irradiation. NIR-light-induced red, green, and blue (RGB) reflections have been leveraged only by varying the power density of the IR laser. Some chiral switches are found to confer helix inversion to the cholesteric systems, which qualifies the CLCs for applications where circularly polarized light is involved. Dynamic and static primary RGB reflection colors have been achieved in a single film. LC BPs have been fabricated and investigated in the context of self-organized 3D photonic band gap (PBG) materials, and dynamic phototuning of the PBG over the visible region has been achieved. Omnidirectional lasing and tuning of the laser emission wavelength have also been attained in monodisperse photoresponsive CLC microshells fabricated by a capillary-based microfluidic technique. This Account covers the research and development in our laboratory starting from the design concepts and synthesis of photodynamic chiral molecular switches to their applications in the fabrication of photoresponsive CLCs and BPs. Potential and demonstrated practical applications of photoresponsive CLCs, microshells, and BPs are discussed, and the Account concludes with a brief forecast of what lies beyond the horizon in this rapidly expanding and fascinating field.

Towards the identification of the loci of adaptive evolution

PubMed Central

Pardo-Diaz, Carolina; Salazar, Camilo; Jiggins, Chris D

2015-01-01

1. Establishing the genetic and molecular basis underlying adaptive traits is one of the major goals of evolutionary geneticists in order to understand the connection between genotype and phenotype and elucidate the mechanisms of evolutionary change. Despite considerable effort to address this question, there remain relatively few systems in which the genes shaping adaptations have been identified. 2. Here, we review the experimental tools that have been applied to document the molecular basis underlying evolution in several natural systems, in order to highlight their benefits, limitations and suitability. In most cases, a combination of DNA, RNA and functional methodologies with field experiments will be needed to uncover the genes and mechanisms shaping adaptation in nature. PMID:25937885

Adaptive Impact-Driven Detection of Silent Data Corruption for HPC Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di, Sheng; Cappello, Franck

For exascale HPC applications, silent data corruption (SDC) is one of the most dangerous problems because there is no indication that there are errors during the execution. We propose an adaptive impact-driven method that can detect SDCs dynamically. The key contributions are threefold. (1) We carefully characterize 18 real-world HPC applications and discuss the runtime data features, as well as the impact of the SDCs on their execution results. (2) We propose an impact-driven detection model that does not blindly improve the prediction accuracy, but instead detects only influential SDCs to guarantee user-acceptable execution results. (3) Our solution can adaptmore » to dynamic prediction errors based on local runtime data and can automatically tune detection ranges for guaranteeing low false alarms. Experiments show that our detector can detect 80-99.99% of SDCs with a false alarm rate less that 1% of iterations for most cases. The memory cost and detection overhead are reduced to 15% and 6.3%, respectively, for a large majority of applications.« less

Does conflict help or hurt cognitive control? Initial evidence for an inverted U-shape relationship between perceived task difficulty and conflict adaptation.

PubMed

van Steenbergen, Henk; Band, Guido P H; Hommel, Bernhard

2015-01-01

Sequential modulation of congruency effects in conflict tasks indicates that cognitive control quickly adapts to changing task demands. We investigated in four experiments how this behavioral congruency-sequence effect relates to different levels of perceived task difficulty in a flanker and a Stroop task. In addition, online measures of pupil diameter were used as a physiological index of effort mobilization. Consistent with motivational accounts predicting that increased levels of perceived task difficulty will increase effort mobilization only up to a certain limit, reliable dynamic conflict-driven adjustment in cognitive control was only observed when task difficulty was relatively low. Instead, tasks tentatively associated with high levels of difficulty showed no or reversed conflict adaptation. Although the effects could not be linked consistently to effects in self-reported task difficulty in all experiments, regression analyses showed associations between perceived task difficulty and conflict adaptation in some of the experiments, which provides some initial evidence for an inverted U-shape relationship between perceived difficulty and adaptations in cognitive control. Furthermore, high levels of task difficulty were associated with a conflict-driven reduction in pupil dilation, suggesting that pupil dilation can be used as a physiological marker of mental overload. Our findings underscore the importance of developing models that are grounded in motivational accounts of cognitive control.

Does conflict help or hurt cognitive control? Initial evidence for an inverted U-shape relationship between perceived task difficulty and conflict adaptation

PubMed Central

van Steenbergen, Henk; Band, Guido P. H.; Hommel, Bernhard

2015-01-01

Sequential modulation of congruency effects in conflict tasks indicates that cognitive control quickly adapts to changing task demands. We investigated in four experiments how this behavioral congruency-sequence effect relates to different levels of perceived task difficulty in a flanker and a Stroop task. In addition, online measures of pupil diameter were used as a physiological index of effort mobilization. Consistent with motivational accounts predicting that increased levels of perceived task difficulty will increase effort mobilization only up to a certain limit, reliable dynamic conflict-driven adjustment in cognitive control was only observed when task difficulty was relatively low. Instead, tasks tentatively associated with high levels of difficulty showed no or reversed conflict adaptation. Although the effects could not be linked consistently to effects in self-reported task difficulty in all experiments, regression analyses showed associations between perceived task difficulty and conflict adaptation in some of the experiments, which provides some initial evidence for an inverted U-shape relationship between perceived difficulty and adaptations in cognitive control. Furthermore, high levels of task difficulty were associated with a conflict-driven reduction in pupil dilation, suggesting that pupil dilation can be used as a physiological marker of mental overload. Our findings underscore the importance of developing models that are grounded in motivational accounts of cognitive control. PMID:26217287

The nearly neutral and selection theories of molecular evolution under the fisher geometrical framework: substitution rate, population size, and complexity.

PubMed

Razeto-Barry, Pablo; Díaz, Javier; Vásquez, Rodrigo A

2012-06-01

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population's phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models.

The Nearly Neutral and Selection Theories of Molecular Evolution Under the Fisher Geometrical Framework: Substitution Rate, Population Size, and Complexity

PubMed Central

Razeto-Barry, Pablo; Díaz, Javier; Vásquez, Rodrigo A.

2012-01-01

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population’s phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models. PMID:22426879

Sex speeds adaptation by altering the dynamics of molecular evolution.

PubMed

McDonald, Michael J; Rice, Daniel P; Desai, Michael M

2016-03-10

Sex and recombination are pervasive throughout nature despite their substantial costs. Understanding the evolutionary forces that maintain these phenomena is a central challenge in biology. One longstanding hypothesis argues that sex is beneficial because recombination speeds adaptation. Theory has proposed several distinct population genetic mechanisms that could underlie this advantage. For example, sex can promote the fixation of beneficial mutations either by alleviating interference competition (the Fisher-Muller effect) or by separating them from deleterious load (the ruby in the rubbish effect). Previous experiments confirm that sex can increase the rate of adaptation, but these studies did not observe the evolutionary dynamics that drive this effect at the genomic level. Here we present the first, to our knowledge, comparison between the sequence-level dynamics of adaptation in experimental sexual and asexual Saccharomyces cerevisiae populations, which allows us to identify the specific mechanisms by which sex speeds adaptation. We find that sex alters the molecular signatures of evolution by changing the spectrum of mutations that fix, and confirm theoretical predictions that it does so by alleviating clonal interference. We also show that substantially deleterious mutations hitchhike to fixation in adapting asexual populations. In contrast, recombination prevents such mutations from fixing. Our results demonstrate that sex both speeds adaptation and alters its molecular signature by allowing natural selection to more efficiently sort beneficial from deleterious mutations.

Contrasted zinc hyperaccumulation levels between metallicolous and non-metallicolous populations of Arabidopsis halleri is driven by divergent selection

NASA Astrophysics Data System (ADS)

Babst-Kostecka, Alicja; Waldmann, Patrik; Pauwels, Maxime; Schat, Henk; Bourceaux, Angélique; Saumitou-Laprade, Pierre; Grodzińska, Krystyna; Frérot, Hélène

2017-04-01

Approximately 400 species that can survive and reproduce in metalliferous environments have developed "metal hyperaccumulation" capacity, allowing them to allocate large amounts of trace elements to their aerial parts without showing severe toxicity symptoms. The potential of hyperaccumulators to be applied in phytoremediation efforts is of great research and commercial interest. Yet, the genetic basis and evolutionary significance of this trait are to date insufficiently understood. This lack of knowledge limits the efficiency and large-scale use of such plants in reducing soil pollution through "green and clean technologies" (phytoremediation). In this context, the objective of this study was to find some evidence of selection acting on metal hyperaccumulation, thus supporting the existence of genetic adaptation for this trait. Here, we collected six metallicolous and five non-metallicolous populations of the pseudometallophyte model species Arabidopsis halleri in Poland that are genetically and geographically close. We asexually propagated genotypes that were sampled in natural populations to produce several clones of each individual. These were subsequently used in a soil culture experiment with artificially zinc-contaminated compost for accumulation assessment. The zinc content of shoots was determined after five weeks of culture using the colorimetric reagent zincon. The heritability and the genetic differentiation of the zinc accumulation trait were estimated (Qst statistic) and the latter was compared to the differentiation at neutral molecular markers (Fst statistic). Despite significantly (P<0.001) lower zinc concentrations in metallicolous compared to non-metallicolous plants, we observed a rather continuous range of zinc hyperaccumulation capacities with multiple genotypes from both edaphic types in between. Overall, zinc concentrations were high in most plants, with only a few metallicolous individuals not reaching the threshold concentration for zinc hyperaccumulation (3000 mg kg-1) under these experimental conditions. The heritability estimates of zinc concentration in shoots for each population ranged from 0.277 to 0.903, and were considerably higher in metallicolous than non-metallicolous populations. The results of Qst-Fst comparisons suggested that differences in zinc hyperaccumulation levels between metallicolous and non-metallicolous populations may be driven by divergent selection, supporting the occurrence of local adaptation. These findings encourage further genetic and genomic research to uncover the genetic basis of local adaptation of A. halleri to contaminated environments. In particular, due to their enhanced zinc hyperaccumulation capacities non-metallicolous populations may be particularly promising for phytoremediation efforts.

Adaptation of Laser Microdissection Technique for the Study of a Spontaneous Metastatic Mammary Carcinoma Mouse Model by NanoString Technologies

PubMed Central

Saylor, Karen L.; Anver, Miriam R.; Salomon, David S.; Golubeva, Yelena G.

2016-01-01

Laser capture microdissection (LCM) of tissue is an established tool in medical research for collection of distinguished cell populations under direct microscopic visualization for molecular analysis. LCM samples have been successfully analyzed in a number of genomic and proteomic downstream molecular applications. However, LCM sample collection and preparation procedure has to be adapted to each downstream analysis platform. In this present manuscript we describe in detail the adaptation of LCM methodology for the collection and preparation of fresh frozen samples for NanoString analysis based on a study of a model of mouse mammary gland carcinoma and its lung metastasis. Our adaptation of LCM sample preparation and workflow to the requirements of the NanoString platform allowed acquiring samples with high RNA quality. The NanoString analysis of such samples provided sensitive detection of genes of interest and their associated molecular pathways. NanoString is a reliable gene expression analysis platform that can be effectively coupled with LCM. PMID:27077656

Adaptive microwave impedance memory effect in a ferromagnetic insulator.

PubMed

Lee, Hanju; Friedman, Barry; Lee, Kiejin

2016-12-14

Adaptive electronics, which are often referred to as memristive systems as they often rely on a memristor (memory resistor), are an emerging technology inspired by adaptive biological systems. Dissipative systems may provide a proper platform to implement an adaptive system due to its inherent adaptive property that parameters describing the system are optimized to maximize the entropy production for a given environment. Here, we report that a non-volatile and reversible adaptive microwave impedance memory device can be realized through the adaptive property of the dissipative structure of the driven ferromagnetic system. Like the memristive device, the microwave impedance of the device is modulated as a function of excitation microwave passing through the device. This kind of new device may not only helpful to implement adaptive information processing technologies, but also may be useful to investigate and understand the underlying mechanism of spontaneous formation of complex and ordered structures.

Adaptive microwave impedance memory effect in a ferromagnetic insulator

PubMed Central

Lee, Hanju; Friedman, Barry; Lee, Kiejin

2016-01-01

Adaptive electronics, which are often referred to as memristive systems as they often rely on a memristor (memory resistor), are an emerging technology inspired by adaptive biological systems. Dissipative systems may provide a proper platform to implement an adaptive system due to its inherent adaptive property that parameters describing the system are optimized to maximize the entropy production for a given environment. Here, we report that a non-volatile and reversible adaptive microwave impedance memory device can be realized through the adaptive property of the dissipative structure of the driven ferromagnetic system. Like the memristive device, the microwave impedance of the device is modulated as a function of excitation microwave passing through the device. This kind of new device may not only helpful to implement adaptive information processing technologies, but also may be useful to investigate and understand the underlying mechanism of spontaneous formation of complex and ordered structures. PMID:27966536

Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization

USDA-ARS?s Scientific Manuscript database

The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization. We investigated the molecular and structural similarities between Bla g 5, a major glutathione-S transferase (GST) allergen of cockroaches, and the GST of Wucherer...

The Case for "Story-Driven" Biology Education

ERIC Educational Resources Information Center

Schattner, Peter

2015-01-01

Can learning molecular biology and genetics be enjoyable? Of course it can. Biologists know their field is exciting and fascinating and that learning how cells and molecules shape the living world is extraordinarily interesting. But can students who are not already inclined towards science also be convinced that learning molecular biology is…

Mutation as a Stress Response and the Regulation of Evolvability

PubMed Central

Galhardo, Rodrigo S.; Hastings, P. J.; Rosenberg, Susan M.

2010-01-01

Our concept of a stable genome is evolving to one in which genomes are plastic and responsive to environmental changes. Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially accelerating adaptive evolution. The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes. The first is the regulation of mutagenesis in time by cellular stress responses, which promote random mutations specifically when cells are poorly adapted to their environments, i.e., when they are stressed. A second theme is the possible restriction of random mutagenesis in genomic space, achieved via coupling of mutation-generating machinery to local events such as DNA-break repair or transcription. Such localization may minimize accumulation of deleterious mutations in the genomes of rare fitter mutants, and promote local concerted evolution. Although mutagenesis induced by stresses other than direct damage to DNA was previously controversial, evidence for the existence of various stress-induced mutagenesis programs is now overwhelming and widespread. Such mechanisms probably fuel evolution of microbial pathogenesis and antibiotic-resistance, and tumor progression and chemotherapy resistance, all of which occur under stress, driven by mutations. The emerging commonalities in stress-induced-mutation mechanisms provide hope for new therapeutic interventions for all of these processes. PMID:17917874

Radiation of extant cetaceans driven by restructuring of the oceans.

PubMed

Steeman, Mette E; Hebsgaard, Martin B; Fordyce, R Ewan; Ho, Simon Y W; Rabosky, Daniel L; Nielsen, Rasmus; Rahbek, Carsten; Glenner, Henrik; Sørensen, Martin V; Willerslev, Eske

2009-12-01

The remarkable fossil record of whales and dolphins (Cetacea) has made them an exemplar of macroevolution. Although their overall adaptive transition from terrestrial to fully aquatic organisms is well known, this is not true for the radiation of modern whales. Here, we explore the diversification of extant cetaceans by constructing a robust molecular phylogeny that includes 87 of 89 extant species. The phylogeny and divergence times are derived from nuclear and mitochondrial markers, calibrated with fossils. We find that the toothed whales are monophyletic, suggesting that echolocation evolved only once early in that lineage some 36-34 Ma. The rorqual family (Balaenopteridae) is restored with the exclusion of the gray whale, suggesting that gulp feeding evolved 18-16 Ma. Delphinida, comprising all living dolphins and porpoises other than the Ganges/Indus dolphins, originated about 26 Ma; it contains the taxonomically rich delphinids, which began diversifying less than 11 Ma. We tested 2 hypothesized drivers of the extant cetacean radiation by assessing the tempo of lineage accumulation through time. We find no support for a rapid burst of speciation early in the history of extant whales, contrasting with expectations of an adaptive radiation model. However, we do find support for increased diversification rates during periods of pronounced physical restructuring of the oceans. The results imply that paleogeographic and paleoceanographic changes, such as closure of major seaways, have influenced the dynamics of radiation in extant cetaceans.

Dissociation of Circadian and Circatidal Timekeeping in the Marine Crustacean Eurydice pulchra

PubMed Central

Zhang, Lin; Hastings, Michael H.; Green, Edward W.; Tauber, Eran; Sladek, Martin; Webster, Simon G.; Kyriacou, Charalambos P.; Wilcockson, David C.

2013-01-01

Summary Background Tidal (12.4 hr) cycles of behavior and physiology adapt intertidal organisms to temporally complex coastal environments, yet their underlying mechanism is unknown. However, the very existence of an independent “circatidal” clock has been disputed, and it has been argued that tidal rhythms arise as a submultiple of a circadian clock, operating in dual oscillators whose outputs are held in antiphase i.e., ∼12.4 hr apart. Results We demonstrate that the intertidal crustacean Eurydice pulchra (Leach) exhibits robust tidal cycles of swimming in parallel to circadian (24 hr) rhythms in behavioral, physiological and molecular phenotypes. Importantly, ∼12.4 hr cycles of swimming are sustained in constant conditions, they can be entrained by suitable stimuli, and they are temperature compensated, thereby meeting the three criteria that define a biological clock. Unexpectedly, tidal rhythms (like circadian rhythms) are sensitive to pharmacological inhibition of Casein kinase 1, suggesting the possibility of shared clock substrates. However, cloning the canonical circadian genes of E. pulchra to provide molecular markers of circadian timing and also reagents to disrupt it by RNAi revealed that environmental and molecular manipulations that confound circadian timing do not affect tidal timing. Thus, competent circadian timing is neither an inevitable nor necessary element of tidal timekeeping. Conclusions We demonstrate that tidal rhythms are driven by a dedicated circatidal pacemaker that is distinct from the circadian system of E. pulchra, thereby resolving a long-standing debate regarding the nature of the circatidal mechanism. PMID:24076244

NMR data-driven structure determination using NMR-I-TASSER in the CASD-NMR experiment

PubMed Central

Jang, Richard; Wang, Yan

2015-01-01

NMR-I-TASSER, an adaption of the I-TASSER algorithm combining NMR data for protein structure determination, recently joined the second round of the CASD-NMR experiment. Unlike many molecular dynamics-based methods, NMR-I-TASSER takes a molecular replacement-like approach to the problem by first threading the target through the PDB to identify structural templates which are then used for iterative NOE assignments and fragment structure assembly refinements. The employment of multiple templates allows NMR-I-TASSER to sample different topologies while convergence to a single structure is not required. Retroactive and blind tests of the CASD-NMR targets from Rounds 1 and 2 demonstrate that even without using NOE peak lists I-TASSER can generate correct structure topology with 15 of 20 targets having a TM-score above 0.5. With the addition of NOE-based distance restraints, NMR-I-TASSER significantly improved the I-TASSER models with all models having the TM-score above 0.5. The average RMSD was reduced from 5.29 to 2.14 Å in Round 1 and 3.18 to 1.71 Å in Round 2. There is no obvious difference in the modeling results with using raw and refined peak lists, indicating robustness of the pipeline to the NOE assignment errors. Overall, despite the low-resolution modeling the current NMR-I-TASSER pipeline provides a coarse-grained structure folding approach complementary to traditional molecular dynamics simulations, which can produce fast near-native frameworks for atomic-level structural refinement. PMID:25737244

Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes.

PubMed

Reed-Geaghan, Erin G; Wright, Margaret C; See, Lauren A; Adelman, Peter C; Lee, Kuan Hsien; Koerber, H Richard; Maricich, Stephen M

2016-04-13

The extent to which the skin instructs peripheral somatosensory neuron maturation is unknown. We studied this question in Merkel cell-neurite complexes, where slowly adapting type I (SAI) neurons innervate skin-derived Merkel cells. Transgenic mice lacking Merkel cells had normal dorsal root ganglion (DRG) neuron numbers, but fewer DRG neurons expressed the SAI markers TrkB, TrkC, and Ret. Merkel cell ablation also decreased downstream TrkB signaling in DRGs, and altered the expression of genes associated with SAI development and function. Skin- and Merkel cell-specific deletion of Bdnf during embryogenesis, but not postnatal Bdnf deletion or Ntf3 deletion, reproduced these results. Furthermore, prototypical SAI electrophysiological signatures were absent from skin regions where Bdnf was deleted in embryonic Merkel cells. We conclude that BDNF produced by Merkel cells during a precise embryonic period guides SAI neuron development, providing the first direct evidence that the skin instructs sensory neuron molecular and functional maturation. Peripheral sensory neurons show incredible phenotypic and functional diversity that is initiated early by cell-autonomous and local environmental factors found within the DRG. However, the contribution of target tissues to subsequent sensory neuron development remains unknown. We show that Merkel cells are required for the molecular and functional maturation of the SAI neurons that innervate them. We also show that this process is controlled by BDNF signaling. These findings provide new insights into the regulation of somatosensory neuron development and reveal a novel way in which Merkel cells participate in mechanosensation. Copyright © 2016 the authors 0270-6474/16/364362-15$15.00/0.

Integrating evolutionary and functional approaches to infer adaptation at specific loci.

PubMed

Storz, Jay F; Wheat, Christopher W

2010-09-01

Inferences about adaptation at specific loci are often exclusively based on the static analysis of DNA sequence variation. Ideally,population-genetic evidence for positive selection serves as a stepping-off point for experimental studies to elucidate the functional significance of the putatively adaptive variation. We argue that inferences about adaptation at specific loci are best achieved by integrating the indirect, retrospective insights provided by population-genetic analyses with the more direct, mechanistic insights provided by functional experiments. Integrative studies of adaptive genetic variation may sometimes be motivated by experimental insights into molecular function, which then provide the impetus to perform population genetic tests to evaluate whether the functional variation is of adaptive significance. In other cases, studies may be initiated by genome scans of DNA variation to identify candidate loci for recent adaptation. Results of such analyses can then motivate experimental efforts to test whether the identified candidate loci do in fact contribute to functional variation in some fitness-related phenotype. Functional studies can provide corroborative evidence for positive selection at particular loci, and can potentially reveal specific molecular mechanisms of adaptation.

Modelling of particle-laden flow inside nanomaterials.

PubMed

Chan, Yue; Wylie, Jonathan J; Xia, Liang; Ren, Yong; Chen, Yung-Tsang

2016-08-01

In this paper, we demonstrate the usage of the Nernst-Planck equation in conjunction with mean-field theory to investigate particle-laden flow inside nanomaterials. Most theoretical studies in molecular encapsulation at the nanoscale do not take into account any macroscopic flow fields that are crucial in squeezing molecules into nanostructures. Here, a multi-scale idea is used to address this issue. The macroscopic transport of gas is described by the Nernst-Planck equation, whereas molecular interactions between gases and between the gas and the host material are described using a combination of molecular dynamics simulation and mean-field theory. In particular, we investigate flow-driven hydrogen storage inside doubly layered graphene sheets and graphene-oxide frameworks (GOFs). At room temperature and with slow velocity fields, we find that a single molecular layer is formed almost instantaneously on the inner surface of the graphene sheets, while molecular ligands between GOFs induce multi-layers. For higher velocities, multi-layers are also formed between graphene. For even larger velocities, the cavity of graphene is filled entirely with hydrogen, whereas for GOFs there exist two voids inside each periodic unit. The flow-driven hydrogen storage inside GOFs with various ligand densities is also investigated.

Modelling of particle-laden flow inside nanomaterials

NASA Astrophysics Data System (ADS)

Chan, Yue; Wylie, Jonathan J.; Xia, Liang; Ren, Yong; Chen, Yung-Tsang

2016-08-01

In this paper, we demonstrate the usage of the Nernst-Planck equation in conjunction with mean-field theory to investigate particle-laden flow inside nanomaterials. Most theoretical studies in molecular encapsulation at the nanoscale do not take into account any macroscopic flow fields that are crucial in squeezing molecules into nanostructures. Here, a multi-scale idea is used to address this issue. The macroscopic transport of gas is described by the Nernst-Planck equation, whereas molecular interactions between gases and between the gas and the host material are described using a combination of molecular dynamics simulation and mean-field theory. In particular, we investigate flow-driven hydrogen storage inside doubly layered graphene sheets and graphene-oxide frameworks (GOFs). At room temperature and with slow velocity fields, we find that a single molecular layer is formed almost instantaneously on the inner surface of the graphene sheets, while molecular ligands between GOFs induce multi-layers. For higher velocities, multi-layers are also formed between graphene. For even larger velocities, the cavity of graphene is filled entirely with hydrogen, whereas for GOFs there exist two voids inside each periodic unit. The flow-driven hydrogen storage inside GOFs with various ligand densities is also investigated.

Optical gain in an optically driven three-level ? system in atomic Rb vapor

NASA Astrophysics Data System (ADS)

Ballmann, C. W.; Yakovlev, V. V.

2018-06-01

In this work, we report experimentally achieved optical gain of a weak probe beam in a three-level ? system in a low density Rubidium vapor cell driven by a single pump beam. The maximum measured gain of the probe beam was about 0.12%. This work could lead to new approaches for enhancing molecular spectroscopy applications.

M(o)TOR of aging: MTOR as a universal molecular hypothalamus.

PubMed

Blagosklonny, Mikhail V

2013-07-01

A recent ground-breaking publication described hypothalamus-driven programmatic aging. As a Russian proverb goes "everything new is well-forgotten old". In 1958, Dilman proposed that aging and its related diseases are programmed by the hypothalamus. This theory, supported by beautiful experiments, remained unnoticed just to be re-discovered recently. Yet, it does not explain all manifestations of aging. And would organism age without hypothalamus? Do sensing pathways such as MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a "molecular hypothalamus" in every cell? Are hypothalamus-driven alterations simply a part of quasi-programmed aging manifested by hyperfunction and secondary signal-resistance? Here are some answers.

QTAIM and Stress Tensor Characterization of Intramolecular Interactions Along Dynamics Trajectories of a Light-Driven Rotary Molecular Motor.

PubMed

Wang, Lingling; Huan, Guo; Momen, Roya; Azizi, Alireza; Xu, Tianlv; Kirk, Steven R; Filatov, Michael; Jenkins, Samantha

2017-06-29

A quantum theory of atoms in molecules (QTAIM) and stress tensor analysis was applied to analyze intramolecular interactions influencing the photoisomerization dynamics of a light-driven rotary molecular motor. For selected nonadiabatic molecular dynamics trajectories characterized by markedly different S 1 state lifetimes, the electron densities were obtained using the ensemble density functional theory method. The analysis revealed that torsional motion of the molecular motor blades from the Franck-Condon point to the S 1 energy minimum and the S 1 /S 0 conical intersection is controlled by two factors: greater numbers of intramolecular bonds before the hop-time and unusually strongly coupled bonds between the atoms of the rotor and the stator blades. This results in the effective stalling of the progress along the torsional path for an extended period of time. This finding suggests a possibility of chemical tuning of the speed of photoisomerization of molecular motors and related molecular switches by reshaping their molecular backbones to decrease or increase the degree of coupling and numbers of intramolecular bond critical points as revealed by the QTAIM/stress tensor analysis of the electron density. Additionally, the stress tensor scalar and vector analysis was found to provide new methods to follow the trajectories, and from this, new insight was gained into the behavior of the S 1 state in the vicinity of the conical intersection.

Specialized Motor-Driven dusp1 Expression in the Song Systems of Multiple Lineages of Vocal Learning Birds

PubMed Central

Horita, Haruhito; Kobayashi, Masahiko; Liu, Wan-chun; Oka, Kotaro; Jarvis, Erich D.; Wada, Kazuhiro

2012-01-01

Mechanisms for the evolution of convergent behavioral traits are largely unknown. Vocal learning is one such trait that evolved multiple times and is necessary in humans for the acquisition of spoken language. Among birds, vocal learning is evolved in songbirds, parrots, and hummingbirds. Each time similar forebrain song nuclei specialized for vocal learning and production have evolved. This finding led to the hypothesis that the behavioral and neuroanatomical convergences for vocal learning could be associated with molecular convergence. We previously found that the neural activity-induced gene dual specificity phosphatase 1 (dusp1) was up-regulated in non-vocal circuits, specifically in sensory-input neurons of the thalamus and telencephalon; however, dusp1 was not up-regulated in higher order sensory neurons or motor circuits. Here we show that song motor nuclei are an exception to this pattern. The song nuclei of species from all known vocal learning avian lineages showed motor-driven up-regulation of dusp1 expression induced by singing. There was no detectable motor-driven dusp1 expression throughout the rest of the forebrain after non-vocal motor performance. This pattern contrasts with expression of the commonly studied activity-induced gene egr1, which shows motor-driven expression in song nuclei induced by singing, but also motor-driven expression in adjacent brain regions after non-vocal motor behaviors. In the vocal non-learning avian species, we found no detectable vocalizing-driven dusp1 expression in the forebrain. These findings suggest that independent evolutions of neural systems for vocal learning were accompanied by selection for specialized motor-driven expression of the dusp1 gene in those circuits. This specialized expression of dusp1 could potentially lead to differential regulation of dusp1-modulated molecular cascades in vocal learning circuits. PMID:22876306

Programmable snapping composites with bio-inspired architecture.

PubMed

Schmied, Jascha U; Le Ferrand, Hortense; Ermanni, Paolo; Studart, André R; Arrieta, Andres F

2017-03-13

The development of programmable self-shaping materials enables the onset of new and innovative functionalities in many application fields. Commonly, shape adaptation is achieved by exploiting diffusion-driven swelling or nano-scale phase transition, limiting the change of shape to slow motion predominantly determined by the environmental conditions and/or the materials specificity. To address these shortcomings, we report shape adaptable programmable shells that undergo morphing via a snap-through mechanism inspired by the Dionaea muscipula leaf, known as the Venus fly trap. The presented shells are composite materials made of epoxy reinforced by stiff anisotropic alumina micro-platelets oriented in specific directions. By tailoring the microstructure via magnetically-driven alignment of the platelets, we locally tune the pre-strain and stiffness anisotropy of the composite. This novel approach enables the fabrication of complex shapes showing non-orthotropic curvatures and stiffness gradients, radically extending the design space when compared to conventional long-fibre reinforced multi-stable composites. The rare combination of large stresses, short actuation times and complex shapes, results in hinge-free artificial shape adaptable systems with large design freedom for a variety of morphing applications.

Fast Outflow of Molecular Gas in the Seyfert Galaxy IC 5063

NASA Astrophysics Data System (ADS)

Morganti, Raffaella; Oosterloo, T.; Oonk, R.; Tadhunter, C.

2017-11-01

AGN-driven gas outflows may play an important role in the evolution of galaxies, as they impact on the growth on the central supermassive black hole as well on the star formation of the host galaxy. Much of the detailed physics of these gas outflows, and their actual impact on the host galaxy, is still not well understood. We present a detailed analysis, using ALMA observations, of the radio-jet driven outflow of molecular gas in the nearby radio-loud Seyfert galaxy IC 5063 which allows to derive important physical parameters of the gas and the outflow which, in turn, provide crucial input to numerical models. In recent years, a surprising result in the field of AGN-driven outflows has been that the cold phases of the gas (atomic and molecular) in some galaxies are the massive components of these outflows, despite the huge amounts of energy involved in driving these outflows. However, why most of the outflowing gas should be molecular/atomic, and in general, what are the physical conditions of the gas in the outflows and what really drives them, are still open questions. We present the results obtained from ALMA observations of multiple CO transitions and other molecules of what appears to be a textbook case of a jet-driven multi- phase outflow in the central regions of the Seyfert galaxy IC 5063. The data on multiple transitions allow us to derive the physical conditions in the different regions of the outflowing molecular gas. The signature of the impact of the radio jet is clearly seen in the spatial distribution of the excitation temperature and pressure of the outflowing gas, with the highest excitation and pressure found for the gas with the highest outflow velocities. We obtain a detailed three- dimensional picture of the outflow, and its kinematics, and find that outflowing molecular gas is present across the entire region co-spatial with the radio plasma, providing unambiguous evidence that the radio jets/cocoon are responsible for the outflow. The detailed information about the physical condition of the gas in a fast outflow will serve as template for the signatures of the impact of a radio plasma jet on a gas-rich ISM and its associated star formation, and guide the studies of outflows in other galaxies, including higher redshift objects.

Sequence-Based Analysis of Thermal Adaptation and Protein Energy Landscapes in an Invasive Blue Mussel (Mytilus galloprovincialis).

PubMed

Saarman, Norah P; Kober, Kord M; Simison, W Brian; Pogson, Grant H

2017-10-01

Adaptive responses to thermal stress in poikilotherms plays an important role in determining competitive ability and species distributions. Amino acid substitutions that affect protein stability and modify the thermal optima of orthologous proteins may be particularly important in this context. Here, we examine a set of 2,770 protein-coding genes to determine if proteins in a highly invasive heat tolerant blue mussel (Mytilus galloprovincialis) contain signals of adaptive increases in protein stability relative to orthologs in a more cold tolerant M. trossulus. Such thermal adaptations might help to explain, mechanistically, the success with which the invasive marine mussel M. galloprovincialis has displaced native species in contact zones in the eastern (California) and western (Japan) Pacific. We tested for stabilizing amino acid substitutions in warm tolerant M. galloprovincialis relative to cold tolerant M. trossulus with a generalized linear model that compares in silico estimates of recent changes in protein stability among closely related congeners. Fixed substitutions in M. galloprovincialis were 3,180.0 calories per mol per substitution more stabilizing at genes with both elevated dN/dS ratios and transcriptional responses to heat stress, and 705.8 calories per mol per substitution more stabilizing across all 2,770 loci investigated. Amino acid substitutions concentrated in a small number of genes were more stabilizing in M. galloprovincialis compared with cold tolerant M. trossulus. We also tested for, but did not find, enrichment of a priori GO terms in genes with elevated dN/dS ratios in M. galloprovincialis. This might indicate that selection for thermodynamic stability is generic across all lineages, and suggests that the high change in estimated protein stability that we observed in M. galloprovincialis is driven by selection for extra stabilizing substitutions, rather than by higher incidence of selection in a greater number of genes in this lineage. Nonetheless, our finding of more stabilizing amino acid changes in the warm adapted lineage is important because it suggests that adaption for thermal stability has contributed to M. galloprovincialis' superior tolerance to heat stress, and that pairing tests for positive selection and tests for transcriptional response to heat stress can identify candidates of protein stability adaptation. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Impacts of Various Environments Factors and Adaptive Management Strategies on Food Crops in the 21st Century Based on a Land Surface Model

NASA Astrophysics Data System (ADS)

Jain, A. K.; Lin, T. S.; Lawrence, P.; Kheshgi, H. S.

2017-12-01

Environmental factors - characterized by increasing levels of CO2, and changes in temperature and precipitation patterns - present potential risks to global food supply. To date, understanding of environmental factors' effects on crop production remains uncertain due to (1) uncertainties in projected trends of these factors and their spatial and temporal variability; (2) uncertainties in the physiological, genetic and molecular basis of crop adaptation to adaptive management practices (e.g. change in planting time, irrigation and N fertilization etc.) and (3) uncertainties in current land surface models to estimate the response of crop production to changes in environmental factors and management strategies. In this study we apply a process-based land surface model, the Integrated Science Assessment model (ISAM), to assess the impact of various environmental factors and management strategies on the production of row crops (corn, soybean and wheat) at regional and global scales. Results are compared to corresponding simulations performed with the crop model in the Community Land Model (CLM4.5). Each model is driven with historical atmospheric forcing data (1901-2005), and projected atmospheric forcing data under RCP 4.5 or RCP 8.5 (2006-2100) from CESM CMIP5 simulations to estimate the effects of different climate change projections on potential productivity of food crops at a global scale. For each set of atmospheric forcing data, production of each crop is simulated with and without inclusion of adaptive management practices (e.g. application of irrigation, N fertilization, change in planting time and crop cultivars etc.) to assess the effect of adaptation on projected crop production over the 21st century. In detail, three questions are addressed: (1) what is the impact of different climate change projections on global crop production; (2) what is the effect of adaptive management practices on projected crop production; and (3) how do differences in model mechanisms in ISAM and CLM4.5 impact projected global crop production and adaptive management practices (irrigation and N fertilizer) over the 21st century. The major outcomes of this study will help to understand the uncertainties in potential productivity of food crops under different environmental conditions and management practices.

Operationalising resilience in longitudinal studies: a systematic review of methodological approaches.

PubMed

Cosco, T D; Kaushal, A; Hardy, R; Richards, M; Kuh, D; Stafford, M

2017-01-01

Over the life course, we are invariably faced with some form of adversity. The process of positively adapting to adverse events is known as 'resilience'. Despite the acknowledgement of 2 common components of resilience, that is, adversity and positive adaptation, no consensus operational definition has been agreed. Resilience operationalisations have been reviewed in a cross-sectional context; however, a review of longitudinal methods of operationalising resilience has not been conducted. The present study conducts a systematic review across Scopus and Web of Science capturing studies of ageing that posited operational definitions of resilience in longitudinal studies of ageing. Thirty-six studies met inclusion criteria. Non-acute events, for example, cancer, were the most common form of adversity identified and psychological components, for example, the absence of depression, the most common forms of positive adaptation. Of the included studies, 4 used psychometrically driven methods, that is, repeated administration of established resilience metrics, 9 used definition-driven methods, that is, a priori establishment of resilience components and criteria, and 23 used data-driven methods, that is, techniques that identify resilient individuals using latent variable models. Acknowledging the strengths and limitations of each operationalisation is integral to the appropriate application of these methods to life course and longitudinal resilience research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Statistical Inference for Data Adaptive Target Parameters.

PubMed

Hubbard, Alan E; Kherad-Pajouh, Sara; van der Laan, Mark J

2016-05-01

Consider one observes n i.i.d. copies of a random variable with a probability distribution that is known to be an element of a particular statistical model. In order to define our statistical target we partition the sample in V equal size sub-samples, and use this partitioning to define V splits in an estimation sample (one of the V subsamples) and corresponding complementary parameter-generating sample. For each of the V parameter-generating samples, we apply an algorithm that maps the sample to a statistical target parameter. We define our sample-split data adaptive statistical target parameter as the average of these V-sample specific target parameters. We present an estimator (and corresponding central limit theorem) of this type of data adaptive target parameter. This general methodology for generating data adaptive target parameters is demonstrated with a number of practical examples that highlight new opportunities for statistical learning from data. This new framework provides a rigorous statistical methodology for both exploratory and confirmatory analysis within the same data. Given that more research is becoming "data-driven", the theory developed within this paper provides a new impetus for a greater involvement of statistical inference into problems that are being increasingly addressed by clever, yet ad hoc pattern finding methods. To suggest such potential, and to verify the predictions of the theory, extensive simulation studies, along with a data analysis based on adaptively determined intervention rules are shown and give insight into how to structure such an approach. The results show that the data adaptive target parameter approach provides a general framework and resulting methodology for data-driven science.

An autonomous chemically fuelled small-molecule motor

NASA Astrophysics Data System (ADS)

Wilson, Miriam R.; Solà, Jordi; Carlone, Armando; Goldup, Stephen M.; Lebrasseur, Nathalie; Leigh, David A.

2016-06-01

Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.

Left-right asymmetry specification in amphioxus: review and prospects.

PubMed

Soukup, Vladimir

2017-01-01

Extant bilaterally symmetrical animals usually show asymmetry in the arrangement of their inner organs. However, the exaggerated left-right (LR) asymmetry in amphioxus represents a true peculiarity among them. The amphioxus larva shows completely disparate fates of left and right body sides, so that organs associated with pharynx are either positioned exclusively on the left or on the right side. Moreover, segmented paraxial structures such as muscle blocks and their neuronal innervation show offset arrangement between the sides making it difficult to propose any explanation or adaptivity to larval and adult life. First LR asymmetries can be traced back to an early embryonic period when morphological asymmetries are preceded by molecular asymmetries driven by the action of the Nodal signaling pathway. This review sums up recent advances in understanding LR asymmetry specification in amphioxus and proposes upstream events that may regulate asymmetric Nodal signaling. These events include the presence of the vertebrate-like LR organizer and a cilia-driven fluid flow that may be involved in the breaking of bilateral symmetry. The upstream pathways comprising the ion flux, Delta/Notch, Wnt/β-catenin and Wnt/PCP are hypothesized to regulate both formation of the LR organizer and expression of the downstream Nodal signaling pathway genes. These suggestions are in line with what we know from vertebrate and ambulacrarian LR axis specification and are directly testable by experimental manipulations. Thanks to the phylogenetic position of amphioxus, the proposed mechanisms may be helpful in understanding the evolution of LR axis specification across deuterostomes.

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

PubMed Central

Chitsazzadeh, Vida; Coarfa, Cristian; Drummond, Jennifer A.; Nguyen, Tri; Joseph, Aaron; Chilukuri, Suneel; Charpiot, Elizabeth; Adelmann, Charles H.; Ching, Grace; Nguyen, Tran N.; Nicholas, Courtney; Thomas, Valencia D.; Migden, Michael; MacFarlane, Deborah; Thompson, Erika; Shen, Jianjun; Takata, Yoko; McNiece, Kayla; Polansky, Maxim A.; Abbas, Hussein A.; Rajapakshe, Kimal; Gower, Adam; Spira, Avrum; Covington, Kyle R.; Xiao, Weimin; Gunaratne, Preethi; Pickering, Curtis; Frederick, Mitchell; Myers, Jeffrey N.; Shen, Li; Yao, Hui; Su, Xiaoping; Rapini, Ronald P.; Wheeler, David A.; Hawk, Ernest T.; Flores, Elsa R.; Tsai, Kenneth Y.

2016-01-01

Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. PMID:27574101

Polyvinylpyrrolidone-induced anisotropic growth of gold nanoprisms in plasmon-driven synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, Yueming; DuChene, Joseph S.; Wang, Yi-Chung

After more than a decade, it is still unknown whether the plasmon-mediated growth of silver nanostructures can be extended to the synthesis of other noble metals, as the molecular mechanisms governing the growth process remain elusive. Herein, we demonstrate the plasmon-driven synthesis of gold nanoprisms and elucidate the details of the photochemical growth mechanism at the single-nanoparticle level. Our investigation reveals that the surfactant polyvinylpyrrolidone preferentially adsorbs along the nanoprism perimeter and serves as a photochemical relay to direct the anisotropic growth of gold nanoprisms. This discovery confers a unique function to polyvinylpyrrolidone that is fundamentally diferent from its widelymore » accepted role as a crystal-face-blocking ligand. Additionally, we find that nanocrystal twinning exerts a profound influence on the kinetics of this photochemical process by controlling the transport of plasmon-generated hot electrons to polyvinylpyrrolidone. These insights establish a molecular-level description of the underlying mechanisms regulating the plasmon-driven synthesis of gold nanoprisms.« less

Polyvinylpyrrolidone-induced anisotropic growth of gold nanoprisms in plasmon-driven synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, Yueming; DuChene, Joseph S.; Wang, Yi-Chung

After more than a decade, it is still unknown whether the plasmon-mediated growth of silver nanostructures can be extended to the synthesis of other noble metals, as the molecular mechanisms governing the growth process remain elusive. In this paper, we demonstrate the plasmon-driven synthesis of gold nanoprisms and elucidate the details of the photochemical growth mechanism at the single-nanoparticle level. Our investigation reveals that the surfactant polyvinylpyrrolidone preferentially adsorbs along the nanoprism perimeter and serves as a photochemical relay to direct the anisotropic growth of gold nanoprisms. This discovery confers a unique function to polyvinylpyrrolidone that is fundamentally different frommore » its widely accepted role as a crystal-face-blocking ligand. Additionally, we find that nanocrystal twinning exerts a profound influence on the kinetics of this photochemical process by controlling the transport of plasmon-generated hot electrons to polyvinylpyrrolidone. Finally, these insights establish a molecular-level description of the underlying mechanisms regulating the plasmon-driven synthesis of gold nanoprisms.« less

AnchorDock: Blind and Flexible Anchor-Driven Peptide Docking.

PubMed

Ben-Shimon, Avraham; Niv, Masha Y

2015-05-05

The huge conformational space stemming from the inherent flexibility of peptides is among the main obstacles to successful and efficient computational modeling of protein-peptide interactions. Current peptide docking methods typically overcome this challenge using prior knowledge from the structure of the complex. Here we introduce AnchorDock, a peptide docking approach, which automatically targets the docking search to the most relevant parts of the conformational space. This is done by precomputing the free peptide's structure and by computationally identifying anchoring spots on the protein surface. Next, a free peptide conformation undergoes anchor-driven simulated annealing molecular dynamics simulations around the predicted anchoring spots. In the challenging task of a completely blind docking test, AnchorDock produced exceptionally good results (backbone root-mean-square deviation ≤ 2.2Å, rank ≤15) for 10 of 13 unbound cases tested. The impressive performance of AnchorDock supports a molecular recognition pathway that is driven via pre-existing local structural elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Polyvinylpyrrolidone-induced anisotropic growth of gold nanoprisms in plasmon-driven synthesis

DOE PAGES

Zhai, Yueming; DuChene, Joseph S.; Wang, Yi-Chung; ...

2016-07-04

After more than a decade, it is still unknown whether the plasmon-mediated growth of silver nanostructures can be extended to the synthesis of other noble metals, as the molecular mechanisms governing the growth process remain elusive. In this paper, we demonstrate the plasmon-driven synthesis of gold nanoprisms and elucidate the details of the photochemical growth mechanism at the single-nanoparticle level. Our investigation reveals that the surfactant polyvinylpyrrolidone preferentially adsorbs along the nanoprism perimeter and serves as a photochemical relay to direct the anisotropic growth of gold nanoprisms. This discovery confers a unique function to polyvinylpyrrolidone that is fundamentally different frommore » its widely accepted role as a crystal-face-blocking ligand. Additionally, we find that nanocrystal twinning exerts a profound influence on the kinetics of this photochemical process by controlling the transport of plasmon-generated hot electrons to polyvinylpyrrolidone. Finally, these insights establish a molecular-level description of the underlying mechanisms regulating the plasmon-driven synthesis of gold nanoprisms.« less

Statistical and molecular analyses of evolutionary significance of red-green color vision and color blindness in vertebrates.

PubMed

Yokoyama, Shozo; Takenaka, Naomi

2005-04-01

Red-green color vision is strongly suspected to enhance the survival of its possessors. Despite being red-green color blind, however, many species have successfully competed in nature, which brings into question the evolutionary advantage of achieving red-green color vision. Here, we propose a new method of identifying positive selection at individual amino acid sites with the premise that if positive Darwinian selection has driven the evolution of the protein under consideration, then it should be found mostly at the branches in the phylogenetic tree where its function had changed. The statistical and molecular methods have been applied to 29 visual pigments with the wavelengths of maximal absorption at approximately 510-540 nm (green- or middle wavelength-sensitive [MWS] pigments) and at approximately 560 nm (red- or long wavelength-sensitive [LWS] pigments), which are sampled from a diverse range of vertebrate species. The results show that the MWS pigments are positively selected through amino acid replacements S180A, Y277F, and T285A and that the LWS pigments have been subjected to strong evolutionary conservation. The fact that these positively selected M/LWS pigments are found not only in animals with red-green color vision but also in those with red-green color blindness strongly suggests that both red-green color vision and color blindness have undergone adaptive evolution independently in different species.

AMR Studies of Star Formation: Simulations and Simulated Observations

NASA Astrophysics Data System (ADS)

Offner, Stella; McKee, C. F.; Klein, R. I.

2009-01-01

Molecular clouds are typically observed to be approximately virialized with gravitational and turbulent energy in balance, yielding a star formation rate of a few percent. The origin and characteristics of the observed supersonic turbulence are poorly understood, and without continued energy injection the turbulence is predicted to decay within a cloud dynamical time. Recent observations and analytic work have suggested a strong connection between the initial stellar mass function, the core mass function, and turbulence characteristics. The role of magnetic fields in determining core lifetimes, shapes, and kinematic properties remains hotly debated. Simulations are a formidable tool for studying the complex process of star formation and addressing these puzzles. I present my results modeling low-mass star formation using the ORION adaptive mesh refinement (AMR) code. I investigate the properties of forming cores and protostars in simulations in which the turbulence is driven to maintain virial balance and where it is allowed to decay. I will discuss simulated observations of cores in dust emission and in molecular tracers and compare to observations of local star-forming clouds. I will also present results from ORION cluster simulations including flux-limited diffusion radiative transfer and show that radiative feedback, even from low-mass stars, has a significant effect on core fragmentation, disk properties, and the IMF. Finally, I will discuss the new simulation frontier of AMR multigroup radiative transfer.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups

PubMed Central

Curtis, Christina; Shah, Sohrab P.; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M.; Dunning, Mark J.; Speed, Doug; Lynch, Andy G.; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D.; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-01-01

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome. PMID:22522925

Application of Petri Nets in Bone Remodeling

PubMed Central

Li, Lingxi; Yokota, Hiroki

2009-01-01

Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs) have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs), which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings. PMID:19838338

Star formation induced by cloud-cloud collisions and galactic giant molecular cloud evolution

NASA Astrophysics Data System (ADS)

Kobayashi, Masato I. N.; Kobayashi, Hiroshi; Inutsuka, Shu-ichiro; Fukui, Yasuo

2018-05-01

Recent millimeter/submillimeter observations towards nearby galaxies have started to map the whole disk and to identify giant molecular clouds (GMCs) even in the regions between galactic spiral structures. Observed variations of GMC mass functions in different galactic environments indicates that massive GMCs preferentially reside along galactic spiral structures whereas inter-arm regions have many small GMCs. Based on the phase transition dynamics from magnetized warm neutral medium to molecular clouds, Kobayashi et al. (2017, ApJ, 836, 175) proposes a semi-analytical evolutionary description for GMC mass functions including a cloud-cloud collision (CCC) process. Their results show that CCC is less dominant in shaping the mass function of GMCs than the accretion of dense H I gas driven by the propagation of supersonic shock waves. However, their formulation does not take into account the possible enhancement of star formation by CCC. Millimeter/submillimeter observations within the Milky Way indicate the importance of CCC in the formation of star clusters and massive stars. In this article, we reformulate the time-evolution equation largely modified from Kobayashi et al. (2017, ApJ, 836, 175) so that we additionally compute star formation subsequently taking place in CCC clouds. Our results suggest that, although CCC events between smaller clouds are more frequent than the ones between massive GMCs, CCC-driven star formation is mostly driven by massive GMCs ≳ 10^{5.5} M_{⊙} (where M⊙ is the solar mass). The resultant cumulative CCC-driven star formation may amount to a few 10 percent of the total star formation in the Milky Way and nearby galaxies.

Natural Selection and Adaptive Evolution of Leptin in the Ochotona Family Driven by the Cold Environmental Stress

PubMed Central

Yang, Jie; Wang, Zhen Long; Zhao, Xin Quan; Wang, De Peng; Qi, De Lin; Xu, Bao Hong; Ren, Yong Hong; Tian, Hui Fang

2008-01-01

Background Environmental stress can accelerate the evolutionary rate of specific stress-response proteins and create new functions specialized for different environments, enhancing an organism's fitness to stressful environments. Pikas (order Lagomorpha), endemic, non-hibernating mammals in the modern Holarctic Region, live in cold regions at either high altitudes or high latitudes and have a maximum distribution of species diversification confined to the Qinghai-Tibet Plateau. Variations in energy metabolism are remarkable for them living in cold environments. Leptin, an adipocyte-derived hormone, plays important roles in energy homeostasis. Methodology/Principal Findings To examine the extent of leptin variations within the Ochotona family, we cloned the entire coding sequence of pika leptin from 6 species in two regions (Qinghai-Tibet Plateau and Inner Mongolia steppe in China) and the leptin sequences of plateau pikas (O. curzonia) from different altitudes on Qinghai-Tibet Plateau. We carried out both DNA and amino acid sequence analyses in molecular evolution and compared modeled spatial structures. Our results show that positive selection (PS) acts on pika leptin, while nine PS sites located within the functionally significant segment 85-119 of leptin and one unique motif appeared only in pika lineages-the ATP synthase α and β subunit signature site. To reveal the environmental factors affecting sequence evolution of pika leptin, relative rate test was performed in pikas from different altitudes. Stepwise multiple regression shows that temperature is significantly and negatively correlated with the rates of non-synonymous substitution (Ka) and amino acid substitution (Aa), whereas altitude does not significantly affect synonymous substitution (Ks), Ka and Aa. Conclusions/Significance Our findings support the viewpoint that adaptive evolution may occur in pika leptin, which may play important roles in pikas' ecological adaptation to extreme environmental stress. We speculate that cold, and probably not hypoxia, may be the primary environmental factor for driving adaptive evolution of pika leptin. PMID:18213380

The importance of immune gene variability (MHC) in evolutionary ecology and conservation

PubMed Central

Sommer, Simone

2005-01-01

Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of adaptive genetic variability with respect to human impact and conservation, and implications for future studies. PMID:16242022

Laser-driven clockwise molecular rotation for a transient spinning waveplate.

PubMed

York, Andrew G

2009-08-03

Our simulations show a copropagating pair of laser pulses polarized in two different directions can selectively excite clockwise or counterclockwise molecular rotation in a gas of linear molecules. The resulting birefringence of the gas rotates on a femtosecond timescale and shows a periodic revival structure. The total duration of the pulse pair can be subpicosecond, allowing molecular alignment at the high densities and temperatures necessary to create a transient spinning waveplate.

Integrative pathway knowledge bases as a tool for systems molecular medicine.

PubMed

Liang, Mingyu

2007-08-20

There exists a sense of urgency to begin to generate a cohesive assembly of biomedical knowledge as the pace of knowledge accumulation accelerates. The urgency is in part driven by the emergence of systems molecular medicine that emphasizes the combination of systems analysis and molecular dissection in the future of medical practice and research. A potentially powerful approach is to build integrative pathway knowledge bases that link organ systems function with molecules.

Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing.

PubMed

Hong, Jungeui; Gresham, David

2017-11-01

Quantitative analysis of next-generation sequencing (NGS) data requires discriminating duplicate reads generated by PCR from identical molecules that are of unique origin. Typically, PCR duplicates are identified as sequence reads that align to the same genomic coordinates using reference-based alignment. However, identical molecules can be independently generated during library preparation. Misidentification of these molecules as PCR duplicates can introduce unforeseen biases during analyses. Here, we developed a cost-effective sequencing adapter design by modifying Illumina TruSeq adapters to incorporate a unique molecular identifier (UMI) while maintaining the capacity to undertake multiplexed, single-index sequencing. Incorporation of UMIs into TruSeq adapters (TrUMIseq adapters) enables identification of bona fide PCR duplicates as identically mapped reads with identical UMIs. Using TrUMIseq adapters, we show that accurate removal of PCR duplicates results in improved accuracy of both allele frequency (AF) estimation in heterogeneous populations using DNA sequencing and gene expression quantification using RNA-Seq.

Climbing plants: attachment adaptations and bioinspired innovations.

PubMed

Burris, Jason N; Lenaghan, Scott C; Stewart, C Neal

2018-04-01

Climbing plants have unique adaptations to enable them to compete for sunlight, for which they invest minimal resources for vertical growth. Indeed, their stems bear relatively little weight, as they traverse their host substrates skyward. Climbers possess high tensile strength and flexibility, which allows them to utilize natural and manmade structures for support and growth. The climbing strategies of plants have intrigued scientists for centuries, yet our understanding about biochemical adaptations and their molecular undergirding is still in the early stages of research. Nonetheless, recent discoveries are promising, not only from a basic knowledge perspective, but also for bioinspired product development. Several adaptations, including nanoparticle and adhesive production will be reviewed, as well as practical translation of these adaptations to commercial applications. We will review the botanical literature on the modes of adaptation to climb, as well as specialized organs-and cellular innovations. Finally, recent molecular and biochemical data will be reviewed to assess the future needs and new directions for potential practical products that may be bioinspired by climbing plants.

Toward Hamiltonian Adaptive QM/MM: Accurate Solvent Structures Using Many-Body Potentials.

PubMed

Boereboom, Jelle M; Potestio, Raffaello; Donadio, Davide; Bulo, Rosa E

2016-08-09

Adaptive quantum mechanical (QM)/molecular mechanical (MM) methods enable efficient molecular simulations of chemistry in solution. Reactive subregions are modeled with an accurate QM potential energy expression while the rest of the system is described in a more approximate manner (MM). As solvent molecules diffuse in and out of the reactive region, they are gradually included into (and excluded from) the QM expression. It would be desirable to model such a system with a single adaptive Hamiltonian, but thus far this has resulted in distorted structures at the boundary between the two regions. Solving this long outstanding problem will allow microcanonical adaptive QM/MM simulations that can be used to obtain vibrational spectra and dynamical properties. The difficulty lies in the complex QM potential energy expression, with a many-body expansion that contains higher order terms. Here, we outline a Hamiltonian adaptive multiscale scheme within the framework of many-body potentials. The adaptive expressions are entirely general, and complementary to all standard (nonadaptive) QM/MM embedding schemes available. We demonstrate the merit of our approach on a molecular system defined by two different MM potentials (MM/MM'). For the long-range interactions a numerical scheme is used (particle mesh Ewald), which yields energy expressions that are many-body in nature. Our Hamiltonian approach is the first to provide both energy conservation and the correct solvent structure everywhere in this system.

Empirically Supported Interventions for Sexual and Gender Minority Youth.

PubMed

Austin, Ashley; Craig, Shelley L

2015-01-01

When empirically supported treatments (ESTs) are effectively adapted for use with minority populations, they may be more efficacious. As such, there is a need to adapt existing ESTs for use with diverse sexual and gender minority youth (SGMY). The unique bias-based challenges faced by SGMY require the integration of affirmative practices into ESTs to effectively address the specific needs of this underserved group of youth. The primary purpose of the authors in this article is to present a clearly articulated stakeholder driven model for developing an affirmative adapted version of cognitive behavioral therapy (CBT) for use with diverse SGMY. The authors' approach to adaptation follows the "adapt and evaluate" framework for enhancing cultural congruence of interventions for minority groups. A community based participatory research approach, consistent with a stakeholder driven process, is utilized to develop the intervention from the ground up through the voices of the target community. Researchers conducted 3 focus groups with culturally diverse SGMY to explore salient aspects of youths' cultural and SGM identities in order to inform the intervention and ensure its applicability to a wide range of SGMY. Focus group data is analyzed and integrated into an existing group-based CBT intervention. The following themes emerge as critical to affirmative work with diverse SGMY: (1) the interplay between cultural norms, gender norms, sexual orientation, and gender identity; (2) the complex role of religious community within the lives of SGMY; and (3) consideration of extended family and cultural community as youth navigate their SGM identities.

Sources and Sinks: A Stochastic Model of Evolution in Heterogeneous Environments

NASA Astrophysics Data System (ADS)

Hermsen, Rutger; Hwa, Terence

2010-12-01

We study evolution driven by spatial heterogeneity in a stochastic model of source-sink ecologies. A sink is a habitat where mortality exceeds reproduction so that a local population persists only due to immigration from a source. Immigrants can, however, adapt to conditions in the sink by mutation. To characterize the adaptation rate, we derive expressions for the first arrival time of adapted mutants. The joint effects of migration, mutation, birth, and death result in two distinct parameter regimes. These results may pertain to the rapid evolution of drug-resistant pathogens and insects.

Age and Adaptive Functioning in Children and Adolescents with ASD: The Effects of Intellectual Functioning and ASD Symptom Severity.

PubMed

Hill, Trenesha L; Gray, Sarah A O; Kamps, Jodi L; Enrique Varela, R

2015-12-01

The present study examined the moderating effects of intellectual functioning and ASD symptom severity on the relation between age and adaptive functioning in 220 youth with autism spectrum disorder (ASD). Regression analysis indicated that intellectual functioning and ASD symptom severity moderated the relation between age and adaptive functioning. For younger children with lower intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Similarly, for older children with higher intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Analyses by subscales suggest that this pattern is driven by the Conceptual subscale. Clinical and research implications are discussed.

Age and Adaptive Functioning in Children and Adolescents with ASD: The Effects of Intellectual Functioning and ASD Symptom Severity

PubMed Central

Hill, Trenesha L.; Gray, Sarah A. O.; Kamps, Jodi L.; Varela, R. Enrique

2016-01-01

The present study examined the moderating effects of intellectual functioning and ASD symptom severity on the relation between age and adaptive functioning in 220 youth with autism spectrum disorder (ASD). Regression analysis indicated that intellectual functioning and ASD symptom severity moderated the relation between age and adaptive functioning. For younger children with lower intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Similarly, for older children with higher intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Analyses by subscales suggest that this pattern is driven by the Conceptual subscale. Clinical and research implications are discussed. PMID:26174048

A Distributed Value of Information (VoI)-Based Approach for Mission-Adaptive Context-Aware Information Management and Presentation

DTIC Science & Technology

2016-05-16

metrics involve regulating automation of complex systems , such as aircraft .12 Additionally, adaptive management of content in user interfaces has also...both the user and environmental context would aid in deciding how to present the information to the Warfighter. The prototype system currently...positioning system , and rate sensors can provide user - specific context to disambiguate physiologic data. The consumer “quantified self” market has driven

Mudskippers and Their Genetic Adaptations to an Amphibious Lifestyle.

PubMed

You, Xinxin; Sun, Min; Li, Jia; Bian, Chao; Chen, Jieming; Yi, Yunhai; Yu, Hui; Shi, Qiong

2018-02-07

Mudskippers are the largest group of amphibious teleost fish that are uniquely adapted to live on mudflats. During their successful transition from aqueous life to terrestrial living, these fish have evolved morphological and physiological modifications of aerial vision and olfaction, higher ammonia tolerance, aerial respiration, improved immunological defense against terrestrial pathogens, and terrestrial locomotion using protruded pectoral fins. Comparative genomic and transcriptomic data have been accumulated and analyzed for understanding molecular mechanisms of the terrestrial adaptations. Our current review provides a general introduction to mudskippers and recent research advances of their genetic adaptations to the amphibious lifestyle, which will be helpful for understanding the evolutionary transition of vertebrates from water to land. Our insights into the genomes and transcriptomes will also support molecular breeding, functional identification, and natural compound screening.

Hybrid vehicle powertrain system with power take-off driven vehicle accessory

DOEpatents

Beaty, Kevin D.; Bockelmann, Thomas R.; Zou, Zhanijang; Hope, Mark E.; Kang, Xiaosong; Carpenter, Jeffrey L.

2006-09-12

A hybrid vehicle powertrain system includes a first prime mover, a first prime mover driven power transmission mechanism having a power take-off adapted to drive a vehicle accessory, and a second prime mover. The second prime mover is operable to drive the power transmission mechanism alone or in combination with the first prime mover to provide power to the power take-off through the power transmission mechanism. The invention further includes methods for operating a hybrid vehicle powertrain system.

Tension Stiffened and Tendon Actuated Manipulator

NASA Technical Reports Server (NTRS)

Dorsey, John T. (Inventor); Mercer, Charles D. (Inventor); Ganoe, George G. (Inventor); Doggett, William R. (Inventor); King, Bruce D. (Inventor); Jones, Thomas C. (Inventor); Corbin, Cole K. (Inventor)

2015-01-01

A tension stiffened and tendon actuated manipulator is provided performing robotic-like movements when acquiring a payload. The manipulator design can be adapted for use in-space, lunar or other planetary installations as it is readily configurable for acquiring and precisely manipulating a payload in both a zero-g environment and in an environment with a gravity field. The manipulator includes a plurality of link arms, a hinge connecting adjacent link arms together to allow the adjacent link arms to rotate relative to each other and a cable actuation and tensioning system provided between adjacent link arms. The cable actuation and tensioning system includes a spreader arm and a plurality of driven and non-driven elements attached to the link arms and the spreader arm. At least one cable is routed around the driven and non-driven elements for actuating the hinge.

Photoperiodic growth control in perennial trees.

PubMed

Azeez, Abdul; Sane, Aniruddha P

2015-01-01

Plants have to cope with changing seasons and adverse environmental conditions. Being sessile, plants have developed elaborate mechanisms for their survival that allow them to sense and adapt to the environment and reproduce successfully. A major adaptive trait for the survival of trees of temperate and boreal forests is the induction of growth cessation in anticipation of winters. In the last few years enormous progress has been made to elucidate the molecular mechanisms underlying SDs induced growth cessation in model perennial tree hybrid aspen (Populus tremula × P. tremuloides). In this review we discuss the molecular mechanism underlying photoperiodic control of growth cessation and adaptive responses.

A cascade reaction network mimicking the basic functional steps of adaptive immune response

NASA Astrophysics Data System (ADS)

Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

2015-10-01

Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

Non-orthogonal spin-adaptation of coupled cluster methods: A new implementation of methods including quadruple excitations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthews, Devin A., E-mail: dmatthews@utexas.edu; Stanton, John F.

2015-02-14

The theory of non-orthogonal spin-adaptation for closed-shell molecular systems is applied to coupled cluster methods with quadruple excitations (CCSDTQ). Calculations at this level of detail are of critical importance in describing the properties of molecular systems to an accuracy which can meet or exceed modern experimental techniques. Such calculations are of significant (and growing) importance in such fields as thermodynamics, kinetics, and atomic and molecular spectroscopies. With respect to the implementation of CCSDTQ and related methods, we show that there are significant advantages to non-orthogonal spin-adaption with respect to simplification and factorization of the working equations and to creating anmore » efficient implementation. The resulting algorithm is implemented in the CFOUR program suite for CCSDT, CCSDTQ, and various approximate methods (CCSD(T), CC3, CCSDT-n, and CCSDT(Q))« less

Current fluctuations in periodically driven systems

NASA Astrophysics Data System (ADS)

Barato, Andre C.; Chetrite, Raphael

2018-05-01

Small nonequelibrium systems driven by an external periodic protocol can be described by Markov processes with time-periodic transition rates. In general, current fluctuations in such small systems are large and may play a crucial role. We develop a theoretical formalism to evaluate the rate of such large deviations in periodically driven systems. We show that the scaled cumulant generating function that characterizes current fluctuations is given by a maximal Floquet exponent. Comparing deterministic protocols with stochastic protocols, we show that, with respect to large deviations, systems driven by a stochastic protocol with an infinitely large number of jumps are equivalent to systems driven by deterministic protocols. Our results are illustrated with three case studies: a two-state model for a heat engine, a three-state model for a molecular pump, and a biased random walk with a time-periodic affinity.

Advancing our understanding of plant adaptation to metal polluted environments - new insights from Biscutella laevigata

NASA Astrophysics Data System (ADS)

Babst-Kostecka, Alicja; Waldmann, Patrik; Frérot, Hélène; Vollenweider, Pierre

2016-04-01

The legacy of industrial pollution alters ecosystems, particularly at post-mining sites where metal trace elements have created toxic conditions that trigger rapid plant adaptation. Apart from the purely scientific merits, in-depth knowledge of the mechanisms underlying plant adaptation to metal contamination is beneficial for the economic and societal sectors because of its application in bioengineering (e.g. phytoremediation or biofortification). An important process is the evolution and/or enhancement of metal tolerance, a trait that has predominantly been studied by applying acute metal stress on species that allocate large quantities of certain metals to their foliage (so-called hyperaccumulators). As the vast majority of vascular plants does not hyperaccumulate metals, more efforts are needed to investigate non-hyperaccumulating species and thereby broaden understanding of biological mechanisms underlying metal tolerance. The pseudometallophyte Biscutella laevigata has shown potential in this respect, but its characteristics are insufficiently understood. We determined the zinc tolerance level and various plant responses to environmentally relevant zinc concentrations in ten metallicolous and non-metallicolous B. laevigata populations. In a two-phase hydroponic experiment, we scored multiple morphological and physiological traits (e.g. biomass, visible stress symptoms, element content in foliage) and assessed phenotypic variability within plant families. The structure of these quantitative traits was compared to that of neutral molecular markers to test, whether natural selection caused population differentiation in zinc tolerance. While all genotypes were tolerant compared to a zinc sensitive reference species, we found congruent trends toward higher tolerance in metallicolous compared to non-metallicolous plants. We identified the most indicative parameters for these differences and find that enhanced zinc tolerance in metallicolous populations is driven by divergent selection in response to metal contamination. These findings promote B. laevigata as constitutively zinc tolerant but non-hyperaccumulating organism to study plant adaptation to contaminated environments. Remarkably, tolerance differences between edaphic types emerged already at an environmentally relevant zinc concentration. This opens an unusual perspective on plant adaptation that should be tested in other non-hyperaccumulating species.

Integrative Systems Biology for Data Driven Knowledge Discovery

PubMed Central

Greene, Casey S.; Troyanskaya, Olga G.

2015-01-01

Integrative systems biology is an approach that brings together diverse high throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost effective manner. Using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of yet unknown components of a system of interest and how its malfunction leads to disease. PMID:21044756

Molecular thinking for nanoplasmonic design.

PubMed

Guerrero-Martínez, Andrés; Grzelczak, Marek; Liz-Marzán, Luis M

2012-05-22

The development of nanoplasmonics has been tremendous during the past two decades, driven in part by the improvements in colloidal synthesis of nanocrystals and manipulation of nanoparticle surface functionalities. This has granted access not only to exquisite control over the morphology of nanoparticles but also to novel multiparticle nanostructures with a variety of organizational motifs. Driven by such new possibilities, completely unforeseen plasmonic effects have been found, which let us think about applications in a variety of fields. In this Perspective, we discuss the evolution of plasmonic nanomaterials and their corresponding properties and correlations with molecular concepts that have been around for a long time. Additional thinking along these lines may lead to further expansion of nanoplasmonics and to multiple surprising discoveries in this field.

Self-organization, entropy and allostery.

PubMed

Kornev, Alexandr P

2018-06-19

Allostery is a fundamental regulatory mechanism in biology. Although generally accepted that it is a dynamics-driven process, the exact molecular mechanism of allosteric signal transmission is hotly debated. We argue that allostery is as a part of a bigger picture that also includes fractal-like properties of protein interior, hierarchical protein folding and entropy-driven molecular recognition. Although so far all these phenomena were studied separately, they stem from the same common root: self-organization of polypeptide chains and, thus, has to be studied collectively. This merge will allow the cross-referencing of a broad spectrum of multi-disciplinary data facilitating progress in all these fields. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Solving Immunology?

PubMed Central

Vodovotz, Yoram; Xia, Ashley; Read, Elizabeth L.; Bassaganya-Riera, Josep; Hafler, David A.; Sontag, Eduardo; Wang, Jin; Tsang, John S.; Day, Judy D.; Kleinstein, Steven; Butte, Atul J.; Altman, Matthew C; Hammond, Ross; Sealfon, Stuart C.

2016-01-01

Emergent responses of the immune system result from integration of molecular and cellular networks over time and across multiple organs. High-content and high-throughput analysis technologies, concomitantly with data-driven and mechanistic modeling, hold promise for systematic interrogation of these complex pathways. However, connecting genetic variation and molecular mechanisms to individual phenotypes and health outcomes has proven elusive. Gaps remain in data, and disagreements persist about the value of mechanistic modeling for immunology. Here, we present the perspectives that emerged from the NIAID workshop “Complex Systems Science, Modeling and Immunity” and subsequent discussions regarding the potential synergy of high-throughput data acquisition, data-driven modeling and mechanistic modeling to define new mechanisms of immunological disease and to accelerate the translation of these insights into therapies. PMID:27986392

B13+ : a photodriven molecular Wankel engine.

PubMed

Zhang, Jin; Sergeeva, Alina P; Sparta, Manuel; Alexandrova, Anastassia N

2012-08-20

Revved-up rotary: A molecular Wankel motor, the dual-ring structure B(13)(+), is driven by circularly-polarized infrared electromagnetic radiation. Calculations show that this illumination leads to a guided unidirectional rotation of the outer ring, which is achieved with rotational frequency of the order of 300 GHz. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Light-powered micromotor driven by geometry-assisted, asymmetric photon-heating and subsequent gas convection

NASA Astrophysics Data System (ADS)

Han, Li-Hsin; Wu, Shaomin; Condit, J. Christopher; Kemp, Nate J.; Milner, Thomas E.; Feldman, Marc D.; Chen, Shaochen

2010-05-01

We report on the design, fabrication, and analysis of a light-driven micromotor. The micromotor was created from a nanoporous polymer with close-packed gold nanoparticles which generate heat by absorbing light. The blades of the micromotor were curved, forming convex and concave sides. Upon lateral irradiation, by geometric effect the convex side transfers more photon-generated heat to the surrounding gas molecules, causing a convective motion of gas and leading to the rotation of the micromotor. The light-driven motions of gas molecules were analyzed using molecular dynamics modeling.

Robust rotation of rotor in a thermally driven nanomotor

PubMed Central

Cai, Kun; Yu, Jingzhou; Shi, Jiao; Qin, Qing-Hua

2017-01-01

In the fabrication of a thermally driven rotary nanomotor with the dimension of a few nanometers, fabrication and control precision may have great influence on rotor’s stability of rotational frequency (SRF). To investigate effects of uncertainty of some major factors including temperature, tube length, axial distance between tubes, diameter of tubes and the inward radial deviation (IRD) of atoms in stators on the frequency’s stability, theoretical analysis integrating with numerical experiments are carried out. From the results obtained via molecular dynamics simulation, some key points are illustrated for future fabrication of the thermal driven rotary nanomotor. PMID:28393898

A New Radio Spectral Line Survey of Planetary Nebulae: Exploring Radiatively Driven Heating and Chemistry of Molecular Gas

NASA Astrophysics Data System (ADS)

Bublitz, Jesse

Planetary nebulae contain shells of cold gas and dust whose heating and chemistry is likely driven by UV and X-ray emission from their central stars and from wind-collision-generated shocks. We present the results of a survey of molecular line emissions in the 88 - 235 GHz range from nine nearby (<1.5 kpc) planetary nebulae using the 30 m telescope at the Institut de Radioastronomie Millimetrique. Rotational transitions of nine molecules, including the well-studied CO isotopologues and chemically important trace species, were observed and the results compared with and augmented by previous studies of molecular gas in PNe. Lines of the molecules HCO+, HNC, HCN, and CN, which were detected in most objects, represent new detections for five planetary nebulae in our study. Flux ratios were analyzed to identify correlations between the central star and/or nebular ultraviolet/X-ray luminosities and the molecular chemistries of the nebulae. Analysis reveals the apparent dependence of the HNC/HCN line ratio on PN central star UV luminosity. There exists no such clear correlation between PN X-rays and various diagnostics of PN molecular chemistry. The correlation between HNC/HCN ratio and central star UV luminosity hints at the potential of molecular emission line studies of PNe for improving our understanding of the role that high-energy radiation plays in the heating and chemistry of photodissociation regions.

Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors

NASA Astrophysics Data System (ADS)

Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T.; Giuseppone, Nicolas

2015-02-01

Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

THE MOLECULAR WIND IN THE NEAREST SEYFERT GALAXY CIRCINUS REVEALED BY ALMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zschaechner, Laura K.; Walter, Fabian; Farina, Emanuele P.

2016-12-01

We present ALMA observations of the inner 1′ (1.2 kpc) of the Circinus galaxy, the nearest Seyfert. We target CO (1–0) in the region associated with a well-known multiphase outflow driven by the central active galactic nucleus (AGN). While the geometry of Circinus and its outflow make disentangling the latter difficult, we see indications of outflowing molecular gas at velocities consistent with the ionized outflow. We constrain the mass of the outflowing molecular gas to be 1.5 × 10{sup 5}−5.1 × 10{sup 6} M {sub ⊙}, yielding a molecular outflow rate of 0.35–12.3 M {sub ⊙} yr{sup −1}. The values within this range aremore » comparable to the star formation (SF) rate in Circinus, indicating that the outflow indeed regulates SF to some degree. The molecular outflow in Circinus is considerably lower in mass and energetics than previously studied AGN-driven outflows, especially given its high ratio of AGN luminosity to bolometric luminosity. The molecular outflow in Circinus is, however, consistent with some trends put forth by Cicone et al., including a linear relation between kinetic power and AGN luminosity, as well as its momentum rate versus bolometric luminosity (although the latter places Circinus among the starburst galaxies in that sample). We detect additional molecular species including CN and C{sup 17}O.« less

The Nurse Leader Role in Crisis Management.

PubMed

Edmonson, Cole; Sumagaysay, Dio; Cueman, Marie; Chappell, Stacey

2016-09-01

Leaders from the American Organization of Nurse Executives describe the dynamic state of today's healthcare system related to crisis management. Adaptive leadership, driven by strong values and morality, can guide leaders and organizations through the most difficult times.

DFT Performance Prediction in FFTW

NASA Astrophysics Data System (ADS)

Gu, Liang; Li, Xiaoming

Fastest Fourier Transform in the West (FFTW) is an adaptive FFT library that generates highly efficient Discrete Fourier Transform (DFT) implementations. It is one of the fastest FFT libraries available and it outperforms many adaptive or hand-tuned DFT libraries. Its success largely relies on the huge search space spanned by several FFT algorithms and a set of compiler generated C code (called codelets) for small size DFTs. FFTW empirically finds the best algorithm by measuring the performance of different algorithm combinations. Although the empirical search works very well for FFTW, the search process does not explain why the best plan found performs best, and the search overhead grows polynomially as the DFT size increases. The opposite of empirical search is model-driven optimization. However, it is widely believed that model-driven optimization is inferior to empirical search and is particularly powerless to solve problems as complex as the optimization of DFT.

Biotechnological production of value-added carotenoids from microalgae: Emerging technology and prospects.

PubMed

Wichuk, Kristine; Brynjólfsson, Sigurður; Fu, Weiqi

2014-01-01

We recently evaluated the relationship between abiotic environmental stresses and lutein biosynthesis in the green microalga Dunaliella salina and suggested a rational design of stress-driven adaptive evolution experiments for carotenoids production in microalgae. Here, we summarize our recent findings regarding the biotechnological production of carotenoids from microalgae and outline emerging technology in this field. Carotenoid metabolic pathways are characterized in several representative algal species as they pave the way for biotechnology development. The adaptive evolution strategy is highlighted in connection with enhanced growth rate and carotenoid metabolism. In addition, available genetic modification tools are described, with emphasis on model species. A brief discussion on the role of lights as limiting factors in carotenoid production in microalgae is also included. Overall, our analysis suggests that light-driven metabolism and the photosynthetic efficiency of microalgae in photobioreactors are the main bottlenecks in enhancing biotechnological potential of carotenoid production from microalgae.

Can clues from evolution unlock the molecular development of the cerebellum?

PubMed

Butts, Thomas; Chaplin, Natalie; Wingate, Richard J T

2011-02-01

The cerebellum sits at the rostral end of the vertebrate hindbrain and is responsible for sensory and motor integration. Owing to its relatively simple architecture, it is one of the most powerful model systems for studying brain evolution and development. Over the last decade, the combination of molecular fate mapping techniques in the mouse and experimental studies, both in vitro and in vivo, in mouse and chick have significantly advanced our understanding of cerebellar neurogenesis in space and time. In amniotes, the most numerous cell type in the cerebellum, and indeed the brain, is the cerebellar granule neurons, and these are born from a transient secondary proliferative zone, the external granule layer (EGL), where proliferation is driven by sonic hedgehog signalling and causes cerebellar foliation. Recent studies in zebrafish and sharks have shown that while the molecular mechanisms of neurogenesis appear conserved across vertebrates, the EGL as a site of shh-driven transit amplification is not, and is therefore implicated as a key amniote innovation that facilitated the evolution of the elaborate foliated cerebella found in birds and mammals. Ellucidating the molecular mechanisms underlying the origin of the EGL in evolution could have significant impacts on our understanding of the molecular details of cerebellar development.

Fault Detection for Nonlinear Process With Deterministic Disturbances: A Just-In-Time Learning Based Data Driven Method.

PubMed

Yin, Shen; Gao, Huijun; Qiu, Jianbin; Kaynak, Okyay

2017-11-01

Data-driven fault detection plays an important role in industrial systems due to its applicability in case of unknown physical models. In fault detection, disturbances must be taken into account as an inherent characteristic of processes. Nevertheless, fault detection for nonlinear processes with deterministic disturbances still receive little attention, especially in data-driven field. To solve this problem, a just-in-time learning-based data-driven (JITL-DD) fault detection method for nonlinear processes with deterministic disturbances is proposed in this paper. JITL-DD employs JITL scheme for process description with local model structures to cope with processes dynamics and nonlinearity. The proposed method provides a data-driven fault detection solution for nonlinear processes with deterministic disturbances, and owns inherent online adaptation and high accuracy of fault detection. Two nonlinear systems, i.e., a numerical example and a sewage treatment process benchmark, are employed to show the effectiveness of the proposed method.

Temperature-driven adaptation of the bacterial community in peat measured by using thymidine and leucine incorporation.

PubMed

Ranneklev, S B; Bååth, E

2001-03-01

The temperature-driven adaptation of the bacterial community in peat was studied, by altering temperature to simulate self-heating and a subsequent return to mesophilic conditions. The technique used consisted of extracting the bacterial community from peat using homogenization-centrifugation and measuring the rates of thymidine (TdR) or leucine (Leu) incorporation by the extracted bacterial community at different temperatures. Increasing the peat incubation temperature from 25 degrees C to 35, 45, or 55 degrees C resulted in a selection of bacterial communities whose optimum temperatures for activity correlated to the peat incubation temperatures. Although TdR and Leu incorporations were significantly correlated, the Leu/TdR incorporation ratios were affected by temperature. Higher Leu/TdR incorporation ratios were found at higher temperatures of incubation of the extracted bacterial community. Higher Leu/TdR incorporation ratios were also found for bacteria in peat samples incubated at higher temperatures. The reappearance of the mesophilic community and disappearance of the thermophilic community when the incubation temperature of the peat was shifted down were monitored by measuring TdR incorporation at 55 degrees C (thermophilic activity) and 25 degrees C (mesophilic activity). Shifting the peat incubation temperature from 55 to 25 degrees C resulted in a recovery of the mesophilic activity, with a subsequent disappearance of the thermophilic activity. The availability of substrate for bacterial growth varied over time and among different peat samples. To avoid confounding effects of substrate availability, a temperature adaptation index was calculated. This index consisted of the log(10) ratio of TdR incorporation at 55 and 25 degrees C. The temperature index decreased linearly with time, indicating that no thermophilic activity would be detected by the TdR technique 1 month after the temperature downshift. There were no differences between the slopes of the temperature adaptation indices over time for peat samples incubated at 55 degrees C 3 or 11 days before incubation at 25 degrees C. Thus, different levels of bacterial activity did not affect the temperature-driven adaptation of the bacterial community.

Temperature-Driven Adaptation of the Bacterial Community in Peat Measured by Using Thymidine and Leucine Incorporation

PubMed Central

Ranneklev, Sissel Brit; Bååth, Erland

2001-01-01

The temperature-driven adaptation of the bacterial community in peat was studied, by altering temperature to simulate self-heating and a subsequent return to mesophilic conditions. The technique used consisted of extracting the bacterial community from peat using homogenization-centrifugation and measuring the rates of thymidine (TdR) or leucine (Leu) incorporation by the extracted bacterial community at different temperatures. Increasing the peat incubation temperature from 25°C to 35, 45, or 55°C resulted in a selection of bacterial communities whose optimum temperatures for activity correlated to the peat incubation temperatures. Although TdR and Leu incorporations were significantly correlated, the Leu/TdR incorporation ratios were affected by temperature. Higher Leu/TdR incorporation ratios were found at higher temperatures of incubation of the extracted bacterial community. Higher Leu/TdR incorporation ratios were also found for bacteria in peat samples incubated at higher temperatures. The reappearance of the mesophilic community and disappearance of the thermophilic community when the incubation temperature of the peat was shifted down were monitored by measuring TdR incorporation at 55°C (thermophilic activity) and 25°C (mesophilic activity). Shifting the peat incubation temperature from 55 to 25°C resulted in a recovery of the mesophilic activity, with a subsequent disappearance of the thermophilic activity. The availability of substrate for bacterial growth varied over time and among different peat samples. To avoid confounding effects of substrate availability, a temperature adaptation index was calculated. This index consisted of the log10 ratio of TdR incorporation at 55 and 25°C. The temperature index decreased linearly with time, indicating that no thermophilic activity would be detected by the TdR technique 1 month after the temperature downshift. There were no differences between the slopes of the temperature adaptation indices over time for peat samples incubated at 55°C 3 or 11 days before incubation at 25°C. Thus, different levels of bacterial activity did not affect the temperature-driven adaptation of the bacterial community. PMID:11229900

A General and Efficient Method for Incorporating Precise Spike Times in Globally Time-Driven Simulations

PubMed Central

Hanuschkin, Alexander; Kunkel, Susanne; Helias, Moritz; Morrison, Abigail; Diesmann, Markus

2010-01-01

Traditionally, event-driven simulations have been limited to the very restricted class of neuronal models for which the timing of future spikes can be expressed in closed form. Recently, the class of models that is amenable to event-driven simulation has been extended by the development of techniques to accurately calculate firing times for some integrate-and-fire neuron models that do not enable the prediction of future spikes in closed form. The motivation of this development is the general perception that time-driven simulations are imprecise. Here, we demonstrate that a globally time-driven scheme can calculate firing times that cannot be discriminated from those calculated by an event-driven implementation of the same model; moreover, the time-driven scheme incurs lower computational costs. The key insight is that time-driven methods are based on identifying a threshold crossing in the recent past, which can be implemented by a much simpler algorithm than the techniques for predicting future threshold crossings that are necessary for event-driven approaches. As run time is dominated by the cost of the operations performed at each incoming spike, which includes spike prediction in the case of event-driven simulation and retrospective detection in the case of time-driven simulation, the simple time-driven algorithm outperforms the event-driven approaches. Additionally, our method is generally applicable to all commonly used integrate-and-fire neuronal models; we show that a non-linear model employing a standard adaptive solver can reproduce a reference spike train with a high degree of precision. PMID:21031031

MOLECULAR DETECTION OF CRYPTOSPORIDIUM OOCYSTS IN WATER: THE CHALLENGE AND PROMISE

EPA Science Inventory

Because of the presence of host-adapted Cryptosporidium species and genotypes, molecular tools can help assess the source and hazardous potential of Cryptosporidium oocysts in water. The development and use of molecular tools in the analysis of environmental samples have gone tho...

Ontogenetic and evolutionary effects of predation and competition on nine-spined stickleback (Pungitius pungitius) body size.

PubMed

Välimäki, Kaisa; Herczeg, Gábor

2012-07-01

1. Individual- and population-level variation in body size and growth often correlates with many fitness traits. Predation and food availability are expected to affect body size and growth as important agents of both natural selection and phenotypic plasticity. How differences in predation and food availability affect body size/growth during ontogeny in populations adapted to different predation and competition regimes is rarely studied. 2. Nine-spined stickleback (Pungitius pungitius) populations originating from habitats with varying levels of predation and competition are known to be locally adapted to their respective habitats in terms of body size and growth. Here, we studied how different levels of perceived predation risk and competition during ontogeny affect the reaction norms of body size and growth in (i) marine and pond populations adapted to different levels of predation and competition and (ii) different sexes. We reared nine-spined stickleback in a factorial experiment under two levels of perceived predation risk (present/absent) and competition (high/low food supply). 3. We found divergence in the reaction norms at two levels: (i) predation-adapted marine stickleback had stronger reactions to predatory cues than intraspecific competition-adapted pond stickleback, the latter being more sensitive to available food than the marine fish and (ii) females reacting more strongly to the treatments than males. 4. The repeated, habitat-dependent nature of the differences suggests that natural selection is the agent behind the observed patterns. Our results suggest that genetic adaptation to certain environmental factors also involves an increase in the range of expressible phenotypic plasticity. We found support for this phenomenon at two levels: (i) across populations driven by habitat type and (ii) within populations driven by sex. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

Changes in auditory nerve responses across the duration of sinusoidally amplitude-modulated electric pulse-train stimuli.

PubMed

Hu, Ning; Miller, Charles A; Abbas, Paul J; Robinson, Barbara K; Woo, Jihwan

2010-12-01

Response rates of auditory nerve fibers (ANFs) to electric pulse trains change over time, reflecting substantial spike-rate adaptation that depends on stimulus parameters. We hypothesize that adaptation affects the representation of amplitude-modulated pulse trains used by cochlear prostheses to transmit speech information to the auditory system. We recorded cat ANF responses to sinusoidally amplitude-modulated (SAM) trains with 5,000 pulse/s carriers. Stimuli delivered by a monopolar intracochlear electrode had fixed modulation frequency (100 Hz) and depth (10%). ANF responses were assessed by spike-rate measures, while representation of modulation was evaluated by vector strength (VS) and the fundamental component of the fast Fourier transform (F(0) amplitude). These measures were assessed across the 400 ms duration of pulse-train stimuli, a duration relevant to speech stimuli. Different stimulus levels were explored and responses were categorized into four spike-rate groups to assess level effects across ANFs. The temporal pattern of rate adaptation to modulated trains was similar to that of unmodulated trains, but with less rate adaptation. VS to the modulator increased over time and tended to saturate at lower spike rates, while F(0) amplitude typically decreased over time for low driven rates and increased for higher driven rates. VS at moderate and high spike rates and degree of F(0) amplitude temporal changes at low and moderate spike rates were positively correlated with the degree of rate adaptation. Thus, high-rate carriers will modify the ANF representation of the modulator over time. As the VS and F(0) measures were sensitive to adaptation-related changes over different spike-rate ranges, there is value in assessing both measures.

Charge Effect on the Formation of Polyoxometalate-Based Supramolecular Polygons Driven by Metal Coordination.

PubMed

Piot, Madeleine; Hupin, Sébastien; Lavanant, Hélène; Afonso, Carlos; Bouteiller, Laurent; Proust, Anna; Izzet, Guillaume

2017-07-17

The metal-driven self-assembly of a Keggin-based hybrid bearing two remote pyridine units was investigated. The resulting supramolecular species were identified by combination of 2D diffusion NMR spectroscopy (DOSY) and electrospray ionization mass spectrometry (ESI-MS) as a mixture of molecular triangles and squares. This behavior is different from that of the structural analogue Dawson-based hybrid displaying a higher charge, which only led to the formation of molecular triangles. This study highlights the decisive effect of the charge of the POMs in their self-assembly processes that disfavors the formation of large assemblies. An isothermal titration calorimetry (ITC) experiment confirmed the stronger binding in the case of the Keggin hybrids. A correlation between the diffusion coefficient D and the molecular mass M of the POM-based building block and its coordination oligomers was also observed. We show that the diffusion coefficient of these compounds is mainly determined by their occupied volume rather than by their shape.

Renewable Molecular Flasks with NADH Models: Combination of Light-Driven Proton Reduction and Biomimetic Hydrogenation of Benzoxazinones.

PubMed

Zhao, Liang; Wei, Jianwei; Lu, Junhua; He, Cheng; Duan, Chunying

2017-07-17

Using small molecules with defined pockets to catalyze chemical transformations resulted in attractive catalytic syntheses that echo the remarkable properties of enzymes. By modulating the active site of a nicotinamide adenine dinucleotide (NADH) model in a redox-active molecular flask, we combined biomimetic hydrogenation with in situ regeneration of the active site in a one-pot transformation using light as a clean energy source. This molecular flask facilitates the encapsulation of benzoxazinones for biomimetic hydrogenation of the substrates within the inner space of the flask using the active sites of the NADH models. The redox-active metal centers provide an active hydrogen source by light-driven proton reduction outside the pocket, allowing the in situ regeneration of the NADH models under irradiation. This new synthetic platform, which offers control over the location of the redox events, provides a regenerating system that exhibits high selectivity and efficiency and is extendable to benzoxazinone and quinoxalinone systems. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isocitrate dehydrogenase-mutant glioma: Evolving clinical and therapeutic implications.

PubMed

Miller, Julie J; Shih, Helen A; Andronesi, Ovidiu C; Cahill, Daniel P

2017-12-01

The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with other recurrent molecular alterations, including 1p/19q codeletions and tumor suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations, which together help to define a molecular signature that aids in the classification of gliomas and helps to better predict clinical behavior. A confluence of research suggests that glioma development in IDH-mutant and IDH wild-type tumors is driven by different oncogenic processes and responds differently to current treatment paradigms. Herein, the authors discuss the discovery of IDH mutations and associated molecular alterations in glioma, review clinical features common to patients with IDH-mutant glioma, and highlight current understanding of IDH mutation-driven gliomagenesis with implications for emerging treatment strategies. Cancer 2017;123:4535-4546. © 2017 American Cancer Society. © 2017 American Cancer Society.

Molecular dynamics modelling of mechanical properties of polymers for adaptive aerospace structures

NASA Astrophysics Data System (ADS)

Papanikolaou, Michail; Drikakis, Dimitris; Asproulis, Nikolaos

2015-02-01

The features of adaptive structures depend on the properties of the supporting materials. For example, morphing wing structures require wing skin materials, such as rubbers that can withstand the forces imposed by the internal mechanism while maintaining the required aerodynamic properties of the aircraft. In this study, Molecular Dynamics and Minimization simulations are being used to establish well-equilibrated models of Ethylene-Propylene-Diene Monomer (EPDM) elastomer systems and investigate their mechanical properties.

Optimization of complex slater-type functions with analytic derivative methods for describing photoionization differential cross sections.

PubMed

Matsuzaki, Rei; Yabushita, Satoshi

2017-05-05

The complex basis function (CBF) method applied to various atomic and molecular photoionization problems can be interpreted as an L2 method to solve the driven-type (inhomogeneous) Schrödinger equation, whose driven term being dipole operator times the initial state wave function. However, efficient basis functions for representing the solution have not fully been studied. Moreover, the relation between their solution and that of the ordinary Schrödinger equation has been unclear. For these reasons, most previous applications have been limited to total cross sections. To examine the applicability of the CBF method to differential cross sections and asymmetry parameters, we show that the complex valued solution to the driven-type Schrödinger equation can be variationally obtained by optimizing the complex trial functions for the frequency dependent polarizability. In the test calculations made for the hydrogen photoionization problem with five or six complex Slater-type orbitals (cSTOs), their complex valued expansion coefficients and the orbital exponents have been optimized with the analytic derivative method. Both the real and imaginary parts of the solution have been obtained accurately in a wide region covering typical molecular regions. Their phase shifts and asymmetry parameters are successfully obtained by extrapolating the CBF solution from the inner matching region to the asymptotic region using WKB method. The distribution of the optimized orbital exponents in the complex plane is explained based on the close connection between the CBF method and the driven-type equation method. The obtained information is essential to constructing the appropriate basis sets in future molecular applications. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sex, Scavengers, and Chaperones: Transcriptome Secrets of Divergent Symbiodinium Thermal Tolerances.

PubMed

Levin, Rachel A; Beltran, Victor H; Hill, Ross; Kjelleberg, Staffan; McDougald, Diane; Steinberg, Peter D; van Oppen, Madeleine J H

2016-09-01

Corals rely on photosynthesis by their endosymbiotic dinoflagellates (Symbiodinium spp.) to form the basis of tropical coral reefs. High sea surface temperatures driven by climate change can trigger the loss of Symbiodinium from corals (coral bleaching), leading to declines in coral health. Different putative species (genetically distinct types) as well as conspecific populations of Symbiodinium can confer differing levels of thermal tolerance to their coral host, but the genes that govern dinoflagellate thermal tolerance are unknown. Here we show physiological and transcriptional responses to heat stress by a thermo-sensitive (physiologically susceptible at 32 °C) type C1 Symbiodinium population and a thermo-tolerant (physiologically healthy at 32 °C) type C1 Symbiodinium population. After nine days at 32 °C, neither population exhibited physiological stress, but both displayed up-regulation of meiosis genes by ≥ 4-fold and enrichment of meiosis functional gene groups, which promote adaptation. After 13 days at 32 °C, the thermo-sensitive population suffered a significant decrease in photosynthetic efficiency and increase in reactive oxygen species (ROS) leakage from its cells, whereas the thermo-tolerant population showed no signs of physiological stress. Correspondingly, only the thermo-tolerant population demonstrated up-regulation of a range of ROS scavenging and molecular chaperone genes by ≥ 4-fold and enrichment of ROS scavenging and protein-folding functional gene groups. The physiological and transcriptional responses of the Symbiodinium populations to heat stress directly correlate with the bleaching susceptibilities of corals that harbored these same Symbiodinium populations. Thus, our study provides novel, foundational insights into the molecular basis of dinoflagellate thermal tolerance and coral bleaching. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Keck OSIRIS Nearby AGN Survey: Tracing Inflow within the Central 200 pc of Seyfert Galaxies

NASA Astrophysics Data System (ADS)

Hicks, Erin K. S.; Müller-Sánchez, Francisco; Malkan, Matthew A.; Yu, Po-Chieh

2016-08-01

In an effort to identify the fundamental processes driving feeding and feedback in AGN we turn to local Seyfert galaxies and rely on a multi-wavelength approach. With the integral field unit OSIRIS and adaptive optics we characterize the nuclear stars and gas down to scales of 5-30 parsecs in a sample of 40 Seyfert galaxies with the Keck OSIRIS Nearby AGN (KONA) survey. The complex gas kinematics in these near-IR data are interpreted using an integrative approach through comparison with data available at a range of wavelengths. We present first results from the survey with a focus on work aimed at constraining the mechanism(s) driving inflow of material within the central 200 pc. Particularly useful in the identification of inflow mechanisms (e.g. nuclear spiral, external accretion) is spatial correlation of the molecular gas distribution and kinematics with dust features revealed in HST imaging (optical and near-IR). Also informative is comparison with X-ray emission to identify locations likely influenced by interactions with outflows. The stellar kinematics in the sample galaxies (traced by CO bandheads at 2.3 microns) indicate a stellar population within the central few 100 parsecs in circular rotation, and in the majority of the galaxies the molecular gas (traced by H2 emission at 2.1218 microns) is found to have a rotating component co-spatial with the stellar disk. A significant fraction of the galaxies also exhibit kinematic signatures of inflow superimposed on this disk rotation, with inflow driven by secular and non-secular processes identified. We explore statistical trends of the nuclear stellar and molecular gas properties, including primary fueling mechanism, with Seyfert type, AGN luminosity, and host environment with the goal of disentangling which properties are fundamental to the nature of the AGN.

NASA Tech Briefs, April 2007

NASA Technical Reports Server (NTRS)

2007-01-01

Topics include: Wearable Environmental and Physiological Sensing Unit; Broadband Phase Retrieval for Image-Based Wavefront Sensing; Filter Function for Wavefront Sensing Over a Field of View; Iterative-Transform Phase Retrieval Using Adaptive Diversity; Wavefront Sensing With Switched Lenses for Defocus Diversity; Smooth Phase Interpolated Keying; Maintaining Stability During a Conducted-Ripple EMC Test; Photodiode Preamplifier for Laser Ranging With Weak Signals; Advanced High-Definition Video Cameras; Circuit for Full Charging of Series Lithium-Ion Cells; Analog Nonvolatile Computer Memory Circuits; JavaGenes Molecular Evolution; World Wind 3D Earth Viewing; Lithium Dinitramide as an Additive in Lithium Power Cells; Accounting for Uncertainties in Strengths of SiC MEMS Parts; Ion-Conducting Organic/Inorganic Polymers; MoO3 Cathodes for High-Temperature Lithium Thin-Film Cells; Counterrotating-Shoulder Mechanism for Friction Stir Welding; Strain Gauges Indicate Differential-CTE-Induced Failures; Antibodies Against Three Forms of Urokinase; Understanding and Counteracting Fatigue in Flight Crews; Active Correction of Aberrations of Low-Quality Telescope Optics; Dual-Beam Atom Laser Driven by Spinor Dynamics; Rugged, Tunable Extended-Cavity Diode Laser; Balloon for Long-Duration, High-Altitude Flight at Venus; and Wide-Temperature-Range Integrated Operational Amplifier.

Vegetable Grafting as a Tool to Improve Drought Resistance and Water Use Efficiency

PubMed Central

Kumar, Pradeep; Rouphael, Youssef; Cardarelli, Mariateresa; Colla, Giuseppe

2017-01-01

Drought is one of the most prevalent limiting factors causing considerable losses in crop productivity, inflicting economic as well as nutritional insecurity. One of the greatest challenges faced by the scientific community in the next few years is to minimize the yield losses caused by drought. Drought resistance is a complex quantitative trait controlled by many genes. Thus, introgression of drought resistance traits into high yielding genotypes has been a challenge to plant breeders. Vegetable grafting using rootstocks has emerged as a rapid tool in tailoring plants to better adapt to suboptimal growing conditions. This has induced changes in shoot physiology. Grafting applications have expanded mainly in Solanaceous crops and cucurbits, which are commonly grown in arid and semi-arid areas characterized by long drought periods. The current review gives an overview of the recent scientific literature on root-shoot interaction and rootstock-driven alteration of growth, yield, and fruit quality in grafted vegetable plants under drought stress. Further, we elucidate the drought resistance mechanisms of grafted vegetables at the morpho-physiological, biochemical, and molecular levels. PMID:28713405

NF-κB and the link between inflammation and cancer.

PubMed

DiDonato, Joseph A; Mercurio, Frank; Karin, Michael

2012-03-01

The nuclear factor-κB (NF-κB) transcription factor family has been considered the central mediator of the inflammatory process and a key participant in innate and adaptive immune responses. Coincident with the molecular cloning of NF-κB/RelA and identification of its kinship to the v-Rel oncogene, it was anticipated that NF-κB itself would be involved in cancer development. Oncogenic activating mutations in NF-κB genes are rare and have been identified only in some lymphoid malignancies, while most NF-κB activating mutations in lymphoid malignancies occur in upstream signaling components that feed into NF-κB. NF-κB activation is also prevalent in carcinomas, in which NF-κB activation is mainly driven by inflammatory cytokines within the tumor microenvironment. Importantly, however, in all malignancies, NF-κB acts in a cell type-specific manner: activating survival genes within cancer cells and inflammation-promoting genes in components of the tumor microenvironment. Yet, the complex biological functions of NF-κB have made its therapeutic targeting a challenge. © 2012 John Wiley & Sons A/S.

There is more than one way to model an elephant. Experiment-driven modeling of the actin cytoskeleton.

PubMed

Ditlev, Jonathon A; Mayer, Bruce J; Loew, Leslie M

2013-02-05

Mathematical modeling has established its value for investigating the interplay of biochemical and mechanical mechanisms underlying actin-based motility. Because of the complex nature of actin dynamics and its regulation, many of these models are phenomenological or conceptual, providing a general understanding of the physics at play. But the wealth of carefully measured kinetic data on the interactions of many of the players in actin biochemistry cries out for the creation of more detailed and accurate models that could permit investigators to dissect interdependent roles of individual molecular components. Moreover, no human mind can assimilate all of the mechanisms underlying complex protein networks; so an additional benefit of a detailed kinetic model is that the numerous binding proteins, signaling mechanisms, and biochemical reactions can be computationally organized in a fully explicit, accessible, visualizable, and reusable structure. In this review, we will focus on how comprehensive and adaptable modeling allows investigators to explain experimental observations and develop testable hypotheses on the intracellular dynamics of the actin cytoskeleton. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

There is More Than One Way to Model an Elephant. Experiment-Driven Modeling of the Actin Cytoskeleton

PubMed Central

Ditlev, Jonathon A.; Mayer, Bruce J.; Loew, Leslie M.

2013-01-01

Mathematical modeling has established its value for investigating the interplay of biochemical and mechanical mechanisms underlying actin-based motility. Because of the complex nature of actin dynamics and its regulation, many of these models are phenomenological or conceptual, providing a general understanding of the physics at play. But the wealth of carefully measured kinetic data on the interactions of many of the players in actin biochemistry cries out for the creation of more detailed and accurate models that could permit investigators to dissect interdependent roles of individual molecular components. Moreover, no human mind can assimilate all of the mechanisms underlying complex protein networks; so an additional benefit of a detailed kinetic model is that the numerous binding proteins, signaling mechanisms, and biochemical reactions can be computationally organized in a fully explicit, accessible, visualizable, and reusable structure. In this review, we will focus on how comprehensive and adaptable modeling allows investigators to explain experimental observations and develop testable hypotheses on the intracellular dynamics of the actin cytoskeleton. PMID:23442903

Concurrent exercise training: do opposites distract?

PubMed Central

Coffey, Vernon G.

2016-01-01

Abstract Specificity is a core principle of exercise training to promote the desired adaptations for maximising athletic performance. The principle of specificity of adaptation is underpinned by the volume, intensity, frequency and mode of contractile activity and is most evident when contrasting the divergent phenotypes that result after undertaking either prolonged endurance or resistance training. The molecular profiles that generate the adaptive response to different exercise modes have undergone intense scientific scrutiny. Given divergent exercise induces similar signalling and gene expression profiles in skeletal muscle of untrained or recreationally active individuals, what is currently unclear is how the specificity of the molecular response is modified by prior training history. The time course of adaptation and when ‘phenotype specificity’ occurs has important implications for exercise prescription. This context is essential when attempting to concomitantly develop resistance to fatigue (through endurance‐based exercise) and increased muscle mass (through resistance‐based exercise), typically termed ‘concurrent training’. Chronic training studies provide robust evidence that endurance exercise can attenuate muscle hypertrophy and strength but the mechanistic underpinning of this ‘interference’ effect with concurrent training is unknown. Moreover, despite the potential for several key regulators of muscle metabolism to explain an incompatibility in adaptation between endurance and resistance exercise, it now seems likely that multiple integrated, rather than isolated, effectors or processes generate the interference effect. Here we review studies of the molecular responses in skeletal muscle and evidence for the interference effect with concurrent training within the context of the specificity of training adaptation. PMID:27506998

Intensity distributions and isolated attosecond pulse generation from molecular high-order harmonic generation in H2+ driven by nonhomogeneous field

NASA Astrophysics Data System (ADS)

Feng, Liqiang; Chu, Tianshu

2017-10-01

Intensity distributions and isolated attosecond pulse generation from the molecular high-order harmonic generation (MHHG) in H2+ and T2+ driven by the nonhomogeneous field have been theoretically investigated. (i) Generally speaking, the intensities of the harmonics driven by the homogeneous field can be enhanced as the initial vibrational state increases and much more intense harmonics can be obtained from the light nuclei. However, with the introduction of the nonhomogeneous effect, the enhanced ratios of the harmonic yields are decreased as the initial vibrational state increases. Moreover, the intensities of the harmonics from H2+ and T2+ are very sensitive to the nonhomogeneous effect of the laser field. (ii) The contributions of the MHHG from the two-H nuclei present the periodic variation as a function of the laser phase for the case of the symmetric nonhomogeneous field. However, for the case of the positive and the negative asymmetric nonhomogeneous fields, the left-H and the right-H play the dominating role in the MHHG, respectively. Moreover, as the angle between the laser polarization direction and the molecular axis increases, the intensity differences of the harmonics from the two-H nuclei are increased. (iii) By properly adding a half-cycle pulse into the positive asymmetric nonhomogeneous field, a supercontinuum with the bandwidth of 279 eV and an isolated 25 as pulse can be obtained.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

PubMed

Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

2016-07-21

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

PubMed Central

Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

2016-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene’s expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment. PMID:27468205

Highly efficient and robust molecular ruthenium catalysts for water oxidation

PubMed Central

Duan, Lele; Araujo, Carlos Moyses; Ahlquist, Mårten S.G.; Sun, Licheng

2012-01-01

Water oxidation catalysts are essential components of light-driven water splitting systems, which could convert water to H2 driven by solar radiation (H2O + hν → 1/2O2 + H2). The oxidation of water (H2O → 1/2O2 + 2H+ + 2e-) provides protons and electrons for the production of dihydrogen (2H+ + 2e- → H2), a clean-burning and high-capacity energy carrier. One of the obstacles now is the lack of effective and robust water oxidation catalysts. Aiming at developing robust molecular Ru-bda (H2bda = 2,2′-bipyridine-6,6′-dicarboxylic acid) water oxidation catalysts, we carried out density functional theory studies, correlated the robustness of catalysts against hydration with the highest occupied molecular orbital levels of a set of ligands, and successfully directed the synthesis of robust Ru-bda water oxidation catalysts. A series of mononuclear ruthenium complexes [Ru(bda)L2] (L = pyridazine, pyrimidine, and phthalazine) were subsequently synthesized and shown to effectively catalyze CeIV-driven [CeIV = Ce(NH4)2(NO3)6] water oxidation with high oxygen production rates up to 286 s-1 and high turnover numbers up to 55,400. PMID:22753518

Discovering the Deregulated Molecular Functions Involved in Malignant Transformation of Endometriosis to Endometriosis-Associated Ovarian Carcinoma Using a Data-Driven, Function-Based Analysis

PubMed Central

Chang, Chia-Ming; Yang, Yi-Ping; Chuang, Jen-Hua; Chuang, Chi-Mu; Lin, Tzu-Wei; Wang, Peng-Hui; Yu, Mu-Hsien

2017-01-01

The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC. PMID:29113136

A two level mutation-selection model of cultural evolution and diversity.

PubMed

Salazar-Ciudad, Isaac

2010-11-21

Cultural evolution is a complex process that can happen at several levels. At the level of individuals in a population, each human bears a set of cultural traits that he or she can transmit to its offspring (vertical transmission) or to other members of his or her society (horizontal transmission). The relative frequency of a cultural trait in a population or society can thus increase or decrease with the relative reproductive success of its bearers (individual's level) or the relative success of transmission (called the idea's level). This article presents a mathematical model on the interplay between these two levels. The first aim of this article is to explore when cultural evolution is driven by the idea's level, when it is driven by the individual's level and when it is driven by both. These three possibilities are explored in relation to (a) the amount of interchange of cultural traits between individuals, (b) the selective pressure acting on individuals, (c) the rate of production of new cultural traits, (d) the individual's capacity to remember cultural traits and to the population size. The aim is to explore the conditions in which cultural evolution does not lead to a better adaptation of individuals to the environment. This is to contrast the spread of fitness-enhancing ideas, which make individual bearers better adapted to the environment, to the spread of "selfish" ideas, which spread well simply because they are easy to remember but do not help their individual bearers (and may even hurt them). At the same time this article explores in which conditions the adaptation of individuals is maximal. The second aim is to explore how these factors affect cultural diversity, or the amount of different cultural traits in a population. This study suggests that a larger interchange of cultural traits between populations could lead to cultural evolution not improving the adaptation of individuals to their environment and to a decrease of cultural diversity. Copyright © 2010 Elsevier Ltd. All rights reserved.

Leaf anatomy of two reciprocally non-monophyletic mountain plants (Heliosperma spp.): does heritable adaptation to divergent growing sites accompany the onset of speciation?

PubMed

Bertel, Clara; Schönswetter, Peter; Frajman, Božo; Holzinger, Andreas; Neuner, Gilbert

2017-05-01

Evolution is driven by natural selection, favouring individuals adapted in phenotypic traits to the environmental conditions at their growing site. To shed light on ecological and (epi-) genetically based differentiation between Heliosperma pusillum and Heliosperma veselskyi, two reciprocally non-monophyletic, but morphologically and ecologically divergent species from the south-eastern Alps, we studied various leaf anatomical traits and investigated chloroplast ultrastructure in leaves of the two species grown either in their natural habitat or in a common garden. The alpine H. pusillum occurs in open, wet rock habitats, whereas its close relative H. veselskyi is restricted to dry, shady habitats below overhanging rocks in the montane belt. H. pusillum exhibited higher thickness of leaves and palisade layers as adjustments and/or adaptations to higher irradiance and a higher stomatal area index reflecting better water availability. Traits were adjusted plastically, but differed between species grown in a common garden, suggesting that the differentiation between the two species is not solely based on phenotypic plasticity but also has a genetic basis. Our study thus supports the hypothesis that differentiation between the highly interfertile species is likely driven by natural selection.

Neutral and selection-driven decay of sexual traits in asexual stick insects

PubMed Central

Schwander, Tanja; Crespi, Bernard J.; Gries, Regine; Gries, Gerhard

2013-01-01

Environmental shifts and lifestyle changes may result in formerly adaptive traits becoming non-functional or maladaptive. The subsequent decay of such traits highlights the importance of natural selection for adaptations, yet its causes have rarely been investigated. To study the fate of formerly adaptive traits after lifestyle changes, we evaluated sexual traits in five independently derived asexual lineages, including traits that are specific to males and therefore not exposed to selection. At least four of the asexual lineages retained the capacity to produce males that display normal courtship behaviours and are able to fertilize eggs of females from related sexual species. The maintenance of male traits may stem from pleiotropy, or from these traits only regressing via drift, which may require millions of years to generate phenotypic effects. By contrast, we found parallel decay of sexual traits in females. Asexual females produced altered airborne and contact signals, had modified sperm storage organs, and lost the ability to fertilize their eggs, impeding reversals to sexual reproduction. Female sexual traits were decayed even in recently derived asexuals, suggesting that trait changes following the evolution of asexuality, when they occur, proceed rapidly and are driven by selective processes rather than drift. PMID:23782880

Evolutionary and plastic responses of freshwater invertebrates to climate change: realized patterns and future potential.

PubMed

Stoks, Robby; Geerts, Aurora N; De Meester, Luc

2014-01-01

We integrated the evidence for evolutionary and plastic trait changes in situ in response to climate change in freshwater invertebrates (aquatic insects and zooplankton). The synthesis on the trait changes in response to the expected reductions in hydroperiod and increases in salinity indicated little evidence for adaptive, plastic, and genetic trait changes and for local adaptation. With respect to responses to temperature, there are many studies on temporal trait changes in phenology and body size in the wild that are believed to be driven by temperature increases, but there is a general lack of rigorous demonstration whether these trait changes are genetically based, adaptive, and causally driven by climate change. Current proof for genetic trait changes under climate change in freshwater invertebrates stems from a limited set of common garden experiments replicated in time. Experimental thermal evolution experiments and common garden warming experiments associated with space-for-time substitutions along latitudinal gradients indicate that besides genetic changes, also phenotypic plasticity and evolution of plasticity are likely to contribute to the observed phenotypic changes under climate change in aquatic invertebrates. Apart from plastic and genetic thermal adjustments, also genetic photoperiod adjustments are widespread and may even dominate the observed phenological shifts.

Adaptive model-based assistive control for pneumatic direct driven soft rehabilitation robots.

PubMed

Wilkening, Andre; Ivlev, Oleg

2013-06-01

Assistive behavior and inherent compliance are assumed to be the essential properties for effective robot-assisted therapy in neurological as well as in orthopedic rehabilitation. This paper presents two adaptive model-based assistive controllers for pneumatic direct driven soft rehabilitation robots that are based on separated models of the soft-robot and the patient's extremity, in order to take into account the individual patient's behavior, effort and ability during control, what is assumed to be essential to relearn lost motor functions in neurological and facilitate muscle reconstruction in orthopedic rehabilitation. The high inherent compliance of soft-actuators allows for a general human-robot interaction and provides the base for effective and dependable assistive control. An inverse model of the soft-robot with estimated parameters is used to achieve robot transparency during treatment and inverse adaptive models of the individual patient's extremity allow the controllers to learn on-line the individual patient's behavior and effort and react in a way that assist the patient only as much as needed. The effectiveness of the controllers is evaluated with unimpaired subjects using a first prototype of a soft-robot for elbow training. Advantages and disadvantages of both controllers are analyzed and discussed.

Nanoscale rotary motors driven by electron tunneling.

PubMed

Wang, Boyang; Vuković, Lela; Král, Petr

2008-10-31

We examine by semiclassical molecular dynamics simulations the possibility of driving nanoscale rotary motors by electron tunneling. The model systems studied have a carbon nanotube shaft with covalently attached "isolating" molecular stalks ending with "conducting" blades. Periodic charging and discharging of the blades at two metallic electrodes maintains an electric dipole on the blades that is rotated by an external electric field. Our simulations demonstrate that these molecular motors can be efficient under load and in the presence of noise and defects.

Radiation of Extant Cetaceans Driven by Restructuring of the Oceans

PubMed Central

Steeman, Mette E.; Hebsgaard, Martin B.; Fordyce, R. Ewan; Ho, Simon Y. W.; Rabosky, Daniel L.; Nielsen, Rasmus; Rahbek, Carsten; Glenner, Henrik; Sørensen, Martin V.; Willerslev, Eske

2009-01-01

Abstract The remarkable fossil record of whales and dolphins (Cetacea) has made them an exemplar of macroevolution. Although their overall adaptive transition from terrestrial to fully aquatic organisms is well known, this is not true for the radiation of modern whales. Here, we explore the diversification of extant cetaceans by constructing a robust molecular phylogeny that includes 87 of 89 extant species. The phylogeny and divergence times are derived from nuclear and mitochondrial markers, calibrated with fossils. We find that the toothed whales are monophyletic, suggesting that echolocation evolved only once early in that lineage some 36–34 Ma. The rorqual family (Balaenopteridae) is restored with the exclusion of the gray whale, suggesting that gulp feeding evolved 18–16 Ma. Delphinida, comprising all living dolphins and porpoises other than the Ganges/Indus dolphins, originated about 26 Ma; it contains the taxonomically rich delphinids, which began diversifying less than 11 Ma. We tested 2 hypothesized drivers of the extant cetacean radiation by assessing the tempo of lineage accumulation through time. We find no support for a rapid burst of speciation early in the history of extant whales, contrasting with expectations of an adaptive radiation model. However, we do find support for increased diversification rates during periods of pronounced physical restructuring of the oceans. The results imply that paleogeographic and paleoceanographic changes, such as closure of major seaways, have influenced the dynamics of radiation in extant cetaceans. PMID:20525610

A Triad of Molecular Regions Contribute to the Formation of Two Distinct MHC Class II Conformers

PubMed Central

Drake, Lisa A.; Drake, James R.

2016-01-01

MHC class II molecules present antigen-derived peptides to CD4 T cells to drive the adaptive immune response. Previous work has established that class II αβ dimers can adopt two distinct conformations, driven by the differential pairing of transmembrane domain GxxxG dimerization motifs. These class II conformers differ in their ability to be loaded with antigen-derived peptide and to effectively engage CD4 T cells. Motif 1 (M1) paired I-Ak class II molecules are efficiently loaded with peptides derived from the processing of B cell receptor-bound antigen, have unique B cell signaling properties and high T cell stimulation activity. The 11-5.2 mAb selectively binds M1 paired I-Ak class II molecules. However, the molecular determinants of 11-5.2 binding are currently unclear. Here, we report the ability of a human class II transmembrane domain to drive both M1 and M2 class II conformer formation. Protease sensitivity analysis further strengthens the idea that there are conformational differences between the extracellular domains of M1 and M2 paired class II. Finally, MHC class II chain alignments and site directed mutagenesis reveals a triad of molecular regions that contributes to 11-5.2 mAb binding. In addition to transmembrane GxxxG motif domain pairing, 11-5.2 binding is influenced directly by α chain residue Glu-71 and indirectly by the region around the inter-chain salt bridge formed by α chain Arg-52 and β chain Glu-86. These findings provide insight into the complexity of 11-5.2 mAb recognition of the M1 paired I-Ak class II conformer and further highlight the molecular heterogeneity of peptide-MHC class II complexes that drive T cell antigen recognition. PMID:27148821

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

PubMed Central

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; Cavusoglu, Ahmet H.; Sabharwal, Nina; DeLay, Michael; Driks, Adam; Sahin, Ozgur

2015-01-01

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth's climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. Here, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air–water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on water while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment. PMID:26079632

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

NASA Astrophysics Data System (ADS)

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; Cavusoglu, Ahmet H.; Sabharwal, Nina; Delay, Michael; Driks, Adam; Sahin, Ozgur

2015-06-01

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth's climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. Here, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air-water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on water while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.

Differential expression and emerging functions of non-coding RNAs in cold adaptation.

PubMed

Frigault, Jacques J; Morin, Mathieu D; Morin, Pier Jr

2017-01-01

Several species undergo substantial physiological and biochemical changes to confront the harsh conditions associated with winter. Small mammalian hibernators and cold-hardy insects are examples of natural models of cold adaptation that have been amply explored. While the molecular picture associated with cold adaptation has started to become clearer in recent years, notably through the use of high-throughput experimental approaches, the underlying cold-associated functions attributed to several non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), remain to be better characterized. Nevertheless, key pioneering work has provided clues on the likely relevance of these molecules in cold adaptation. With an emphasis on mammalian hibernation and insect cold hardiness, this work first reviews various molecular changes documented so far in these processes. The cascades leading to miRNA and lncRNA production as well as the mechanisms of action of these non-coding RNAs are subsequently described. Finally, we present examples of differentially expressed non-coding RNAs in models of cold adaptation and elaborate on the potential significance of this modulation with respect to low-temperature adaptation.

Independent Molecular Basis of Convergent Highland Adaptation in Maize

PubMed Central

Takuno, Shohei; Ralph, Peter; Swarts, Kelly; Elshire, Rob J.; Glaubitz, Jeffrey C.; Buckler, Edward S.; Hufford, Matthew B.; Ross-Ibarra, Jeffrey

2015-01-01

Convergent evolution is the independent evolution of similar traits in different species or lineages of the same species; this often is a result of adaptation to similar environments, a process referred to as convergent adaptation. We investigate here the molecular basis of convergent adaptation in maize to highland climates in Mesoamerica and South America, using genome-wide SNP data. Taking advantage of archaeological data on the arrival of maize to the highlands, we infer demographic models for both populations, identifying evidence of a strong bottleneck and rapid expansion in South America. We use these models to then identify loci showing an excess of differentiation as a means of identifying putative targets of natural selection and compare our results to expectations from recently developed theory on convergent adaptation. Consistent with predictions across a wide parameter space, we see limited evidence for convergent evolution at the nucleotide level in spite of strong similarities in overall phenotypes. Instead, we show that selection appears to have predominantly acted on standing genetic variation and that introgression from wild teosinte populations appears to have played a role in highland adaptation in Mexican maize. PMID:26078279

Molecular mechanisms of adaptation emerging from the physics and evolution of nucleic acids and proteins.

PubMed

Goncearenco, Alexander; Ma, Bin-Guang; Berezovsky, Igor N

2014-03-01

DNA, RNA and proteins are major biological macromolecules that coevolve and adapt to environments as components of one highly interconnected system. We explore here sequence/structure determinants of mechanisms of adaptation of these molecules, links between them, and results of their mutual evolution. We complemented statistical analysis of genomic and proteomic sequences with folding simulations of RNA molecules, unraveling causal relations between compositional and sequence biases reflecting molecular adaptation on DNA, RNA and protein levels. We found many compositional peculiarities related to environmental adaptation and the life style. Specifically, thermal adaptation of protein-coding sequences in Archaea is characterized by a stronger codon bias than in Bacteria. Guanine and cytosine load in the third codon position is important for supporting the aerobic life style, and it is highly pronounced in Bacteria. The third codon position also provides a tradeoff between arginine and lysine, which are favorable for thermal adaptation and aerobicity, respectively. Dinucleotide composition provides stability of nucleic acids via strong base-stacking in ApG dinucleotides. In relation to coevolution of nucleic acids and proteins, thermostability-related demands on the amino acid composition affect the nucleotide content in the second codon position in Archaea.

Molecular mechanisms of adaptation emerging from the physics and evolution of nucleic acids and proteins

PubMed Central

Goncearenco, Alexander; Ma, Bin-Guang; Berezovsky, Igor N.

2014-01-01

DNA, RNA and proteins are major biological macromolecules that coevolve and adapt to environments as components of one highly interconnected system. We explore here sequence/structure determinants of mechanisms of adaptation of these molecules, links between them, and results of their mutual evolution. We complemented statistical analysis of genomic and proteomic sequences with folding simulations of RNA molecules, unraveling causal relations between compositional and sequence biases reflecting molecular adaptation on DNA, RNA and protein levels. We found many compositional peculiarities related to environmental adaptation and the life style. Specifically, thermal adaptation of protein-coding sequences in Archaea is characterized by a stronger codon bias than in Bacteria. Guanine and cytosine load in the third codon position is important for supporting the aerobic life style, and it is highly pronounced in Bacteria. The third codon position also provides a tradeoff between arginine and lysine, which are favorable for thermal adaptation and aerobicity, respectively. Dinucleotide composition provides stability of nucleic acids via strong base-stacking in ApG dinucleotides. In relation to coevolution of nucleic acids and proteins, thermostability-related demands on the amino acid composition affect the nucleotide content in the second codon position in Archaea. PMID:24371267

Constitutional dynamic chemistry: bridge from supramolecular chemistry to adaptive chemistry.

PubMed

Lehn, Jean-Marie

2012-01-01

Supramolecular chemistry aims at implementing highly complex chemical systems from molecular components held together by non-covalent intermolecular forces and effecting molecular recognition, catalysis and transport processes. A further step consists in the investigation of chemical systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined functional supramolecular architectures by self-assembly from their components, thus behaving as programmed chemical systems. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibility, so as to allow a continuous change in constitution by reorganization and exchange of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the molecular and supramolecular levels.CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter relies on design for the generation of a target entity, whereas CDC takes advantage of dynamic diversity to allow variation and selection. The implementation of selection in chemistry introduces a fundamental change in outlook. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization with selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation.The merging of the features: -information and programmability, -dynamics and reversibility, -constitution and structural diversity, points to the emergence of adaptive and evolutive chemistry, towards a chemistry of complex matter.

Elucidation of molecular dynamics of invasive species of rice

USDA-ARS?s Scientific Manuscript database

Cultivated rice fields are aggressively invaded by weedy rice in the U.S. and worldwide. Weedy rice results in loss of yield and seed contamination. The molecular dynamics of the evolutionary adaptive traits of weedy rice are not fully understood. To understand the molecular basis and identify the i...

Nutritional strategies to modulate the adaptive response to endurance training.

PubMed

Hawley, John A

2013-01-01

In recent years, advances in molecular biology have allowed scientists to elucidate how endurance exercise training stimulates skeletal muscle remodeling (i.e. promotes mitochondrial biogenesis). A growing field of interest directly arising from our understanding of the molecular bases of training adaptation is how nutrient availability can alter the regulation of many contraction-induced events in muscle in response to endurance exercise. Acutely manipulating substrate availability can exert profound effects on muscle energy stores and patterns of fuel metabolism during exercise, as well as many processes activating gene expression and cell signaling. Accordingly, such interventions when repeated over weeks and months have the potential to modulate numerous adaptive processes in skeletal muscle that ultimately drive the phenotype-specific characteristics observed in highly trained athletes. In this review, the molecular and cellular events that occur in skeletal muscle during and after endurance exercise are discussed and evidence provided to demonstrate that nutrient availability plays an important role in modulating many of the adaptive responses to training. Emphasis is on human studies that have determined the regulatory role of muscle glycogen availability on cell metabolism, endurance training capacity and performance. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

Model-Biased, Data-Driven Adaptive Failure Prediction

NASA Technical Reports Server (NTRS)

Leen, Todd K.

2004-01-01

This final report, which contains a research summary and a viewgraph presentation, addresses clustering and data simulation techniques for failure prediction. The researchers applied their techniques to both helicopter gearbox anomaly detection and segmentation of Earth Observing System (EOS) satellite imagery.

The wind of EG Andromedae is not dust driven

NASA Technical Reports Server (NTRS)

Van Buren, Dave; Dgani, Ruth; Noriega-Crespo, Alberto

1994-01-01

The symbiotic star EG Andromedae has recently been the subject of several studies investigating its wind properties. Late-type giants are usually considered to have winds driven by radiation pressure on dust. Indeed, the derived wind velocity for EG Andromedae is consistent with this model. We point out here that there is no appreciable dust opacity in the wind of EG Andromedae using constraints on extinction limits from International Ultraviolet Explorer (IUE) and far infrared fluxes from Infrared Astronomy Satellite (IRAS). An alternate mechanism must operate in this star. We suggest that the wind can be driven by radiation pressure on molecular lines.

Testability, Test Automation and Test Driven Development for the Trick Simulation Toolkit

NASA Technical Reports Server (NTRS)

Penn, John

2014-01-01

This paper describes the adoption of a Test Driven Development approach and a Continuous Integration System in the development of the Trick Simulation Toolkit, a generic simulation development environment for creating high fidelity training and engineering simulations at the NASA Johnson Space Center and many other NASA facilities. It describes the approach, and the significant benefits seen, such as fast, thorough and clear test feedback every time code is checked into the code repository. It also describes an approach that encourages development of code that is testable and adaptable.

Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

PubMed Central

Franchi, Martino V.; Reeves, Neil D.; Narici, Marco V.

2017-01-01

Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively); however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT) is assumed to produce greater hypertrophy than concentric resistance training (CON RT). Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood. Thus, the present review aims to, (a) critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b) clarify the molecular mechanisms that may regulate such adaptations. We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions. PMID:28725197

Near-Ideal Xylene Selectivity in Adaptive Molecular Pillar[ n]arene Crystals.

PubMed

Jie, Kecheng; Liu, Ming; Zhou, Yujuan; Little, Marc A; Pulido, Angeles; Chong, Samantha Y; Stephenson, Andrew; Hughes, Ashlea R; Sakakibara, Fumiyasu; Ogoshi, Tomoki; Blanc, Frédéric; Day, Graeme M; Huang, Feihe; Cooper, Andrew I

2018-06-06

The energy-efficient separation of alkylaromatic compounds is a major industrial sustainability challenge. The use of selectively porous extended frameworks, such as zeolites or metal-organic frameworks, is one solution to this problem. Here, we studied a flexible molecular material, perethylated pillar[ n]arene crystals ( n = 5, 6), which can be used to separate C8 alkylaromatic compounds. Pillar[6]arene is shown to separate para-xylene from its structural isomers, meta-xylene and ortho-xylene, with 90% specificity in the solid state. Selectivity is an intrinsic property of the pillar[6]arene host, with the flexible pillar[6]arene cavities adapting during adsorption thus enabling preferential adsorption of para-xylene in the solid state. The flexibility of pillar[6]arene as a solid sorbent is rationalized using molecular conformer searches and crystal structure prediction (CSP) combined with comprehensive characterization by X-ray diffraction and 13 C solid-state NMR spectroscopy. The CSP study, which takes into account the structural variability of pillar[6]arene, breaks new ground in its own right and showcases the feasibility of applying CSP methods to understand and ultimately to predict the behavior of soft, adaptive molecular crystals.

Habitat segregation and cryptic adaptation of species of Periophthalmus (Gobioidei: Gobiidae).

PubMed

Polgar, G; Zaccara, S; Babbucci, M; Fonzi, F; Antognazza, C M; Ishak, N; Sulaiman, Z; Crosa, G

2017-05-01

A study was conducted on the habitat distribution of four sympatric species of Periophthalmus (the silver-lined mudskipper Periophthalmus argentilineatus, the slender mudskipper Periophthalmus gracilis, the kalolo mudskipper Periophthalmus kalolo and the Malacca mudskipper Periophthalmus malaccensis) from northern Sulawesi. Molecular phylogenetic reconstructions based on one mtDNA marker (16S) were used to validate the morphological taxa, identifying five molecular clades. Periophthalmus argentilineatus includes two molecular species, which are named Periophthalmus argentilineatus clades F and K. Multivariate direct gradient analysis show that these species form three distinct ecological guilds, with the two molecular species occurring in different guilds. Periophthalmus clade F is ecologically eurytypic; Periophthalmus clade K and P. kalolo are prevalent in ecosystems isolated by strong oceanic currents and at shorter distances from the sea; P. gracilis plus P. malaccensis are prevalent in ecosystems connected by shallow coastal waters, in vegetated habitats at larger distances from the sea. This indicates for the first time that mudskipper species exhibit a range of adaptations to semiterrestrialism not only within genera, but even within morphospecies, delineating a much more complex adaptive scenario than previously assumed. © 2017 The Fisheries Society of the British Isles.

Molecular mechanisms of temperature adaptation

PubMed Central

Bagriantsev, Sviatoslav N; Gracheva, Elena O

2015-01-01

Thermal perception is a fundamental physiological process pertaining to the vast majority of organisms. In vertebrates, environmental temperature is detected by the primary afferents of the somatosensory neurons in the skin, which express a ‘choir’ of ion channels tuned to detect particular temperatures. Nearly two decades of research have revealed a number of receptor ion channels that mediate the perception of several temperature ranges, but most still remain molecularly orphaned. Yet even within this well-researched realm, most of our knowledge largely pertains to two closely related species of rodents, mice and rats. While these are standard biomedical research models, mice and rats provide a limited perspective to elucidate the general principles that drive somatosensory evolution. In recent years, significant advances have been made in understanding the molecular mechanism of temperature adaptation in evolutionarily distant vertebrates and in organisms with acute thermal sensitivity. These studies have revealed the remarkable versatility of the somatosensory system and highlighted adaptations at the molecular level, which often include changes in biophysical properties of ion channels from the transient receptor potential family. Exploiting non-standard animal models has the potential to provide unexpected insights into general principles of thermosensation and thermoregulation, unachievable using the rodent model alone. PMID:25433072

Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep.

PubMed

Gizowski, C; Zaelzer, C; Bourque, C W

2016-09-29

Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth's 24-hour light cycle. Although the molecular processes that establish periodicity in clock neurons of the suprachiasmatic nucleus (SCN) are well understood, the mechanisms by which axonal projections from the central clock drive behavioural rhythms are unknown. Here we show that the sleep period in mice (Zeitgeber time, ZT0-12) is preceded by an increase in water intake promoted entirely by the central clock, and not motivated by physiological need. Mice denied this surge experienced significant dehydration near the end of the sleep period, indicating that this water intake contributes to the maintenance of overnight hydromineral balance. Furthermore, this effect relies specifically on the activity of SCN vasopressin (VP) neurons that project to thirst neurons in the OVLT (organum vasculosum lamina terminalis), where VP is released as a neurotransmitter. SCN VP neurons become electrically active during the anticipatory period (ZT21.5-23.5), and depolarize and excite OVLT neurons through the activation of postsynaptic VP V1a receptors and downstream non-selective cation channels. Optogenetic induction of VP release before the anticipatory period (basal period; ZT19.5-21.5) excited OVLT neurons and prompted a surge in water intake. Conversely, optogenetic inhibition of VP release during the anticipatory period inhibited the firing of OVLT neurons and prevented the corresponding increase in water intake. Our findings reveal the existence of anticipatory thirst, and demonstrate this behaviour to be driven by excitatory peptidergic neurotransmission mediated by VP release from central clock neurons.

Protective and destructive immunity in the periodontium: Part 1--innate and humoral immunity and the periodontium.

PubMed

Teng, Y-T A

2006-03-01

Based on the results of recent research in the field, the present paper will discuss the protective and destructive aspects of the innate vs. adaptive (humoral and cell-mediated) immunity associated with the bacterial virulent factors or antigenic determinants during periodontal pathogenesis. Attention will be focused on: (i) the Toll-like receptors (TLR), the innate immune repertoire for recognizing the unique molecular patterns of microbial components that trigger innate and adaptive immunity for effective host defenses, in some general non-oral vs. periodontal microbial infections; (ii) T-cell-mediated immunity, Th-cytokines, and osteoclastogenesis in periodontal disease progression; and (iii) some molecular techniques developed and used to identify critical microbial virulence factors or antigens associated with host immunity (using Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis as the model species). Therefore, further understanding of the molecular interactions and mechanisms associated with the host's innate and adaptive immune responses will facilitate the development of new and innovative therapeutics for future periodontal treatments.

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

PubMed Central

Vega, Rick B.; Konhilas, John P.; Kelly, Daniel P.; Leinwand, Leslie A.

2017-01-01

Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations. PMID:28467921

Conformational adaptation and manipulation of manganese tetra(4-pyridyl)porphyrin molecules on Cu(111)

NASA Astrophysics Data System (ADS)

Chen, Xianwen; Lei, Shulai; Lotze, Christian; Czekelius, Constantin; Paulus, Beate; Franke, Katharina J.

2017-03-01

Porphyrins are highly flexible molecules and well known to adapt to their local environment via conformational changes. We studied the self-assembly of manganese meso-tetra(4-pyridyl)porphyrin (Mn-TPyP) molecules on a Cu(111) surface by low temperature scanning tunneling microscopy (STM) and atomic force microscopy (ATM). We observe molecular chains along the ⟨1 1 ¯ 0 ⟩ direction of the substrate. Within these chains, we identify two molecular conformations, which differ by the orientation of the upward bending of the macrocycle. Using density functional theory, we show that this saddle shape is a consequence of the rotation and inclination of the pyridyl groups towards Cu adatoms, which stabilize the metal-organic chains. The molecular conformations obey a strict alternation, reflecting the mutual enforcement of conformational adaptation in densely packed structures. Tunneling electrons from the STM tip can induce changes in the orientation of the pyridyl endgroups. The switching behaviour varies with the different adsorption configurations.

Molecular graph convolutions: moving beyond fingerprints

NASA Astrophysics Data System (ADS)

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-08-01

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

Easy GROMACS: A Graphical User Interface for GROMACS Molecular Dynamics Simulation Package

NASA Astrophysics Data System (ADS)

Dizkirici, Ayten; Tekpinar, Mustafa

2015-03-01

GROMACS is a widely used molecular dynamics simulation package. Since it is a command driven program, it is difficult to use this program for molecular biologists, biochemists, new graduate students and undergraduate researchers who are interested in molecular dynamics simulations. To alleviate the problem for those researchers, we wrote a graphical user interface that simplifies protein preparation for a classical molecular dynamics simulation. Our program can work with various GROMACS versions and it can perform essential analyses of GROMACS trajectories as well as protein preparation. We named our open source program `Easy GROMACS'. Easy GROMACS can give researchers more time for scientific research instead of dealing with technical intricacies.

Molecular graph convolutions: moving beyond fingerprints.

PubMed

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-08-01

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph-atoms, bonds, distances, etc.-which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

Most Colorful Example of Genetic Assimilation? Exploring the Evolutionary Destiny of Recurrent Phenotypic Accommodation.

PubMed

Badyaev, Alexander V; Potticary, Ahva L; Morrison, Erin S

2017-08-01

Evolution of adaptation requires both generation of novel phenotypic variation and retention of a locally beneficial subset of this variation. Such retention can be facilitated by genetic assimilation, the accumulation of genetic and molecular mechanisms that stabilize induced phenotypes and assume progressively greater control over their reliable production. A particularly strong inference into genetic assimilation as an evolutionary process requires a system where it is possible to directly evaluate the extent to which an induced phenotype is progressively incorporated into preexisting developmental pathways. Evolution of diet-dependent pigmentation in birds-where external carotenoids are coopted into internal metabolism to a variable degree before being integrated with a feather's developmental processes-provides such an opportunity. Here we combine a metabolic network view of carotenoid evolution with detailed empirical study of feather modifications to show that the effect of physical properties of carotenoids on feather structure depends on their metabolic modification, their environmental recurrence, and biochemical redundancy, as predicted by the genetic assimilation hypothesis. Metabolized carotenoids caused less stochastic variation in feather structure and were more closely integrated with feather growth than were dietary carotenoids of the same molecular weight. These patterns were driven by the recurrence of organism-carotenoid associations: commonly used dietary carotenoids and biochemically redundant derived carotenoids caused less stochastic variation in feather structure than did rarely used or biochemically unique compounds. We discuss implications of genetic assimilation processes for the evolutionary diversification of diet-dependent animal coloration.

Modifications to Axially Symmetric Simulations Using New DSMC (2007) Algorithms

NASA Technical Reports Server (NTRS)

Liechty, Derek S.

2008-01-01

Several modifications aimed at improving physical accuracy are proposed for solving axially symmetric problems building on the DSMC (2007) algorithms introduced by Bird. Originally developed to solve nonequilibrium, rarefied flows, the DSMC method is now regularly used to solve complex problems over a wide range of Knudsen numbers. These new algorithms include features such as nearest neighbor collisions excluding the previous collision partners, separate collision and sampling cells, automatically adaptive variable time steps, a modified no-time counter procedure for collisions, and discontinuous and event-driven physical processes. Axially symmetric solutions require radial weighting for the simulated molecules since the molecules near the axis represent fewer real molecules than those farther away from the axis due to the difference in volume of the cells. In the present methodology, these radial weighting factors are continuous, linear functions that vary with the radial position of each simulated molecule. It is shown that how one defines the number of tentative collisions greatly influences the mean collision time near the axis. The method by which the grid is treated for axially symmetric problems also plays an important role near the axis, especially for scalar pressure. A new method to treat how the molecules are traced through the grid is proposed to alleviate the decrease in scalar pressure at the axis near the surface. Also, a modification to the duplication buffer is proposed to vary the duplicated molecular velocities while retaining the molecular kinetic energy and axially symmetric nature of the problem.

H2 metabolism is widespread and diverse among human colonic microbes

PubMed Central

Wolf, Patricia G.; Biswas, Ambarish; Morales, Sergio E.; Greening, Chris; Gaskins, H. Rex

2016-01-01

ABSTRACT Microbial molecular hydrogen (H2) cycling is central to metabolic homeostasis and microbial composition in the human gastrointestinal tract. Molecular H2 is produced as an endproduct of carbohydrate fermentation and is reoxidised primarily by sulfate-reduction, acetogenesis, and methanogenesis. However, the enzymatic basis for these processes is incompletely understood and the hydrogenases responsible have not been investigated. In this work, we surveyed the genomic and metagenomic distribution of hydrogenase-encoding genes in the human colon to infer dominant mechanisms of H2 cycling. The data demonstrate that 70% of gastrointestinal microbial species listed in the Human Microbiome Project encode the genetic capacity to metabolise H2. A wide variety of anaerobically-adapted hydrogenases were present, with [FeFe]-hydrogenases predominant. We subsequently analyzed the hydrogenase gene content of stools from 20 healthy human subjects. The hydrogenase gene content of all samples was overwhelmingly dominated by fermentative and electron-bifurcating [FeFe]-hydrogenases emerging from the Bacteroidetes and Firmicutes. This study supports that H2 metabolism in the human gut is driven by fermentative H2 production and interspecies H2 transfer. However, it suggests that electron-bifurcation rather than respiration is the dominant mechanism of H2 reoxidation in the human colon, generating reduced ferredoxin to sustain carbon-fixation (e.g. acetogenesis) and respiration (via the Rnf complex). This work provides the first comprehensive bioinformatic insight into the mechanisms of H2 metabolism in the human colon. PMID:27123663

Estrogen and female reproductive tract innervation: cellular and molecular mechanisms of autonomic neuroplasticity

PubMed Central

Brauer, M. Mónica; Smith, Peter G.

2014-01-01

The female reproductive tract undergoes remarkable functional and structural changes associated with cycling, conception and pregnancy, and it is likely advantageous to both individual and species to alter relationships between reproductive tissues and innervation. For several decades, it has been appreciated that the mammalian uterus undergoes massive sympathetic axon depletion in late pregnancy, possibly representing an adaptation to promote smooth muscle quiescence and sustained blood flow. Innervation to other structures such as cervix and vagina also undergo pregnancy-related changes in innervation that may facilitate parturition. These tissues provide highly tractable models for examining cellular and molecular mechanisms underlying peripheral nervous system plasticity. Studies show that estrogen elicits rapid degeneration of sympathetic terminal axons in myometrium, which regenerate under low-estrogen conditions. Degeneration is mediated by the target tissue: under estrogen's influence, the myometrium produces proteins repulsive to sympathetic axons including BDNF, neurotrimin, semaphorins, and pro-NGF, and extracellular matrix components are remodeled. Interestingly, nerve depletion does not involve diminished levels of classical sympathetic neurotrophins that promote axon growth. Estrogen also affects sympathetic neuron neurotrophin receptor expression in ways that appear to favor pro-degenerative effects of the target tissue. In contrast to the uterus, estrogen depletes vaginal autonomic and nociceptive axons, with the latter driven in part by estrogen-induced suppression BMP4 synthesis. These findings illustrate that hormonally mediated physiological plasticity is a highly complex phenomenon involving multiple, predominantly repulsive target-derived factors acting in concert to achieve rapid and selective reductions in innervation. PMID:25530517

Adaptive Finite Element Methods for Continuum Damage Modeling

NASA Technical Reports Server (NTRS)

Min, J. B.; Tworzydlo, W. W.; Xiques, K. E.

1995-01-01

The paper presents an application of adaptive finite element methods to the modeling of low-cycle continuum damage and life prediction of high-temperature components. The major objective is to provide automated and accurate modeling of damaged zones through adaptive mesh refinement and adaptive time-stepping methods. The damage modeling methodology is implemented in an usual way by embedding damage evolution in the transient nonlinear solution of elasto-viscoplastic deformation problems. This nonlinear boundary-value problem is discretized by adaptive finite element methods. The automated h-adaptive mesh refinements are driven by error indicators, based on selected principal variables in the problem (stresses, non-elastic strains, damage, etc.). In the time domain, adaptive time-stepping is used, combined with a predictor-corrector time marching algorithm. The time selection is controlled by required time accuracy. In order to take into account strong temperature dependency of material parameters, the nonlinear structural solution a coupled with thermal analyses (one-way coupling). Several test examples illustrate the importance and benefits of adaptive mesh refinements in accurate prediction of damage levels and failure time.

A Meta-Analysis of Urban Climate Change Adaptation ...

EPA Pesticide Factsheets

The concentration of people, infrastructure, and ecosystem services in urban areas make them prime sites for climate change adaptation. While advances have been made in developing frameworks for adaptation planning and identifying both real and potential barriers to action, empirical work evaluating urban adaptation planning processes has been relatively piecemeal. Existing assessments of current experience with urban adaptation provide necessarily broad generalizations based on the available peer-reviewed literature. This paper uses a meta-analysis of U.S. cities’ current experience with urban adaptation planning drawing from 54 sources that include peer-reviewed literature, government reports, white papers, and reports published by non-governmental organizations. The analysis specifically evaluates the institutional support structures being developed for urban climate change adaptation. The results demonstrate that adaptation planning is driven by a desire to reduce vulnerability and often catalyzes new collaborations and coordination mechanisms in urban governance. As a result, building capacity for urban climate change adaptation planning requires a focus not only on city governments themselves but also on the complex horizontal and vertical networks that have arisen around such efforts. Existing adaptation planning often lacks attention to equity issues, social vulnerability, and the influence of non-climatic factors on vulnerability. Engaging city govern

Phenotype-driven molecular autopsy for sudden cardiac death.

PubMed

Cann, F; Corbett, M; O'Sullivan, D; Tennant, S; Hailey, H; Grieve, J H K; Broadhurst, P; Rankin, R; Dean, J C S

2017-01-01

A phenotype-driven approach to molecular autopsy based in a multidisciplinary team comprising clinical and laboratory genetics, forensic medicine and cardiology is described. Over a 13 year period, molecular autopsy was undertaken in 96 sudden cardiac death cases. A total of 46 cases aged 1-40 years had normal hearts and suspected arrhythmic death. Seven (15%) had likely pathogenic variants in ion channelopathy genes [KCNQ1 (1), KCNH2 (4), SCN5A (1), RyR2(1)]. Fifty cases aged between 2 and 67 had a cardiomyopathy. Twenty-five had arrhythmogenic right ventricular cardiomyopathy (ARVC), 10 dilated cardiomyopathy (DCM) and 15 hypertrophic cardiomyopathy (HCM). Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1). Uptake of cascade screening in relatives was higher when a molecular diagnosis was made at autopsy. In three families, variants previously published as pathogenic were detected, but clinical investigation revealed no abnormalities in carrier relatives. With a conservative approach to defining pathogenicity of sequence variants incorporating family phenotype information and population genomic data, a molecular diagnosis was made in 15% of sudden arrhythmic deaths and 18% of cardiomyopathy deaths. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sentimental value and its influence on hedonic adaptation.

PubMed

Yang, Yang; Galak, Jeff

2015-11-01

Sentimental value is a highly prevalent, yet largely understudied phenomenon. We introduce the construct of sentimental value and investigate how and why sentimental value influences hedonic adaptation. Across 7 studies, we examine the antecedents of sentimental value and demonstrate its effect on hedonic adaptation using both naturally occurring and experimentally manipulated items with sentimental value. We further test the underlying process linking sentimental value and hedonic adaptation by showing that whereas feature-related utility decreases for all items with time, sentimental value typically does not, and that sentimental value moderates the influence of the decrement in feature-related utility on hedonic adaptation. Moreover, this moderating effect of sentimental value is driven by a shift in focus from features of the item to the associations that item possess. We conclude with a discussion of related phenomena and implications for individuals. (c) 2015 APA, all rights reserved).

Accounting for sequential trial effects in the flanker task: conflict adaptation or associative priming?

PubMed

Nieuwenhuis, Sander; Stins, John F; Posthuma, Danielle; Polderman, Tinca J C; Boomsma, Dorret I; de Geus, Eco J

2006-09-01

The conflict-control loop theory proposes that the detection of conflict in information processing triggers an increase in cognitive control, resulting in improved performance on the subsequent trial. This theory seems consistent with the robust finding that conflict susceptibility is reduced following correct trials associated with high conflict: the conflict adaptation effect. However, despite providing favorable conditions for eliciting and detecting conflict-triggered performance adjustments, none of the five experiments reported here provide unequivocal evidence of such adjustments. Instead, the results corroborate and extend earlier findings by demonstrating that the conflict adaptation effect, at least in the flanker task, is only present for a specific subset of trial sequences that is characterized by a response repetition. This pattern of results provides strong evidence that the conflict adaptation effect reflects associative stimulus-response priming instead of conflict-driven adaptations in cognitive control.

Racial-Ethnic Identity and Adjustment in Canadian Indigenous Adolescents

ERIC Educational Resources Information Center

Gfellner, Barbara M.; Armstrong, Helen D.

2013-01-01

This study supported associations between three theoretically driven conceptualizations of racial and ethnic identity (REI; Multigroup Ethnic Identity Measure; Multidimensional Racial Identity Measure; Bicultural Identity Measure) and with adaptive functioning among Canadian indigenous adolescents in middle school to high school. Age differences…

Concurrent exercise training: do opposites distract?

PubMed

Coffey, Vernon G; Hawley, John A

2017-05-01

Specificity is a core principle of exercise training to promote the desired adaptations for maximising athletic performance. The principle of specificity of adaptation is underpinned by the volume, intensity, frequency and mode of contractile activity and is most evident when contrasting the divergent phenotypes that result after undertaking either prolonged endurance or resistance training. The molecular profiles that generate the adaptive response to different exercise modes have undergone intense scientific scrutiny. Given divergent exercise induces similar signalling and gene expression profiles in skeletal muscle of untrained or recreationally active individuals, what is currently unclear is how the specificity of the molecular response is modified by prior training history. The time course of adaptation and when 'phenotype specificity' occurs has important implications for exercise prescription. This context is essential when attempting to concomitantly develop resistance to fatigue (through endurance-based exercise) and increased muscle mass (through resistance-based exercise), typically termed 'concurrent training'. Chronic training studies provide robust evidence that endurance exercise can attenuate muscle hypertrophy and strength but the mechanistic underpinning of this 'interference' effect with concurrent training is unknown. Moreover, despite the potential for several key regulators of muscle metabolism to explain an incompatibility in adaptation between endurance and resistance exercise, it now seems likely that multiple integrated, rather than isolated, effectors or processes generate the interference effect. Here we review studies of the molecular responses in skeletal muscle and evidence for the interference effect with concurrent training within the context of the specificity of training adaptation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Insights into the sequence parameters for halophilic adaptation.

PubMed

Nath, Abhigyan

2016-03-01

The sequence parameters for halophilic adaptation are still not fully understood. To understand the molecular basis of protein hypersaline adaptation, a detailed analysis is carried out, and investigated the likely association of protein sequence attributes to halophilic adaptation. A two-stage strategy is implemented, where in the first stage a supervised machine learning classifier is build, giving an overall accuracy of 86 % on stratified tenfold cross validation and 90 % on blind testing set, which are better than the previously reported results. The second stage consists of statistical analysis of sequence features and possible extraction of halophilic molecular signatures. The results of this study showed that, halophilic proteins are characterized by lower average charge, lower K content, and lower S content. A statistically significant preference/avoidance list of sequence parameters is also reported giving insights into the molecular basis of halophilic adaptation. D, Q, E, H, P, T, V are significantly preferred while N, C, I, K, M, F, S are significantly avoided. Among amino acid physicochemical groups, small, polar, charged, acidic and hydrophilic groups are preferred over other groups. The halophilic proteins also showed a preference for higher average flexibility, higher average polarity and avoidance for higher average positive charge, average bulkiness and average hydrophobicity. Some interesting trends observed in dipeptide counts are also reported. Further a systematic statistical comparison is undertaken for gaining insights into the sequence feature distribution in different residue structural states. The current analysis may facilitate the understanding of the mechanism of halophilic adaptation clearer, which can be further used for rational design of halophilic proteins.

Primary Molecular Disorders and Secondary Biological Adaptations in Bartter Syndrome

PubMed Central

Deschênes, Georges; Fila, Marc

2011-01-01

Bartter syndrome is a hereditary disorder that has been characterized by the association of hypokalemia, alkalosis, and the hypertrophy of the juxtaglomerular complex with secondary hyperaldosteronism and normal blood pressure. By contrast, the genetic causes of Bartter syndrome primarily affect molecular structures directly involved in the sodium reabsorption at the level of the Henle loop. The ensuing urinary sodium wasting and chronic sodium depletion are responsible for the contraction of the extracellular volume, the activation of the renin-aldosterone axis, the secretion of prostaglandins, and the biological adaptations of downstream tubular segments, meaning the distal convoluted tubule and the collecting duct. These secondary biological adaptations lead to hypokalemia and alkalosis, illustrating a close integration of the solutes regulation in the tubular structures. PMID:21941653

Molecular Bases of cyclodextrin Adapter Interactions with Engineered Protein Nanopores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banerjee, A.; Mikhailova, E; Cheley, S

2010-01-01

Engineered protein pores have several potential applications in biotechnology: as sensor elements in stochastic detection and ultrarapid DNA sequencing, as nanoreactors to observe single-molecule chemistry, and in the construction of nano- and micro-devices. One important class of pores contains molecular adapters, which provide internal binding sites for small molecules. Mutants of the {alpha}-hemolysin ({alpha}HL) pore that bind the adapter {beta}-cyclodextrin ({beta}CD) {approx}10{sup 4} times more tightly than the wild type have been obtained. We now use single-channel electrical recording, protein engineering including unnatural amino acid mutagenesis, and high-resolution x-ray crystallography to provide definitive structural information on these engineered protein nanoporesmore » in unparalleled detail.« less

Climate-Driven Reshuffling of Species and Genes: Potential Conservation Roles for Species Translocations and Recombinant Hybrid Genotypes

PubMed Central

Scriber, Jon Mark

2013-01-01

Comprising 50%–75% of the world’s fauna, insects are a prominent part of biodiversity in communities and ecosystems globally. Biodiversity across all levels of biological classifications is fundamentally based on genetic diversity. However, the integration of genomics and phylogenetics into conservation management may not be as rapid as climate change. The genetics of hybrid introgression as a source of novel variation for ecological divergence and evolutionary speciation (and resilience) may generate adaptive potential and diversity fast enough to respond to locally-altered environmental conditions. Major plant and herbivore hybrid zones with associated communities deserve conservation consideration. This review addresses functional genetics across multi-trophic-level interactions including “invasive species” in various ecosystems as they may become disrupted in different ways by rapid climate change. “Invasive genes” (into new species and populations) need to be recognized for their positive creative potential and addressed in conservation programs. “Genetic rescue” via hybrid translocations may provide needed adaptive flexibility for rapid adaptation to environmental change. While concerns persist for some conservationists, this review emphasizes the positive aspects of hybrids and hybridization. Specific implications of natural genetic introgression are addressed with a few examples from butterflies, including transgressive phenotypes and climate-driven homoploid recombinant hybrid speciation. Some specific examples illustrate these points using the swallowtail butterflies (Papilionidae) with their long-term historical data base (phylogeographical diversity changes) and recent (3-decade) climate-driven temporal and genetic divergence in recombinant homoploid hybrids and relatively recent hybrid speciation of Papilio appalachiensis in North America. Climate-induced “reshuffling” (recombinations) of species composition, genotypes, and genomes may become increasingly ecologically and evolutionarily predictable, but future conservation management programs are more likely to remain constrained by human behavior than by lack of academic knowledge. PMID:26462579

The role of parasite-driven selection in shaping landscape genomic structure in red grouse (Lagopus lagopus scotica).

PubMed

Wenzel, Marius A; Douglas, Alex; James, Marianne C; Redpath, Steve M; Piertney, Stuart B

2016-01-01

Landscape genomics promises to provide novel insights into how neutral and adaptive processes shape genome-wide variation within and among populations. However, there has been little emphasis on examining whether individual-based phenotype-genotype relationships derived from approaches such as genome-wide association (GWAS) manifest themselves as a population-level signature of selection in a landscape context. The two may prove irreconcilable as individual-level patterns become diluted by high levels of gene flow and complex phenotypic or environmental heterogeneity. We illustrate this issue with a case study that examines the role of the highly prevalent gastrointestinal nematode Trichostrongylus tenuis in shaping genomic signatures of selection in red grouse (Lagopus lagopus scotica). Individual-level GWAS involving 384 SNPs has previously identified five SNPs that explain variation in T. tenuis burden. Here, we examine whether these same SNPs display population-level relationships between T. tenuis burden and genetic structure across a small-scale landscape of 21 sites with heterogeneous parasite pressure. Moreover, we identify adaptive SNPs showing signatures of directional selection using F(ST) outlier analysis and relate population- and individual-level patterns of multilocus neutral and adaptive genetic structure to T. tenuis burden. The five candidate SNPs for parasite-driven selection were neither associated with T. tenuis burden on a population level, nor under directional selection. Similarly, there was no evidence of parasite-driven selection in SNPs identified as candidates for directional selection. We discuss these results in the context of red grouse ecology and highlight the broader consequences for the utility of landscape genomics approaches for identifying signatures of selection. © 2015 John Wiley & Sons Ltd.

Climate-Driven Reshuffling of Species and Genes: Potential Conservation Roles for Species Translocations and Recombinant Hybrid Genotypes.

PubMed

Scriber, Jon Mark

2013-12-24

Comprising 50%-75% of the world's fauna, insects are a prominent part of biodiversity in communities and ecosystems globally. Biodiversity across all levels of biological classifications is fundamentally based on genetic diversity. However, the integration of genomics and phylogenetics into conservation management may not be as rapid as climate change. The genetics of hybrid introgression as a source of novel variation for ecological divergence and evolutionary speciation (and resilience) may generate adaptive potential and diversity fast enough to respond to locally-altered environmental conditions. Major plant and herbivore hybrid zones with associated communities deserve conservation consideration. This review addresses functional genetics across multi-trophic-level interactions including "invasive species" in various ecosystems as they may become disrupted in different ways by rapid climate change. "Invasive genes" (into new species and populations) need to be recognized for their positive creative potential and addressed in conservation programs. "Genetic rescue" via hybrid translocations may provide needed adaptive flexibility for rapid adaptation to environmental change. While concerns persist for some conservationists, this review emphasizes the positive aspects of hybrids and hybridization. Specific implications of natural genetic introgression are addressed with a few examples from butterflies, including transgressive phenotypes and climate-driven homoploid recombinant hybrid speciation. Some specific examples illustrate these points using the swallowtail butterflies (Papilionidae) with their long-term historical data base (phylogeographical diversity changes) and recent (3-decade) climate-driven temporal and genetic divergence in recombinant homoploid hybrids and relatively recent hybrid speciation of Papilio appalachiensis in North America. Climate-induced "reshuffling" (recombinations) of species composition, genotypes, and genomes may become increasingly ecologically and evolutionarily predictable, but future conservation management programs are more likely to remain constrained by human behavior than by lack of academic knowledge.

Experience-driven plasticity in binocular vision

PubMed Central

Klink, P. Christiaan; Brascamp, Jan W.; Blake, Randolph; van Wezel, Richard J.A.

2010-01-01

Summary Experience-driven neuronal plasticity allows the brain to adapt its functional connectivity to recent sensory input. Here we use binocular rivalry [1], an experimental paradigm where conflicting images are presented to the individual eyes, to demonstrate plasticity in the neuronal mechanisms that convert visual information from two separated retinas into single perceptual experiences. Perception during binocular rivalry tended to initially consist of alternations between exclusive representations of monocularly defined images, but upon prolonged exposure, mixture percepts became more prevalent. The completeness of suppression, reflected in the incidence of mixture percepts, plausibly reflects the strength of inhibition that likely plays a role in binocular rivalry [2]. Recovery of exclusivity was possible, but required highly specific binocular stimulation. Documenting the prerequisites for these observed changes in perceptual exclusivity, our experiments suggest experience-driven plasticity at interocular inhibitory synapses, driven by the (lack of) correlated activity of neurons representing the conflicting stimuli. This form of plasticity is consistent with a previously proposed, but largely untested, anti-Hebbian learning mechanism for inhibitory synapses in vision [3, 4]. Our results implicate experience-driven plasticity as one governing principle in the neuronal organization of binocular vision. PMID:20674360

New perspectives on adolescent motivated behavior: attention and conditioning

PubMed Central

Ernst, Monique; Daniele, Teresa; Frantz, Kyle

2011-01-01

Adolescence is a critical transition period, during which fundamental changes prepare the adolescent for becoming an adult. Heuristic models of the neurobiology of adolescent behavior have emerged, promoting the central role of reward and motivation, coupled with cognitive immaturities. Here, we bring focus to two basic sets of processes, attention and conditioning, which are essential for adaptive behavior. Using the dual-attention model developed by Corbetta and Shulman (2002), which identifies a stimulus-driven and a goal-driven attention network, we propose a balance that favors stimulus-driven attention over goal-driven attention in youth. Regarding conditioning, we hypothesize that stronger associations tend to be made between environmental cues and appetitive stimuli, and weaker associations with aversive stimuli, in youth relative to adults. An attention system geared to prioritize stimulus-driven attention, together with more powerful associative learning with appetitive incentives, contribute to shape patterns of adolescent motivated behavior. This proposed bias in attention and conditioning function could facilitate the impulsive, novelty-seeking and risk-taking behavior that is typical of many adolescents. PMID:21977221

Limited angle CT reconstruction by simultaneous spatial and Radon domain regularization based on TV and data-driven tight frame

NASA Astrophysics Data System (ADS)

Zhang, Wenkun; Zhang, Hanming; Wang, Linyuan; Cai, Ailong; Li, Lei; Yan, Bin

2018-02-01

Limited angle computed tomography (CT) reconstruction is widely performed in medical diagnosis and industrial testing because of the size of objects, engine/armor inspection requirements, and limited scan flexibility. Limited angle reconstruction necessitates usage of optimization-based methods that utilize additional sparse priors. However, most of conventional methods solely exploit sparsity priors of spatial domains. When CT projection suffers from serious data deficiency or various noises, obtaining reconstruction images that meet the requirement of quality becomes difficult and challenging. To solve this problem, this paper developed an adaptive reconstruction method for limited angle CT problem. The proposed method simultaneously uses spatial and Radon domain regularization model based on total variation (TV) and data-driven tight frame. Data-driven tight frame being derived from wavelet transformation aims at exploiting sparsity priors of sinogram in Radon domain. Unlike existing works that utilize pre-constructed sparse transformation, the framelets of the data-driven regularization model can be adaptively learned from the latest projection data in the process of iterative reconstruction to provide optimal sparse approximations for given sinogram. At the same time, an effective alternating direction method is designed to solve the simultaneous spatial and Radon domain regularization model. The experiments for both simulation and real data demonstrate that the proposed algorithm shows better performance in artifacts depression and details preservation than the algorithms solely using regularization model of spatial domain. Quantitative evaluations for the results also indicate that the proposed algorithm applying learning strategy performs better than the dual domains algorithms without learning regularization model

Computational Properties of the Hippocampus Increase the Efficiency of Goal-Directed Foraging through Hierarchical Reinforcement Learning

PubMed Central

Chalmers, Eric; Luczak, Artur; Gruber, Aaron J.

2016-01-01

The mammalian brain is thought to use a version of Model-based Reinforcement Learning (MBRL) to guide “goal-directed” behavior, wherein animals consider goals and make plans to acquire desired outcomes. However, conventional MBRL algorithms do not fully explain animals' ability to rapidly adapt to environmental changes, or learn multiple complex tasks. They also require extensive computation, suggesting that goal-directed behavior is cognitively expensive. We propose here that key features of processing in the hippocampus support a flexible MBRL mechanism for spatial navigation that is computationally efficient and can adapt quickly to change. We investigate this idea by implementing a computational MBRL framework that incorporates features inspired by computational properties of the hippocampus: a hierarchical representation of space, “forward sweeps” through future spatial trajectories, and context-driven remapping of place cells. We find that a hierarchical abstraction of space greatly reduces the computational load (mental effort) required for adaptation to changing environmental conditions, and allows efficient scaling to large problems. It also allows abstract knowledge gained at high levels to guide adaptation to new obstacles. Moreover, a context-driven remapping mechanism allows learning and memory of multiple tasks. Simulating dorsal or ventral hippocampal lesions in our computational framework qualitatively reproduces behavioral deficits observed in rodents with analogous lesions. The framework may thus embody key features of how the brain organizes model-based RL to efficiently solve navigation and other difficult tasks. PMID:28018203

Adaptively restrained molecular dynamics in LAMMPS

NASA Astrophysics Data System (ADS)

Kant Singh, Krishna; Redon, Stephane

2017-07-01

Adaptively restrained molecular dynamics (ARMD) is a recently introduced particles simulation method that switches positional degrees of freedom on and off during simulation in order to speed up calculations. In the NVE ensemble, ARMD allows users to trade between precision and speed while, in the NVT ensemble, it makes it possible to compute statistical averages faster. Despite the conceptual simplicity of the approach, however, integrating it in existing molecular dynamics packages is non-trivial, in particular since implemented potentials should a priori be rewritten to take advantage of frozen particles and achieve a speed-up. In this paper, we present novel algorithms for integrating ARMD in LAMMPS, a popular multi-purpose molecular simulation package. In particular, we demonstrate how to enable ARMD in LAMMPS without having to re-implement all available force fields. The proposed algorithms are assessed on four different benchmarks, and show how they allow us to speed up simulations up to one order of magnitude.

Molecular engineering of antibodies for therapeutic and diagnostic purposes

PubMed Central

Ducancel, Frédéric; Muller, Bruno H.

2012-01-01

During the past ten years, monoclonal antibodies (mAbs) have taken center stage in the field of targeted therapy and diagnosis. This increased interest in mAbs is due to their binding accuracy (affinity and specificity) together with the original molecular and structural rules that govern interactions with their cognate antigen. In addition, the effector properties of antibodies constitute a second major advantage associated with their clinical use. The development of molecular and structural engineering and more recently of in vitro evolution of antibodies has opened up new perspectives in the de novo design of antibodies more adapted to clinical and diagnostic use. Thus, efforts are regularly made by researchers to improve or modulate antibody recognition properties, to adapt their pharmacokinetics, engineer their stability, and control their immunogenicity. This review presents the latest molecular engineering results on mAbs with therapeutic and diagnostic applications. PMID:22684311

From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry.

PubMed

Lehn, Jean-Marie

2007-02-01

Supramolecular chemistry has developed over the last forty years as chemistry beyond the molecule. Starting with the investigation of the basis of molecular recognition, it has explored the implementation of molecular information in the programming of chemical systems towards self-organisation processes, that may occur either on the basis of design or with selection of their components. Supramolecular entities are by nature constitutionally dynamic by virtue of the lability of non-covalent interactions. Importing such features into molecular chemistry, through the introduction of reversible bonds into molecules, leads to the emergence of a constitutional dynamic chemistry, covering both the molecular and supramolecular levels. It considers chemical objects and systems capable of responding to external solicitations by modification of their constitution through component exchange or reorganisation. It thus opens the way towards an adaptive and evolutive chemistry, a further step towards the chemistry of complex matter.

Improved Breast Cancer Detection Using a Novel In Situ Method to Visualize Clonality.

DTIC Science & Technology

1998-07-01

photosensitivity and laser driven systems are encouraging, and suggest the possibility of high-throughput systems. Biolithography may thus provide new opportunities for molecular diagnostics of solid tumors.

Solving Immunology?

PubMed

Vodovotz, Yoram; Xia, Ashley; Read, Elizabeth L; Bassaganya-Riera, Josep; Hafler, David A; Sontag, Eduardo; Wang, Jin; Tsang, John S; Day, Judy D; Kleinstein, Steven H; Butte, Atul J; Altman, Matthew C; Hammond, Ross; Sealfon, Stuart C

2017-02-01

Emergent responses of the immune system result from the integration of molecular and cellular networks over time and across multiple organs. High-content and high-throughput analysis technologies, concomitantly with data-driven and mechanistic modeling, hold promise for the systematic interrogation of these complex pathways. However, connecting genetic variation and molecular mechanisms to individual phenotypes and health outcomes has proven elusive. Gaps remain in data, and disagreements persist about the value of mechanistic modeling for immunology. Here, we present the perspectives that emerged from the National Institute of Allergy and Infectious Disease (NIAID) workshop 'Complex Systems Science, Modeling and Immunity' and subsequent discussions regarding the potential synergy of high-throughput data acquisition, data-driven modeling, and mechanistic modeling to define new mechanisms of immunological disease and to accelerate the translation of these insights into therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Crystal nucleation of colloidal hard dumbbells

NASA Astrophysics Data System (ADS)

Ni, Ran; Dijkstra, Marjolein

2011-01-01

Using computer simulations, we investigate the homogeneous crystal nucleation in suspensions of colloidal hard dumbbells. The free energy barriers are determined by Monte Carlo simulations using the umbrella sampling technique. We calculate the nucleation rates for the plastic crystal and the aperiodic crystal phase using the kinetic prefactor as determined from event driven molecular dynamics simulations. We find good agreement with the nucleation rates determined from spontaneous nucleation events observed in event driven molecular dynamics simulations within error bars of one order of magnitude. We study the effect of aspect ratio of the dumbbells on the nucleation of plastic and aperiodic crystal phases, and we also determine the structure of the critical nuclei. Moreover, we find that the nucleation of the aligned close-packed crystal structure is strongly suppressed by a high free energy barrier at low supersaturations and slow dynamics at high supersaturations.

Ultrafast Nanoscale Raman Thermometry Proves Heating Is Not a Primary Mechanism for Plasmon-Driven Photocatalysis.

PubMed

Keller, Emily L; Frontiera, Renee R

2018-06-08

Plasmonic materials efficiently convert light to various forms of energies for many applications, including photocatalysis, photovoltaics, and photothermal therapies. In particular, plasmonic photocatalysts hold incredible promise for highly selective sunlight-driven catalysis through the generation of highly energetic holes and electrons used to drive chemical reactions. However, plasmons are also known to generate heat, and the partitioning of photoexcitation energy into hot carriers and heat on molecularly relevant time scales is not well understood, yet plays a crucial role in designing and understanding these photocatalysts. Using an ultrafast surface-enhanced Raman thermometry technique, we probe the effective temperature, equivalent to the mode-specific increase of vibrational kinetic energy, of molecules adsorbed to gold nanoparticle aggregates in the most active hot spots on the picosecond time scale of chemical reactivity. This represents the first measurement of vibrational energy deposition for coupled molecular-plasmonic systems on the picosecond time scale of molecular motion. We find that upon plasmon excitation, the adsorbates in the hot spots undergo an initial energy transfer within several picoseconds that changes the effective temperature of the system by less than 100 K, even at peak flux values 10 8 times stronger than focused sunlight. The energy quickly dissipates from the adsorbates into the surroundings in less than 5 ps, even at the highest values of photoexcitation. This surprisingly modest energy transfer of the most active regions of the plasmonic materials on the ultrafast time scale decisively proves that most plasmonic photocatalysis is not primarily thermally driven.

Ancient homology underlies adaptive mimetic diversity across butterflies

PubMed Central

Gallant, Jason R.; Imhoff, Vance E.; Martin, Arnaud; Savage, Wesley K.; Chamberlain, Nicola L.; Pote, Ben L.; Peterson, Chelsea; Smith, Gabriella E.; Evans, Benjamin; Reed, Robert D.; Kronforst, Marcus R.; Mullen, Sean P.

2014-01-01

Convergent evolution provides a rare, natural experiment with which to test the predictability of adaptation at the molecular level. Little is known about the molecular basis of convergence over macro-evolutionary timescales. Here we use a combination of positional cloning, population genomic resequencing, association mapping and developmental data to demonstrate that positionally orthologous nucleotide variants in the upstream region of the same gene, WntA, are responsible for parallel mimetic variation in two butterfly lineages that diverged >65 million years ago. Furthermore, characterization of spatial patterns of WntA expression during development suggests that alternative regulatory mechanisms underlie wing pattern variation in each system. Taken together, our results reveal a strikingly predictable molecular basis for phenotypic convergence over deep evolutionary time. PMID:25198507

Na+-driven bacterial flagellar motors.

PubMed

Imae, Y; Atsumi, T

1989-12-01

Bacterial flagellar motors are the reversible rotary engine which propels the cell by rotating a helical flagellar filament as a screw propeller. The motors are embedded in the cytoplasmic membrane, and the energy for rotation is supplied by the electrochemical potential of specific ions across the membrane. Thus, the analysis of motor rotation at the molecular level is linked to an understanding of how the living system converts chemical energy into mechanical work. Based on the coupling ions, the motors are divided into two types; one is the H+-driven type found in neutrophiles such as Bacillus subtilis and Escherichia coli and the other is the Na+-driven type found in alkalophilic Bacillus and marine Vibrio. In this review, we summarize the current status of research on the rotation mechanism of the Na+-driven flagellar motors, which introduces several new aspects in the analysis.

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus.

PubMed

O'Hanlon, Karen A; Margison, Geoffrey P; Hatch, Amy; Fitzpatrick, David A; Owens, Rebecca A; Doyle, Sean; Jones, Gary W

2012-09-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O(6)-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O(6)-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system.

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

PubMed Central

O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

2012-01-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

Mudskippers and Their Genetic Adaptations to an Amphibious Lifestyle

PubMed Central

You, Xinxin; Sun, Min; Li, Jia; Bian, Chao; Chen, Jieming; Yu, Hui; Shi, Qiong

2018-01-01

Simple Summary Mudskippers are an interesting group of goggle-eyed amphibious fish that can live both in water and on land. They are a useful model for obtaining insights into the genetic mechanisms underlying the terrestrial adaptations of amphibious fish. This review summarizes the morphological and physiological modifications of representative mudskippers, and focuses on the recent advancement of genomic studies on their genetic adaptations to the amphibious lifestyle. Abstract Mudskippers are the largest group of amphibious teleost fish that are uniquely adapted to live on mudflats. During their successful transition from aqueous life to terrestrial living, these fish have evolved morphological and physiological modifications of aerial vision and olfaction, higher ammonia tolerance, aerial respiration, improved immunological defense against terrestrial pathogens, and terrestrial locomotion using protruded pectoral fins. Comparative genomic and transcriptomic data have been accumulated and analyzed for understanding molecular mechanisms of the terrestrial adaptations. Our current review provides a general introduction to mudskippers and recent research advances of their genetic adaptations to the amphibious lifestyle, which will be helpful for understanding the evolutionary transition of vertebrates from water to land. Our insights into the genomes and transcriptomes will also support molecular breeding, functional identification, and natural compound screening. PMID:29414871

Natural variation and the capacity to adapt to ocean acidification in the keystone sea urchin Strongylocentrotus purpuratus.

PubMed

Kelly, Morgan W; Padilla-Gamiño, Jacqueline L; Hofmann, Gretchen E

2013-08-01

A rapidly growing body of literature documents the potential negative effects of CO2 -driven ocean acidification (OA) on marine organisms. However, nearly all this work has focused on the effects of future conditions on modern populations, neglecting the role of adaptation. Rapid evolution can alter demographic responses to environmental change, ultimately affecting the likelihood of population persistence, but the capacity for adaptation will differ among populations and species. Here, we measure the capacity of the ecologically important purple sea urchin Strongylocentrotus purpuratus to adapt to OA, using a breeding experiment to estimate additive genetic variance for larval size (an important component of fitness) under future high-pCO2 /low-pH conditions. Although larvae reared under future conditions were smaller than those reared under present-day conditions, we show that there is also abundant genetic variation for body size under elevated pCO2 , indicating that this trait can evolve. The observed heritability of size was 0.40 ± 0.32 (95% CI) under low pCO2 , and 0.50 ± 0.30 under high-pCO2 conditions. Accounting for the observed genetic variation in models of future larval size and demographic rates substantially alters projections of performance for this species in the future ocean. Importantly, our model shows that after incorporating the effects of adaptation, the OA-driven decrease in population growth rate is up to 50% smaller, than that predicted by the 'no-adaptation' scenario. Adults used in the experiment were collected from two sites on the coast of the Northeast Pacific that are characterized by different pH regimes, as measured by autonomous sensors. Comparing results between sites, we also found subtle differences in larval size under high-pCO2 rearing conditions, consistent with local adaptation to carbonate chemistry in the field. These results suggest that spatially varying selection may help to maintain genetic variation necessary for adaptation to future OA. © 2013 John Wiley & Sons Ltd.

Integrated Adaptive Scenarios for Ariculture: Synergies and Tradeoffs.

NASA Astrophysics Data System (ADS)

Malek, K.; Rajagopalan, K.; Adam, J. C.; Brady, M.; Stockle, C.; Liu, M.; Kruger, C. E.

2017-12-01

A wide variety of factors can drive adaptation of the agricultural production sector in response to climate change. Warming and increased growing season length can lead to adoption of newer plant varieties as well as increases in double cropping systems. Changes in expectations of drought frequency or economic factors could lead to adoption of new technology (such as irrigation technology or water trading systems) or crop choices with a view of reducing farm-level risk, and these choices can result in unintended system wide effects. These are all examples of producer adaptation decisions made with a long-term (multiple decades) view. In addition, producers respond to short-term (current year) shocks - such as drought events - through management strategies that include deficit irrigation, fallowing, nutrient management, and engaging in water trading. The effects of these short- and long-term decisions are not independent, and can drive or be driven by the other. For example, investment in new irrigation systems (long-term) can be driven by expectations of short-term crop productivity losses in drought years. Similarly, the capacity to manage for short-term shocks will depend on crop type and variety as well as adopted irrigation technologies. Our overarching objective is to understand the synergies and tradeoffs that exist when combining three potential long-term adaptation strategies and two short-term adaptation strategies, with a view of understanding the synergies and tradeoffs. We apply the integrated crop-hydrology modeling framework VIC-CropSyst, along with the water management module Yakima RiverWare to address these questions over our test area, the Yakima River basin. We consider adoption of a) more efficient irrigation technologies, slower growing crop varieties, and increased prevalence of double cropping systems as long-term adaptation strategies; and b) fallowing and deficit irrigation as short-term responses to droughts. We evaluate the individual and combined effect of these strategies on agricultural production. Preliminary results indicate that long-term adaptation strategies impact short-run adaptive capacities to drought shocks. The strategies are complementary under certain situations and results in tradeoffs in other situations, and we characterize these differences.

Communication: Low-energy free-electron driven molecular engineering: In situ preparation of intrinsically short-lived carbon-carbon covalent dimer of CO

NASA Astrophysics Data System (ADS)

Davis, Daly; Sajeev, Y.

2017-02-01

Molecular modification induced through the resonant attachment of a low energy electron (LEE) is a novel approach for molecular engineering. In this communication, we explore the possibility to use the LEE as a quantum tool for the in situ preparation of short lived molecules. Using ab initio quantum chemical methods, this possibility is best illustrated for the in situ preparation of the intrinsically short-lived carbon-carbon covalent dimer of CO from a glyoxal molecule. The chemical conversion of glyoxal to the covalent dimer of CO is initiated and driven by the resonant capture of a near 11 eV electron by the glyoxal molecule. The resulting two-particle one-hole (2p-1h) negative ion resonant state (NIRS) of the glyoxal molecule undergoes a barrierless radical dehydrogenation reaction and produces the covalent dimer of CO. The autoionization electron spectra from the 2p-1h NIRS at the dissociation limit of the dehydrogenation reaction provides access to the electronic states of the CO dimer. The overall process is an example of a catalytic electron reaction channel.

Generation of Raman lasers from nitrogen molecular ions driven by ultraintense laser fields

NASA Astrophysics Data System (ADS)

Yao, Jinping; Chu, Wei; Liu, Zhaoxiang; Xu, Bo; Chen, Jinming; Cheng, Ya

2018-03-01

Atmospheric lasing has aroused much interest in the past few years. The ‘air–laser’ opens promising potential for remote chemical sensing of trace gases with high sensitivity and specificity. At present, several approaches have been successfully implemented for generating highly coherent laser beams in atmospheric condition, including both amplified-spontaneous emission, and narrow-bandwidth stimulated emission in the forward direction in the presence of self-generated or externally injected seed pulses. Here, we report on generation of multiple-wavelength Raman lasers from nitrogen molecular ions ({{{N}}}2+), driven by intense mid-infrared laser fields. Intuitively, the approach appears problematic for the small nonlinear susceptibility of {{{N}}}2+ ions, whereas the efficiency of Raman laser can be significantly promoted in near-resonant condition. More surprisingly, a Raman laser consisting of a supercontinuum spanning from ∼310 to ∼392 nm has been observed resulting from a series near-resonant nonlinear processes including four-wave mixing, stimulated Raman scattering and cross phase modulation. To date, extreme nonlinear optics in molecular ions remains largely unexplored, which provides an alternative means for air–laser-based remote sensing applications.

Coarse-grained simulations of protein-protein association: an energy landscape perspective.

PubMed

Ravikumar, Krishnakumar M; Huang, Wei; Yang, Sichun

2012-08-22

Understanding protein-protein association is crucial in revealing the molecular basis of many biological processes. Here, we describe a theoretical simulation pipeline to study protein-protein association from an energy landscape perspective. First, a coarse-grained model is implemented and its applications are demonstrated via molecular dynamics simulations for several protein complexes. Second, an enhanced search method is used to efficiently sample a broad range of protein conformations. Third, multiple conformations are identified and clustered from simulation data and further projected on a three-dimensional globe specifying protein orientations and interacting energies. Results from several complexes indicate that the crystal-like conformation is favorable on the energy landscape even if the landscape is relatively rugged with metastable conformations. A closer examination on molecular forces shows that the formation of associated protein complexes can be primarily electrostatics-driven, hydrophobics-driven, or a combination of both in stabilizing specific binding interfaces. Taken together, these results suggest that the coarse-grained simulations and analyses provide an alternative toolset to study protein-protein association occurring in functional biomolecular complexes. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Coarse-Grained Simulations of Protein-Protein Association: An Energy Landscape Perspective

PubMed Central

Ravikumar, Krishnakumar M.; Huang, Wei; Yang, Sichun

2012-01-01

Understanding protein-protein association is crucial in revealing the molecular basis of many biological processes. Here, we describe a theoretical simulation pipeline to study protein-protein association from an energy landscape perspective. First, a coarse-grained model is implemented and its applications are demonstrated via molecular dynamics simulations for several protein complexes. Second, an enhanced search method is used to efficiently sample a broad range of protein conformations. Third, multiple conformations are identified and clustered from simulation data and further projected on a three-dimensional globe specifying protein orientations and interacting energies. Results from several complexes indicate that the crystal-like conformation is favorable on the energy landscape even if the landscape is relatively rugged with metastable conformations. A closer examination on molecular forces shows that the formation of associated protein complexes can be primarily electrostatics-driven, hydrophobics-driven, or a combination of both in stabilizing specific binding interfaces. Taken together, these results suggest that the coarse-grained simulations and analyses provide an alternative toolset to study protein-protein association occurring in functional biomolecular complexes. PMID:22947945

Variable-camber systems integration and operational performance of the AFTI/F-111 mission adaptive wing

NASA Technical Reports Server (NTRS)

Smith, John W.; Lock, Wilton P.; Payne, Gordon A.

1992-01-01

The advanced fighter technology integration, the AFTI/F-111 aircraft, is a preproduction F-111A testbed research airplane that was fitted with a smooth variable-camber mission adaptive wing. The camber was positioned and controlled by flexing the upper skins through rotary actuators and linkages driven by power drive units. The wing camber and control system are described. The measured servoactuator frequency responses are presented along with analytical predictions derived from the integrated characteristics of the control elements. A mission adaptive wing system chronology is used to illustrate and assess the reliability and dependability of the servoactuator system during 1524 hours of ground tests and 145 hours of flight testing.

Challenge and Change

ERIC Educational Resources Information Center

Mehaffy, George L.

2012-01-01

In the past twenty years, various industries have been forever altered by technology: newspapers, book publishing, the photography business, and many more. Higher education too faces unprecedented challenges primarily driven by rapid changes in technology. To meet these challenges and adapt to these changes, new models are needed. Six challenges…

Microbial-driven arsenic cycling in rice paddies amended with monosodium methanearsonate

USDA-ARS?s Scientific Manuscript database

Rice consumption is the second largest contributor to human arsenic exposure worldwide and is linked to many serious diseases. Because rice is uniquely adapted for agricultural production under flooded soils, arsenic species solubilized in such environments can be effectively transported into plant ...

In situ insights into shock-driven reactive flow

NASA Astrophysics Data System (ADS)

Dattelbaum, Dana

2017-06-01

Shock-driven reactions are commonplace. Examples include the detonation of high explosives, shock-driven dissociation of polymers, and transformation of carbon from graphite to diamond phases. The study of shock-driven chemical reactions is important for understanding reaction thresholds, their mechanisms and rates, and associated state sensitivities under the extreme conditions generated by shock compression. Reactions are distinguished by their thermicity - e.g. the volume and enthalpy changes along the reaction coordinate. A survey of the hallmarks of shock-driven reactivity for a variety of simple molecules and polymers will be presented, including benzene, acetylenes and nitriles, and formic acid. Many of the examples will illustrate the nature of the reactive flow through particle velocity wave profiles measured by in situ electromagnetic gauging in gas gun-driven plate impact experiments. General trends will be presented linking molecular moieties, shock temperatures, and reaction state sensitivities. Progress in applying bond-specific diagnostics will also be presented, including time-resolved Raman spectroscopy, and recent results of in situ x-ray diffraction of carbon at the Linac Coherent Light Souce (LCLS) free electron laser.

Olfaction, navigation, and the origin of isocortex

PubMed Central

Aboitiz, Francisco; Montiel, Juan F.

2015-01-01

There are remarkable similarities between the brains of mammals and birds in terms of microcircuit architecture, despite obvious differences in gross morphology and development. While in reptiles and birds the most expanding component (the dorsal ventricular ridge) displays an overall nuclear shape and derives from the lateral and ventral pallium, in mammals a dorsal pallial, six-layered isocortex shows the most remarkable elaboration. Regardless of discussions about possible homologies between mammalian and avian brains, a main question remains in explaining the emergence of the mammalian isocortex, because it represents a unique phenotype across amniotes. In this article, we propose that the origin of the isocortex was driven by behavioral adaptations involving olfactory driven goal-directed and navigating behaviors. These adaptations were linked with increasing sensory development, which provided selective pressure for the expansion of the dorsal pallium. The latter appeared as an interface in olfactory-hippocampal networks, contributing somatosensory information for navigating behavior. Sensory input from other modalities like vision and audition were subsequently recruited into this expanding region, contributing to multimodal associative networks. PMID:26578863

Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors.

PubMed

Patin, Etienne; Hasan, Milena; Bergstedt, Jacob; Rouilly, Vincent; Libri, Valentina; Urrutia, Alejandra; Alanio, Cécile; Scepanovic, Petar; Hammer, Christian; Jönsson, Friederike; Beitz, Benoît; Quach, Hélène; Lim, Yoong Wearn; Hunkapiller, Julie; Zepeda, Magge; Green, Cherie; Piasecka, Barbara; Leloup, Claire; Rogge, Lars; Huetz, François; Peguillet, Isabelle; Lantz, Olivier; Fontes, Magnus; Di Santo, James P; Thomas, Stéphanie; Fellay, Jacques; Duffy, Darragh; Quintana-Murci, Lluís; Albert, Matthew L

2018-03-01

The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.

Cloudweaver: Adaptive and Data-Driven Workload Manager for Generic Clouds

NASA Astrophysics Data System (ADS)

Li, Rui; Chen, Lei; Li, Wen-Syan

Cloud computing denotes the latest trend in application development for parallel computing on massive data volumes. It relies on clouds of servers to handle tasks that used to be managed by an individual server. With cloud computing, software vendors can provide business intelligence and data analytic services for internet scale data sets. Many open source projects, such as Hadoop, offer various software components that are essential for building a cloud infrastructure. Current Hadoop (and many others) requires users to configure cloud infrastructures via programs and APIs and such configuration is fixed during the runtime. In this chapter, we propose a workload manager (WLM), called CloudWeaver, which provides automated configuration of a cloud infrastructure for runtime execution. The workload management is data-driven and can adapt to dynamic nature of operator throughput during different execution phases. CloudWeaver works for a single job and a workload consisting of multiple jobs running concurrently, which aims at maximum throughput using a minimum set of processors.

m-BIRCH: an online clustering approach for computer vision applications

NASA Astrophysics Data System (ADS)

Madan, Siddharth K.; Dana, Kristin J.

2015-03-01

We adapt a classic online clustering algorithm called Balanced Iterative Reducing and Clustering using Hierarchies (BIRCH), to incrementally cluster large datasets of features commonly used in multimedia and computer vision. We call the adapted version modified-BIRCH (m-BIRCH). The algorithm uses only a fraction of the dataset memory to perform clustering, and updates the clustering decisions when new data comes in. Modifications made in m-BIRCH enable data driven parameter selection and effectively handle varying density regions in the feature space. Data driven parameter selection automatically controls the level of coarseness of the data summarization. Effective handling of varying density regions is necessary to well represent the different density regions in data summarization. We use m-BIRCH to cluster 840K color SIFT descriptors, and 60K outlier corrupted grayscale patches. We use the algorithm to cluster datasets consisting of challenging non-convex clustering patterns. Our implementation of the algorithm provides an useful clustering tool and is made publicly available.

Excited state dynamics & optical control of molecular motors

NASA Astrophysics Data System (ADS)

Wiley, Ted; Sension, Roseanne

2014-03-01

Chiral overcrowded alkenes are likely candidates for light driven rotary molecular motors. At their core, these molecular motors are based on the chromophore stilbene, undergoing ultrafast cis/trans photoisomerization about their central double bond. Unlike stilbene, the photochemistry of molecular motors proceeds in one direction only. This unidirectional rotation is a result of helicity in the molecule induced by steric hindrance. However, the steric hindrance which ensures unidirectional excited state rotation, has the unfortunate consequence of producing large ground state barriers which dramatically decrease the overall rate of rotation. These molecular scale ultrafast motors have only recently been studied by ultrafast spectroscopy. Our lab has studied the photochemistry and photophysics of a ``first generation'' molecular motor with UV-visible transient absorption spectroscopy. We hope to use optical pulse shaping to enhance the efficiency and turnover rate of these molecular motors.

Patterns of host adaptation in Frankliniella occidentalis among vegetable crops

USDA-ARS?s Scientific Manuscript database

The current study examined the variation in life table characteristics, and physiological, biochemical, and molecular bases of western flower thrips, Frankliniella occidentalis (Pergande) host adaptation patterns. The main objective was to determine whether host availability affects insect preferenc...

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

Non-invasive molecular imaging for preclinical cancer therapeutic development

PubMed Central

O'Farrell, AC; Shnyder, SD; Marston, G; Coletta, PL; Gill, JH

2013-01-01

Molecular and non-invasive imaging are rapidly emerging fields in preclinical cancer drug discovery. This is driven by the need to develop more efficacious and safer treatments, the advent of molecular-targeted therapeutics, and the requirements to reduce and refine current preclinical in vivo models. Such bioimaging strategies include MRI, PET, single positron emission computed tomography, ultrasound, and optical approaches such as bioluminescence and fluorescence imaging. These molecular imaging modalities have several advantages over traditional screening methods, not least the ability to quantitatively monitor pharmacodynamic changes at the cellular and molecular level in living animals non-invasively in real time. This review aims to provide an overview of non-invasive molecular imaging techniques, highlighting the strengths, limitations and versatility of these approaches in preclinical cancer drug discovery and development. PMID:23488622

Singing-driven gene expression in the developing songbird brain

PubMed Central

Johnson, Frank; Whitney, Osceola

2014-01-01

Neural and behavioral development arises from an integration of genetic and environmental influences, yet specifying the nature of this interaction remains a primary problem in neuroscience. Here, we review molecular and behavioral studies that focus on the role of singing-driven gene expression during neural and vocal development in the male zebra finch (Taeniopygia guttata), a songbird that learns a species-typical vocal pattern during juvenile development by imitating an adult male tutor. A primary aim of our lab has been to identify naturally-occurring environmental influences that shape the propensity to sing. This ethological approach underlies our theoretical perspective, which is to integrate the significance of singing-driven gene expression into a broader ecological context. PMID:16129463

Light-operated machines based on threaded molecular structures.

PubMed

Credi, Alberto; Silvi, Serena; Venturi, Margherita

2014-01-01

Rotaxanes and related species represent the most common implementation of the concept of artificial molecular machines, because the supramolecular nature of the interactions between the components and their interlocked architecture allow a precise control on the position and movement of the molecular units. The use of light to power artificial molecular machines is particularly valuable because it can play the dual role of "writing" and "reading" the system. Moreover, light-driven machines can operate without accumulation of waste products, and photons are the ideal inputs to enable autonomous operation mechanisms. In appropriately designed molecular machines, light can be used to control not only the stability of the system, which affects the relative position of the molecular components but also the kinetics of the mechanical processes, thereby enabling control on the direction of the movements. This step forward is necessary in order to make a leap from molecular machines to molecular motors.

Immobilization of a molecular catalyst on carbon nanotubes for highly efficient electro-catalytic water oxidation.

PubMed

Li, Fusheng; Li, Lin; Tong, Lianpeng; Daniel, Quentin; Göthelid, Mats; Sun, Licheng

2014-11-21

Electrochemically driven water oxidation has been performed using a molecular water oxidation catalyst immobilized on hybrid carbon nanotubes and nano-material electrodes. A high turnover frequency (TOF) of 7.6 s(-1) together with a high catalytic current density of 2.2 mA cm(-2) was successfully obtained at an overpotential of 480 mV after 1 h of bulk electrolysis.

An antilock molecular braking system.

PubMed

Sun, Wei-Ting; Huang, Shou-Ling; Yao, Hsuan-Hsiao; Chen, I-Chia; Lin, Ying-Chih; Yang, Jye-Shane

2012-08-17

A light-driven molecular brake displaying an antilock function is constructed by introducing a nonradiative photoinduced electron transfer (PET) decay channel to compete with the trans (brake-off) → cis (brake-on) photoisomerization. A fast release of the brake can be achieved by deactivating the PET process through addition of protons. The cycle of irradiation-protonation-irradiation-deprotonation conducts the brake function and mimics the antilock braking system (ABS) of vehicles.

Coupled Phases and Combinatorial Selection in Fluctuating Hydrothermal Pools: A Scenario to Guide Experimental Approaches to the Origin of Cellular Life

PubMed Central

Damer, Bruce; Deamer, David

2015-01-01

Hydrothermal fields on the prebiotic Earth are candidate environments for biogenesis. We propose a model in which molecular systems driven by cycles of hydration and dehydration in such sites undergo chemical evolution in dehydrated films on mineral surfaces followed by encapsulation and combinatorial selection in a hydrated bulk phase. The dehydrated phase can consist of concentrated eutectic mixtures or multilamellar liquid crystalline matrices. Both conditions organize and concentrate potential monomers and thereby promote polymerization reactions that are driven by reduced water activity in the dehydrated phase. In the case of multilamellar lipid matrices, polymers that have been synthesized are captured in lipid vesicles upon rehydration to produce a variety of molecular systems. Each vesicle represents a protocell, an “experiment” in a natural version of combinatorial chemistry. Two kinds of selective processes can then occur. The first is a physical process in which relatively stable molecular systems will be preferentially selected. The second is a chemical process in which rare combinations of encapsulated polymers form systems capable of capturing energy and nutrients to undergo growth by catalyzed polymerization. Given continued cycling over extended time spans, such combinatorial processes will give rise to molecular systems having the fundamental properties of life. PMID:25780958

A study of some non-equilibrium driven models and their contribution to the understanding of molecular motors

NASA Astrophysics Data System (ADS)

Mazilu, Irina; Gonzalez, Joshua

2008-03-01

From the point of view of a physicist, a bio-molecular motor represents an interesting non-equilibrium system and it is directly amenable to an analysis using standard methods of non-equilibrium statistical physics. We conduct a rigorous Monte Carlo study of three different driven lattice gas models that retain the basic behavior of three types of cytoskeletal molecular motors. Our models incorporate novel features such as realistic dynamics rules and complex motor-motor interactions. We are interested to have a deeper understanding of how various parameters influence the macroscopic behavior of these systems, what is the density profile and if the system undergoes a phase transition. On the analytical front, we computed the steady-state probability distributions exactly for the one of the models using the matrix method that was established in 1993 by B. Derrida et al. We also explored the possibilities offered by the ``Bethe ansatz'' method by mapping some well studied spin models into asymmetric simple exclusion models (already analyzed using computer simulations), and to use the results obtained for the spin models in finding an exact solution for our problem. We have exhaustive computational studies of the kinesin and dynein molecular motor models that prove to be very useful in checking our analytical work.

Microtubule defects influence kinesin-based transport in vitro.

NASA Astrophysics Data System (ADS)

Xu, Jing

Microtubules are protein polymers that form ``molecular highways'' for long-range transport within living cells. Molecular motors actively step along microtubules to shuttle cellular materials between the nucleus and the cell periphery; this transport is critical for the survival and health of all eukaryotic cells. Structural defects in microtubules exist, but whether these defects impact molecular motor-based transport remains unknown. Here, we report a new, to our knowledge, approach that allowed us to directly investigate the impact of such defects. Using a modified optical-trapping method, we examined the group function of a major molecular motor, conventional kinesin, when transporting cargos along individual microtubules. We found that microtubule defects influence kinesin-based transport in vitro. The effects depend on motor number: cargos driven by a few motors tended to unbind prematurely from the microtubule, whereas cargos driven by more motors tended to pause. To our knowledge, our study provides the first direct link between microtubule defects and kinesin function. The effects uncovered in our study may have physiological relevance in vivo. Supported by the UC Merced (to J.X.), NIH (NS048501 to S.J.K.), NSF (EF-1038697 to A.G.), and the James S. McDonnell Foundation (to A.G.). Work carried out at the Aspen Center for Physics was supported by NSF Grant PHY-1066293.

Temperature-dependent resetting of the molecular circadian oscillator in Drosophila

PubMed Central

Goda, Tadahiro; Sharp, Brandi; Wijnen, Herman

2014-01-01

Circadian clocks responsible for daily time keeping in a wide range of organisms synchronize to daily temperature cycles via pathways that remain poorly understood. To address this problem from the perspective of the molecular oscillator, we monitored temperature-dependent resetting of four of its core components in the fruitfly Drosophila melanogaster: the transcripts and proteins for the clock genes period (per) and timeless (tim). The molecular circadian cycle in adult heads exhibited parallel responses to temperature-mediated resetting at the levels of per transcript, tim transcript and TIM protein. Early phase adjustment specific to per transcript rhythms was explained by clock-independent temperature-driven transcription of per. The cold-induced expression of Drosophila per contrasts with the previously reported heat-induced regulation of mammalian Period 2. An altered and more readily re-entrainable temperature-synchronized circadian oscillator that featured temperature-driven per transcript rhythms and phase-shifted TIM and PER protein rhythms was found for flies of the ‘Tim 4’ genotype, which lacked daily tim transcript oscillations but maintained post-transcriptional temperature entrainment of tim expression. The accelerated molecular and behavioural temperature entrainment observed for Tim 4 flies indicates that clock-controlled tim expression constrains the rate of temperature cycle-mediated circadian resetting. PMID:25165772

Molecular dynamics simulation of a piston driven shock wave in a hard sphere gas. Final Contractor ReportPh.D. Thesis

NASA Technical Reports Server (NTRS)

Woo, Myeung-Jouh; Greber, Isaac

1995-01-01

Molecular dynamics simulation is used to study the piston driven shock wave at Mach 1.5, 3, and 10. A shock tube, whose shape is a circular cylinder, is filled with hard sphere molecules having a Maxwellian thermal velocity distribution and zero mean velocity. The piston moves and a shock wave is generated. All collisions are specular, including those between the molecules and the computational boundaries, so that the shock development is entirely causal, with no imposed statistics. The structure of the generated shock is examined in detail, and the wave speed; profiles of density, velocity, and temperature; and shock thickness are determined. The results are compared with published results of other methods, especially the direct simulation Monte-Carlo method. Property profiles are similar to those generated by direct simulation Monte-Carlo method. The shock wave thicknesses are smaller than the direct simulation Monte-Carlo results, but larger than those of the other methods. Simulation of a shock wave, which is one-dimensional, is a severe test of the molecular dynamics method, which is always three-dimensional. A major challenge of the thesis is to examine the capability of the molecular dynamics methods by choosing a difficult task.

Adaptive Molecular Evolution for 13,000 Phage Generations

PubMed Central

Wichman, Holly A.; Millstein, Jack; Bull, J. J.

2005-01-01

Bacteriophage φX174 was evolved on a continuous supply of sensitive hosts for 180 days (∼13,000 phage generations). The average rate of nucleotide substitution was nearly 0.2% (11 substitutions)/20 days, and, surprisingly, substitutions accumulated in a clock-like manner throughout the study, except for a low rate during the first 20 days. Rates of silent and missense substitutions varied over time and among genes. Approximately 40% of the 71 missense changes and 25% of the 58 silent changes have been observed in previous adaptations; the rate of parallel substitution was highest in the early phase of the evolution, but 7% of the later changes had evolved in previous studies of much shorter duration. Several lines of evidence suggest that most of the changes were adaptive, even many of the silent substitutions. The sustained, high rate of adaptive evolution for 180 days defies a model of adaptation to a constant environment. We instead suggest that continuing molecular evolution reflects a potentially indefinite arms race, stemming from high levels of co-infection and the resulting conflict among genomes competing within the same cell. PMID:15687276

A comparative study of cold- and warm-adapted Endonucleases A using sequence analyses and molecular dynamics simulations.

PubMed

Michetti, Davide; Brandsdal, Bjørn Olav; Bon, Davide; Isaksen, Geir Villy; Tiberti, Matteo; Papaleo, Elena

2017-01-01

The psychrophilic and mesophilic endonucleases A (EndA) from Aliivibrio salmonicida (VsEndA) and Vibrio cholera (VcEndA) have been studied experimentally in terms of the biophysical properties related to thermal adaptation. The analyses of their static X-ray structures was no sufficient to rationalize the determinants of their adaptive traits at the molecular level. Thus, we used Molecular Dynamics (MD) simulations to compare the two proteins and unveil their structural and dynamical differences. Our simulations did not show a substantial increase in flexibility in the cold-adapted variant on the nanosecond time scale. The only exception is a more rigid C-terminal region in VcEndA, which is ascribable to a cluster of electrostatic interactions and hydrogen bonds, as also supported by MD simulations of the VsEndA mutant variant where the cluster of interactions was introduced. Moreover, we identified three additional amino acidic substitutions through multiple sequence alignment and the analyses of MD-based protein structure networks. In particular, T120V occurs in the proximity of the catalytic residue H80 and alters the interaction with the residue Y43, which belongs to the second coordination sphere of the Mg2+ ion. This makes T120V an amenable candidate for future experimental mutagenesis.

NMR studies on Na+ transport in Synechococcus PCC 6311

NASA Technical Reports Server (NTRS)

Nitschmann, W. H.; Packer, L.

1992-01-01

The freshwater cyanobacterium Synechococcus PCC 6311 is able to adapt to grow after sudden exposure to salt (NaCl) stress. We have investigated the mechanism of Na+ transport in these cells during adaptation to high salinity. Na+ influx under dark aerobic conditions occurred independently of delta pH or delta psi across the cytoplasmic membrane, ATPase activity, and respiratory electron transport. These findings are consistent with the existence of Na+/monovalent anion cotransport or simultaneous Na+/H+ +anion/OH- exchange. Na+ influx was dependent on Cl-, Br-, NO3-, or NO2-. No Na+ uptake occurred after addition of NaI, NaHCO3, or Na2SO4. Na+ extrusion was absolutely dependent on delta pH and on an ATPase activity and/or on respiratory electron transport. This indicates that Na+ extrusion via Na+/H+ exchange is driven by primary H+ pumps in the cytoplasmic membrane. Cells grown for 4 days in 0.5 m NaCl medium, "salt-grown cells," differ from control cells by a lower maximum velocity of Na+ influx and by lower steady-state ratios of [Na+]in/[Na+]out. These results indicate that cells grown in high-salt medium increase their capacity to extrude Na+. During salt adaptation Na+ extrusion driven by respiratory electron transport increased from about 15 to 50%.

Evolutionary and plastic responses of freshwater invertebrates to climate change: realized patterns and future potential

PubMed Central

Stoks, Robby; Geerts, Aurora N; De Meester, Luc

2014-01-01

We integrated the evidence for evolutionary and plastic trait changes in situ in response to climate change in freshwater invertebrates (aquatic insects and zooplankton). The synthesis on the trait changes in response to the expected reductions in hydroperiod and increases in salinity indicated little evidence for adaptive, plastic, and genetic trait changes and for local adaptation. With respect to responses to temperature, there are many studies on temporal trait changes in phenology and body size in the wild that are believed to be driven by temperature increases, but there is a general lack of rigorous demonstration whether these trait changes are genetically based, adaptive, and causally driven by climate change. Current proof for genetic trait changes under climate change in freshwater invertebrates stems from a limited set of common garden experiments replicated in time. Experimental thermal evolution experiments and common garden warming experiments associated with space-for-time substitutions along latitudinal gradients indicate that besides genetic changes, also phenotypic plasticity and evolution of plasticity are likely to contribute to the observed phenotypic changes under climate change in aquatic invertebrates. Apart from plastic and genetic thermal adjustments, also genetic photoperiod adjustments are widespread and may even dominate the observed phenological shifts. PMID:24454547

Model-driven discovery of underground metabolic functions in Escherichia coli.

PubMed

Guzmán, Gabriela I; Utrilla, José; Nurk, Sergey; Brunk, Elizabeth; Monk, Jonathan M; Ebrahim, Ali; Palsson, Bernhard O; Feist, Adam M

2015-01-20

Enzyme promiscuity toward substrates has been discussed in evolutionary terms as providing the flexibility to adapt to novel environments. In the present work, we describe an approach toward exploring such enzyme promiscuity in the space of a metabolic network. This approach leverages genome-scale models, which have been widely used for predicting growth phenotypes in various environments or following a genetic perturbation; however, these predictions occasionally fail. Failed predictions of gene essentiality offer an opportunity for targeting biological discovery, suggesting the presence of unknown underground pathways stemming from enzymatic cross-reactivity. We demonstrate a workflow that couples constraint-based modeling and bioinformatic tools with KO strain analysis and adaptive laboratory evolution for the purpose of predicting promiscuity at the genome scale. Three cases of genes that are incorrectly predicted as essential in Escherichia coli--aspC, argD, and gltA--are examined, and isozyme functions are uncovered for each to a different extent. Seven isozyme functions based on genetic and transcriptional evidence are suggested between the genes aspC and tyrB, argD and astC, gabT and puuE, and gltA and prpC. This study demonstrates how a targeted model-driven approach to discovery can systematically fill knowledge gaps, characterize underground metabolism, and elucidate regulatory mechanisms of adaptation in response to gene KO perturbations.

Clusters of community exposure to coastal flooding hazards based on storm and sea level rise scenarios—implications for adaptation networks in the San Francisco Bay region

USGS Publications Warehouse

Hummel, Michelle; Wood, Nathan J.; Schweikert, Amy; Stacey, Mark T.; Jones, Jeanne; Barnard, Patrick L.; Erikson, Li H.

2018-01-01

Sea level is projected to rise over the coming decades, further increasing the extent of flooding hazards in coastal communities. Efforts to address potential impacts from climate-driven coastal hazards have called for collaboration among communities to strengthen the application of best practices. However, communities currently lack practical tools for identifying potential partner communities based on similar hazard exposure characteristics. This study uses statistical cluster analysis to identify similarities in community exposure to flooding hazards for a suite of sea level rise and storm scenarios. We demonstrate this approach using 63 jurisdictions in the San Francisco Bay region of California (USA) and compare 21 distinct exposure variables related to residents, employees, and structures for six hazard scenario combinations of sea level rise and storms. Results indicate that cluster analysis can provide an effective mechanism for identifying community groupings. Cluster compositions changed based on the selected societal variables and sea level rise scenarios, suggesting that a community could participate in multiple networks to target specific issues or policy interventions. The proposed clustering approach can serve as a data-driven foundation to help communities identify other communities with similar adaptation challenges and to enhance regional efforts that aim to facilitate adaptation planning and investment prioritization.

BIRC3 is a biomarker of mesenchymal habitat of glioblastoma, and a mediator of survival adaptation in hypoxia-driven glioblastoma habitats.

PubMed

Wang, Dapeng; Berglund, Anders E; Kenchappa, Rajappa S; MacAulay, Robert J; Mulé, James J; Etame, Arnold B

2017-08-24

Tumor hypoxia is an established facilitator of survival adaptation and mesenchymal transformation in glioblastoma (GBM). The underlying mechanisms that direct hypoxia-mediated survival in GBM habitats are unclear. We previously identified BIRC3 as a mediator of therapeutic resistance in GBM to standard temozolomide (TMZ) chemotherapy and radiotherapy (RT). Here we report that BIRC3 is a biomarker of the hypoxia-mediated adaptive mesenchymal phenotype of GBM. Specifically, in the TCGA dataset elevated BIRC3 gene expression was identified as a superior and selective biomarker of mesenchymal GBM versus neural, proneural and classical subtypes. Further, BIRC3 protein was highly expressed in the tumor cell niches compared to the perivascular niche across multiple regions in GBM patient tissue microarrays. Tumor hypoxia was found to mechanistically induce BIRC3 expression through HIF1-alpha signaling in GBM cells. Moreover, in human GBM xenografts robust BIRC3 expression was noted within hypoxic regions of the tumor. Importantly, selective inhibition of BIRC3 reversed therapeutic resistance of GBM cells to RT in hypoxic microenvironments through enhanced activation of caspases. Collectively, we have uncovered a novel role for BIRC3 as a targetable biomarker and mediator of hypoxia-driven habitats in GBM.

Tangible Models and Haptic Representations Aid Learning of Molecular Biology Concepts

ERIC Educational Resources Information Center

Johannes, Kristen; Powers, Jacklyn; Couper, Lisa; Silberglitt, Matt; Davenport, Jodi

2016-01-01

Can novel 3D models help students develop a deeper understanding of core concepts in molecular biology? We adapted 3D molecular models, developed by scientists, for use in high school science classrooms. The models accurately represent the structural and functional properties of complex DNA and Virus molecules, and provide visual and haptic…

Teaching Applied Genetics and Molecular Biology to Agriculture Engineers. Application of the European Credit Transfer System

ERIC Educational Resources Information Center

Weiss, J.; Egea-Cortines, M.

2008-01-01

We have been teaching applied molecular genetics to engineers and adapted the teaching methodology to the European Credit Transfer System. We teach core principles of genetics that are universal and form the conceptual basis of most molecular technologies. The course then teaches widely used techniques and finally shows how different techniques…

Whither or wither geomicrobiology in the era of 'community metagenomics'

USGS Publications Warehouse

Oremland, R.S.; Capone, D.G.; Stolz, J.F.; Fuhrman, J.

2005-01-01

Molecular techniques are valuable tools that can improve our understanding of the structure of microbial communities. They provide the ability to probe for life in all niches of the biosphere, perhaps even supplanting the need to cultivate microorganisms or to conduct ecophysiological investigations. However, an overemphasis and strict dependence on such large information-driven endeavours as environmental metagenomics could overwhelm the field, to the detriment of microbial ecology. We now call for more balanced, hypothesis-driven research efforts that couple metagenomics with classic approaches.

Adaptive radiation versus 'radiation' and 'explosive diversification': why conceptual distinctions are fundamental to understanding evolution.

PubMed

Givnish, Thomas J

2015-07-01

Adaptive radiation is the rise of a diversity of ecological roles and role-specific adaptations within a lineage. Recently, some researchers have begun to use 'adaptive radiation' or 'radiation' as synonymous with 'explosive species diversification'. This essay aims to clarify distinctions between these concepts, and the related ideas of geographic speciation, sexual selection, key innovations, key landscapes and ecological keys. Several examples are given to demonstrate that adaptive radiation and explosive diversification are not the same phenomenon, and that focusing on explosive diversification and the analysis of phylogenetic topology ignores much of the rich biology associated with adaptive radiation, and risks generating confusion about the nature of the evolutionary forces driving species diversification. Some 'radiations' involve bursts of geographic speciation or sexual selection, rather than adaptive diversification; some adaptive radiations have little or no effect on speciation, or even a negative effect. Many classic examples of 'adaptive radiation' appear to involve effects driven partly by geographic speciation, species' dispersal abilities, and the nature of extrinsic dispersal barriers; partly by sexual selection; and partly by adaptive radiation in the classical sense, including the origin of traits and invasion of adaptive zones that result in decreased diversification rates but add to overall diversity. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

Characterization of Outer Space Radiation Induced Changes in Extremophiles Utilizing Deep Space Gateway Opportunities

NASA Astrophysics Data System (ADS)

Venkateswaran, K.; Wang, C.; Smith, D.; Mason, C.; Landry, K.; Rettberg, P.

2018-02-01

Extremophilic microbial survival, adaptation, biological functions, and molecular mechanisms associated with outer space radiation can be tested by exposing them onto Deep Space Gateway hardware (inside/outside) using microbiology and molecular biology techniques.

Viruses are a dominant driver of protein adaptation in mammals.

PubMed

Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

2016-05-17

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.

Viruses are a dominant driver of protein adaptation in mammals

PubMed Central

Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

2016-01-01

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001 PMID:27187613

Preface: Special Topic on Frontiers in Molecular Scale Electronics

NASA Astrophysics Data System (ADS)

Evers, Ferdinand; Venkataraman, Latha

2017-03-01

The electronic, mechanical, and thermoelectric properties of molecular scale devices have fascinated scientists across several disciplines in natural sciences and engineering. The interest is partially technological, driven by the fast miniaturization of integrated circuits that now have reached characteristic features at the nanometer scale. Equally important, a very strong incentive also exists to elucidate the fundamental aspects of structure-function relations for nanoscale devices, which utilize molecular building blocks as functional units. Thus motivated, a rich research field has established itself, broadly termed "Molecular Electronics," that hosts a plethora of activities devoted to this goal in chemistry, physics, and electrical engineering. This Special Topic on Frontiers of Molecular Scale Electronics captures recent theoretical and experimental advances in the field.

Molecular graph convolutions: moving beyond fingerprints

PubMed Central

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-01-01

Molecular “fingerprints” encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement. PMID:27558503

Galactic-scale Feedback Observed in the 3C 298 Quasar Host Galaxy

NASA Astrophysics Data System (ADS)

Vayner, Andrey; Wright, Shelley A.; Murray, Norman; Armus, Lee; Larkin, James E.; Mieda, Etsuko

2017-12-01

We present high angular resolution multiwavelength data of the 3C 298 radio-loud quasar host galaxy (z = 1.439) taken using the W.M. Keck Observatory OSIRIS integral field spectrograph (IFS) with adaptive optics, the Atacama Large Millimeter/submillimeter Array (ALMA), the Hubble Space Telescope (HST) WFC3, and the Very Large Array (VLA). Extended emission is detected in the rest-frame optical nebular emission lines Hβ, [O III], Hα, [N II], and [S II], as well as in the molecular lines CO (J = 3‑2) and (J = 5‑4). Along the path of the relativistic jets of 3C 298, we detect conical outflows in ionized gas emission with velocities of up to 1700 {km} {{{s}}}-1 and an outflow rate of 450–1500 {M}ȯ {{yr}}-1 extended over 12 kpc. Near the spatial center of the conical outflow, CO (J = 3‑2) emission shows a molecular gas disk with a rotational velocity of ±150 {km} {{{s}}}-1 and total molecular mass ({M}{{{H}}2}) of 6.6+/- 0.36× {10}9 {M}ȯ . On the blueshifted side of the molecular disk, we observe broad extended emission that is due to a molecular outflow with a rate of 2300 {M}ȯ {{yr}}-1 and depletion timescale of 3 Myr. We detect no narrow Hα emission in the outflow regions, suggesting a limit on star formation of 0.3 {M}ȯ {{yr}}-1 {{kpc}}-2. Quasar-driven winds are evacuating the molecular gas reservoir, thereby directly impacting star formation in the host galaxy. The observed mass of the supermassive black hole is {10}9.37{--9.56} {M}ȯ , and we determine a dynamical bulge mass of {M}{bulge}=1{--}1.7× {10}10\\tfrac{R}{1.6 {kpc}} {M}ȯ . The bulge mass of 3C 298 lies 2–2.5 orders of magnitude below the expected value from the local galactic bulge—supermassive black hole mass ({M}{bulge}{--}{M}{BH}) relationship. A second galactic disk observed in nebular emission is offset from the quasar by 9 kpc, suggesting that the system is an intermediate-stage merger. These results show that galactic-scale negative feedback is occurring early in the merger phase of 3C 298, well before the coalescence of the galactic nuclei and assembly on the local {M}{bulge}{--}{M}{BH} relationship.

(2+1) -dimensional stable spatial Raman solitons

NASA Astrophysics Data System (ADS)

Shverdin, M. Y.; Yavuz, D. D.; Walker, D. R.

2004-03-01

We analyze the formation, propagation, and interaction of stable two-frequency (2+1) -dimensional solitons, formed in a Raman media driven near maximum molecular coherence. The propagating light is trapped in the two transverse dimensions.

Mechanochemical Association Reaction of Interfacial Molecules Driven by Shear.

PubMed

Khajeh, Arash; He, Xin; Yeon, Jejoon; Kim, Seong H; Martini, Ashlie

2018-05-29

Shear-driven chemical reaction mechanisms are poorly understood because the relevant reactions are often hidden between two solid surfaces moving in relative motion. Here, this phenomenon is explored by characterizing shear-induced polymerization reactions that occur during vapor phase lubrication of α-pinene between sliding hydroxylated and dehydroxylated silica surfaces, complemented by reactive molecular dynamics simulations. The results suggest that oxidative chemisorption of the α-pinene molecules at reactive surface sites, which transfers oxygen atoms from the surface to the adsorbate molecule, is the critical activation step. Such activation takes place more readily on the dehydroxylated surface. During this activation, the most strained part of the α-pinene molecules undergoes a partial distortion from its equilibrium geometry, which appears to be related to the critical activation volume for mechanical activation. Once α-pinene molecules are activated, association reactions occur between the newly attached oxygen and one of the carbon atoms in another molecule, forming ether bonds. These findings have general implications for mechanochemistry because they reveal that shear-driven reactions may occur through reaction pathways very different from their thermally induced counterparts and specifically the critical role of molecular distortion in such reactions.

Electrochemically-Driven Insertion of Biological Nanodiscs into Solid State Membrane Pores as a Basis for "Pore-In-Pore" Membranes.

PubMed

Farajollahi, Farid; Seidenstücker, Axel; Altintoprak, Klara; Walther, Paul; Ziemann, Paul; Plettl, Alfred; Marti, Othmar; Wege, Christina; Gliemann, Hartmut

2018-04-13

Nanoporous membranes are of increasing interest for many applications, such as molecular filters, biosensors, nanofluidic logic and energy conversion devices. To meet high-quality standards, e.g., in molecular separation processes, membranes with well-defined pores in terms of pore diameter and chemical properties are required. However, the preparation of membranes with narrow pore diameter distributions is still challenging. In the work presented here, we demonstrate a strategy, a "pore-in-pore" approach, where the conical pores of a solid state membrane produced by a multi-step top-down lithography procedure are used as a template to insert precisely-formed biomolecular nanodiscs with exactly defined inner and outer diameters. These nanodiscs, which are the building blocks of tobacco mosaic virus-deduced particles, consist of coat proteins, which self-assemble under defined experimental conditions with a stabilizing short RNA. We demonstrate that the insertion of the nanodiscs can be driven either by diffusion due to a concentration gradient or by applying an electric field along the cross-section of the solid state membrane. It is found that the electrophoresis-driven insertion is significantly more effective than the insertion via the concentration gradient.

Electrochemically-Driven Insertion of Biological Nanodiscs into Solid State Membrane Pores as a Basis for “Pore-In-Pore” Membranes

PubMed Central

Farajollahi, Farid; Seidenstücker, Axel; Altintoprak, Klara; Walther, Paul; Ziemann, Paul; Plettl, Alfred; Wege, Christina; Gliemann, Hartmut

2018-01-01

Nanoporous membranes are of increasing interest for many applications, such as molecular filters, biosensors, nanofluidic logic and energy conversion devices. To meet high-quality standards, e.g., in molecular separation processes, membranes with well-defined pores in terms of pore diameter and chemical properties are required. However, the preparation of membranes with narrow pore diameter distributions is still challenging. In the work presented here, we demonstrate a strategy, a “pore-in-pore” approach, where the conical pores of a solid state membrane produced by a multi-step top-down lithography procedure are used as a template to insert precisely-formed biomolecular nanodiscs with exactly defined inner and outer diameters. These nanodiscs, which are the building blocks of tobacco mosaic virus-deduced particles, consist of coat proteins, which self-assemble under defined experimental conditions with a stabilizing short RNA. We demonstrate that the insertion of the nanodiscs can be driven either by diffusion due to a concentration gradient or by applying an electric field along the cross-section of the solid state membrane. It is found that the electrophoresis-driven insertion is significantly more effective than the insertion via the concentration gradient. PMID:29652841

Control of microtubule trajectory within an electric field by altering surface charge density

PubMed Central

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-01

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins. PMID:25567007

Control of microtubule trajectory within an electric field by altering surface charge density.

PubMed

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-08

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins.

Adaptive molecular evolution of the two-pore channel 1 gene TPC1 in the karst-adapted genus Primulina (Gesneriaceae)

PubMed Central

Tao, Junjie; Feng, Chao; Ai, Bin; Kang, Ming

2016-01-01

Background and Aims Limestone karst areas possess high floral diversity and endemism. The genus Primulina, which contributes to the unique calcicole flora, has high species richness and exhibit specific soil-based habitat associations that are mainly distributed on calcareous karst soils. The adaptive molecular evolutionary mechanism of the genus to karst calcium-rich environments is still not well understood. The Ca2+-permeable channel TPC1 was used in this study to test whether its gene is involved in the local adaptation of Primulina to karst high-calcium soil environments. Methods Specific amplification and sequencing primers were designed and used to amplify the full-length coding sequences of TPC1 from cDNA of 76 Primulina species. The sequence alignment without recombination and the corresponding reconstructed phylogeny tree were used in molecular evolutionary analyses at the nucleic acid level and amino acid level, respectively. Finally, the identified sites under positive selection were labelled on the predicted secondary structure of TPC1. Key Results Seventy-six full-length coding sequences of Primulina TPC1 were obtained. The length of the sequences varied between 2220 and 2286 bp and the insertion/deletion was located at the 5′ end of the sequences. No signal of substitution saturation was detected in the sequences, while significant recombination breakpoints were detected. The molecular evolutionary analyses showed that TPC1 was dominated by purifying selection and the selective pressures were not significantly different among species lineages. However, significant signals of positive selection were detected at both TPC1 codon level and amino acid level, and five sites under positive selective pressure were identified by at least three different methods. Conclusions The Ca2+-permeable channel TPC1 may be involved in the local adaptation of Primulina to karst Ca2+-rich environments. Different species lineages suffered similar selective pressure associated with calcium in karst environments, and episodic diversifying selection at a few sites may play a major role in the molecular evolution of Primulina TPC1. PMID:27582362

Behavior driven testing in ALMA telescope calibration software

NASA Astrophysics Data System (ADS)

Gil, Juan P.; Garces, Mario; Broguiere, Dominique; Shen, Tzu-Chiang

2016-07-01

ALMA software development cycle includes well defined testing stages that involves developers, testers and scientists. We adapted Behavior Driven Development (BDD) to testing activities applied to Telescope Calibration (TELCAL) software. BDD is an agile technique that encourages communication between roles by defining test cases using natural language to specify features and scenarios, what allows participants to share a common language and provides a high level set of automated tests. This work describes how we implemented and maintain BDD testing for TELCAL, the infrastructure needed to support it and proposals to expand this technique to other subsystems.

Salinity Tolerance Mechanism of Economic Halophytes From Physiological to Molecular Hierarchy for Improving Food Quality

PubMed Central

Xu, Chongzhi; Tang, Xiaoli; Shao, Hongbo; Wang, Hongyan

2016-01-01

Soil salinity is becoming the key constraints factor to agricultural production. Therefore, the plant especially the crops possessing capacities of salt tolerance will be of great economic significance. The adaptation or tolerance of plant to salinity stress involves a series of physiological, metabolic and molecular mechanisms. Halophytes are the kind of organisms which acquire special salt tolerance mechanisms to respond to the salt tress and ensure normal growth and development under saline conditions in their lengthy evolutionary adaptation, so understanding how halophytes respond to salinity stress will provide us with methods and tactics to foster and develop salt resistant varieties of crops. The strategies in physiological and molecular level adopted by halophytes are various including the changes in photosynthetic and transpiration rate, the sequestration of Na+ to extracellular or vacuole, the regulation of stomata aperture and stomatal density, the accumulation and synthesis of the phytohormones as well as the relevant gene expression underlying these physiological traits, such as the stress signal transduction, the regulation of the transcription factors, the activation and expression of the transporter genes, the activation or inhibition of the synthetases and so on. This review focuses on the research advances of the regulating mechanisms in halophytes from physiological to molecular, which render the halophytes tolerance and adaption to salinity stress. PMID:27252587

Integrated direct/indirect adaptive robust motion trajectory tracking control of pneumatic cylinders

NASA Astrophysics Data System (ADS)

Meng, Deyuan; Tao, Guoliang; Zhu, Xiaocong

2013-09-01

This paper studies the precision motion trajectory tracking control of a pneumatic cylinder driven by a proportional-directional control valve. An integrated direct/indirect adaptive robust controller is proposed. The controller employs a physical model based indirect-type parameter estimation to obtain reliable estimates of unknown model parameters, and utilises a robust control method with dynamic compensation type fast adaptation to attenuate the effects of parameter estimation errors, unmodelled dynamics and disturbances. Due to the use of projection mapping, the robust control law and the parameter adaption algorithm can be designed separately. Since the system model uncertainties are unmatched, the recursive backstepping technology is adopted to design the robust control law. Extensive comparative experimental results are presented to illustrate the effectiveness of the proposed controller and its performance robustness to parameter variations and sudden disturbances.